TMEM127

Overview

TMEM127 (Transmembrane Protein 127) encodes a transmembrane protein that negatively regulates the mTOR pathway by promoting lysosomal degradation of mTOR complex components. Germline loss-of-function mutations in TMEM127 are a rare hereditary cause of pheochromocytoma, described in 2010. TMEM127-mutant tumors cluster with the kinase signaling molecular subtype, alongside RET, NF1, HRAS, and BRAF-driven tumors.

Alterations observed in the corpus

  • Rare germline events identified in the TCGA PCC/PGL cohort (pcpg_tcga_pub, n=173); TMEM127 germline mutations occur at ≤2% frequency and cluster in the kinase signaling mRNA subtype. PMID:28162975
  • TMEM127 germline was mutually exclusive with other major driver gene events (p < 1e-4) in the same cohort. PMID:28162975

Cancer types (linked)

  • PHC / PGNG: TMEM127 germline mutation is a rare hereditary driver of PCC, enriched in the kinase signaling subtype alongside NF1, RET, and HRAS mutations. PMID:28162975

Co-occurrence and mutual exclusivity

Therapeutic relevance

  • TMEM127 loss activates mTOR; mTOR inhibitors (everolimus, temsirolimus) are a rationale-driven therapeutic hypothesis, though not tested in this study. PMID:28162975

Open questions

  • Prospective evidence for mTOR inhibitor efficacy in TMEM127-mutant PCC/PGL is not established in the corpus. PMID:28162975

Sources

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