TSPAN12

Chr 7

tetraspanin 12

Also known as: EVR5, NET-2, NET2, TM4SF12

NCBI Gene: 23554 ENSG00000106025 UniProt: O95859

This transmembrane protein regulates norrin signaling pathways essential for retinal vascularization and acts as a regulator of membrane proteinases including ADAM10 and MMP14. Mutations cause exudative vitreoretinopathy 5, an autosomal dominant disorder affecting retinal blood vessel development. The gene shows significant constraint against loss-of-function variants (LOEUF 0.457), indicating intolerance to protein-truncating mutations.

ResearchSummary from RefSeq, OMIM, UniProt

The protein encoded by this gene is a member of the transmembrane 4 superfamily, also known as the tetraspanin family. Most of these members are cell-surface proteins that are characterized by the presence of four hydrophobic domains. The proteins mediate signal transduction events that play a role in the regulation of cell development, activation, growth and motility. [provided by RefSeq, Jul 2008]

ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtVitreoretinopathy, exudative 5

Clinical highlights

Gene-disease validity (ClinGen)

TSPAN12-related exudative vitreoretinopathy · SDDefinitivesufficient 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

—

P/LP missense

0.46

LOEUF

LOF*

Mechanism· G2P

Some data sources returned errors (1)

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