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GeneE
50 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.
JAK1
Janus kinase 1
Chromosome 1 Β· 1p31.3
NCBI Gene: 3716Ensembl: ENSG00000162434.14HGNC: HGNC:6190UniProt: A0A8V8TPQ9
528PubMed Papers
21Diseases
25Drugs
4Pathogenic Variants
FUNCTIONAL ROLE
Highly ConstrainedHub GeneKinase
RESEARCH IMPACT
Highly StudiedTrending
CLINICAL
FDA Approved TargetOMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
response to antibioticpositive regulation of homotypic cell-cell adhesioninterleukin-15-mediated signaling pathwayinterleukin-4-mediated signaling pathwayrheumatoid arthritisautoinflammation, immune dysregulation, and eosinophiliaEczematoid dermatitisatopic eczema
✦AI Summary

JAK1 is a non-receptor tyrosine kinase that mediates cytokine and interferon signaling through the JAK-STAT pathway 1. JAK1 serves as a kinase partner for type I interferon receptor IFNAR2, where interferon binding triggers JAK1 phosphorylation of IFNAR2 to create docking sites for STAT proteins 2. JAK1 directly phosphorylates STAT proteins and transactivates other JAK kinases associated with signaling receptors 1. Additionally, JAK1 functions with IL-2 and IL-10 receptors to mediate interleukin signaling 34. Dysregulated JAK1 signaling associates with multiple pathologies. Gain-of-function JAK1 variants cause severe atopy with enhanced myelopoiesis, Th cell skewing, and marked eosinophilia; JAK1/2 inhibitor ruxolitinib treatment of affected children improved growth and allergic inflammation 5. In inflammatory skin diseases, elevated keratin 6A promotes JAK1-STAT3 activation in keratinocytes by reducing JAK1 ubiquitination, exacerbating rosacea and psoriasis-like inflammation 6. JAK1 polymorphism rs310241 associates with allergic rhinitis susceptibility 7. Clinically, selective JAK1 inhibitors (upadacitinib, abrocitinib) effectively treat moderate-to-severe atopic dermatitis and rheumatoid arthritis 89. Ruxolitinib inhibits basophil and mast cell mediator release, providing therapeutic potential for inflammatory disorders 10. JAK1 also integrates STING and type I interferon signaling in endothelium to promote tumor vasculature normalization and CD8+ T cell infiltration 11.

Sources cited
1
JAK1 is a non-receptor tyrosine kinase involved in IFN-alpha/beta/gamma signal pathway and IFNAR2 signaling
PMID: 16239216
2
JAK1 phosphorylates IFNAR2 upon interferon binding, creating STAT protein docking sites
PMID: 7759950
3
JAK1 is a kinase partner for the IL-2 receptor
PMID: 11909529
4
JAK1 is a kinase partner for the IL-10 receptor
PMID: 12133952
5
JAK1 gain-of-function variants cause severe atopy with eosinophilia; JAK1/2 inhibitor ruxolitinib improves symptoms
PMID: 36546480
6
Keratin 6A promotes JAK1-STAT3 activation in keratinocytes by reducing JAK1 ubiquitination, exacerbating skin inflammation
PMID: 40346694
7
JAK1 polymorphism rs310241 associates with allergic rhinitis susceptibility
PMID: 27007833
8
Upadacitinib, a JAK1 inhibitor, received FDA approval for rheumatoid arthritis treatment
PMID: 31642025
9
JAK1 inhibitors treat moderate-to-severe atopic dermatitis with shorter efficacy duration than dupilumab
PMID: 40317605
10
JAK1/2 inhibitor ruxolitinib inhibits mediator release from basophils and mast cells
PMID: 39188724
11
JAK1 integrates STING and type I interferon signaling in endothelium to promote antitumor immunity
PMID: 39817453
Disease Associationsβ“˜21
rheumatoid arthritisOpen Targets
0.69Moderate
autoinflammation, immune dysregulation, and eosinophiliaOpen Targets
0.69Moderate
Eczematoid dermatitisOpen Targets
0.60Moderate
atopic eczemaOpen Targets
0.59Moderate
myelofibrosisOpen Targets
0.58Moderate
COVID-19Open Targets
0.55Moderate
graft versus host diseaseOpen Targets
0.54Moderate
polycythemia veraOpen Targets
0.54Moderate
ulcerative colitisOpen Targets
0.53Moderate
psoriatic arthritisOpen Targets
0.52Moderate
primary myelofibrosisOpen Targets
0.51Moderate
myeloproliferative disorderOpen Targets
0.51Moderate
juvenile idiopathic arthritisOpen Targets
0.50Moderate
neoplasmOpen Targets
0.50Moderate
alopecia areataOpen Targets
0.50Moderate
hypothyroidismOpen Targets
0.50Moderate
VitiligoOpen Targets
0.48Moderate
essential thrombocythemiaOpen Targets
0.47Moderate
myxedemaOpen Targets
0.46Moderate
prostate adenocarcinomaOpen Targets
0.42Moderate
Autoinflammation, immune dysregulation, and eosinophiliaUniProt
Pathogenic Variants4
NM_002227.4(JAK1):c.1901C>A (p.Ala634Asp)Likely pathogenic
Inborn genetic diseases|Autoinflammation, immune dysregulation, and eosinophilia
β˜…β˜†β˜†β˜†2024β†’ Residue 634
NM_002227.4(JAK1):c.2347C>T (p.Leu783Phe)Likely pathogenic
Acute megakaryoblastic leukemia in down syndrome
β˜…β˜†β˜†β˜†2020β†’ Residue 783
NM_002227.4(JAK1):c.1786C>G (p.His596Asp)Pathogenic
Autoinflammation, immune dysregulation, and eosinophilia
β˜†β˜†β˜†β˜†2022β†’ Residue 596
NM_002227.4(JAK1):c.2108G>T (p.Ser703Ile)Pathogenic
Autoinflammation, immune dysregulation, and eosinophilia
β˜†β˜†β˜†β˜†2020β†’ Residue 703
View on ClinVar β†—
Drug Targets25
ABROCITINIBApproved
Tyrosine-protein kinase JAK1 inhibitor
BARICITINIBApproved
Tyrosine-protein kinase JAK1 inhibitor
juvenile idiopathic arthritis
BREPOCITINIBPhase III
Tyrosine-protein kinase TYK2 inhibitor
dermatomyositis
CERDULATINIBPhase II
Tyrosine-protein kinase JAK1 inhibitor
B-cell non-Hodgkins lymphoma
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
GLPG-0555Phase I
Tyrosine-protein kinase JAK1 inhibitor
osteoarthritis
GOLIDOCITINIBPhase II
Tyrosine-protein kinase JAK1 inhibitor
unspecified peripheral T-cell lymphoma
GUSACITINIBPhase II
Janus Kinase (JAK) inhibitor
Eczematoid dermatitis
INCB-047986Phase II
Tyrosine-protein kinase JAK1 inhibitor
rheumatoid arthritis
ITACITINIBPhase III
Tyrosine-protein kinase JAK1 inhibitor
graft versus host disease
IZENCITINIBPhase II/III
Janus Kinase (JAK) inhibitor
ulcerative colitis
MOMELOTINIBApproved
Activin receptor type-1 inhibitor
myelofibrosis
MOMELOTINIB DIHYDROCHLORIDE MONOHYDRATEApproved
Activin receptor type-1 inhibitor
myelofibrosis
NEZULCITINIBPhase II
Janus Kinase (JAK) inhibitor
COVID-19
PEFICITINIBPhase III
Janus Kinase (JAK) inhibitor
psoriasis vulgaris
RUXOLITINIBApproved
Tyrosine-protein kinase JAK1 inhibitor
essential thrombocythemia
RUXOLITINIB PHOSPHATEApproved
Tyrosine-protein kinase JAK1 inhibitor
graft versus host disease
SOLCITINIBPhase II
Tyrosine-protein kinase JAK1 inhibitor
systemic lupus erythematosus
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
IL5RAProtein interaction100%IL15RAProtein interaction100%IL24Protein interaction100%IL19Protein interaction100%IFNL2Protein interaction100%IFNL3Protein interaction100%
Tissue Expression6 tissues
Lung
100%
Brain
81%
Ovary
70%
Heart
70%
Bone Marrow
56%
Liver
43%
Gene Interaction Network
Click a node to explore
JAK1IL5RAIL15RAIL24IL19IFNL2IFNL3
PROTEIN STRUCTURE
Preparing viewer…
PDB6N7A Β· 1.33 Γ… Β· X-ray
View on RCSB β†—
Constraintβ“˜
LOEUFβ“˜
0.17Highly Constrained
pLIβ“˜
1.00Intolerant
Observed/Expected LoF0.11 [0.07–0.17]
RankingsWhere JAK1 stands among ~20K protein-coding genes
  • #485of 20,598
    Most Researched528 Β· top 5%
  • #113of 1,025
    FDA-Approved Drug Targets13 Β· top quartile
  • #3,666of 5,498
    Most Pathogenic Variants4
  • #287of 17,882
    Most Constrained (LOEUF)0.17 Β· top 5%
Genes detectedJAK1
Sources retrieved50 papers
Response timeβ€”
πŸ“„ Sources
50β–Ό
1
METTL3 promotes colorectal cancer progression through activating JAK1/STAT3 signaling pathway.
PMID: 38001065
Cell Death Dis Β· 2023
1.00
2
Endothelial STING-JAK1 interaction promotes tumor vasculature normalization and antitumor immunity.
PMID: 39817453
J Clin Invest Β· 2025
0.90
3
JAK1 promotes HDV replication and is a potential target for antiviral therapy.
PMID: 37925078
J Hepatol Β· 2024
0.80
4
The JAK1/JAK2 inhibitor ruxolitinib inhibits mediator release from human basophils and mast cells.
PMID: 39188724
Front Immunol Β· 2024
0.80
5
SO
PMID: 39353391
Int Immunopharmacol Β· 2024
0.78