ADCY1

adenylate cyclase 1, the group of Adenylate cyclases

Basic information

Region (hg38): 7:45574139-45723116

Previous symbols: [ "DFNB44" ]

Links

ENSG00000164742 ∙ NCBI:107 ∙ OMIM:103072 ∙ HGNC:232 ∙ Uniprot:Q08828 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• autosomal recessive nonsyndromic hearing loss 44 (Limited), mode of inheritance: AR
• hearing loss, autosomal recessive (Supportive), mode of inheritance: AR
• hearing loss, autosomal recessive (Limited), mode of inheritance: AR
• autosomal recessive nonsyndromic hearing loss 44 (Limited), mode of inheritance: Unknown
• hearing loss, autosomal recessive (Limited), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Deafness, autosomal dominant 44	AR	Audiologic/Otolaryngologic	Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development	Audiologic/Otolaryngologic	15583425; 24482543

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ADCY1 gene.

• not provided (185 variants)
• not specified (22 variants)
• Inborn genetic diseases (21 variants)
• Autosomal recessive nonsyndromic hearing loss 44 (7 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ADCY1 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	50	4	56
missense			53	4	2	59
nonsense						0
start loss						0
frameshift			1			1
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region			6	4	2	12
non coding				42	39	81
Total	0	0	56	96	45

Variants in ADCY1

This is a list of pathogenic ClinVar variants found in the ADCY1 region.

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

Position	Type	Phenotype	Significance	ClinVar
7-45574547-G-C			Uncertain significance (Jul 19, 2022)
7-45574559-CGCGGCGGAGGCG-C			Uncertain significance (Jul 14, 2023)
7-45574559-C-CGCGGCGGAGGCG			Uncertain significance (Sep 09, 2023)
7-45574570-C-A			Likely benign (Dec 19, 2023)
7-45574592-G-A			Uncertain significance (Dec 24, 2023)
7-45574628-C-T		Inborn genetic diseases	Uncertain significance (Mar 16, 2022)
7-45574632-G-C			Uncertain significance (Nov 17, 2022)
7-45574643-C-G		Inborn genetic diseases	Uncertain significance (Jul 25, 2023)
7-45574685-C-T			Likely benign (Jan 20, 2024)
7-45574716-A-G		Inborn genetic diseases	Uncertain significance (May 03, 2023)
7-45574747-C-T			Likely benign (Jun 03, 2023)
7-45574760-G-A			Uncertain significance (May 15, 2023)
7-45574774-G-A			Likely benign (Dec 20, 2022)
7-45574777-C-G			Benign (Dec 28, 2023)
7-45574791-C-T			Benign/Likely benign (Jul 25, 2023)
7-45574794-C-G			Uncertain significance (Dec 27, 2023)
7-45574801-C-G			Benign/Likely benign (Jan 25, 2024)
7-45574816-C-A			Likely benign (Jun 05, 2021)
7-45574821-G-A			Uncertain significance (Dec 20, 2022)
7-45574843-C-T			Likely benign (Feb 22, 2022)
7-45574880-T-C			Uncertain significance (Jul 06, 2022)
7-45574893-C-T		Inborn genetic diseases	Uncertain significance (Jan 20, 2024)
7-45574894-C-T			Likely benign (Dec 22, 2022)
7-45574930-C-A		Inborn genetic diseases	Uncertain significance (Jan 27, 2022)
7-45574930-C-T			Likely benign (Apr 15, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ADCY1	protein_coding	protein_coding	ENST00000297323	20	148977

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.997	0.00253	125733	0	15	125748	0.0000596

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	4.38	347	665	0.522	0.0000408	7205
Missense in Polyphen		87	263.14	0.33062		2645
Synonymous	0.195	287	291	0.985	0.0000192	2381
Loss of Function	5.51	7	48.4	0.145	0.00000259	526

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000887	0.0000887
Ashkenazi Jewish	0.0000995	0.0000992
East Asian	0.000110	0.000109
Finnish	0.00	0.00
European (Non-Finnish)	0.0000440	0.0000439
Middle Eastern	0.000110	0.000109
South Asian	0.000131	0.000131
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Catalyzes the formation of the signaling molecule cAMP in response to G-protein signaling. Mediates responses to increased cellular Ca(2+)/calmodulin levels (By similarity). May be involved in regulatory processes in the central nervous system. May play a role in memory and learning. Plays a role in the regulation of the circadian rhythm of daytime contrast sensitivity probably by modulating the rhythmic synthesis of cyclic AMP in the retina (By similarity). {ECO:0000250|UniProtKB:O88444, ECO:0000250|UniProtKB:P19754}.
• Disease: DISEASE: Deafness, autosomal recessive, 44 (DFNB44) [MIM:610154]: A form of non-syndromic deafness characterized by prelingual profound hearing loss affecting all frequencies. {ECO:0000269|PubMed:24482543}. Note=The disease is caused by mutations 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);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);Amoebiasis - Homo sapiens (human);Thermogenesis - Homo sapiens (human);Adrenergic signaling in cardiomyocytes - Homo sapiens (human);Longevity regulating pathway - Homo sapiens (human);Chagas disease (American trypanosomiasis) - 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);Progesterone-mediated oocyte maturation - Homo sapiens (human);Proton Pump Inhibitor Pathway, Pharmacodynamics;Selective Serotonin Reuptake Inhibitor Pathway, Pharmacodynamics;Beta-agonist/Beta-blocker Pathway, Pharmacodynamics;Common Pathways Underlying Drug Addiction;Myometrial Relaxation and Contraction Pathways;G Protein Signaling Pathways;BDNF-TrkB Signaling;Cannabinoid receptor signaling;Chemokine signaling pathway;Phosphodiesterases in neuronal function;Calcium Regulation in the Cardiac Cell;Signaling by GPCR;Signal Transduction;gata3 participate in activating the th2 cytokine genes expression;regulation of ck1/cdk5 by type 1 glutamate receptors;phospholipids as signalling intermediaries;cystic fibrosis transmembrane conductance regulator (cftr) and beta 2 adrenergic receptor (b2ar) pathway;ion channels and their functional role in vascular endothelium;regulation of bad phosphorylation;activation of csk by camp-dependent protein kinase inhibits signaling through the t cell receptor;chrebp regulation by carbohydrates and camp;thrombin signaling and protease-activated receptors;how progesterone initiates the oocyte maturation;activation of camp-dependent protein kinase pka;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;regulation of spermatogenesis by crem;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: 0.181

Intolerance Scores

• loftool: 0.134
• rvis_EVS: -1.39
• rvis_percentile_EVS: 4.25

Haploinsufficiency Scores

• pHI: 0.282
• hipred: Y
• hipred_score: 0.819
• ghis: 0.687

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.399

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Adcy1
• Phenotype: homeostasis/metabolism phenotype; 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); 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)

Zebrafish Information Network

• Gene name: adcy1b
• Affected structure: auditory receptor cell
• Phenotype tag: abnormal
• Phenotype quality: decreased functionality

Gene ontology

• Biological process: renal water homeostasis;cAMP biosynthetic process;G protein-coupled receptor signaling pathway;adenylate cyclase-activating G protein-coupled receptor signaling pathway;adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway;axonogenesis;brain development;long-term memory;circadian rhythm;response to lithium ion;cAMP-mediated signaling;positive regulation of CREB transcription factor activity;regulation of circadian rhythm;cellular response to calcium ion;cellular response to glucagon stimulus;neuroinflammatory response;positive regulation of long-term synaptic potentiation;cellular response to forskolin;regulation of synaptic vesicle exocytosis
• Cellular component: nucleus;cytoplasm;plasma membrane;integral component of plasma membrane;membrane raft;extracellular exosome;Schaffer collateral - CA1 synapse;hippocampal mossy fiber to CA3 synapse;glutamatergic synapse;integral component of postsynaptic density membrane
• Molecular function: adenylate cyclase activity;calmodulin binding;ATP binding;calcium- and calmodulin-responsive adenylate cyclase activity;metal ion binding