TUBGCP2

Chr 10AR

tubulin gamma complex component 2

Also known as: ALP4, GCP-2, GCP2, Grip103, PAMDDFS, SPBC97, SPC97, Spc97p

NCBI Gene: 10844ENSG00000130640UniProt: Q9BSJ2

Predicted to enable gamma-tubulin binding activity. Predicted to contribute to microtubule minus-end binding activity. Involved in brain development and neuron migration. Located in centrosome; ciliary basal body; and nucleoplasm. Implicated in pachygyria, microcephaly, developmental delay, and dysmorphic facies, with or without seizures. [provided by Alliance of Genome Resources, Jul 2025]

Primary Disease Associations & Inheritance

Pachygyria, microcephaly, developmental delay, and dysmorphic facies, with or without seizuresMIM #618737
AR
UniProtCortical dysplasia, complex, with other brain malformations 15
386
ClinVar variants
99
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— TUBGCP2
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
99 Pathogenic / Likely Pathogenic· 211 VUS of 386 total submissions
Some data sources returned errors (1)

pubmed: 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.
0.68LOEUF
pLI 0.000
Z-score 3.21
OE 0.47 (0.33–0.68)
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.
1.24Z-score
OE missense 0.85 (0.79–0.92)
491 obs / 574.7 exp
Tolerant

Mild missense constraint

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.0.47 (0.33–0.68)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.85 (0.79–0.92)
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.1.07
0≤1.21.6
LoF obs/exp: 20 / 42.6Missense obs/exp: 491 / 574.7Syn Z: -0.94

ClinVar Variant Classifications

386 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic95
Likely Pathogenic4
VUS211
Likely Benign57
Benign12
Conflicting7
95
Pathogenic
4
Likely Pathogenic
211
VUS
57
Likely Benign
12
Benign
7
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
1
1
93
0
95
Likely Pathogenic
0
0
4
0
4
VUS
3
185
21
2
211
Likely Benign
0
11
14
32
57
Benign
0
0
6
6
12
Conflicting
—7
Total419713840386

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

View in ClinVar →

Protein Context — Lollipop Plot

TUBGCP2 · protein map & ClinVar variants

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

Gene2Phenotype Curations

TUBGCP2-related microcephaly and lissencephaly spectrum disorders

strong
ARUndeterminedUncertain
Dev. Disorders
G2P ↗

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Pachygyria, microcephaly, developmental delay, and dysmorphic facies, with or without seizures

MIM #618737

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
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.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools