SOCS3

Chr 17

suppressor of cytokine signaling 3

Also known as: ATOD4, CIS3, Cish3, SOCS-3, SSI-3, SSI3

NCBI Gene: 9021ENSG00000184557UniProt: O14543

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 is induced by various cytokines, including IL6, IL10, and interferon (IFN)-gamma. The protein encoded by this gene can bind to JAK2 kinase, and inhibit the activity of JAK2 kinase. Studies of the mouse counterpart of this gene suggested the roles of this gene in the negative regulation of fetal liver hematopoiesis, and placental development. [provided by RefSeq, Jul 2008]

1
Active trials
14
Pathogenic / LP
48
ClinVar variants
5
Pubs (1 yr)
1.9
Missense Z
0.66
LOEUF
Clinical Summary— SOCS3
⚡
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.75) — some intolerance to loss-of-function variants.
📋
ClinVar Variants
14 Pathogenic / Likely Pathogenic· 30 VUS of 48 total submissions
💊
Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

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.
0.66LOEUF
pLI 0.746
Z-score 1.97
OE 0.00 (0.00–0.66)
Moderately constrained

Typical tolerance to LoF variation

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.
1.86Z-score
OE missense 0.56 (0.46–0.67)
78 obs / 140.0 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 (0.00–0.66)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.56 (0.46–0.67)
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.1.15
0≤1.21.6
LoF obs/exp: 0 / 4.5Missense obs/exp: 78 / 140.0Syn Z: -0.94

ClinVar Variant Classifications

48 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic13
Likely Pathogenic1
VUS30
Likely Benign3
Benign1
13
Pathogenic
1
Likely Pathogenic
30
VUS
3
Likely Benign
1
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
13
0
13
Likely Pathogenic
0
0
1
0
1
VUS
0
28
2
0
30
Likely Benign
0
2
1
0
3
Benign
0
1
0
0
1
Total03117048

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

View in ClinVar →

Protein Context — Lollipop Plot

SOCS3 · protein map & ClinVar variants

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

Clinical Literature
Landmark / reviewRecent case evidence
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
SOCS3 Acts as an Onco-immunological Biomarker With Value in Assessing the Tumor Microenvironment, Pathological Staging, Histological Subtypes, Therapeutic Effect, and Prognoses of Several Types of Cancer
Dai L et al.·Front Oncol
2022
SOCS3 deficiency in cardiomyocytes elevates sensitivity of ischemic preconditioning that synergistically ameliorates myocardial ischemia reperfusion injury
Nohara S et al.·PLoS One
2021
Expression of mycobacterium tuberculosis induced SOCS3 and STAT3 and the implications on innate immunity in TB patients vs healthy contacts in high TB/HIV endemic setting: A cross-sectional analytical study
Lungu P et al.·PLoS One
2022Cohort
Association of Aberrant Promoter Methylation Changes in the Suppressor of Cytokine Signaling 3 (SOCS3) Gene with Susceptibility to Crohn's Disease
Sanati G et al.·Avicenna J Med Biotechnol
2022
Association between SOCS3 hypermethylation and HBV-related hepatocellular carcinoma and effect of sex and age
Zheng H et al.·Medicine (Baltimore)
2021
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Knockdown of SOX4 attenuates sepsis myocardial injury by inhibiting the EZH2/H3K27me3/SOCS3 axis.
Zhao H et al.·Mamm Genome
2026
Hyaluronic Acid Hydrogel-Mediated Delivery of MSC-Derived Exo-FGF21 Promotes Spinal Cord Injury Repair via STAT3/SOCS3 Signaling.
Xiao X et al.·Biotechnol Bioeng
2026
Glycolytic reprogramming of resident alveolar macrophages contributes to reduced SOCS3 secretion in non-small cell lung cancer.
Speth JM et al.·Front Immunol
2025Open Access
Mesenchymal stromal cells alleviate pulmonary arterial hypertension by suppressing pulmonary arterial adventitial fibroblast activation and extracellular matrix remodeling via the SOCS3/STAT3 pathway.
Wang J et al.·Stem Cell Res Ther
2026Open AccessFunctional
[Corrigendum] Isolinderalactone enhances the inhibition of SOCS3 on STAT3 activity by decreasing miR‑30c in breast cancer.
Yen MC et al.·Oncol Rep
2026Open Access
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