SOCS1
Chr 16ADsuppressor of cytokine signaling 1
Also known as: AISIMD, CIS1, CISH1, JAB, SOCS-1, SSI-1, SSI1, TIP-3
The protein functions as an essential negative regulator of interferon and cytokine signaling by inhibiting the JAK/STAT pathway and promoting degradation of target proteins through its role in an E3 ubiquitin ligase complex. Mutations cause autosomal dominant autoinflammatory syndrome, familial, with or without immunodeficiency, affecting the immune system through dysregulated cytokine responses. The gene shows moderate constraint against loss-of-function variants (LOEUF 1.068), consistent with its role in immune regulation.
Definitive — sufficient evidence for diagnostic panels
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly tolerant — LoF variants common in population
Mild missense constraint
The Badonyi & Marsh model scores gain-of-function highest, but genomic evidence most strongly supports loss-of-function (haploinsufficiency) as the primary mechanism.
Literature Evidence
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
0 submitted variants in ClinVar
Protein Context — Lollipop Plot
SOCS1 · 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
A Phase 1/2 Study of KSQ-004EX, Autologous Tumor Infiltrating Lymphocytes Engineered to Inactivate Genes Encoding SOCS1 and Regnase-1, in Patients With Select Advanced Solid Tumors
RECRUITINGProspective Cohort Study of Liver Cancer Patients Treated With Proton Beam Therapy
ENROLLING BY INVITATIONA Phase 1/2 Study of KSQ-001EX, Autologous Tumor Infiltrating Lymphocytes Engineered to Inactivate the SOCS1 Gene, in Patients With Select Advanced Solid Tumors
ACTIVE NOT RECRUITINGExternal Resources
Links to major genomics databases and tools