KLHL22
Chr 22kelch like family member 22
Also known as: KELCHL
KLHL22 encodes a substrate-specific adapter protein that functions as part of a ubiquitin ligase complex, mediating chromosome alignment during cell division and regulating the mTORC1 pathway through degradation of DEPDC5. Mutations cause autosomal recessive developmental and epileptic encephalopathy with early-onset seizures and developmental delay. The gene shows significant constraint against loss-of-function variants (LOEUF 0.44), indicating that complete loss of protein function is likely pathogenic.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
More LoF-intolerant than ~75% of genes
Moderately missense-constrained (top ~2.5%)
The highest-scoring mechanism for this gene is gain-of-function.
Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
0 submitted variants in ClinVar
Protein Context — Lollipop Plot
KLHL22 · 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