TUBB2B

Chr 6AD

tubulin beta 2B class IIb

Also known as: CDCBM7, PMGYSA, bA506K6.1

NCBI Gene: 347733 ENSG00000137285 UniProt: Q9BVA1 OMIM: 612850

The encoded protein is a beta-tubulin isoform that binds GTP and serves as a major component of microtubules in the cytoskeleton. Mutations cause autosomal dominant asymmetric polymicrogyria and complex cortical dysplasia with other brain malformations. The high pLI score (0.99) indicates the gene is extremely intolerant to loss-of-function mutations, suggesting haploinsufficiency as the likely pathogenic mechanism.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

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]

GeneReviews OMIM ResearchGenerating clinical summary…

DNmechanismAD1 OMIM phenotype

VCEP Guidelines: Brain MalformationsReleased

View Specifications ClinGen Panel

Clinical Summary— TUBB2B

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Gene-Disease Validity (ClinGen)

complex cortical dysplasia with other brain malformations · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

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ClinVar Variants

72 unique Pathogenic / Likely Pathogenic· 93 VUS of 246 total submissions

Explore recent and relevant literature in Research Assistant →

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GeneReview available — TUBB2B

Authoritative clinical overview · Recommended first read

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Some data sources returned errors (1)

gnomad: TimeoutError: The operation was aborted due to timeout

Population Genetics & Constraint

gnomAD

Constraint data not available from gnomAD.

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

definitiveTUBB2B-related polymicrogyria asymmetricDNAD

This gene — mechanism propensity

0.5477th %ile

GOF

0.4382th %ile

LOF

0.64top 25%

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.

LOF1 literature citation

DN1 literature citation

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

DNTUBB2B codes for one of the isotypes of beta-tubulin and dominant negative variants in this gene result in distinctive malformations of cortical development (MCD), including dysgyria, dysmorphic basal ganglia and cerebellar anomalies.1

LOFThus, confirming that these specific developmental brain malformations are due to TUBB2A and TUBB2B haploinsufficiency.2

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

References

ClinVar Variant Classifications

246 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic21

Likely Pathogenic51

VUS93

Likely Benign53

Benign8

Conflicting15

Pathogenic

Likely Pathogenic

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	21	0	0	21
Likely Pathogenic	1	50	0	0	51
VUS	5	80	3	5	93
Likely Benign	0	3	9	41	53
Benign	0	0	7	1	8
Conflicting	—				15
Total	6	154	19	47	241

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

View in ClinVar →

51 pathogenic / likely-pathogenic (of 60) ClinVar copy-number / structural variants overlap TUBB2B — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →