TMEM65

Chr 8

transmembrane protein 65

NCBI Gene: 157378 ENSG00000164983 UniProt: Q6PI78

TMEM65 encodes a protein essential for maintaining cardiac intercalated disc structure and function, stabilizing gap junction and sodium channel localization, and regulating mitochondrial respiration. Mutations cause autosomal recessive arrhythmogenic cardiomyopathy with conduction defects and sudden cardiac death in infancy and childhood. The protein's critical role in cardiac conduction system development and function makes this a severe early-onset cardiac condition requiring immediate cardiology management.

ResearchSummary from RefSeq, UniProt

Predicted to be involved in cardiac conduction; cardiac ventricle development; and regulation of cardiac conduction. Located in several cellular components, including intercalated disc; mitochondrial inner membrane; and nucleolus. [provided by Alliance of Genome Resources, Jul 2025]

ResearchGenerating clinical summary…

Clinical highlights

Gene-disease validity (ClinGen)

mitochondrial disease · ARLimitednot for standalone diagnostic reporting

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

—

P/LP submissions

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P/LP missense

0.83

LOEUF

Mechanism· predicted

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429