KBTBD11
Chr 8kelch repeat and BTB domain containing 11
Also known as: KLHDC7C
The protein functions as a substrate adaptor for the CRL3 ubiquitin ligase complex, targeting specific proteins for degradation. Mutations cause autosomal recessive intellectual disability with seizures and skeletal abnormalities. The gene shows tolerance to loss-of-function variants in the general population (pLI 0.06, LOEUF 1.0), suggesting the recessive inheritance pattern aligns with population constraint data.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly tolerant — LoF variants common in population
Mild missense constraint
This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
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
360 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 | 117 | 0 | 117 |
Likely Pathogenic | 0 | 0 | 7 | 0 | 7 |
VUS | 0 | 186 | 34 | 0 | 220 |
Likely Benign | 0 | 5 | 3 | 0 | 8 |
Benign | 0 | 0 | 1 | 0 | 1 |
| Total | 0 | 191 | 162 | 0 | 353 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
KBTBD11 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
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