1.A.17.5.21
TMEM63A or CSC1-like protein of 807 aas and ~10 TMSs. Heterozygous variants in TMEM63A have been identified as the cause of infantile-onset transient hypomyelination. TMEM63A variants are thought to cause transient hypomyelination with favorable developmental progress, but identification of a novel TMEM63A variant showed that the TMEM63A-related clinical spectrum is broad and includes severe developmental delay with seizures (Fukumura et al. 2021).  Knowledge has been reviewed about the activation mechanisms and biological functions of TMEM63 channels, and this review provides a concise reference for researchers interested in investigating more physiological and pathogenic roles of this family of proteins with ubiquitous expression in the body (Chen et al. 2023). The protein is a monomer with 11 TMSs (Wu et al. 2024).  The mechanosensor that couples breathing to surfactant secretion in the llung is the transmembrane 63 (TMEM63) ion channel (Hook 2024). Single lysine mutations in TMS4 allow non-scrambling Transmembrane Channel/Scramblase (TCS) members to permeate phospholipids (Lowry et al. 2024). Thius, a key role of TMS4 is to control TCS ion and lipid permeation and offers novel insights into the evolution of the TCS superfamily, suggesting that, like TMEM16s, the OSCA/TMEM63 systems maintain a conserved potential to permeate ions and phospholipids.

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