PRKAA1

Overview

PRKAA1 encodes the alpha-1 catalytic subunit of AMP-activated protein kinase (AMPK), a central energy sensor that regulates cellular metabolism. GWAS studies have identified PRKAA1 variants as low-penetrance gastric cancer susceptibility loci. AMPK pathway activity intersects with mTOR signaling and cellular energy homeostasis relevant to gastric carcinogenesis.

Alterations observed in the corpus

  • Low-penetrance GWAS susceptibility locus for gastric cancer; individually small risk increment but clustering in a single family may partly explain familial aggregation of gastric cancer PMID:24816255

Cancer types (linked)

  • Gastric cancer (STAD): PRKAA1 identified as a low-penetrance gastric cancer risk locus from GWAS; co-evaluated with MUC1, PSCA, and PLCE1 in familial non-hereditary gastric cancer (FNHGC) risk assessment PMID:24816255

Co-occurrence and mutual exclusivity

  • Co-evaluated with other low-penetrance gastric cancer susceptibility loci including MUC1, PSCA, and PLCE1 PMID:24816255

Therapeutic relevance

  • No direct therapeutic targeting in the current corpus; PRKAA1 variant status may contribute to polygenic risk stratification for gastric cancer screening, though clinical actionability remains unestablished PMID:24816255

Open questions

  • Polygenic risk scores for gastric cancer incorporating PRKAA1 are not yet validated for clinical use; small per-variant effect sizes and limited ancestry portability remain barriers PMID:24816255

Sources

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