TRHR (thyrotropin releasing hormone receptor)

Gene

• Entrez ID: 7201
• Gene name: Thyrotropin releasing hormone receptor
• Gene symbol: TRHR
• Synonyms (NCBI Gene): CHNG7, TRH-R
• Chromosome: 8
• Chromosome location: 8q23.1
• Summary: 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

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs121917847	C>T	Pathogenic	Stop gained, coding sequence variant
rs771222349	T>A,C	Pathogenic	Missense variant, coding sequence variant
rs1586182837	C>G	Pathogenic	Missense variant, coding sequence variant
rs1586182912	TCAATAACAG>A	Pathogenic	Inframe indel, coding sequence variant

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0004930	Function	G protein-coupled receptor activity	IEA
GO:0004997	Function	Thyrotropin-releasing hormone receptor activity	IBA
GO:0004997	Function	Thyrotropin-releasing hormone receptor activity	IEA
GO:0004997	Function	Thyrotropin-releasing hormone receptor activity	TAS	8395824
GO:0005515	Function	Protein binding	IPI	28514442, 32296183, 33961781
GO:0005886	Component	Plasma membrane	IEA
GO:0005886	Component	Plasma membrane	TAS	8395824
GO:0007165	Process	Signal transduction	IEA
GO:0007186	Process	G protein-coupled receptor signaling pathway	IEA
GO:0007186	Process	G protein-coupled receptor signaling pathway	TAS	8395824
GO:0007200	Process	Phospholipase C-activating G protein-coupled receptor signaling pathway	IBA
GO:0016020	Component	Membrane	IEA

Other IDs

• MIM: 188545
• HGNC: 12299
• e!Ensembl: ENSG00000174417

Protein

• UniProt ID: P34981
• Protein name: Thyrotropin-releasing hormone receptor (TRH-R) (Thyroliberin receptor)
• Protein 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. {ECO:0000269|PubMed:26735259, ECO:0000269|PubMed
• PDB: 7WKD, 7X1T, 7X1U, 7XW9
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00001	7tm_1	42 → 320	7 transmembrane receptor (rhodopsin family)	Family

• Sequence:

  MENETVSELNQTQLQPRAVVALEYQVVTILLVLIICGLGIVGNIMVVLVVMRTKHMRTPT
  NCYLVSLAVADLMVLVAAGLPNITDSIYGSWVYGYVGCLCITYLQYLGINASSCSITAFT
  IERYIAICHPIKAQFLCTFSRAKKIIIFVWAFTSLYCMLWFFLLDLNISTYKDAIVISCG
  YKISRNYYSPIYLMDFGVFYVVPMILATVLYGFIARILFLNPIPSDPKENSKTWKNDSTH
  QNTNLNVNTSNRCFNSTVSSRKQVTKMLAVVVILFALLWMPYRTLVVVNSFLSSPFQENW
  FLLFCRICIYLNSAINPVIYNLMSQKFRAAFRKLCNCKQKPTEKPANYSVALNYSVIKES
  DHFSTELDDITVTDTYLSATKVSFDDTCLASEVSFSQS

• Sequence length: 398

Pathways

KEGG:

Calcium signaling pathway
Neuroactive ligand-receptor interaction
Hormone signaling

Reactome:

Peptide ligand-binding receptors
G alpha (q) signalling events

Associated diseases

Evidence Score:

• ★☆☆☆☆  Gene-disease association found in Text Mining only
• ★★☆☆☆  Found in Text Mining and Unknown/Other Associations
• ★★★☆☆  Reported in Unknown/Other Associations across ≥2 Sources
• ★★★★☆  ClinVar: Pathogenic/Likely Pathogenic (<5 Variants)
• ★★★★★  ClinVar: Pathogenic/Likely Pathogenic (≥5 Variants)

Causal
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession	Evidence Score
Hypothyroidism, congenital, nongoitrous, 7	Likely pathogenic; Pathogenic	rs1586182912, rs121917847, rs1586182837, rs771222349	RCV004577711 RCV004577712 RCV004577917 RCV004577918	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
ANDROGENETIC ALOPECIA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
BRACHYCEPHALY	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CONGENITAL CENTRAL HYPOTHYROIDISM DUE TO THYROTROPIN-RELEASING HORMONE RECEPTOR DEFICIENCY	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CORNEAL NEOVASCULARIZATION	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CORONARY ATHEROSCLEROSIS	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
FEMALE INFERTILITY	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
GLOBAL DEVELOPMENTAL DELAY	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
HYPERTENSIVE DISEASE	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
HYPOTHYROIDISM	—	CTD, Disgenet CTD, Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
KERATITIS	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
METABOLIC SYNDROME	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MILD INTELLECTUAL DISABILITY	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
OLIGODENDROGLIOMA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SCHIZOPHRENIA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
THYROID HORMONE RESISTANCE SYNDROME	—	CTD, Disgenet CTD, Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
TRHR-related disorder	Likely benign; Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
TYPE 2 DIABETES MELLITUS	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Acromegaly	Acromegaly	Pubtator	14599121	Associate	★☆☆☆☆ Found in Text Mining only
Acromegaly	Acromegaly	BEFREE	8396925		★☆☆☆☆ Found in Text Mining only
Adenoma	Adenoma	BEFREE	11298082, 14599121, 8396925		★☆☆☆☆ Found in Text Mining only
Adenoma	Adenoma	LHGDN	14599121		★☆☆☆☆ Found in Text Mining only
Autism Spectrum Disorder	Autism	Pubtator	28358038	Associate	★☆☆☆☆ Found in Text Mining only
Autism Spectrum Disorders	Autism Spectrum Disorder	BEFREE	28358038		★☆☆☆☆ Found in Text Mining only
Central hypothyroidism	Central hypothyroidism	BEFREE	28419241		★☆☆☆☆ Found in Text Mining only
Central hypothyroidism	Central hypothyroidism	CTD_human_DG	9141550		★☆☆☆☆ Found in Text Mining only
Congenital central hypothyroidism	Congenital Central Hypothyroidism	BEFREE	27603907		★☆☆☆☆ Found in Text Mining only
Congenital central hypothyroidism due to thyrotropin-releasing hormone receptor deficiency	Congenital central hypothyroidism	ORPHANET_DG	20537182, 22851492		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Congenital exomphalos	Congenital Exomphalos	HPO_DG			★☆☆☆☆ Found in Text Mining only
Congenital Hypothyroidism	Congenital Hypothyroidism	BEFREE	26735259		★☆☆☆☆ Found in Text Mining only
Congenital Hypothyroidism	Congenital hypothyroidism	Pubtator	34200080	Associate	★☆☆☆☆ Found in Text Mining only
Dyssomnias	Dyssomnia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Generalized Thyroid Hormone Resistance	Thyroid Hormone Resistance	CTD_human_DG	9141550		★☆☆☆☆ Found in Text Mining only
Global developmental delay	Developmental Delay	HPO_DG			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Growth Hormone-Secreting Pituitary Adenoma	Somatotroph Adenoma	BEFREE	8396925		★☆☆☆☆ Found in Text Mining only
Hypertensive disease	Hypertension	BEFREE	11566956		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Hypothyroidism	Hypothyroidism	Pubtator	26735259, 27603907, 28515030, 32319661	Associate	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Hypothyroidism	Hypothyroidism	BEFREE	29462796		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Hypothyroidism	Hypothyroidism	CTD_human_DG	9141550		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Hypothyroidism	Hypothyroidism	HPO_DG			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Macroglossia	Macroglossia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Migraine Disorders	Migraine	Pubtator	32968778	Associate	★☆☆☆☆ Found in Text Mining only
Neoplasms	Neoplasms	BEFREE	8772588		★☆☆☆☆ Found in Text Mining only
Non-Functioning Pituitary Gland Neoplasm	Pituitary adenoma	BEFREE	11298082		★☆☆☆☆ Found in Text Mining only
Obesity	Obesity	Pubtator	33668547	Associate	★☆☆☆☆ Found in Text Mining only
Primary Hypothyroidism	Hypothyroidism	CTD_human_DG	9141550		★☆☆☆☆ Found in Text Mining only
Prolactinoma	Prolactinoma	BEFREE	11298082		★☆☆☆☆ Found in Text Mining only
Resistance to thyrotropin-releasing hormone syndrome	Resistance To Thyrotropin-Releasing Hormone Syndrome	Orphanet			★☆☆☆☆ Found in Text Mining only
Sarcopenia	Sarcopenia	Pubtator	32076017	Associate	★☆☆☆☆ Found in Text Mining only
Secondary hypothyroidism	Hypothyroidism	CTD_human_DG	9141550		★☆☆☆☆ Found in Text Mining only
Sleep Disorders	Sleep Disorders	HPO_DG			★☆☆☆☆ Found in Text Mining only
Thyroid Hormone Resistance Syndrome	Thyroid Hormone Resistance	CTD_human_DG	9141550		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Thyrotropin-Releasing Hormone Resistance, Generalized	Thyrotropin-releasing hormone resistance	GENOMICS_ENGLAND_DG	19213692		★☆☆☆☆ Found in Text Mining only