TUBB4A
Chr 19ADtubulin beta 4A class IVa
Also known as: DYT4, TUBB4, beta-5
This gene encodes a beta tubulin protein that heterodimerizes with alpha tubulin to form microtubules, which are essential components of the cellular cytoskeleton. Mutations cause autosomal dominant dystonia-4 (torsion dystonia) and hypomyelinating leukodystrophy-6 through a dominant-negative mechanism where mutant proteins disrupt normal microtubule function. Both conditions follow autosomal dominant inheritance with the dystonia typically presenting with focal onset and the leukodystrophy causing developmental delays and motor dysfunction.
Definitive — sufficient evidence for diagnostic panels
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Typical tolerance to LoF variation
Highly missense-constrained (top ~0.1%)
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.
Literature Evidence
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
0 submitted variants in ClinVar
Protein Context — Lollipop Plot
TUBB4A · 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
External Resources
Links to major genomics databases and tools