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: O15524OMIM: 603597

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]

OMIMResearchGenerating clinical summary…
LOFmechanismADLOEUF 1.071 OMIM phenotype
Clinical Summary— SOCS1
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Gene-Disease Validity (ClinGen)
autoinflammatory syndrome with immunodeficiency · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.59) — some intolerance to loss-of-function variants.
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ClinVar Variants
13 unique Pathogenic / Likely Pathogenic· 63 VUS of 95 total submissions
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Clinical Trials
3 active or recruiting trials — potential therapeutic options may be available
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint?
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?
0.83Z-score
OE missense 0.75 (0.62–0.92)
67 obs / 89.0 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?
LoF OE?0.00 (0.00–1.07)
0≤0.351.4
Missense OE?0.75 (0.62–0.92)
0≤0.61.4
Synonymous OE?1.61
0≤1.21.6
LoF obs/exp: 0 / 2.7Missense obs/exp: 67 / 89.0Syn Z: -3.09

This gene — mechanism propensity

DN
0.4784th %ile
GOF
0.5955th %ile
LOF
0.56top 25%

The Badonyi & Marsh model scores gain-of-function highest, but genomic evidence most strongly supports loss-of-function (haploinsufficiency) as the primary mechanism.

LOF1 literature citation · 69% of P/LP variants are LoF

Literature Evidence

LOFImmune dysregulation and multisystem inflammatory syndrome in children (MIS-C) in individuals with haploinsufficiency of SOCS1.1

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

References

  1. 1.PMID 32853638 ↗

ClinVar Variant Classifications

95 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic6
Likely Pathogenic7
VUS63
Likely Benign6
Benign3
Conflicting1
6
Pathogenic
7
Likely Pathogenic
63
VUS
6
Likely Benign
3
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
5
1
0
0
6
Likely Pathogenic
4
3
0
0
7
VUS
3
58
1
1
63
Likely Benign
0
2
0
4
6
Benign
0
1
1
1
3
Conflicting
—1
Total12652686

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

View in ClinVar →

18 pathogenic / likely-pathogenic (of 30) ClinVar copy-number / structural variants overlap SOCS1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →

Protein Context — Lollipop Plot

SOCS1 · protein map & ClinVar variants

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

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