TMEM127

Chr 2AD

transmembrane protein 127

Also known as: PPGL8

NCBI Gene: 55654 ENSG00000135956 UniProt: O75204 OMIM: 613403

TMEM127 encodes a transmembrane protein that localizes to endosomes, Golgi, and lysosomes where it participates in protein trafficking and controls cell proliferation by negatively regulating mTORC1 signaling. Mutations cause autosomal dominant susceptibility to pheochromocytoma, typically presenting in adulthood. The gene shows low constraint against loss-of-function variants, which is consistent with its role as a tumor suppressor gene.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a transmembrane protein with four predicted transmembrane domains. The protein is associated with a subpopulation of vesicular organelles corresponding to early endosomal structures, with the Golgi, and with lysosomes, and may participate in protein trafficking between these structures. Mutations in this gene and several other genes cause pheochromocytomas. Alternatively spliced transcript variants encoding the same protein have been identified. [provided by RefSeq, Aug 2022]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Pheochromocytoma/paraganglioma syndrome 8MIM #621687

Clinical highlights

Gene-disease validity (ClinGen)

hereditary pheochromocytoma-paraganglioma · ADDefinitivesufficient evidence for diagnostic panels

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.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

1.15

LOEUF

LOF

Mechanism· G2P

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GeneReview available — TMEM127