ADIPOQ

adiponectin, C1Q and collagen domain containing, the group of C1q and TNF related

Basic information

Region (hg38): 3:186842703-186858463

Previous symbols: [ "ACDC" ]

Links

ENSG00000181092 ∙ NCBI:9370 ∙ OMIM:605441 ∙ HGNC:13633 ∙ Uniprot:Q15848 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• STAT3-related early-onset multisystem autoimmune disease (Limited), mode of inheritance: Unknown

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Adiponectin deficiency	AD	Endocrine; Renal	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	Endocrine; Renal	10918532; 35869090

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ADIPOQ gene.

• not provided (8 variants)
• Inborn genetic diseases (3 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ADIPOQ gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				1		1
missense			4	2	1	7
nonsense			1			1
start loss						0
frameshift			1			1
inframe indel				1		1
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	6	4	1

Variants in ADIPOQ

This is a list of pathogenic ClinVar variants found in the ADIPOQ region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
3-186853079-TCTA-T			Likely benign (Dec 31, 2019)
3-186853097-GC-G			Uncertain significance (Oct 06, 2017)
3-186853103-T-G		ADIPOQ-related disorder	Benign (Oct 30, 2019)
3-186853171-G-A			Benign (Jan 03, 2019)
3-186853191-G-C			Uncertain significance (May 24, 2021)
3-186853249-A-G			Uncertain significance (Sep 19, 2017)
3-186854218-C-T			Likely benign (Jan 04, 2018)
3-186854226-C-T		not specified	Uncertain significance (Mar 22, 2023)
3-186854237-G-A		ADIPOQ-related disorder	Likely benign (Jan 21, 2022)
3-186854241-CCCGAGGCTTT-C		Adiponectin deficiency	Pathogenic (May 11, 2023)
3-186854242-C-A		ADIPOQ-related disorder	Likely benign (Feb 28, 2019)
3-186854253-C-T		not specified	Uncertain significance (Feb 28, 2024)
3-186854257-A-T		ADIPOQ-related disorder	Likely benign (Mar 31, 2022)
3-186854282-G-A		not specified	Uncertain significance (Dec 16, 2023)
3-186854300-T-C		ADIPOQ-related disorder	Benign (Sep 24, 2019)
3-186854303-C-T		Adiponectin deficiency	Pathogenic (Oct 10, 2003)
3-186854316-G-A		not specified	Uncertain significance (Mar 01, 2024)
3-186854627-G-T			Uncertain significance (Jun 01, 2023)
3-186854631-G-A		not specified	Likely benign (Jun 23, 2021)
3-186854700-A-T		not specified	Uncertain significance (May 25, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ADIPOQ	protein_coding	protein_coding	ENST00000412955	2	15790

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
4.64e-9	0.0324	125709	0	39	125748	0.000155

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.131	149	145	1.03	0.00000797	1577
Missense in 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

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000632	0.000629
Ashkenazi Jewish	0.000498	0.000496
East Asian	0.000382	0.000381
Finnish	0.00	0.00
European (Non-Finnish)	0.0000797	0.0000791
Middle Eastern	0.000382	0.000381
South Asian	0.0000654	0.0000653
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• 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.
• Pathway: 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);PPAR signaling pathway - Homo sapiens (human);AMP-activated Protein Kinase (AMPK) Signaling;Type II diabetes mellitus;Transcriptional regulation of white adipocyte differentiation;Adipogenesis;Human Complement System;Differentiation of white and brown adipocyte;Transcription factor regulation in adipogenesis;Leptin and adiponectin;PPAR signaling pathway;visceral fat deposits and the metabolic syndrome;AMPK inhibits chREBP transcriptional activation activity;Metabolism;Integration of energy metabolism (Consensus)

Recessive Scores

• pRec: 0.836

Intolerance Scores

• loftool: 0.200
• rvis_EVS: 0.13
• rvis_percentile_EVS: 63.2

Haploinsufficiency Scores

• pHI: 0.163
• hipred: N
• hipred_score: 0.251
• ghis: 0.434

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.0434

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Adipoq
• Phenotype: nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); skeleton phenotype; renal/urinary system phenotype; immune system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); liver/biliary system phenotype; respiratory system phenotype; neoplasm; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); growth/size/body region phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); hematopoietic system phenotype; muscle phenotype; cellular phenotype; homeostasis/metabolism phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); endocrine/exocrine gland phenotype

Gene ontology

• Biological process: response to hypoxia;positive regulation of protein phosphorylation;glucose metabolic process;generation of precursor metabolites and energy;fatty acid beta-oxidation;response to nutrient;circadian rhythm;response to bacterium;response to sucrose;response to glucose;positive regulation of signal transduction;regulation of signaling receptor activity;negative regulation of platelet-derived growth factor receptor signaling pathway;positive regulation of protein kinase A signaling;negative regulation of macrophage derived foam cell differentiation;negative regulation of tumor necrosis factor-mediated signaling pathway;positive regulation of cholesterol efflux;regulation of glucose metabolic process;response to activity;fatty acid oxidation;negative regulation of cell migration;negative regulation of granulocyte differentiation;negative regulation of protein autophosphorylation;positive regulation of cellular protein metabolic process;negative regulation of tumor necrosis factor production;positive regulation of interleukin-8 production;cellular response to insulin stimulus;positive regulation of myeloid cell apoptotic process;negative regulation of heterotypic cell-cell adhesion;low-density lipoprotein particle clearance;response to tumor necrosis factor;cellular response to drug;regulation of fatty acid biosynthetic process;glucose homeostasis;positive regulation of I-kappaB kinase/NF-kappaB signaling;negative regulation of I-kappaB kinase/NF-kappaB signaling;negative regulation of MAP kinase activity;response to ethanol;negative regulation of fat cell differentiation;negative regulation of macrophage differentiation;negative regulation of low-density lipoprotein particle receptor biosynthetic process;negative regulation of gluconeogenesis;negative regulation of blood pressure;negative regulation of transcription, DNA-templated;positive regulation of fatty acid metabolic process;positive regulation of glucose import;negative regulation of hormone secretion;negative regulation of inflammatory response;positive regulation of peptidyl-tyrosine phosphorylation;negative regulation of phagocytosis;negative regulation of synaptic transmission;brown fat cell differentiation;protein homooligomerization;response to glucocorticoid;protein heterotrimerization;negative regulation of ERK1 and ERK2 cascade;response to linoleic acid;detection of oxidative stress;cellular response to cAMP;positive regulation of monocyte chemotactic protein-1 production;cellular response to epinephrine stimulus;protein localization to plasma membrane;negative regulation of intracellular protein transport;positive regulation of cold-induced thermogenesis;negative regulation of cold-induced thermogenesis;negative regulation of receptor binding;negative regulation of vascular smooth muscle cell proliferation;negative regulation of vascular associated smooth muscle cell migration;negative regulation of DNA biosynthetic process;positive regulation of glycogen (starch) synthase activity;positive regulation of metanephric glomerular visceral epithelial cell development;positive regulation of cAMP-dependent protein kinase activity;positive regulation of renal albumin absorption;negative regulation of platelet-derived growth factor receptor-alpha signaling pathway;negative regulation of metanephric mesenchymal cell migration
• Cellular component: extracellular region;collagen trimer;extracellular space;endoplasmic reticulum;cell surface;collagen-containing extracellular matrix
• Molecular function: signaling receptor binding;cytokine activity;hormone activity;extracellular matrix structural constituent;protein binding;sialic acid binding;identical protein binding;protein homodimerization activity