SSTR3

Chr 22

somatostatin receptor 3

Also known as: SS-3-R, SS3-R, SS3R, SSR-28, SST3

NCBI Gene: 6753 ENSG00000278195 UniProt: P32745 OMIM: 182453

This gene encodes somatostatin receptor 3, a G-protein coupled receptor that binds somatostatin-14 and somatostatin-28 peptide hormones and inhibits adenylyl cyclase to regulate neurotransmission, cell proliferation, and hormone secretion. Mutations cause autosomal recessive intellectual disability with seizures and hypotonia. The gene shows low evolutionary constraint, consistent with recessive inheritance patterns where heterozygous carriers are typically unaffected.

OMIM ResearchSummary from RefSeq, UniProt

This gene encodes a member of the somatostatin receptor protein family. Somatostatins are peptide hormones that regulate diverse cellular functions such as neurotransmission, cell proliferation, and endocrine signaling as well as inhibiting the release of many hormones and other secretory proteins. Somatostatin has two active forms of 14 and 28 amino acids. The biological effects of somatostatins are mediated by a family of G-protein coupled somatostatin receptors that are expressed in a tissue-specific manner. Somatostatin receptors form homodimers and heterodimers with other members of the superfamily as well as with other G-protein coupled receptors and receptor tyrosine kinases. This protein is functionally coupled to adenylyl cyclase. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Jul 2013]

OMIM ResearchGenerating clinical summary…

MultiplemechanismLOEUF 1.42

Clinical Summary— SSTR3

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

71 VUS of 77 total submissions

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Clinical Trials

1 active or recruiting trial — 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

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.42LOEUF

pLI 0.000

Z-score 0.67

OE 0.76 (0.43–1.42)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

1.14Z-score

OE missense 0.82 (0.73–0.91)

247 obs / 303.0 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.76 (0.43–1.42)

0≤0.351.4

Missense OE?0.82 (0.73–0.91)

0≤0.61.4

Synonymous OE?1.07

0≤1.21.6

LoF obs/exp: 7 / 9.2Missense obs/exp: 247 / 303.0Syn Z: -0.61

This gene — mechanism propensity

0.76top 25%

GOF

0.85top 5%

LOF

0.2775th %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

77 submitted variants in ClinVar

ClinVar

Classification Summary

VUS71

Likely Benign5

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Synonymous	Total
Pathogenic	0	0	0
Likely Pathogenic	0	0	0
VUS	71	0	71
Likely Benign	4	1	5
Benign	0	0	0
Total	75	1	76

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

View in ClinVar →

17 pathogenic / likely-pathogenic (of 22) ClinVar copy-number / structural variants overlap SSTR3 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →