PRKDC

Chr 8AR

protein kinase, DNA-activated, catalytic subunit

Also known as: DNA-PKC, DNA-PKcs, DNAPK, DNAPKc, DNPK1, HYRC, HYRC1, IMD26

NCBI Gene: 5591 ENSG00000253729 UniProt: P78527 OMIM: 600899

The protein functions as the catalytic subunit of DNA-dependent protein kinase (DNA-PK), a serine/threonine kinase essential for DNA double-strand break repair through non-homologous end joining and for V(D)J recombination required for adaptive immune system development. Mutations cause severe combined immunodeficiency with sensitivity to ionizing radiation, following an autosomal recessive inheritance pattern. The gene is highly constrained against loss-of-function variants (pLI = 1, LOEUF = 0.052), reflecting its critical role in DNA repair and immune function.

OMIM ResearchSummary from RefSeq, UniProt

This gene encodes the catalytic subunit of the DNA-dependent protein kinase (DNA-PK). It functions with the Ku70/Ku80 heterodimer protein in DNA double strand break repair and recombination. The protein encoded is a member of the PI3/PI4-kinase family.[provided by RefSeq, Jul 2010]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Immunodeficiency 26, with or without neurologic abnormalitiesMIM #615966

Clinical highlights

Gene-disease validity (ClinGen)

severe combined immunodeficiency due to DNA-PKcs deficiency · ARDefinitivesufficient evidence for diagnostic panels

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

109

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.05

LOEUF· LoF intol.

LOF

Mechanism· predicted