SOCS6

Chr 18

suppressor of cytokine signaling 6

Also known as: CIS-4, CIS4, HSPC060, SOCS-4, SOCS-6, SOCS4, SSI4, STAI4

NCBI Gene: 9306ENSG00000170677UniProt: O14544

SOCS6 encodes a suppressor of cytokine signaling protein that negatively regulates cytokine signal transduction and promotes degradation of specific receptor tyrosine kinases through ubiquitination. The gene is highly constrained against loss-of-function variants (pLI=0.99, LOEUF=0.22), but no specific Mendelian disease has been definitively associated with SOCS6 mutations in humans to date. Given its role in cytokine signaling regulation, mutations would likely affect immune system function and hematopoietic processes.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
20
Pubs (1 yr)
138
P/LP submissions
0%
P/LP missense
0.22
LOEUF· LoF intol.
LOF
Mechanism· predicted
Clinical Summary— SOCS6
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.99). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
136 unique Pathogenic / Likely Pathogenic· 60 VUS of 206 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint
0.22LOEUF
pLI 0.989
Z-score 3.40
OE 0.00 (0.00–0.22)
Highly constrained

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

Missense Constraint
0.85Z-score
OE missense 0.87 (0.79–0.96)
283 obs / 326.4 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.00 (0.00–0.22)
0≤0.351.4
Missense OE0.87 (0.79–0.96)
0≤0.61.4
Synonymous OE1.04
0≤1.21.6
LoF obs/exp: 0 / 13.5Missense obs/exp: 283 / 326.4Syn Z: -0.37
DN
0.3991th %ile
GOF
0.4974th %ile
LOF
0.72top 10%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.22

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

206 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic126
Likely Pathogenic10
VUS60
Likely Benign4
Benign1
126
Pathogenic
10
Likely Pathogenic
60
VUS
4
Likely Benign
1
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
126
0
126
Likely Pathogenic
0
0
10
0
10
VUS
0
46
14
0
60
Likely Benign
0
4
0
0
4
Benign
0
0
0
1
1
Total0501501201

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

View in ClinVar →

Protein Context — Lollipop Plot

SOCS6 · 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

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
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Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
SOCS6 Promotes Mitochondrial Fission and Cardiomyocyte Apoptosis and Is Negatively Regulated by Quaking-Mediated miR-19b
Zhang P et al.·Oxid Med Cell Longev
2022
SOCS6 promotes radiosensitivity and decreases cancer cell stemness in esophageal squamous cell carcinoma by regulating c-Kit ubiquitylation
Sun X et al.·Cancer Cell Int
2021
Down-regulation of SOCS6: an unfavorable prognostic factor for gastrointestinal stromal tumor proven by survival analysis
Ouyang J et al.·Diagn Pathol
2021
MIP From Legionella pneumophila Influences the Phagocytosis and Chemotaxis of RAW264.7 Macrophages by Regulating the lncRNA GAS5/miR-21/SOCS6 Axis
Shen Y et al.·Front Cell Infect Microbiol
2022
Inhibition of SOCS6 confers radioresistance in esophageal squamous cell carcinoma.
Ma R et al.·Biochem Biophys Res Commun
2021
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Serum levels of SOCS6 are decreased in diabetic retinopathy and are related to severity of the disease.
Li L et al.·Adv Clin Exp Med
2023
Suppressor of cytokine signaling 6 in cancer development and therapy: Deciphering its emerging and suppressive roles.
Yang Z et al.·Cytokine Growth Factor Rev
2022Review
SOCS6 Functions as a Tumor Suppressor by Inducing Apoptosis and Inhibiting Angiogenesis in Human Prostate Cancer.
Yuan D et al.·Curr Cancer Drug Targets
2018
[Expression and clinical significance of SIRT1 and SOCS6 in gingival tissue of patients with severe chronic periodontitis].
Yang S et al.·Shanghai Kou Qiang Yi Xue
2025Cohort
HnRNPU-AS1 inhibits the proliferation, migration and invasion of HCC cells and induces autophagy through miR-556-3p/ miR-580-3p/SOCS6 axis.
Zhang L et al.·Cancer Biomark
2022
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

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