ADCY9

adenylate cyclase 9, the group of Adenylate cyclases

Basic information

Region (hg38): 16:3953386-4116442

Links

ENSG00000162104 ∙ NCBI:115 ∙ OMIM:603302 ∙ HGNC:240 ∙ Uniprot:O60503 ∙ 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 ADCY9 gene.

• Inborn genetic diseases (45 variants)
• not provided (24 variants)
• Neurodevelopmental disorder (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ADCY9 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				7	10	17
missense			44	5	1	50
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region				2		2
non coding				1		1
Total	0	0	44	13	11

Variants in ADCY9

This is a list of pathogenic ClinVar variants found in the ADCY9 region.

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

Position	Type	Phenotype	Significance	ClinVar
16-3965875-C-T		not specified	Uncertain significance (Jun 06, 2023)
16-3965901-C-A		not specified	Uncertain significance (Jan 12, 2024)
16-3965908-C-A		not specified	Uncertain significance (Sep 28, 2022)
16-3965993-C-T		not specified	Uncertain significance (Dec 21, 2023)
16-3966037-T-C		not specified	Uncertain significance (Jun 21, 2023)
16-3966049-C-T		not specified	Uncertain significance (Apr 25, 2022)
16-3966128-T-C		not specified	Uncertain significance (Aug 29, 2022)
16-3966233-C-T		not specified	Uncertain significance (Jan 04, 2024)
16-3966315-G-A			Likely benign (Jun 13, 2018)
16-3966344-C-T			Likely benign (Oct 01, 2022)
16-3966354-G-A			Benign (Dec 31, 2019)
16-3966400-A-G		not specified	Uncertain significance (Jan 17, 2024)
16-3966442-T-C		not specified	Uncertain significance (Nov 23, 2021)
16-3966455-C-T		not specified	Uncertain significance (Aug 15, 2023)
16-3966507-G-A			Benign (Dec 31, 2019)
16-3966555-C-G		not specified	Uncertain significance (Feb 10, 2022)
16-3966674-C-A		not specified	Uncertain significance (Aug 15, 2023)
16-3966739-C-G		Neurodevelopmental disorder	Uncertain significance (Jan 01, 2019)
16-3966843-G-A			Benign/Likely benign (Jan 01, 2023)
16-3966873-G-T			Likely benign (Nov 15, 2018)
16-3966932-G-A		not specified	Uncertain significance (May 31, 2023)
16-3966939-C-G			Likely benign (Dec 01, 2022)
16-3966953-G-T		not specified	Uncertain significance (Nov 13, 2023)
16-3974682-C-G		not specified	Uncertain significance (Mar 01, 2024)
16-3974694-G-C		not specified	Uncertain significance (May 16, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ADCY9	protein_coding	protein_coding	ENST00000294016	10	162799

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.979	0.0206	125722	0	26	125748	0.000103

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.25	730	831	0.878	0.0000572	8882
Missense in Polyphen		176	265.52	0.66286		2941
Synonymous	-2.93	457	384	1.19	0.0000312	2722
Loss of Function	5.28	8	47.2	0.170	0.00000235	532

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000217	0.000214
Ashkenazi Jewish	0.00	0.00
East Asian	0.000109	0.000109
Finnish	0.00	0.00
European (Non-Finnish)	0.0000617	0.0000615
Middle Eastern	0.000109	0.000109
South Asian	0.000361	0.000359
Other	0.000326	0.000326

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Adenylyl cyclase that catalyzes the formation of the signaling molecule cAMP in response to activation of G protein- coupled receptors (PubMed:9628827, PubMed:12972952, PubMed:15879435, PubMed:10987815). Contributes to signaling cascades activated by CRH (corticotropin-releasing factor), corticosteroids and beta-adrenergic receptors (PubMed:9628827). {ECO:0000269|PubMed:10987815, ECO:0000269|PubMed:12972952, ECO:0000269|PubMed:15879435, ECO:0000269|PubMed:9628827}.
• 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);Endocrine and other factor-regulated calcium reabsorption - 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);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;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;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: 0.179

Intolerance Scores

• loftool: 0.0303
• rvis_EVS: -1.78
• rvis_percentile_EVS: 2.28

Haploinsufficiency Scores

• pHI: 0.162
• hipred: Y
• hipred_score: 0.638
• ghis: 0.603

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.563

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Adcy9
• Phenotype: hematopoietic system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); 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); embryo phenotype; liver/biliary system phenotype; respiratory system phenotype; immune system phenotype; skeleton phenotype; digestive/alimentary 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); hearing/vestibular/ear phenotype; craniofacial phenotype; vision/eye phenotype; homeostasis/metabolism phenotype

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;cellular response to glucagon stimulus;adenylate cyclase-activating adrenergic receptor signaling pathway
• Cellular component: plasma membrane;integral component of plasma membrane;integral component of membrane;axon;dendrite
• Molecular function: adenylate cyclase activity;ATP binding;metal ion binding