TUBA4A
Chr 2ADARtubulin alpha 4a
Also known as: ALS22, CMYO26, FTDALS9, H2-ALPHA, OZEMA23, SPAX11, TUBA1
This gene encodes an alpha tubulin protein that forms heterodimers with beta tubulin to constitute microtubules, the major structural components of the cellular cytoskeleton. Mutations cause autosomal dominant spastic ataxia, frontotemporal dementia with or without amyotrophic lateral sclerosis, and autosomal recessive congenital myopathy, affecting the nervous system and skeletal muscle. The gene shows moderate constraint against loss-of-function variants (LOEUF 0.62), and inheritance patterns vary by phenotype with both dominant and recessive forms described.
Moderate evidence — consider for supplementary testing
2 total gene-disease associations curated
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
156 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 | 2 | 10 | 32 | 0 | 44 |
Likely Pathogenic | 4 | 3 | 2 | 0 | 9 |
VUS | 3 | 28 | 6 | 1 | 38 |
Likely Benign | 0 | 1 | 9 | 35 | 45 |
Benign | 0 | 0 | 12 | 4 | 16 |
Conflicting | — | 1 | |||
| Total | 9 | 42 | 61 | 40 | 153 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
TUBA4A · 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