JAK1
Chr 1ADJanus kinase 1
Also known as: AIIDE, JAK1A, JAK1B, JTK3
The JAK1 protein is a tyrosine kinase that phosphorylates STAT proteins and serves as a critical component in interferon and cytokine signaling pathways, including IL-2, IL-6, and IL-10 receptor signaling. Mutations cause autoinflammation, immune dysregulation, and eosinophilia with autosomal dominant inheritance. This gene is highly constrained against loss-of-function variants, indicating that such mutations are likely to have significant clinical consequences.
Primary Disease Associations & Inheritance
Definitive — sufficient evidence for diagnostic panels
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly LoF-intolerant (top ~10% of genes)
Highly missense-constrained (top ~0.1%)
This gene has evidence for multiple mechanisms of pathogenicity (loss-of-function and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to loss-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
Literature Evidence
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.
ClinVar Variant Classifications
0 submitted variants in 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.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
Observatory of Prolymphocytic Leukemia T
RECRUITINGIL-6, IL-12, IL-15 and IL-23 Expression Levels in Rheumatoid Arthritis Patients
NOT YET RECRUITINGA Study Testing Emactinib Sulfate With Chemotherapy and Immunotherapy Before Surgery for Advanced Head and Neck Cancer
RECRUITINGSKIN Disease Profiling by an Exploratory, pRospective, Biomarker Study in dermatoloGY Practice (SKINERGY)
RECRUITINGAnalysis of Drug Resistance in Immune Checkpoint Inhibitors of Non-small Cell Lung Cancer
RECRUITINGCART123 Cells With or Without Ruxolitinib in Relapsed/Refractory Acute Myeloid Leukemia
NOT YET RECRUITINGSynergistic Effect of Elemene Plus TKIs Compared With TKIs in EGFR-mutated Advanced NSCLC：Prospective Study
RECRUITINGA Clinical Trial of TQ05105 Tablets Combined With TQB3617 Capsules in the Treatment of Myelofibrosis (MF)
RECRUITINGExternal Resources
Links to major genomics databases and tools