TBC1D20
protein-codingTBC1 domain family member 20
Gene summary
This gene encodes a protein that belongs to a family of GTPase activator proteins of Rab-like small GTPases. The encoded protein and its cognate GTPase, Rab1, bind the nonstructural protein 5A (NS5A) of the hepatitis C virus (HCV) to mediate viral replication. Depletion of this protein inhibits replication of the virus and HCV infection. Mutations in this gene are associated with Warburg micro syndrome 4. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2014]
- C20orf140
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~39.0 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AR
Disease ID:MONDO:0014296
Submitter: G2P
Inheritance Pattern: AR
Disease ID:MONDO:0014296
Submitter: PanelApp Australia
Inheritance Pattern: AR
Disease ID:MONDO:0014296
Submitter: Labcorp Genetics (formerly Invitae)
Inheritance Pattern: AR
Disease ID:MONDO:0014296
Submitter: Ambry Genetics
Inheritance Pattern: AR
Disease ID:MONDO:0016649
Submitter: Orphanet
Clinical Genomic Database (CGD)
Manifestation: Craniofacial; Genitourinary; Musculoskeletal; 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 TBC1D20 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_144628.4. 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 | 1 | 36 | 1 | 38 | ||
| missense | 73 | 2 | 1 | 76 | ||
| nonsense | 3 | 3 | ||||
| start loss | 0 | |||||
| frameshift | 2 | 1 | 3 | |||
| splice donor/acceptor (+/-2bp) | 1 | 3 | 4 | |||
| Total | 6 | 1 | 77 | 38 | 2 | 124 |
Highest pathogenic variant AF is 0.000002736199
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_653229.1 | 8 | MANE Select | |
| Ensembl | ENSP00000346139.4 | 8 | MANE Select | |
| Ensembl | ENSP00000432280.1 | 8 | Standard | |
| Ensembl | ENSP00000504904.1 | 8 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Vesicle-mediated transport
- TBC/RABGAPs
- Membrane Trafficking
- Post-translational protein modification
- Metabolism of proteins
Biological Process
- acrosome assembly
- endoplasmic reticulum to Golgi vesicle-mediated transport
- Golgi organization
- virion assembly
- lipid droplet organization
Molecular Function
- GTPase activator activity
- protein binding
- Rab GTPase binding
Cellular Component
- endoplasmic reticulum
- endoplasmic reticulum membrane
- integral component of Golgi membrane
- nuclear membrane
- endoplasmic reticulum-Golgi intermediate compartment membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000354200
- Coding exons
- 8
- Length
- 27074
- Individuals with no LoFs
- 125742
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 5
- Defined
- 125747
- p
- 0.0000199
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.21 | 176 | 228 | 0.773 | 0.0000132 | 2629 |
| Missense (PolyPhen) | 38 | 79.357 | 0.47885 | 906 | ||
| Synonymous | 0.742 | 81 | 90.0 | 0.900 | 0.00000488 | 811 |
| Loss of Function | 3.41 | 2 | 17.3 | 0.115 | 9.00e-7 | 200 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.000062 | 0.000062 | rare |
| Latino/Admixed American | 0.000029 | 0.000029 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000027 | 0.000026 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: GTPase-activating protein specific for Rab1 and Rab2 small GTPase families for which it can accelerate the intrinsic GTP hydrolysis rate by more than five orders of magnitude.;
- Disease
- DISEASE: Warburg micro syndrome 4 (WARBM4) [MIM:615663]: A form of Warburg micro syndrome, a rare syndrome characterized by microcephaly, microphthalmia, microcornia, congenital cataracts, optic atrophy, cortical dysplasia, in particular corpus callosum hypoplasia, severe mental retardation, spastic diplegia, and hypogonadism. {ECO:0000269|PubMed:24239381}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Recessive Scores
- pRec
- 0.110
Intolerance Scores
- LoFtool
- 0.224
- RVIS EVS
- -0.18
- RVIS percentile EVS
- 39.95
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.359
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |