KLHDC4
Chr 16kelch domain containing 4
The protein functions as a kelch domain-containing adaptor that regulates protein degradation through the ubiquitin-proteasome system. Mutations cause autosomal recessive intellectual disability with seizures and developmental delay. This gene shows low constraint against loss-of-function variants, consistent with a recessive inheritance pattern where both copies must be affected to cause disease.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly tolerant — LoF variants common in population
Tolerant to missense variation
ClinVar Variant Classifications
259 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 0 | 0 | 43 | 0 | 43 |
Likely Pathogenic | 0 | 0 | 9 | 0 | 9 |
VUS | 0 | 144 | 25 | 0 | 169 |
Likely Benign | 0 | 10 | 3 | 1 | 14 |
Benign | 0 | 0 | 0 | 0 | 0 |
| Total | 0 | 154 | 80 | 1 | 235 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
KLHDC4 · 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