TBC1D7
protein-codingTBC1 domain family member 7, the group of TSC complex
Gene summary
This gene encodes a member of the TBC-domain containing protein family. The encoded protein functions as a subunit of the tuberous sclerosis TSC1-TSC2 complex which plays a role in the regulation of cellular growth and differentiation. Mutations in this gene have been associated with autosomal recessive megalencephaly. Alternative splicing results in multiple transcript variants. Naturally occurring readthrough transcription occurs between this locus and downstream LOC100130357. [provided by RefSeq, Jan 2016]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~62.0 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AR
Disease ID:MONDO:0009544
Submitter: Labcorp Genetics (formerly Invitae)
Inheritance Pattern: AR
Disease ID:MONDO:0009544
Submitter: PanelApp Australia
Inheritance Pattern: AR
Disease ID:MONDO:0009544
Submitter: Ambry Genetics
Inheritance Pattern: AR
Disease ID:MONDO:0009544
Submitter: Genomics England PanelApp
Clinical Genomic Database (CGD)
Manifestation: Craniofacial; Gastrointestinal; Musculoskeletal; Neurologic; Ophthalmologic; Renal
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 TBC1D7 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_016495.6. 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 | 22 | 5 | 28 | ||
| missense | 62 | 8 | 1 | 71 | ||
| nonsense | 1 | 2 | 3 | |||
| start loss | 0 | |||||
| frameshift | 3 | 3 | 1 | 7 | ||
| splice donor/acceptor (+/-2bp) | 1 | 3 | 4 | |||
| Total | 4 | 4 | 69 | 30 | 6 | 113 |
Highest pathogenic variant AF is 0.00005452056
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_057579.1 | 7 | MANE Select | |
| Ensembl | ENSP00000368602.3 | 7 | MANE Select | |
| RefSeq | NP_001137436.1 | 7 | Standard | |
| RefSeq | NP_001137437.1 | 7 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- mTOR signaling pathway - Homo sapiens (human)
- Vesicle-mediated transport
- TBC/RABGAPs
- Membrane Trafficking
- Rab regulation of trafficking
Biological Process
- positive regulation of protein ubiquitination
- negative regulation of TOR signaling
- positive regulation of GTPase activity
- response to growth factor
- activation of GTPase activity
Molecular Function
- GTPase activator activity
- protein binding
- Rab GTPase binding
Cellular Component
- cytosol
- cytoplasmic vesicle
- ciliary basal body
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000606214
- Coding exons
- 7
- Length
- 62042
- Individuals with no LoFs
- 125705
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 43
- Defined
- 125748
- p
- 0.000171
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.144 | 168 | 173 | 0.969 | 0.0000102 | 1924 |
| Missense (PolyPhen) | 39 | 58.126 | 0.67095 | 695 | ||
| Synonymous | -0.382 | 67 | 63.1 | 1.06 | 0.00000382 | 537 |
| Loss of Function | -0.291 | 17 | 15.8 | 1.08 | 8.17e-7 | 194 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0.00012 | 0.00012 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00017 | 0.00011 | rare |
| Finnish | 0.00019 | 0.00018 | rare |
| European (Non-Finnish) | 0.00027 | 0.00026 | rare |
| South Asian | 0.000099 | 0.000098 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Component of the TSC-TBC complex, that contains TBC1D7 in addition to the TSC1-TSC2 complex and consists of the functional complex possessing GTPase-activating protein (GAP) activity toward RHEB in response to alterations in specific cellular growth conditions. The small GTPase RHEB is a direct activator of the protein kinase activity of mTORC1 and the TSC-TBC complex acts as a negative regulator of mTORC1 signaling cascade by acting as a GAP for RHEB. Participates in the proper sensing of growth factors and glucose, but not amino acids, by mTORC1. It is unclear whether TBC1D7 acts as a GTPase-activating protein and additional studies are required to answer this question. {ECO:0000269|PubMed:22795129}.;
Intolerance Scores
- LoFtool
- 0.978
- RVIS EVS
- -0.16
- RVIS percentile EVS
- 41.91
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.783
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |