ADIPOQ

Summary

ADIPOQ (adiponectin, C1Q and collagen domain containing, HGNC:13633) is a protein-coding gene on chromosome 3q27.3, encoding Adiponectin (Q15848). Important adipokine involved in the control of fat metabolism and insulin sensitivity, with direct anti-diabetic, anti-atherogenic and anti-inflammatory activities.

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.

Source: NCBI Gene 9370 — RefSeq curated summary.

At a glance

• Gene–disease (curated): STAT3-related early-onset multisystem autoimmune disease (Limited, GenCC)
• GWAS associations: 15
• Clinical variants (ClinVar): 47 total — 8 pathogenic, 1 likely-pathogenic
• Phenotypes (HPO): 6
• MANE Select transcript: NM_004797

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:13633
Approved symbol	ADIPOQ
Name	adiponectin, C1Q and collagen domain containing
Location	3q27.3
Locus type	gene with protein product
Status	Approved
Aliases	ACRP30, apM1, GBP28, adiponectin
Ensembl gene	ENSG00000181092
Ensembl biotype	protein_coding
OMIM	605441
Entrez	9370

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 4 protein_coding

ENST00000320741, ENST00000444204, ENST00000881747, ENST00000956685

RefSeq mRNA: 2 — MANE Select: NM_004797 NM_001177800, NM_004797

CCDS: CCDS3284

Canonical transcript exons

ENST00000320741 — 3 exons

Exon	Start	End
ENSE00001222280	186853051	186853272
ENSE00001376216	186842710	186842749
ENSE00001765971	186854184	186858463

Expression profiles

Bgee: expression breadth ubiquitous, 171 present calls, max score 99.14.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 39.6633 / max 5144.0059, expressed in 124 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
40316	36.5216	120
40315	3.0320	77
40317	0.1097	36

Top tissues by expression

279 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
synovial joint	UBERON:0002217	99.14	gold quality
pericardium	UBERON:0002407	98.61	gold quality
skin of hip	UBERON:0001554	97.78	gold quality
adipose tissue	UBERON:0001013	97.76	gold quality
subcutaneous adipose tissue	UBERON:0002190	97.67	gold quality
adipose tissue of abdominal region	UBERON:0007808	96.68	gold quality
omental fat pad	UBERON:0010414	96.51	gold quality
peritoneum	UBERON:0002358	96.36	gold quality
connective tissue	UBERON:0002384	95.91	gold quality
parotid gland	UBERON:0001831	95.47	gold quality
mammary duct	UBERON:0001765	94.99	gold quality
thoracic mammary gland	UBERON:0005200	93.56	gold quality
mammary gland	UBERON:0001911	93.30	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	91.47	gold quality
epithelium of mammary gland	UBERON:0003244	91.40	gold quality
vena cava	UBERON:0004087	90.74	gold quality
superficial temporal artery	UBERON:0001614	86.35	gold quality
layer of synovial tissue	UBERON:0007616	84.71	gold quality
cardiac muscle of right atrium	UBERON:0003379	82.47	gold quality
trabecular bone tissue	UBERON:0002483	80.66	gold quality
cranial nerve II	UBERON:0000941	80.07	gold quality
parietal pleura	UBERON:0002400	79.41	gold quality
deltoid	UBERON:0001476	79.24	gold quality
left coronary artery	UBERON:0001626	78.16	gold quality
coronary artery	UBERON:0001621	78.14	gold quality
hindlimb stylopod muscle	UBERON:0004252	76.37	gold quality
tibial nerve	UBERON:0001323	76.11	gold quality
gall bladder	UBERON:0002110	76.11	gold quality
saliva-secreting gland	UBERON:0001044	75.61	gold quality
body of tongue	UBERON:0011876	75.33	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	4.44

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

1 targets.

Target	Regulation
NOX4	Repression

Upstream regulators (CollecTRI, top): ATF1, ATF3, CEBPA, CEBPB, CEBPD, CEBPG, CNBP, CREB1, DDIT3, ESR1, ESR2, ETS2, FOXC1, FOXO1, HIF1A, ID3, IRF6, LRP3, MAF, MYB, NCOA1, NCOA2, NFATC4, NFYA, NR0B2, NR3C2, NR5A2, NRF1, PITX2, PPARA, PPARG, PREB, SH3PXD2B, SNAI1, SP1, SP3, SREBF1, STAT3, TCF3, TFAP2A

miRNA regulators (miRDB)

155 targeting ADIPOQ, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-12118	100.00	65.88	1270
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-3134	100.00	66.43	777
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-4534	99.99	66.58	1907
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-6891-5P	99.98	66.53	1372
HSA-MIR-3173-3P	99.98	66.49	1217
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-548AT-5P	99.96	70.83	2666
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-559	99.95	72.28	3609

Literature-anchored findings (GeneRIF, showing 40)

• regulation of apM1 gene expression in adipose tissue (PMID:11700024)
• Genetic variation in the gene encoding adiponectin is associated with an increased risk of type 2 diabetes in the Japanese population. (PMID:11812766)
• Haplotype is associated with obesity and other features of the insulin resistance syndrome (PMID:12086965)
• mutation is associated with low plasma adiponectin concentration and type 2 diabetes. (PMID:12086969)
• inverse correlation found between adiponectin and leptin with serum leptin concentrations increased in women with high body mass index (PMID:12153737)
• identification of regulatory elements in this gene’s promoter: role of SP1/SP3 and TNF-alpha as regulatory pathways (PMID:12378384)
• dysregulation of adiponectin gene expression in first degree relatives of type 2 diabetic patients (PMID:12388136)
• in overweight/obese Asians, the plasma adiponectin levels significantly correlated with various indices of metabolic syndrome except hypertension (PMID:12429873)
• an association between adiponectin and the metabolic and cardiovascular complications of obesity (PMID:12436346)
• Adiponectin and leptin levels in HIV-infected subjects with insulin resistance and body fat redistribution (PMID:12473840)
• Structure-function studies of the adipocyte-secreted hormone Acrp30/adiponectin show a profound sexual dimorphism of Acrp30 levels and complex distribution in serum (PMID:12496257)
• significant negative correlation was found between plasma adiponectin concentration and mean, systolic, and diastolic BP, suggesting that adiponectin contributes to the clinical course of essential hypertension. (PMID:12517687)
• Plasma levels predict insulin sensitivity of both glucose and lipid metabolism. (PMID:12540592)
• Increased plasma adiponectin and decreased plasma TNF-alpha may underlie the improvement of insulin resistance with glimepiride. (PMID:12547850)
• data suggest that both adiponectin and leptin are associated with central body fat distribution, and serum adiponectin concentrations are determined predominantly by the visceral fat compartment (PMID:12634431)
• presented findings indicate that adiponectin promotes lipid oxidation in humans resulting in lower intracellular lipid content in human muscle (PMID:12660875)
• adipose tissue depot-specific expression of adiponectin may influence the pattern of serum adiponectin concentrations and subsequent disease risk (PMID:12660876)
• a significant decrease of adiponectin plasma levels during the steady state of hyperinsulinemic euglycemic clamp was found. Hyperinsulinemia caused a significant decrease of adiponectin plasma levels under euglycemic conditions (PMID:12660877)
• study provides further evidence that IL-6, leptin, and adiponectin are associated with impaired fibrinolysis in overweight hypertensive humans (PMID:12660878)
• data suggest a transcriptional mechanism leading to decreased adiponectin plasma levels in obese women and demonstrate that low levels of adiponectin are associated with higher levels of C-reactive protein and interleukin-6 (PMID:12663465)
• data suggest a strong relationship between adiponectin and body composition in HIV-infected patients (PMID:12679439)
• preoperative adiponectin concentrations may be predictive of the extent of weight loss and changes in adiponectin are predictive of decreased apolipoprotein B and improved insulin action after gastric bypass surgery (PMID:12679444)
• data suggest that the reduction of fat mass may play the major role in the control of adiponectin release, with respect to changes in insulin sensitivity (PMID:12679468)
• data suggest that the decreased production of adiponectin in lipoatrophic adipose tissue may contribute to hepatic insulin resistance in HIV-positive HAART-treated patients (PMID:12679491)
• this adipocyte protein may serve to mitigate endothelial damage triggered by dyslipidemia and other risk factors in patients with chronic renal diseases. (PMID:12694320)
• Adiponectin levels were significantly lower in HIV-infected men with lipodystrophy as compared to both HIV-infected and healthy controls; adiponectin deficiency may play a role in the insulin resistance associated with HIV lipodystrophy (PMID:12713059)
• Circulating levels are reduced in nonobese but insulin-resistant first-degree relatives of type 2 diabetic patients. (PMID:12716750)
• plasma adiponectin levels are reduced in adolescent obesity and related to insulin resistance, independent of total body fat and central adiposity (PMID:12727947)
• Function in homeostatic control of glucose, lipid, and energy metabolism. Dysregulation may be involved in disorders covering metabolic X syndrome, such as insulin resistance, obesity, type 2 diabetes, and coronary artery disease. Review. (PMID:12728641)
• The inverse relationship between plasma adiponectin and cytokines in vivo and the cytokine-induced reduction in adiponectin mRNA in vitro suggests that endogenous cytokines may inhibit adiponectin. (PMID:12736161)
• body mass index was inversely correlated with the dose of G allele; expression levels of adiponectin affected insulin-stimulated glucose uptake in differentiated adipocytes (PMID:12750819)
• the potential effects of adiponectin on glucose uptake into adipose cells (PMID:12765944)
• marker of inflammation in Pima Indians at risk for NIDDM (PMID:12766104)
• I164T mutation is associated with hypoadiponectinemia through disturbed secretion into plasma, which may contribute to the development of the metabolic syndrome. (PMID:12788102)
• Adiponectin concentrations change according to variations of fat mass. Insulin sensitivity per se probably does not play pivotal role in control of adiponectin levels in PCOS women. (PMID:12788865)
• Circulating adiponectin differentially modulates insulin action and thyroid-axis, inflammatory cytokines, and the adrenal cortex might intervene in this modulation. (PMID:12788878)
• Serum adiponectin and soluble leptin receptor levels might be influenced by common regulatory factors and challenge the notion that cortisol may have a direct inhibitory effect on adiponectin in humans. Out-of-phase with leptin diurnal rhythms. (PMID:12788897)
• Exercise training-induced increase in insulin sensitivity is not dependent on increase in adiponectinemia in healthy men. (PMID:12803245)
• Adiponectin is a genetic factor associated with insulin sensitivity. Interactions with PPARgamma2 genotypes modified this association. (PMID:12827242)
• Adiponectin-containing supernatant consistently induced expression of adiponectin mRNA in human myotubes from eight different donors. (PMID:12827245)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	adipoqa	ENSDARG00000062228
danio_rerio	adipoqb	ENSDARG00000100086
mus_musculus	Adipoq	ENSMUSG00000022878
rattus_norvegicus	Adipoq	ENSRNOG00000001821

Paralogs (23): C1QTNF3 (ENSG00000082196), COL19A1 (ENSG00000082293), PDCD7 (ENSG00000090470), COL10A1 (ENSG00000123500), C1QL1 (ENSG00000131094), C1QTNF6 (ENSG00000133466), C1QL2 (ENSG00000144119), COL8A1 (ENSG00000144810), C1QTNF2 (ENSG00000145861), C1QC (ENSG00000159189), C1QTNF7 (ENSG00000163145), C1QL3 (ENSG00000165985), COL8A2 (ENSG00000171812), C1QTNF4 (ENSG00000172247), C1QB (ENSG00000173369), C1QA (ENSG00000173372), C1QTNF1 (ENSG00000173918), OTOL1 (ENSG00000182447), C1QTNF8 (ENSG00000184471), C1QL4 (ENSG00000186897), C1QTNF9B (ENSG00000205863), C1QTNF5 (ENSG00000223953), C1QTNF9 (ENSG00000240654)

Protein

Protein identifiers

Adiponectin — Q15848 (reviewed: Q15848)

Alternative names: 30 kDa adipocyte complement-related protein, Adipocyte complement-related 30 kDa protein, Adipocyte, C1q and collagen domain-containing protein, Adipose most abundant gene transcript 1 protein, Gelatin-binding protein

All UniProt accessions (2): A8K660, Q15848

UniProt curated annotations — full annotation on UniProt →

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 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.

Subunit / interactions. Homomultimer. Forms trimers, hexamers and 12- to 18-mers. The trimers (low molecular weight complexes / LMW) are assembled via non-covalent interactions of the collagen-like domains in a triple helix and hydrophobic interactions within the globular C1q domain. Several trimers can associate to form disulfide-linked hexamers (middle molecular weight complexes / MMW) and larger complexes (higher molecular weight / HMW). The HMW-complex assembly is also modulated by the degree of lysine hydroxylation and glycosylation. LMW, MMW and HMW complexes bind to HBEGF, MMW and HMW complexes bind to PDGFB, and HMW complex binds to FGF2. Interacts with CTRP9 via the C1q domain (heterotrimeric complex).

Subcellular location. Secreted.

Tissue specificity. Synthesized exclusively by adipocytes and secreted into plasma.

Post-translational modifications. HMW complexes are more extensively glycosylated than smaller oligomers. Hydroxylation and glycosylation of the lysine residues within the collagen-like domain of adiponectin seem to be critically involved in regulating the formation and/or secretion of HMW complexes and consequently contribute to the insulin-sensitizing activity of adiponectin in hepatocytes. O-glycosylated. Not N-glycosylated. O-linked glycans on hydroxylysines consist of Glc-Gal disaccharides bound to the oxygen atom of post-translationally added hydroxyl groups. Sialylated to varying degrees depending on tissue. Thr-22 appears to be the major site of sialylation. Higher sialylation found in SGBS adipocytes than in HEK fibroblasts. Sialylation is not required neither for heterodimerization nor for secretion. Not sialylated on the glycosylated hydroxylysines. Desialylated forms are rapidly cleared from the circulation. Succination of Cys-36 by the Krebs cycle intermediate fumarate, which leads to S-(2-succinyl)cysteine residues, inhibits polymerization and secretion of adiponectin. Adiponectin is a major target for succination in both adipocytes and adipose tissue of diabetic mammals. It was proposed that succination of proteins is a biomarker of mitochondrial stress and accumulation of Krebs cycle intermediates in adipose tissue in diabetes and that succination of adiponectin may contribute to the decrease in plasma adiponectin in diabetes.

Disease relevance. Adiponectin deficiency (ADPOD) [MIM:612556] An autosomal dominant condition characterized by very low concentrations of plasma adiponectin. Levels of adiponectin are decreased in obesity and may contribute to a chronic state of inflammation that leads to insulin resistance, type 2 diabetes, coronary artery disease, myocardial infarction, non-alcoholic steatohepatitis, and kidney disease. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. Polymerization and secretion of adiponectin is inhibited by succination of cysteine residues by the Krebs cycle intermediate fumarate, which leads to S-(2-succinyl)cysteine residues.

Domain organisation. The C1q domain is commonly called the globular domain.

Polymorphism. Genetic variations in ADIPOQ influence the variance in adiponectin serum levels and define the adiponectin serum levels quantitative trait locus 1 (ADIPQTL1) [MIM:612556].

Miscellaneous. Variants Arg-84 and Ser-90 show impaired formation of HMW complexes whereas variants Cys-112 and Thr-164 show impaired secretion of adiponectin in any form. HMW-complex blood contents are higher in females than in males, are increased in males by castration and decreased again upon subsequent testosterone treatment, which blocks HMW-complex secretion. In type 2 diabetic patients, both the ratios of HMW to total adiponectin and the degree of adiponectin glycosylation are significantly decreased as compared with healthy controls.

RefSeq proteins (2): NP_001171271, NP_004788* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001073	C1q_dom	Domain
IPR008160	Collagen	Repeat
IPR008983	Tumour_necrosis_fac-like_dom	Homologous_superfamily
IPR050392	Collagen/C1q_domain	Family

Pfam: PF00386, PF01391

UniProt features (58 total): modified residue 13, strand 10, mutagenesis site 9, sequence variant 8, glycosylation site 6, site 4, domain 2, signal peptide 1, chain 1, disulfide bond 1, region of interest 1, compositionally biased region 1, turn 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
6U66	X-RAY DIFFRACTION	0.99
4DOU	X-RAY DIFFRACTION	2
6U6N	X-RAY DIFFRACTION	2.15

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q15848-F1	81.34	0.55

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (4): 62 (not hydroxylated); 86 (not hydroxylated); 104 (not hydroxylated); 230 (not glycosylated)

Post-translational modifications (13): 33, 36, 44, 47, 53, 65, 68, 71, 76, 77, 91, 95, 101

Disulfide bonds (1): 36

Glycosylation sites (6): 21, 22, 65, 68, 77, 101

Mutagenesis-validated functional residues (9):

Position	Phenotype
20	no change in sialylated isoforms.
21	some loss of sialylated isoforms.
22	abolishes sialylated isoforms.
33	no effect on formation of hmw multimers.
36	impaired formation of mmw and hmw multimers.
65	impaired formation of hmw multimers; when associated with r-68.
68	impaired formation of hmw multimers; when associated with r-65.
77	impaired formation of hmw multimers; when associated with r-101.
101	impaired formation of hmw multimers; when associated with r-77.

Function

Pathways and Gene Ontology

Reactome pathways

12 pathways

ID	Pathway
R-HSA-163680	AMPK inhibits chREBP transcriptional activation activity
R-HSA-381340	Transcriptional regulation of white adipocyte differentiation
R-HSA-9841922	MLL4 and MLL3 complexes regulate expression of PPARG target genes in adipogenesis and hepatic steatosis
R-HSA-1266738	Developmental Biology
R-HSA-1430728	Metabolism
R-HSA-163685	Integration of energy metabolism
R-HSA-212165	Epigenetic regulation of gene expression
R-HSA-74160	Gene expression (Transcription)
R-HSA-9818564	Epigenetic regulation of gene expression by MLL3 and MLL4 complexes
R-HSA-9843745	Adipogenesis
R-HSA-9851695	Epigenetic regulation of adipogenesis genes by MLL3 and MLL4 complexes
R-HSA-9917777	Epigenetic regulation by WDR5-containing histone modifying complexes

MSigDB gene sets: 486 (showing top): GOBP_MYELOID_CELL_DIFFERENTIATION, GOBP_CIRCADIAN_RHYTHM, GOBP_PLATELET_DERIVED_GROWTH_FACTOR_RECEPTOR_SIGNALING_PATHWAY, REACTOME_TRANSCRIPTIONAL_REGULATION_OF_WHITE_ADIPOCYTE_DIFFERENTIATION, GOBP_LIPID_MODIFICATION, GOBP_NEGATIVE_REGULATION_OF_MAP_KINASE_ACTIVITY, GOBP_NEGATIVE_REGULATION_OF_ERK1_AND_ERK2_CASCADE, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_RESPONSE_TO_ETHANOL, GOBP_FATTY_ACID_CATABOLIC_PROCESS, GOBP_CARBOHYDRATE_TRANSPORT, GOBP_REGULATION_OF_FAT_CELL_DIFFERENTIATION, GOBP_NEGATIVE_REGULATION_OF_CELL_DEVELOPMENT, KEGG_ADIPOCYTOKINE_SIGNALING_PATHWAY, GOBP_REGULATION_OF_BLOOD_PRESSURE

