JAK1

Chr 1

Janus kinase 1

Also known as: AIIDE, JAK1A, JAK1B, JTK3

NCBI Gene: 3716ENSG00000162434UniProt: P23458

This gene encodes a membrane protein that is a member of a class of protein-tyrosine kinases (PTK) characterized by the presence of a second phosphotransferase-related domain immediately N-terminal to the PTK domain. The encoded kinase phosphorylates STAT proteins (signal transducers and activators of transcription) and plays a key role in interferon-alpha/beta, interferon-gamma, and cytokine signal transduction. This gene plays a crucial role in effecting the expression of genes that mediate inflammation, epithelial remodeling, and metastatic cancer progression. This gene is a key component of the interleukin-6 (IL-6)/JAK1/STAT3 immune and inflammation response and is a therapeutic target for alleviating cytokine storms. The kinase activity of this gene is directly inhibited by the suppressor of cytokine signalling 1 (SOCS1) protein. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2020]

ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtAutoinflammation, immune dysregulation, and eosinophilia

Clinical highlights

Gene-disease validity (ClinGen)
autoinflammation, immune dysregulation, and eosinophilia · ADDefinitivesufficient evidence for diagnostic panels
Interpreting a novel variant
This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.
7
Active trials
1149
Pubs (1 yr)
—
P/LP submissions
—
P/LP missense
0.21
LOEUF· LoF intol.
Multiple*
Mechanism· predicted
Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Dual constrained — LoF & missense intolerant
LoF Constraint?
0.21LOEUF
pLI 1.000
Z-score 6.44
OE 0.11 (0.06–0.21)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?
4.61Z-score
OE missense 0.50 (0.45–0.55)
332 obs / 666.8 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios?
LoF OE?0.11 (0.06–0.21)
0≤0.351.4
Missense OE?0.50 (0.45–0.55)
0≤0.61.4
Synonymous OE?0.96
0≤1.21.6
LoF obs/exp: 7 / 61.4Missense obs/exp: 332 / 666.8Syn Z: 0.47

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

JAK1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
Acute Myeloid Leukemia (AML)

CART123 Cells With or Without Ruxolitinib in Relapsed/Refractory Acute Myeloid Leukemia

RECRUITING
NCT07464951Phase PHASE1Stephan Grupp MD PhDStarted 2026-05-14
Anti-CD123 LV redirected T cells (CART123)Ruxolitinib (JAKAVI®)
Chronic Spontaneous Urticaria (CSU)Hidradenitis Suppurativa (HS)Psoriasis (PsO)

SKIN Disease Profiling by an Exploratory, pRospective, Biomarker Study in dermatoloGY Practice (SKINERGY)

RECRUITING
NCT07021495Leiden University Medical CenterStarted 2025-07-29
Prolymphocytic LeukemiaT-cell Leukemia

Observatory of Prolymphocytic Leukemia T

RECRUITING
NCT04411043French Innovative Leukemia OrganisationStarted 2020-07-01
Molecular caracterization
Mycosis FungoidesCutaneous T-cell Lymphoma

Topical JAK-Inhibition of Early-Stage CTCL

NOT YET RECRUITING
NCT07781449Phase PHASE2Aarhus University HospitalStarted 2026-09
delgocitinib
Non-Small Cell Lung Cancer

Analysis of Drug Resistance in Immune Checkpoint Inhibitors of Non-small Cell Lung Cancer

RECRUITING
NCT04977791Shanghai Chest HospitalStarted 2016-07-21
Anti-PD-1/PD-L1 monoclonal antibody
Myelofibrosis

A Clinical Trial of TQ05105 Tablets Combined With TQB3617 Capsules in the Treatment of Myelofibrosis (MF)

RECRUITING
NCT06122831Phase PHASE1, PHASE2Chia Tai Tianqing Pharmaceutical Group Co., Ltd.Started 2023-12-12
TQ05105 TabletsTQB3617 Capsules
Head and Neck Cancer Squamous Cell Carcinoma

A Study Testing Emactinib Sulfate With Chemotherapy and Immunotherapy Before Surgery for Advanced Head and Neck Cancer

RECRUITING
NCT07457346Phase PHASE2Second Affiliated Hospital, Zhejiang University, School of MedicineStarted 2026-01-01
cisplatin+ nab-paclitaxel +adebrelimab + imaxitinib

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients