TRH

thyrotropin releasing hormone, the group of Receptor ligands|Neuropeptides

Basic information

Region (hg38): 3:129974687-129977935

Links

ENSG00000170893 ∙ NCBI:7200 ∙ OMIM:613879 ∙ HGNC:12298 ∙ Uniprot:P20396 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

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

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TRH 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				5	4	9
missense			13	2	2	17
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region					1	1
non coding						0
Total	0	0	13	7	6

Variants in TRH

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

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

Position	Type	Phenotype	Significance	ClinVar
3-129975838-C-G		not specified	Benign (-)
3-129975841-G-A		Brachycephaly;Seizure;Chorea;Generalized hypotonia;Global developmental delay	Uncertain significance (-)
3-129975844-C-G		not specified	Uncertain significance (Jun 22, 2024)
3-129975869-G-T		not specified	Uncertain significance (May 31, 2023)
3-129975893-C-G		not specified	Uncertain significance (Oct 03, 2022)
3-129975918-G-A			Likely benign (Jun 01, 2018)
3-129975921-G-A		TRH-related disorder	Likely benign (Apr 24, 2019)
3-129975943-G-A		not specified	Uncertain significance (Dec 20, 2021)
3-129976002-G-A		TRH-related disorder	Likely benign (May 08, 2019)
3-129976009-G-C		not specified	Uncertain significance (Apr 23, 2024)
3-129976695-C-T		not specified • Hypothalamic hypothyroidism	Benign (Sep 10, 2021)
3-129976702-C-A		not specified	Uncertain significance (Jun 23, 2023)
3-129976703-C-T		TRH-related disorder	Likely benign (Jul 05, 2023)
3-129976735-G-A			Benign/Likely benign (Aug 20, 2018)
3-129976801-G-T		not specified	Uncertain significance (Nov 07, 2022)
3-129976871-T-C		not specified	Benign (-)
3-129976906-G-A		not specified	Uncertain significance (Jan 09, 2024)
3-129976998-G-A		not specified	Uncertain significance (Sep 16, 2021)
3-129977040-C-T		not specified	Uncertain significance (Oct 05, 2021)
3-129977050-C-T			Benign/Likely benign (Mar 01, 2023)
3-129977087-G-A			Benign (Jun 27, 2018)
3-129977104-C-T		not specified	Uncertain significance (Feb 16, 2023)
3-129977105-G-A		TRH-related disorder	Likely benign (Aug 29, 2022)
3-129977111-T-C		not specified • Hypothalamic hypothyroidism	Benign (Sep 10, 2021)
3-129977163-C-T		Hypothalamic hypothyroidism	Uncertain significance (Feb 28, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TRH	protein_coding	protein_coding	ENST00000302649	2	3634

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.000891	0.811	125714	0	31	125745	0.000123

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.228	152	144	1.05	0.00000833	1530
Missense in Polyphen		47	45.176	1.0404		475
Synonymous	-0.377	61	57.4	1.06	0.00000287	504
Loss of Function	1.12	6	9.79	0.613	6.04e-7	93

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000123	0.000123
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000544	0.0000544
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.000186	0.000185
Middle Eastern	0.0000544	0.0000544
South Asian	0.000163	0.000163
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: As a component of the hypothalamic-pituitary-thyroid axis, it controls the secretion of thyroid-stimulating hormone (TSH) and is involved in thyroid hormone synthesis regulation. It also operates as modulator of hair growth. It promotes hair-shaft elongation, prolongs the hair cycle growth phase (anagen) and antagonizes its termination (catagen) by TGFB2. It stimulates proliferation and inhibits apoptosis of hair matrix keratinocytes. {ECO:0000269|PubMed:19825978}.
• Pathway: Thyroxine (Thyroid Hormone) Production;Signaling by GPCR;Signal Transduction;GPCR signaling-G alpha q;GPCR signaling-cholera toxin;GPCR signaling-pertussis toxin;Peptide ligand-binding receptors;Class A/1 (Rhodopsin-like receptors);GPCR ligand binding;GPCR signaling-G alpha s Epac and ERK;GPCR signaling-G alpha s PKA and ERK;GPCR signaling-G alpha i;G alpha (q) signalling events;GPCR downstream signalling (Consensus)

Recessive Scores

• pRec: 0.272

Intolerance Scores

• loftool: 0.572
• rvis_EVS: 0.02
• rvis_percentile_EVS: 55.45

Haploinsufficiency Scores

• pHI: 0.176
• hipred: N
• hipred_score: 0.180
• ghis: 0.393

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.307

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Trh
• Phenotype: homeostasis/metabolism phenotype; endocrine/exocrine gland phenotype; growth/size/body region phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan)

Gene ontology

• Biological process: response to hypoxia;histamine metabolic process;signal transduction;G protein-coupled receptor signaling pathway;cell-cell signaling;adult walking behavior;response to cold;response to glucose;hormone-mediated signaling pathway;regulation of signaling receptor activity;negative regulation of glutamate secretion;positive regulation of gamma-aminobutyric acid secretion;positive regulation of insulin secretion;eating behavior;response to ethanol;response to corticosterone;negative regulation of feeding behavior
• Cellular component: extracellular region;nucleus;plasma membrane;secretory granule
• Molecular function: thyrotropin-releasing hormone activity