This gene encodes a member of the peptidase M1 family. The encoded protein is an extracellular peptidase that specifically cleaves and inactivates the neuropeptide thyrotropin-releasing hormone.[provided by RefSeq, Dec 2008] See more...

Aliases for TRHDE Gene

Aliases for TRHDE Gene

  • Thyrotropin Releasing Hormone Degrading Enzyme 2 3 5
  • TRH-Specific Aminopeptidase 2 3 4
  • Pyroglutamyl-Peptidase II 2 3 4
  • PAP-II 2 3 4
  • TRH-DE 2 3 4
  • Thyrotropin-Releasing Hormone-Degrading Ectoenzyme 3 4
  • Pyroglutamyl Aminopeptidase II 2 3
  • TRH-Degrading Ectoenzyme 3 4
  • Thyroliberinase 3 4
  • PGPEP2 2 3
  • Thyrotropin-Releasing Hormone Degrading Enzyme 2
  • EC 4
  • TRHDE 5

External Ids for TRHDE Gene

Previous GeneCards Identifiers for TRHDE Gene

  • GC12P072453
  • GC12P072618
  • GC12P070952
  • GC12P069714

Summaries for TRHDE Gene

Entrez Gene Summary for TRHDE Gene

  • This gene encodes a member of the peptidase M1 family. The encoded protein is an extracellular peptidase that specifically cleaves and inactivates the neuropeptide thyrotropin-releasing hormone.[provided by RefSeq, Dec 2008]

GeneCards Summary for TRHDE Gene

TRHDE (Thyrotropin Releasing Hormone Degrading Enzyme) is a Protein Coding gene. Diseases associated with TRHDE include Fraser Syndrome 1. Gene Ontology (GO) annotations related to this gene include metallopeptidase activity and aminopeptidase activity. An important paralog of this gene is ANPEP.

UniProtKB/Swiss-Prot Summary for TRHDE Gene

No data available for CIViC Summary , Tocris Summary , Gene Wiki entry , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for TRHDE Gene

Genomics for TRHDE Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for TRHDE 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
GH12J072269 Promoter/Enhancer 1.8 EPDnew Ensembl ENCODE CraniofacialAtlas dbSUPER 608.7 +186.5 186536 8.8 ZSCAN4 POLR2A EZH2 CEBPA CTCF CEBPB RAD21 FOS ZBTB17 JUND TRHDE TRHDE-AS1 lnc-TPH2-3
GH12J072075 Promoter 0.4 EPDnew 600.4 -11.6 -11628 0.1 NR2F2 TRHDE piR-36588-095 lnc-TRHDE-3 TPH2
GH12J072087 Promoter 0.3 EPDnew 600.7 0.0 -19 0.1 TRHDE piR-36588-095 lnc-TRHDE-3 TPH2
GH12J072088 Enhancer 0.2 FANTOM5 614.4 +0.8 779 0.2 TRHDE TPH2 lnc-TRHDE-3 piR-39341-090
GH12J072293 Enhancer 0.9 FANTOM5 Ensembl ENCODE 22 +208.6 208594 4.3 JUND CEBPB NFE2 FOS BHLHE40 MAFK NFE2L2 TRHDE TPH2 TRHDE-AS1 lnc-ZFC3H1-13
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around TRHDE on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for TRHDE

Top Transcription factor binding sites by QIAGEN in the TRHDE gene promoter:
  • AML1a
  • CUTL1
  • FOXO1
  • FOXO1a
  • Gfi-1
  • HNF-1A
  • USF-1
  • USF-1:USF-2
  • USF1
  • USF2

Genomic Locations for TRHDE Gene

Genomic Locations for TRHDE Gene
583,493 bases
Plus strand
578,377 bases
Plus strand

Genomic View for TRHDE Gene

Genes around TRHDE on UCSC Golden Path with GeneCards custom track

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

RefSeq DNA sequence for TRHDE Gene

Proteins for TRHDE Gene

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

    Protein Symbol:
    Recommended name:
    Thyrotropin-releasing hormone-degrading ectoenzyme
    Protein Accession:
    Secondary Accessions:
    • A5PL19
    • Q6UWJ4

    Protein attributes for TRHDE Gene

    1024 amino acids
    Molecular mass:
    117000 Da
    Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
    Quaternary structure:
    • Homodimer; disulfide-linked.

neXtProt entry for TRHDE Gene

Post-translational modifications for TRHDE Gene

  • Glycosylation at Asn89, Asn160, Asn175, Asn222, Asn338, Asn605, Asn634, Asn649, Asn663, Asn684, Asn800, and Asn906
  • Modification sites at PhosphoSitePlus

Other Protein References for TRHDE Gene

No data available for DME Specific Peptides for TRHDE Gene

Domains & Families for TRHDE Gene

Gene Families for TRHDE Gene

Human Protein Atlas (HPA):
  • Enzymes
  • Predicted intracellular proteins
  • Predicted membrane proteins

Protein Domains for TRHDE Gene

  • Membrane alanyl dipeptidase (M1) family signature

Suggested Antigen Peptide Sequences for TRHDE Gene

GenScript: Design optimal peptide antigens:
  • Thyroliberinase (TRHDE_HUMAN)

Graphical View of Domain Structure for InterPro Entry



  • Belongs to the peptidase M1 family.
  • Belongs to the peptidase M1 family.
genes like me logo Genes that share domains with TRHDE: view

Function for TRHDE Gene

Molecular function for TRHDE Gene

UniProtKB/Swiss-Prot Function:
Specific inactivation of TRH after its release.
UniProtKB/Swiss-Prot CatalyticActivity:
Reaction=Release of the N-terminal pyroglutamyl group from pGlu-|-His-Xaa tripeptides and pGlu-|-His-Xaa-Gly tetrapeptides.; EC=;.
GENATLAS Biochemistry:
TRH (thyrotropin releasing hormone) degrading ectoenzyme specific neuropeptidase,restrictively expressed in tissue with highest expression in brain

Enzyme Numbers (IUBMB) for TRHDE Gene

Phenotypes From GWAS Catalog for TRHDE Gene

Gene Ontology (GO) - Molecular Function for TRHDE Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0004177 aminopeptidase activity IEA,TAS 10491199
GO:0008233 peptidase activity IEA --
GO:0008237 metallopeptidase activity IEA --
GO:0008270 zinc ion binding IEA,IBA 21873635
GO:0016787 hydrolase activity IEA --
genes like me logo Genes that share ontologies with TRHDE: view
genes like me logo Genes that share phenotypes with TRHDE: view

Animal Models for TRHDE Gene

MGI Knock Outs for TRHDE:

Animal Model Products

  • Taconic Biosciences Mouse Models for TRHDE

CRISPR Products

miRNA for TRHDE Gene

miRTarBase miRNAs that target TRHDE

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for TRHDE

No data available for Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for TRHDE Gene

Localization for TRHDE Gene

Subcellular locations from UniProtKB/Swiss-Prot for TRHDE Gene

Membrane. Single-pass type II membrane protein.

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 TRHDE gene
Compartment Confidence
plasma membrane 5
extracellular 4
cytoskeleton 1
mitochondrion 1
nucleus 1
endoplasmic reticulum 1
cytosol 1

Gene Ontology (GO) - Cellular Components for TRHDE Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005737 cytoplasm IBA 21873635
GO:0005886 plasma membrane IBA 21873635
GO:0005887 integral component of plasma membrane TAS 10491199
GO:0016020 membrane IEA --
GO:0016021 integral component of membrane IEA --
genes like me logo Genes that share ontologies with TRHDE: view

No data available for Subcellular locations from the Human Protein Atlas (HPA) for TRHDE Gene

Pathways & Interactions for TRHDE Gene

PathCards logo

SuperPathways for TRHDE Gene

No Data Available

Gene Ontology (GO) - Biological Process for TRHDE Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006508 proteolysis IEA,IBA 21873635
GO:0007165 signal transduction TAS 10491199
GO:0007267 cell-cell signaling TAS 10491199
GO:0043171 peptide catabolic process IBA 21873635
genes like me logo Genes that share ontologies with TRHDE: view

No data available for Pathways by source and SIGNOR curated interactions for TRHDE Gene

Drugs & Compounds for TRHDE Gene

(2) Drugs for TRHDE Gene - From: Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials

(2) Additional Compounds for TRHDE Gene - From: Novoseek

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

Transcripts for TRHDE Gene

mRNA/cDNA for TRHDE Gene

6 NCBI additional mRNA sequence :
7 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for TRHDE

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

No ASD Table

Relevant External Links for TRHDE Gene

GeneLoc Exon Structure for

Expression for TRHDE Gene

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

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

This gene is overexpressed in Pancreas (x4.9).

Protein differential expression in normal tissues from HIPED for TRHDE Gene

This gene is overexpressed in Urine (64.9).

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

Protein tissue co-expression partners for TRHDE Gene

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for TRHDE

SOURCE GeneReport for Unigene cluster for TRHDE Gene:


mRNA Expression by UniProt/SwissProt for TRHDE Gene:

Tissue specificity: Predominantly expressed in brain.

Evidence on tissue expression from TISSUES for TRHDE Gene

  • Lung(4.1)
  • Nervous system(2.9)
genes like me logo Genes that share expression patterns with TRHDE: view

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

Orthologs for TRHDE Gene

This gene was present in the common ancestor of animals.

Orthologs for TRHDE Gene

Organism Taxonomy Gene Similarity Type Details
(Pan troglodytes)
Mammalia TRHDE 30 31
  • 98.83 (n)
(Bos Taurus)
Mammalia TRHDE 30 31
  • 92.7 (n)
(Ornithorhynchus anatinus)
Mammalia TRHDE 31
  • 91 (a)
(Canis familiaris)
Mammalia TRHDE 30 31
  • 90.6 (n)
(Rattus norvegicus)
Mammalia Trhde 30
  • 90.2 (n)
(Mus musculus)
Mammalia Trhde 30 17 31
  • 90.14 (n)
(Monodelphis domestica)
Mammalia TRHDE 31
  • 86 (a)
(Gallus gallus)
Aves TRHDE 30 31
  • 83.97 (n)
(Anolis carolinensis)
Reptilia -- 31
  • 82 (a)
-- 31
  • 65 (a)
Tropical Clawed Frog
(Silurana tropicalis)
Amphibia trhde 30
  • 74.01 (n)
(Danio rerio)
Actinopterygii TRHDE (1 of 2) 31
  • 68 (a)
LOC562409 30
  • 67.61 (n)
TRHDE (2 of 2) 31
  • 67 (a)
Fruit Fly
(Drosophila melanogaster)
Insecta CG11951 32
  • 34 (a)
CG14516 32
  • 32 (a)
SP1029 32
  • 30 (a)
CG2111 32
  • 29 (a)
sda 32
  • 29 (a)
BG:DS00365.1 32
  • 27 (a)
CG3502 32
  • 27 (a)
CG5849 32
  • 27 (a)
CG9806 32
  • 27 (a)
CG6071 32
  • 24 (a)
CG4467 31 32
  • 21 (a)
(Caenorhabditis elegans)
Secernentea Y67D8C.9 32
  • 33 (a)
T07F10.1 32
  • 29 (a)
R03G8.4 32
  • 28 (a)
R03G8.6 32
  • 27 (a)
T16G12.1 32
  • 26 (a)
Y42A5A.1 32
  • 26 (a)
F49B2.6 31
  • 25 (a)
AC3.5 32
  • 22 (a)
Species where no ortholog for TRHDE was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium 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)
  • 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)
  • Rice (Oryza sativa)
  • Rice Blast Fungus (Magnaporthe grisea)
  • Schistosome Parasite (Schistosoma mansoni)
  • Sea Anemone (Nematostella vectensis)
  • Sea Vase (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)
  • Wheat (Triticum aestivum)

Evolution for TRHDE Gene

Gene Tree for TRHDE (if available)
Gene Tree for TRHDE (if available)
Evolutionary constrained regions (ECRs) for TRHDE: view image

Paralogs for TRHDE Gene

Paralogs for TRHDE Gene

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

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

Variants for TRHDE Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for TRHDE Gene

SNP ID Clinical significance and condition Chr 12 pos Variation AA Info Type
709904 Benign: not provided 72,652,349(+) A/C SYNONYMOUS_VARIANT
784247 Benign: not provided 72,273,276(+) G/A NON_CODING_TRANSCRIPT_VARIANT,SYNONYMOUS_VARIANT
784248 Benign: not provided 72,621,104(+) T/C INTRON_VARIANT
rs796052150 Likely Benign: Long QT syndrome 72,575,305(+) A/T MISSENSE_VARIANT

Additional dbSNP identifiers (rs#s) for TRHDE Gene

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

Variant ID Type Subtype PubMed ID
dgv2709n54 CNV loss 21841781
dgv85e215 CNV deletion 23714750
esv1226093 CNV deletion 17803354
esv1942657 CNV deletion 18987734
esv2166520 CNV deletion 18987734
esv23503 CNV loss 19812545
esv2422452 CNV duplication 17116639
esv2661304 CNV deletion 23128226
esv2666571 CNV deletion 23128226
esv2676770 CNV deletion 23128226
esv2746052 CNV deletion 23290073
esv2746054 CNV deletion 23290073
esv2746055 CNV deletion 23290073
esv2746056 CNV deletion 23290073
esv2746057 CNV deletion 23290073
esv2759908 CNV loss 17122850
esv3164593 CNV deletion 24192839
esv3305554 CNV mobile element insertion 20981092
esv3310106 CNV mobile element insertion 20981092
esv3361330 CNV insertion 20981092
esv3361841 CNV insertion 20981092
esv3427905 CNV insertion 20981092
esv3549392 CNV deletion 23714750
esv3549395 CNV deletion 23714750
esv3580320 CNV loss 25503493
esv3629929 CNV loss 21293372
esv3629931 CNV loss 21293372
esv3629932 CNV loss 21293372
esv3629933 CNV loss 21293372
esv3786 CNV loss 18987735
esv3892219 CNV loss 25118596
esv3892220 CNV loss 25118596
esv987864 CNV deletion 20482838
nsv1044083 CNV gain 25217958
nsv1054725 CNV loss 25217958
nsv1069678 CNV deletion 25765185
nsv1132364 CNV duplication 24896259
nsv1145613 CNV deletion 24896259
nsv1154009 CNV duplication 26484159
nsv469465 CNV gain 19166990
nsv469466 CNV loss 19166990
nsv521839 CNV loss 19592680
nsv559362 CNV loss 21841781
nsv559363 CNV gain 21841781
nsv559364 CNV loss 21841781
nsv771 CNV insertion 18451855
nsv772 CNV deletion 18451855
nsv818925 CNV loss 17921354
nsv832452 CNV gain 17160897
nsv832453 CNV gain+loss 17160897
nsv832454 CNV gain 17160897
nsv957265 CNV deletion 24416366

Variation tolerance for TRHDE Gene

Residual Variation Intolerance Score: 2.83% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 1.59; 30.64% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for TRHDE Gene

SNPedia medical, phenotypic, and genealogical associations of SNPs for

SNP Genotyping and Copy Number Assay Products

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

Disorders for TRHDE Gene

MalaCards: The human disease database

(1) MalaCards diseases for TRHDE Gene - From: DISEASES

Disorder Aliases PubMed IDs
fraser syndrome 1
  • frasrs1
- elite association - COSMIC cancer census association via MalaCards
Search TRHDE in MalaCards View complete list of genes associated with diseases

Additional Disease Information for TRHDE

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

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

Publications for TRHDE Gene

  1. Human TRH-degrading ectoenzyme cDNA cloning, functional expression, genomic structure and chromosomal assignment. (PMID: 10491199) Schomburg L … Bauer K (European journal of biochemistry 1999) 2 3 4 23
  2. The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment. (PMID: 12975309) Clark HF … Gray A (Genome research 2003) 2 3 4
  3. Genome-wide association study of rheumatoid arthritis in Koreans: population-specific loci as well as overlap with European susceptibility loci. (PMID: 21452313) Freudenberg J … Bae SC (Arthritis and rheumatism 2011) 3 41
  4. Chemerin, a novel adipokine in the regulation of angiogenesis. (PMID: 20237162) Bozaoglu K … Jowett JB (The Journal of clinical endocrinology and metabolism 2010) 3 41
  5. Variation at the NFATC2 locus increases the risk of thiazolidinedione-induced edema in the Diabetes REduction Assessment with ramipril and rosiglitazone Medication (DREAM) study. (PMID: 20628086) Bailey SD … DREAM investigators (Diabetes care 2010) 3 41

Products for TRHDE Gene

Sources for TRHDE Gene