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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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TOB1
transducer of ERBB2, 1
Chromosome 17 · 17q21.33
NCBI Gene: 10140Ensembl: ENSG00000141232.6HGNC: HGNC:11979UniProt: P50616
81PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Highly Constrained
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
negative regulation of nuclear-transcribed mRNA poly(A) tail shorteningpositive regulation of nuclear-transcribed mRNA poly(A) tail shorteningpositive regulation of nuclear-transcribed mRNA catabolic process, deadenylation-dependent decayprotein bindingneurodegenerative diseaseAbdominal painLimb painHeadache
✦AI Summary

TOB1 (transducer of ERBB2, 1) is a tumor-suppressor protein that functions as a negative regulator of cell proliferation through mRNA deadenylation and cell cycle control. TOB1 mediates its anti-proliferative effects by associating with deadenylase subunits of the CCR4-NOT complex 1, and recruits CNOT7 to facilitate mRNA deadenylation and decay. This mechanism reduces expression of cyclins D1 and CDK while inducing CDK inhibitors 1. Beyond mRNA regulation, TOB1 antagonizes oncogenic signaling pathways by inhibiting β-catenin-regulated transcription, antagonizing AKT signaling, and activating pro-apoptotic proteins like BAX while suppressing anti-apoptotic BCL-2 and BCL-XL 1. In cancer progression, TOB1 is frequently downregulated through promoter hypermethylation in esophageal squamous cell carcinoma 2. Homozygous TOB1 deletion promotes lung, liver, and lymph node cancer development in mice 1. Conversely, TOB1 overexpression inhibits cancer cell migration and invasion while restricting xenograft growth 1. MicroRNA-32-5p suppresses TOB1 expression in colorectal cancer, promoting radioresistance and metastatic phenotypes 3. In gastric cancer, TOB1 phosphorylation at T172 and S320 promotes malignant progression, while phosphorylation inhibition restores tumor-suppressive activity 4. Additionally, TOB1 in neutrophils regulates immunotherapy efficacy in gastric cancer 5.

Sources cited
1
TOB1 tumor suppressor mechanism: mRNA deadenylation, cyclin/CDK regulation, β-catenin inhibition, AKT antagonism, BAX activation, and BCL-2/BCL-XL suppression
PMID: 26694352
2
TOB1 downregulation through CpG hypermethylation in esophageal squamous cell carcinoma and its role as tumor suppressor
PMID: 36002674
3
miR-32-5p directly suppresses TOB1 expression in colorectal cancer, promoting radioresistance, migration, and invasion
PMID: 31814731
4
TOB1 phosphorylation at T172 and S320 promotes gastric cancer proliferation and progression
PMID: 31497236
5
TOB1 expression in CD66b+ neutrophils influences gastric cancer prognosis and immunotherapy efficacy
PMID: 38617839
6
TOB1 maintains high expression in human Th17 cells and prevents TCR-mediated cell cycle progression
PMID: 24307243
7
TOB1 3' UTR mutations identified as cancer driver in PCAWG pan-cancer analysis
PMID: 32025015
Disease Associationsⓘ20
neurodegenerative diseaseOpen Targets
0.33Weak
Abdominal painOpen Targets
0.22Weak
Limb painOpen Targets
0.22Weak
HeadacheOpen Targets
0.19Weak
gastric cancerOpen Targets
0.11Weak
neoplasmOpen Targets
0.08Suggestive
inflammatory bowel diseaseOpen Targets
0.08Suggestive
colorectal cancerOpen Targets
0.08Suggestive
non-small cell lung carcinomaOpen Targets
0.08Suggestive
esophageal squamous cell carcinomaOpen Targets
0.07Suggestive
breast cancerOpen Targets
0.07Suggestive
osteoarthritis, hipOpen Targets
0.07Suggestive
experimental autoimmune encephalomyelitisOpen Targets
0.06Suggestive
osteoarthritis, kneeOpen Targets
0.05Suggestive
total hip arthroplastyOpen Targets
0.05Suggestive
total joint arthroplastyOpen Targets
0.05Suggestive
nail-patella syndromeOpen Targets
0.04Suggestive
myeloid sarcomaOpen Targets
0.04Suggestive
melorheostosisOpen Targets
0.04Suggestive
autosomal recessive osteopetrosis 6Open Targets
0.04Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
CNOT10Protein interaction100%CNOT11Protein interaction100%CNOT6Protein interaction100%CNOT6LProtein interaction100%CNOT2Protein interaction98%CNOT3Protein interaction98%
Tissue Expression6 tissues
Liver
100%
Bone Marrow
48%
Heart
35%
Ovary
25%
Brain
17%
Lung
16%
Gene Interaction Network
Click a node to explore
TOB1CNOT10CNOT11CNOT6CNOT6LCNOT2CNOT3
PROTEIN STRUCTURE
Preparing viewer…
PDB2Z15 · 2.30 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.27Highly Constrained
pLIⓘ
1.00Intolerant
Observed/Expected LoF0.08 [0.03–0.27]
RankingsWhere TOB1 stands among ~20K protein-coding genes
  • #5,910of 20,598
    Most Researched81
  • #884of 17,882
    Most Constrained (LOEUF)0.27 · top 5%
Genes detectedTOB1
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Analyses of non-coding somatic drivers in 2,658 cancer whole genomes.
PMID: 32025015
Nature · 2020
1.00
2
A novel cell-cycle-indicator, mVenus-p27K-, identifies quiescent cells and visualizes G0-G1 transition.
PMID: 24500246
Sci Rep · 2014
0.90
3
Methylation Mediated Downregulation of TOB1-AS1 and TOB1 Correlates with Malignant Progression and Poor Prognosis of Esophageal Squamous Cell Carcinoma.
PMID: 36002674
Dig Dis Sci · 2023
0.80
4
Transducer of ERBB2.1 (TOB1) as a Tumor Suppressor: A Mechanistic Perspective.
PMID: 26694352
Int J Mol Sci · 2015
0.70
5
MiR-32-5p Regulates Radiosensitization, Migration And Invasion Of Colorectal Cancer Cells By Targeting TOB1 Gene.
PMID: 31814731
Onco Targets Ther · 2019
0.60