TUBA1A

Chr 12AD

tubulin alpha 1a

NCBI Gene: 7846ENSG00000167552UniProt: Q71U36

Tubulin is the major constituent of microtubules, a cylinder consisting of laterally associated linear protofilaments composed of alpha- and beta-tubulin heterodimers. Microtubules grow by the addition of GTP-tubulin dimers to the microtubule end, where a stabilizing cap forms. Below the cap, tubulin dimers are in GDP-bound state, owing to GTPase activity of alpha-tubulin

Primary Disease Associations & Inheritance

Lissencephaly 3MIM #611603
AD
442
ClinVar variants
91
Pathogenic / LP
0.97
pLI score· haploinsufficient
0
Active trials
Clinical Summary— TUBA1A
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.97). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
91 Pathogenic / Likely Pathogenic· 48 VUS of 442 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Dual constrained — LoF & missense intolerant
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.32LOEUF
pLI 0.967
Z-score 3.34
OE 0.07 (0.02–0.32)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
5.58Z-score
OE missense 0.03 (0.01–0.05)
7 obs / 260.7 exp
Constrained

Extremely missense-constrained (top ~0.01%)

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.07 (0.02–0.32)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.03 (0.01–0.05)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.10
0≤1.21.6
LoF obs/exp: 1 / 15.0Missense obs/exp: 7 / 260.7Syn Z: -0.77

ClinVar Variant Classifications

442 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic37
Likely Pathogenic54
VUS48
Likely Benign40
Benign6
Conflicting11
37
Pathogenic
54
Likely Pathogenic
48
VUS
40
Likely Benign
6
Benign
11
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
35
2
0
37
Likely Pathogenic
0
52
2
0
54
VUS
2
42
4
0
48
Likely Benign
0
0
11
29
40
Benign
0
0
4
2
6
Conflicting
—11
Total21292331196

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View 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.

Gene2Phenotype Curations

TUBA1A-related tubulinopathy

definitive
ADUndeterminedAltered Gene Product Structure
Dev. Disorders
G2P ↗
missense variantstop gained NMD escapingframeshift variant NMD escaping

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Lissencephaly 3

MIM #611603

Molecular basis of disorder known

Autosomal dominant
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Integrated ubiquitomics characterization of hepatocellular carcinomas.
Lin XT et al.·Hepatology
2025
The mutational and phenotypic spectrum of TUBA1A-associated tubulinopathy.
Hebebrand M et al.·Orphanet J Rare Dis
2019Review
Characterization of the Epileptogenic Phenotype and Response to Antiseizure Medications in Lissencephaly Patients.
Proepper CR et al.·Neuropediatrics
2024Cohort
TUBA1A mutation-associated lissencephaly: case report and review of the literature.
Sohal AP et al.·Pediatr Neurol
2012Review
Prenatal phenotyping of fetal tubulinopathies: A multicenter retrospective case series.
Brar BK et al.·Prenat Diagn
2022Review
Epilepsy in Tubulinopathy: Personal Series and Literature Review.
Romaniello R et al.·Cells
2019Review
Complementing the phenotypical spectrum of TUBA1A tubulinopathy and its role in early-onset epilepsies.
Schröter J et al.·Eur J Hum Genet
2022
Insights on the Role of α- and β-Tubulin Isotypes in Early Brain Development.
Tantry MSA et al.·Mol Neurobiol
2023Review
The genetics of lissencephaly.
Fry AE et al.·Am J Med Genet C Semin Med Genet
2014Review
Clinically Relevant Genes Identified in Cerebral Palsy Cohorts Following Evaluation of the Clinical Description and Phenotype: A Systematic Review.
Wilson YA et al.·J Child Neurol
2024Review
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools