SMR3A

Chr 4

submaxillary gland androgen regulated protein 3A

Also known as: P-B1, PBI, PRL5, PROL5

NCBI Gene: 26952 ENSG00000109208 UniProt: Q99954 OMIM: 618340

The SMR3A protein is predicted to function as an endopeptidase inhibitor involved in regulating pain perception and may have protective or detoxification roles. Currently, no specific diseases have been definitively associated with mutations in this gene based on the available data. The inheritance pattern for SMR3A-related conditions has not been established.

OMIM ResearchSummary from RefSeq, UniProt

Predicted to enable endopeptidase inhibitor activity. Predicted to be involved in regulation of sensory perception of pain. Predicted to be located in extracellular region. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

DNmechanismLOEUF 1.73

Clinical Summary— SMR3A

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Population Constraint (gnomAD)

Constrained for loss-of-function variants (OE-LoF 0.00) despite low pLI — interpret in context.

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ClinVar Variants

21 VUS of 24 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?

1.73LOEUF

pLI 0.391

Z-score 0.92

OE 0.00 (0.00–1.73)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.59Z-score

OE missense 1.20 (1.00–1.44)

84 obs / 70.1 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.00 (0.00–1.73)

0≤0.351.4

Missense OE?1.20 (1.00–1.44)

0≤0.61.4

Synonymous OE?0.81

0≤1.21.6

LoF obs/exp: 0 / 1.0Missense obs/exp: 84 / 70.1Syn Z: 0.75

This gene — mechanism propensity

0.89top 5%

GOF

0.6051th %ile

LOF

0.11100th %ile

The highest-scoring mechanism for this gene is dominant-negative.

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

24 submitted variants in ClinVar

ClinVar

Classification Summary

VUS21

Likely Benign2

Benign1

VUS

Likely Benign

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	21	0	21
Likely Benign	2	0	2
Benign	0	1	1
Total	23	1	24

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

View in ClinVar →

23 pathogenic / likely-pathogenic (of 35) ClinVar copy-number / structural variants overlap SMR3A — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →