RBMY1A1

Chr Y

RNA binding motif protein Y-linked family 1 member A1

Also known as: RBM, RBM1, RBM2, RBMY, RBMY1C, YRRM1, YRRM2

NCBI Gene: 5940 ENSG00000234414 UniProt: P0DJD3

The protein is an RNA-binding protein that regulates pre-mRNA splicing and is required for sperm development. Mutations cause male infertility due to azoospermia or severe oligospermia, with inheritance following a Y-linked pattern since the gene is located on the Y chromosome. The gene shows relatively low constraint to loss-of-function variants (pLI 0.29, LOEUF 1.89), consistent with its specialized role in male reproductive function.

ResearchSummary from RefSeq, UniProt

This gene encodes a protein containing an RNA-binding motif in the N-terminus and four SRGY (serine, arginine, glycine, tyrosine) boxes in the C-terminus. This protein is thought to function as a splicing regulator during spermatogenesis. Multiple closely related paralogs of this gene are found in a gene cluster in the AZFb azoospermia factor region of chromosome Y. Most of these related copies are thought to be pseudogenes, though several likely encode functional proteins. [provided by RefSeq, Mar 2016]

ResearchGenerating clinical summary…

DNmechanismLOEUF 1.89

Clinical Summary— RBMY1A1

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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

1 VUS of 1 total submissions

Explore recent and relevant literature in Research Assistant →

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?

1.89LOEUF

pLI 0.290

Z-score 0.28

OE 0.00 (0.00–1.89)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.34Z-score

OE missense 0.00 (0.00–1.75)

0 obs / 0.9 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.00 (0.00–1.89)

0≤0.351.4

Missense OE?0.00 (0.00–1.75)

0≤0.61.4

Synonymous OE?0.00

0≤1.21.6

LoF obs/exp: 0 / 0.1Missense obs/exp: 0 / 0.9Syn Z: 0.43

This gene — mechanism propensity

0.78top 25%

GOF

0.4776th %ile

LOF

0.3744th %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

1 submitted variants in ClinVar

ClinVar

Classification Summary

VUS1

VUS

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Total
Pathogenic	0	0
Likely Pathogenic	0	0
VUS	1	1
Likely Benign	0	0
Benign	0	0
Total	1	1

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

View in ClinVar →

71 pathogenic / likely-pathogenic (of 89) ClinVar copy-number / structural variants overlap RBMY1A1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →