TRH
protein-codingthyrotropin releasing hormone, the group of Receptor ligands|Neuropeptides
Gene summary
This gene encodes a member of the thyrotropin-releasing hormone family. Cleavage of the encoded proprotein releases mature thyrotropin-releasing hormone, which is a tripeptide hypothalamic regulatory hormone. The human proprotein contains six thyrotropin-releasing hormone tripeptides. Thyrotropin-releasing hormone is involved in the regulation and release of thyroid-stimulating hormone, as well as prolactin. Deficiency of this hormone has been associated with hypothalamic hypothyroidism. [provided by RefSeq, May 2013]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~3.2 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to TRH variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_007117.5. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 5 | 1 | 6 | |||
| missense | 31 | 4 | 1 | 36 | ||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 31 | 9 | 2 | 42 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_009048.1 | 2 | MANE Select | |
| Ensembl | ENSP00000303452.3 | 2 | MANE Select | |
| Ensembl | ENSP00000426522.1 | 2 | Standard | |
| Ensembl | ENSP00000426522.1 | 2 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Thyroxine (Thyroid Hormone) Production
- Signaling by GPCR
- Signal Transduction
- GPCR signaling-G alpha q
- GPCR signaling-cholera toxin
Biological Process
- response to hypoxia
- histamine metabolic process
- signal transduction
- G protein-coupled receptor signaling pathway
- cell-cell signaling
Molecular Function
- thyrotropin-releasing hormone activity
Cellular Component
- extracellular region
- nucleus
- plasma membrane
- secretory granule
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000302649
- Coding exons
- 2
- Length
- 3634
- Individuals with no LoFs
- 125714
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 31
- Defined
- 125745
- p
- 0.000123
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.228 | 152 | 144 | 1.05 | 0.00000833 | 1530 |
| Missense (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 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00012 | 0.00012 | rare |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.000054 | 0.000054 | rare |
| Finnish | 0.000046 | 0.000046 | rare |
| European (Non-Finnish) | 0.00019 | 0.00018 | rare |
| South Asian | 0.00016 | 0.00016 | rare |
| Other | 0.00016 | 0.00016 | rare |
dbNSFP Gene Annotations
Source:
- 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}.;
Recessive Scores
- pRec
- 0.272
Intolerance Scores
- LoFtool
- 0.572
- RVIS EVS
- 0.02
- RVIS percentile EVS
- 55.45
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- S
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.307
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |