UQCRH

Overview

UQCRH (Ubiquinol-Cytochrome C Reductase Hinge Protein) encodes a subunit of mitochondrial Complex III (the cytochrome bc1 complex) of the electron transport chain. As a component of oxidative phosphorylation, UQCRH loss or downregulation may contribute to metabolic reprogramming toward aerobic glycolysis (Warburg effect) — a hallmark of clear cell renal cell carcinoma. UQCRH has not been described as a canonical cancer driver in prior literature.

Alterations observed in the corpus

  • Hypermethylated in 36% of CCRCC tumors in the TCGA comprehensive molecular characterization; identified as the top inverse expression-versus-methylation correlate genome-wide — promoter methylation associated with transcriptional silencing; not previously linked to CCRCC prior to this study PMID:23792563

Cancer types (linked)

  • KIRC: promoter hypermethylation with concordant expression loss in 36% of TCGA CCRCC samples; the strong methylation–expression inverse correlation nominating it as an epigenetically silenced gene in this tumor type PMID:23792563

Co-occurrence and mutual exclusivity

  • Epigenetic silencing of UQCRH in CCRCC is consistent with the broader metabolic reprogramming landscape characterized in the same TCGA study, including alterations to SETD2, VHL, and mTOR-pathway genes that collectively shift tumors toward a Warburg phenotype PMID:23792563

Therapeutic relevance

  • No direct therapeutic implications reported in the corpus. Silencing of Complex III components may render tumors more dependent on glycolysis, potentially relevant to metabolic targeting strategies.

Open questions

  • Whether UQCRH methylation is a passenger event reflecting broad epigenetic dysregulation or a selected driver of metabolic vulnerability in CCRCC requires functional validation.
  • Correlation with clinical outcomes (survival, response to mTOR inhibitors) was not reported for UQCRH specifically in this study.

Sources

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