KLHL25

Chr 15

kelch like family member 25

Also known as: ENC-2, ENC2

NCBI Gene: 64410 ENSG00000183655 UniProt: Q9H0H3 OMIM: 619893

KLHL25 encodes a substrate-specific adapter protein that functions within the BCR (BTB-CUL3-RBX1) E3 ubiquitin ligase complex to regulate protein translation homeostasis and lipid metabolism through targeted degradation of EIF4EBP1 and ACLY proteins. Pathogenic variants cause autosomal recessive developmental and epileptic encephalopathy with microcephaly, involving the central nervous system with seizures and developmental delays typically manifesting in early infancy. The gene shows tolerance to loss-of-function variation in the general population, suggesting that biallelic variants are required for disease manifestation.

OMIM ResearchSummary from RefSeq, UniProt

Enables ubiquitin-like ligase-substrate adaptor activity. Involved in several processes, including positive regulation of CD4-positive, CD25-positive, alpha-beta regulatory T cell differentiation; regulation of fatty acid metabolic process; and ubiquitin-dependent protein catabolic process. Located in cytoplasm. Part of Cul3-RING ubiquitin ligase complex. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

LOEUF 1.92

Clinical Summary— KLHL25

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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