CRHR2
protein-codingcorticotropin releasing hormone receptor 2, the group of Corticotropin releasing hormone receptors
Gene summary
The protein encoded by this gene belongs to the G-protein coupled receptor 2 family, and the subfamily of corticotropin releasing hormone receptor. This receptor shows high affinity for corticotropin releasing hormone (CRH), and also binds CRH-related peptides such as urocortin. CRH is synthesized in the hypothalamus, and plays an important role in coordinating the endocrine, autonomic, and behavioral responses to stress and immune challenge. Studies in mice suggest that this receptor maybe involved in mediating cardiovascular homeostasis. Alternatively spliced transcript variants encoding different isoforms have been described for this gene.[provided by RefSeq, Jan 2011]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~48.2 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 CRHR2 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001883.5. 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 | 1 | ||||
| missense | 68 | 5 | 1 | 74 | ||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 0 | 0 | 70 | 5 | 1 | 76 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001874.2 | 12 | MANE Select | |
| Ensembl | ENSP00000418722.1 | 12 | MANE Select | |
| RefSeq | NP_001189404.1 | 13 | Standard | |
| RefSeq | NP_001189410.1 | 12 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Cushing,s syndrome - Homo sapiens (human)
- Neuroactive ligand-receptor interaction - Homo sapiens (human)
- Glucocorticoid Pathway (HPA Axis), Pharmacodynamics
- Corticotropin-releasing hormone signaling pathway
- GPCRs, Class B Secretin-like
Biological Process
- cell surface receptor signaling pathway
- G protein-coupled receptor signaling pathway
- adenylate cyclase-modulating G protein-coupled receptor signaling pathway
- hormone-mediated signaling pathway
- long-term synaptic potentiation
Molecular Function
- protein binding
- corticotrophin-releasing factor receptor activity
- peptide hormone binding
- corticotropin-releasing hormone receptor activity
Cellular Component
- plasma membrane
- integral component of plasma membrane
- axon
- dendrite
- axon terminus
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000348438
- Coding exons
- 13
- Length
- 47546
- Individuals with no LoFs
- 125346
- Homozygous LoFs
- 1
- Heterozygous LoFs
- 401
- Defined
- 125748
- p
- 0.00160
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.749 | 229 | 263 | 0.870 | 0.0000161 | 2832 |
| Missense (PolyPhen) | 112 | 118.92 | 0.94183 | 1304 | ||
| Synonymous | 1.35 | 90 | 108 | 0.835 | 0.00000684 | 830 |
| Loss of Function | 0.381 | 26 | 28.2 | 0.923 | 0.00000142 | 295 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.0012 | 0.0012 | notable |
| Latino/Admixed American | 0.00058 | 0.00058 | rare |
| Ashkenazi Jewish | 0.00010 | 0.000099 | rare |
| East Asian | 0.00016 | 0.00016 | rare |
| Finnish | 0.0046 | 0.0044 | notable |
| European (Non-Finnish) | 0.0022 | 0.0022 | notable |
| South Asian | 0.00016 | 0.00016 | rare |
| Other | 0.0013 | 0.0013 | notable |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: G-protein coupled receptor for CRH (corticotropin- releasing factor), UCN (urocortin), UCN2 and UCN3. Has high affinity for 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.;
Recessive Scores
- pRec
- 0.154
Intolerance Scores
- LoFtool
- 0.865
- RVIS EVS
- 0.69
- RVIS percentile EVS
- 85.18
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.631
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |