PRKDC
Chr 8ARprotein kinase, DNA-activated, catalytic subunit
Also known as: DNA-PKC, DNA-PKcs, DNAPK, DNAPKc, DNPK1, HYRC, HYRC1, IMD26
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.
Definitive — sufficient evidence for diagnostic panels
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Among the most LoF-intolerant genes (~top 3%)
Moderately missense-constrained (top ~2.5%)
The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.
ClinVar Variant Classifications
0 submitted variants in ClinVar
Protein Context — Lollipop Plot
PRKDC · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
External Resources
Links to major genomics databases and tools