AVPR1A
protein-codingarginine vasopressin receptor 1A, the group of Arginine vasopressin and oxytocin receptors
Gene summary
The protein encoded by this gene acts as receptor for arginine vasopressin. This receptor belongs to the subfamily of G-protein coupled receptors which includes AVPR1B, V2R and OXT receptors. Its activity is mediated by G proteins which stimulate a phosphatidylinositol-calcium second messenger system. The receptor mediates cell contraction and proliferation, platelet aggregation, release of coagulation factor and glycogenolysis. [provided by RefSeq, Jul 2008]
- AVPR1
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~8.4 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AD
Disease ID:MONDO:0005258
Submitter: PanelApp Australia
Inheritance Pattern: Unknown
Disease ID:MONDO:0005258
Submitter: ClinGen
The arginine vasopressin receptor 1A (*AVPR1A*) was considered a candidate gene in autism spectrum disorder (ASD) based on reports focused on linkage studies and animal models. Experimental evidence showed that *AVPR1A* is possibly involved in social behaviors, including affiliation and attachment (PMID: 24924430). However, the association studies were underpowered. In two studies, transmission disequilibrium between *AVPR1A* microsatellites and autism was found but most were not statistically significant (PMID: 12082568, 16520824). In another study, investigators screened *AVPR1A* exons in 125 independent autistic probands (PMID: 15098001). However, the study did not demonstrate a disease-causing variant in the coding sequence, and the authors noted that differences in *AVPR1A* at the amino-acid level are unlikely to confer genetic vulnerability to autism. Experimental evidence is available, but in the absence of human genetic evidence, these data were not scored. In summary, there is no valid genetic evidence to support a relationship between *AVPR1A* and autism spectrum disorder. Approved by the ClinGen Intellectual Disability and Autism Gene Curation Expert Panel on March 1, 2022 (SOP Version 9).
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to AVPR1A variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_000706.5. 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 | 2 | |||
| missense | 51 | 1 | 1 | 53 | ||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 51 | 2 | 2 | 55 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_000697.1 | 2 | MANE Select | |
| Ensembl | ENSP00000299178.3 | 2 | MANE Select | |
| Ensembl | ENSP00000449822.1 | 3 | Standard | |
| Ensembl | ENSP00000805314.1 | 2 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Calcium signaling pathway - Homo sapiens (human)
- Vascular smooth muscle contraction - Homo sapiens (human)
- Phospholipase D signaling pathway - Homo sapiens (human)
- Neuroactive ligand-receptor interaction - Homo sapiens (human)
- Peptide GPCRs
Biological Process
- regulation of systemic arterial blood pressure by vasopressin
- maternal aggressive behavior
- positive regulation of systemic arterial blood pressure
- generation of precursor metabolites and energy
- G protein-coupled receptor signaling pathway
Molecular Function
- vasopressin receptor activity
- protein kinase C binding
- protein binding
- peptide hormone binding
- V1A vasopressin receptor binding
Cellular Component
- endosome
- plasma membrane
- integral component of plasma membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000299178
- Coding exons
- 2
- Length
- 5709
- Individuals with no LoFs
- 125579
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 169
- Defined
- 125748
- p
- 0.000672
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.0135 | 242 | 241 | 1.00 | 0.0000121 | 2733 |
| Missense (PolyPhen) | 65 | 69.705 | 0.9325 | 861 | ||
| Synonymous | -0.670 | 109 | 100 | 1.08 | 0.00000554 | 850 |
| Loss of Function | 0.762 | 11 | 14.1 | 0.781 | 6.89e-7 | 131 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00037 | 0.00037 | rare |
| Latino/Admixed American | 0.00014 | 0.00014 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.0069 | 0.0069 | notable |
| Finnish | 0.000083 | 0.000046 | rare |
| European (Non-Finnish) | 0.00017 | 0.00017 | rare |
| South Asian | 0.00026 | 0.00026 | rare |
| Other | 0.00049 | 0.00049 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Receptor for arginine vasopressin. The activity of this receptor is mediated by G proteins which activate a phosphatidyl- inositol-calcium second messenger system. Has been involved in social behaviors, including affiliation and attachment. {ECO:0000269|PubMed:12082568}.;
Recessive Scores
- pRec
- 0.165
Intolerance Scores
- LoFtool
- 0.725
- RVIS EVS
- -0.25
- RVIS percentile EVS
- 35.99
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.565
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |