KCNJ3

Overview

KCNJ3 encodes the G-protein-activated inwardly rectifying potassium channel 1 (GIRK1), a member of the inward-rectifier potassium channel family involved in cell excitability and signaling. In extra-cranial malignant rhabdoid tumor (MRT), KCNJ3 harbors recurrent intronic mutations associated with increased gene expression, though the functional mechanism has not been resolved.

Alterations observed in the corpus

  • Intronic mutations in KCNJ3 detected in 8/40 extra-cranial MRT cases; mutations are associated with increased KCNJ3 expression, though whether the mechanism is direct regulatory disruption or a sequencing artifact in a frequently rearranged region is unresolved. PMID:26977886

Cancer types (linked)

  • MRT (Malignant Rhabdoid Tumor): Recurrent intronic KCNJ3 mutations in 20% (8/40) of extra-cranial MRT with associated increased expression. PMID:26977886

Co-occurrence and mutual exclusivity

  • Mutations occur in the background of SMARCB1 biallelic inactivation, which is the dominant driver in 39/40 cases in this cohort. PMID:26977886

Therapeutic relevance

  • No therapeutic implications described in the corpus.

Open questions

  • The mechanism by which intronic KCNJ3 mutations increase expression is unresolved; regulatory disruption vs. sequencing artifact in rearranged regions cannot be distinguished from the current data. PMID:26977886

Sources

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