TUBG1

Chr 17AD

tubulin gamma 1

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

NCBI Gene: 7283ENSG00000131462UniProt: P23258

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]

Primary Disease Associations & Inheritance

Cortical dysplasia, complex, with other brain malformations 4MIM #615412
AD
0
ClinVar variants
0
Pathogenic / LP
0.13
pLI score
0
Active trials
Clinical Summary— TUBG1
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.26) despite low pLI — interpret in context.
Some data sources returned errors (1)

clinvarCount: Error: NCBI fetch failed: 429 https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esearch.fcgi

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Missense constrained — critical functional residues
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
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?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
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?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.26 (0.14–0.52)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.30 (0.25–0.36)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.99
0≤1.21.6
LoF obs/exp: 6 / 22.9Missense obs/exp: 82 / 276.4Syn Z: 0.07

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

TUBG1 · protein map & ClinVar variants

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

Gene2Phenotype Curations

TUBG1-related posteriorly predominant pachygyria and severe microcephaly

strong
ADUndeterminedAltered Gene Product Structure
Dev. Disorders
G2P ↗
missense variantinframe deletioninframe insertion

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
TUBULIN, GAMMA-1; TUBG1
MIM #191135 · *

Cortical dysplasia, complex, with other brain malformations 4

MIM #615412

Molecular basis of disorder known

Autosomal dominant
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
De novo variants underlying monogenic syndromes with intellectual disability in a neurodevelopmental cohort from India.
Pande S et al.·Eur J Hum Genet
2024Cohort
Two New Cases Expand the Phenotypic Spectrum of TUBG1 Missense Variants.
Urreizti R et al.·Am J Med Genet A
2025Case report
Insights on the Role of α- and β-Tubulin Isotypes in Early Brain Development.
Tantry MSA et al.·Mol Neurobiol
2023Review
TuBG1 promotes hepatocellular carcinoma via ATR/P53-apoptosis and cycling pathways.
Zhang Y et al.·Hepatobiliary Pancreat Dis Int
2024
Characterization of the Epileptogenic Phenotype and Response to Antiseizure Medications in Lissencephaly Patients.
Proepper CR et al.·Neuropediatrics
2024Cohort
Mutations in TUBG1, DYNC1H1, KIF5C and KIF2A cause malformations of cortical development and microcephaly.
Poirier K et al.·Nat Genet
2013
TUBG1 missense variants underlying cortical malformations disrupt neuronal locomotion and microtubule dynamics but not neurogenesis.
Ivanova EL et al.·Nat Commun
2019
[Clinical phenotype and genetic analysis of a child with Cortical dysplasia, complex, with other brain malformations 4 and epilepsy due to a TUBG1 gene variant].
Chen S et al.·Zhonghua Yi Xue Yi Chuan Xue Za Zhi
2025Case report
Clinical characteristics and radiological features of tubulinopathy: A single-center retrospective study in Japan.
Ikegawa T et al.·Brain Dev
2025
A novel TUBG1 mutation with neurodevelopmental disorder caused by malformations of cortical development.
Shen R et al.·Biomed Res Int
2021Case report
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools