TUBB6

Chr 18AD

tubulin beta 6 class V

Also known as: FPVEPD, HsT1601, TUBB-5

NCBI Gene: 84617 ENSG00000176014 UniProt: Q9BUF5 OMIM: 615103

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.

OMIM ResearchSummary from RefSeq, UniProt

Predicted to enable GTP binding activity. Predicted to be a structural constituent of cytoskeleton. Predicted to be involved in microtubule cytoskeleton organization and mitotic cell cycle. Located in microtubule. [provided by Alliance of Genome Resources, Jun 2026]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

?Facial palsy, congenital, with ptosis and velopharyngeal dysfunctionMIM #617732

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.04

LOEUF

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.04LOEUF

pLI 0.000

Z-score 1.46

OE 0.58 (0.34–1.04)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

2.64Z-score

OE missense 0.57 (0.50–0.65)

171 obs / 299.4 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.58 (0.34–1.04)

0≤0.351.4

Missense OE?0.57 (0.50–0.65)

0≤0.61.4

Synonymous OE?0.94

0≤1.21.6

LoF obs/exp: 8 / 13.9Missense obs/exp: 171 / 299.4Syn Z: 0.53

Background carrier burden — how many people carry a rare variant somewhere in TUBB6?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 140

572 rare PASS variants

Rare truncating (LoF)

1 in 1,100

85 rare PASS variants

Rare synonymous (reference)

1 in 140

294 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for TUBB6. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 140	1 in 1,800
South Asian	~43k	1 in 110	1 in 930
Remaining (unassigned)	~30k	1 in 130	1 in 1,800
European (Finnish)	~27k	1 in 440	≈ 1 in 6,300
Admixed American	~22k	1 in 97	1 in 2,000
African / African American	~21k	1 in 140	1 in 2,300
East Asian	~20k	1 in 120	1 in 2,100
Ashkenazi Jewish	~13k	1 in 210	1 in 1,300
Middle Eastern	~2,884	1 in 100	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 1 marginal. Genomes: all 4.? see exons ↓