SMIM1

Chr 1

small integral membrane protein 1 (Vel blood group)

Also known as: Vel

NCBI Gene: 388588 ENSG00000235169 UniProt: B2RUZ4

This protein regulates red blood cell formation and serves as the antigen for the Vel blood group system. Autosomal recessive mutations cause Vel-negative blood group status, which can lead to hemolytic transfusion reactions and hemolytic disease of the newborn when Vel-negative individuals are exposed to Vel-positive blood. The gene shows low constraint to loss-of-function variation in the general population.

ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a small, conserved protein that participates in red blood cell formation. The encoded protein is localized to the cell membrane and is the antigen for the Vel blood group. Alternative splicing results in different transcript variants that encode the same protein. [provided by RefSeq, Dec 2013]

ResearchGenerating clinical summary…

MultiplemechanismLOEUF 1.82

Clinical Summary— SMIM1

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Population Constraint (gnomAD)

Low constraint (pLI 0.03) — loss-of-function variants are relatively tolerated in the population.

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Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.82LOEUF

pLI 0.033

Z-score 0.29

OE 0.80 (0.31–1.82)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.83Z-score

OE missense 0.66 (0.49–0.89)

31 obs / 46.9 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.80 (0.31–1.82)

0≤0.351.4

Missense OE?0.66 (0.49–0.89)

0≤0.61.4

Synonymous OE?0.85

0≤1.21.6

LoF obs/exp: 2 / 2.5Missense obs/exp: 31 / 46.9Syn Z: 0.53

This gene — mechanism propensity

0.7228th %ile

GOF

0.6832th %ile

LOF

0.3260th %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.