ADCY2

adenylate cyclase 2, the group of Adenylate cyclases

Basic information

Region (hg38): 5:7396137-7830081

Links

ENSG00000078295 ∙ NCBI:108 ∙ OMIM:103071 ∙ HGNC:233 ∙ Uniprot:Q08462 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ADCY2 gene.

• Inborn genetic diseases (20 variants)
• not provided (8 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ADCY2 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	2	3
missense			21			21
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region					1	1
non coding					2	2
Total	0	0	21	1	4

Variants in ADCY2

This is a list of pathogenic ClinVar variants found in the ADCY2 region.

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

Position	Type	Phenotype	Significance	ClinVar
5-7396376-C-G		not specified	Uncertain significance (Sep 25, 2023)
5-7396411-T-C		not specified	Uncertain significance (Jan 03, 2024)
5-7396418-G-C		not specified	Uncertain significance (Jul 26, 2021)
5-7396432-C-T		not specified	Uncertain significance (Jun 29, 2022)
5-7396486-G-T		not specified	Uncertain significance (Jan 23, 2024)
5-7520818-C-G			Uncertain significance (-)
5-7698290-A-G			Uncertain significance (Jul 26, 2022)
5-7707770-G-T		not specified	Uncertain significance (Apr 07, 2023)
5-7709239-T-A		not specified	Uncertain significance (Jun 24, 2022)
5-7709298-T-A		ADCY2-related disorder	Uncertain significance (Dec 15, 2023)
5-7709311-G-C		not specified	Uncertain significance (Nov 10, 2022)
5-7712907-ATC-A			Benign (Jul 31, 2017)
5-7743697-C-T		not specified	Uncertain significance (Feb 23, 2023)
5-7743729-G-A		not specified	Uncertain significance (Mar 29, 2023)
5-7757480-T-C		not specified	Uncertain significance (Nov 09, 2023)
5-7757528-G-A		not specified	Uncertain significance (May 22, 2023)
5-7757553-A-G			Likely benign (Mar 01, 2024)
5-7757569-A-C		not specified	Uncertain significance (Nov 12, 2021)
5-7757569-A-T		not specified	Uncertain significance (Dec 13, 2021)
5-7757573-C-A		not specified	Uncertain significance (Sep 30, 2021)
5-7757573-C-G		not specified	Uncertain significance (Aug 13, 2021)
5-7757576-T-C		not specified	Uncertain significance (Jun 02, 2023)
5-7757579-T-C		not specified	Uncertain significance (Mar 30, 2022)
5-7757581-A-G		not specified	Uncertain significance (Feb 21, 2024)
5-7757582-A-G		not specified	Uncertain significance (Mar 11, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ADCY2	protein_coding	protein_coding	ENST00000338316	25	433874

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.999	0.00102	123681	52	2015	125748	0.00825

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	4.25	343	647	0.530	0.0000374	7160
Missense in Polyphen		46	204.7	0.22471		2266
Synonymous	0.867	248	266	0.932	0.0000174	2109
Loss of Function	5.89	8	55.2	0.145	0.00000267	654

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0169	0.0162
Ashkenazi Jewish	0.0166	0.0160
East Asian	0.00317	0.00305
Finnish	0.00553	0.00542
European (Non-Finnish)	0.00723	0.00704
Middle Eastern	0.00317	0.00305
South Asian	0.0140	0.0135
Other	0.0131	0.0128

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Catalyzes the formation of the signaling molecule cAMP in response to G-protein signaling (PubMed:15385642). Down-stream signaling cascades mediate changes in gene expression patterns and lead to increased IL6 production. Functions in signaling cascades downstream of the muscarinic acetylcholine receptors (By similarity). {ECO:0000250|UniProtKB:P26769, ECO:0000269|PubMed:15385642}.
• 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);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);Glucagon signaling pathway - 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);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);Morphine addiction - Homo sapiens (human);Ovarian steroidogenesis - Homo sapiens (human);Insulin secretion - Homo sapiens (human);Melanogenesis - Homo sapiens (human);Nicotine Pathway (Dopaminergic Neuron), Pharmacodynamics;Progesterone-mediated oocyte maturation - Homo sapiens (human);Proton Pump Inhibitor Pathway, Pharmacodynamics;Selective Serotonin Reuptake Inhibitor Pathway, Pharmacodynamics;Beta-agonist/Beta-blocker Pathway, Pharmacodynamics;Excitatory Neural Signalling Through 5-HTR 4 and Serotonin;Intracellular Signalling Through Adenosine Receptor A2b and Adenosine;Intracellular Signalling Through Adenosine Receptor A2a and Adenosine;Intracellular Signalling Through Prostacyclin Receptor and Prostacyclin;Corticotropin Activation of Cortisol Production;Excitatory Neural Signalling Through 5-HTR 7 and Serotonin ;Excitatory Neural Signalling Through 5-HTR 6 and Serotonin ;Vasopressin Regulation of Water Homeostasis;Intracellular Signalling Through PGD2 receptor and Prostaglandin D2;Intracellular Signalling Through LHCGR Receptor and Luteinizing Hormone/Choriogonadotropin;Intracellular Signalling Through FSH Receptor and Follicle Stimulating Hormone;Intracellular Signalling Through Histamine H2 Receptor and Histamine;Dopamine Activation of Neurological Reward System;Nicotine Activity on Dopaminergic Neurons;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;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;PKA activation in glucagon signalling;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: 0.665

Intolerance Scores

• loftool: 0.104
• rvis_EVS: 0.12
• rvis_percentile_EVS: 62.17

Haploinsufficiency Scores

• pHI: 0.478
• hipred: Y
• hipred_score: 0.825
• ghis: 0.487

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.831

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Adcy2

Gene ontology

• Biological process: renal water homeostasis;cAMP biosynthetic process;G protein-coupled receptor signaling pathway;adenylate cyclase-modulating G protein-coupled receptor signaling pathway;adenylate cyclase-activating G protein-coupled receptor signaling pathway;adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway;cAMP-mediated signaling;cellular response to glucagon stimulus;cellular response to forskolin
• Cellular component: cytoplasm;plasma membrane;integral component of plasma membrane;membrane;dendrite;membrane raft
• Molecular function: magnesium ion binding;adenylate cyclase activity;ATP binding;adenylate cyclase binding;manganese ion binding;protein heterodimerization activity