CRHR1
protein-codingcorticotropin releasing hormone receptor 1, the group of Corticotropin releasing hormone receptors
Gene summary
This gene encodes a G-protein coupled receptor that binds neuropeptides of the corticotropin releasing hormone family that are major regulators of the hypothalamic-pituitary-adrenal pathway. The encoded protein is essential for the activation of signal transduction pathways that regulate diverse physiological processes including stress, reproduction, immune response and obesity. Alternative splicing results in multiple transcript variants. Naturally-occurring readthrough transcription between this gene and upstream GeneID:147081 results in transcripts that encode isoforms that share similarity with the products of this gene. [provided by RefSeq, Aug 2016]
- CRHR
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~51.6 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 CRHR1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_004382.5. 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 | 1 | 2 | 2 | 5 | ||
| missense | 49 | 4 | 2 | 55 | ||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 51 | 6 | 4 | 61 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_004373.2 | 13 | MANE Select | |
| Ensembl | ENSP00000326060.6 | 13 | MANE Select | |
| RefSeq | NP_001138618.1 | 14 | Standard | |
| RefSeq | NP_001138619.1 | 12 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Cushing,s syndrome - Homo sapiens (human)
- Long-term depression - Homo sapiens (human)
- Neuroactive ligand-receptor interaction - Homo sapiens (human)
- Glucocorticoid Pathway (HPA Axis), Pharmacodynamics
- Corticotropin-releasing hormone signaling pathway
Biological Process
- immune response
- cell surface receptor signaling pathway
- G protein-coupled receptor signaling pathway
- adenylate cyclase-activating G protein-coupled receptor signaling pathway
- activation of adenylate cyclase activity
Molecular Function
- protein binding
- corticotrophin-releasing factor receptor activity
- peptide hormone binding
- corticotropin-releasing hormone receptor activity
- corticotropin-releasing hormone binding
Cellular Component
- endosome
- plasma membrane
- integral component of plasma membrane
- integral component of membrane
- intrinsic component of plasma membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000398285
- Coding exons
- 14
- Length
- 213928
- Individuals with no LoFs
- 125188
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 70
- Defined
- 125258
- p
- 0.000279
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.73 | 196 | 277 | 0.708 | 0.0000173 | 2889 |
| Missense (PolyPhen) | 29 | 70.499 | 0.41135 | 759 | ||
| Synonymous | 0.763 | 101 | 111 | 0.908 | 0.00000690 | 873 |
| Loss of Function | 2.71 | 12 | 27.2 | 0.440 | 0.00000131 | 283 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00013 | 0.00012 | rare |
| Latino/Admixed American | 0.00052 | 0.00041 | rare |
| Ashkenazi Jewish | 0.00025 | 0.00020 | rare |
| East Asian | 0.00029 | 0.00028 | rare |
| Finnish | 0.00088 | 0.00084 | rare |
| European (Non-Finnish) | 0.00016 | 0.00015 | rare |
| South Asian | 0.00028 | 0.00026 | rare |
| Other | 0.00079 | 0.00066 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: G-protein coupled receptor for CRH (corticotropin- releasing factor) and UCN (urocortin). Has high affinity for CRH and UCN. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and down-stream effectors, such as adenylate cyclase. Promotes the activation of adenylate cyclase, leading to increased intracellular cAMP levels. Inhibits the activity of the calcium channel CACNA1H. Required for normal embryonic development of the adrenal gland and for normal hormonal responses to stress. Plays a role in the response to anxiogenic stimuli. {ECO:0000269|PubMed:18292205, ECO:0000269|PubMed:18801728, ECO:0000269|PubMed:23576434, ECO:0000269|PubMed:23863939}.;
Recessive Scores
- pRec
- 0.389
Intolerance Scores
- LoFtool
- 0.701
- RVIS EVS
- -0.09
- RVIS percentile EVS
- 46.92
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.719
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |