TUBB2B

Chr 6

tubulin beta 2B class IIb

Also known as: CDCBM7, PMGYSA, bA506K6.1

NCBI Gene: 347733 ENSG00000137285 UniProt: Q9BVA1

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 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 ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtCortical dysplasia, complex, with other brain malformations 7

Clinical highlights

Gene–disease validity (ClinGen · GenCC)

Definitive · complex cortical dysplasia with other brain malformations · AD · ClinGen 2020
Definitive · complex cortical dysplasia with other brain malformations 7 · AD · G2P
Limited · congenital fibrosis of extraocular muscles · AD · Genomics England PanelApp — not for standalone diagnostic reporting
Supportive · cerebellar ataxia, intellectual disability, and dysequilibrium · AR · Orphanet

+1 more curated pair

Interpreting a novel variant

A dominant-negative effect is the curated mechanism (Gene2Phenotype), so a variant that simply removes the protein may not be the pathogenic class here — missense variants in functional domains often carry more weight.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.22

LOEUF· LoF intol.

DN*

Mechanism· G2P

📖

GeneReview available — TUBB2B

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Dual constrained — LoF & missense intolerant

LoF Constraint?

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?

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?

LoF OE?0.00 (0.00–0.22)

0≤0.351.4

Missense OE?0.11 (0.08–0.15)

0≤0.61.4

Synonymous OE?0.82

0≤1.21.6

LoF obs/exp: 0 / 13.4Missense obs/exp: 30 / 264.1Syn Z: 1.53

Background carrier burden — how many people carry a rare variant somewhere in TUBB2B?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 920

72 rare PASS variants

Rare truncating (LoF)

1 in 37,000

11 rare PASS variants

Rare synonymous (reference)

1 in 310

187 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for TUBB2B. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 8 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 510	1 in 25,000
South Asian	~43k	1 in 1,700	≈ 1 in 43,000
Remaining (unassigned)	~30k	1 in 4,200	≈ 1 in 15,000
European (Finnish)	~27k	1 in 1,900	≈ 1 in 26,000
Admixed American	~22k	1 in 1,200	none seen
African / African American	~21k	1 in 1,200	none seen
East Asian	~20k	1 in 780	none seen
Ashkenazi Jewish	~13k	1 in 550	none seen

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 3 of 4 coding exons well covered in gnomAD exomes; exon 4 marginal. Genomes: 3 of 4 (exon 4 below).? see exons ↓