TUBA3E

Chr 2

tubulin alpha 3e

NCBI Gene: 112714 ENSG00000152086 UniProt: Q6PEY2 OMIM: 619918

TUBA3E encodes an alpha-tubulin protein that forms heterodimers with beta-tubulin to create microtubules, which are essential components of the cellular cytoskeleton involved in cell structure, division, and intracellular transport. Mutations cause microlissencephaly with global developmental delay, inherited in an autosomal dominant pattern. The gene shows very high constraint against loss-of-function variants, indicating that such mutations are likely incompatible with normal development.

OMIM ResearchSummary from RefSeq, UniProt

Microtubules of the eukaryotic cytoskeleton perform essential and diverse functions and are composed of a heterodimer of alpha and beta tubulin. The genes encoding these microtubule constituents are part of the tubulin superfamily, which is composed of six distinct families. Genes from the alpha, beta and gamma tubulin families are found in all eukaryotes. The alpha and beta tubulins represent the major components of microtubules, while gamma tubulin plays a critical role in the nucleation of microtubule assembly. This gene encodes an alpha tubulin that highly conserved among species. A missense mutation in this gene has been potentially linked to microlissencephaly and global developmental delay. [provided by RefSeq, Jul 2016]

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.36

LOEUF

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.36LOEUF

pLI 0.000

Z-score 0.51

OE 0.86 (0.56–1.36)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.30Z-score

OE missense 1.05 (0.95–1.16)

299 obs / 284.9 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.86 (0.56–1.36)

0≤0.351.4

Missense OE?1.05 (0.95–1.16)

0≤0.61.4

Synonymous OE?0.98

0≤1.21.6

LoF obs/exp: 13 / 15.1Missense obs/exp: 299 / 284.9Syn Z: 0.14

Background carrier burden — how many people carry a rare variant somewhere in TUBA3E?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 97

528 rare PASS variants

Rare truncating (LoF)

1 in 360

47 rare PASS variants

Rare synonymous (reference)

1 in 88

204 rare PASS variants

Rare missense and truncating variants are carried at similar rates in TUBA3E; this gene does not show strong loss-of-function constraint by this measure. 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 1,200
South Asian	~43k	1 in 50	1 in 530
Remaining (unassigned)	~30k	1 in 58	1 in 1,800
European (Finnish)	~27k	1 in 200	≈ 1 in 27,000
Admixed American	~22k	1 in 73	1 in 1,800
African / African American	~21k	1 in 47	1 in 780
East Asian	~20k	1 in 81	1 in 2,300
Ashkenazi Jewish	~13k	1 in 350	none seen
Middle Eastern	~2,884	1 in 65	≈ 1 in 2,800

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): 4 of 5 coding exons well covered in gnomAD exomes; exon 1 marginal. Genomes: 4 of 5 (exon 1 below).? see exons ↓