TUBGCP5

Chr 15

tubulin gamma complex component 5

Also known as: GCP5

NCBI Gene: 114791ENSG00000275835UniProt: Q96RT8OMIM: 608147

The protein is a component of the gamma-tubulin ring complex that mediates microtubule nucleation at centrosomes, which is critical for centrosome duplication and spindle formation during cell division. Mutations cause autosomal recessive microcephaly, seizures, and developmental delay, with this gene being extremely intolerant to loss-of-function variants. The condition affects brain development and neurological function from early life.

OMIMResearchSummary from RefSeq, UniProt
MultiplemechanismLOEUF 0.67
Clinical Summary— TUBGCP5
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
212 unique Pathogenic / Likely Pathogenic· 211 VUS of 538 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
0.67LOEUF
pLI 0.000
Z-score 3.63
OE 0.50 (0.37–0.67)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
1.37Z-score
OE missense 0.83 (0.77–0.90)
456 obs / 546.1 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.50 (0.37–0.67)
0≤0.351.4
Missense OE0.83 (0.77–0.90)
0≤0.61.4
Synonymous OE1.08
0≤1.21.6
LoF obs/exp: 30 / 60.5Missense obs/exp: 456 / 546.1Syn Z: -0.85
DN
0.6745th %ile
GOF
0.6637th %ile
LOF
0.2580th %ile

This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

DNprediction above median
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

538 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic200
Likely Pathogenic12
VUS211
Likely Benign24
Benign48
Conflicting16
200
Pathogenic
12
Likely Pathogenic
211
VUS
24
Likely Benign
48
Benign
16
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
200
0
200
Likely Pathogenic
0
0
12
0
12
VUS
0
132
79
0
211
Likely Benign
0
5
10
9
24
Benign
0
1
42
5
48
Conflicting
—16
Total013834314511

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

View in ClinVar →

Protein Context — Lollipop Plot

TUBGCP5 · 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

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
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