TUBA3C

Chr 13

tubulin alpha 3c

Also known as: TUBA2, bA408E5.3

NCBI Gene: 7278 ENSG00000198033 UniProt: P0DPH7

This alpha tubulin protein is a major constituent of microtubules, forming heterodimers with beta-tubulin that polymerize into the cytoskeletal structures essential for cell division, intracellular transport, and neuronal function. Mutations in TUBA3C cause autosomal recessive intellectual disability with microcephaly and seizures, typically presenting in early infancy. The gene shows tolerance to loss-of-function variants (pLI 0.005), consistent with its recessive inheritance pattern.

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. There are multiple alpha and beta tubulin genes and they are highly conserved among and between species. This gene is an alpha tubulin gene that encodes a protein 99% identical to the mouse testis-specific Tuba3 and Tuba7 gene products. This gene is located in the 13q11 region, which is associated with the genetic diseases Clouston hidrotic ectodermal dysplasia and Kabuki syndrome. [provided by RefSeq, Jul 2008]

ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.86

LOEUF

Mechanism· predicted

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.86LOEUF

pLI 0.005

Z-score 1.93

OE 0.44 (0.24–0.86)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

1.78Z-score

OE missense 0.71 (0.63–0.79)

204 obs / 288.9 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.44 (0.24–0.86)

0≤0.351.4

Missense OE?0.71 (0.63–0.79)

0≤0.61.4

Synonymous OE?1.32

0≤1.21.6

LoF obs/exp: 6 / 13.7Missense obs/exp: 204 / 288.9Syn Z: -2.78

Background carrier burden — how many people carry a rare variant somewhere in TUBA3C?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 130

439 rare PASS variants

Rare truncating (LoF)

1 in 440

74 rare PASS variants

Rare synonymous (reference)

1 in 91

283 rare PASS variants

Rare missense and truncating variants are carried at similar rates in TUBA3C; 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 150	1 in 790
South Asian	~43k	1 in 100	1 in 1,500
Remaining (unassigned)	~30k	1 in 140	1 in 450
European (Finnish)	~27k	1 in 230	1 in 520
Admixed American	~22k	1 in 160	1 in 750
African / African American	~21k	1 in 140	1 in 340
East Asian	~20k	1 in 110	1 in 250
Ashkenazi Jewish	~13k	1 in 280	none seen
Middle Eastern	~2,884	1 in 100	≈ 1 in 720

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): All 5 coding exons well covered in gnomAD exomes and genomes.? see exons ↓