TOB1

Chr 17

transducer of ERBB2, 1

Also known as: APRO5, APRO6, PIG49, TOB, TROB, TROB1

NCBI Gene: 10140ENSG00000141232UniProt: P50616

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]

0
Active trials
0
Pathogenic / LP
0
ClinVar variants
3
Pubs (1 yr)
1.5
Missense Z
0.31
LOEUF· LoF intolerant
Clinical Summary— TOB1
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.95). One damaged copy is likely sufficient to cause disease.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.31LOEUF
pLI 0.954
Z-score 2.88
OE 0.00 (0.00–0.31)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
1.45Z-score
OE missense 0.70 (0.61–0.81)
134 obs / 190.4 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.00 (0.00–0.31)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.70 (0.61–0.81)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.10
0≤1.21.6
LoF obs/exp: 0 / 9.6Missense obs/exp: 134 / 190.4Syn Z: -0.67
DN
0.3693th %ile
GOF
0.3788th %ile
LOF
0.78top 5%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.31

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

TOB1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Landmark / reviewRecent case evidence
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Reprogramming of hsa_circ_0008719 and its target miR-3615 induced by TOB1 in exosomes of gastric cancer cells: a contribution to inhibit gastric cancer progression.
Qian N et al.·Sci Rep
2025Open Access
Long Noncoding RNA TOB1-AS1 Represses Cervical Cancer Cell Proliferation, Invasion, and Migration via the MicroRNA-27a-3p/Thioredoxin-Interacting Protein Molecular Axis.
Wang Y et al.·Kaohsiung J Med Sci
2025Open Access
The impact of ERN1 endoribonuclease activity inhibition on TOB1, HBEGF, and TWIST1 genes expression in U87MG glioblastoma cells.
Minchenko OH et al.·Endocr Regul
2025
TOB1 inhibits the gastric cancer progression by focal adhesion pathway and ERK pathway based on transcriptional and metabolic sequencing.
He H et al.·BMC Cancer
2024Open Access
Loss of Tob1 promotes muscle regeneration through muscle stem cell expansion.
Kitajima Y et al.·J Cell Sci
2024
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients