TBC1D10C
protein-codingTBC1 domain family member 10C
Gene summary
The protein encoded by this gene has an N-terminal Rab-GTPase domain and a binding site at the C-terminus for calcineurin, and is an inhibitor of both the Ras signaling pathway and calcineurin, a phosphatase regulated by calcium and calmodulin. Genes encoding similar proteins are located on chromosomes 16 and 22. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2013]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~6.2 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to TBC1D10C variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001369496.1. 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 | 4 | |||
| missense | 81 | 2 | 83 | |||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 3 | 3 | ||||
| Total | 0 | 0 | 86 | 5 | 0 | 91 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001356425.1 | 9 | MANE Select | |
| Ensembl | ENSP00000443654.1 | 9 | MANE Select | |
| RefSeq | NP_001243437.1 | 8 | Standard | |
| RefSeq | NP_001356421.1 | 7 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Neutrophil degranulation
- Vesicle-mediated transport
- TBC/RABGAPs
- Membrane Trafficking
- Innate Immune System
Biological Process
- intracellular protein transport
- retrograde transport, endosome to Golgi
- neutrophil degranulation
- negative regulation of B cell activation
- negative regulation of ERK1 and ERK2 cascade
Molecular Function
- GTPase activator activity
- protein binding
- Rab GTPase binding
Cellular Component
- cytosol
- plasma membrane
- membrane
- filopodium membrane
- ficolin-1-rich granule membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000312390
- Coding exons
- 9
- Length
- 6175
- Individuals with no LoFs
- 125506
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 41
- Defined
- 125547
- p
- 0.000163
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.920 | 237 | 280 | 0.845 | 0.0000191 | 2753 |
| Missense (PolyPhen) | 96 | 129.22 | 0.74294 | 1239 | ||
| Synonymous | -0.212 | 126 | 123 | 1.02 | 0.00000792 | 978 |
| Loss of Function | 3.34 | 6 | 23.4 | 0.256 | 0.00000133 | 232 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0.000030 | 0.000029 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.000054 | 0.000054 | rare |
| Finnish | 0.00057 | 0.00055 | rare |
| European (Non-Finnish) | 0.00023 | 0.00022 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0.00034 | 0.00033 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Inhibits the Ras signaling pathway through its intrinsic Ras GTPase-activating protein (GAP) activity. Acts as a negative feedback inhibitor of the calcineurin signaling pathway that also mediates crosstalk between calcineurin and Ras. {ECO:0000269|PubMed:17230191}.;
Recessive Scores
- pRec
- 0.116
Intolerance Scores
- LoFtool
- 0.598
- RVIS EVS
- -0.85
- RVIS percentile EVS
- 11.06
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.287
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |