TUBA1A
Chr 12ADtubulin alpha 1a
Also known as: B-ALPHA-1, LIS3, TUBA3
This gene encodes alpha tubulin, a major component of microtubules that is predominantly expressed in differentiated neurologic cells and essential for proper neuronal migration during brain development. Heterozygous loss-of-function mutations cause autosomal dominant lissencephaly type 3 (LIS3), characterized by microcephaly, intellectual disability, and early-onset epilepsy. The pathogenic mechanism involves disrupted microtubule function leading to defective neuronal migration and abnormal cortical development.
Definitive — sufficient evidence for diagnostic panels
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly LoF-intolerant (top ~10% of genes)
Extremely missense-constrained (top ~0.01%)
This gene has evidence for multiple mechanisms of pathogenicity (loss-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to loss-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
Literature Evidence
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.
ClinVar Variant Classifications
0 submitted variants in ClinVar
Protein Context — Lollipop Plot
TUBA1A · 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