TMEFF2

Chr 2

transmembrane protein with EGF like and two follistatin like domains 2

Also known as: CT120.2, HPP1, TENB2, TPEF, TR, TR-2

NCBI Gene: 23671ENSG00000144339UniProt: Q9UIK5

This gene encodes a member of the tomoregulin family of transmembrane proteins. This protein has been shown to function as both an oncogene and a tumor suppressor depending on the cellular context and may regulate prostate cancer cell invasion. Multiple soluble forms of this protein have been identified that arise from both an alternative splice variant and ectodomain shedding. Additionally, this gene has been found to be hypermethylated in multiple cancer types. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2015]

50
ClinVar variants
28
Pathogenic / LP
0.00
pLI score
2
Active trials
Clinical Summary— TMEFF2
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
28 Pathogenic / Likely Pathogenic· 21 VUS of 50 total submissions
💊
Clinical Trials
2 active or recruiting trials — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
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.
0.74LOEUF
pLI 0.000
Z-score 2.54
OE 0.45 (0.28–0.74)
Tolerant

Typical tolerance to LoF variation

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.
1.60Z-score
OE missense 0.69 (0.60–0.79)
140 obs / 204.4 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.0.45 (0.28–0.74)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.69 (0.60–0.79)
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.0.89
0≤1.21.6
LoF obs/exp: 11 / 24.6Missense obs/exp: 140 / 204.4Syn Z: 0.79

ClinVar Variant Classifications

50 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic27
Likely Pathogenic1
VUS21
Benign1
27
Pathogenic
1
Likely Pathogenic
21
VUS
1
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
27
0
27
Likely Pathogenic
0
0
1
0
1
VUS
0
18
3
0
21
Likely Benign
0
0
0
0
0
Benign
0
1
0
0
1
Total01931050

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

View in ClinVar →

Protein Context — Lollipop Plot

TMEFF2 · 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
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
TMEFF2 deregulation contributes to gastric carcinogenesis and indicates poor survival outcome.
Sun T et al.·Clin Cancer Res
2014
A first-in-human study of JNJ-70218902, a bispecific T-cell-redirecting antibody against TMEFF2 in metastatic castration-resistant prostate cancer.
Calvo E et al.·Oncologist
2025Clinical trial
DNA methylation based biomarkers in colorectal cancer: A systematic review.
Lam K et al.·Biochim Biophys Acta
2016Review
A truncated isoform of TMEFF2 encodes a secreted protein in prostate cancer cells.
Quayle SN et al.·Genomics
2006
Hypermethylated DNA as a biomarker for colorectal cancer: a systematic review.
Rasmussen SL et al.·Colorectal Dis
2016Review
Quantitative DNA methylation analysis of selected genes in endometrial carcinogenesis.
Chen YC et al.·Taiwan J Obstet Gynecol
2015
Preclinical validation of anti-TMEFF2-auristatin E-conjugated antibodies in the treatment of prostate cancer.
Afar DE et al.·Mol Cancer Ther
2004
Accurate detection of upper tract urothelial carcinoma in tissue and urine by means of quantitative GDF15, TMEFF2 and VIM promoter methylation.
Monteiro-Reis S et al.·Eur J Cancer
2014
Urine cell-based DNA methylation classifier for monitoring bladder cancer.
van der Heijden AG et al.·Clin Epigenetics
2018
A TMEFF2-regulated cell cycle derived gene signature is prognostic of recurrence risk in prostate cancer.
Georgescu C et al.·BMC Cancer
2019
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
Breast Cancer

Carboplatin and Nab-Paclitaxel With or Without Vorinostat in Treating Women With Newly Diagnosed Operable Breast Cancer

ACTIVE NOT RECRUITING
NCT00616967Phase PHASE2Sidney Kimmel Comprehensive Cancer Center at Johns HopkinsStarted 2008-05
carboplatinpaclitaxel albumin-stabilized nanoparticle formulationvorinostat
Breast CancerTumor, BreastBreast Tumor

TRAIL-R2 and HER2 Bi-Specific Chimeric Antigen Receptor (CAR) T Cells for the Treatment of Metastatic Breast Cancer

NOT YET RECRUITING
NCT06251544Phase PHASE1Baylor College of MedicineStarted 2026-06
HTR2 T CellsHTR2 T Cells

External Resources

Links to major genomics databases and tools