Transmembrane protein 43 (TMEM43)

Transmembrane protein 43 (TMEM43) is an evolutionarily conserved integral membrane protein predominantly localized at the inner nuclear membrane, where it organizes and stabilizes nuclear envelope complexes by interacting with A- and B-type lamins and emerin[1][2][3]. As a multi-pass membrane protein containing four transmembrane domains, TMEM43 is essential for maintaining nuclear envelope integrity and for tethering key structural proteins. Defects in TMEM43, such as the p.S358L missense mutation, are the cause of a severe, autosomal dominant form of arrhythmogenic right ventricular cardiomyopathy (ARVC5), which features ventricular arrhythmias, fibrofatty myocardial replacement, conduction defects, and an increased risk of sudden cardiac death. TMEM43 also plays a role in innate immune signaling (through cGAS-STING and EGFR→NF-κB pathways) and in the function of gap junction channels in cochlear support cells, with mutations linked to auditory neuropathy spectrum disorders[1][2][3]. No approved drugs currently target TMEM43 directly, but it remains an important gene in cardiovascular and neuromuscular disease risk assessment.

Other names

LUMAARVC5ARVD5EDMD7AUNA3AUNA2MGC3222DKFZp586G1919Protein LUMAtransmembrane protein 43

null (no approved drugs with directly characterized mechanisms of action for TMEM43 targeting)