RBM8A

Chr 1

RNA binding motif protein 8A

Also known as: BOV-1A, BOV-1B, BOV-1C, C1DELq21.1, DEL1q21.1, MDS014, RBM8, TAR

NCBI Gene: 9939 ENSG00000265241 UniProt: Q9Y5S9

The protein is a core component of the exon junction complex that marks splice sites on mature mRNAs and is required for pre-mRNA splicing, mRNA export, translation regulation, and nonsense-mediated decay. Mutations cause thrombocytopenia-absent radius (TAR) syndrome, which presents in infancy with severe bleeding due to low platelet counts and bilateral absence of the radius bones. TAR syndrome follows autosomal recessive inheritance and the gene shows moderate constraint against loss-of-function variants (LOEUF 0.564).

GeneReviews ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a protein with a conserved RNA-binding motif. The protein is found predominantly in the nucleus, although it is also present in the cytoplasm. It is preferentially associated with mRNAs produced by splicing, including both nuclear mRNAs and newly exported cytoplasmic mRNAs. It is thought that the protein remains associated with spliced mRNAs as a tag to indicate where introns had been present, thus coupling pre- and post-mRNA splicing events. Previously, it was thought that two genes encode this protein, RBM8A and RBM8B; it is now thought that the RBM8B locus is a pseudogene. There are two alternate translation start codons with this gene, which result in two forms of the protein. An allele mutation and a low-frequency noncoding single-nucleotide polymorphism (SNP) in this gene cause thrombocytopenia-absent radius (TAR) syndrome. [provided by RefSeq, Jul 2013]

GeneReviews ResearchGenerating clinical summary…

LOFmechanismLOEUF 0.56

Clinical Summary— RBM8A

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Gene-Disease Validity (ClinGen)

thrombocytopenia-absent radius syndrome · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)

Moderately constrained gene (pLI 0.57) — some intolerance to loss-of-function variants.

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ClinVar Variants

14 unique Pathogenic / Likely Pathogenic· 22 VUS of 105 total submissions

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GeneReview available — RBM8A

Authoritative clinical overview · Recommended first read

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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

Moderate LoF intolerance

LoF Constraint?

0.56LOEUF

pLI 0.573

Z-score 2.54

OE 0.18 (0.07–0.56)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

2.16Z-score

OE missense 0.43 (0.34–0.55)

49 obs / 113.9 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.18 (0.07–0.56)

0≤0.351.4

Missense OE?0.43 (0.34–0.55)

0≤0.61.4

Synonymous OE?0.87

0≤1.21.6

LoF obs/exp: 2 / 11.2Missense obs/exp: 49 / 113.9Syn Z: 0.66

ClinVar Variant Classifications

105 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic13

Likely Pathogenic1

VUS22

Likely Benign58

Benign7

Conflicting3

Pathogenic

Likely Pathogenic

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	5	0	8	0	13
Likely Pathogenic	1	0	0	0	1
VUS	0	17	4	1	22
Likely Benign	0	1	38	19	58
Benign	0	0	7	0	7
Conflicting	—				3
Total	6	18	57	20	104

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

View in ClinVar →

135 pathogenic / likely-pathogenic (of 215) ClinVar copy-number / structural variants overlap RBM8A — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →