ADCY8

adenylate cyclase 8, the group of Adenylate cyclases

Basic information

Region (hg38): 8:130780300-131040909

Previous symbols: [ "ADCY3" ]

Links

ENSG00000155897 ∙ NCBI:114 ∙ OMIM:103070 ∙ HGNC:239 ∙ Uniprot:P40145 ∙ 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 ADCY8 gene.

• Inborn genetic diseases (43 variants)
• not provided (6 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ADCY8 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				2	4	6
missense			43			43
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	43	2	4

Variants in ADCY8

This is a list of pathogenic ClinVar variants found in the ADCY8 region.

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

Position	Type	Phenotype	Significance	ClinVar
8-130780464-G-A		not specified	Uncertain significance (Feb 17, 2022)
8-130780466-C-T		not specified	Uncertain significance (May 30, 2023)
8-130780534-A-G			Benign (Jul 23, 2018)
8-130780564-C-T			Benign (Jul 23, 2018)
8-130780565-G-A		not specified	Uncertain significance (Dec 03, 2021)
8-130780566-C-T		not specified	Uncertain significance (Jul 20, 2021)
8-130780613-G-T		not specified	Uncertain significance (Jul 15, 2021)
8-130780614-G-C		not specified	Uncertain significance (Aug 10, 2021)
8-130780674-T-A		not specified	Uncertain significance (Dec 21, 2023)
8-130780690-C-G		not specified	Uncertain significance (Mar 24, 2023)
8-130780697-C-T		not specified	Uncertain significance (Oct 20, 2021)
8-130780764-C-T		not specified	Uncertain significance (Aug 16, 2021)
8-130780770-C-A		not specified	Uncertain significance (Dec 19, 2022)
8-130783754-C-T		not specified	Uncertain significance (Jan 04, 2022)
8-130783778-A-G		not specified	Uncertain significance (Jan 08, 2024)
8-130783799-C-T		not specified	Uncertain significance (Mar 22, 2023)
8-130783801-C-T		not specified	Uncertain significance (Apr 07, 2022)
8-130800510-C-T			Benign (Apr 26, 2018)
8-130800537-C-T			Likely benign (Apr 23, 2018)
8-130814101-G-A		not specified	Uncertain significance (Dec 21, 2022)
8-130847491-G-A		not specified	Uncertain significance (Sep 27, 2022)
8-130867892-C-T		not specified	Uncertain significance (Mar 24, 2023)
8-130884591-C-T		not specified	Uncertain significance (Feb 10, 2022)
8-130884595-A-G		not specified	Uncertain significance (Feb 13, 2024)
8-130904001-C-T		not specified	Uncertain significance (Jul 25, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ADCY8	protein_coding	protein_coding	ENST00000286355	18	262126

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00000178	1.00	125698	0	50	125748	0.000199

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.57	599	717	0.835	0.0000407	8130
Missense in Polyphen		154	225.74	0.68221		2550
Synonymous	0.253	294	300	0.981	0.0000173	2535
Loss of Function	4.32	20	54.3	0.368	0.00000292	612

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000398	0.000398
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000545	0.0000544
Finnish	0.000139	0.000139
European (Non-Finnish)	0.000283	0.000281
Middle Eastern	0.0000545	0.0000544
South Asian	0.000197	0.000196
Other	0.000164	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: This is a membrane-bound, calcium-stimulable adenylyl cyclase. May be involved in learning, in memory and in drug dependence (By similarity). {ECO:0000250}.
• 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);Long-term potentiation - 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);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);Taste 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;Beta-agonist/Beta-blocker Pathway, Pharmacodynamics;Common Pathways Underlying Drug Addiction;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;Glucagon-like Peptide-1 (GLP1) regulates insulin secretion;Regulation of insulin secretion;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: 0.192

Intolerance Scores

• loftool: 0.288
• rvis_EVS: -1.28
• rvis_percentile_EVS: 5.17

Haploinsufficiency Scores

• pHI: 0.677
• hipred: Y
• hipred_score: 0.698
• ghis: 0.597

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.490

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Adcy8
• Phenotype: behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); 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); 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); growth/size/body region phenotype; homeostasis/metabolism phenotype

Zebrafish Information Network

• Gene name: adcy8
• Affected structure: retinal ganglion cell
• Phenotype tag: abnormal
• Phenotype quality: mislocalised

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;positive regulation of cytosolic calcium ion concentration;learning or memory;memory;long-term memory;locomotory behavior;glucose mediated signaling pathway;positive regulation of synaptic plasticity;positive regulation of CREB transcription factor activity;activation of protein kinase A activity;positive regulation of insulin secretion involved in cellular response to glucose stimulus;opioid receptor signaling pathway;glucose homeostasis;protein complex oligomerization;protein homooligomerization;regulation of cytosolic calcium ion concentration;cellular response to calcium ion;cellular response to morphine;cellular response to glucose stimulus;cellular response to glucagon stimulus;regulation of cellular response to stress;neuroinflammatory response;positive regulation of long-term synaptic potentiation;positive regulation of long-term synaptic depression;cellular response to forskolin
• Cellular component: plasma membrane;integral component of plasma membrane;caveola;clathrin-coated pit;postsynaptic density;actin cytoskeleton;membrane;basolateral plasma membrane;apical plasma membrane;axon;dendrite;neuronal cell body membrane;plasma membrane raft;membrane raft;presynaptic active zone;excitatory synapse;Schaffer collateral - CA1 synapse;hippocampal mossy fiber to CA3 synapse;glutamatergic synapse;integral component of presynaptic membrane
• Molecular function: actin binding;adenylate cyclase activity;calmodulin binding;ATP binding;calcium- and calmodulin-responsive adenylate cyclase activity;protein homodimerization activity;metal ion binding;protein heterodimerization activity;protein dimerization activity;protein phosphatase 2A binding