TUBG1

Chr 17AD

tubulin gamma 1

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

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.

OMIMResearchSummary from RefSeq, OMIM, UniProt
DNmechanismADLOEUF 0.521 OMIM phenotype
VCEP Guidelines: Brain MalformationsReleased
View SpecificationsClinGen Panel
Clinical SummaryTUBG1
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Gene-Disease Validity (ClinGen)
lissencephaly spectrum disorders · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.26) despite low pLI — interpret in context.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Missense constrained — critical functional residues
LoF Constraint
0.52LOEUF
pLI 0.129
Z-score 3.27
OE 0.26 (0.140.52)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
4.16Z-score
OE missense 0.30 (0.250.36)
82 obs / 276.4 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios
LoF OE0.26 (0.140.52)
00.351.4
Missense OE0.30 (0.250.36)
00.61.4
Synonymous OE0.99
01.21.6
LoF obs/exp: 6 / 22.9Missense obs/exp: 82 / 276.4Syn Z: 0.07
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
strongTUBG1-related posteriorly predominant pachygyria and severe microcephalyOTHERAD
DN
0.7327th %ile
GOF
0.5464th %ile
LOF
0.3065th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median · 1 literature citation

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Literature Evidence

DNIn view of the fact that both KIF2A alleles are expressed in patient fibroblasts (Supplementary Fig. 4b) and the KIF2A molecule functions as a dimer22, our in vitro and in vivo data are consistent with a dominant-negative effect of these mutations.PMID:23603762

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

0 submitted variants in 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.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