TMEM63C

Chr 14AR

transmembrane protein 63C

Also known as: C14orf171, CSC1, SPG87, hTMEM63C, hsCSC1

NCBI Gene: 57156 ENSG00000165548 UniProt: Q9P1W3 OMIM: 619953

TMEM63C encodes an osmosensitive cation channel that is activated by hypotonic stress and is enriched at mitochondria-ER contact sites where it regulates organelle morphology and mitochondrial function in motor neuron axons. Biallelic mutations cause spastic paraplegia 87, an autosomal recessive disorder affecting the corticospinal tracts. The gene shows moderate constraint against loss-of-function variants (LOEUF 0.398), and the protein is also required for kidney glomerular filtration barrier integrity.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

Enables calcium-activated cation channel activity. Involved in monoatomic cation transport. Predicted to be located in endoplasmic reticulum membrane. Predicted to be active in plasma membrane. Implicated in hereditary spastic paraplegia 87. Biomarker of focal segmental glomerulosclerosis. [provided by Alliance of Genome Resources, Apr 2025]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Spastic paraplegia 87, autosomal recessiveMIM #619966

Clinical highlights

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.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

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P/LP missense

0.40

LOEUF

Multiple*

Mechanism· predicted