ADCY4

adenylate cyclase 4, the group of Adenylate cyclases

Basic information

Region (hg38): 14:24318348-24335093

Links

ENSG00000129467 ∙ NCBI:196883 ∙ OMIM:600292 ∙ HGNC:235 ∙ Uniprot:Q8NFM4 ∙ 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 ADCY4 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ADCY4 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				3		3
missense			53	1		54
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region				1	1	2
non coding						0
Total	0	0	53	4	0

Variants in ADCY4

This is a list of pathogenic ClinVar variants found in the ADCY4 region.

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

Position	Type	Phenotype	Significance	ClinVar
14-24318439-G-A		not specified	Uncertain significance (Nov 09, 2021)
14-24318515-G-T		not specified	Uncertain significance (Jun 10, 2022)
14-24318526-T-G		not specified	Uncertain significance (Jun 18, 2024)
14-24318556-T-C		not specified	Uncertain significance (Oct 26, 2022)
14-24318572-C-A			Benign (Sep 15, 2017)
14-24318768-A-T		not specified	Uncertain significance (Apr 11, 2023)
14-24319178-A-G		not specified	Uncertain significance (Apr 15, 2024)
14-24319191-G-T		not specified	Uncertain significance (Aug 08, 2023)
14-24319194-T-C		not specified	Uncertain significance (Dec 20, 2023)
14-24319336-G-A		not specified	Uncertain significance (Apr 20, 2024)
14-24319345-C-T		not specified	Uncertain significance (Dec 08, 2023)
14-24319765-C-T		not specified	Uncertain significance (Aug 22, 2023)
14-24319791-C-T		not specified	Uncertain significance (Jul 12, 2022)
14-24319815-G-A		not specified	Uncertain significance (Dec 22, 2023)
14-24319837-G-A		not specified	Uncertain significance (Jul 27, 2023)
14-24319861-C-T		not specified	Uncertain significance (Sep 16, 2021)
14-24322076-C-T		not specified	Uncertain significance (Mar 28, 2022)
14-24322101-C-T		not specified	Uncertain significance (Apr 22, 2024)
14-24322154-G-A		not specified	Uncertain significance (Apr 27, 2024)
14-24322628-C-T		not specified	Uncertain significance (Dec 12, 2023)
14-24322949-G-A		not specified	Uncertain significance (Jan 07, 2022)
14-24322971-G-A			Likely benign (Mar 01, 2022)
14-24323036-T-C		not specified	Uncertain significance (Mar 29, 2024)
14-24323367-A-G		not specified	Uncertain significance (Mar 31, 2024)
14-24323382-A-G		not specified	Uncertain significance (Feb 11, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ADCY4	protein_coding	protein_coding	ENST00000310677	25	16745

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.08e-18	0.836	125526	0	222	125748	0.000883

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.43	530	631	0.840	0.0000374	6838
Missense in Polyphen		184	261.97	0.70236		2753
Synonymous	0.485	263	273	0.963	0.0000159	2274
Loss of Function	2.20	37	54.6	0.678	0.00000276	607

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000828	0.000828
Ashkenazi Jewish	0.000513	0.000496
East Asian	0.000277	0.000272
Finnish	0.00182	0.00180
European (Non-Finnish)	0.00109	0.00106
Middle Eastern	0.000277	0.000272
South Asian	0.000723	0.000686
Other	0.00147	0.00147

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Catalyzes the formation of the signaling molecule cAMP in response to G-protein signaling. {ECO:0000250|UniProtKB:P26770}.
• 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);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;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: 0.165

Intolerance Scores

• loftool: 0.370
• rvis_EVS: -2.32
• rvis_percentile_EVS: 1.19

Haploinsufficiency Scores

• pHI: 0.0900
• hipred: N
• hipred_score: 0.335
• ghis: 0.578

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.645

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Adcy4
• Phenotype: normal phenotype

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;cellular response to glucagon stimulus
• Cellular component: cytoplasm;plasma membrane;integral component of plasma membrane;membrane;dendrite
• Molecular function: adenylate cyclase activity;protein kinase C binding;protein binding;ATP binding;metal ion binding