This gene encodes a G protein-coupled receptor for thyrotropin-releasing hormone (TRH). Upon binding to TRH, this receptor activates the inositol phospholipid-calcium-protein kinase C transduction pathway. Mutations in this gene have been associated with generalized thyrotropin-releasing hormone resistance. [provided by RefSeq, Sep 2011] See more...

Aliases for TRHR Gene

Aliases for TRHR Gene

  • Thyrotropin Releasing Hormone Receptor 2 3 5
  • Thyrotropin-Releasing Hormone Receptor 2 3 4
  • Thyroliberin Receptor 3 4
  • TRH-R 3 4
  • CHNG7 3
  • TRHR 5

External Ids for TRHR Gene

Previous GeneCards Identifiers for TRHR Gene

  • GC08P110167
  • GC08P109768
  • GC08P110056
  • GC08P110168
  • GC08P105422

Summaries for TRHR Gene

Entrez Gene Summary for TRHR Gene

  • This gene encodes a G protein-coupled receptor for thyrotropin-releasing hormone (TRH). Upon binding to TRH, this receptor activates the inositol phospholipid-calcium-protein kinase C transduction pathway. Mutations in this gene have been associated with generalized thyrotropin-releasing hormone resistance. [provided by RefSeq, Sep 2011]

GeneCards Summary for TRHR Gene

TRHR (Thyrotropin Releasing Hormone Receptor) is a Protein Coding gene. Diseases associated with TRHR include Hypothyroidism, Congenital, Nongoitrous, 7 and Hypothyroidism. Among its related pathways are Peptide ligand-binding receptors and Signaling by GPCR. Gene Ontology (GO) annotations related to this gene include G protein-coupled receptor activity and thyrotropin-releasing hormone receptor activity. An important paralog of this gene is NMUR2.

UniProtKB/Swiss-Prot Summary for TRHR Gene

  • Receptor for thyrotropin-releasing hormone (TRH). Upon ligand binding, this G-protein-coupled receptor triggers activation of the phosphatidylinositol (IP3)-calcium-protein kinase C (PKC) pathway.

Tocris Summary for TRHR Gene

  • Thyrotropin-releasing hormone (TRH) receptors are Gq/11-protein-coupled receptors that promote thyroid-stimulating hormone (TSH) and prolactin (PRL) release. Two TRH receptor subtypes, TRH1 and TRH2, have been identified in rats but only TRH1 has been found in humans.

Gene Wiki entry for TRHR Gene

No data available for CIViC Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for TRHR Gene

Genomics for TRHR Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for TRHR Gene
GeneHancer (GH) Identifier GH Type GH
Score
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH08J109052 Enhancer 0.6 Ensembl 11.1 -34.0 -33987 0.8 BCL11A PRDM10 BATF IKZF1 ATF2 TCF12 TARDBP IKZF2 MTA2 NBN TRHR piR-36588-442 HSALNG0067696 ENSG00000253796 TMEM74
GH08J109025 Enhancer 0.4 Ensembl 10 -60.8 -60769 1 JUND GATA2 CHD2 EP300 ENSG00000253796 TRHR PKHD1L1 RF00017-6700 HSALNG0067696 LOC107984017 TMEM74
GH08J109065 Enhancer 0.9 Ensembl ENCODE 0.4 -20.6 -20584 0.8 NCOR1 NFIC TAL1 ZNF316 NFE2 PRDM10 STAT5A FOXM1 HDAC2 FOXK2 PKHD1L1 ENSG00000253796 piR-45035-179 HSALNG0067700 TRHR TMEM74
GH08J109064 Enhancer 0.7 Ensembl 0.4 -22.2 -22184 0.4 NCOR1 ZNF592 TAL1 SMARCA4 EGR1 TCF12 TEAD4 DPF2 ARID1B SMARCE1 ENSG00000253796 HSALNG0067696 HSALNG0067700 piR-45035-179 TRHR TMEM74
GH08J109082 Enhancer 0.3 Ensembl 0.7 -3.6 -3620 1.4 EP300 HSALNG0067701-001 HSALNG0067701-002 PKHD1L1 TRHR TMEM74
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

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

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

Top Transcription factor binding sites by QIAGEN in the TRHR gene promoter:
  • AP-1
  • c-Fos
  • c-Jun
  • c-Myb
  • Evi-1
  • FosB
  • Fra-1
  • JunB
  • JunD
  • RFX1

Genomic Locations for TRHR Gene

Latest Assembly
chr8:109,086,585-109,121,565
(GRCh38/hg38)
Size:
34,981 bases
Orientation:
Plus strand

Previous Assembly
chr8:110,098,814-110,133,794
(GRCh37/hg19 by Entrez Gene)
Size:
34,981 bases
Orientation:
Plus strand

chr8:110,098,850-110,131,813
(GRCh37/hg19 by Ensembl)
Size:
32,964 bases
Orientation:
Plus strand

Genomic View for TRHR Gene

Genes around TRHR on UCSC Golden Path with GeneCards custom track

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

RefSeq DNA sequence for TRHR Gene

Proteins for TRHR Gene

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

    Protein Symbol:
    P34981-TRFR_HUMAN
    Recommended name:
    Thyrotropin-releasing hormone receptor
    Protein Accession:
    P34981
    Secondary Accessions:
    • Q2M339

    Protein attributes for TRHR Gene

    Size:
    398 amino acids
    Molecular mass:
    45085 Da
    Quaternary structure:
    No Data Available

neXtProt entry for TRHR Gene

Post-translational modifications for TRHR Gene

  • Glycosylation at Asn3 and Asn10
  • Modification sites at PhosphoSitePlus

Other Protein References for TRHR Gene

ENSEMBL proteins:
REFSEQ proteins:

No data available for DME Specific Peptides for TRHR Gene

Domains & Families for TRHR Gene

Gene Families for TRHR Gene

HGNC:
IUPHAR :
Human Protein Atlas (HPA):
  • FDA approved drug targets
  • G-protein coupled receptors
  • Predicted membrane proteins
  • Transporters

Protein Domains for TRHR Gene

InterPro:
Blocks:
  • Thyrotrophin-releasing hormone receptor signature

Suggested Antigen Peptide Sequences for TRHR Gene

GenScript: Design optimal peptide antigens:
  • Thyroliberin receptor (TRFR_HUMAN)

Graphical View of Domain Structure for InterPro Entry

P34981

UniProtKB/Swiss-Prot:

TRFR_HUMAN :
  • Belongs to the G-protein coupled receptor 1 family.
Family:
  • Belongs to the G-protein coupled receptor 1 family.
genes like me logo Genes that share domains with TRHR: view

Function for TRHR Gene

Molecular function for TRHR Gene

UniProtKB/Swiss-Prot Function:
Receptor for thyrotropin-releasing hormone (TRH). Upon ligand binding, this G-protein-coupled receptor triggers activation of the phosphatidylinositol (IP3)-calcium-protein kinase C (PKC) pathway.
GENATLAS Biochemistry:
thyrotropin releasing hormone receptor,neurotransmitter and neuro regulator,involved in the thyroid hormones secretion and metabolic pathway

Phenotypes From GWAS Catalog for TRHR Gene

Gene Ontology (GO) - Molecular Function for TRHR Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0004930 G protein-coupled receptor activity IEA --
GO:0004997 thyrotropin-releasing hormone receptor activity TAS,IBA 21873635
GO:0005515 protein binding IPI 32296183
genes like me logo Genes that share ontologies with TRHR: view
genes like me logo Genes that share phenotypes with TRHR: view

Human Phenotype Ontology for TRHR Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Models for TRHR Gene

MGI Knock Outs for TRHR:

Animal Models for research

  • Taconic Biosciences Mouse Models for TRHR

Inhibitory RNAs for research

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

No data available for Enzyme Numbers (IUBMB) , Transcription Factor Targets and HOMER Transcription for TRHR Gene

Localization for TRHR Gene

Subcellular locations from UniProtKB/Swiss-Prot for TRHR Gene

Cell membrane. Multi-pass membrane protein.

Subcellular locations from

COMPARTMENTS
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 TRHR gene
Compartment Confidence
plasma membrane 5
nucleus 2
extracellular 1
cytoskeleton 1
mitochondrion 1
endoplasmic reticulum 1
endosome 1
cytosol 1
golgi apparatus 1

Gene Ontology (GO) - Cellular Components for TRHR Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005886 plasma membrane TAS --
GO:0005887 integral component of plasma membrane TAS 8395824
GO:0016020 membrane IEA --
GO:0016021 integral component of membrane IEA --
genes like me logo Genes that share ontologies with TRHR: view

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

Pathways & Interactions for TRHR Gene

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

Gene Ontology (GO) - Biological Process for TRHR Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0007165 signal transduction IEA --
GO:0007186 G protein-coupled receptor signaling pathway TAS --
GO:0007200 phospholipase C-activating G protein-coupled receptor signaling pathway IBA 21873635
genes like me logo Genes that share ontologies with TRHR: view

No data available for SIGNOR curated interactions for TRHR Gene

Drugs & Compounds for TRHR Gene

(10) Drugs for TRHR Gene - From: DrugBank, DGIdb, IUPHAR, HMDB, Tocris, and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Protirelin Approved, Investigational Pharma Target, ligand 0
taltirelin Pharma Agonist, Full agonist Synthetic thyrotropin-releasing hormone analog 0
MeTRH Pharma Agonist, Partial agonist 0
Calcium Nutra 6959

(5) Additional Compounds for TRHR Gene - From: Novoseek

Name Synonyms Role CAS Number PubChem IDs PubMed IDs

(1) Tocris Compounds for TRHR Gene

Compound Action Cas Number
Taltirelin Synthetic thyrotropin-releasing hormone analog 103300-74-9
genes like me logo Genes that share compounds with TRHR: view

Transcripts for TRHR Gene

mRNA/cDNA for TRHR Gene

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

Inhibitory RNAs for research

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

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

No ASD Table

Relevant External Links for TRHR Gene

GeneLoc Exon Structure for
TRHR

Expression for TRHR Gene

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

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

This gene is overexpressed in Pituitary (x17.6).

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

SOURCE GeneReport for Unigene cluster for TRHR Gene:

Hs.3022

Evidence on tissue expression from TISSUES for TRHR Gene

  • Nervous system(4.4)

Phenotype-based relationships between genes and organs from Gene ORGANizer for TRHR Gene

Germ Layers:
  • ectoderm
  • endoderm
  • mesoderm
Systems:
  • cardiovascular
  • digestive
  • endocrine
  • integumentary
  • nervous
  • reproductive
  • respiratory
  • skeletal muscle
  • skeleton
Regions:
Head and neck:
  • brain
  • ear
  • eye
  • face
  • head
  • hypothalamus
  • jaw
  • lip
  • mandible
  • maxilla
  • mouth
  • neck
  • pharynx
  • pituitary gland
  • skull
  • thyroid
  • tongue
Thorax:
  • heart
  • lung
Abdomen:
  • abdominal wall
  • intestine
  • large intestine
  • liver
  • small intestine
Pelvis:
  • rectum
  • uterus
General:
  • blood
  • blood vessel
  • coagulation system
  • peripheral nerve
  • peripheral nervous system
  • red blood cell
  • skin
genes like me logo Genes that share expression patterns with TRHR: view

Primer products for research

No data available for Protein differential expression in normal tissues , Protein expression , Protein tissue co-expression partners and mRNA Expression by UniProt/SwissProt for TRHR Gene

Orthologs for TRHR Gene

This gene was present in the common ancestor of animals.

Orthologs for TRHR Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
Mammalia TRHR 29 30
  • 99.5 (n)
OneToOne
Dog
(Canis familiaris)
Mammalia TRHR 29 30
  • 94.47 (n)
OneToOne
Cow
(Bos Taurus)
Mammalia TRHR 29 30
  • 92.96 (n)
OneToOne
Mouse
(Mus musculus)
Mammalia Trhr 29 16 30
  • 90.48 (n)
OneToOne
Oppossum
(Monodelphis domestica)
Mammalia TRHR 30
  • 90 (a)
OneToOne
Rat
(Rattus norvegicus)
Mammalia Trhr 29
  • 89.8 (n)
Platypus
(Ornithorhynchus anatinus)
Mammalia TRHR 30
  • 80 (a)
OneToOne
Chicken
(Gallus gallus)
Aves TRHR 29 30
  • 76.19 (n)
OneToOne
Lizard
(Anolis carolinensis)
Reptilia TRHR 30
  • 82 (a)
OneToOne
Tropical Clawed Frog
(Silurana tropicalis)
Amphibia trhr 29
  • 74.17 (n)
African clawed frog
(Xenopus laevis)
Amphibia trhr-A 29
Zebrafish
(Danio rerio)
Actinopterygii trhra 29 30
  • 66.57 (n)
OneToMany
trhrb 30
  • 64 (a)
OneToMany
African malaria mosquito
(Anopheles gambiae)
Insecta GPRNPR1 29
  • 47 (n)
Fruit Fly
(Drosophila melanogaster)
Insecta ETHR 30
  • 22 (a)
OneToOne
Worm
(Caenorhabditis elegans)
Secernentea C30F12.6 31
  • 39 (a)
npr-15 30
  • 23 (a)
OneToMany
npr-33 30
  • 19 (a)
OneToMany
Species where no ortholog for TRHR was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • 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 TRHR Gene

ENSEMBL:
Gene Tree for TRHR (if available)
TreeFam:
Gene Tree for TRHR (if available)
Aminode:
Evolutionary constrained regions (ECRs) for TRHR: view image
Alliance of Genome Resources:
Additional Orthologs for TRHR

Paralogs for TRHR Gene

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

Variants for TRHR Gene

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

SNP ID Clinical significance and condition Chr 08 pos Variation AA Info Type
rs121917847 Pathogenic: Hypothyroidism, congenital, nongoitrous, 7 109,087,561(+) C/T
NM_003301.7(TRHR):c.49C>T (p.Arg17Ter)
NONSENSE
rs147019235 Likely Benign: not provided 109,119,324(+) G/A
NM_003301.7(TRHR):c.1066G>A (p.Val356Ile)
MISSENSE
rs150719639 Likely Benign: not provided 109,088,001(+) G/A
NM_003301.7(TRHR):c.489G>A (p.Leu163=)
SYNONYMOUS
rs1586182837 Likely Pathogenic: Hypothyroidism, congenital, nongoitrous, 7 109,087,754(+) C/G
NM_003301.6(TRHR):c.242C>G (p.Pro81Arg)
MISSENSE
rs1586182912 Likely Pathogenic: Hypothyroidism, congenital, nongoitrous, 7 109,087,855(+) TCAATAACAG/A
NM_003301.6(TRHR):c.343_352delinsA (p.Ser115_Ala118delinsThr)
INFRAME_INDEL

dbSNP identifiers (rs#s) for variants without ClinVar clinical significance for TRHR Gene

All consequence types are included: molecular consequences (e.g. missense, synonymous), and location-based (e.g. intron, upstream).

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

Variant ID Type Subtype PubMed ID
esv1010309 CNV insertion 20482838
esv3305632 CNV mobile element insertion 20981092
esv3305891 CNV mobile element insertion 20981092
esv3308427 CNV mobile element insertion 20981092
esv3395093 CNV insertion 20981092
esv3398027 CNV insertion 20981092
esv3404380 CNV insertion 20981092
nsv1117845 CNV deletion 24896259

Variation tolerance for TRHR Gene

Residual Variation Intolerance Score: 28.5% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 0.79; 16.54% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for TRHR Gene

Human Gene Mutation Database (HGMD)
TRHR
SNPedia medical, phenotypic, and genealogical associations of SNPs for
TRHR
Leiden Open Variation Database (LOVD)
TRHR

SNP Genotyping and Copy Number Assays for research

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

Disorders for TRHR Gene

MalaCards: The human disease database

(10) MalaCards diseases for TRHR Gene - From: OMI, CVR, GTR, ORP, SWI, COP, and GCD

Disorder Aliases PubMed IDs
hypothyroidism, congenital, nongoitrous, 7
  • chng7
hypothyroidism
  • thyroid deficiency
hypothyroidism, central, with testicular enlargement
  • chte
central congenital hypothyroidism
  • secondary hypothyroidism
acromegaly
  • growth hormone excess
- elite association - COSMIC cancer census association via MalaCards
Search TRHR in MalaCards View complete list of genes associated with diseases

UniProtKB/Swiss-Prot

TRFR_HUMAN
  • Hypothyroidism, congenital, non-goitrous, 7 (CHNG7) [MIM:618573]: A form of central hypothyroidism, a disorder characterized by sub-optimal thyroid hormone secretion, due to insufficient stimulation by thyrotropin of an otherwise normal thyroid gland. It may be caused by congenital or acquired disorders of the pituitary gland or hypothalamus. CHNG7 is a congenital, autosomal recessive form characterized by normal-to-low T4 and normal-to-high thyrotropin levels, and reduced or absent pituitary responsiveness to thyrotropin-releasing hormone. Patients may exhibit short stature, growth retardation, and delayed bone age, as well as lethargy or fatigue. {ECO:0000269 PubMed:19213692, ECO:0000269 PubMed:26735259, ECO:0000269 PubMed:28419241, ECO:0000269 PubMed:9141550}. Note=The disease is caused by variants affecting the gene represented in this entry.

Genatlas disease for TRHR Gene

isolated central hypothyroidism with TSH and PRL levels unresponsive to TRH (inactivating mutations of TRHR)

Additional Disease Information for TRHR

Human Genome Epidemiology Navigator
(HuGE)
Atlas
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
Open Targets Platform
Open Targets Platform
genes like me logo Genes that share disorders with TRHR: view

Publications for TRHR Gene

  1. A novel mechanism for isolated central hypothyroidism: inactivating mutations in the thyrotropin-releasing hormone receptor gene. (PMID: 9141550) Collu R … Van Vliet G (The Journal of clinical endocrinology and metabolism 1997) 3 4 22 72
  2. Genome-wide association and replication studies identified TRHR as an important gene for lean body mass. (PMID: 19268274) Liu XG … Deng HW (American journal of human genetics 2009) 3 22 40
  3. Sex differences in environmental and genetic factors for hypertension. (PMID: 18724972) Ruixing Y … Yuming C (The American journal of medicine 2008) 3 22 40
  4. Structural and functional organization of the gene encoding the human thyrotropin-releasing hormone receptor. (PMID: 9886052) Matre V … Gautvik KM (Journal of neurochemistry 1999) 3 4 22
  5. Genomic organization and promoter function of the human thyrotropin-releasing hormone receptor gene. (PMID: 8703031) Iwasaki T … Mori M (The Journal of biological chemistry 1996) 3 4 22

Products for TRHR Gene

Sources for TRHR Gene