TOB1
protein-codingtransducer of ERBB2, 1, the group of BTG/Tob family
Gene summary
This gene encodes a member of the transducer of erbB-2 /B-cell translocation gene protein family. Members of this family are anti-proliferative factors that have the potential to regulate cell growth. The encoded protein may function as a tumor suppressor. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Aug 2011]
- TROB1
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~5.8 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 TOB1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_005749.4. 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 | 0 | |||||
| missense | 35 | 35 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 2 | 2 | ||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 37 | 0 | 0 | 37 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_005740.1 | 1 | MANE Select | |
| Ensembl | ENSP00000427695.1 | 1 | MANE Select | |
| RefSeq | NP_001230806.1 | 1 | Standard | |
| RefSeq | NP_001230814.1 | 1 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| tob1a | Danio rerio | Structure: post-vent region Quality: kinked abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- RNA degradation - Homo sapiens (human)
- Bone Morphogenic Protein (BMP) Signalling and Regulation
- Exercise-induced Circadian Regulation
Biological Process
- negative regulation of cell population proliferation
- positive regulation of signal transduction
- regulation of gene expression
- negative regulation of translation
- negative regulation of BMP signaling pathway
Molecular Function
- transcription corepressor activity
- SH3/SH2 adaptor activity
- protein binding
- receptor tyrosine kinase binding
- SMAD binding
Cellular Component
- nucleus
- cytoplasm
- CCR4-NOT complex
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000499247
- Coding exons
- 1
- Length
- 5756
- Individuals with no LoFs
- 125745
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 2
- Defined
- 125747
- p
- 0.00000795
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.45 | 134 | 190 | 0.704 | 0.00000963 | 2307 |
| Missense (PolyPhen) | 39 | 72.275 | 0.5396 | 845 | ||
| Synonymous | -0.669 | 78 | 70.8 | 1.10 | 0.00000374 | 660 |
| Loss of Function | 2.88 | 0 | 9.64 | 0.00 | 4.09e-7 | 121 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| 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 | 0.0 | absent |
| South Asian | 0.000033 | 0.000033 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Anti-proliferative protein; the function is mediated by association with deadenylase subunits of the CCR4-NOT complex (PubMed:8632892, PubMed:23236473). Mediates CPEB3-accelerated mRNA deadenylation by binding to CPEB3 and recruiting CNOT7 which leads to target mRNA deadenylation and decay (PubMed:21336257). {ECO:0000269|PubMed:21336257, ECO:0000269|PubMed:23236473, ECO:0000269|PubMed:8632892}.;
Recessive Scores
- pRec
- 0.221
Intolerance Scores
- RVIS EVS
- -0.27
- RVIS percentile EVS
- 34.32
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.843
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |