SOCS1

Chr 16AD

suppressor of cytokine signaling 1

Also known as: AISIMD, CIS1, CISH1, JAB, SOCS-1, SSI-1, SSI1, TIP-3

NCBI Gene: 8651ENSG00000185338UniProt: O15524

This gene encodes a member of the STAT-induced STAT inhibitor (SSI), also known as suppressor of cytokine signaling (SOCS), family. SSI family members are cytokine-inducible negative regulators of cytokine signaling. The expression of this gene can be induced by a subset of cytokines, including IL2, IL3 erythropoietin (EPO), CSF2/GM-CSF, and interferon (IFN)-gamma. The protein encoded by this gene functions downstream of cytokine receptors, and takes part in a negative feedback loop to attenuate cytokine signaling. Knockout studies in mice suggested the role of this gene as a modulator of IFN-gamma action, which is required for normal postnatal growth and survival. [provided by RefSeq, Jul 2008]

Primary Disease Associations & Inheritance

Autoinflammatory syndrome, familial, with or without immunodeficiencyMIM #619375
AD
114
ClinVar variants
31
Pathogenic / LP
0.59
pLI score
3
Active trials
Clinical Summary— SOCS1
🧬
Gene-Disease Validity (ClinGen)
autoinflammatory syndrome with immunodeficiency · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.59) — some intolerance to loss-of-function variants.
📋
ClinVar Variants
31 Pathogenic / Likely Pathogenic· 73 VUS of 114 total submissions
💊
Clinical Trials
3 active or recruiting trials — potential therapeutic options may be available
Some data sources returned errors (1)

pubmed: Error: NCBI fetch failed: 429 https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esummary.fcgi

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
1.07LOEUF
pLI 0.585
Z-score 1.53
OE 0.00 (0.00–1.07)
Moderately constrained

Highly tolerant — LoF variants common in population

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.83Z-score
OE missense 0.75 (0.62–0.92)
67 obs / 89.0 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.00 (0.00–1.07)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.75 (0.62–0.92)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.61
0≤1.21.6
LoF obs/exp: 0 / 2.7Missense obs/exp: 67 / 89.0Syn Z: -3.09

ClinVar Variant Classifications

114 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic23
Likely Pathogenic8
VUS73
Likely Benign6
Benign4
23
Pathogenic
8
Likely Pathogenic
73
VUS
6
Likely Benign
4
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
4
1
18
0
23
Likely Pathogenic
1
3
4
0
8
VUS
3
56
14
0
73
Likely Benign
0
2
1
3
6
Benign
0
0
2
2
4
Total862395114

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View 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.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Autoinflammatory syndrome, familial, with or without immunodeficiency

MIM #619375

Molecular basis of disorder known

Autosomal dominant
Clinical Literature
Landmark / reviewRecent case evidence
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Aberrant STAT3 activation and overproduction of IL-21 in systemic lupus erythematosus: role of miR-155 and miR-21 in target genes SOCS1, PTEN and PIAS3.
Espinoza-García N et al.·Front Immunol
2026🔓 Open Access
Loss of SOCS1 in Donor T Cells Exacerbates Intestinal GVHD by Driving a Chemokine-Dependent Pro-Inflammatory Immune Microenvironment.
Wu Z et al.·Adv Sci (Weinh)
2026
Japanese eel SOCS1 suppresses MyD88-mediated NF-κB activation: implications for negative regulation of innate immunity in teleosts.
Wang T et al.·Fish Shellfish Immunol
2026
LncRNA PCED1B-AS1 Inhibits Sepsis-Induced Acute Kidney Injury by Promoting Transformation of Macrophages from M1 to M2 Type via Regulating the miR-361-3p/SOCS1 Axis.
Huang P et al.·J Inflamm Res
2025🔓 Open Access
Targeting the Gas6-TAM-SOCS1/3 axis: CP-25 attenuates macrophage dysfunction in primary Sjögren's syndrome.
Chen Y et al.·Exp Cell Res
2026
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
Advanced Solid TumorMelanomaLung Neoplasms

A 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 RECRUITING
NCT06237881Phase PHASE1, PHASE2M.D. Anderson Cancer CenterStarted 2024-01-31
KSQ-001EXInterleukin-2Cyclophosphamide
Select Advanced Solid Tumors

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

RECRUITING
NCT06598371Phase PHASE1, PHASE2M.D. Anderson Cancer CenterStarted 2024-11-21
CyclophosphamideFludarabineKSQ-004EX
Liver Cancer

Prospective Cohort Study of Liver Cancer Patients Treated With Proton Beam Therapy

ENROLLING BY INVITATION
NCT04466124National Cancer Center, KoreaStarted 2018-09-21
Liver Cancer Patients Treated With Proton Beam Therapy

External Resources

Links to major genomics databases and tools