SSTR4

Chr 20

somatostatin receptor 4

Also known as: SS-4-R, SS4-R, SS4R, SST4

SSTR4 encodes a G protein-coupled receptor for somatostatin-14 that inhibits adenylyl cyclase and mediates antiproliferative signaling, with highest expression in brain and lung tissue. Mutations cause autosomal recessive intellectual disability with seizures and growth hormone deficiency. The gene shows very low constraint against loss-of-function variants (pLI near 0), consistent with recessive inheritance where heterozygous carriers are typically unaffected.

OMIMResearchSummary from RefSeq, UniProt
MultiplemechanismLOEUF 1.96
Clinical SummarySSTR4
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
21 unique Pathogenic / Likely Pathogenic· 63 VUS of 91 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.96LOEUF
pLI 0.000
Z-score -2.23
OE 1.84 (1.141.96)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-0.23Z-score
OE missense 1.04 (0.941.15)
279 obs / 268.3 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE1.84 (1.141.96)
00.351.4
Missense OE1.04 (0.941.15)
00.61.4
Synonymous OE0.83
01.21.6
LoF obs/exp: 15 / 8.1Missense obs/exp: 279 / 268.3Syn Z: 1.55
DN
0.7131th %ile
GOF
0.82top 10%
LOF
0.3260th %ile

This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

GOFprediction above median
DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

91 submitted variants in ClinVar

Classification Summary

Pathogenic18
Likely Pathogenic3
VUS63
Likely Benign3
Benign4
18
Pathogenic
3
Likely Pathogenic
63
VUS
3
Likely Benign
4
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
18
0
18
Likely Pathogenic
0
0
3
0
3
VUS
0
62
1
0
63
Likely Benign
0
3
0
0
3
Benign
0
0
0
4
4
Total06522491

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

View in ClinVar →

Protein Context — Lollipop Plot

SSTR4 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
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