ADIPOR1
protein-codingadiponectin receptor 1, the group of Progestin and adipoQ receptor family|Adiponectin receptors
Gene summary
This gene encodes a protein which acts as a receptor for adiponectin, a hormone secreted by adipocytes which regulates fatty acid catabolism and glucose levels. Binding of adiponectin to the encoded protein results in activation of an AMP-activated kinase signaling pathway which affects levels of fatty acid oxidation and insulin sensitivity. A pseudogene of this gene is located on chromosome 14. Multiple alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Mar 2014]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~17.7 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: SD
Disease ID:MONDO:0019200
Submitter: PanelApp Australia
Inheritance Pattern: AD
Disease ID:MONDO:0019200
Submitter: Franklin by Genoox
A heterozygous mutation in ADIPOR1 (c.929A > G) that results in an amino acid substitution (p.Y310C) was identified to co-segregate with retinitis pigmentosa in a Chinese family. The p.Y310C mutation, predicted to affect the structure and function of the protein, was confirmed to affect protein folding and its subcellular localization in vitro. In addition, knockdown of adipor1 expression in a zebrafish model with morpholino (MO) preferentially reduced the number of rod photoreceptors, with no effect on the number of cones, a phenotype that is characteristic of RP. Furthermore, the knockdown phenotype was partially rescued by injecting wild-type, but not mutant, human ADIPOR1 mRNA.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to ADIPOR1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_015999.6. 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 | 7 | 54 | 3 | 64 | ||
| missense | 1 | 83 | 2 | 86 | ||
| nonsense | 1 | 1 | ||||
| start loss | 1 | 1 | ||||
| frameshift | 4 | 4 | ||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 1 | 0 | 97 | 56 | 3 | 157 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_057083.2 | 7 | MANE Select | |
| Ensembl | ENSP00000341785.5 | 7 | MANE Select | |
| RefSeq | NP_001277482.1 | 7 | Standard | |
| RefSeq | NP_001277486.1 | 7 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| adipor1b | Danio rerio | Structure: retinal rod cell Quality: decreased amount abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Adipocytokine signaling pathway - Homo sapiens (human)
- Non-alcoholic fatty liver disease (NAFLD) - Homo sapiens (human)
- AMPK signaling pathway - Homo sapiens (human)
- Longevity regulating pathway - Homo sapiens (human)
- AMP-activated Protein Kinase (AMPK) Signaling
Biological Process
- hormone-mediated signaling pathway
- negative regulation of epithelial cell migration
- negative regulation of epithelial to mesenchymal transition
- regulation of glucose metabolic process
- regulation of lipid metabolic process
Molecular Function
- protein kinase binding
- signaling receptor activity
- identical protein binding
- metal ion binding
- protein heterodimerization activity
Cellular Component
- plasma membrane
- membrane
- integral component of membrane
- intrinsic component of plasma membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000340990
- Coding exons
- 7
- Length
- 17750
- Individuals with no LoFs
- 125741
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 6
- Defined
- 125747
- p
- 0.0000239
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 2.82 | 105 | 224 | 0.469 | 0.0000126 | 2453 |
| Missense (PolyPhen) | 21 | 56.465 | 0.37191 | 724 | ||
| Synonymous | 0.0802 | 82 | 82.9 | 0.989 | 0.00000463 | 756 |
| Loss of Function | 3.08 | 3 | 16.5 | 0.181 | 7.67e-7 | 191 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0.000029 | 0.000029 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.000054 | 0.000054 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000036 | 0.000035 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Receptor for ADIPOQ, an essential hormone secreted by adipocytes that regulates glucose and lipid metabolism (PubMed:25855295, PubMed:12802337). Required for normal glucose and fat homeostasis and for maintaining a normal body weight. ADIPOQ-binding activates a signaling cascade that leads to increased AMPK activity, and ultimately to increased fatty acid oxidation, increased glucose uptake and decreased gluconeogenesis. Has high affinity for globular adiponectin and low affinity for full-length adiponectin (By similarity). {ECO:0000250|UniProtKB:Q91VH1, ECO:0000269|PubMed:12802337, ECO:0000269|PubMed:25855295}.;
Recessive Scores
- pRec
- 0.265
Intolerance Scores
- LoFtool
- 0.223
- RVIS EVS
- -0.3
- RVIS percentile EVS
- 32.62
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- K
- Indispensability pred.
- N
- Indispensability score
- 0.303
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Low | Medium |
| Primary Immunodeficiency | Medium | Low | Medium |
| Cancer | Medium | Medium | Medium |