GO Biological Process (75): response to hypoxia (GO:0001666), glucose metabolic process (GO:0006006), generation of precursor metabolites and energy (GO:0006091), fatty acid beta-oxidation (GO:0006635), response to nutrient (GO:0007584), circadian rhythm (GO:0007623), response to bacterium (GO:0009617), response to sucrose (GO:0009744), response to glucose (GO:0009749), positive regulation of signal transduction (GO:0009967), gene expression (GO:0010467), negative regulation of platelet-derived growth factor receptor signaling pathway (GO:0010642), negative regulation of macrophage derived foam cell differentiation (GO:0010745), negative regulation of tumor necrosis factor-mediated signaling pathway (GO:0010804), positive regulation of cholesterol efflux (GO:0010875), regulation of glucose metabolic process (GO:0010906), response to activity (GO:0014823), fatty acid oxidation (GO:0019395), negative regulation of cell migration (GO:0030336), negative regulation of granulocyte differentiation (GO:0030853), negative regulation of tumor necrosis factor production (GO:0032720), positive regulation of interleukin-8 production (GO:0032757), cellular response to insulin stimulus (GO:0032869), positive regulation of myeloid cell apoptotic process (GO:0033034), adiponectin-activated signaling pathway (GO:0033211), negative regulation of heterotypic cell-cell adhesion (GO:0034115), low-density lipoprotein particle clearance (GO:0034383), response to tumor necrosis factor (GO:0034612), glucose homeostasis (GO:0042593), positive regulation of canonical NF-kappaB signal transduction (GO:0043123), negative regulation of canonical NF-kappaB signal transduction (GO:0043124), negative regulation of MAP kinase activity (GO:0043407), response to ethanol (GO:0045471), negative regulation of fat cell differentiation (GO:0045599), negative regulation of macrophage differentiation (GO:0045650), negative regulation of gluconeogenesis (GO:0045721), negative regulation of blood pressure (GO:0045776), negative regulation of DNA-templated transcription (GO:0045892), positive regulation of fatty acid metabolic process (GO:0045923), positive regulation of D-glucose import across plasma membrane (GO:0046326)

GO Molecular Function (9): signaling receptor binding (GO:0005102), cytokine activity (GO:0005125), hormone activity (GO:0005179), sialic acid binding (GO:0033691), protein homodimerization activity (GO:0042803), protein serine/threonine kinase activator activity (GO:0043539), extracellular matrix structural constituent (GO:0005201), protein binding (GO:0005515), identical protein binding (GO:0042802)

GO Cellular Component (7): extracellular region (GO:0005576), collagen trimer (GO:0005581), obsolete extracellular space (GO:0005615), endoplasmic reticulum (GO:0005783), cell surface (GO:0009986), extracellular matrix (GO:0031012), protein-containing complex (GO:0032991)

Reactome top-level categories

Rollup of top-9 pathways:

Category	Pathways
Integration of energy metabolism	1
Adipogenesis	1
Epigenetic regulation of adipogenesis genes by MLL3 and MLL4 complexes	1
Metabolism	1
Gene expression (Transcription)	1
Epigenetic regulation by WDR5-containing histone modifying complexes	1
Developmental Biology	1
Epigenetic regulation of gene expression by MLL3 and MLL4 complexes	1
Epigenetic regulation of gene expression	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein binding	2
receptor ligand activity	2
cellular anatomical structure	2
response to stress	1
response to decreased oxygen levels	1
hexose metabolic process	1
metabolic process	1
fatty acid catabolic process	1
fatty acid ligase activity	1
fatty acid oxidation	1
response to nutrient levels	1
response to chemical	1
rhythmic process	1
response to other organism	1
response to disaccharide	1
response to hexose	1
signal transduction	1
regulation of signal transduction	1
positive regulation of cell communication	1
positive regulation of signaling	1
positive regulation of response to stimulus	1
macromolecule biosynthetic process	1
negative regulation of signal transduction	1
regulation of platelet-derived growth factor receptor signaling pathway	1
platelet-derived growth factor receptor signaling pathway	1
macrophage derived foam cell differentiation	1
regulation of macrophage derived foam cell differentiation	1
negative regulation of cell differentiation	1
negative regulation of cytokine-mediated signaling pathway	1
regulation of tumor necrosis factor-mediated signaling pathway	1
tumor necrosis factor-mediated signaling pathway	1
regulation of cholesterol efflux	1
positive regulation of cholesterol transport	1
cholesterol efflux	1
glucose metabolic process	1
regulation of carbohydrate metabolic process	1
regulation of small molecule metabolic process	1
response to stimulus	1
fatty acid metabolic process	1
lipid oxidation	1

Protein interactions and networks

STRING

3508 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ADIPOQ	ADIPOR1	Q96A54	999
ADIPOQ	ADIPOR2	Q86V24	999
ADIPOQ	CDH13	P55290	996
ADIPOQ	LEP	P41159	983
ADIPOQ	INS	P01308	961
ADIPOQ	RETN	Q9HD89	949
ADIPOQ	PPARG	P37231	926
ADIPOQ	RETNLB	Q9BQ08	926
ADIPOQ	PPARA	Q07869	912
ADIPOQ	PPARGC1A	Q9UBK2	893
ADIPOQ	APPL1	Q9UKG1	893
ADIPOQ	IL6	P05231	890
ADIPOQ	CRP	P02741	882
ADIPOQ	SLC2A4	P14672	877
ADIPOQ	NAMPT	P43490	876

IntAct

203 interactions, top by confidence:

A	B	Type	Score
ADIPOQ	SGTA	psi-mi:“MI:0915”(physical association)	0.780
SGTA	ADIPOQ	psi-mi:“MI:0915”(physical association)	0.780
ADIPOQ	SYNE4	psi-mi:“MI:0915”(physical association)	0.720
ADIPOQ	BNIP3L	psi-mi:“MI:0915”(physical association)	0.560
ADIPOQ	KASH5	psi-mi:“MI:0915”(physical association)	0.560
ADIPOQ	NEMP1	psi-mi:“MI:0915”(physical association)	0.560
ADIPOQ	PVR	psi-mi:“MI:0915”(physical association)	0.560
ADIPOQ	FCGR1A	psi-mi:“MI:0915”(physical association)	0.560
ADIPOQ	BTNL9	psi-mi:“MI:0915”(physical association)	0.560
ADIPOQ	MRM1	psi-mi:“MI:0915”(physical association)	0.560
ADIPOQ	SCN3B	psi-mi:“MI:0915”(physical association)	0.560
ADIPOQ	CD79A	psi-mi:“MI:0915”(physical association)	0.560
ADIPOQ	SLC22A23	psi-mi:“MI:0915”(physical association)	0.560
ADIPOQ	MFF	psi-mi:“MI:0915”(physical association)	0.560
KEL	ADIPOQ	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (105): ADIPOQ (Two-hybrid), CCDC155 (Two-hybrid), SYNE4 (Two-hybrid), BNIP3L (Two-hybrid), CCDC155 (Two-hybrid), SGTA (Two-hybrid), SYNE4 (Two-hybrid), ADIPOQ (Two-hybrid), ADIPOQ (Two-hybrid), ADIPOQ (Two-hybrid), ADIPOQ (Two-hybrid), ADIPOQ (Two-hybrid), ADIPOQ (Two-hybrid), ADIPOQ (Two-hybrid), ADIPOQ (Two-hybrid)

ESM2 similar proteins: A0A060WQA3, A5PN28, A6NHN0, B2RNN3, P02745, P02746, P02747, P08125, P0C862, P12106, P14106, P20849, P23206, P23805, P31720, P31721, P31722, P35246, P35247, P35248, P42916, P50404, P83371, P98085, P98086, Q02105, Q05306, Q05722, Q0II24, Q0VF58, Q14993, Q15848, Q1PBC5, Q2KIV9, Q3Y5Z3, Q4ZJM7, Q4ZJN1, Q5E9E3, Q60994, Q641F3

Diamond homologs: A0A060WQA3, A5PN28, A6NHN0, B2RNN3, O75973, O88992, P02745, P02746, P08125, P0C862, P14106, P14282, P23206, P25067, P25318, P27658, P31720, P31721, P83371, P98085, P98086, Q00780, Q02105, Q03692, Q05306, Q05A80, Q06575, Q06576, Q06577, Q0II24, Q15848, Q2KIU3, Q2KIX7, Q3Y5Z3, Q4ZJM7, Q4ZJM9, Q4ZJN1, Q5E9E3, Q5FVH0, Q5RJ80

SIGNOR signaling

5 interactions.

A	Effect	B	Mechanism
ADIPOQ	up-regulates	ADIPOR2	binding
ADIPOQ	up-regulates	ADIPOR1	binding
TFAP2B	“down-regulates quantity by repression”	ADIPOQ	“transcriptional regulation”
COLGALT1	“up-regulates activity”	ADIPOQ	palmitoylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 62 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell	5	12.4×	5e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

47 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	8
Likely pathogenic	1
Uncertain significance	24
Likely benign	8
Benign	2

Top pathogenic / likely-pathogenic (9)

Variant ID	HGVS	Classification
148900	GRCh38/hg38 3q27.3-29(chr3:186765148-194409416)x1	Pathogenic
150107	GRCh38/hg38 3q27.2-27.3(chr3:184843627-187461008)x3	Pathogenic
2501708	NM_004797.4(ADIPOQ):c.276_285del (p.Gly93fs)	Pathogenic
253655	GRCh37/hg19 3q27.3-28(chr3:186291045-191037240)x1	Pathogenic
394816	GRCh37/hg19 3q27.2-27.3(chr3:185419048-186575415)x1	Pathogenic
4990	NM_004797.4(ADIPOQ):c.334C>T (p.Arg112Cys)	Pathogenic
523279	GRCh37/hg19 3q27.1-28(chr3:184300169-188285627)	Pathogenic
832891	NC_000003.11:g.(?186256465)(187009440_?)del	Pathogenic
1809046	GRCh37/hg19 3q27.1-28(chr3:184170962-188047867)x1	Likely pathogenic

