TUBB2B

Chr 6AD

tubulin beta 2B class IIb

Also known as: CDCBM7, PMGYSA, bA506K6.1

NCBI Gene: 347733ENSG00000137285UniProt: Q9BVA1

The protein encoded by this gene is a beta isoform of tubulin, which binds GTP and is a major component of microtubules. This gene is highly similar to TUBB2A and TUBB2C. Defects in this gene are a cause of asymmetric polymicrogyria. [provided by RefSeq, Mar 2010]

Primary Disease Associations & Inheritance

Cortical dysplasia, complex, with other brain malformations 7MIM #610031
AD
293
ClinVar variants
121
Pathogenic / LP
0.99
pLI score· haploinsufficient
0
Active trials
Clinical Summary— TUBB2B
🧬
Gene-Disease Validity (ClinGen)
complex cortical dysplasia with other brain malformations · 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 0.99). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
121 Pathogenic / Likely Pathogenic· 97 VUS of 293 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.
0.22LOEUF
pLI 0.988
Z-score 3.40
OE 0.00 (0.00–0.22)
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.
5.12Z-score
OE missense 0.11 (0.08–0.15)
30 obs / 264.1 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.0.00 (0.00–0.22)
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.0.82
0≤1.21.6
LoF obs/exp: 0 / 13.4Missense obs/exp: 30 / 264.1Syn Z: 1.53

ClinVar Variant Classifications

293 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic66
Likely Pathogenic55
VUS97
Likely Benign53
Benign8
Conflicting14
66
Pathogenic
55
Likely Pathogenic
97
VUS
53
Likely Benign
8
Benign
14
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
20
46
0
66
Likely Pathogenic
0
49
6
0
55
VUS
4
78
10
5
97
Likely Benign
0
3
10
40
53
Benign
0
0
7
1
8
Conflicting
—14
Total41507946293

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

View in ClinVar →

Protein Context — Lollipop Plot

TUBB2B · protein map & ClinVar variants

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

Gene2Phenotype Curations

TUBB2B-related polymicrogyria asymmetric

definitive
ADDominant NegativeAltered Gene Product Structure
Dev. DisordersEye
G2P ↗

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
TUBULIN, BETA-2B; TUBB2B
MIM #612850 · *

Cortical dysplasia, complex, with other brain malformations 7

MIM #610031

Molecular basis of disorder known

Autosomal dominant
📖
GeneReview available — TUBB2B
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Targeting TUBB2B inhibits triple-negative breast cancer growth and brain-metastatic colonization.
He Q et al.·J Exp Clin Cancer Res
2025
Exome Sequencing and the Identification of New Genes and Shared Mechanisms in Polymicrogyria.
Akula SK et al.·JAMA Neurol
2023Functional
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
Epilepsy in Tubulinopathy: Personal Series and Literature Review.
Romaniello R et al.·Cells
2019Review
Attenuated Clinical Forms of Tubulinopathies in Children and Adults: A Series of 24 Individuals.
Durizot M et al.·Pediatr Neurol
2025Cohort
[Analysis of TUBB2B gene variant in a fetus with complex cortical dysplasia with other brain malformations-7].
Yan L et al.·Zhonghua Yi Xue Yi Chuan Xue Za Zhi
2022
Clinical characteristics and radiological features of tubulinopathy: A single-center retrospective study in Japan.
Ikegawa T et al.·Brain Dev
2025
Associated analysis of PER1/TUBB2B with endometrial cancer development caused by circadian rhythm disorders.
Wang Z et al.·Med Oncol
2020
Overlapping cortical malformations and mutations in TUBB2B and TUBA1A.
Cushion TD et al.·Brain
2013
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