TUBGCP2

protein-coding

tubulin gamma complex associated protein 2, the group of Tubulin gamma complex associated protein family

Gene summary

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. Implicated in pachygyria, microcephaly, developmental delay, and dysmorphic facies, with or without seizures. [provided by Alliance of Genome Resources, Jun 2026]

MANE transcript

NM_006659.4

Inheritance

ClinVar variants

P:4U:160B:53

Top phenotype

Cortical dysplasia, complex, with other brain malformations 15

gnomAD constraint

pLI —, LoF o/e 0.47

Max pathogenic AF

—

Genomic locus

chr10:133,278,635-133,318,823

External References & Databases

Ensembl (ENSG00000130640)

Transcript & Mutation Effects

hg38 • Region Span ~40.2 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

pachygyria, microcephaly, developmental delay, and dysmorphic facies, with or without seizuresSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0032893

Submitter: PanelApp Australia

pachygyria, microcephaly, developmental delay, and dysmorphic facies, with or without seizuresSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0032893

Submitter: Labcorp Genetics (formerly Invitae)

pachygyria, microcephaly, developmental delay, and dysmorphic facies, with or without seizuresLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0032893

Submitter: Ambry Genetics

pachygyria, microcephaly, developmental delay, and dysmorphic facies, with or without seizuresSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0032893

Submitter: G2P

Clinical Genomic Database (CGD)

Cortical dysplasia, complex, with other brain malformations 15AR

Manifestation: Craniofacial; Neurologic; Ophthalmologic

Intervention: General

Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing

Refs: 31630790

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to TUBGCP2 variants in ClinVar

5 Conditions Cataloged

not specifiedTotal: 164

not providedTotal: 69

TUBGCP2-related disorderTotal: 31

Pachygyria, microcephaly, developmental delay, and dysmorphic facies, with or without seizuresTotal: 14

Abnormality of neuronal migrationTotal: 4

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_006659.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			4 clinvar	39 clinvar	1 clinvar	44
missense	1 clinvar	1 clinvar	145 clinvar	13 clinvar		160
nonsense			1 clinvar			1
start loss						0
frameshift		1 clinvar	3 clinvar			4
splice donor/acceptor (+/-2bp)	1 clinvar		7 clinvar			8
Total	2	2	160	52	1	217

Highest pathogenic variant AF is 0.00006691168

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 89 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_006659.4	RefSeq	NP_006650.1	17	MANE Select
ENST00000252936.8	Ensembl	ENSP00000252936.3	17	MANE Select
NM_001256617.2	RefSeq	NP_001243546.1	18	Standard
NM_001256618.2	RefSeq	NP_001243547.1	15	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Recruitment of mitotic centrosome proteins and complexes
Centrosome maturation
G2/M Transition
Mitotic G2-G2/M phases
Recruitment of NuMA to mitotic centrosomes

Biological Process

mitotic cell cycle
microtubule nucleation
cytoplasmic microtubule organization
spindle assembly
meiotic cell cycle

Molecular Function

protein binding
gamma-tubulin binding
microtubule minus-end binding

Cellular Component

spindle pole
equatorial microtubule organizing center
gamma-tubulin complex
nucleoplasm
centrosome

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000543663
Coding exons: 18
Length: 32707
Individuals with no LoFs: 125685
Homozygous LoFs: 0
Heterozygous LoFs: 63
Defined: 125748
p: 0.000251

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.24	491	575	0.854	0.0000370	6081
Missense (PolyPhen)		151	187.6	0.80491		2043
Synonymous	-0.942	283	264	1.07	0.0000197	1827
Loss of Function	3.21	20	42.6	0.470	0.00000207	489

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000062	0.000062	rare
Latino/Admixed American	0.00023	0.00023	rare
Ashkenazi Jewish	0.00020	0.00020	rare
East Asian	0.00022	0.00022	rare
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.00034	0.00034	rare
South Asian	0.00016	0.00016	rare
Other	0.00049	0.00049	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Gamma-tubulin complex is necessary for microtubule nucleation at the centrosome.;

Recessive Scores

pRec: 0.274

Intolerance Scores

LoFtool: 0.721
RVIS EVS: -0.88
RVIS percentile EVS: 10.58

Essentials

Essential (CRISPR): E
Essential (CRISPR2): E
Indispensability pred.: E
Indispensability score: 0.907

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium