TRHR

thyrotropin releasing hormone receptor, the group of Peptide receptors

Basic information

Region (hg38): 8:109086584-109121565

Links

ENSG00000174417 ∙ NCBI:7201 ∙ OMIM:188545 ∙ HGNC:12299 ∙ Uniprot:P34981 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• hypothyroidism, congenital, nongoitrous, 7 (Strong), mode of inheritance: AR
• resistance to thyrotropin-releasing hormone syndrome (Supportive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Hypothyroidism, congenital, nongoitrous, 7	AR	Endocrine	Individuals may manifest with sequalae of hypothyroidism, and medical treatment (with thyroid hormone replacement) can be effective	Endocrine	9141550; 19213692; 26735259; 28419241

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the TRHR gene.

• not provided (6 variants)
• Inborn genetic diseases (6 variants)
• Hypothyroidism, congenital, nongoitrous, 7 (3 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TRHR gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				1	2	3
missense		1	7	2		10
nonsense	1					1
start loss						0
frameshift						0
inframe indel		1				1
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	1	2	7	3	2

Highest pathogenic variant AF is 0.0000263

Variants in TRHR

This is a list of pathogenic ClinVar variants found in the TRHR region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
8-109087521-C-T		TRHR-related disorder	Likely benign (Nov 13, 2023)
8-109087547-C-T		Inborn genetic diseases	Uncertain significance (Mar 14, 2023)
8-109087561-C-T		Hypothyroidism, congenital, nongoitrous, 7	Pathogenic (Feb 14, 2020)
8-109087635-A-G		TRHR-related disorder	Benign/Likely benign (Jan 22, 2024)
8-109087663-A-C			Uncertain significance (Dec 01, 2022)
8-109087744-G-A		Inborn genetic diseases	Uncertain significance (Jan 12, 2024)
8-109087754-C-G		Hypothyroidism, congenital, nongoitrous, 7	Likely pathogenic (Feb 14, 2020)
8-109087802-G-C		Inborn genetic diseases	Uncertain significance (Sep 29, 2023)
8-109087813-A-G		Inborn genetic diseases	Uncertain significance (Nov 21, 2022)
8-109087855-TCAATAACAG-A		Hypothyroidism, congenital, nongoitrous, 7	Likely pathogenic (Feb 14, 2020)
8-109087891-A-G			Likely benign (Dec 31, 2019)
8-109087904-T-C		Hypothyroidism, congenital, nongoitrous, 7	Pathogenic (Sep 06, 2019)
8-109087944-G-C		Inborn genetic diseases	Uncertain significance (Jul 26, 2022)
8-109088001-G-A			Likely benign (Nov 09, 2018)
8-109088045-C-A		Inborn genetic diseases	Uncertain significance (May 01, 2022)
8-109088189-A-C		Inborn genetic diseases	Uncertain significance (Sep 27, 2021)
8-109088220-T-C		TRHR-related disorder	Likely benign (Aug 06, 2019)
8-109119186-T-C		Inborn genetic diseases	Uncertain significance (Dec 28, 2022)
8-109119283-C-T		Inborn genetic diseases	Uncertain significance (Jan 31, 2024)
8-109119324-G-A			Likely benign (Feb 01, 2023)
8-109119407-T-C			Benign (Dec 31, 2019)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TRHR	protein_coding	protein_coding	ENST00000518632	2	32964

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.271	0.724	125675	0	69	125744	0.000274

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.944	163	201	0.813	0.00000954	2624
Missense in Polyphen		45	68.452	0.6574		922
Synonymous	0.147	75	76.6	0.979	0.00000387	788
Loss of Function	2.43	3	12.2	0.247	6.25e-7	156

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000291	0.0000291
Ashkenazi Jewish	0.00	0.00
East Asian	0.000109	0.000109
Finnish	0.000231	0.000185
European (Non-Finnish)	0.000513	0.000457
Middle Eastern	0.000109	0.000109
South Asian	0.000261	0.000261
Other	0.000327	0.000326

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Receptor for thyrotropin-releasing hormone. This receptor is mediated by G proteins which activate a phosphatidylinositol-calcium second messenger system.
• Pathway: Calcium signaling pathway - Homo sapiens (human);Neuroactive ligand-receptor interaction - Homo sapiens (human);Peptide GPCRs;GPCRs, Class A Rhodopsin-like;Signaling by GPCR;Signal Transduction;Peptide ligand-binding receptors;Class A/1 (Rhodopsin-like receptors);GPCR ligand binding;G alpha (q) signalling events;GPCR downstream signalling (Consensus)

Recessive Scores

• pRec: 0.229

Intolerance Scores

• loftool: 0.703
• rvis_EVS: -0.29
• rvis_percentile_EVS: 32.94

Haploinsufficiency Scores

• pHI: 0.220
• hipred: N
• hipred_score: 0.496
• ghis: 0.441

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.339

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Trhr
• Phenotype: behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); growth/size/body region phenotype; endocrine/exocrine gland phenotype; homeostasis/metabolism phenotype

Gene ontology

• Biological process: G protein-coupled receptor signaling pathway
• Cellular component: plasma membrane;integral component of plasma membrane
• Molecular function: thyrotropin-releasing hormone receptor activity