BRME1

Chr 19

break repair meiotic recombinase recruitment factor 1

Also known as: C19orf57, MEIOK21

NCBI Gene: 79173 ENSG00000132016 UniProt: Q0VDD7 OMIM: 619276

BRME1 encodes a meiotic recombination factor that is essential for double-strand break repair and crossover formation during meiosis, particularly critical for spermatogenesis and male fertility. Mutations in BRME1 cause autosomal recessive male infertility due to meiotic arrest. The gene shows low constraint against loss-of-function variants, consistent with its specialized role in reproductive function rather than essential developmental processes.

OMIM ResearchSummary from RefSeq, UniProt

Predicted to enable damaged DNA binding activity. Predicted to be involved in meiosis I; protein localization to site of double-strand break; and spermatogenesis. Predicted to be located in chromosome. Predicted to be active in site of double-strand break. [provided by Alliance of Genome Resources, Apr 2025]

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.78

LOEUF

—

Mechanism

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.78LOEUF

pLI 0.000

Z-score 2.36

OE 0.46 (0.28–0.78)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.38Z-score

OE missense 0.95 (0.87–1.03)

354 obs / 374.5 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.46 (0.28–0.78)

0≤0.351.4

Missense OE?0.95 (0.87–1.03)

0≤0.61.4

Synonymous OE?0.98

0≤1.21.6

LoF obs/exp: 10 / 21.9Missense obs/exp: 354 / 374.5Syn Z: 0.18

Background carrier burden — how many people carry a rare variant somewhere in BRME1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 36

872 rare PASS variants

Rare truncating (LoF)

1 in 370

133 rare PASS variants

Rare synonymous (reference)

1 in 150

367 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for BRME1. 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 67	1 in 980
South Asian	~43k	1 in 38	1 in 340
Remaining (unassigned)	~30k	1 in 32	1 in 940
European (Finnish)	~27k	1 in 160	1 in 1,800
Admixed American	~22k	1 in 34	1 in 660
African / African American	~21k	1 in 45	1 in 740
East Asian	~20k	1 in 69	1 in 940
Ashkenazi Jewish	~13k	1 in 430	≈ 1 in 4,300
Middle Eastern	~2,884	1 in 55	1 in 480

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): All 8 coding exons well covered in gnomAD exomes and genomes.? see exons ↓