T-B+ severe combined immunodeficiency due to JAK3 deficiency: genes and variants
T-B+ severe combined immunodeficiency due to JAK3 deficiency is linked to 3 analyzed proteins (JAK3, PTPRC and IL7R). 22 DNA variants are known to cause it; 256 more are uncertain, and 0 of those already look disease-causing on computable evidence.
Last updated 2026-09-30. Research information, not medical advice.
Genes linked to T-B+ severe combined immunodeficiency due to JAK3 deficiency
JAK3: Tyrosine-protein kinase JAK3
It carries signals from cytokine receptors using the common gamma chain and is essential for T-cell and NK-cell development. Biallelic loss-of-function variants cause severe combined immunodeficiency, while activating somatic variants occur in selected leukemias and lymphomas.
22 disease-causing and 256 uncertain variants in JAK3 are linked to T-B+ severe combined immunodeficiency due to JAK3 deficiency.
PTPRC: Receptor-type tyrosine-protein phosphatase C
It controls phosphorylation of Src-family kinases and is essential for effective antigen-receptor signaling in nearly all nucleated blood cells. Biallelic loss-of-function variants can cause severe combined immunodeficiency.
0 disease-causing and 0 uncertain variants in PTPRC are linked to T-B+ severe combined immunodeficiency due to JAK3 deficiency.
IL7R: Interleukin-7 receptor subunit alpha
It transmits survival and developmental signals required for T-cell and lymphoid homeostasis. Biallelic loss-of-function variants cause T-cell-negative, B-cell-positive severe combined immunodeficiency, while somatic activating alterations occur in acute lymphoblastic leukemia.
0 disease-causing and 0 uncertain variants in IL7R are linked to T-B+ severe combined immunodeficiency due to JAK3 deficiency.
Where T-B+ severe combined immunodeficiency due to JAK3 deficiency variants cluster
- JAK3 Protein kinase 1 (positions 521–781): 8 of 22 disease-causing changes, 1.6× more than its size predicts.
- JAK3 SH2 (positions 375–475): 4 of 22 disease-causing changes, 2.0× more than its size predicts.
Known disease-causing variants in T-B+ severe combined immunodeficiency due to JAK3 deficiency
| Variant | Position | Protein part | Clinical label |
|---|---|---|---|
| JAK3 C193Y | 193 | FERM | Disease-causing (★★★) |
| JAK3 R582W | 582 | Protein kinase 1 | Disease-causing (★★★) |
| JAK3 R403H | 403 | SH2 | Disease-causing (★★★) |
| JAK3 R103C | 103 | FERM | Disease-causing (★★) |
| JAK3 R103H | 103 | FERM | Disease-causing (★★) |
| JAK3 D144V | 144 | FERM | Disease-causing (★★) |
| JAK3 G589S | 589 | Protein kinase 1 | Disease-causing (★★) |
| JAK3 R775H | 775 | Protein kinase 1 | Disease-causing (★★) |
| JAK3 R651W | 651 | Protein kinase 1 | Disease-causing (★★) |
| JAK3 T714M | 714 | Protein kinase 1 | Disease-causing (★★) |
| JAK3 R402H | 402 | SH2 | Disease-causing (★★) |
| JAK3 G528D | 528 | Protein kinase 1 | Disease-causing (★) |
| JAK3 R350W | 350 | FERM | Disease-causing (★) |
| JAK3 G397V | 397 | SH2 | Disease-causing (★) |
| JAK3 V146G | 146 | FERM | Disease-causing (★) |
| JAK3 L369P | 369 | Disease-causing (★) | |
| JAK3 I430T | 430 | SH2 | Disease-causing (★) |
| JAK3 E1019K | 1019 | Protein kinase 2 | Disease-causing (★) |
| JAK3 D784N | 784 | Disease-causing (★) | |
| JAK3 Y100C | 100 | FERM | Disease-causing |
| JAK3 V599G | 599 | Protein kinase 1 | Disease-causing |
| JAK3 W709R | 709 | Protein kinase 1 | Disease-causing |
Which prediction tools work for T-B+ severe combined immunodeficiency due to JAK3 deficiency
How often each tool ranks a disease-causing variant above a harmless one (AUROC × 100).
- CADD: 99 out of 100
- CATVariant: 96 out of 100 (learned from overlapping clinical labels, so this is optimistic)
- phyloP: 95 out of 100
- PolyPhen-2: 94 out of 100 (learned from overlapping clinical labels, so this is optimistic)
- REVEL: 91 out of 100 (learned from overlapping clinical labels, so this is optimistic)
- SIFT: 89 out of 100
Diseases related to T-B+ severe combined immunodeficiency due to JAK3 deficiency
- Severe combined immunodeficiency disease, also linked to IL7R and JAK3
- Severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-positive, also linked to JAK3
- Essential thrombocythemia, also linked to JAK3
- Hypothyroidism, also linked to IL7R
- Acquired polycythemia vera, also linked to JAK3
Frequently asked questions
Which genes are linked to T-B+ severe combined immunodeficiency due to JAK3 deficiency?
In CATVariant, T-B+ severe combined immunodeficiency due to JAK3 deficiency is linked to 3 analyzed proteins: JAK3 (Tyrosine-protein kinase JAK3), PTPRC (Receptor-type tyrosine-protein phosphatase C) and IL7R (Interleukin-7 receptor subunit alpha).
How many genetic variants are linked to T-B+ severe combined immunodeficiency due to JAK3 deficiency?
515 variants: 22 are classified as disease-causing (pathogenic or likely pathogenic) in ClinVar and 256 are of uncertain significance or have conflicting reports.
Which uncertain variants in T-B+ severe combined immunodeficiency due to JAK3 deficiency look disease-causing?
None of the uncertain variants currently reaches the likely-pathogenic range on computable evidence alone.
Which variant effect predictor works best for T-B+ severe combined immunodeficiency due to JAK3 deficiency?
Among tools not trained on clinical labels, CADD separates this disease's known disease-causing variants from harmless ones best (AUROC 0.99, based on 17 disease-causing and 51 harmless variants).
About this data
Variant–disease links come from ClinVar, Open Targets and UniProt, pooled from the latest public CATVariant analysis of each human protein. Evidence scores use the ACMG/AMP Bayesian points scale with computable criteria only (position among known disease variants, rarity in gnomAD, calibrated predictors, deep mutational scanning); there is no family or patient data, so they prioritise variants for expert review and never classify them.
Download every variant as CSV · Browse all diseases · Methods · About the Center