SpliceAI

756 predictions. Top by Δscore:

Variant	Effect	Δscore
3:186842746:GAGG:G	donor_gain	0.9900
3:186842748:GG:G	donor_gain	0.9900
3:186842749:GG:G	donor_gain	0.9900
3:186854759:GCTT:G	donor_gain	0.9900
3:186842750:G:GG	donor_gain	0.9800
3:186842751:T:A	donor_loss	0.9800
3:186851103:CAG:C	acceptor_gain	0.9700
3:186851104:A:AG	acceptor_gain	0.9700
3:186851104:AGA:A	acceptor_gain	0.9700
3:186851105:G:GG	acceptor_gain	0.9700
3:186851105:GA:G	acceptor_gain	0.9700
3:186851105:GAG:G	acceptor_gain	0.9700
3:186851105:GAGGA:G	acceptor_gain	0.9700
3:186854179:CTTA:C	acceptor_loss	0.9700
3:186854181:TA:T	acceptor_loss	0.9700
3:186854183:G:GA	acceptor_loss	0.9700
3:186854540:G:GT	donor_gain	0.9600
3:186854776:G:GT	donor_gain	0.9500
3:186854182:A:AG	acceptor_gain	0.9400
3:186854183:G:GG	acceptor_gain	0.9400
3:186854621:G:GT	donor_gain	0.9400
3:186853048:CAGGG:C	acceptor_gain	0.9300
3:186854181:TAG:T	acceptor_gain	0.9300
3:186842745:AGAGG:A	donor_gain	0.9200
3:186842746:GAGGG:G	donor_gain	0.9200
3:186854585:G:GT	donor_gain	0.9200
3:186842747:AGG:A	donor_gain	0.9100
3:186842748:GGG:G	donor_gain	0.9100
3:186848754:A:AG	donor_gain	0.9100
3:186853578:T:G	acceptor_gain	0.9100

AlphaMissense

1583 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:186854312:T:C	F115L	0.997
3:186854314:C:A	F115L	0.997
3:186854314:C:G	F115L	0.997
3:186854315:A:C	S116R	0.997
3:186854317:T:A	S116R	0.997
3:186854317:T:G	S116R	0.997
3:186854363:T:C	F132L	0.997
3:186854365:T:A	F132L	0.997
3:186854365:T:G	F132L	0.997
3:186854418:T:C	F150S	0.997
3:186854313:T:C	F115S	0.996
3:186854364:T:C	F132S	0.996
3:186854417:T:C	F150L	0.996
3:186854419:C:A	F150L	0.996
3:186854419:C:G	F150L	0.996
3:186854425:C:G	C152W	0.996
3:186854448:T:C	F160S	0.996
3:186854418:T:G	F150C	0.995
3:186854441:T:G	Y158D	0.995
3:186854607:T:C	L213P	0.995
3:186854670:T:C	F234S	0.995
3:186854313:T:G	F115C	0.994
3:186854561:T:C	S198P	0.994
3:186854601:T:A	V211D	0.994
3:186854435:G:T	G156W	0.993
3:186854453:T:G	Y162D	0.993
3:186854607:T:A	L213H	0.993
3:186854663:T:C	S232P	0.993
3:186854669:T:C	F234L	0.993
3:186854671:C:A	F234L	0.993

dbSNP variants (sampled 300 via entrez): RS1000490867 (3:186842571 A>G), RS1000733570 (3:186842822 C>T), RS1000743263 (3:186843074 C>A), RS1000844554 (3:186854422 C>T), RS1001164255 (3:186854386 G>A), RS1001172647 (3:186858238 G>A), RS1001239850 (3:186858760 A>C,G), RS1001383146 (3:186848536 T>C), RS1001567876 (3:186840891 G>T), RS1001579869 (3:186845710 A>G), RS1001682500 (3:186852709 A>G), RS1001947670 (3:186842428 T>C), RS1002025046 (3:186853467 T>C,G), RS1002105522 (3:186848055 C>T), RS1002233335 (3:186853812 G>A)

Disease associations

OMIM: gene MIM:605441 | disease phenotypes: MIM:257920

GenCC curated gene-disease

Disease	Classification	Inheritance
STAT3-related early-onset multisystem autoimmune disease	Limited	Unknown

Mondo (2): 3MC syndrome 1 (MONDO:0009770), STAT3-related early-onset multisystem autoimmune disease (MONDO:0014414)

Orphanet (2): 3MC syndrome (Orphanet:293843), Michels syndrome (Orphanet:2506)

HPO phenotypes

6 total (6 of 6 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0001677	Coronary artery atherosclerosis
HP:0003581	Adult onset
HP:0003774	Stage 5 chronic kidney disease
HP:0005978	Type II diabetes mellitus
HP:0030685	Decreased adiponectin level

GWAS associations

15 associations (top):

Study	Trait	p-value
GCST000319_1	Adiponectin levels	5.000000e-08
GCST000537_1	Adiponectin levels	1.000000e-41
GCST000538_1	Adiponectin levels	3.000000e-12
GCST000538_3	Adiponectin levels	9.000000e-19
GCST000812_1	Adiponectin levels	1.000000e-19
GCST001122_5	Adiponectin levels	4.000000e-08
GCST001463_2	Adiponectin levels	2.000000e-42
GCST001465_6	Adiponectin levels	5.000000e-44
GCST001574_6	Activated partial thromboplastin time	2.000000e-203
GCST002233_10	Adiponectin levels	7.000000e-07
GCST002233_5	Adiponectin levels	2.000000e-22
GCST002938_35	Copper levels	7.000000e-06
GCST003095_1	Adiponectin levels (BMI-adjusted)	4.000000e-07
GCST003096_2	Adiponectin levels	8.000000e-06
GCST004289_1	Adiponectin levels in pregnancy	9.000000e-06

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004502	adiponectin measurement
EFO:0007737	BMI-adjusted adiponectin measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

PharmGKB clinical annotations

1 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs2241766	Efficacy	3	pioglitazone	Diabetes Mellitus

PharmGKB variants

23 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs182052	ADIPOQ		0.00	0
rs266729	ADIPOQ		0.00	0
rs822391	ADIPOQ		0.00	0
rs822393	ADIPOQ		0.00	0
rs822396	ADIPOQ		0.00	0
rs1063537	ADIPOQ		0.00	0
rs1063538	ADIPOQ		0.00	0
rs1063539	ADIPOQ		0.00	0
rs1501299	ADIPOQ		0.00	0
rs1656930	ADIPOQ		0.00	0
rs2036373	ADIPOQ		0.00	0
rs2082940	ADIPOQ		0.00	0
rs2241766	ADIPOQ	3	2.75	1	pioglitazone
rs2241767	ADIPOQ		0.00	0
rs3774261	ADIPOQ		0.00	0
rs3821799	ADIPOQ		0.00	0
rs6773957	ADIPOQ		0.00	0
rs7627128	ADIPOQ		0.00	0
rs9882205	ADIPOQ		0.00	0
rs12495941	ADIPOQ		0.00	0
rs16861194	ADIPOQ		0.00	0
rs16861210	ADIPOQ		0.00	0
rs17300539	ADIPOQ		0.00	0

CTD chemical–gene interactions

146 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Rosiglitazone	decreases reaction, increases expression, increases secretion, affects response to substance, increases reaction (+1 more)	21
Dexamethasone	affects reaction, affects cotreatment, decreases reaction, increases expression, increases secretion (+1 more)	13
1-Methyl-3-isobutylxanthine	decreases reaction, increases expression, increases secretion, decreases expression, increases reaction (+2 more)	11
bisphenol A	affects cotreatment, increases reaction, increases secretion, decreases expression, decreases secretion (+1 more)	7
Diethylhexyl Phthalate	increases reaction, increases secretion, decreases secretion, decreases methylation, increases abundance (+3 more)	5
Niacin	affects binding, increases reaction, increases expression	5
sodium arsenite	increases abundance, affects cotreatment, affects reaction, decreases reaction, increases expression (+2 more)	4
Resveratrol	affects cotreatment, decreases expression, affects secretion, decreases reaction, increases expression	4
Pioglitazone	affects cotreatment, decreases reaction, increases reaction, increases secretion, increases expression	4
tributyltin	affects cotreatment, increases expression, increases reaction, increases secretion	3
3,4,5,3’,4’-pentachlorobiphenyl	decreases expression, decreases reaction, affects expression	3
butylbenzyl phthalate	affects cotreatment, increases expression, increases reaction, increases secretion	3
candesartan	affects cotreatment, increases expression, increases reaction, decreases expression	3
2-chloro-5-nitrobenzanilide	affects cotreatment, decreases reaction, increases expression, increases secretion, increases reaction	3
T 0070907	increases expression, decreases expression, affects cotreatment, affects reaction, increases reaction (+2 more)	3
Arsenic	affects response to substance, decreases expression, increases abundance, increases reaction	3
oxybenzone	increases expression, increases reaction, affects cotreatment	2
triphenyl phosphate	increases expression	2
mono-(2-ethylhexyl)phthalate	decreases methylation, increases abundance, increases expression	2
butylparaben	affects cotreatment, increases reaction, increases secretion, increases expression	2
avobenzone	affects cotreatment, increases expression, increases reaction, increases secretion, affects reaction	2
bisphenol S	increases expression	2
Troglitazone	increases expression	2
Benzbromarone	increases expression	2
Glucose	affects cotreatment, increases expression, increases reaction, increases secretion	2
Indomethacin	affects cotreatment, increases expression	2
Fenofibrate	affects cotreatment, increases expression, decreases expression, decreases reaction	2
Triclosan	decreases expression	2
Ramipril	increases expression, increases reaction, decreases expression	2
Amlodipine	increases expression	2

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.