SMR3B

Chr 4

submaxillary gland androgen regulated protein 3B

Also known as: P-B, PBII, PRL3, PROL3, SMR1B

NCBI Gene: 10879ENSG00000171201UniProt: P02814OMIM: 611593

The SMR3B protein is predicted to function as an endopeptidase inhibitor that regulates peptidase activity and may be involved in pain perception. This gene is not highly constrained against loss-of-function variants and no definitive disease associations have been established in the current datasets. Clinical significance of SMR3B variants in pediatric neurological conditions remains to be determined.

OMIMResearchSummary from RefSeq
MultiplemechanismLOEUF 1.74
Clinical Summary— SMR3B
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.00) despite low pLI — interpret in context.
📋
ClinVar Variants
22 unique Pathogenic / Likely Pathogenic· 27 VUS of 53 total submissions
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
1.74LOEUF
pLI 0.387
Z-score 0.90
OE 0.00 (0.00–1.74)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-0.88Z-score
OE missense 1.37 (1.11–1.69)
62 obs / 45.3 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.00 (0.00–1.74)
0≤0.351.4
Missense OE1.37 (1.11–1.69)
0≤0.61.4
Synonymous OE1.30
0≤1.21.6
LoF obs/exp: 0 / 0.9Missense obs/exp: 62 / 45.3Syn Z: -0.96
DN
0.80top 25%
GOF
0.6833th %ile
LOF
0.12100th %ile

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

DNprediction above median
GOFprediction 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

53 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic21
Likely Pathogenic1
VUS27
Likely Benign2
Benign1
21
Pathogenic
1
Likely Pathogenic
27
VUS
2
Likely Benign
1
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
21
0
21
Likely Pathogenic
0
0
1
0
1
VUS
0
17
10
0
27
Likely Benign
0
0
2
0
2
Benign
1
0
0
0
1
Total11734052

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

View in ClinVar →

Protein Context — Lollipop Plot

SMR3B · 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

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
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

No open access results found

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