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GeneE
26 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
β“˜GeneE is for informational purposes only. It is not a substitute for professional medical advice, diagnosis, or treatment.
JAK3
Janus kinase 3
Chromosome 19 Β· 19p13.11
NCBI Gene: 3718Ensembl: ENSG00000105639.21HGNC: HGNC:6193UniProt: P52333
274PubMed Papers
21Diseases
19Drugs
137Pathogenic Variants
FUNCTIONAL ROLE
Hub GeneKinase
RESEARCH IMPACT
TrendingVariant-Rich
CLINICAL
FDA Approved TargetOMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
extrinsic component of cytoplasmic side of plasma membranenegative regulation of T-helper 17 cell lineage commitmentprotein phosphatase bindinginterleukin-15-mediated signaling pathwayT-B+ severe combined immunodeficiency due to JAK3 deficiencyrheumatoid arthritisulcerative colitismyelofibrosis
✦AI Summary

JAK3 (Janus kinase 3) is a non-receptor tyrosine kinase that plays essential roles in immune system development and function through cytokine signaling pathways 1. JAK3 mediates signaling downstream of cytokine receptors that share the common gamma chain, including IL-2R, IL-4R, IL-7R, and IL-15R 1. Upon cytokine binding, JAK3 becomes activated and phosphorylates STAT proteins (particularly STAT3, STAT5, and STAT6), which then dimerize and translocate to the nucleus to regulate gene transcription 2. The JAK3 gene is located on chromosome 19.1 and consists of 19 exons 3. Mutations in JAK3 cause severe combined immunodeficiency (SCID) characterized by absent T cells and NK cells but normal B cell numbers (T-B+NK- phenotype) 4. This complete developmental block in T cell maturation can be corrected through gene targeting approaches 4. JAK3 has emerged as a therapeutic target, with JAK3 inhibitors showing promise in immunosuppression for organ transplantation and in treating steroid-resistant asthma by suppressing ILC2 cells 56. Specific JAK3 mutations can also influence cancer therapy responses by modulating PD-L1 expression through the STAT3 pathway 2.

Sources cited
1
JAK3 mediates cytokine signaling through STAT protein phosphorylation and nuclear translocation
PMID: 10781830
2
JAK3 gene structure consists of 19 exons and is located on chromosome 19p13.1
PMID: 8921370
3
JAK3 mutations cause SCID with T-B+NK- phenotype and complete block in T cell development
PMID: 26321643
4
JAK3 inhibition shows therapeutic promise for immunosuppression
PMID: 16193102
5
JAK3 inhibitors suppress ILC2 cells and treat steroid-resistant asthma
PMID: 38117887
6
JAK3 mutations affect PD-L1 expression through STAT3 pathway and cancer therapy responses
PMID: 40199606
Disease Associationsβ“˜21
T-B+ severe combined immunodeficiency due to JAK3 deficiencyOpen Targets
0.85Strong
rheumatoid arthritisOpen Targets
0.61Moderate
ulcerative colitisOpen Targets
0.60Moderate
myelofibrosisOpen Targets
0.59Moderate
alopecia areataOpen Targets
0.57Moderate
atopic eczemaOpen Targets
0.56Moderate
Eczematoid dermatitisOpen Targets
0.55Moderate
severe combined immunodeficiencyOpen Targets
0.54Moderate
psoriatic arthritisOpen Targets
0.52Moderate
severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-positiveOpen Targets
0.51Moderate
VitiligoOpen Targets
0.51Moderate
essential thrombocythemiaOpen Targets
0.48Moderate
Omenn syndromeOpen Targets
0.48Moderate
janus kinase-3 deficiencyOpen Targets
0.46Moderate
T-B- severe combined immunodeficiencyOpen Targets
0.46Moderate
T-B+ severe combined immunodeficiencyOpen Targets
0.46Moderate
T+ B+ severe combined immunodeficiencyOpen Targets
0.46Moderate
neoplasmOpen Targets
0.46Moderate
polycythemia veraOpen Targets
0.43Moderate
Crohn's diseaseOpen Targets
0.41Moderate
Severe combined immunodeficiency autosomal recessive T-cell-negative/B-cell-positive/NK-cell-negativeUniProt
Pathogenic Variants137
NM_000215.4(JAK3):c.1333C>T (p.Arg445Ter)Pathogenic
T-B+ severe combined immunodeficiency due to JAK3 deficiency
β˜…β˜…β˜…β˜†2024β†’ Residue 445
NM_000215.4(JAK3):c.1695C>A (p.Cys565Ter)Pathogenic
T-B+ severe combined immunodeficiency due to JAK3 deficiency|not provided
β˜…β˜…β˜…β˜†2024β†’ Residue 565
NM_000215.4(JAK3):c.2311C>T (p.Arg771Ter)Pathogenic
T-B+ severe combined immunodeficiency due to JAK3 deficiency
β˜…β˜…β˜…β˜†2024β†’ Residue 771
NM_000215.4(JAK3):c.1351C>T (p.Arg451Ter)Pathogenic
not provided|T-B+ severe combined immunodeficiency due to JAK3 deficiency|Severe combined immunodeficiency disease
β˜…β˜…β˜…β˜†2023β†’ Residue 451
NM_000215.4(JAK3):c.1837C>T (p.Arg613Ter)Pathogenic
T-B+ severe combined immunodeficiency due to JAK3 deficiency
β˜…β˜…β˜…β˜†2023β†’ Residue 613
NM_000215.4(JAK3):c.175A>T (p.Lys59Ter)Likely pathogenic
T-B+ severe combined immunodeficiency due to JAK3 deficiency
β˜…β˜…β˜…β˜†2023β†’ Residue 59
NM_000215.4(JAK3):c.2680+89G>ALikely pathogenic
T-B+ severe combined immunodeficiency due to JAK3 deficiency
β˜…β˜…β˜…β˜†2023
NM_000215.4(JAK3):c.678_679del (p.Cys227fs)Pathogenic
Severe combined immunodeficiency disease|not provided|T-B+ severe combined immunodeficiency due to JAK3 deficiency
β˜…β˜…β˜…β˜†2023β†’ Residue 227
NM_000215.4(JAK3):c.1744C>T (p.Arg582Trp)Likely pathogenic
Severe combined immunodeficiency disease|T-B+ severe combined immunodeficiency due to JAK3 deficiency
β˜…β˜…β˜…β˜†2023β†’ Residue 582
NM_000215.4(JAK3):c.1205G>A (p.Arg402His)Likely pathogenic
T-B+ severe combined immunodeficiency due to JAK3 deficiency|Severe combined immunodeficiency disease
β˜…β˜…β˜†β˜†2025β†’ Residue 402
NM_000215.4(JAK3):c.1432dup (p.Arg478fs)Pathogenic
not provided|T-B+ severe combined immunodeficiency due to JAK3 deficiency
β˜…β˜…β˜†β˜†2025β†’ Residue 478
NM_000215.4(JAK3):c.307C>T (p.Arg103Cys)Pathogenic
not provided|T-B+ severe combined immunodeficiency due to JAK3 deficiency|Severe combined immunodeficiency disease
β˜…β˜…β˜†β˜†2025β†’ Residue 103
NM_000215.4(JAK3):c.1019C>A (p.Ser340Ter)Pathogenic
not provided|T-B+ severe combined immunodeficiency due to JAK3 deficiency
β˜…β˜…β˜†β˜†2025β†’ Residue 340
NM_000215.4(JAK3):c.2680+3G>CPathogenic
T-B+ severe combined immunodeficiency due to JAK3 deficiency
β˜…β˜…β˜†β˜†2025
NM_000215.4(JAK3):c.3208-1G>APathogenic
not provided|T-B+ severe combined immunodeficiency due to JAK3 deficiency
β˜…β˜…β˜†β˜†2025
NM_000215.4(JAK3):c.308G>A (p.Arg103His)Pathogenic
not provided|T-B+ severe combined immunodeficiency due to JAK3 deficiency|Severe combined immunodeficiency disease
β˜…β˜…β˜†β˜†2025β†’ Residue 103
NM_000215.4(JAK3):c.3085dup (p.Ser1029fs)Pathogenic
T-B+ severe combined immunodeficiency due to JAK3 deficiency|Severe combined immunodeficiency disease
β˜…β˜…β˜†β˜†2025β†’ Residue 1029
NM_000215.4(JAK3):c.2978G>A (p.Trp993Ter)Likely pathogenic
T-B+ severe combined immunodeficiency due to JAK3 deficiency
β˜…β˜…β˜†β˜†2024β†’ Residue 993
NM_000215.4(JAK3):c.1765G>A (p.Gly589Ser)Pathogenic
not provided|T-B+ severe combined immunodeficiency due to JAK3 deficiency|Severe combined immunodeficiency disease|Adenoid cystic carcinoma
β˜…β˜…β˜†β˜†2024β†’ Residue 589
NM_000215.4(JAK3):c.2712C>A (p.Tyr904Ter)Pathogenic
T-B+ severe combined immunodeficiency due to JAK3 deficiency|Severe combined immunodeficiency disease
β˜…β˜…β˜†β˜†2024β†’ Residue 904
View on ClinVar β†—
Drug Targets19
AT-9283Phase III
Serine/threonine-protein kinase Aurora-A inhibitor
CERDULATINIBPhase II
Tyrosine-protein kinase JAK1 inhibitor
B-cell non-Hodgkins lymphoma
DECERNOTINIBPhase II/III
Tyrosine-protein kinase JAK3 inhibitor
rheumatoid arthritis
DELGOCITINIBApproved
Janus Kinase (JAK) inhibitor
atopic eczema
DEURUXOLITINIB PHOSPHATEApproved
Tyrosine-protein kinase TYK2 inhibitor
alopecia areata
FILGOTINIBPhase III
Tyrosine-protein kinase JAK2 inhibitor
rheumatoid arthritis
FILGOTINIB MALEATEApproved
Tyrosine-protein kinase JAK2 inhibitor
rheumatoid arthritis
GUSACITINIBPhase II
Janus Kinase (JAK) inhibitor
Eczematoid dermatitis
IZENCITINIBPhase II/III
Janus Kinase (JAK) inhibitor
ulcerative colitis
NEZULCITINIBPhase II
Janus Kinase (JAK) inhibitor
COVID-19
PEFICITINIBPhase III
Janus Kinase (JAK) inhibitor
psoriasis vulgaris
R-348Phase II
Tyrosine-protein kinase SYK inhibitor
dry eye syndrome
RITLECITINIBApproved
Tyrosine-protein kinase JAK3 inhibitor
alopecia areata
RITLECITINIB TOSYLATEApproved
Tyrosine-protein kinase JAK3 inhibitor
alopecia areata
RUXOLITINIBApproved
Tyrosine-protein kinase JAK1 inhibitor
essential thrombocythemia
TOFACITINIBApproved
Janus Kinase (JAK) inhibitor
rheumatoid arthritis
TOFACITINIB CITRATEApproved
Janus Kinase (JAK) inhibitor
UPADACITINIBApproved
Tyrosine-protein kinase JAK1 inhibitor
rheumatoid arthritis
UPADACITINIB HEMIHYDRATEApproved
Tyrosine-protein kinase JAK1 inhibitor
rheumatoid arthritis
Related Genes
GHRProtein interaction100%IFNA4Protein interaction100%IFNA5Protein interaction100%IFNA6Protein interaction100%IFNA7Protein interaction100%IFNA8Protein interaction100%
Tissue Expression6 tissues
Ovary
100%
Lung
89%
Bone Marrow
85%
Liver
15%
Brain
10%
Heart
6%
Gene Interaction Network
Click a node to explore
JAK3GHRIFNA4IFNA5IFNA6IFNA7IFNA8
PROTEIN STRUCTURE
Preparing viewer…
PDB5LWM Β· 1.55 Γ… Β· X-ray
View on RCSB β†—
Constraintβ“˜
LOEUFβ“˜
0.93LoF Tolerant
pLIβ“˜
0.00Tolerant
Observed/Expected LoF0.78 [0.66–0.93]
RankingsWhere JAK3 stands among ~20K protein-coding genes
  • #1,335of 20,598
    Most Researched274 Β· top 10%
  • #153of 1,025
    FDA-Approved Drug Targets10 Β· top quartile
  • #563of 5,498
    Most Pathogenic Variants137 Β· top quartile
  • #8,629of 17,882
    Most Constrained (LOEUF)0.93
Genes detectedJAK3
Sources retrieved26 papers
Response timeβ€”
πŸ“„ Sources
26β–Ό
1
JAK3 inhibitor suppresses multipotent ILC2s and attenuates steroid-resistant asthma.
PMID: 38117887
Sci Adv Β· 2023
1.00
2
The Jak-STAT pathway.
PMID: 10781830
Mol Immunol Β· 2000
0.90
3
JAK protein kinase inhibitors.
PMID: 16193102
Drug News Perspect Β· 2005
0.80
4
Regulation of JAK3 expression and activation in human B cells and B cell malignancies.
PMID: 7594533
J Immunol Β· 1995
0.76
5
Modeling Human Severe Combined Immunodeficiency and Correction by CRISPR/Cas9-Enhanced Gene Targeting.
PMID: 26321643
Cell Rep Β· 2015
0.70