TUBGCP4

Chr 15AR

tubulin gamma complex component 4

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

NCBI Gene: 27229ENSG00000137822UniProt: Q9UGJ1

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]

Primary Disease Associations & Inheritance

Microcephaly and chorioretinopathy, autosomal recessive, 3MIM #616335
AR
0
Active trials
41
Pathogenic / LP
508
ClinVar variants
1
Pubs (1 yr)
2.6
Missense Z
0.72
LOEUF
Clinical Summary— TUBGCP4
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
41 Pathogenic / Likely Pathogenic· 151 VUS of 508 total submissions

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 OE0.50 (0.35–0.72)
0≤0.351.4
Missense OE0.62 (0.56–0.69)
0≤0.61.4
Synonymous OE0.95
0≤1.21.6
LoF obs/exp: 21 / 42.2Missense obs/exp: 227 / 365.8Syn Z: 0.42
GOF
DN
0.5870th %ile
GOF
0.6542th %ile
LOF
0.2970th %ile

The highest-scoring mechanism for this gene is gain-of-function.

GOFprediction above median

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.

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

ClinVar Variant Classifications

508 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic31
Likely Pathogenic10
VUS151
Likely Benign274
Benign40
Conflicting2
31
Pathogenic
10
Likely Pathogenic
151
VUS
274
Likely Benign
40
Benign
2
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
10
0
21
0
31
Likely Pathogenic
6
0
3
1
10
VUS
2
129
18
2
151
Likely Benign
0
1
161
112
274
Benign
0
0
39
1
40
Conflicting
—2
Total18130242116508

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

View in ClinVar →

TUBGCP4 · protein map & ClinVar variants

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

Gene2Phenotype Curations

TUBGCP4-related microcephaly with chorioretinopathy

strong
ARLoss Of FunctionAbsent Gene Product
Dev. DisordersEye
G2P ↗

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

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Landmark / reviewRecent case evidence
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients