TUBGCP6

Chr 22AR

tubulin gamma complex component 6

NCBI Gene: 85378ENSG00000128159UniProt: Q96RT7

Component of the gamma-tubulin ring complex (gTuRC) which mediates microtubule nucleation (PubMed:11694571, PubMed:38305685, PubMed:38609661, PubMed:39321809). The gTuRC regulates the minus-end nucleation of alpha-beta tubulin heterodimers that grow into microtubule protafilaments, a critical step in centrosome duplication and spindle formation (PubMed:38305685, PubMed:38609661, PubMed:39321809)

Primary Disease Associations & Inheritance

Microcephaly and chorioretinopathy, autosomal recessive, 1MIM #251270
AR
2472
ClinVar variants
0
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— TUBGCP6
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
2472 total variants — no pathogenic classifications of 2472 total submissions
Some data sources returned errors (1)

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

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
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.
0.93LOEUF
pLI 0.000
Z-score 2.10
OE 0.74 (0.60–0.93)
Tolerant

Typical tolerance to LoF variation

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.
-0.94Z-score
OE missense 1.08 (1.03–1.13)
1215 obs / 1125.8 exp
Tolerant

Tolerant to missense variation

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.0.74 (0.60–0.93)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.08 (1.03–1.13)
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.1.24
0≤1.21.6
LoF obs/exp: 59 / 79.2Missense obs/exp: 1215 / 1125.8Syn Z: -4.14

ClinVar Variant Classifications

2472 submitted variants in ClinVar

ClinVar

Classification Summary

Protein Context — Lollipop Plot

TUBGCP6 · protein map & ClinVar variants

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

Gene2Phenotype Curations

TUBGCP6-related microcephaly with chorioretinopathy with or without developmental delay

definitive
ARLoss Of FunctionAbsent Gene Product
Dev. DisordersEye
G2P ↗

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Microcephaly and chorioretinopathy, autosomal recessive, 1

MIM #251270

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Biallelic variants in TUBGCP6 result in microcephaly and chorioretinopathy 1: Report of four cases and a literature review.
Thomas-Wilson A et al.·Am J Med Genet A
2023Review
Genotype Phenotype Correlation and Variability in Microcephaly Associated With Chorioretinopathy or Familial Exudative Vitreoretinopathy.
Shurygina MF et al.·Invest Ophthalmol Vis Sci
2020
WBP11 is required for splicing the TUBGCP6 pre-mRNA to promote centriole duplication.
Park EM et al.·J Cell Biol
2020
Clinical and Molecular Characterization of Familial Exudative Vitreoretinopathy Associated With Microcephaly.
Hull S et al.·Am J Ophthalmol
2019
Lissencephaly in an epilepsy cohort: Molecular, radiological and clinical aspects.
Kolbjer S et al.·Eur J Paediatr Neurol
2021Cohort
[Application of chromosome microarray analysis for fetuses with multicystic dysplastic kidney].
Chen F et al.·Zhonghua Yi Xue Yi Chuan Xue Za Zhi
2016
Genetic mapping and exome sequencing identify variants associated with five novel diseases.
Puffenberger EG et al.·PLoS One
2012
Rare missense TUBGCP5 gene variant in a patient with primary microcephaly.
Maver A et al.·Eur J Med Genet
2019Case report
Mutations in PLK4, encoding a master regulator of centriole biogenesis, cause microcephaly, growth failure and retinopathy.
Martin CA et al.·Nat Genet
2014
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.

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External Resources

Links to major genomics databases and tools