TMEM63A
Chr 1ADtransmembrane protein 63A
Also known as: HLD19, KIAA0792, hTMEM63A
TMEM63A encodes a mechanosensitive cation channel that regulates lysosomal morphology and is essential for surfactant secretion in lung alveolar cells, playing a critical role in the baby's first breath and lifelong respiration. Mutations cause hypomyelinating leukodystrophy 19 with transient infantile onset, affecting both the central nervous system and respiratory function. The condition follows autosomal dominant inheritance, and the gene shows very low constraint against loss-of-function variants.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Typical tolerance to LoF variation
Mild missense constraint
This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
0 submitted variants in ClinVar
Protein Context — Lollipop Plot
TMEM63A · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
No active trials found for this gene.
Search ClinicalTrials.gov →External Resources
Links to major genomics databases and tools