TNS3

Chr 7

tensin 3

Also known as: TEM6, TENS1

NCBI Gene: 64759ENSG00000136205UniProt: Q68CZ2

Predicted to enable guanyl-nucleotide exchange factor adaptor activity. Predicted to be involved in positive regulation of Rac protein signal transduction and positive regulation of guanyl-nucleotide exchange factor activity. Predicted to act upstream of or within several processes, including bone resorption; negative regulation of Rho protein signal transduction; and podosome assembly. Located in cytosol and focal adhesion. [provided by Alliance of Genome Resources, Apr 2025]

293
ClinVar variants
17
Pathogenic / LP
1.00
pLI score· haploinsufficient
0
Active trials
Clinical Summary— TNS3
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
17 Pathogenic / Likely Pathogenic· 218 VUS of 293 total submissions

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.
0.19LOEUF
pLI 1.000
Z-score 6.57
OE 0.10 (0.05–0.19)
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.
0.94Z-score
OE missense 0.91 (0.86–0.96)
785 obs / 863.1 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.0.10 (0.05–0.19)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.91 (0.86–0.96)
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.1.08
0≤1.21.6
LoF obs/exp: 6 / 61.7Missense obs/exp: 785 / 863.1Syn Z: -1.22

ClinVar Variant Classifications

293 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic17
VUS218
Likely Benign38
Benign19
Conflicting1
17
Pathogenic
218
VUS
38
Likely Benign
19
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
17
0
17
Likely Pathogenic
0
0
0
0
0
VUS
0
212
6
0
218
Likely Benign
0
20
2
16
38
Benign
1
9
4
5
19
Conflicting
—1
Total12412921293

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

TNS3 · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
TENSIN 3; TNS3
MIM #606825 · *
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
MLL3 suppresses tumorigenesis through regulating TNS3 enhancer activity.
Zheng JY et al.·Cell Death Dis
2021
The molecular and clinical role of Tensin 1/2/3 in cancer.
Mainsiouw L et al.·J Cell Mol Med
2023Review
Pharmacological targeting of TNS3 with histone deacetylase inhibitor as a therapeutic strategy in esophageal squamous cell carcinoma.
Shi Y et al.·Aging (Albany NY)
2021
EIF4A3-mediated oncogenic circRNA hsa_circ_0001165 advances esophageal squamous cell carcinoma progression through the miR-381-3p/TNS3 pathway.
Zhang X et al.·Cell Biol Toxicol
2024
Musashi-1 Enhances Glioblastoma Cell Migration and Cytoskeletal Dynamics through Translational Inhibition of Tensin3.
Chen HY et al.·Sci Rep
2017
Cytogenetic and molecular characterization of a de-novo t(2p;7p) translocation involving TNS3 and EXOC6B genes in a boy with a complex syndromic phenotype.
Borsani G et al.·Eur J Med Genet
2008Case report
Functional characterisation of human cells harbouring a novel t(2p;7p) translocation involving TNS3 and EXOC6B genes.
Ludwig D et al.·BMC Med Genet
2013Functional
ETS1, a Target Gene of the EWSR1::FLI1 Fusion Oncoprotein, Regulates the Expression of the Focal Adhesion Protein TENSIN3.
Ebegboni VJ et al.·Mol Cancer Res
2024
A dual phenotype of MDA-MB-468 cancer cells reveals mutual regulation of tensin3 and adhesion plasticity.
Veß A et al.·J Cell Sci
2017
Novel somatic alterations in unicentric and idiopathic multicentric Castleman disease.
Goodman AM et al.·Eur J Haematol
2021
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Analysis of TNS3-203 and LRRFIP1-211 Transcripts as Oral Cancer Biomarkers.
Zeljic K et al.·J Oral Pathol Med
2025
Abnormal TNS3 gene methylation in patients with congenital scoliosis.
Wu Y et al.·BMC Musculoskelet Disord
2022🔓 Open AccessCohort
A multi-omics study links TNS3 and SEPT7 to long-term former smoking NSCLC survival.
Shen S et al.·NPJ Precis Oncol
2021🔓 Open Access
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools