TUBG1

Chr 17AD

tubulin gamma 1

Also known as: CDCBM4, GCP-1, TUBG, TUBGCP1

NCBI Gene: 7283 ENSG00000131462 UniProt: P23258 OMIM: 191135

The protein is gamma-tubulin, a key component of the gamma-tubulin ring complex that mediates microtubule nucleation at the centrosome, which is critical for centrosome duplication and spindle formation during cell division. Mutations cause cortical dysplasia with complex brain malformations and follow an autosomal dominant inheritance pattern. The gene is moderately constrained against loss-of-function variants (LOEUF 0.52), reflecting its essential role in cellular division and brain development.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a member of the tubulin superfamily. The encoded protein localizes to the centrosome where it binds to microtubules as part of a complex referred to as the gamma-tubulin ring complex. The protein mediates microtubule nucleation and is required for microtubule formation and progression of the cell cycle. A pseudogene of this gene is found on chromosome 7. [provided by RefSeq, Jan 2009]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Cortical dysplasia, complex, with other brain malformations 4MIM #615412

Clinical highlights

Gene–disease validity (ClinGen)

Definitive · lissencephaly spectrum disorders · AD · ClinGen 2022

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.52

LOEUF

Mechanism· predicted

📖

GeneReview available — TUBG1

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Missense constrained — critical functional residues

LoF Constraint?

0.52LOEUF

pLI 0.129

Z-score 3.27

OE 0.26 (0.14–0.52)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

4.16Z-score

OE missense 0.30 (0.25–0.36)

82 obs / 276.4 exp

Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios?

LoF OE?0.26 (0.14–0.52)

0≤0.351.4

Missense OE?0.30 (0.25–0.36)

0≤0.61.4

Synonymous OE?0.99

0≤1.21.6

LoF obs/exp: 6 / 22.9Missense obs/exp: 82 / 276.4Syn Z: 0.07

Background carrier burden — how many people carry a rare variant somewhere in TUBG1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 380

313 rare PASS variants

Rare truncating (LoF)

1 in 3,300

53 rare PASS variants

Rare synonymous (reference)

1 in 110

255 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for TUBG1. 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 530	1 in 4,100
South Asian	~43k	1 in 200	1 in 1,200
Remaining (unassigned)	~30k	1 in 240	1 in 3,700
European (Finnish)	~27k	1 in 320	1 in 4,400
Admixed American	~22k	1 in 300	≈ 1 in 11,000
African / African American	~21k	1 in 410	≈ 1 in 5,600
East Asian	~20k	1 in 230	1 in 2,100
Ashkenazi Jewish	~13k	1 in 1,200	none seen
Middle Eastern	~2,884	≈ 1 in 950	≈ 1 in 960

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 11 coding exons well covered in gnomAD exomes and genomes.? see exons ↓