ADCY3

adenylate cyclase 3, the group of Adenylate cyclases

Basic information

Region (hg38): 2:24819169-24920237

Links

ENSG00000138031 ∙ NCBI:109 ∙ OMIM:600291 ∙ HGNC:234 ∙ Uniprot:O60266 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• body mass index quantitative trait locus 19 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Obesity, susceptibility to, 19	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Endocrine	29311636; 29311637

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ADCY3 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ADCY3 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				79	11	90
missense			93	7	1	101
nonsense			1			1
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)		1				1
splice region			3	10	2	15
non coding			3	19	8	30
Total	0	1	97	105	20

Variants in ADCY3

This is a list of pathogenic ClinVar variants found in the ADCY3 region.

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

Position	Type	Phenotype	Significance	ClinVar
2-24819923-C-T		ADCY3-related disorder	Likely benign (Jan 27, 2020)
2-24819928-C-CCATTCAGGAGTTGTCCACCACCTGG		ADCY3-related disorder	Uncertain significance (Mar 22, 2024)
2-24819936-G-T		ADCY3-related disorder	Uncertain significance (Jan 31, 2024)
2-24819938-G-T		ADCY3-related disorder	Uncertain significance (May 10, 2024)
2-24819944-C-T		ADCY3-related disorder	Likely benign (Oct 25, 2019)
2-24819963-G-A		Inborn genetic diseases • ADCY3-related disorder	Uncertain significance (Oct 02, 2023)
2-24819967-C-T			Uncertain significance (Aug 17, 2021)
2-24819969-G-C		ADCY3-related disorder	Uncertain significance (Aug 27, 2024)
2-24819977-A-G		ADCY3-related disorder	Benign (May 26, 2021)
2-24820001-C-T		ADCY3-related disorder	Likely benign (Feb 13, 2023)
2-24820003-G-A		ADCY3-related disorder	Uncertain significance (Sep 03, 2024)
2-24820010-CAAG-C		BODY MASS INDEX QUANTITATIVE TRAIT LOCUS 19 • ADCY3-related disorder	Uncertain significance; risk factor (Dec 30, 2023)
2-24820015-A-C		Inborn genetic diseases	Uncertain significance (Jan 08, 2024)
2-24820030-C-CCCCCTT		ADCY3-related disorder	Uncertain significance (Apr 16, 2024)
2-24820032-C-G		ADCY3-related disorder	Uncertain significance (Oct 29, 2023)
2-24820036-TCC-T		ADCY3-related disorder	Uncertain significance (Aug 23, 2024)
2-24820051-TG-T		BODY MASS INDEX QUANTITATIVE TRAIT LOCUS 19	risk factor (Feb 26, 2018)
2-24820060-G-A		ADCY3-related disorder	Uncertain significance (Mar 28, 2024)
2-24820060-G-T		ADCY3-related disorder	Likely benign (May 05, 2021)
2-24820061-C-T		ADCY3-related disorder	Likely benign (Mar 18, 2022)
2-24820064-C-T		ADCY3-related disorder	Likely benign (Apr 06, 2021)
2-24820071-C-T		ADCY3-related disorder	Uncertain significance (Aug 19, 2024)
2-24820078-C-T		Inborn genetic diseases • ADCY3-related disorder	Uncertain significance (Mar 25, 2022)
2-24820109-T-C		ADCY3-related disorder	Likely benign (Oct 24, 2023)
2-24820122-G-A		ADCY3-related disorder	Likely benign (Nov 01, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ADCY3	protein_coding	protein_coding	ENST00000260600	21	100671

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.95e-11	1.00	125703	0	45	125748	0.000179

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.57	541	738	0.733	0.0000483	7508
Missense in Polyphen		152	287.6	0.52852		2936
Synonymous	-0.938	334	313	1.07	0.0000219	2275
Loss of Function	3.47	27	54.7	0.494	0.00000293	585

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000583	0.000578
Ashkenazi Jewish	0.00	0.00
East Asian	0.000272	0.000272
Finnish	0.00	0.00
European (Non-Finnish)	0.000190	0.000185
Middle Eastern	0.000272	0.000272
South Asian	0.000198	0.000196
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Catalyzes the formation of the signaling molecule cAMP in response to G-protein signaling. Participates in signaling cascades triggered by odorant receptors via its function in cAMP biosynthesis. Required for the perception of odorants. Required for normal sperm motility and normal male fertility. Plays a role in regulating insulin levels and body fat accumulation in response to a high fat diet. {ECO:0000250|UniProtKB:Q8VHH7}.
• Disease: DISEASE: Obesity (OBESITY) [MIM:601665]: A condition characterized by an increase of body weight beyond the limitation of skeletal and physical requirements, as the result of excessive accumulation of body fat. {ECO:0000269|PubMed:29311636, ECO:0000269|PubMed:29311637}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.
• Pathway: Inflammatory mediator regulation of TRP channels - Homo sapiens (human);Platelet activation - Homo sapiens (human);Cortisol synthesis and secretion - Homo sapiens (human);Relaxin signaling pathway - Homo sapiens (human);Aldosterone synthesis and secretion - Homo sapiens (human);Regulation of lipolysis in adipocytes - Homo sapiens (human);Oxytocin signaling pathway - Homo sapiens (human);Retrograde endocannabinoid signaling - Homo sapiens (human);GABAergic synapse - Homo sapiens (human);Glutamatergic synapse - Homo sapiens (human);Cushing,s syndrome - Homo sapiens (human);Oocyte meiosis - Homo sapiens (human);Dilated cardiomyopathy (DCM) - Homo sapiens (human);Thyroid hormone synthesis - Homo sapiens (human);Longevity regulating pathway - multiple species - Homo sapiens (human);GnRH signaling pathway - Homo sapiens (human);Bile secretion - Homo sapiens (human);Vasopressin-regulated water reabsorption - Homo sapiens (human);Gap junction - Homo sapiens (human);Gastric acid secretion - Homo sapiens (human);Chemokine signaling pathway - Homo sapiens (human);HTLV-I infection - Homo sapiens (human);Circadian entrainment - Homo sapiens (human);Thermogenesis - Homo sapiens (human);Adrenergic signaling in cardiomyocytes - Homo sapiens (human);Longevity regulating pathway - Homo sapiens (human);Calcium signaling pathway - Homo sapiens (human);cAMP signaling pathway - Homo sapiens (human);Apelin signaling pathway - Homo sapiens (human);Estrogen signaling pathway - Homo sapiens (human);Vascular smooth muscle contraction - Homo sapiens (human);Vibrio cholerae infection - Homo sapiens (human);Rap1 signaling pathway - Homo sapiens (human);Salivary secretion - Homo sapiens (human);Pancreatic secretion - Homo sapiens (human);Phospholipase D signaling pathway - Homo sapiens (human);Purine metabolism - Homo sapiens (human);Pathways in cancer - Homo sapiens (human);cGMP-PKG signaling pathway - Homo sapiens (human);Cholinergic synapse - Homo sapiens (human);Olfactory transduction - Homo sapiens (human);Morphine addiction - Homo sapiens (human);Ovarian steroidogenesis - Homo sapiens (human);Insulin secretion - Homo sapiens (human);Melanogenesis - Homo sapiens (human);Progesterone-mediated oocyte maturation - Homo sapiens (human);Proton Pump Inhibitor Pathway, Pharmacodynamics;Platelet Aggregation Inhibitor Pathway, Pharmacodynamics;Beta-agonist/Beta-blocker Pathway, Pharmacodynamics;Human Thyroid Stimulating Hormone (TSH) signaling pathway;Myometrial Relaxation and Contraction Pathways;G Protein Signaling Pathways;Chemokine signaling pathway;Phosphodiesterases in neuronal function;Calcium Regulation in the Cardiac Cell;Signaling by GPCR;Signal Transduction;Glucagon signaling in metabolic regulation;GPCR Adenosine A2A receptor;GPCR signaling-cholera toxin;GPCR signaling-pertussis toxin;Purine metabolism;Metabolism;PKA activation;PKA-mediated phosphorylation of CREB;G alpha (s) signalling events;Calmodulin induced events;CaM pathway;Transport of small molecules;Neuronal System;GPCR signaling-G alpha s Epac and ERK;Hedgehog ,off, state;GPCR signaling-G alpha s PKA and ERK;Signaling by Hedgehog;Purine nucleotides nucleosides metabolism;Adenylate cyclase inhibitory pathway;Inhibition of adenylate cyclase pathway;Activation of GABAB receptors;DAG and IP3 signaling;GABA B receptor activation;Ca-dependent events;PLC beta mediated events;GABA receptor activation;Neurotransmitter receptors and postsynaptic signal transmission;Transmission across Chemical Synapses;Adenylate cyclase activating pathway;G-protein mediated events;Opioid Signalling;G alpha (i) signalling events;G alpha (z) signalling events;CREB phosphorylation through the activation of Adenylate Cyclase;PKA activation in glucagon signalling;Post NMDA receptor activation events;Activation of NMDA receptor and postsynaptic events;GPCR signaling-G alpha i;Vasopressin regulates renal water homeostasis via Aquaporins;Aquaporin-mediated transport;Integration of energy metabolism;GPCR downstream signalling;Intracellular signaling by second messengers;LPA4-mediated signaling events;LPA receptor mediated events;Endothelins (Consensus)

Recessive Scores

• pRec: 0.177

Intolerance Scores

• loftool: 0.244
• rvis_EVS: -2.17
• rvis_percentile_EVS: 1.42

Haploinsufficiency Scores

• pHI: 0.415
• hipred: Y
• hipred_score: 0.578
• ghis: 0.581

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.489

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Adcy3
• 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); taste/olfaction phenotype; reproductive system phenotype; normal phenotype; 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; 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); renal/urinary system phenotype; liver/biliary system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan)

Gene ontology

• Biological process: renal water homeostasis;cAMP biosynthetic process;signal transduction;G protein-coupled receptor signaling pathway;adenylate cyclase-activating G protein-coupled receptor signaling pathway;adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway;single fertilization;acrosome reaction;sensory perception of smell;olfactory learning;flagellated sperm motility;cellular response to glucagon stimulus;cellular response to forskolin
• Cellular component: cytoplasm;Golgi apparatus;plasma membrane;integral component of plasma membrane;cilium;membrane;integral component of membrane
• Molecular function: adenylate cyclase activity;calmodulin binding;ATP binding;metal ion binding