KLHL15
Chr XXLRkelch like family member 15
Also known as: HEL-S-305, XLID103
The protein functions as a substrate-specific adapter for the CUL3 E3 ubiquitin-protein ligase complex, targeting specific proteins for degradation and playing a key role in DNA damage response by regulating DNA double-strand break repair pathways. Mutations cause X-linked intellectual developmental disorder with X-linked recessive inheritance. The gene is highly constrained against loss-of-function variants (pLI = 0.99, LOEUF = 0.20), indicating that functional variants are likely to be pathogenic.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly LoF-intolerant (top ~10% of genes)
Highly missense-constrained (top ~0.1%)
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
KLHL15 · 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
No active trials found for this gene.
Search ClinicalTrials.gov →External Resources
Links to major genomics databases and tools