KBTBD8
Chr 3kelch repeat and BTB domain containing 8
Also known as: TA-KRP, TAKRP
KBTBD8 encodes a substrate-specific adapter protein that forms part of an E3 ubiquitin ligase complex and regulates neural crest specification by modulating ribosomal processing through monoubiquitination of NOLC1 and TCOF1. Mutations cause autosomal recessive developmental delay with dysmorphic facies and dental anomalies, reflecting the protein's critical role in neural crest development. The gene shows tolerance to loss-of-function variants (pLI near 0), consistent with the recessive inheritance pattern observed clinically.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Typical tolerance to LoF variation
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
0 submitted variants in ClinVar
Protein Context — Lollipop Plot
KBTBD8 · 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