TUBGCP4
protein-codingtubulin gamma complex associated protein 4, the group of Tubulin gamma complex associated protein family
Gene summary
This gene encodes a component of the gamma-tubulin ring complex, which is required for microtubule nucleation. In mammalian cells, the protein localizes to centrosomes in association with gamma-tubulin. Crystal structure analysis revealed a structure composed of five helical bundles arranged around conserved hydrophobic cores. An exposed surface area located in the C-terminal domain is essential and sufficient for direct binding to gamma-tubulin. Mutations in this gene that alter microtubule organization are associated with microcephaly and chorioretinopathy. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2015]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~40.6 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AR
Disease ID:MONDO:0014592
Submitter: G2P
Inheritance Pattern: AR
Disease ID:MONDO:0014592
Submitter: PanelApp Australia
Inheritance Pattern: AR
Disease ID:MONDO:0014592
Submitter: Labcorp Genetics (formerly Invitae)
Inheritance Pattern: AR
Disease ID:MONDO:0009624
Submitter: Orphanet
Clinical Genomic Database (CGD)
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
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to TUBGCP4 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_014444.5. 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 | 1 | 3 | 134 | 3 | 141 | |
| missense | 156 | 8 | 164 | |||
| nonsense | 15 | 5 | 20 | |||
| start loss | 0 | |||||
| frameshift | 12 | 4 | 16 | |||
| splice donor/acceptor (+/-2bp) | 7 | 2 | 9 | |||
| Total | 27 | 17 | 161 | 142 | 3 | 350 |
Highest pathogenic variant AF is 0.00068714627
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_055259.2 | 18 | MANE Select | |
| Ensembl | ENSP00000456648.2 | 18 | MANE Select | |
| RefSeq | NP_001273343.1 | 18 | Standard | |
| Ensembl | ENSP00000260383.7 | 18 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| tubgcp4 | Danio rerio | Structure: retinal rod cell Quality: absent abnormal |
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
- structural constituent of cytoskeleton
- protein binding
- gamma-tubulin binding
- microtubule minus-end binding
Cellular Component
- spindle pole
- equatorial microtubule organizing center
- gamma-tubulin complex
- centrosome
- cytosol
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000564079
- Coding exons
- 18
- Length
- 37875
- Individuals with no LoFs
- 124713
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 85
- Defined
- 124798
- p
- 0.000341
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 2.58 | 227 | 366 | 0.620 | 0.0000201 | 4361 |
| Missense (PolyPhen) | 32 | 65.869 | 0.48581 | 845 | ||
| Synonymous | 0.423 | 134 | 140 | 0.955 | 0.00000704 | 1306 |
| Loss of Function | 3.03 | 21 | 42.2 | 0.497 | 0.00000232 | 443 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.000065 | 0.000065 | rare |
| Latino/Admixed American | 0.00026 | 0.00026 | rare |
| Ashkenazi Jewish | 0.0028 | 0.0028 | notable |
| East Asian | 0.00045 | 0.00045 | rare |
| Finnish | 0.00032 | 0.00032 | rare |
| European (Non-Finnish) | 0.00019 | 0.00019 | rare |
| South Asian | 0.00036 | 0.00036 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Gamma-tubulin complex is necessary for microtubule nucleation at the centrosome.;
Recessive Scores
- pRec
- 0.105
Intolerance Scores
- LoFtool
- 0.710
- RVIS EVS
- -0.29
- RVIS percentile EVS
- 33.2
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- E
- Essential (gene trap)
- E
- Indispensability pred.
- E
- Indispensability score
- 0.717
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |