ADIPOQ
protein-codingadiponectin, C1Q and collagen domain containing, the group of C1q and TNF related
Gene summary
This gene is expressed in adipose tissue exclusively. It encodes a protein with similarity to collagens X and VIII and complement factor C1q. The encoded protein circulates in the plasma and is involved with metabolic and hormonal processes. Mutations in this gene are associated with adiponectin deficiency. Multiple alternatively spliced variants, encoding the same protein, have been identified. [provided by RefSeq, Apr 2010]
- ACDC
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~15.8 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: Unknown
Disease ID:MONDO:0014414
Submitter: Labcorp Genetics (formerly Invitae)
Clinical Genomic Database (CGD)
Manifestation: Endocrine; Renal
Intervention: Endocrine; Renal
Rationale: The condition involves risk of diabetes mellitus with predisposition to end-stage renal disease, and specific medical approaches based on the molecular diagnosis have been suggested as potentially beneficial
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to ADIPOQ variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_004797.4. 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 | 5 | 5 | ||||
| missense | 1 | 23 | 3 | 27 | ||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 1 | 1 | 2 | |||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 2 | 0 | 25 | 8 | 0 | 35 |
Highest pathogenic variant AF is 0.00001797384
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_004788.1 | 2 | MANE Select | |
| Ensembl | ENSP00000320709.2 | 2 | MANE Select | |
| RefSeq | NP_001171271.1 | 2 | Standard | |
| Ensembl | ENSP00000389814.2 | 2 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Adipocytokine signaling pathway - Homo sapiens (human)
- Type II diabetes mellitus - Homo sapiens (human)
- Non-alcoholic fatty liver disease (NAFLD) - Homo sapiens (human)
- AMPK signaling pathway - Homo sapiens (human)
- Longevity regulating pathway - Homo sapiens (human)
Biological Process
- response to hypoxia
- positive regulation of protein phosphorylation
- glucose metabolic process
- generation of precursor metabolites and energy
- fatty acid beta-oxidation
Molecular Function
- signaling receptor binding
- cytokine activity
- hormone activity
- extracellular matrix structural constituent
- protein binding
Cellular Component
- extracellular region
- collagen trimer
- extracellular space
- endoplasmic reticulum
- cell surface
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000412955
- Coding exons
- 2
- Length
- 15790
- Individuals with no LoFs
- 125709
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 39
- Defined
- 125748
- p
- 0.000155
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.131 | 149 | 145 | 1.03 | 0.00000797 | 1577 |
| Missense (PolyPhen) | 48 | 60.677 | 0.79108 | 658 | ||
| Synonymous | 0.0490 | 61 | 61.5 | 0.992 | 0.00000366 | 506 |
| Loss of Function | -1.02 | 11 | 7.92 | 1.39 | 4.21e-7 | 91 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00037 | 0.00037 | rare |
| Latino/Admixed American | 0.00026 | 0.00026 | rare |
| Ashkenazi Jewish | 0.00050 | 0.00050 | rare |
| East Asian | 0.00038 | 0.00038 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000080 | 0.000079 | rare |
| South Asian | 0.000065 | 0.000065 | rare |
| Other | 0.00016 | 0.00016 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Important adipokine involved in the control of fat metabolism and insulin sensitivity, with direct anti-diabetic, anti-atherogenic and anti-inflammatory activities. Stimulates AMPK phosphorylation and activation in the liver and the skeletal muscle, enhancing glucose utilization and fatty-acid combustion. Antagonizes TNF-alpha by negatively regulating its expression in various tissues such as liver and macrophages, and also by counteracting its effects. Inhibits endothelial NF-kappa-B signaling through a cAMP-dependent pathway. May play a role in cell growth, angiogenesis and tissue remodeling by binding and sequestering various growth factors with distinct binding affinities, depending on the type of complex, LMW, MMW or HMW. {ECO:0000269|PubMed:11479627}.;
- Disease
- DISEASE: Adiponectin deficiency (ADPND) [MIM:612556]: A condition that results in very low concentrations of plasma adiponectin. {ECO:0000269|PubMed:10918532}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Diabetes mellitus, non-insulin-dependent (NIDDM) [MIM:125853]: A multifactorial disorder of glucose homeostasis caused by a lack of sensitivity to the body's own insulin. Affected individuals usually have an obese body habitus and manifestations of a metabolic syndrome characterized by diabetes, insulin resistance, hypertension and hypertriglyceridemia. The disease results in long-term complications that affect the eyes, kidneys, nerves, and blood vessels. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.;
Recessive Scores
- pRec
- 0.836
Intolerance Scores
- LoFtool
- 0.200
- RVIS EVS
- 0.13
- RVIS percentile EVS
- 63.2
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.0434
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |