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Aliases for TMEFF2 Gene

Aliases for TMEFF2 Gene

  • Transmembrane Protein With EGF Like And Two Follistatin Like Domains 2 2 3 5
  • Transmembrane Protein With EGF-Like And Two Follistatin-Like Domains 3 4
  • Cancer/Testis Antigen Family 120, Member 2 2 3
  • Hyperplastic Polyposis Protein 1 3 4
  • Transmembrane Protein TENB2 2 3
  • TENB2 3 4
  • HPP1 3 4
  • TPEF 3 4
  • TR-2 3 4
  • Transmembrane Protein With EGF-Like And Two Follistatin-Like Domains 2 2
  • Tomoregulin-2 3
  • Tomoregulin 2
  • CT120.2 3
  • TR 3

External Ids for TMEFF2 Gene

Previous GeneCards Identifiers for TMEFF2 Gene

  • GC02M190998
  • GC02M191517
  • GC02M192777
  • GC02M193017
  • GC02M192640
  • GC02M192522
  • GC02M184672

Summaries for TMEFF2 Gene

Entrez Gene Summary for TMEFF2 Gene

  • 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]

GeneCards Summary for TMEFF2 Gene

TMEFF2 (Transmembrane Protein With EGF Like And Two Follistatin Like Domains 2) is a Protein Coding gene. Diseases associated with TMEFF2 include Colorectal Cancer and Glass Syndrome. Among its related pathways are Validated targets of C-MYC transcriptional repression. An important paralog of this gene is TMEFF1.

UniProtKB/Swiss-Prot for TMEFF2 Gene

  • May be a survival factor for hippocampal and mesencephalic neurons. The shedded form up-regulates cancer cell proliferation, probably by promoting ERK1/2 phosphorylation.

Gene Wiki entry for TMEFF2 Gene

Additional gene information for TMEFF2 Gene

No data available for CIViC summary , Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for TMEFF2 Gene

Genomics for TMEFF2 Gene

GeneHancer (GH) Regulatory Elements for TMEFF2 Gene

Promoters and enhancers for TMEFF2 Gene
GeneHancer (GH) Identifier GH Type GH
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH02I192194 Promoter/Enhancer 1.7 EPDnew Ensembl ENCODE dbSUPER 550.8 +0.5 461 2.1 KLF17 ZNF76 ZEB1 ZNF335 GLIS2 ZNF213 SCRT2 RCOR1 ZNF548 ZNF391 TMEFF2 GC02M192181
GH02I191864 Enhancer 1.4 Ensembl ENCODE dbSUPER 10.3 +329.5 329454 4.2 FOXA2 MLX ARID4B SIN3A DMAP1 YY1 SLC30A9 FOS SP5 NFYC TMEFF2 CAVIN2 LOC105373813 DNAJB1P1
GH02I191869 Enhancer 1.2 Ensembl ENCODE dbSUPER 10.3 +326.3 326308 0.4 ELF3 FOXA2 MLX ZNF48 RAD21 RARA ZNF143 THAP11 ZNF654 SP5 TMEFF2 DNAJB1P1 CAVIN2 LOC105373813
GH02I192162 Enhancer 1.1 Ensembl ENCODE dbSUPER 10.8 +33.2 33233 0.6 CTCF FOXA2 RB1 ZNF384 IRF4 ZSCAN9 RAD21 CC2D1A RFXANK ARID2 CAVIN2 LOC105373813 TMEFF2 LOC729254 GC02M192181 GC02M192080
GH02I191812 Enhancer 0.9 Ensembl ENCODE 10.9 +383.3 383348 0.5 CTCF ARID4B DNMT3B ZSCAN9 RAD21 TEAD3 ARID2 ZNF143 SMC3 PRDM10 LOC105373813 CAVIN2 TMEFF2 GC02P191798 LOC729254
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data dump

GeneHancers around TMEFF2 on UCSC Golden Path with GeneCards custom track

Top Transcription factor binding sites by QIAGEN in the TMEFF2 gene promoter:

Genomic Locations for TMEFF2 Gene

Genomic Locations for TMEFF2 Gene
246,667 bases
Minus strand

Genomic View for TMEFF2 Gene

Genes around TMEFF2 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
TMEFF2 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for TMEFF2 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for TMEFF2 Gene

Proteins for TMEFF2 Gene

  • Protein details for TMEFF2 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Recommended name:
    Protein Accession:
    Secondary Accessions:
    • Q2FA44
    • Q4ZFW4
    • Q53H90
    • Q53RE1
    • Q8N2R5
    • Q9NR15
    • Q9NSS5
    • Q9P2Y9
    • Q9UK65

    Protein attributes for TMEFF2 Gene

    374 amino acids
    Molecular mass:
    41428 Da
    Quaternary structure:
    No Data Available
    • Sequence=BAA90820.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Mitochondrial contamination starting in position 361.; Evidence={ECO:0000305};

    Three dimensional structures from OCA and Proteopedia for TMEFF2 Gene

    Alternative splice isoforms for TMEFF2 Gene


neXtProt entry for TMEFF2 Gene

Post-translational modifications for TMEFF2 Gene

  • A soluble form (TMEFF2-ECD) is produced by proteolytic shedding. This shedding can be induced by phorbol ester or proinflammatory cytokines such as TNFalpha, and is mediated by ADAM17.
  • N-glycosylated. Contains chondroitin sulfate glycosaminoglycans.
  • Glycosylation at isoforms=2, 355, isoforms=2204, and posLast=230230
  • Modification sites at PhosphoSitePlus

Other Protein References for TMEFF2 Gene

No data available for DME Specific Peptides for TMEFF2 Gene

Domains & Families for TMEFF2 Gene

Gene Families for TMEFF2 Gene

Human Protein Atlas (HPA):
  • Predicted membrane proteins

Protein Domains for TMEFF2 Gene

Suggested Antigen Peptide Sequences for TMEFF2 Gene

Graphical View of Domain Structure for InterPro Entry



  • Belongs to the tomoregulin family.
  • Belongs to the tomoregulin family.
genes like me logo Genes that share domains with TMEFF2: view

Function for TMEFF2 Gene

Molecular function for TMEFF2 Gene

UniProtKB/Swiss-Prot Function:
May be a survival factor for hippocampal and mesencephalic neurons. The shedded form up-regulates cancer cell proliferation, probably by promoting ERK1/2 phosphorylation.
UniProtKB/Swiss-Prot Induction:
Down-regulated in tumor cell lines in response to a high level of methylation in the 5 region. The CpG island methylation correlates with TMEFF2 silencing in tumor cell lines.

Phenotypes From GWAS Catalog for TMEFF2 Gene

Gene Ontology (GO) - Molecular Function for TMEFF2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0003674 molecular_function ND --
genes like me logo Genes that share ontologies with TMEFF2: view
genes like me logo Genes that share phenotypes with TMEFF2: view

Animal Models for TMEFF2 Gene

MGI Knock Outs for TMEFF2:

Animal Model Products

  • Taconic Biosciences Mouse Models for TMEFF2

Clone Products

No data available for Enzyme Numbers (IUBMB) , Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for TMEFF2 Gene

Localization for TMEFF2 Gene

Subcellular locations from UniProtKB/Swiss-Prot for TMEFF2 Gene

Isoform 1: Membrane; Single-pass type I membrane protein.
Isoform 2: Membrane; Single-pass type I membrane protein.
Isoform 3: Secreted.

Subcellular locations from

Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for TMEFF2 gene
Compartment Confidence
extracellular 5
plasma membrane 3
cytoskeleton 2

Subcellular locations from the

Human Protein Atlas (HPA)
  • Cytokinetic bridge (1)
  • Microtubules (1)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for TMEFF2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005576 extracellular region IEA --
GO:0016020 membrane IEA --
GO:0016021 integral component of membrane NAS 10903839
genes like me logo Genes that share ontologies with TMEFF2: view

Pathways & Interactions for TMEFF2 Gene

genes like me logo Genes that share pathways with TMEFF2: view

Pathways by source for TMEFF2 Gene

1 BioSystems pathway for TMEFF2 Gene

Interacting Proteins for TMEFF2 Gene

STRING Interaction Network Preview (showing 2 interactants - click image to see details)
Selected Interacting proteins: ENSP00000272771 Q9UIK5-TEFF2_HUMAN for TMEFF2 Gene via STRING IID

Gene Ontology (GO) - Biological Process for TMEFF2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0030336 negative regulation of cell migration IDA 24632071
GO:0044319 wound healing, spreading of cells IDA 24632071
GO:0045720 negative regulation of integrin biosynthetic process IMP 24632071
GO:0051497 negative regulation of stress fiber assembly IDA 24632071
genes like me logo Genes that share ontologies with TMEFF2: view

No data available for SIGNOR curated interactions for TMEFF2 Gene

Drugs & Compounds for TMEFF2 Gene

(1) Additional Compounds for TMEFF2 Gene - From: Novoseek

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
genes like me logo Genes that share compounds with TMEFF2: view

Transcripts for TMEFF2 Gene

Unigene Clusters for TMEFF2 Gene

Transmembrane protein with EGF-like and two follistatin-like domains 2:
Representative Sequences:

Clone Products

Alternative Splicing Database (ASD) splice patterns (SP) for TMEFF2 Gene

No ASD Table

Relevant External Links for TMEFF2 Gene

GeneLoc Exon Structure for
ECgene alternative splicing isoforms for

Expression for TMEFF2 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and CGAP SAGE for TMEFF2 Gene

mRNA differential expression in normal tissues according to GTEx for TMEFF2 Gene

This gene is overexpressed in Brain - Hypothalamus (x5.2), Brain - Anterior cingulate cortex (BA24) (x4.9), Brain - Amygdala (x4.9), Brain - Cortex (x4.5), Brain - Hippocampus (x4.5), Brain - Frontal Cortex (BA9) (x4.3), and Brain - Substantia nigra (x4.1).

Protein differential expression in normal tissues from HIPED for TMEFF2 Gene

This gene is overexpressed in Frontal cortex (44.5) and Fetal Brain (24.5).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, PaxDb, and MOPED for TMEFF2 Gene

Protein tissue co-expression partners for TMEFF2 Gene

- Elite partner

NURSA nuclear receptor signaling pathways regulating expression of TMEFF2 Gene:


SOURCE GeneReport for Unigene cluster for TMEFF2 Gene:


mRNA Expression by UniProt/SwissProt for TMEFF2 Gene:

Tissue specificity: Highly expressed in adult and fetal brain, spinal cord and prostate. Expressed in all brain regions except the pituitary gland, with highest levels in amygdala and corpus callosum. Expressed in the pericryptal myofibroblasts and other stromal cells of normal colonic mucosa. Expressed in prostate carcinoma. Down-regulated in colorectal cancer. Present in Alzheimer disease plaques (at protein level). Isoform 3 is expressed weakly in testis and at high levels in normal and cancerous prostate.

Evidence on tissue expression from TISSUES for TMEFF2 Gene

  • Nervous system(4.8)
  • Intestine(4.3)
genes like me logo Genes that share expression patterns with TMEFF2: view

No data available for Phenotype-based relationships between genes and organs from Gene ORGANizer for TMEFF2 Gene

Orthologs for TMEFF2 Gene

This gene was present in the common ancestor of chordates.

Orthologs for TMEFF2 Gene

Organism Taxonomy Gene Similarity Type Details
(Pan troglodytes)
Mammalia TMEFF2 33 34
  • 99.91 (n)
(Monodelphis domestica)
Mammalia TMEFF2 34
  • 96 (a)
(Bos Taurus)
Mammalia TMEFF2 33 34
  • 94.92 (n)
(Mus musculus)
Mammalia Tmeff2 33 16 34
  • 93.49 (n)
(Canis familiaris)
Mammalia TMEFF2 33 34
  • 92.87 (n)
(Ornithorhynchus anatinus)
Mammalia TMEFF2 34
  • 67 (a)
(Gallus gallus)
Aves TMEFF2 33 34
  • 86.62 (n)
(Anolis carolinensis)
Reptilia TMEFF2 34
  • 89 (a)
(Danio rerio)
Actinopterygii tmeff2b 33 34
  • 66.98 (n)
tmeff2a 34
  • 65 (a)
Species where no ortholog for TMEFF2 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • fruit fly (Drosophila melanogaster)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rat (Rattus norvegicus)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea squirt (Ciona intestinalis)
  • sea squirt (Ciona savignyi)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • tropical clawed frog (Silurana tropicalis)
  • wheat (Triticum aestivum)
  • worm (Caenorhabditis elegans)

Evolution for TMEFF2 Gene

Gene Tree for TMEFF2 (if available)
Gene Tree for TMEFF2 (if available)

Paralogs for TMEFF2 Gene

Paralogs for TMEFF2 Gene

(2) SIMAP similar genes for TMEFF2 Gene using alignment to 2 proteins:

genes like me logo Genes that share paralogs with TMEFF2: view

Variants for TMEFF2 Gene

Sequence variations from dbSNP and Humsavar for TMEFF2 Gene

SNP ID Clin Chr 02 pos Variation AA Info Type
rs1000020137 -- 191,977,324(-) G/T genic_downstream_transcript_variant, intron_variant
rs1000020483 -- 192,072,967(-) T/A genic_downstream_transcript_variant, intron_variant
rs1000039580 -- 192,025,943(-) G/A genic_downstream_transcript_variant, intron_variant
rs1000052702 -- 192,157,147(-) A/G genic_downstream_transcript_variant, intron_variant
rs1000061060 -- 192,135,806(-) C/T genic_downstream_transcript_variant, intron_variant

Structural Variations from Database of Genomic Variants (DGV) for TMEFF2 Gene

Variant ID Type Subtype PubMed ID
esv1001512 CNV deletion 20482838
esv1367658 CNV insertion 17803354
esv1451304 CNV insertion 17803354
esv3304058 CNV mobile element insertion 20981092
esv3305318 CNV mobile element insertion 20981092
esv3308473 CNV mobile element insertion 20981092
esv3310364 CNV mobile element insertion 20981092
esv3324099 CNV insertion 20981092
esv3360588 CNV insertion 20981092
esv3443085 CNV insertion 20981092
esv3593780 CNV loss 21293372
nsv1072474 CNV deletion 25765185
nsv1116816 CNV deletion 24896259
nsv1133488 CNV deletion 24896259
nsv1136456 CNV deletion 24896259
nsv437307 CNV loss 16327808
nsv478508 CNV novel sequence insertion 20440878
nsv511831 CNV loss 21212237
nsv584068 CNV loss 21841781
nsv834495 CNV loss 17160897

Variation tolerance for TMEFF2 Gene

Residual Variation Intolerance Score: 28.8% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 2.35; 41.78% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for TMEFF2 Gene

SNPedia medical, phenotypic, and genealogical associations of SNPs for

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for TMEFF2 Gene

Disorders for TMEFF2 Gene

MalaCards: The human disease database

(4) MalaCards diseases for TMEFF2 Gene - From: DISEASES, Novoseek, and GeneCards

Disorder Aliases PubMed IDs
colorectal cancer
  • crc
glass syndrome
  • glass
prostate cancer
  • prostate cancer, susceptibility to
colon mucinous adenocarcinoma
  • colonic mucinous adenocarcinoma
- elite association - COSMIC cancer census association via MalaCards

Additional Disease Information for TMEFF2

Genetic Association Database
Human Genome Epidemiology Navigator
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
genes like me logo Genes that share disorders with TMEFF2: view

No data available for UniProtKB/Swiss-Prot and Genatlas for TMEFF2 Gene

Publications for TMEFF2 Gene

  1. Phorbol ester-induced shedding of the prostate cancer marker transmembrane protein with epidermal growth factor and two follistatin motifs 2 is mediated by the disintegrin and metalloproteinase-17. (PMID: 17942404) Ali N … Knaüper V (The Journal of biological chemistry 2007) 3 4 22 58
  2. A truncated isoform of TMEFF2 encodes a secreted protein in prostate cancer cells. (PMID: 16439095) Quayle SN … Sadar MD (Genomics 2006) 3 4 22 58
  3. Identification and characterization of TMEFF2, a novel survival factor for hippocampal and mesencephalic neurons. (PMID: 10903839) Horie M … Tanigami A (Genomics 2000) 2 3 4 58
  4. The gene for a novel transmembrane protein containing epidermal growth factor and follistatin domains is frequently hypermethylated in human tumor cells. (PMID: 10987305) Liang G … Jones PA (Cancer research 2000) 3 4 22 58
  5. A novel epidermal growth factor-like molecule containing two follistatin modules stimulates tyrosine phosphorylation of erbB-4 in MKN28 gastric cancer cells. (PMID: 10600548) Uchida T … Sakamoto C (Biochemical and biophysical research communications 1999) 3 4 22 58

Products for TMEFF2 Gene

Sources for TMEFF2 Gene

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