TUBB2A

Chr 6AD

tubulin beta 2A class IIa

Also known as: CDCBM5, TUBB, TUBB2

NCBI Gene: 7280ENSG00000137267UniProt: Q13885

Microtubules, key participants in processes such as mitosis and intracellular transport, are composed of heterodimers of alpha- and beta-tubulins. The protein encoded by this gene is a beta-tubulin. Defects in this gene are associated with complex cortical dysplasia with other brain malformations-5. Two transcript variants encoding distinct isoforms have been found for this gene. [provided by RefSeq, Jul 2015]

Primary Disease Associations & Inheritance

Cortical dysplasia, complex, with other brain malformations 5MIM #615763
AD
335
ClinVar variants
80
Pathogenic / LP
0.93
pLI score· haploinsufficient
0
Active trials
Clinical Summary— TUBB2A
🧬
Gene-Disease Validity (ClinGen)
tubulinopathy · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.93). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
80 Pathogenic / Likely Pathogenic· 115 VUS of 335 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.
0.36LOEUF
pLI 0.935
Z-score 3.10
OE 0.08 (0.03–0.36)
Highly constrained

More LoF-intolerant than ~75% 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.
5.26Z-score
OE missense 0.11 (0.08–0.15)
31 obs / 277.9 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.0.08 (0.03–0.36)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.11 (0.08–0.15)
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.1.01
0≤1.21.6
LoF obs/exp: 1 / 13.1Missense obs/exp: 31 / 277.9Syn Z: -0.06

ClinVar Variant Classifications

335 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic50
Likely Pathogenic30
VUS115
Likely Benign103
Benign22
Conflicting15
50
Pathogenic
30
Likely Pathogenic
115
VUS
103
Likely Benign
22
Benign
15
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
7
43
0
50
Likely Pathogenic
0
24
6
0
30
VUS
2
90
22
1
115
Likely Benign
0
8
17
78
103
Benign
0
1
15
6
22
Conflicting
—15
Total213010385335

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

View in ClinVar →

Protein Context — Lollipop Plot

TUBB2A · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

TUBB2A-related cortical dysplasia, complex, with other brain malformations

definitive
ADUndeterminedAltered Gene Product Structure
Dev. Disorders
G2P ↗
missense variantinframe deletioninframe insertion

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
TUBULIN, BETA-2A; TUBB2A
MIM #615101 · *

Cortical dysplasia, complex, with other brain malformations 5

MIM #615763

Molecular basis of disorder known

Autosomal dominant
📖
GeneReview available — TUBB2A
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Integrated analysis of single-cell RNA-seq and spatial transcriptomics to identify the lactylation-related protein TUBB2A as a potential biomarker for glioblastoma in cancer cells by machine learning.
Xu Y et al.·Front Immunol
2025
Prenatal phenotyping of fetal tubulinopathies: A multicenter retrospective case series.
Brar BK et al.·Prenat Diagn
2022Review
Insights on the Role of α- and β-Tubulin Isotypes in Early Brain Development.
Tantry MSA et al.·Mol Neurobiol
2023Review
Attenuated Clinical Forms of Tubulinopathies in Children and Adults: A Series of 24 Individuals.
Durizot M et al.·Pediatr Neurol
2025Cohort
Generation of an induced pluripotent stem cell line (DHMCi009-A) from an individual with TUBB2A tubulinopathy.
Schröter J et al.·Stem Cell Res
2022
De novo pathogenic variant in TUBB2A presenting with arthrogryposis multiplex congenita, brain abnormalities, and severe developmental delay.
Ejaz R et al.·Am J Med Genet A
2017Case report
Defining the phenotypical spectrum associated with variants in TUBB2A.
Brock S et al.·J Med Genet
2021
Defective kinesin binding of TUBB2A causes progressive spastic ataxia syndrome resembling sacsinopathy.
Sferra A et al.·Hum Mol Genet
2018
De Novo TUBB2A Variant Presenting With Anterior Temporal Pachygyria.
Rodan LH et al.·J Child Neurol
2017Case report
Clinical characteristics and radiological features of tubulinopathy: A single-center retrospective study in Japan.
Ikegawa T et al.·Brain Dev
2025
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