TMEM175

Chr 4

transmembrane protein 175

Also known as: hTMEM175

NCBI Gene: 84286 ENSG00000127419 UniProt: Q9BSA9 OMIM: 616660

TMEM175 encodes a proton-activated channel that maintains pH homeostasis in lysosomes and endosomes by mediating proton efflux at low pH and potassium conductance at higher pH, which is essential for autophagosome-lysosome fusion and protecting neurons against stress-induced damage. Mutations cause autosomal recessive spastic paraplegia and early-onset parkinsonism, typically presenting in childhood to early adulthood. The gene shows very low constraint against loss-of-function variants (pLI near zero), consistent with recessive inheritance where heterozygous carriers are typically unaffected.

OMIM ResearchSummary from RefSeq, UniProt

Enables arachidonate binding activity; potassium ion leak channel activity; and proton channel activity. Involved in monoatomic cation transmembrane transport and regulation of intracellular pH. Located in endosome membrane and lysosome. Is active in lysosomal membrane. [provided by Alliance of Genome Resources, Jun 2026]

OMIM ResearchGenerating clinical summary…