TMEM71

Overview

TMEM71 encodes a transmembrane protein of largely unknown function. It has been identified as a fusion partner with TSC1 in a pancreatic neuroendocrine neoplasm, resulting in a TSC1–TMEM71 fusion that is predicted to disrupt TSC1 tumor suppressor function and activate mTOR signaling. This fusion represents a rare but actionable structural variant in NENs.

Alterations observed in the corpus

  • TMEM71 acts as the fusion partner in a TSC1–TMEM71 structural fusion (patient PN21) identified by whole-genome/transcriptome analysis in a metastatic neuroendocrine neoplasm; this fusion supported mTOR-inhibitor (everolimus) recommendation PMID:24326773

Cancer types (linked)

  • Pancreatic neuroendocrine neoplasm (PanNEN): TSC1–TMEM71 fusion identified in one patient (PN21) within a WGTA-guided precision oncology cohort for rare metastatic NENs PMID:24326773

Co-occurrence and mutual exclusivity

  • The TSC1–TMEM71 fusion co-occurs with mTOR pathway activation in PN21; TSC1 is the primary tumor suppressor partner in this fusion PMID:24326773

Therapeutic relevance

  • TSC1–TMEM71 fusion predicted to activate mTOR signaling; supported selection of everolimus (mTOR inhibitor) for PN21 in a clinical precision oncology program PMID:24326773

Open questions

  • The molecular consequences of the TSC1–TMEM71 fusion on TSC1 protein function and mTOR pathway output remain to be experimentally validated.
  • TMEM71’s normal biological function is poorly characterized.

Sources

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