PRKAG1

Overview

PRKAG1 (Protein Kinase AMP-Activated Non-Catalytic Subunit Gamma 1) encodes a regulatory gamma subunit of AMP-activated protein kinase (AMPK). It harbors a mutation analogous to known activating substitutions in PRKAG2 in an independent chromophobe renal cell carcinoma (chRCC) cohort, implicating the AMPK metabolic axis in chRCC pathogenesis.

Alterations observed in the corpus

  • p.Arg299Gln mutation identified in an independent chRCC validation cohort; analogous to PRKAG2 p.Arg531Gln (CBS4 AMP-binding domain substitution), predicted activating by analogy to glycogen storage cardiomyopathy mutants PMID:25401301

Cancer types (linked)

  • chRCC: recurrent AMPK regulatory subunit mutation suggesting a metabolic axis as a driver PMID:25401301

Co-occurrence and mutual exclusivity

  • PRKAG1 p.Arg299Gln parallels PRKAG2 CBS4 mutations in chRCC, suggesting convergent AMPK activation via either gamma subunit PMID:25401301

Therapeutic relevance

  • Combined PRKAG1/PRKAG2 and PDHB mutations in chRCC define a metabolically deregulated subtype, potentially actionable via AMPK or PDH modulators; no clinical data available PMID:25401301

Open questions

  • Whether PRKAG1 p.Arg299Gln is truly activating in the tumor context requires direct functional validation; the analogy to PRKAG2 cardiomyopathy mutants is circumstantial PMID:25401301

Sources

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