TUBB6

Chr 18AD

tubulin beta 6 class V

Also known as: FPVEPD, HsT1601, TUBB-5

TUBB6 encodes a beta-tubulin protein that forms microtubules through polymerization with alpha-tubulin, serving as a major structural component of the cellular cytoskeleton and mitotic spindle. Mutations cause autosomal dominant congenital fibrosis of the extraocular muscles type 4 (CFEOM4), characterized by restrictive ophthalmoplegia and ptosis present from birth. The gene shows low constraint to loss-of-function variation, suggesting the pathogenic variants likely affect protein function through other mechanisms.

OMIMResearchSummary from RefSeq, UniProt
DNmechanismADLOEUF 1.041 OMIM phenotype
Clinical SummaryTUBB6
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.04LOEUF
pLI 0.000
Z-score 1.46
OE 0.58 (0.341.04)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
2.64Z-score
OE missense 0.57 (0.500.65)
171 obs / 299.4 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.58 (0.341.04)
00.351.4
Missense OE0.57 (0.500.65)
00.61.4
Synonymous OE0.94
01.21.6
LoF obs/exp: 8 / 13.9Missense obs/exp: 171 / 299.4Syn Z: 0.53
DN
0.79top 25%
GOF
0.5464th %ile
LOF
0.3260th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

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.

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

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

TUBB6 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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