TUBGCP2

Chr 10AR

tubulin gamma complex component 2

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

NCBI Gene: 10844 ENSG00000130640 UniProt: Q9BSJ2 OMIM: 617817

The TUBGCP2 protein is a component of the gamma-tubulin ring complex that mediates microtubule nucleation, which is critical for centrosome duplication and spindle formation during cell division. Biallelic mutations cause autosomal recessive pachygyria, microcephaly, developmental delay, and dysmorphic facies, with or without seizures. This gene shows low constraint against loss-of-function variants (LOEUF 0.68), and the associated disorder affects brain development and neuronal migration.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

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]

OMIM ResearchGenerating clinical summary…

MultiplemechanismARLOEUF 0.681 OMIM phenotype

Clinical Summary— TUBGCP2

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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

2 unique Pathogenic / Likely Pathogenic· 196 VUS of 309 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?

0.68LOEUF

pLI 0.000

Z-score 3.21

OE 0.47 (0.33–0.68)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

1.24Z-score

OE missense 0.85 (0.79–0.92)

491 obs / 574.7 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.47 (0.33–0.68)

0≤0.351.4

Missense OE?0.85 (0.79–0.92)

0≤0.61.4

Synonymous OE?1.07

0≤1.21.6

LoF obs/exp: 20 / 42.6Missense obs/exp: 491 / 574.7Syn Z: -0.94

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

strongTUBGCP2-related microcephaly and lissencephaly spectrum disordersOTHERAR

This gene — mechanism propensity

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

0.6357th %ile

GOF

0.6638th %ile

LOF

0.3065th %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

309 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic2

VUS196

Likely Benign59

Benign10

Conflicting7

Pathogenic

196

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	1	1	0	0	2
Likely Pathogenic	0	0	0	0	0
VUS	5	187	2	2	196
Likely Benign	0	11	14	34	59
Benign	0	0	5	5	10
Conflicting	—				7
Total	6	199	21	41	274

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

View in ClinVar →

98 pathogenic / likely-pathogenic (of 119) ClinVar copy-number / structural variants overlap TUBGCP2 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →