TTC21B
Chr 2ADARtetratricopeptide repeat domain 21B
Also known as: ATD4, CFAP60, FAP60, FLA17, IFT139, IFT139B, JBTS11, NPHP12
This protein is a component of the intraflagellar transport complex A that is essential for retrograde ciliary transport and negatively modulates sonic hedgehog signaling. Mutations cause nephronophthisis 12 and short-rib thoracic dysplasia 4 with or without polydactyly through both autosomal recessive and autosomal dominant inheritance patterns. The pathogenic mechanism involves dominant-negative effects that disrupt normal ciliary function.
Definitive — sufficient evidence for diagnostic panels
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Typical tolerance to LoF variation
Tolerant to missense variation
The highest-scoring mechanism for this gene is dominant-negative.
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
TTC21B · 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