RBM8A

Chr 1AR

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 OMIM: 605313

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 OMIM 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 OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Thrombocytopenia-absent radius syndromeMIM #274000

Clinical highlights

Gene-disease validity (ClinGen)

thrombocytopenia-absent radius syndrome · ARDefinitivesufficient evidence for diagnostic panels

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype) and the gene is intolerant of it in the population — truncating, frameshift and canonical splice variants carry more prior weight here than missense.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

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P/LP missense

0.56

LOEUF

LOF

Mechanism· G2P

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GeneReview available — RBM8A