ADCYAP1R1
protein-codingADCYAP receptor type I, the group of Vasoactive intestinal peptide family receptors
Gene summary
This gene encodes type I adenylate cyclase activating polypeptide receptor, which is a membrane-associated protein and shares significant homology with members of the glucagon/secretin receptor family. This receptor mediates diverse biological actions of adenylate cyclase activating polypeptide 1 and is positively coupled to adenylate cyclase. Multiple alternatively spliced transcript variants encoding distinct isoforms have been identified. [provided by RefSeq, Dec 2010]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~59.2 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 ADCYAP1R1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001118.5. 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 | 46 | 3 | 49 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 2 | 2 | ||||
| Total | 0 | 0 | 48 | 3 | 1 | 52 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001109.2 | 15 | MANE Select | |
| Ensembl | ENSP00000306620.4 | 15 | MANE Select | |
| RefSeq | NP_001186564.1 | 16 | Standard | |
| RefSeq | NP_001186565.1 | 16 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| adcyap1r1b | Danio rerio | Structure: hypothalamus Quality: has fewer parts of type abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Circadian entrainment - Homo sapiens (human)
- cAMP signaling pathway - Homo sapiens (human)
- Renin secretion - Homo sapiens (human)
- Neuroactive ligand-receptor interaction - Homo sapiens (human)
- Insulin secretion - Homo sapiens (human)
Biological Process
- cell surface receptor signaling pathway
- G protein-coupled receptor signaling pathway
- activation of phospholipase C activity
- spermatogenesis
- positive regulation of calcium ion transport into cytosol
Molecular Function
- vasoactive intestinal polypeptide receptor activity
- protein binding
- adenylate cyclase binding
- G protein-coupled peptide receptor activity
- peptide hormone binding
Cellular Component
- endosome
- rough endoplasmic reticulum
- plasma membrane
- integral component of plasma membrane
- caveola
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000396211
- Coding exons
- 16
- Length
- 59014
- Individuals with no LoFs
- 125717
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 31
- Defined
- 125748
- p
- 0.000123
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.39 | 219 | 285 | 0.768 | 0.0000158 | 3270 |
| Missense (PolyPhen) | 85 | 112.01 | 0.75888 | 1273 | ||
| Synonymous | -0.134 | 112 | 110 | 1.02 | 0.00000638 | 921 |
| Loss of Function | 2.17 | 20 | 33.5 | 0.596 | 0.00000186 | 343 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00025 | 0.00025 | rare |
| Latino/Admixed American | 0.000058 | 0.000058 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00011 | 0.00011 | rare |
| Finnish | 0.00028 | 0.00028 | rare |
| European (Non-Finnish) | 0.00013 | 0.00012 | rare |
| South Asian | 0.00010 | 0.000098 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: This is a receptor for PACAP-27 and PACAP-38. The activity of this receptor is mediated by G proteins which activate adenylyl cyclase. May regulate the release of adrenocorticotropin, luteinizing hormone, growth hormone, prolactin, epinephrine, and catecholamine. May play a role in spermatogenesis and sperm motility. Causes smooth muscle relaxation and secretion in the gastrointestinal tract.;
Recessive Scores
- pRec
- 0.119
Intolerance Scores
- LoFtool
- 0.593
- RVIS EVS
- -0.16
- RVIS percentile EVS
- 41.91
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.391
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |