Database JAK3base Version 2.5 File jak3pub.html Date 27-Sep-2007 Curator Mauno Vihinen Address Institute of Medical Technology Address FI-33014 University of Tampere, Finland Phone +358-3-3551 7735 Fax +358-3-3551 7710 Email Mauno.Vihinen@uta.fi URL http://bioinf.uta.fi/JAK3base/ FTP ftp://protein.uta.fi/pub/jak3pub.dat IDR factfile http://bioinf.uta.fi/xml/idr/ff/FF9.xml Gene JAK3 Disease autosomal recessive severe combined immunodeficiency OMIM 600173 GDB 376460 Sequence IDRefSeq:D0095; IDRefSeq:C0095; UniProt:P52333 Numbering start of the entry Funding Tampere University Hospital Medical Research Fund Funding European Union Comments sequence entry reference in every entry // ID M1V(1a),Intron 19(1a); standard; MUTATION; IR1, Accession J0023 Systematic name Allele 1: g.5057A>G, c.1A>G, r.1a>g, p.Met1Val Systematic name Allele 2: g.IVS19+3G>C, c.2680+3G>C, r.2680+3g>c Original code P22a ref. [1]; Patient 1 ref. [2] Description Allele 1; missense mutation in the exon 2 altering Description initiation codon Description Allele 2; point mutation in the intron 19 Date 29-Dec-2000 (Rel. 2, Created) Date 08-Mar-2007 (Rel. 2, Last updated, Version 2) RefNumber [1] RefCrossRef PUBMED; 11668610 RefAuthors Notarangelo, L. D., Mella, P., Jones, A., de Saint Basile, RefAuthors G., Savoldi, G., Cranston, T., Vihinen, M., Schumacher, R. RefAuthors F. RefTitle Mutations in severe combined immune deficiency (SCID) due RefTitle to JAK3 deficiency. RefLoc Hum Mutat:255-263 (2001) RefNumber [2] RefCrossRef PUBMED; 11668621 RefAuthors Mella, P., Schumacher, R. F., Cranston, T., de Saint RefAuthors Basile, G., Savoldi, G., Notarangelo, L. D. RefTitle Eleven novel JAK3 mutations in patients with severe RefTitle combined immunodeficiency-including the first patients RefTitle with mutations in the kinase domain. RefLoc Hum Mutat:355-356 (2001) FeatureHeader allele; 1 Feature dna; 1 Feature /rnalink: 2 Feature /name: point Feature /loc: IDRefSeq: D0095: 5057 Feature /change: a -> g Feature /genomic_region: exon; 2 Feature rna; 2 Feature /dnalink: 1 Feature /aalink: 3 Feature /name: missense Feature /loc: IDRefSeq: C0095: 60 Feature /codon: atg -> gtg; 1 Feature aa; 3 Feature /rnalink: 2 Feature /name: aa substitution Feature /loc: UniProt: P52333; JAK3_HUMAN: 1 Feature /change: M -> V Feature /domain: IR1 FeatureHeader allele; 2 Feature dna; 4 Feature /rnalink: 5 Feature /name: point Feature /loc: IDRefSeq: D0095: 16958 Feature /change: g -> c Feature /genomic_region: intron; 19 Feature rna; 5 Feature /dnalink: 4 Feature /aalink: 6 Feature /name: unknown Feature /inexloc: +3 Feature aa; 6 Feature /rnalink: 5 Feature /name: unknown Protein level Undetectable Diagnosis T-B+ severe combined immunodeficiency Sex XX Relative JAK3; J0024; brother IgG Normal CD3 low CD16/56 Decreased% CD19 Normal Response PHA: Decreased // ID M1V(1b),Intron 19(1b); standard; MUTATION; IR1, Accession J0024 Systematic name Allele 1: g.5057A>G, c.1A>G, r.1a>g, p.Met1Val Systematic name Allele 2: g.IVS19+3G>C, c.2680+3G>C, r.2680+3g>c Original code P22b ref. [1]; Patient 2 ref. [2] Description Allele 1; missense mutation in the exon 2 altering Description initiation codon Description Allele 2; point mutation in the intron 19 Date 29-Dec-2000 (Rel. 2, Created) Date 08-Mar-2007 (Rel. 2, Last updated, Version 2) RefNumber [1] RefCrossRef PUBMED; 11668610 RefAuthors Notarangelo, L. D., Mella, P., Jones, A., de Saint Basile, RefAuthors G., Savoldi, G., Cranston, T., Vihinen, M., Schumacher, R. RefAuthors F. RefTitle Mutations in severe combined immune deficiency (SCID) due RefTitle to JAK3 deficiency. RefLoc Hum Mutat:255-263 (2001) RefNumber [2] RefCrossRef PUBMED; 11668621 RefAuthors Mella, P., Schumacher, R. F., Cranston, T., de Saint RefAuthors Basile, G., Savoldi, G., Notarangelo, L. D. RefTitle Eleven novel JAK3 mutations in patients with severe RefTitle combined immunodeficiency-including the first patients RefTitle with mutations in the kinase domain. RefLoc Hum Mutat:355-356 (2001) FeatureHeader allele; 1 Feature dna; 1 Feature /rnalink: 2 Feature /name: point Feature /loc: IDRefSeq: D0095: 5057 Feature /change: a -> g Feature /genomic_region: exon; 2 Feature rna; 2 Feature /dnalink: 1 Feature /aalink: 3 Feature /name: missense Feature /loc: IDRefSeq: C0095: 60 Feature /codon: atg -> gtg; 1 Feature aa; 3 Feature /rnalink: 2 Feature /name: aa substitution Feature /loc: UniProt: P52333; JAK3_HUMAN: 1 Feature /change: M -> V Feature /domain: IR1 FeatureHeader allele; 2 Feature dna; 4 Feature /rnalink: 5 Feature /name: point Feature /loc: IDRefSeq: D0095: 16958 Feature /change: g -> c Feature /genomic_region: intron; 19 Feature rna; 5 Feature /dnalink: 4 Feature /aalink: 6 Feature /name: unknown Feature /inexloc: +3 Feature aa; 6 Feature /rnalink: 5 Feature /name: unknown Protein level Undetectable Diagnosis T-B+ severe combined immunodeficiency Sex XY Age 7 months Relative JAK3; J0023; sister Total lymphoc 2380 lymph/uL IgA 27 IgG 29 IgM 147 CD3 Low CD4 Very low CD8 20% CD16/56 Low CD19 High Therapy BMT: Sister Therapy BMT age: 96 months Therapy BMT outcome: Deceased Response PHA: Very low // ID #G36X146(1),#G36X146(1); standard; MUTATION; IR1,IR1 Accession J0028 Systematic name Allele 1 and 2: g.5164delG, c.108delG, r.108delg, Systematic name p.Gln39fsX107 Original code Patient 6 Description Allele 1 and 2: A frame shift deletion mutation in the exon Description 2 leading to a premature stop codon in the IR1 domain Date 14-Mar-2007 (Rel. 2, Created) Date 14-Mar-2007 (Rel. 2, Last updated, Version 1) RefNumber [1] RefCrossRef PUBMED; 14615376 RefAuthors Roberts, J. L., Lengi, A., Brown, S. M., Chen, M., Zhou, RefAuthors Y. J., O'Shea, J. J., Buckley, R. H. RefTitle Janus kinase 3 (JAK3) deficiency: clinical, immunologic, RefTitle and molecular analyses of 10 patients and outcomes of stem RefTitle cell transplantation. RefLoc Blood:2009-2018 (2004) FeatureHeader allele; 1 Feature dna; 1 Feature /rnalink: 2 Feature /name: deletion Feature /loc: IDRefSeq: D0095: 5164 Feature /change: -g Feature /genomic_region: exon; 2 Feature rna; 2 Feature /dnalink: 1 Feature /aalink: 3 Feature /name: frameshift Feature /loc: IDRefSeq: C0095: 167 Feature aa; 3 Feature /rnalink: 2 Feature /name: out of frame translation; premature termination Feature /loc: UniProt: P52333; JAK3_HUMAN: 36 Feature /change: G -> Feature /change: GPPSAYLSPL GTTWLRTCAC RLPRPAASCL CTTPSLLWPR Feature /change: RTCPAGSPRA TSSPWRMPAP KSCCTGFAFT SPIGLGWRSA Feature /change: TASGYARIWP VLSLTCQSWS TSLPSTAVTW X Feature /domain: IR1 FeatureHeader allele; 2 Feature dna; 4 Feature /rnalink: 5 Feature /name: deletion Feature /loc: IDRefSeq: D0095: 5164 Feature /change: -g Feature /genomic_region: exon; 2 Feature rna; 5 Feature /dnalink: 4 Feature /aalink: 6 Feature /name: frameshift Feature /loc: IDRefSeq: C0095: 167 Feature aa; 6 Feature /rnalink: 5 Feature /name: out of frame translation; premature termination Feature /loc: UniProt: P52333; JAK3_HUMAN: 36 Feature /change: G -> Feature /change: GPPSAYLSPL GTTWLRTCAC RLPRPAASCL CTTPSLLWPR Feature /change: RTCPAGSPRA TSSPWRMPAP KSCCTGFAFT SPIGLGWRSA Feature /change: TASGYARIWP VLSLTCQSWS TSLPSTAVTW X Feature /domain: IR1 Diagnosis T-B- severe combined immunodeficiency // ID #A57-1(1),D169E(1); standard; MUTATION; JH7,JH6 Accession J0025 Systematic name Allele 1: g.5227_5229delTGC, c.171_173delTGC, Systematic name r.171_173delugc, p.Ala57del Systematic name Allele 2: g.6388C>A, c.507C>A, r.507c>a, p.Asp169Glu Original code Patient 2 Description Allele 1: An inframe deletion in the exon 2 leading to an Description amino acid change in the JH7 domain Description Allele 2: A point mutation in the exon 5 leading to an Description amino acid change in the JH7 domain Date 13-Mar-2007 (Rel. 2, Created) Date 13-Mar-2007 (Rel. 2, Last updated, Version 1) RefNumber [1] RefCrossRef PUBMED; 14615376 RefAuthors Roberts, J. L., Lengi, A., Brown, S. M., Chen, M., Zhou, RefAuthors Y. J., O'Shea, J. J., Buckley, R. H. RefTitle Janus kinase 3 (JAK3) deficiency: clinical, immunologic, RefTitle and molecular analyses of 10 patients and outcomes of stem RefTitle cell transplantation. RefLoc Blood:2009-2018 (2004) RefNumber [2] RefCrossRef PUBMED; 11741532 RefAuthors Zhou, Y. J., Chen, M., Cusack, N. A., Kimmel, L. H., RefAuthors Magnuson, K. S., Boyd, J. G., Lin, W., Roberts, J. L., RefAuthors Lengi, A., Buckley, R. H., Geahlen, R. L., Candotti, F., RefAuthors Gadina, M., Changelian, P. S., O'Shea, J. J. RefTitle Unexpected effects of FERM domain mutations on catalytic RefTitle activity of jak3: structural implication for janus RefTitle kinases. RefLoc Mol Cell:959-969 (2001) FeatureHeader allele; 1 Feature dna; 1 Feature /rnalink: 2 Feature /name: deletion Feature /loc: IDRefSeq: D0095: 5227..5229 Feature /change: -tgc Feature /genomic_region: exon; 2 Feature rna; 2 Feature /dnalink: 1 Feature /aalink: 3 Feature /name: inframe deletion Feature /loc: IDRefSeq: C0095: 230..232 Feature aa; 3 Feature /rnalink: 2 Feature /name: deletion; inframe Feature /loc: UniProt: P52333; JAK3_HUMAN: 57..58 Feature /change: AA -> A Feature /domain: JH7 FeatureHeader allele; 2 Feature dna; 4 Feature /rnalink: 5 Feature /name: point Feature /loc: IDRefSeq: D0095: 6388 Feature /change: c -> a Feature /genomic_region: exon; 5 Feature rna; 5 Feature /dnalink: 4 Feature /aalink: 6 Feature /name: missense Feature /loc: IDRefSeq: C0095: 566 Feature /codon: gac -> gaa; 3 Feature aa; 6 Feature /rnalink: 5 Feature /name: aa substitution Feature /loc: UniProt: P52333; JAK3_HUMAN: 169 Feature /change: D -> E Feature /domain: JH6 Diagnosis T-B- severe combined immunodeficiency Sex XY // ID A58P(1),#C1024X1037(1); standard; MUTATION; JH7,JH1 Accession J0016 Systematic name Allele 1: g.5228G>C, c.172G>C, r.172g>c, p.Ala58Pro Systematic name Allele 2: g.18947delC, c.3072delC, r.3072delc, Systematic name p.Cys1024fsX13 Description Allele 1: A point mutation in the exon 2 leading to an Description amino acid change in the JH7 domain Description Allele 2: A frame shift deletion mutation in the exon 22 Description leading to a premature stop codon in the JH7 domain Date 13-Oct-2000 (Rel. 1, Created) Date 08-Mar-2007 (Rel. 2, Last updated, Version 3) RefNumber [1] RefCrossRef PUBMED; 10900158 RefAuthors Vihinen, M., Villa, A., Mella, P., Schumacher, R. F., RefAuthors Savoldi, G., O'Shea, J. J., Candotti, F., Notarangelo, RefAuthors L. D. RefTitle Molecular modeling of the Jak3 kinase domains and RefTitle structural basis for severe combined immunodeficiency RefLoc Clin. Immunol. 96:108-118(2000) RefNumber [2] RefCrossRef PUBMED; 11668610 RefAuthors Notarangelo, L. D., Mella, P., Jones, A., de Saint Basile, RefAuthors G., Savoldi, G., Cranston, T., Vihinen, M., Schumacher, R. RefAuthors F. RefTitle Mutations in severe combined immune deficiency (SCID) due RefTitle to JAK3 deficiency. RefLoc Hum Mutat:255-263 (2001) RefNumber [3] RefCrossRef PUBMED; 11668621 RefAuthors Mella, P., Schumacher, R. F., Cranston, T., de Saint RefAuthors Basile, G., Savoldi, G., Notarangelo, L. D. RefTitle Eleven novel JAK3 mutations in patients with severe RefTitle combined immunodeficiency-including the first patients RefTitle with mutations in the kinase domain. RefLoc Hum Mutat:355-356 (2001) FeatureHeader allele; 1 Feature dna; 1 Feature /rnalink: 2 Feature /name: point Feature /loc: IDRefSeq: D0095: 5228 Feature /change: g -> c Feature /genomic_region: exon; 2 Feature rna; 2 Feature /dnalink: 1 Feature /aalink: 3 Feature /name: missense Feature /loc: IDRefSeq: C0095: 231 Feature /codon: gcc -> ccc; 1 Feature aa; 3 Feature /rnalink: 2 Feature /name: aa substitution Feature /loc: UniProt: P52333; JAK3_HUMAN: 58 Feature /change: A -> P Feature /domain: JH7 FeatureHeader allele; 2 Feature dna; 4 Feature /rnalink: 5 Feature /name: deletion Feature /loc: IDRefSeq: D0095: 18947 Feature /change: -c Feature /genomic_region: exon; 22 Feature rna; 5 Feature /dnalink: 4 Feature /aalink: 6 Feature /name: frameshift Feature /loc: IDRefSeq: C0095: 3131 Feature aa; 6 Feature /rnalink: 5 Feature /name: out of frame translation; premature termination Feature /loc: UniProt: P52333; JAK3_HUMAN: 1024 Feature /change: C -> WTKAAAPRPS SCGX Feature /domain: JH1 Diagnosis T-B+ severe combined immunodeficiency; mild phenotype Symptoms Recurrent respiratory tract infections; persistent Symptoms candidiasis; Protein struct Allele 2; Truncation ref [1] Sex XX Age 19 months Total lymphoc 1630 lymph/uL IgA 259 IgE 24.6 IgG 1670 IgM 171 CD3 8% CD4 4% CD8 4.6% CD16/56 0.3% CD19 91.3% Therapy BMT: MUD Therapy BMT age: 27 months Therapy BMT outcome: A/w Response PHA: Absent // ID Y100C(1),Y100C(1); standard; MUTATION; JH7,JH7 Accession J0001 Systematic name Allele 1 and 2: g.5688A>G, c.299A>G, r.299a>g, p.Tyr100Cys Original code G.M. ref [1]; Gr.Ma. ref [3]; P1 ref [4] Description Allele 1 and 2: A point mutation in the exon 3 leading to Description an amino acid change in the JH7 domain Date 08-Sep-1998 (Rel. 1, Created) Date 08-Mar-2007 (Rel. 2, Last updated, Version 5) RefNumber [1] RefCrossRef PUBMED; 7659163 RefAuthors Macchi, P., Villa, A., Giliani, S., Sacco, M. G., Frattini, RefAuthors A., Porta, F., Ugazio, A. G.,Johnston, J. A., Candotti, F., RefAuthors O'Shea, J. J., Vezzoni, P., Notarangelo, L. D. RefTitle Mutations of Jak-3 gene in patients with autosomal severe RefTitle combined immune deficiency (SCID) RefLoc Nature 377:65-68 (1995) RefNumber [2] RefCrossRef PUBMED; 10075926 RefAuthors Cacalano, N. A., Migone, T. S., Bazan, F., Hanson, E. P., RefAuthors Chen, M., Candotti, F., O'Shea, J. J., Johnston, J. A. RefTitle Autosomal SCID caused by a point mutation in the RefTitle N-terminus of Jak3: mapping of the Jak3-receptor RefTitle interaction domain RefLoc EMBO J. 18:1549-1558(1999) RefNumber [3] RefCrossRef PUBMED; 10982185 RefAuthors Schumacher, R. F., Mella, P., Badolato, R., Fiorini, M., RefAuthors Savoldi, G., Giliani, S., Villa, A., Candotti, F., RefAuthors Tampalini, A., O'Shea, J. J., Notarangelo, L. D. RefTitle Complete genomic organization of the human JAK3 gene and RefTitle mutation analysis in severe combined immunodeficiency by RefTitle single-strand conformation polymorphism RefLoc Hum. Genet. 106:73-79(2000) RefNumber [4] RefCrossRef PUBMED; 11668610 RefAuthors Notarangelo, L. D., Mella, P., Jones, A., de Saint Basile, RefAuthors G., Savoldi, G., Cranston, T., Vihinen, M., Schumacher, R. RefAuthors F. RefTitle Mutations in severe combined immune deficiency (SCID) due RefTitle to JAK3 deficiency. RefLoc Hum Mutat:255-263 (2001) DB CrossRef OMIM; 600173.0001 DB CrossRef SWISSCHANGE; JAK3_HUMAN_10 DB CrossRef SWISS-PROT; P52333:100_100 FeatureHeader allele; 1 Feature dna; 1 Feature /rnalink: 2 Feature /name: point Feature /loc: IDRefSeq: D0095: 5688 Feature /change: a -> g Feature /genomic_region: exon; 3 Feature rna; 2 Feature /dnalink: 1 Feature /aalink: 3 Feature /name: missense Feature /loc: IDRefSeq: C0095: 358 Feature /codon: tac -> tgc; 2 Feature aa; 3 Feature /rnalink: 2 Feature /name: aa substitution Feature /loc: UniProt: P52333; JAK3_HUMAN: 100 Feature /change: Y -> C Feature /domain: JH7 FeatureHeader allele; 2 Feature dna; 4 Feature /rnalink: 5 Feature /name: point Feature /loc: IDRefSeq: D0095: 5688 Feature /change: a -> g Feature /genomic_region: exon; 3 Feature rna; 5 Feature /dnalink: 4 Feature /aalink: 6 Feature /name: missense Feature /loc: IDRefSeq: C0095: 358 Feature /codon: tac -> tgc; 2 Feature aa; 6 Feature /rnalink: 5 Feature /name: aa substitution Feature /loc: UniProt: P52333; JAK3_HUMAN: 100 Feature /change: Y -> C Feature /domain: JH7 mRNA level Much reduced Protein struct Prevents kinase-receptor interaction ref [2] Sex XY Age 5 months Parents Consanguineous Ethnic origin Italy Total lymphoc 4332 lymph/uL IgA 30 IgE 3 IgG 39 IgM 37 CD3 53% CD4 53% CD8 1.5% CD16/56 1% CD19 23% Therapy BMT: MUD Therapy BMT age: 12 months Therapy BMT outcome: A/w Response PHA: Absent // ID P151R(1),?; standard; MUTATION; JH6, Accession J0009 Systematic name Allele 1: g.6333C>G, c.452C>G, r.452c>g, p.Pro151Arg Original code P.M.C. ref [1]; P2 ref [2] Description Allele 1: A point mutation in the exon 5 leading to Description an amino acid change in the JH6 domain Description Allele 2; unknown Date 13-Oct-2000 (Rel. 1, Created) Date 08-Mar-2007 (Rel. 2, Last updated, Version 3) RefNumber [1] RefCrossRef PUBMED; 10982185 RefAuthors Schumacher, R. F., Mella, P., Badolato, R., Fiorini, M., RefAuthors Savoldi, G., Giliani, S., Villa, A., Candotti, F., RefAuthors Tampalini, A., O'Shea, J. J., Notarangelo, L. D. RefTitle Complete genomic organization of the human JAK3 gene and RefTitle mutation analysis in severe combined immunodeficiency by RefTitle single-strand conformation polymorphism RefLoc Hum. Genet. 106:73-79(2000) RefNumber [2] RefCrossRef PUBMED; 11668610 RefAuthors Notarangelo, L. D., Mella, P., Jones, A., de Saint Basile, RefAuthors G., Savoldi, G., Cranston, T., Vihinen, M., Schumacher, R. RefAuthors F. RefTitle Mutations in severe combined immune deficiency (SCID) due RefTitle to JAK3 deficiency. RefLoc Hum Mutat:255-263 (2001) FeatureHeader allele; 1 Feature dna; 1 Feature /rnalink: 2 Feature /name: point Feature /loc: IDRefSeq: D0095: 6333 Feature /change: c -> g Feature /genomic_region: exon; 5 Feature rna; 2 Feature /dnalink: 1 Feature /aalink: 3 Feature /name: missense Feature /loc: IDRefSeq: C0095: 511 Feature /codon: ccc -> cgc; 2 Feature aa; 3 Feature /rnalink: 2 Feature /name: aa substitution Feature /loc: UniProt: P52333; JAK3_HUMAN: 151 Feature /change: P -> R Feature /domain: JH6 FeatureHeader allele; 2 Feature dna; 4 Feature /rnalink: 5 Feature /name: unknown Feature rna; 5 Feature /dnalink: 4 Feature /aalink: 6 Feature /name: unknown Feature aa; 6 Feature /rnalink: 5 Feature /name: unknown Diagnosis T-B+ severe combined immunodeficiency Sex XX Age 10 months Ethnic origin Italy Total lymphoc 2520 lymph/uL IgA 11 IgE 49 IgG nd IgM 121 CD3 11% CD4 7% CD8 2% CD16/56 2% CD19 70% Therapy BMT: Ident Therapy BMT age: 11 months Therapy BMT outcome: A/w Response PHA: Absent // ID @G393X409(1),C565X(1); standard; MUTATION; JH4,JH2 Accession J0003 Systematic name Allele 1: g.9168dupG, c.1178dupG, r.1178dupg, p.Ser394fsX15 Systematic name Allele 2: g.11536C>A, c.1695C>A, r.1695c>a, p.Cys565X Original code C.M. ref [1]; @391X408,C565X(1); P21 ref [2]; @G392X409(1); Original code P1 ref [3] Description Allele 1: A frame shift duplication mutation in the exon 9 Description leading to a premature stop codon in the JH4 domain Description Allele 2: A point mutation in the exon 12 leading to a Description premature stop codon in the JH4 domain Date 08-Sep-1998 (Rel. 1, Created) Date 09-Mar-2007 (Rel. 2, Last updated, Version 6) RefNumber [1] RefCrossRef PUBMED; 7481768 RefAuthors Russell, S. M., Tayebi, N., Nakajima, H., Riedy, M. C., RefAuthors Roberts, J. L., Aman, M. A., Migone, T.-S., Noguchi, M., RefAuthors Markert, M. L., Buckley, R. H., O'Shea, J. J., RefAuthors Leonard, W. J. RefTitle Mutation of Jak3 in a patient with SCID: Essential role of RefTitle Jak3 in lymphoid development RefLoc Science 270:797-800 (1995) RefNumber [2] RefCrossRef PUBMED; 11668610 RefAuthors Notarangelo, L. D., Mella, P., Jones, A., de Saint Basile, RefAuthors G., Savoldi, G., Cranston, T., Vihinen, M., Schumacher, R. RefAuthors F. RefTitle Mutations in severe combined immune deficiency (SCID) due RefTitle to JAK3 deficiency. RefLoc Hum Mutat 18:255-263 (2001) RefNumber [3] RefCrossRef PUBMED; 15220007 RefAuthors O'Shea, J. J., Husa, M., Li, D., Hofmann, S. R., Watford, RefAuthors W., Roberts, J. L., Buckley, R. H., Changelian, P., RefAuthors Candotti, F. RefTitle Jak3 and the pathogenesis of severe combined RefTitle immunodeficiency. RefLoc Mol Immunol 41:727-737 (2004) DB CrossRef OMIM; 600173.0003 DB CrossRef OMIM; 600173.0004 FeatureHeader allele; 1 Feature dna; 1 Feature /rnalink: 2 Feature /name: duplication Feature /loc: IDRefSeq: D0095: 9169 Feature /change: +g Feature /genomic_region: exon; 9 Feature rna; 2 Feature /dnalink: 1 Feature /aalink: 3 Feature /name: frameshift Feature /loc: IDRefSeq: C0095: 1238 Feature aa; 3 Feature /rnalink: 2 Feature /name: out of frame translation; premature termination Feature /loc: UniProt: P52333; JAK3_HUMAN: 393 Feature /change: G -> GLTSWLLCSP PQPPGLX Feature /domain: JH4 FeatureHeader allele; 2 Feature dna; 4 Feature /rnalink: 5 Feature /name: point Feature /loc: IDRefSeq: D0095: 11536 Feature /change: c -> a Feature /genomic_region: exon; 12 Feature rna; 5 Feature /dnalink: 4 Feature /aalink: 6 Feature /name: nonsense Feature /loc: IDRefSeq: C0095: 1754 Feature /codon: tgc -> tga; 3 Feature aa; 6 Feature /rnalink: 5 Feature /name: out of frame translation; premature termination Feature /loc: UniProt: P52333; JAK3_HUMAN: 565 Feature /change: C -> X Feature /domain: JH2 Diagnosis T-B+ severe combined immunodeficiency Sex XX Total lymphoc ca.3000 lymph/uL IgA nd IgE 2U/mL IgG nd IgM 50 CD3 204 CD4 204 CD8 58 CD16/56 29 CD19 1274 Response PHA: minimal mRNA level Absent Protein level Absent // ID R445X(1a),R445X(1a); standard; MUTATION; JH3,JH3 Accession J0010 Systematic name Allele 1 and 2: g.9889C>T, c.1333C>T, r.1333c>u, p.Arg445X Original code D.R. ref [1]; P3 ref [3] Description Allele 1 and 2: A point mutation in the exon 10 leading to Description a premature stop codon in the JH3 domain Date 13-Oct-2000 (Rel. 1, Created) Date 09-Mar-2007 (Rel. 2, Last updated, Version 3) RefNumber [1] RefCrossRef PUBMED; 10982185 RefAuthors Schumacher, R. F., Mella, P., Badolato, R., Fiorini, M., RefAuthors Savoldi, G., Giliani, S., Villa, A., Candotti, F., RefAuthors Tampalini, A., O'Shea, J. J., Notarangelo, L. D. RefTitle Complete genomic organization of the human JAK3 gene and RefTitle mutation analysis in severe combined immunodeficiency by RefTitle single-strand conformation polymorphism RefLoc Hum. Genet. 106:73-79(2000) RefNumber [2] RefCrossRef PUBMED; 10900158 RefAuthors Vihinen, M., Villa, A., Mella, P., Schumacher, R. F., RefAuthors Savoldi, G., O'Shea, J. J., Candotti, F., Notarangelo, RefAuthors L. D. RefTitle Molecular modeling of the Jak3 kinase domains and RefTitle structural basis for severe combined immunodeficiency RefLoc Clin. Immunol. 96:108-118(2000) RefNumber [3] RefCrossRef PUBMED; 11668610 RefAuthors Notarangelo, L. D., Mella, P., Jones, A., de Saint Basile, RefAuthors G., Savoldi, G., Cranston, T., Vihinen, M., Schumacher, R. RefAuthors F. RefTitle Mutations in severe combined immune deficiency (SCID) due RefTitle to JAK3 deficiency. RefLoc Hum Mutat:255-263 (2001) DB CrossRef OMIM; 600173.0005 FeatureHeader allele; 1 Feature dna; 1 Feature /rnalink: 2 Feature /name: point Feature /loc: IDRefSeq: D0095: 9889 Feature /change: c -> t Feature /CpG; 1 Feature /genomic_region: exon; 10 Feature rna; 2 Feature /dnalink: 1 Feature /aalink: 3 Feature /name: nonsense Feature /loc: IDRefSeq: C0095: 1392 Feature /codon: cga -> tga; 1 Feature aa; 3 Feature /rnalink: 2 Feature /name: out of frame translation; premature termination Feature /loc: UniProt: P52333; JAK3_HUMAN: 445 Feature /change: R -> X Feature /domain: JH3 FeatureHeader allele; 2 Feature dna; 4 Feature /rnalink: 5 Feature /name: point Feature /loc: IDRefSeq: D0095: 9889 Feature /change: c -> t Feature /CpG; 1 Feature /genomic_region: exon; 10 Feature rna; 5 Feature /dnalink: 4 Feature /aalink: 6 Feature /name: nonsense Feature /loc: IDRefSeq: C0095: 1392 Feature /codon: cga -> tga; 1 Feature aa; 6 Feature /rnalink: 5 Feature /name: out of frame translation; premature termination Feature /loc: UniProt: P52333; JAK3_HUMAN: 445 Feature /change: R -> X Feature /domain: JH3 Protein struct Allele 1 and 2; Truncation ref [2] Diagnosis T-B+ severe combined immunodeficiency Sex XX Age 4 months Ethnic origin Italy Relative JAK3; J0011 first degree cousin Total lymphoc 612 lymph/uL IgA 6 IgE nd IgG 66 IgM 12 CD3 11% CD4 1% CD8 8% CD16/56 34% CD19 28% Therapy BMT: MUD Therapy BMT age: 9 months Therapy BMT outcome: A/w Response PHA: Absent // ID R445X(1b),R445X(1b); standard; MUTATION; JH3,JH3 Accession J0011 Systematic name Allele 1 and 2: g.9889C>T, c.1333C>T, r.1333c>u, p.Arg445X Original code M.N. ref [1]; P4 ref [3] Description Allele 1 and 2: A point mutation in the exon 10 leading to Description a premature stop codon in the JH3 domain Date 13-Oct-2000 (Rel. 1, Created) Date 09-Mar-2007 (Rel. 2, Last updated, Version 3) RefNumber [1] RefCrossRef PUBMED; 10982185 RefAuthors Schumacher, R. F., Mella, P., Badolato, R., Fiorini, M., RefAuthors Savoldi, G., Giliani, S., Villa, A., Candotti, F., RefAuthors Tampalini, A., O'Shea, J. J., Notarangelo, L. D. RefTitle Complete genomic organization of the human JAK3 gene and RefTitle mutation analysis in severe combined immunodeficiency by RefTitle single-strand conformation polymorphism RefLoc Hum. Genet. 106:73-79(2000) RefNumber [2] RefCrossRef PUBMED; 10900158 RefAuthors Vihinen, M., Villa, A., Mella, P., Schumacher, R. F., RefAuthors Savoldi, G., O'Shea, J. J., Candotti, F., Notarangelo, RefAuthors L. D. RefTitle Molecular modeling of the Jak3 kinase domains and RefTitle structural basis for severe combined immunodeficiency RefLoc Clin. Immunol. 96:108-118(2000) RefNumber [3] RefCrossRef PUBMED; 11668610 RefAuthors Notarangelo, L. D., Mella, P., Jones, A., de Saint Basile, RefAuthors G., Savoldi, G., Cranston, T., Vihinen, M., Schumacher, R. RefAuthors F. RefTitle Mutations in severe combined immune deficiency (SCID) due RefTitle to JAK3 deficiency. RefLoc Hum Mutat:255-263 (2001) DB CrossRef OMIM; 600173.0005 FeatureHeader allele; 1 Feature dna; 1 Feature /rnalink: 2 Feature /name: point Feature /loc: IDRefSeq: D0095: 9889 Feature /change: c -> t Feature /CpG; 1 Feature /genomic_region: exon; 10 Feature rna; 2 Feature /dnalink: 1 Feature /aalink: 3 Feature /name: nonsense Feature /loc: IDRefSeq: C0095: 1392 Feature /codon: cga -> tga; 1 Feature aa; 3 Feature /rnalink: 2 Feature /name: out of frame translation; premature termination Feature /loc: UniProt: P52333; JAK3_HUMAN: 445 Feature /change: R -> X Feature /domain: JH3 FeatureHeader allele; 2 Feature dna; 4 Feature /rnalink: 5 Feature /name: point Feature /loc: IDRefSeq: D0095: 9889 Feature /change: c -> t Feature /CpG; 1 Feature /genomic_region: exon; 10 Feature rna; 5 Feature /dnalink: 4 Feature /aalink: 6 Feature /name: nonsense Feature /loc: IDRefSeq: C0095: 1392 Feature /codon: cga -> tga; 1 Feature aa; 6 Feature /rnalink: 5 Feature /name: out of frame translation; premature termination Feature /loc: UniProt: P52333; JAK3_HUMAN: 445 Feature /change: R -> X Feature /domain: JH3 Protein struct Allele 1 and 2; Truncation ref [2] Diagnosis T-B+ severe combined immunodeficiency Sex XX Age 1 months Ethnic origin Italy Relative JAK3; J0010 first degree cousin Total lymphoc 612 lymph/uL IgA nd IgE nd IgG nd IgM nd CD3 <3% CD4 nd CD8 nd CD16/56 nd CD19 92% Therapy BMT: None Therapy BMT outcome: Deceased Response PHA: nd // ID R445X(2),C759R(1); standard; MUTATION; JH3,JH2 Accession J0005 Systematic name Allele 1: g.9889C>T, c.1333C>T, r.1333c>u, p.Arg445X Systematic name Allele 2: g.14828T>C, c.2275T>C, r.2275u>c, p.Cys759Arg Original code L.P. ref [1]; 445X,C759R(1); F1PII,1 ref [2]; P5 ref [6] Description Allele 1: A point mutation in the exon 10 leading to a Description premature stop codon in the JH3 domain Description Allele 2: A point mutation in the exon 17 leading to an Description amino acid change in the JH3 domain Date 08-Sep-1998 (Rel. 1, Created) Date 12-Mar-2007 (Rel. 2, Last updated, Version 5) RefNumber [1] RefCrossRef PUBMED; 9354668 RefAuthors Candotti, F., Oakes, S. A., Johnston, J. A., Giliani, S., RefAuthors Schumacher, R. F., Mella, P., Fiorini, M., Ugazio, A. G., RefAuthors Badolato, R., Notarangelo, L. D., Bozzi, F., Macchi, P., RefAuthors Strina, D., Vezzoni, P., Blaese, R. M., O'Shea, J. J., RefAuthors Villa, A. RefTitle Structural and functional basis for JAK3-deficient severe RefTitle combined immunodeficiency RefLoc Blood 90:3996-4003 (1997) RefNumber [2] RefCrossRef PUBMED; 10419614 RefAuthors Schumacher, R. F., Mella, P., Lalatta, F., Fiorini, M., RefAuthors Giliani, S., Villa, A., Candotti, F., Notarangelo, L. D. RefTitle Prenatal diagnosis of JAK3 deficient SCID RefLoc Prenat. Diagn. 19:653-656(1999) RefNumber [3] RefCrossRef PUBMED; 10629052 RefAuthors Chen, M., Cheng, A., Candotti, F., Zhou, Y. J., Hymel, A., RefAuthors Fasth, A., Notarangelo, L. D., O'Shea, J. J. RefTitle Complex effects of naturally occurring mutations in the RefTitle JAK3 pseudokinase domain: evidence for interactions RefTitle between the kinase and pseudokinase domains RefLoc Mol. Cell. Biol. 20:947-956(2000) RefNumber [4] RefCrossRef PUBMED; 10982185 RefAuthors Schumacher, R. F., Mella, P., Badolato, R., Fiorini, M., RefAuthors Savoldi, G., Giliani, S., Villa, A., Candotti, F., RefAuthors Tampalini, A., O'Shea, J. J., Notarangelo, L. D. RefTitle Complete genomic organization of the human JAK3 gene and RefTitle mutation analysis in severe combined immunodeficiency by RefTitle single-strand conformation polymorphism RefLoc Hum. Genet. 106:73-79(2000) RefNumber [5] RefCrossRef PUBMED; 10900158 RefAuthors Vihinen, M., Villa, A., Mella, P., Schumacher, R. F., RefAuthors Savoldi, G., O'Shea, J. J., Candotti, F., Notarangelo, RefAuthors L. D. RefTitle Molecular modeling of the Jak3 kinase domains and RefTitle structural basis for severe combined immunodeficiency RefLoc Clin. Immunol. 96:108-118(2000) RefNumber [6] RefCrossRef PUBMED; 11668610 RefAuthors Notarangelo, L. D., Mella, P., Jones, A., de Saint Basile, RefAuthors G., Savoldi, G., Cranston, T., Vihinen, M., Schumacher, R. RefAuthors F. RefTitle Mutations in severe combined immune deficiency (SCID) due RefTitle to JAK3 deficiency. RefLoc Hum Mutat:255-263 (2001) FeatureHeader allele; 1 Feature dna; 1 Feature /rnalink: 2 Feature /name: point Feature /loc: IDRefSeq: D0095: 9889 Feature /change: c -> t Feature /CpG; 1 Feature /genomic_region: exon; 10 Feature rna; 2 Feature /dnalink: 1 Feature /aalink: 3 Feature /name: nonsense Feature /loc: IDRefSeq: C0095: 1392 Feature /codon: cga -> tga; 1 Feature aa; 3 Feature /rnalink: 2 Feature /name: out of frame translation; premature termination Feature /loc: UniProt: P52333; JAK3_HUMAN: 445 Feature /change: R -> X Feature /domain: JH3 FeatureHeader allele; 2 Feature dna; 4 Feature /rnalink: 5 Feature /name: point Feature /loc: IDRefSeq: D0095: 14828 Feature /change: t -> c Feature /genomic_region: exon; 17 Feature rna; 5 Feature /dnalink: 4 Feature /aalink: 6 Feature /name: missense Feature /loc: IDRefSeq: C0095: 2334 Feature /codon: tgc -> cgc; 1 Feature aa; 6 Feature /rnalink: 5 Feature /name: aa substitution Feature /loc: UniProt: P52333; JAK3_HUMAN: 759 Feature /change: C -> R Feature /domain: JH2 Protein level reduced Kinase activity inactive Protein struct Allele 1; Truncation ref [5] Protein struct Allele 2; Sterical clash ref [5] Diagnosis T-B+ severe combined immunodeficiency Symptoms lower resp; Sex XY Age 2 months Ethnic origin Italy Total lymphoc 2304 lymph/uL IgA 6 IgE 2 IgG 224 IgM 36 CD3 0.5% CD4 0.5% CD8 0.5% CD16/56 1% CD19 93% Therapy BMT: Haplo Therapy BMT age: 3 months Therapy BMT outcome: A/w Response PHA: Absent // ID E481G(1),#E481-115(1); standard; MUTATION; JH3,JH3 Accession J0004 Systematic name Allele 1: g.11084A>G, c.1442A>G, r.1442a>g, p.Glu481Gly Systematic name Allele 2: g.11084_11428del, c.1442_1786del, r.1442_1786del, Systematic name p.Glu481_Ser596del Original code L.E. ref [1,2]; E481G,#482-114(1); P7 ref [4] Description Allele 1: A point mutation in the exon 11 leading to an Description amino acid change in the JH3 domain Description Allele 2; inframe deletion of the exons 11, 12 and 13 Description in the JH3 and JH2 domain Date 08-Sep-1998 (Rel. 1, Created) Date 12-Mar-2007 (Rel. 2, Last updated, Version 5) RefNumber [1] RefCrossRef PUBMED; 9354668 RefAuthors Candotti, F., Oakes, S. A., Johnston, J. A., Giliani, S., RefAuthors Schumacher, R. F., Mella, P., Fiorini, M., Ugazio, A. G., RefAuthors Badolato, R., Notarangelo, L. D., Bozzi, F., Macchi, P., RefAuthors Strina, D., Vezzoni, P., Blaese, R. M., O'Shea, J. J., RefAuthors Villa, A. RefTitle Structural and functional basis for JAK3-deficient severe RefTitle combined immunodeficiency RefLoc Blood 90:3996-4003 (1997) RefNumber [2] RefCrossRef PUBMED; 10982185 RefAuthors Schumacher, R. F., Mella, P., Badolato, R., Fiorini, M., RefAuthors Savoldi, G., Giliani, S., Villa, A., Candotti, F., RefAuthors Tampalini, A., O'Shea, J. J., Notarangelo, L. D. RefTitle Complete genomic organization of the human JAK3 gene and RefTitle mutation analysis in severe combined immunodeficiency by RefTitle single-strand conformation polymorphism RefLoc Hum. Genet. 106:73-79(2000) RefNumber [3] RefCrossRef PUBMED; 10900158 RefAuthors Vihinen, M., Villa, A., Mella, P., Schumacher, R. F., RefAuthors Savoldi, G., O'Shea, J. J., Candotti, F., Notarangelo, RefAuthors L. D. RefTitle Molecular modeling of the Jak3 kinase domains and RefTitle structural basis for severe combined immunodeficiency RefLoc Clin. Immunol. 96:108-118(2000) RefNumber [4] RefCrossRef PUBMED; 11668610 RefAuthors Notarangelo, L. D., Mella, P., Jones, A., de Saint Basile, RefAuthors G., Savoldi, G., Cranston, T., Vihinen, M., Schumacher, R. RefAuthors F. RefTitle Mutations in severe combined immune deficiency (SCID) due RefTitle to JAK3 deficiency. RefLoc Hum Mutat:255-263 (2001) FeatureHeader allele; 1 Feature dna; 1 Feature /rnalink: 2 Feature /name: point Feature /loc: IDRefSeq: D0095: 11084 Feature /change: a -> g Feature /genomic_region: exon; 11 Feature rna; 2 Feature /dnalink: 1 Feature /aalink: 3 Feature /name: missense Feature /loc: IDRefSeq: C0095: 1501 Feature /codon: gaa -> gga; 2 Feature aa; 3 Feature /rnalink: 2 Feature /name: aa substitution Feature /loc: UniProt: P52333; JAK3_HUMAN: 481 Feature /change: E -> G Feature /domain: JH3 FeatureHeader allele; 2 Feature dna; 4 Feature /rnalink: 5 Feature /name: deletion Feature /loc: IDRefSeq: D0095: 11084..11542 Feature /genomic_region: exon; 11, intron; 11, exon; 12 Feature rna; 5 Feature /dnalink: 4 Feature /aalink: 6 Feature /name: inframe deletion Feature /loc: IDRefSeq: C0095: 1501..1845 Feature /change: -aaaagtccaa cctgatcgtg gtccagagag gtcacagccc Feature /change: acccacatca tccttggttc agccccaatc ccaataccag Feature /change: ctgagtcaga tgacatttca caagatccct gctgacagcc Feature /change: tggagtggca tgagaacctg ggccatgggt ccttcaccaa Feature /change: gatttaccgg ggctgtcgcc atgaggtggt ggatggggag Feature /change: gcccgaaaga cagaggtgct gctgaaggtc atggatgcca Feature /change: agcacaagaa ctgcatggag tcattcctgg aagcagcgag Feature /change: cttgatgagc caagtgtcgt accggcatct cgtgctgctc Feature /change: cacggcgtgt gcatggctgg agaca Feature /note: deletion of the exons 11 and 12 and skipping of Feature /note: the exon 13 Feature aa; 6 Feature /rnalink: 5 Feature /name: deletion; inframe Feature /loc: UniProt: P52333; JAK3_HUMAN: 481..596 Feature /change: -EKSNLIVVQR GHSPPTSSLV QPQSQYQLSQ MTFHKIPADS Feature /change: LEWHENLGHG SFTKIYRGCR HEVVDGEARK TEVLLKVMDA Feature /change: KHKNCMESFL EAASLMSQVS YRHLVLLHGV CMAGDS Feature /domain: JH3, JH2 Protein level reduced Protein struct Allele 2; Fold alteration ref [3] Diagnosis T-B+ severe combined immunodeficiency Symptoms lower resp; Sex XY Age 1.5 months Ethnic origin Italy Total lymphoc 3000 lymph/uL IgA 6 IgE 1100 IgG 865 IgM 117 CD3 2% CD4 1% CD8 2% CD16/56 13% CD19 74% Therapy BMT: Haplo Therapy BMT age: 15 months Therapy BMT outcome: Deceased Response PHA: Absent // ID W523X(1),W523X(1); standard; MUTATION; JH2,JH2 Accession J0030 Systematic name Allele 1 and 2: g.11210G>A, c.1568G>A, r.1568g>a, p.Trp523X Original code 5-month-old female Description Allele 1 and 2: A point mutation in the exon 11 leading to Description a premature stop codon in the JH2 domain Date 14-Mar-2007 (Rel. 2, Created) Date 14-Mar-2007 (Rel. 2, Last updated, Version 1) RefNumber [1] RefCrossRef PUBMED; 16190968 RefAuthors Uchiyama, T., Kumaki, S., Fujiwara, M., Nishida, Y., RefAuthors Hakozaki, I., Imai, K., Du, W., Yoshinari, M., Sasahara, RefAuthors Y., Tsuchiya, S. RefTitle A novel JAK3 mutation in a japanese patient with severe RefTitle combined immunodeficiency. RefLoc Pediatr Int:575-578 (2005) FeatureHeader allele; 1 Feature dna; 1 Feature /rnalink: 2 Feature /name: point Feature /loc: IDRefSeq: D0095: 11210 Feature /change: g -> a Feature /genomic_region: exon; 11 Feature rna; 2 Feature /dnalink: 1 Feature /aalink: 3 Feature /name: nonsense Feature /loc: IDRefSeq: C0095: 1627 Feature /codon: tgg -> tag; 2 Feature aa; 3 Feature /rnalink: 2 Feature /name: out of frame translation; premature termination Feature /loc: UniProt: P52333; JAK3_HUMAN: 523 Feature /change: W -> X Feature /domain: JH2 FeatureHeader allele; 2 Feature dna; 4 Feature /rnalink: 5 Feature /name: point Feature /loc: IDRefSeq: D0095: 11210 Feature /change: g -> a Feature /genomic_region: exon; 11 Feature rna; 5 Feature /dnalink: 4 Feature /aalink: 6 Feature /name: nonsense Feature /loc: IDRefSeq: C0095: 1627 Feature /codon: tgg -> tag; 2 Feature aa; 6 Feature /rnalink: 5 Feature /name: out of frame translation; premature termination Feature /loc: UniProt: P52333; JAK3_HUMAN: 523 Feature /change: W -> X Feature /domain: JH2 Diagnosis T-B- severe combined immunodeficiency Symptoms Others: Symptoms lower respiratory infection Sex XX Ethnic origin Mongoloid; Japan // ID R582W(1),R582W(1); standard; MUTATION; JH2,JH2 Accession J0008 Systematic name Allele 1 and 2: g.12303C>T, [c.1744C>T; c.1744C>T + Systematic name c.1797_2009del; c.1744C>T + c.1702_1786del], [p.R582W; Systematic name p.Ser568_Glu639del; p.Ser568fsX12] Original code A.J. ref [3]; P8 ref [5] Description Allele 1 and 2; point mutation in the exon 13 leading Description to a single amino acid change and two alternative splice Description variants Date 08-Sep-1998 (Rel. 1, Created) Date 12-Mar-2007 (Rel. 2, Last updated, Version 5) RefNumber [1] RefCrossRef PUBMED; 785357 RefAuthors Geha, R. S., Malakian, A., LeFranc, G., Chayban, D., RefAuthors Serre, J. L. RefTitle Immunologic reconstitution in severe combined RefTitle immunodeficiency following transplantation with parental RefTitle bone marrow RefLoc Pediatrics 58:451-455(1976) RefNumber [2] RefCrossRef PUBMED; 9753072 RefAuthors Bozzi, F., Lefranc, G., Villa, A., Badolato, R., RefAuthors Schumacher, R. F., Khalil, G., Loislet, J., Bresciani, RefAuthors S., O'Shea, J. J., Vezzoni, P., Notarangelo, L. D., RefAuthors Candotti, F. RefTitle Molecular and biochemical characterization of JAK3 RefTitle deficiency in a patient with severe combined RefTitle immunodeficiency over 20 years after bone marrow RefTitle transplantation: implications for treatment RefLoc Br. J. Haematol 102: 1363-6 (1998) RefNumber [3] RefCrossRef PUBMED; 10982185 RefAuthors Schumacher, R. F., Mella, P., Badolato, R., Fiorini, M., RefAuthors Savoldi, G., Giliani, S., Villa, A., Candotti, F., RefAuthors Tampalini, A., O'Shea, J. J., Notarangelo, L. D. RefTitle Complete genomic organization of the human JAK3 gene and RefTitle mutation analysis in severe combined immunodeficiency by RefTitle single-strand conformation polymorphism RefLoc Hum. Genet. 106:73-79(2000) RefNumber [4] RefCrossRef PUBMED; 10900158 RefAuthors Vihinen, M., Villa, A., Mella, P., Schumacher, R. F., RefAuthors Savoldi, G., O'Shea, J. J., Candotti, F., Notarangelo, RefAuthors L. D. RefTitle Molecular modeling of the Jak3 kinase domains and RefTitle structural basis for severe combined immunodeficiency RefLoc Clin. Immunol. 96:108-118(2000) RefNumber [5] RefCrossRef PUBMED; 11668610 RefAuthors Notarangelo, L. D., Mella, P., Jones, A., de Saint Basile, RefAuthors G., Savoldi, G., Cranston, T., Vihinen, M., Schumacher, R. RefAuthors F. RefTitle Mutations in severe combined immune deficiency (SCID) due RefTitle to JAK3 deficiency. RefLoc Hum Mutat:255-263 (2001) Feature dna; 1 Feature /rnalink: 2 Feature /name: point Feature /loc: IDRefSeq: D0095: 12303 Feature /change: c -> t Feature /CpG; 1 Feature /genomic_region: exon; 13 Feature dna; 2 Feature /rnalink: 5 Feature /name: deletion Feature /loc: IDRefSeq: D0095: unknown Feature /genomic_region: exon; 13, exon; 14 Feature dna; 3 Feature /rnalink: 6 Feature /name: deletion Feature /loc: IDRefSeq: D0095: unknown Feature /genomic_region: exon; 13 Feature rna; 4 Feature /dnalink: 1 Feature /aalink: 7 Feature /name: missense Feature /loc: IDRefSeq: C0095: 1803 Feature /codon: cgg -> tgg; 1 Feature rna; 5 Feature /dnalink: 2 Feature /aalink: 8 Feature /name: inframe deletion; alternative splicing Feature /loc: IDRefSeq: C0095: 1761..1973 Feature /change: -tcattcctgg aagcagcgag cttgatgagc caagtgtcgt Feature /change: accggcatct cgtgctgctc cacggcgtgt gcatggctgg Feature /change: agacagcacc atggtgcagg aatttgtaca cctgggggcc Feature /change: atagacatgt atctgcgaaa acgtggccac ctggtgccag Feature /change: ccagctggaa gctgcaggtg gtcaaacagc tggcctacgc Feature /change: cctcaactat ctg Feature /note: deletion of the exons 13 and 14 Feature rna; 6 Feature /dnalink: 3 Feature /aalink: 9 Feature /name: frameshift; alternative splicing Feature /loc: IDRefSeq: C0095: 1761..1845 Feature /change: -tcattcctgg aagcagcgag cttgatgagc caagtgtcgt Feature /change: accggcatct cgtgctgctc cacggcgtgt gcatggctgg Feature /change: agaca Feature /note: deletion of the exon 13 Feature aa; 7 Feature /rnalink: 4 Feature /name: aa substitution Feature /loc: UniProt: P52333; JAK3_HUMAN: 582 Feature /change: R -> W Feature /domain: JH2 Feature aa; 8 Feature /rnalink: 5 Feature /name: deletion; inframe Feature /loc: UniProt: P52333; JAK3_HUMAN: 568..638 Feature /change: -SFLEAASLMS QVSYRHLVLL HGVCMAGDST MVQEFVHLGA Feature /change: IDMYLRKRGH LVPASWKLQV VKQLAYALNY L Feature /domain: JH2 Feature aa; 9 Feature /rnalink: 6 Feature /name: out of frame translation; premature termination Feature /loc: UniProt: P52333; JAK3_HUMAN: 568..596 Feature /change: SFLEAASLMS QVSYRHLVLL HGVCMAGDS Feature /change: -> APWCRNLYTW GPX Feature /domain: JH2 FeatureHeader allele; 2 Feature dna; 10 Feature /rnalink: 13 Feature /name: point Feature /loc: IDRefSeq: D0095: 12303 Feature /change: c -> t Feature /CpG; 1 Feature /genomic_region: exon; 13 Feature dna; 11 Feature /rnalink: 14 Feature /name: deletion Feature /loc: IDRefSeq: D0095: unknown Feature /genomic_region: exon; 13, exon; 14 Feature dna; 12 Feature /rnalink: 15 Feature /name: deletion Feature /loc: IDRefSeq: D0095: unknown Feature /genomic_region: exon; 13 Feature rna; 13 Feature /dnalink: 10 Feature /aalink: 16 Feature /name: missense Feature /loc: IDRefSeq: C0095: 1803 Feature /codon: cgg -> tgg; 1 Feature rna; 14 Feature /dnalink: 11 Feature /aalink: 17 Feature /name: inframe deletion; alternative splicing Feature /loc: IDRefSeq: C0095: 1761..1973 Feature /change: -tcattcctgg aagcagcgag cttgatgagc caagtgtcgt Feature /change: accggcatct cgtgctgctc cacggcgtgt gcatggctgg Feature /change: agacagcacc atggtgcagg aatttgtaca cctgggggcc Feature /change: atagacatgt atctgcgaaa acgtggccac ctggtgccag Feature /change: ccagctggaa gctgcaggtg gtcaaacagc tggcctacgc Feature /change: cctcaactat ctg Feature /note: deletion of the exons 13 and 14 Feature rna; 15 Feature /dnalink: 12 Feature /aalink: 18 Feature /name: frameshift; alternative splicing Feature /loc: IDRefSeq: C0095: 1761..1845 Feature /change: -tcattcctgg aagcagcgag cttgatgagc caagtgtcgt Feature /change: accggcatct cgtgctgctc cacggcgtgt gcatggctgg Feature /change: agaca Feature /note: deletion of the exon 13 Feature aa; 16 Feature /rnalink: 13 Feature /name: aa substitution Feature /loc: UniProt: P52333; JAK3_HUMAN: 582 Feature /change: R -> W Feature /domain: JH2 Feature aa; 17 Feature /rnalink: 14 Feature /name: deletion; inframe Feature /loc: UniProt: P52333; JAK3_HUMAN: 568..638 Feature /change: -SFLEAASLMS QVSYRHLVLL HGVCMAGDST MVQEFVHLGA Feature /change: IDMYLRKRGH LVPASWKLQV VKQLAYALNY L Feature /domain: JH2 Feature aa; 18 Feature /rnalink: 15 Feature /name: out of frame translation; premature termination Feature /loc: UniProt: P52333; JAK3_HUMAN: 568..596 Feature /change: SFLEAASLMS QVSYRHLVLL HGVCMAGDS Feature /change: -> APWCRNLYTW GPX Feature /domain: JH2 Protein level reduced Protein struct Allele 1 and 2; Altered ligand interaction ref [3] Diagnosis T-B+ severe combined immunodeficiency Sex XX Age 9 months Parents Consanguineous Ethnic origin Lebanon Total lymphoc 792 lymph/uL IgA nd IgE nd IgG Absent IgM nd CD3 0% CD4 nd CD8 nd CD16/56 nd CD19 >80 Therapy BMT: Ident (father) Therapy BMT age: 9 months Therapy BMT outcome: A/w Response PHA: Absent // ID G589S(1),G589S(1); standard; MUTATION; JH2,JH2 Accession J0026 Systematic name Allele 1 and 2: g.12324G>A, c.1765G>A, r.1765g>a, Systematic name p.Gly589Ser Original code Patient 3 Description Allele 1 and 2: A point mutation in the exon 13 leading to Description an amino acid change in the JH2 domain Date 14-Mar-2007 (Rel. 2, Created) Date 14-Mar-2007 (Rel. 2, Last updated, Version 1) RefNumber [1] RefCrossRef PUBMED; 14615376 RefAuthors Roberts, J. L., Lengi, A., Brown, S. M., Chen, M., Zhou, RefAuthors Y. J., O'Shea, J. J., Buckley, R. H. RefTitle Janus kinase 3 (JAK3) deficiency: clinical, immunologic, RefTitle and molecular analyses of 10 patients and outcomes of stem RefTitle cell transplantation. RefLoc Blood:2009-2018 (2004) FeatureHeader allele; 1 Feature dna; 1 Feature /rnalink: 2 Feature /name: point Feature /loc: IDRefSeq: D0095: 12324 Feature /change: g -> a Feature /CpG; 2 Feature /genomic_region: exon; 13 Feature rna; 2 Feature /dnalink: 1 Feature /aalink: 3 Feature /name: missense Feature /loc: IDRefSeq: C0095: 1824 Feature /codon: ggc -> agc; 1 Feature aa; 3 Feature /rnalink: 2 Feature /name: aa substitution Feature /loc: UniProt: P52333; JAK3_HUMAN: 589 Feature /change: G -> S Feature /domain: JH2 FeatureHeader allele; 2 Feature dna; 4 Feature /rnalink: 5 Feature /name: point Feature /loc: IDRefSeq: D0095: 12324 Feature /change: g -> a Feature /CpG; 2 Feature /genomic_region: exon; 13 Feature rna; 5 Feature /dnalink: 4 Feature /aalink: 6 Feature /name: missense Feature /loc: IDRefSeq: C0095: 1824 Feature /codon: ggc -> agc; 1 Feature aa; 6 Feature /rnalink: 5 Feature /name: aa substitution Feature /loc: UniProt: P52333; JAK3_HUMAN: 589 Feature /change: G -> S Feature /domain: JH2 Diagnosis T-B- severe combined immunodeficiency // ID #V590-7(1),#V590-7(1); standard; MUTATION; JH2,JH2 Accession J0006 Systematic name Allele 1 and 2: g.12326C>T, [c.1767C>T + c.1766_1786del], Systematic name p.Val590_Ser596del Original code N.K. ref [1,3]; #585-7,#585-7; P9 ref [5] Description Allele 1 and 2; point mutation create a new cryptic Description splice-site and leading to deletion in JH2 domain Date 08-Sep-1998 (Rel. 1, Created) Date 12-Mar-2007 (Rel. 2, Last updated, Version 5) RefNumber [1] RefCrossRef PUBMED; 9354668 RefAuthors Candotti, F., Oakes, S. A., Johnston, J. A., Giliani, S., RefAuthors Schumacher, R. F., Mella, P., Fiorini, M., Ugazio, A. G., RefAuthors Badolato, R., Notarangelo, L. D., Bozzi, F., Macchi, P., RefAuthors Strina, D., Vezzoni, P., Blaese, R. M., O'Shea, J. J., RefAuthors Villa, A. RefTitle Structural and functional basis for JAK3-deficient severe RefTitle combined immunodeficiency RefLoc Blood 90:3996-4003 (1997) RefNumber [2] RefCrossRef PUBMED; 10629052 RefAuthors Chen, M., Cheng, A., Candotti, F., Zhou, Y. J., Hymel, A., RefAuthors Fasth, A., Notarangelo, L. D., O'Shea, J. J. RefTitle Complex effects of naturally occurring mutations in the RefTitle JAK3 pseudokinase domain: evidence for interactions RefTitle between the kinase and pseudokinase domains RefLoc Mol. Cell. Biol. 20:947-956(2000) RefNumber [3] RefCrossRef PUBMED; 10982185 RefAuthors Schumacher, R. F., Mella, P., Badolato, R., Fiorini, M., RefAuthors Savoldi, G., Giliani, S., Villa, A., Candotti, F., RefAuthors Tampalini, A., O'Shea, J. J., Notarangelo, L. D. RefTitle Complete genomic organization of the human JAK3 gene and RefTitle mutation analysis in severe combined immunodeficiency by RefTitle single-strand conformation polymorphism RefLoc Hum. Genet. 106:73-79(2000) RefNumber [4] RefCrossRef PUBMED; 10900158 RefAuthors Vihinen, M., Villa, A., Mella, P., Schumacher, R. F., RefAuthors Savoldi, G., O'Shea, J. J., Candotti, F., Notarangelo, RefAuthors L. D. RefTitle Molecular modeling of the Jak3 kinase domains and RefTitle structural basis for severe combined immunodeficiency RefLoc Clin. Immunol. 96:108-118(2000) RefNumber [5] RefCrossRef PUBMED; 11668610 RefAuthors Notarangelo, L. D., Mella, P., Jones, A., de Saint Basile, RefAuthors G., Savoldi, G., Cranston, T., Vihinen, M., Schumacher, R. RefAuthors F. RefTitle Mutations in severe combined immune deficiency (SCID) due RefTitle to JAK3 deficiency. RefLoc Hum Mutat:255-263 (2001) FeatureHeader allele; 1 Feature dna; 1 Feature /rnalink: 2 Feature /name: point Feature /loc: IDRefSeq: D0095: 12326 Feature /change: c -> t Feature /CpG; 1 Feature /genomic_region: exon; 13 Feature rna; 2 Feature /dnalink: 1 Feature /aalink: 3 Feature /name: inframe deletion; cryptic splice-site activation Feature /loc: IDRefSeq: C0095: 1825..1845 Feature /change: -gcgtgtgcat ggctggagac a Feature aa; 3 Feature /rnalink: 2 Feature /name: deletion; inframe Feature /loc: UniProt: P52333; JAK3_HUMAN: 590..596 Feature /change: -VCMAGDS Feature /domain: JH2 FeatureHeader allele; 2 Feature dna; 4 Feature /rnalink: 5 Feature /name: point Feature /loc: IDRefSeq: D0095: 12326 Feature /change: c -> t Feature /CpG; 1 Feature /genomic_region: exon; 13 Feature rna; 5 Feature /dnalink: 4 Feature /aalink: 6 Feature /name: inframe deletion; cryptic splice-site activation Feature /loc: IDRefSeq: C0095: 1825..1845 Feature /change: -gcgtgtgcat ggctggagac a Feature aa; 6 Feature /rnalink: 5 Feature /name: deletion; inframe Feature /loc: UniProt: P52333; JAK3_HUMAN: 590..596 Feature /change: -VCMAGDS Feature /domain: JH2 Protein level reduced Kinase activity inactive Protein struct Allele 1 and 2; Fold alteration ref [4] Diagnosis T-B+ severe combined immunodeficiency Symptoms Lower resp; Failure to thrive; Ethnic origin Sweden Parents Consanguineous Total lymphoc 700 lymph/uL IgA nd IgE nd IgG Absent IgM nd CD3 1% CD4 nd CD8 nd CD16/56 1% CD19 96% Therapy BMT: Haplo Therapy BMT outcome: Response PHA: absent Response anti-CD3: absent // ID R651W(1),R651W(1); standard; MUTATION; JH2,JH2 Accession J0021 Systematic name Allele 1 and 2: g.14295C>T, c.1951C>T, r.1951c>u, Systematic name p.Arg651Trp Original code P19 ref. [1]; Patient 6 ref. [2] Description Allele 1 and 2: A point mutation in the exon 15 leading to Description an amino acid change in the JH2 domain Date 29-Dec-2000 (Rel. 2, Created) Date 08-Mar-2007 (Rel. 2, Last updated, Version 2) RefNumber [1] RefCrossRef PUBMED; 11668610 RefAuthors Notarangelo, L. D., Mella, P., Jones, A., de Saint Basile, RefAuthors G., Savoldi, G., Cranston, T., Vihinen, M., Schumacher, R. RefAuthors F. RefTitle Mutations in severe combined immune deficiency (SCID) due RefTitle to JAK3 deficiency. RefLoc Hum Mutat:255-263 (2001) RefNumber [2] RefCrossRef PUBMED; 11668621 RefAuthors Mella, P., Schumacher, R. F., Cranston, T., de Saint RefAuthors Basile, G., Savoldi, G., Notarangelo, L. D. RefTitle Eleven novel JAK3 mutations in patients with severe RefTitle combined immunodeficiency-including the first patients RefTitle with mutations in the kinase domain. RefLoc Hum Mutat:355-356 (2001) FeatureHeader allele; 1 Feature dna; 1 Feature /rnalink: 2 Feature /name: point Feature /loc: IDRefSeq: D0095: 14295 Feature /change: c -> t Feature /CpG; 1 Feature /genomic_region: exon; 15 Feature rna; 2 Feature /dnalink: 1 Feature /aalink: 3 Feature /name: missense Feature /loc: IDRefSeq: C0095: 2010 Feature /codon: cgg -> tgg; 1 Feature aa; 3 Feature /rnalink: 2 Feature /name: aa substitution Feature /loc: UniProt: P52333; JAK3_HUMAN: 651 Feature /change: R -> W Feature /domain: JH2 FeatureHeader allele; 2 Feature dna; 4 Feature /rnalink: 5 Feature /name: point Feature /loc: IDRefSeq: D0095: 14295 Feature /change: c -> t Feature /CpG; 1 Feature /genomic_region: exon; 15 Feature rna; 5 Feature /dnalink: 4 Feature /aalink: 6 Feature /name: missense Feature /loc: IDRefSeq: C0095: 2010 Feature /codon: cgg -> tgg; 1 Feature aa; 6 Feature /rnalink: 5 Feature /name: aa substitution Feature /loc: UniProt: P52333; JAK3_HUMAN: 651 Feature /change: R -> W Feature /domain: JH2 Diagnosis T-B+ severe combined immunodeficiency Age 3 months IgA 20 IgG 140 IgM 200 CD3 0% CD4 0% CD8 0% Therapy BMT: Haplo Therapy BMT outcome: Deceased Response PHA: Absent // ID R651W(2),E694K(1); standard; MUTATION; JH2,JH2 Accession J0018 Systematic name Allele 1: g.14295C>T, c.1951C>T, r.1951c>u, p.Arg651Trp Systematic name Allele 2: g.14503G>A, c.2080G>A, r.2080g>a, p.Glu694Lys Original code P16 ref. [1]; Patient 5 ref. [2] Description Allele 1: A point mutation in the exon 15 leading to an Description amino acid change in the JH2 domain Description Allele 2: A point mutation in the exon 16 leading to an Description amino acid change in the JH2 domain Date 29-Dec-2000 (Rel. 2, Created) Date 08-Mar-2007 (Rel. 2, Last updated, Version 2) RefNumber [1] RefCrossRef PUBMED; 11668610 RefAuthors Notarangelo, L. D., Mella, P., Jones, A., de Saint Basile, RefAuthors G., Savoldi, G., Cranston, T., Vihinen, M., Schumacher, R. RefAuthors F. RefTitle Mutations in severe combined immune deficiency (SCID) due RefTitle to JAK3 deficiency. RefLoc Hum Mutat:255-263 (2001) RefNumber [2] RefCrossRef PUBMED; 11668621 RefAuthors Mella, P., Schumacher, R. F., Cranston, T., de Saint RefAuthors Basile, G., Savoldi, G., Notarangelo, L. D. RefTitle Eleven novel JAK3 mutations in patients with severe RefTitle combined immunodeficiency-including the first patients RefTitle with mutations in the kinase domain. RefLoc Hum Mutat:355-356 (2001) FeatureHeader allele; 1 Feature dna; 1 Feature /rnalink: 2 Feature /name: point Feature /loc: IDRefSeq: D0095: 14295 Feature /change: c -> t Feature /CpG; 1 Feature /genomic_region: exon; 15 Feature rna; 2 Feature /dnalink: 1 Feature /aalink: 3 Feature /name: missense Feature /loc: IDRefSeq: C0095: 2010 Feature /codon: cgg -> tgg; 1 Feature aa; 3 Feature /rnalink: 2 Feature /name: aa substitution Feature /loc: UniProt: P52333; JAK3_HUMAN: 651 Feature /change: R -> W Feature /domain: JH2 FeatureHeader allele; 2 Feature dna; 4 Feature /rnalink: 5 Feature /name: point Feature /loc: IDRefSeq: D0095: 14503 Feature /change: g -> a Feature /CpG; 2 Feature /genomic_region: exon; 16 Feature rna; 5 Feature /dnalink: 4 Feature /aalink: 6 Feature /name: missense Feature /loc: IDRefSeq: C0095: 2139 Feature /codon: gag -> aag; 1 Feature aa; 6 Feature /rnalink: 5 Feature /name: aa substitution Feature /loc: UniProt: P52333; JAK3_HUMAN: 694 Feature /change: E -> K Feature /domain: JH2 Diagnosis T-B+ severe combined immunodeficiency Age 3 months Total lymphoc 5640 m IgA 20 IgG 7150G IgM 90 CD3 48% CD4 18% CD8 35% CD16/56 1% CD19 45% Therapy BMT: Haplo Therapy BMT outcome: Deceased Response PHA: nd // ID P689S(1),P689S(1); standard; MUTATION; JH2,JH2 Accession J0017 Systematic name Allele 1 and 2: g.14488C>T, c.2065C>T, r.2065c>u, Systematic name p.Pro689Ser Original code P15 ref. [1]; Patient 7 ref. [2] Description Allele 1 and 2: A point mutation in the exon 16 leading to Description an amino acid change in the JH2 domain Date 28-Dec-2000 (Rel. 2, Created) Date 08-Mar-2007 (Rel. 2, Last updated, Version 2) RefNumber [1] RefCrossRef PUBMED; 11668610 RefAuthors Notarangelo, L. D., Mella, P., Jones, A., de Saint Basile, RefAuthors G., Savoldi, G., Cranston, T., Vihinen, M., Schumacher, R. RefAuthors F. RefTitle Mutations in severe combined immune deficiency (SCID) due RefTitle to JAK3 deficiency. RefLoc Hum Mutat:255-263 (2001) RefNumber [2] RefCrossRef PUBMED; 11668621 RefAuthors Mella, P., Schumacher, R. F., Cranston, T., de Saint RefAuthors Basile, G., Savoldi, G., Notarangelo, L. D. RefTitle Eleven novel JAK3 mutations in patients with severe RefTitle combined immunodeficiency-including the first patients RefTitle with mutations in the kinase domain. RefLoc Hum Mutat:355-356 (2001) FeatureHeader allele; 1 Feature dna; 1 Feature /rnalink: 2 Feature /name: point Feature /loc: IDRefSeq: D0095: 14488 Feature /change: c -> t Feature /genomic_region: exon; 16 Feature rna; 2 Feature /dnalink: 1 Feature /aalink: 3 Feature /name: missense Feature /loc: IDRefSeq: C0095: 2124 Feature /codon: ccc -> tcc; 1 Feature aa; 3 Feature /rnalink: 2 Feature /name: aa substitution Feature /loc: UniProt: P52333; JAK3_HUMAN: 689 Feature /change: P -> S Feature /domain: JH2 FeatureHeader allele; 2 Feature dna; 4 Feature /rnalink: 5 Feature /name: point Feature /loc: IDRefSeq: D0095: 14488 Feature /change: c -> t Feature /genomic_region: exon; 16 Feature rna; 5 Feature /dnalink: 4 Feature /aalink: 6 Feature /name: missense Feature /loc: IDRefSeq: C0095: 2124 Feature /codon: ccc -> tcc; 1 Feature aa; 6 Feature /rnalink: 5 Feature /name: aa substitution Feature /loc: UniProt: P52333; JAK3_HUMAN: 689 Feature /change: P -> S Feature /domain: JH2 Diagnosis T-B+ severe combined immunodeficiency Age 4 months Total lymphoc 3470 lymph/uL IgA 1 U/ml IgG 9.6 U/ml IgM 14 U/ml CD3 2% CD4 0% CD8 0% CD16/56 nd% CD19 22% Therapy BMT: Haplo Therapy BMT outcome: A/w, warts Response PHA: minimal // ID D707A(1),L956R(1); standard; MUTATION; JH2,JH1 Accession J0031 Systematic name Allele 1: g.14543A>C, c.2120A>C, r.2120a>c, p.Asp707Ala Systematic name Allele 2: g.18135T>G, c.2867T>G, r.2867u>g, p.Leu956Arg Description Allele 1: A point mutation in the exon 16 leading to an Description amino acid change in the JH2 domain Description Allele 2: A point mutation in the exon 21 leading to an Description amino acid change in the JH1 domain Date 06-Apr-2007 (Rel. 2, Created) Date 06-Apr-2007 (Rel. 2, Last updated, Version 1) RefNumber [1] RefLoc Submitted (06-Apr-2007) to JAK3base. RefLoc Inga Astakhova, MD; Ronald Ferdman, MD; Ernie Guzman, MD; RefLoc e-mail ingrid_999_a@yahoo.com FeatureHeader allele; 1 Feature dna; 1 Feature /rnalink: 2 Feature /name: point Feature /loc: IDRefSeq: D0095: 14543 Feature /change: a -> c Feature /genomic_region: exon; 16 Feature rna; 2 Feature /dnalink: 1 Feature /aalink: 3 Feature /name: missense Feature /loc: IDRefSeq: C0095: 2179 Feature /codon: gac -> gcc; 2 Feature aa; 3 Feature /rnalink: 2 Feature /name: aa substitution Feature /loc: UniProt: P52333; JAK3_HUMAN: 707 Feature /change: D -> A Feature /domain: JH2 FeatureHeader allele; 2 Feature dna; 4 Feature /rnalink: 5 Feature /name: point Feature /loc: IDRefSeq: D0095: 18135 Feature /change: t -> g Feature /genomic_region: exon; 21 Feature rna; 5 Feature /dnalink: 4 Feature /aalink: 6 Feature /name: missense Feature /loc: IDRefSeq: C0095: 2926 Feature /codon: ctc -> cgc; 2 Feature aa; 6 Feature /rnalink: 5 Feature /name: aa substitution Feature /loc: UniProt: P52333; JAK3_HUMAN: 956 Feature /change: L -> R Feature /domain: JH1 Diagnosis T-B- severe combined immunodeficiency Symptoms Infections: Symptoms P. Carinii pneumonia; Cytomegalovirus retinis or other Symptoms infection; Oral/cutaneous candidiasis; Age 4 months Sex XY Ethnic origin Caucasoid; USA Family history Not known Relative Mother, 23; father, 27; three healthy brothers 4,3 and 2 at Relative the time of diagnosis WBC 5,350 IgA <7 IgG 38 IgM 25 CD3 1 CD4 1 CD8 1 CD19 91 Lymphocytes Mitogens: 222 Lymphocytes Soluble antigen: 4626 // ID V722I(1),?; standard; MUTATION; JH2, Accession J0012 Systematic name Allele 1: g.14587G>A, c.2164G>A, r.2164g>a, Systematic name p.Val722Ile Original code L.S. ref [1]; P10 ref [3] Description Allele 1: A point mutation in the exon 16 leading to Description an amino acid change in the JH2 domain Description Allele 2; unknown Date 13-Oct-2000 (Rel. 1, Created) Date 09-Mar-2007 (Rel. 2, Last updated, Version 3) RefNumber [1] RefCrossRef PUBMED; 10982185 RefAuthors Schumacher, R. F., Mella, P., Badolato, R., Fiorini, M., RefAuthors Savoldi, G., Giliani, S., Villa, A., Candotti, F., RefAuthors Tampalini, A., O'Shea, J. J., Notarangelo, L. D. RefTitle Complete genomic organization of the human JAK3 gene and RefTitle mutation analysis in severe combined immunodeficiency by RefTitle single-strand conformation polymorphism RefLoc Hum. Genet. 106:73-79(2000) RefNumber [2] RefCrossRef PUBMED; 10900158 RefAuthors Vihinen, M., Villa, A., Mella, P., Schumacher, R. F., RefAuthors Savoldi, G., O'Shea, J. J., Candotti, F., Notarangelo, RefAuthors L. D. RefTitle Molecular modeling of the Jak3 kinase domains and RefTitle structural basis for severe combined immunodeficiency RefLoc Clin. Immunol. 96:108-118(2000) RefNumber [3] RefCrossRef PUBMED; 11668610 RefAuthors Notarangelo, L. D., Mella, P., Jones, A., de Saint Basile, RefAuthors G., Savoldi, G., Cranston, T., Vihinen, M., Schumacher, R. RefAuthors F. RefTitle Mutations in severe combined immune deficiency (SCID) due RefTitle to JAK3 deficiency. RefLoc Hum Mutat:255-263 (2001) FeatureHeader allele; 1 Feature dna; 1 Feature /rnalink: 2 Feature /name: point Feature /loc: IDRefSeq: D0095: 14587 Feature /change: g -> a Feature /CpG; 2 Feature /genomic_region: exon; 16 Feature rna; 2 Feature /dnalink: 1 Feature /aalink: 3 Feature /name: missense Feature /loc: IDRefSeq: C0095: 2223 Feature /codon: gtc -> atc; 1 Feature aa; 3 Feature /rnalink: 2 Feature /name: aa substitution Feature /loc: UniProt: P52333; JAK3_HUMAN: 722 Feature /change: V -> I Feature /domain: JH2 FeatureHeader allele; 2 Feature dna; 4 Feature /rnalink: 5 Feature /name: unknown Feature rna; 5 Feature /dnalink: 4 Feature /aalink: 6 Feature /name: unknown Feature aa; 6 Feature /rnalink: 5 Feature /name: unknown Diagnosis T-B+ severe combined immunodeficiency Protein struct Allele 1; Sterical clash in core ref [2] Ethnic origin Italy // ID Q766X(1),Q766X(1); standard; MUTATION; JH2,JH2 Accession J0019 Systematic name Allele 1 and 2: g.14849C>T, c.2296C>T, r.2296c>u, p.Gln766X Original code P17 ref. [1]; Patient 8 ref. [2] Description Allele 1 and 2: A point mutation in the exon 17 leading to Description a premature stop codon in the JH2 domain Date 29-Dec-2000 (Rel. 2, Created) Date 09-Mar-2007 (Rel. 2, Last updated, Version 2) RefNumber [1] RefCrossRef PUBMED; 11668610 RefAuthors Notarangelo, L. D., Mella, P., Jones, A., de Saint Basile, RefAuthors G., Savoldi, G., Cranston, T., Vihinen, M., Schumacher, R. RefAuthors F. RefTitle Mutations in severe combined immune deficiency (SCID) due RefTitle to JAK3 deficiency. RefLoc Hum Mutat:255-263 (2001) RefNumber [2] RefCrossRef PUBMED; 11668621 RefAuthors Mella, P., Schumacher, R. F., Cranston, T., de Saint RefAuthors Basile, G., Savoldi, G., Notarangelo, L. D. RefTitle Eleven novel JAK3 mutations in patients with severe RefTitle combined immunodeficiency-including the first patients RefTitle with mutations in the kinase domain. RefLoc Hum Mutat:355-356 (2001) FeatureHeader allele; 1 Feature dna; 1 Feature /rnalink: 2 Feature /name: point Feature /loc: IDRefSeq: D0095: 14849 Feature /change: c -> t Feature /genomic_region: exon; 17 Feature rna; 2 Feature /dnalink: 1 Feature /aalink: 3 Feature /name: nonsense Feature /loc: IDRefSeq: C0095: 2355 Feature /codon: cag -> tag; 1 Feature aa; 3 Feature /rnalink: 2 Feature /name: out of frame translation; premature termination Feature /loc: UniProt: P52333; JAK3_HUMAN: 766 Feature /change: Q -> X Feature /domain: JH2 FeatureHeader allele; 2 Feature dna; 4 Feature /rnalink: 5 Feature /name: point Feature /loc: IDRefSeq: D0095: 14849 Feature /change: c -> t Feature /genomic_region: exon; 17 Feature rna; 5 Feature /dnalink: 4 Feature /aalink: 6 Feature /name: nonsense Feature /loc: IDRefSeq: C0095: 2355 Feature /codon: cag -> tag; 1 Feature aa; 6 Feature /rnalink: 5 Feature /name: out of frame translation; premature termination Feature /loc: UniProt: P52333; JAK3_HUMAN: 766 Feature /change: Q -> X Feature /domain: JH2 Diagnosis T-B+ severe combined immunodeficiency Age 5 months Total lymphoc 1020 lymph/uL IgA 260 IgG 1400 IgM 570 CD3 0% CD4 0% CD8 0% CD16/56 1% CD19 19% Therapy BMT: MP Therapy BMT outcome: A/w Response PHA: Absent // ID R771X(1),R771X(1); standard; MUTATION; JH2,JH2 Accession J0022 Systematic name Allele 1 and 2: g.14864C>T, c.2311C>T, r.2311c>u, p.Arg771X Original code P20 ref. [1]; Patient 9 ref. [2] Description Allele 1 and 2: A point mutation in the exon 17 leading to Description a premature stop codon in the JH2 domain Date 29-Dec-2000 (Rel. 2, Created) Date 08-Mar-2007 (Rel. 2, Last updated, Version 2) RefNumber [1] RefCrossRef PUBMED; 11668610 RefAuthors Notarangelo, L. D., Mella, P., Jones, A., de Saint Basile, RefAuthors G., Savoldi, G., Cranston, T., Vihinen, M., Schumacher, R. RefAuthors F. RefTitle Mutations in severe combined immune deficiency (SCID) due RefTitle to JAK3 deficiency. RefLoc Hum Mutat:255-263 (2001) RefNumber [2] RefCrossRef PUBMED; 11668621 RefAuthors Mella, P., Schumacher, R. F., Cranston, T., de Saint RefAuthors Basile, G., Savoldi, G., Notarangelo, L. D. RefTitle Eleven novel JAK3 mutations in patients with severe RefTitle combined immunodeficiency-including the first patients RefTitle with mutations in the kinase domain. RefLoc Hum Mutat:355-356 (2001) FeatureHeader allele; 1 Feature dna; 1 Feature /rnalink: 2 Feature /name: point Feature /loc: IDRefSeq: D0095: 14864 Feature /change: c -> t Feature /CpG; 1 Feature /genomic_region: exon; 17 Feature rna; 2 Feature /dnalink: 1 Feature /aalink: 3 Feature /name: nonsense Feature /loc: IDRefSeq: C0095: 2370 Feature /codon: cga -> tga; 1 Feature aa; 3 Feature /rnalink: 2 Feature /name: out of frame translation; premature termination Feature /loc: UniProt: P52333; JAK3_HUMAN: 771 Feature /change: R -> X Feature /domain: JH2 FeatureHeader allele; 2 Feature dna; 4 Feature /rnalink: 5 Feature /name: point Feature /loc: IDRefSeq: D0095: 14864 Feature /change: c -> t Feature /CpG; 1 Feature /genomic_region: exon; 17 Feature rna; 5 Feature /dnalink: 4 Feature /aalink: 6 Feature /name: nonsense Feature /loc: IDRefSeq: C0095: 2370 Feature /codon: cga -> tga; 1 Feature aa; 6 Feature /rnalink: 5 Feature /name: out of frame translation; premature termination Feature /loc: UniProt: P52333; JAK3_HUMAN: 771 Feature /change: R -> X Feature /domain: JH2 Diagnosis T-B+ severe combined immunodeficiency Age 6 months Total lymphoc 970 lymph/uL IgA 2 IgG Absent IgM 34 CD3 31% CD4 12% CD8 20% CD16/56 2% CD19 66% Therapy BMT outcome: Deceased at 8 months Response PHA: nd // ID L910S(1),Y1023X(1); standard; MUTATION; JH1,JH1 Accession J0013 Systematic name Allele 1: g.17724T>C, c.2729T>C, r.2729u>c, p.Leu910Ser Systematic name Allele 2: g.18944C>A, c.3069C>A, r.3069c>a, p.Tyr1023X Original code Ga.Mi. ref [1]; P12 ref [3]; Description Allele 1: A point mutation in the exon 20 leading to an Description amino acid change in the JH1 domain Description Allele 2: A point mutation in the exon 22 leading to a Description premature stop codon in the JH1 domain Date 13-Oct-2000 (Rel. 1, Created) Date 09-Mar-2007 (Rel. 2, Last updated, Version 3) RefNumber [1] RefCrossRef PUBMED; 10982185 RefAuthors Schumacher, R. F., Mella, P., Badolato, R., Fiorini, M., RefAuthors Savoldi, G., Giliani, S., Villa, A., Candotti, F., RefAuthors Tampalini, A., O'Shea, J. J., Notarangelo, L. D. RefTitle Complete genomic organization of the human JAK3 gene and RefTitle mutation analysis in severe combined immunodeficiency by RefTitle single-strand conformation polymorphism RefLoc Hum. Genet. 106:73-79(2000) RefNumber [2] RefCrossRef PUBMED; 10900158 RefAuthors Vihinen, M., Villa, A., Mella, P., Schumacher, R. F., RefAuthors Savoldi, G., O'Shea, J. J., Candotti, F., Notarangelo, RefAuthors L. D. RefTitle Molecular modeling of the Jak3 kinase domains and RefTitle structural basis for severe combined immunodeficiency RefLoc Clin. Immunol. 96:108-118(2000) RefNumber [3] RefCrossRef PUBMED; 11668610 RefAuthors Notarangelo, L. D., Mella, P., Jones, A., de Saint Basile, RefAuthors G., Savoldi, G., Cranston, T., Vihinen, M., Schumacher, R. RefAuthors F. RefTitle Mutations in severe combined immune deficiency (SCID) due RefTitle to JAK3 deficiency. RefLoc Hum Mutat:255-263 (2001) FeatureHeader allele; 1 Feature dna; 1 Feature /rnalink: 2 Feature /name: point Feature /loc: IDRefSeq: D0095: 17724 Feature /change: t -> c Feature /genomic_region: exon; 20 Feature rna; 2 Feature /dnalink: 1 Feature /aalink: 3 Feature /name: missense Feature /loc: IDRefSeq: C0095: 2788 Feature /codon: ttg -> tcg; 2 Feature aa; 3 Feature /rnalink: 2 Feature /name: aa substitution Feature /loc: UniProt: P52333; JAK3_HUMAN: 910 Feature /change: L -> S Feature /domain: JH1 FeatureHeader allele; 2 Feature dna; 4 Feature /rnalink: 5 Feature /name: point Feature /loc: IDRefSeq: D0095: 18944 Feature /change: c -> a Feature /genomic_region: exon; 22 Feature rna; 5 Feature /dnalink: 4 Feature /aalink: 6 Feature /name: nonsense Feature /loc: IDRefSeq: C0095: 3128 Feature /codon: tac -> taa; 3 Feature aa; 6 Feature /rnalink: 5 Feature /name: out of frame translation; premature termination Feature /loc: UniProt: P52333; JAK3_HUMAN: 1023 Feature /change: Y -> X Feature /domain: JH1 Diagnosis T-B+ severe combined immunodeficiency Protein struct Allele 1; Structural alterations ref [2] Protein struct Allele 2; Truncation ref [2] Diagnosis T-B+ severe combined immunodeficiency Sex XY Age 7 months Ethnic origin Italy Total lymphoc 3104 lymph/uL IgA 23 IgE 2 IgG 152 IgM 54 CD3 0.5% CD4 0.5% CD8 0.5% CD16/56 0.5% CD19 92% Therapy BMT: Haplo Therapy BMT age: 7 months Therapy BMT outcome: A, severe neurol. Impaired Response PHA: Absent // ID Y929X(1),Y929X(1); standard; MUTATION; JH1,JH1 Accession J0029 Systematic name Allele 1 and 2: g.17782delT, c.2787delT, r.2787delu, Systematic name p.Tyr929X Original code Patient 7 Description Allele 1 and 2: A deletion mutation in the exon 20 leading Description to a premature stop codon in the JH1 domain Date 14-Mar-2007 (Rel. 2, Created) Date 14-Mar-2007 (Rel. 2, Last updated, Version 1) RefNumber [1] RefCrossRef PUBMED; 14615376 RefAuthors Roberts, J. L., Lengi, A., Brown, S. M., Chen, M., Zhou, RefAuthors Y. J., O'Shea, J. J., Buckley, R. H. RefTitle Janus kinase 3 (JAK3) deficiency: clinical, immunologic, RefTitle and molecular analyses of 10 patients and outcomes of stem RefTitle cell transplantation. RefLoc Blood:2009-2018 (2004) FeatureHeader allele; 1 Feature dna; 1 Feature /rnalink: 2 Feature /name: deletion Feature /loc: IDRefSeq: D0095: 17782 Feature /change: t -> g Feature /genomic_region: exon; 20 Feature rna; 2 Feature /dnalink: 1 Feature /aalink: 3 Feature /name: nonsense Feature /loc: IDRefSeq: C0095: 2846 Feature /codon: tat -> tag; 3 Feature aa; 3 Feature /rnalink: 2 Feature /name: out of frame translation; premature termination Feature /loc: UniProt: P52333; JAK3_HUMAN: 929 Feature /change: Y -> X Feature /domain: JH1 FeatureHeader allele; 2 Feature dna; 4 Feature /rnalink: 5 Feature /name: deletion Feature /loc: IDRefSeq: D0095: 17782 Feature /change: t -> g Feature /genomic_region: exon; 20 Feature rna; 5 Feature /dnalink: 4 Feature /aalink: 6 Feature /name: nonsense Feature /loc: IDRefSeq: C0095: 2846 Feature /codon: tat -> tag; 3 Feature aa; 6 Feature /rnalink: 5 Feature /name: out of frame translation; premature termination Feature /loc: UniProt: P52333; JAK3_HUMAN: 929 Feature /change: Y -> X Feature /domain: JH1 Diagnosis T-B- severe combined immunodeficiency // ID G987G(1),G987G(1); standard; MUTATION; JH1,JH1 Accession J0027 Systematic name Allele 1 and 2: g.18229C>T, c.c.2960_2978del, r.2960_2978del, Systematic name p.Gln988fsX43 Original code Patient 4 Description Allele 1 and 2: A point mutation in the exon 21 leading to Description aberrant splicing Date 13-Mar-2007 (Rel. 2, Created) Date 13-Mar-2007 (Rel. 2, Last updated, Version 1) RefNumber [1] RefCrossRef PUBMED; 14615376 RefAuthors Roberts, J. L., Lengi, A., Brown, S. M., Chen, M., Zhou, RefAuthors Y. J., O'Shea, J. J., Buckley, R. H. RefTitle Janus kinase 3 (JAK3) deficiency: clinical, immunologic, RefTitle and molecular analyses of 10 patients and outcomes of stem RefTitle cell transplantation. RefLoc Blood:2009-2018 (2004) FeatureHeader allele; 1 Feature dna; 1 Feature /rnalink: 2 Feature /name: point Feature /loc: IDRefSeq: D0095: 18229 Feature /change: c -> t Feature /genomic_region: exon; 21 Feature rna; 2 Feature /dnalink: 1 Feature /aalink: 3 Feature /name: deletion; frameshift Feature /loc: IDRefSeq: C0095: 3019..3037 Feature /change: -gccagagccc cattttctg Feature aa; 3 Feature /rnalink: 2 Feature /name: out of frame translation; premature termination Feature /loc: UniProt: P52333; JAK3_HUMAN: 987..993 Feature /change: GQSPIFW -> Feature /change: GMPPNPSRTT SSLASQTSGA SGSSCTSSSP TATKAAAPRP SSCGX Feature /domain: JH1 FeatureHeader allele; 2 Feature dna; 4 Feature /rnalink: 5 Feature /name: point Feature /loc: IDRefSeq: D0095: 18229 Feature /change: c -> t Feature /genomic_region: exon; 21 Feature rna; 5 Feature /dnalink: 4 Feature /aalink: 6 Feature /name: deletion; frameshift Feature /loc: IDRefSeq: C0095: 3019..3037 Feature /change: -gccagagccc cattttctg Feature aa; 6 Feature /rnalink: 5 Feature /name: out of frame translation; premature termination Feature /loc: UniProt: P52333; JAK3_HUMAN: 987..993 Feature /change: GQSPIFW -> Feature /change: GMPPNPSRTT SSLASQTSGA SGSSCTSSSP TATKAAAPRP SSCGX Feature /domain: JH1 Diagnosis T-B- severe combined immunodeficiency // ID Intron 10(1),Intron 10(1); standard; MUTATION; JH3,JH3 Accession J0007 Systematic name Allele 1 and 2: g.IVS10-2A>G, c.1442_1446delAAAAG, Systematic name p.Glu481fsX36 Original code V.L. ref [1]; P6 ref [3] Description Allele 1 and 2; point mutation in the intron 10 leading to Description frameshift and point mutation leading to stop codon at 517 Description in JH3 domain Date 08-Sep-1998 (Rel. 1, Created) Date 12-Mar-2007 (Rel. 2, Last updated, Version 5) RefNumber [1] RefCrossRef PUBMED; 9354668 RefAuthors Candotti, F., Oakes, S. A., Johnston, J. A., Giliani, S., RefAuthors Schumacher, R. F., Mella, P., Fiorini, M., Ugazio, A. G., RefAuthors Badolato, R., Notarangelo, L. D., Bozzi, F., Macchi, P., RefAuthors Strina, D., Vezzoni, P., Blaese, R. M., O'Shea, J. J., RefAuthors Villa, A. RefTitle Structural and functional basis for JAK3-deficient severe RefTitle combined immunodeficiency RefLoc Blood 90:3996-4003 (1997) RefNumber [2] RefCrossRef PUBMED; 10982185 RefAuthors Schumacher, R. F., Mella, P., Badolato, R., Fiorini, M., RefAuthors Savoldi, G., Giliani, S., Villa, A., Candotti, F., RefAuthors Tampalini, A., O'Shea, J. J., Notarangelo, L. D. RefTitle Complete genomic organization of the human JAK3 gene and RefTitle mutation analysis in severe combined immunodeficiency by RefTitle single-strand conformation polymorphism RefLoc Hum. Genet. 106:73-79(2000) RefNumber [3] RefCrossRef PUBMED; 11668610 RefAuthors Notarangelo, L. D., Mella, P., Jones, A., de Saint Basile, RefAuthors G., Savoldi, G., Cranston, T., Vihinen, M., Schumacher, R. RefAuthors F. RefTitle Mutations in severe combined immune deficiency (SCID) due RefTitle to JAK3 deficiency. RefLoc Hum Mutat:255-263 (2001) FeatureHeader allele; 1 Feature dna; 1 Feature /rnalink; 2 Feature /name: point Feature /loc: IDRefSeq: D0095: 11082 Feature /inexloc: -2 Feature /change: a -> g Feature /genomic_region: intron; 10 Feature rna; 2 Feature /dnalink: 1 Feature /aalink: 3 Feature /name: frameshift Feature /loc: IDRefSeq: C0095: 1501..1505 Feature /change: -aaaag Feature aa; 3 Feature /rnalink: 2 Feature /name: out of frame translation; premature termination Feature /loc: UniProt: P52333; JAK3_HUMAN: 481..482 Feature /change: EK -> VQPDRGPERS QPTHIILGSA PIPIPAESDD ISQDPCX Feature /domain: JH3 FeatureHeader allele; 2 Feature dna; 4 Feature /rnalink: 5 Feature /name: point Feature /loc: IDRefSeq: D0095: 11082 Feature /inexloc: -2 Feature /change: a -> g Feature /genomic_region: intron; 10 Feature rna; 5 Feature /dnalink: 4 Feature /aalink: 6 Feature /name: frameshift Feature /loc: IDRefSeq: C0095: 1501..1505 Feature /change: -aaaag Feature aa; 6 Feature /rnalink: 5 Feature /name: out of frame translation; premature termination Feature /loc: UniProt: P52333; JAK3_HUMAN: 481..482 Feature /change: EK -> VQPDRGPERS QPTHIILGSA PIPIPAESDD ISQDPCX Feature /domain: JH3 Protein level reduced Diagnosis T-B+ severe combined immunodeficiency Symptoms Lower resp; Failure to thrive; Chronic diarrhea; Sex XY Age 3 months Ethnic origin Italy Total lymphoc 1364 lymph/uL IgA 6 IgE nd IgG 132 IgM 22 CD3 <1% CD4 <1% CD8 <1% CD16/56 <1% CD19 77% Therapy BMT: Haplo Therapy BMT age: 5 months Therapy BMT outcome: A/w Response PHA: Absent // ID Intron 13(1),E698X(1); standard; MUTATION; JH2,JH2 Accession J0020 Systematic name Allele 1: g.IVS13-1G>A, c.1787-1G>A, r. Systematic name Allele 2: g.14515G>T, c.2092G>T, r.2092g>u, p.Glu698X Original code P18 ref. [1]; Patient 4 ref. [2] Description Allele 1: A point mutation in the intron 13 Description Allele 2: A point mutation in the exon 16 leading to a Description premature stop codon Date 29-Dec-2000 (Rel. 2, Created) Date 08-Mar-2007 (Rel. 2, Last updated, Version 2) RefNumber [1] RefCrossRef PUBMED; 11668610 RefAuthors Notarangelo, L. D., Mella, P., Jones, A., de Saint Basile, RefAuthors G., Savoldi, G., Cranston, T., Vihinen, M., Schumacher, R. RefAuthors F. RefTitle Mutations in severe combined immune deficiency (SCID) due RefTitle to JAK3 deficiency. RefLoc Hum Mutat:255-263 (2001) RefNumber [2] RefCrossRef PUBMED; 11668621 RefAuthors Mella, P., Schumacher, R. F., Cranston, T., de Saint RefAuthors Basile, G., Savoldi, G., Notarangelo, L. D. RefTitle Eleven novel JAK3 mutations in patients with severe RefTitle combined immunodeficiency-including the first patients RefTitle with mutations in the kinase domain. RefLoc Hum Mutat:355-356 (2001) Feature dna; 1 Feature /rnalink: 2 Feature /name: point Feature /loc: IDRefSeq: D0095: 13422 Feature /change: g -> a Feature /genomic_region: intron; 13 Feature rna; 2 Feature /dnalink: 1 Feature /aalink: 3 Feature /name: unknown Feature /inexloc: -1 Feature aa; 3 Feature /rnalink: 2 Feature /name: unknown FeatureHeader allele; 2 Feature dna; 4 Feature /rnalink: 5 Feature /name: point Feature /loc: IDRefSeq: D0095: 14515 Feature /change: g -> t Feature /genomic_region: exon; 16 Feature rna; 5 Feature /dnalink: 4 Feature /aalink: 6 Feature /name: nonsense Feature /loc: IDRefSeq: C0095: 2151 Feature /codon: gag -> tag; 1 Feature aa; 6 Feature /rnalink: 5 Feature /name: out of frame translation; premature termination Feature /loc: UniProt: P52333; JAK3_HUMAN: 698 Feature /change: E -> X Feature /domain: JH2 Diagnosis T-B+ severe combined immunodeficiency Age Birth Total lymphoc 1020 lymph/uL IgA 2 IgG 112 IU/ml IgM 34 CD3 1% CD4 nd CD8 nd CD16/56 nd CD19 26% Therapy BMT: MSD Therapy BMT outcome: A/w warts Response PHA: Minimal // ID Intron 17(1a),Intron 17(1a); standard; MUTATION; JH2,JH2 Accession J0002 Systematic name Allele 1 and 2: g.IVS17+2T>C, c.2200_2350del, p.Lys734fsX60 Original code C.M. ref [1,3]; P11b ref [4] Description point mutation in the intron 17 leading to deletion of exon Description 17 Date 08-Sep-1998 (Rel. 1, Created) Date 12-Mar-2007 (Rel. 2, Last updated, Version 4) RefNumber [1] RefCrossRef PUBMED; 7659163 RefAuthors Macchi, P., Villa, A., Giliani, S., Sacco, M. G., Frattini, RefAuthors A., Porta, F., Ugazio, A. G.,Johnston, J. A., Candotti, F., RefAuthors O'Shea, J. J., Vezzoni, P., Notarangelo, L. D. RefTitle Mutations of Jak-3 gene in patients with autosomal severe RefTitle combined immune deficiency (SCID) RefLoc Nature 377:65-68 (1995) RefNumber [2] RefCrossRef PUBMED; 8704236 RefAuthors Villa, A., Sironi, M., Macchi, P., Mateucci, C., RefAuthors Notarangelo,L. D., Vezzoni, P., Mantovani, A. RefTitle Monocyte function in a severe combined immunodeficient RefTitle patient with a donor splice site mutation in the Jak3 gene RefLoc Blood 88:817-823 (1996) RefNumber [3] RefCrossRef PUBMED; 10982185 RefAuthors Schumacher, R. F., Mella, P., Badolato, R., Fiorini, M., RefAuthors Savoldi, G., Giliani, S., Villa, A., Candotti, F., RefAuthors Tampalini, A., O'Shea, J. J., Notarangelo, L. D. RefTitle Complete genomic organization of the human JAK3 gene and RefTitle mutation analysis in severe combined immunodeficiency by RefTitle single-strand conformation polymorphism RefLoc Hum. Genet. 106:73-79(2000) RefNumber [4] RefCrossRef PUBMED; 11668610 RefAuthors Notarangelo, L. D., Mella, P., Jones, A., de Saint Basile, RefAuthors G., Savoldi, G., Cranston, T., Vihinen, M., Schumacher, R. RefAuthors F. RefTitle Mutations in severe combined immune deficiency (SCID) due RefTitle to JAK3 deficiency. RefLoc Hum Mutat:255-263 (2001) DB CrossRef OMIM; 600173.0002 FeatureHeader allele; 1 Feature dna; 1 Feature /rnalink: 2 Feature /name: point Feature /loc: IDRefSeq: D0095: 14905 Feature /inexloc: +2 Feature /change: t -> c Feature /genomic_region: intron; 17 Feature rna; 2 Feature /dnalink: 1 Feature /aalink: 3 Feature /name: frameshift Feature /loc: IDRefSeq: C0095: 2259..2409 Feature /change: -aaactccaat tttatgagga ccggcagcag ctgccggccc Feature /change: ccaagtggac agagctggcc ctgctgattc aacagtgcat Feature /change: ggcctatgag ccggtccaga ggccctcctt ccgagccgtc Feature /change: attcgtgacc tcaatagcct catctcttca g Feature aa; 3 Feature /rnalink: 2 Feature /name: out of frame translation; premature termination Feature /loc: UniProt: P52333; JAK3_HUMAN: 734..784 Feature /change: KLQFYEDRQQ LPAPKWTELA LLIQQCMAYE PVQRPSFRAV Feature /change: IRDLNSLISS D Feature /change: -> TMSSSQTPHL VPWHLVMGCG MVPSSMPAKT PRSSRRDTSS Feature /change: TSHSWARATL AAWSCAAMTR X Feature /domain: JH2 FeatureHeader allele; 2 Feature dna; 4 Feature /rnalink: 5 Feature /name: point Feature /loc: IDRefSeq: D0095: 14905 Feature /inexloc: +2 Feature /change: t -> c Feature /genomic_region: intron; 17 Feature rna; 5 Feature /dnalink: 4 Feature /aalink: 6 Feature /name: frameshift Feature /loc: IDRefSeq: C0095: 2259..2409 Feature /change: -aaactccaat tttatgagga ccggcagcag ctgccggccc Feature /change: ccaagtggac agagctggcc ctgctgattc aacagtgcat Feature /change: ggcctatgag ccggtccaga ggccctcctt ccgagccgtc Feature /change: attcgtgacc tcaatagcct catctcttca g Feature aa; 6 Feature /rnalink: 5 Feature /name: out of frame translation; premature termination Feature /loc: UniProt: P52333; JAK3_HUMAN: 734..784 Feature /change: KLQFYEDRQQ LPAPKWTELA LLIQQCMAYE PVQRPSFRAV Feature /change: IRDLNSLISS D Feature /change: -> TMSSSQTPHL VPWHLVMGCG MVPSSMPAKT PRSSRRDTSS Feature /change: TSHSWARATL AAWSCAAMTR X Feature /domain: JH2 Protein level much reduced Diagnosis T-B+ severe combined immunodeficiency Sex XY Age Prenatal Ethnic origin Italy Parents Consanguineous Relative JAK3; J0015 sister Total lymphoc 916 lymph/uL IgA 6 IgE 3 IgG 160 IgM 15 CD3 1% CD4 1% CD8 1% CD16/56 0.5% CD19 87% Therapy BMT: Haplo Therapy BMT age: 4 months Therapy BMT outcome: A/w Response PHA: Absent // ID Intron 17(1b),Intron 17(1b); standard; MUTATION; JH2,JH2 Accession J0015 Systematic name Allele 1 and 2: g.IVS17+2T>C, c.2200_2350del, p.Lys734fsX60 Original code C.A. ref [1]; P11a ref [2] Description point mutation in the intron 17 leading to deletion of exon Description 17 Date 13-Oct-2000 (Rel. 1, Created) Date 12-Mar-2007 (Rel. 2, Last updated, Version 4) RefNumber [1] RefCrossRef PUBMED; 10982185 RefAuthors Schumacher, R. F., Mella, P., Badolato, R., Fiorini, M., RefAuthors Savoldi, G., Giliani, S., Villa, A., Candotti, F., RefAuthors Tampalini, A., O'Shea, J. J., Notarangelo, L. D. RefTitle Complete genomic organization of the human JAK3 gene and RefTitle mutation analysis in severe combined immunodeficiency by RefTitle single-strand conformation polymorphism RefLoc Hum. Genet. 106:73-79(2000) RefNumber [2] RefCrossRef PUBMED; 11668610 RefAuthors Notarangelo, L. D., Mella, P., Jones, A., de Saint Basile, RefAuthors G., Savoldi, G., Cranston, T., Vihinen, M., Schumacher, R. RefAuthors F. RefTitle Mutations in severe combined immune deficiency (SCID) due RefTitle to JAK3 deficiency. RefLoc Hum Mutat:255-263 (2001) DB CrossRef OMIM; 600173.0002 FeatureHeader allele; 1 Feature dna; 1 Feature /rnalink: 2 Feature /name: point Feature /loc: IDRefSeq: D0095: 14905 Feature /inexloc: +2 Feature /change: t -> c Feature /genomic_region: intron; 17 Feature rna; 2 Feature /dnalink: 1 Feature /aalink: 3 Feature /name: frameshift Feature /loc: IDRefSeq: C0095: 2259..2409 Feature /change: -aaactccaat tttatgagga ccggcagcag ctgccggccc Feature /change: ccaagtggac agagctggcc ctgctgattc aacagtgcat Feature /change: ggcctatgag ccggtccaga ggccctcctt ccgagccgtc Feature /change: attcgtgacc tcaatagcct catctcttca g Feature aa; 3 Feature /rnalink: 2 Feature /name: out of frame translation; premature termination Feature /loc: UniProt: P52333; JAK3_HUMAN: 734..784 Feature /change: KLQFYEDRQQ LPAPKWTELA LLIQQCMAYE PVQRPSFRAV Feature /change: IRDLNSLISS D Feature /change: -> TMSSSQTPHL VPWHLVMGCG MVPSSMPAKT PRSSRRDTSS Feature /change: TSHSWARATL AAWSCAAMTR X Feature /domain: JH2 FeatureHeader allele; 2 Feature dna; 4 Feature /rnalink: 5 Feature /name: point Feature /loc: IDRefSeq: D0095: 14905 Feature /inexloc: +2 Feature /change: t -> c Feature /genomic_region: intron; 17 Feature rna; 5 Feature /dnalink: 4 Feature /aalink: 6 Feature /name: frameshift Feature /loc: IDRefSeq: C0095: 2259..2409 Feature /change: -aaactccaat tttatgagga ccggcagcag ctgccggccc Feature /change: ccaagtggac agagctggcc ctgctgattc aacagtgcat Feature /change: ggcctatgag ccggtccaga ggccctcctt ccgagccgtc Feature /change: attcgtgacc tcaatagcct catctcttca g Feature aa; 6 Feature /rnalink: 5 Feature /name: out of frame translation; premature termination Feature /loc: UniProt: P52333; JAK3_HUMAN: 734..784 Feature /change: KLQFYEDRQQ LPAPKWTELA LLIQQCMAYE PVQRPSFRAV Feature /change: IRDLNSLISS D Feature /change: -> TMSSSQTPHL VPWHLVMGCG MVPSSMPAKT PRSSRRDTSS Feature /change: TSHSWARATL AAWSCAAMTR X Feature /domain: JH2 Diagnosis T-B+ severe combined immunodeficiency Sex XX Age 7 months Ethnic origin Italy Parents Consanguineous Relative JAK3; J0002 brother Total lymphoc 2074 lymph/uL IgA 6 IgE nd IgG 49 IgM 57 CD3 1% CD4 1% CD8 0% CD16/56 1% CD19 94% Therapy BMT: Haplo Therapy BMT age: 8 months Therapy BMT outcome: A/w Response PHA: Absent // ID Intron 22(1),Intron 22(1); standard; MUTATION; Accession J0014 Systematic name Allele 1 and 2: g.IVS22+2T>A, c.3096+2T>A, r.3096+2u>a Original code S.B. ref [1]; P13 ref [2] Description Allele 1 and 2; point mutation in the intron 22 Date 13-Oct-2000 (Rel. 1, Created) Date 12-Mar-2007 (Rel. 2, Last updated, Version 4) RefNumber [1] RefCrossRef PUBMED; 10982185 RefAuthors Schumacher, R. F., Mella, P., Badolato, R., Fiorini, M., RefAuthors Savoldi, G., Giliani, S., Villa, A., Candotti, F., RefAuthors Tampalini, A., O'Shea, J. J., Notarangelo, L. D. RefTitle Complete genomic organization of the human JAK3 gene and RefTitle mutation analysis in severe combined immunodeficiency by RefTitle single-strand conformation polymorphism RefLoc Hum. Genet. 106:73-79(2000) RefNumber [2] RefCrossRef PUBMED; 11668610 RefAuthors Notarangelo, L. D., Mella, P., Jones, A., de Saint Basile, RefAuthors G., Savoldi, G., Cranston, T., Vihinen, M., Schumacher, R. RefAuthors F. RefTitle Mutations in severe combined immune deficiency due to JAK3 RefTitle deficiency RefLoc Hum, Mutat. 18:255-63(2001) FeatureHeader allele; 1 Feature dna; 1 Feature /rnalink: 2 Feature /name: point Feature /loc: IDRefSeq: D0095: 18973 Feature /change: t -> a Feature /genomic_region: intron; 22 Feature rna; 2 Feature /dnalink: 1 Feature /aalink: 3 Feature /name: unknown Feature /inexloc: +2 Feature aa; 3 Feature /rnalink: 2 Feature /name: unknown FeatureHeader allele; 2 Feature dna; 4 Feature /rnalink: 5 Feature /name: point Feature /loc: IDRefSeq: D0095: 18973 Feature /change: t -> a Feature /genomic_region: intron; 22 Feature rna; 5 Feature /dnalink: 4 Feature /aalink: 6 Feature /name: unknown Feature /inexloc: +2 Feature aa; 6 Feature /rnalink: 5 Feature /name: unknown Diagnosis T-B+ severe combined immunodeficiency Age 3 months Ethnic origin Great Britain Parents Consanguineous Total lymphoc 3210 lymph/uL IgA 70 IgE nd IgG 4610 IgM 230 CD3 0% CD4 0% CD8 0% CD16/56 0.5% CD19 97% Therapy BMT: No Therapy BMT outcome: Deceased Response PHA: Minimal // ID Intron 22(2),Intron 22(2); standard; MUTATION; Accession J0032 Systematic name Allele 1 and 2: g.IVS22-1G>A, c.3097-1G>A, r. Original code 5-month-old Latina girl Description Allele 1 and 2: A point mutation in the intron 22 leading Description to aberrant splicing Date 27-Sep-2007 (Rel. 2, Created) Date 27-Sep-2007 (Rel. 2, Last updated, Version 1) RefNumber [1] RefCrossRef PUBMED; 17433830 RefAuthors Mjaanes, C. M., Hendershot, R. W., Quinones, R. R., RefAuthors Gelfand, E. W. RefTitle A novel mutation of intron 22 in janus kinase 3-deficient RefTitle severe combined immunodeficiency. RefLoc J Allergy Clin Immunol:1542-1545 (2007) FeatureHeader allele; 1 Feature dna; 1 Feature /rnalink: 2 Feature /name: point Feature /loc: IDRefSeq: D0095: 19255 Feature /change: g -> a Feature /genomic_region: intron; 22 Feature rna; 2 Feature /dnalink: 1 Feature /aalink: 3 Feature /name: unknown Feature /inexloc: -1 Feature aa; 3 Feature /rnalink: 2 Feature /name: unknown FeatureHeader allele; 2 Feature dna; 4 Feature /rnalink: 5 Feature /name: point Feature /loc: IDRefSeq: D0095: 19255 Feature /change: g -> a Feature /genomic_region: intron; 22 Feature rna; 5 Feature /dnalink: 4 Feature /aalink: 6 Feature /name: unknown Feature /inexloc: -1 Feature aa; 6 Feature /rnalink: 5 Feature /name: unknown Diagnosis T-B- severe combined immunodeficiency Symptoms Infections: Symptoms P. Carinii pneumonia; Symptoms Others: Symptoms 3-day history of hypoxia and distress requiring intubation, Actinomyces odontolyticus bacteremia Age 5 mo Sex XX Family history Inherited // //