TUBB4A

Chr 19

tubulin beta 4A class IVa

Also known as: DYT4, TUBB4, beta-5

NCBI Gene: 10382ENSG00000104833UniProt: P04350

This gene encodes a member of the beta tubulin family. Beta tubulins are one of two core protein families (alpha and beta tubulins) that heterodimerize and assemble to form microtubules. Mutations in this gene cause hypomyelinating leukodystrophy-6 and autosomal dominant torsion dystonia-4. Alternate splicing results in multiple transcript variants encoding different isoforms. A pseudogene of this gene is found on chromosome X. [provided by RefSeq, Jan 2014]

GeneReviewsResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtDystonia 4, torsion, autosomal dominant
UniProtLeukodystrophy, hypomyelinating, 6

Clinical highlights

Gene-disease validity (ClinGen)
TUBB4A-related neurologic disorder · ADDefinitivesufficient evidence for diagnostic panels
Interpreting a novel variant
Gain of function 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.
1
Active trials
25
Pubs (1 yr)
—
P/LP submissions
—
P/LP missense
0.67
LOEUF
GOF*
Mechanism· G2P
📖
GeneReview available — TUBB4A
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
Missense constrained — critical functional residues
LoF Constraint?
0.67LOEUF
pLI 0.109
Z-score 2.41
OE 0.29 (0.14–0.67)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?
4.26Z-score
OE missense 0.31 (0.26–0.37)
93 obs / 301.1 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios?
LoF OE?0.29 (0.14–0.67)
0≤0.351.4
Missense OE?0.31 (0.26–0.37)
0≤0.61.4
Synonymous OE?1.16
0≤1.21.6
LoF obs/exp: 4 / 13.6Missense obs/exp: 93 / 301.1Syn Z: -1.48

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

TUBB4A · protein map & ClinVar variants

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

VCEP specificationsLeukodystrophyPilot
Panel ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients