BRMS1

Chr 11

BRMS1 transcriptional repressor and anoikis regulator

NCBI Gene: 25855 ENSG00000174744 UniProt: Q9HCU9 OMIM: 606259

The protein functions as a transcriptional repressor that downregulates NF-kappa-B signaling by promoting deacetylation and is a component of histone deacetylase complexes. Mutations cause intellectual developmental disorder with dysmorphic facies, seizures, and distal limb anomalies, which follows an autosomal dominant inheritance pattern. This gene shows very low constraint against loss-of-function variants, indicating that complete loss of protein function is likely tolerated.

OMIM ResearchSummary from RefSeq, UniProt

This gene reduces the metastatic potential, but not the tumorogenicity, of human breast cancer and melanoma cell lines. The protein encoded by this gene localizes primarily to the nucleus and is a component of the mSin3a family of histone deacetylase complexes (HDAC). The protein contains two coiled-coil motifs and several imperfect leucine zipper motifs. Alternative splicing results in two transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.14

LOEUF

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.14LOEUF

pLI 0.000

Z-score 1.13

OE 0.71 (0.46–1.14)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.11Z-score

OE missense 0.98 (0.86–1.11)

166 obs / 169.9 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.71 (0.46–1.14)

0≤0.351.4

Missense OE?0.98 (0.86–1.11)

0≤0.61.4

Synonymous OE?0.91

0≤1.21.6

LoF obs/exp: 13 / 18.2Missense obs/exp: 166 / 169.9Syn Z: 0.56

Background carrier burden — how many people carry a rare variant somewhere in BRMS1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 140

398 rare PASS variants

Rare truncating (LoF)

1 in 1,200

69 rare PASS variants

Rare synonymous (reference)

1 in 580

118 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for BRMS1. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 170	1 in 3,100
South Asian	~43k	1 in 130	1 in 1,900
Remaining (unassigned)	~30k	1 in 110	1 in 1,900
European (Finnish)	~27k	1 in 440	≈ 1 in 6,700
Admixed American	~22k	1 in 97	1 in 2,200
African / African American	~21k	1 in 170	1 in 1,200
East Asian	~20k	1 in 150	1 in 1,000
Ashkenazi Jewish	~13k	1 in 350	≈ 1 in 4,400
Middle Eastern	~2,884	1 in 100	≈ 1 in 2,900

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 9 of 9 coding exons well covered in gnomAD exomes. Genomes: 8 of 9 (exon 7 below).? see exons ↓