TMEFF2
Chr 2transmembrane protein with EGF like and two follistatin like domains 2
Also known as: CT120.2, HPP1, TENB2, TPEF, TR, TR-2
This gene encodes a transmembrane protein from the tomoregulin family that functions as a survival factor for hippocampal and mesencephalic neurons and can regulate cell proliferation through ERK1/2 signaling. The gene is not well-established in pediatric neurogenetic disorders, with constraint metrics (pLI 0.00007, LOEUF 0.739) indicating tolerance to loss-of-function variants. Current evidence primarily links this gene to cancer biology rather than inherited neurological conditions.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Typical tolerance to LoF variation
Mild missense constraint
This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
0 submitted variants 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.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
TRAIL-R2 and HER2 Bi-Specific Chimeric Antigen Receptor (CAR) T Cells for the Treatment of Metastatic Breast Cancer
NOT YET RECRUITINGCarboplatin and Nab-Paclitaxel With or Without Vorinostat in Treating Women With Newly Diagnosed Operable Breast Cancer
ACTIVE NOT RECRUITINGExternal Resources
Links to major genomics databases and tools