PRKN

The encoded protein functions as an E3 ubiquitin ligase that targets substrate proteins for degradation and plays a critical role in mitochondrial quality control by removing damaged mitochondria through mitophagy. Mutations cause autosomal recessive juvenile-onset Parkinson disease, typically presenting in childhood or adolescence with movement disorders. This gene shows very low constraint against loss-of-function variants (pLI near zero), consistent with its recessive inheritance pattern where single gene copies are typically sufficient for normal function.