USH2A

Chr 1

usherin

Also known as: RP39, US2, USH2, USHRN, dJ1111A8.1

NCBI Gene: 7399 ENSG00000042781 UniProt: O75445

The USH2A protein is a basement membrane component containing laminin, pentaxin, and fibronectin domains that maintains hair bundle ankle formation in cochlear hair cells and the periciliary membrane complex in retinal photoreceptors. Mutations cause autosomal recessive Usher syndrome type 2A (progressive hearing loss with retinitis pigmentosa) and isolated retinitis pigmentosa 39. The gene shows very low constraint against loss-of-function variants, consistent with its recessive inheritance pattern where heterozygous carriers are typically unaffected.

ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a protein that contains laminin EGF motifs, a pentaxin domain, and many fibronectin type III motifs. The protein is found in the basement membrane, and may be important in development and homeostasis of the inner ear and retina. Mutations within this gene have been associated with Usher syndrome type IIa and retinitis pigmentosa. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2008]

ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtUsher syndrome 2A

UniProtRetinitis pigmentosa 39

Clinical highlights

Gene-disease validity (ClinGen)

Usher syndrome type 2 · ARDefinitivesufficient evidence for diagnostic panels

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

113

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.86

LOEUF

LOF

Mechanism· G2P

Some data sources returned errors (1)