TUBGCP4

Chr 15AR

tubulin gamma complex component 4

Also known as: 76P, GCP-4, GCP4, Grip76, MCCRP3

NCBI Gene: 27229 ENSG00000137822 UniProt: Q9UGJ1 OMIM: 609610

This gene encodes a component of the gamma-tubulin ring complex that mediates microtubule nucleation at centrosomes, which is critical for centrosome duplication and spindle formation. Mutations cause microcephaly and chorioretinopathy, autosomal recessive, 3, affecting brain development and the retina. The gene shows high constraint against loss-of-function variants (LOEUF 0.716) and follows autosomal recessive inheritance.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a component of the gamma-tubulin ring complex, which is required for microtubule nucleation. In mammalian cells, the protein localizes to centrosomes in association with gamma-tubulin. Crystal structure analysis revealed a structure composed of five helical bundles arranged around conserved hydrophobic cores. An exposed surface area located in the C-terminal domain is essential and sufficient for direct binding to gamma-tubulin. Mutations in this gene that alter microtubule organization are associated with microcephaly and chorioretinopathy. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2015]

OMIM ResearchGenerating clinical summary…

LOFmechanismARLOEUF 0.721 OMIM phenotype

Clinical Summary— TUBGCP4

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

45 unique Pathogenic / Likely Pathogenic· 191 VUS of 600 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.72LOEUF

pLI 0.000

Z-score 3.03

OE 0.50 (0.35–0.72)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

2.58Z-score

OE missense 0.62 (0.56–0.69)

227 obs / 365.8 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.50 (0.35–0.72)

0≤0.351.4

Missense OE?0.62 (0.56–0.69)

0≤0.61.4

Synonymous OE?0.95

0≤1.21.6

LoF obs/exp: 21 / 42.2Missense obs/exp: 227 / 365.8Syn Z: 0.42

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

strongTUBGCP4-related microcephaly with chorioretinopathyLOFAR

This gene — mechanism propensity

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

0.5870th %ile

GOF

0.6542th %ile

LOF

0.2970th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

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

ClinVar Variant Classifications

600 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic31

Likely Pathogenic14

VUS191

Likely Benign310

Benign42

Conflicting3

Pathogenic

Likely Pathogenic

191

VUS

310

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	29	0	2	0	31
Likely Pathogenic	12	0	1	1	14
VUS	2	167	20	2	191
Likely Benign	0	5	172	133	310
Benign	0	0	38	4	42
Conflicting	—				3
Total	43	172	233	140	591

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

11 pathogenic / likely-pathogenic (of 20) ClinVar copy-number / structural variants overlap TUBGCP4 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →