ADCY10

adenylate cyclase 10, the group of Adenylate cyclases

Basic information

Region (hg38): 1:167809386-167914215

Links

ENSG00000143199 ∙ NCBI:55811 ∙ OMIM:605205 ∙ HGNC:21285 ∙ Uniprot:Q96PN6 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• hypercalciuria, absorptive, 2 (Strong), mode of inheritance: AD
• hypercalciuria, absorptive, 2 (Limited), mode of inheritance: AD
• idiopathic inherited hypercalciuria (Supportive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Hypercalciuria, absorptive, 2	AD	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Renal	11932268

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ADCY10 gene.

• not_provided (372 variants)
• not_specified (170 variants)
• Familial_idiopathic_hypercalciuria (49 variants)
• ADCY10-related_disorder (29 variants)
• Abnormal_sperm_morphology (1 variants)
• Male_infertility (1 variants)
• See_cases (1 variants)
• Reduced_sperm_motility (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ADCY10 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000018417.6. Only rare variants are included in the table.

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.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			3	71	7	81
missense			272	33	4	309
nonsense	11	3	3			17
start loss						0
frameshift	8	2	1			11
splice donor/acceptor (+/-2bp)		7	1			8
Total	19	12	280	104	11

Highest pathogenic variant AF is 0.000304202

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ADCY10	protein_coding	protein_coding	ENST00000367851	32	104829

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
7.38e-41	0.000197	125442	0	306	125748	0.00122

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.455	788	825	0.955	0.0000436	10780
Missense in Polyphen		217	245.12	0.88528		3334
Synonymous	-0.381	309	301	1.03	0.0000168	2853
Loss of Function	1.29	69	81.5	0.846	0.00000455	1003

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00131	0.00131
Ashkenazi Jewish	0.000397	0.000397
East Asian	0.00179	0.00174
Finnish	0.00180	0.00180
European (Non-Finnish)	0.00135	0.00135
Middle Eastern	0.00179	0.00174
South Asian	0.00108	0.00108
Other	0.00147	0.00147

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Catalyzes the formation of the signaling molecule cAMP (PubMed:12609998, PubMed:15659711, PubMed:24616449, PubMed:25040695, PubMed:24567411). May function as sensor that mediates responses to changes in cellular bicarbonate and CO(2) levels (PubMed:15659711, PubMed:17591988). Has a critical role in mammalian spermatogenesis by producing the cAMP which regulates cAMP-responsive nuclear factors indispensable for sperm maturation in the epididymis. Induces capacitation, the maturational process that sperm undergo prior to fertilization (By similarity). Involved in ciliary beat regulation (PubMed:17591988). {ECO:0000250|UniProtKB:Q8C0T9, ECO:0000269|PubMed:15659711, ECO:0000269|PubMed:17591988, ECO:0000269|PubMed:24567411, ECO:0000269|PubMed:24616449, ECO:0000269|PubMed:25040695}.
• Disease: DISEASE: Hypercalciuria absorptive 2 (HCA2) [MIM:143870]: A common type of hypercalciuria, a condition characterized by excessive urinary calcium excretion. Absorptive hypercalciuria is due to gastrointestinal hyperabsorption of calcium and is a frequent cause of calcium oxalate nephrolithiasis. {ECO:0000269|PubMed:11932268}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.
• Pathway: Circadian entrainment - Homo sapiens (human);Thermogenesis - Homo sapiens (human);cAMP signaling pathway - Homo sapiens (human);Apelin signaling pathway - Homo sapiens (human);Purine metabolism - Homo sapiens (human);Purine Nucleoside Phosphorylase Deficiency;Mercaptopurine Action Pathway;Azathioprine Action Pathway;Xanthine Dehydrogenase Deficiency (Xanthinuria);Adenylosuccinate Lyase Deficiency;AICA-Ribosiduria;Thioguanine Action Pathway;Adenine phosphoribosyltransferase deficiency (APRT);Mitochondrial DNA depletion syndrome;Myoadenylate deaminase deficiency;Purine Metabolism;Molybdenum Cofactor Deficiency;Adenosine Deaminase Deficiency;Gout or Kelley-Seegmiller Syndrome;Lesch-Nyhan Syndrome (LNS);Xanthinuria type I;Xanthinuria type II;Endothelin Pathways;Phosphodiesterases in neuronal function;Signal Transduction;GPCR Adenosine A2A receptor;GPCR signaling-cholera toxin;GPCR signaling-pertussis toxin;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;GPCR signaling-G alpha i (Consensus)

Recessive Scores

• pRec: 0.0626

Intolerance Scores

• loftool: 0.982
• rvis_EVS: 0.64
• rvis_percentile_EVS: 83.79

Haploinsufficiency Scores

• pHI: 0.251
• hipred: N
• hipred_score: 0.169

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.152

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Adcy10
• Phenotype: homeostasis/metabolism phenotype; cellular 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); reproductive system phenotype

Gene ontology

• Biological process: epithelial cilium movement;cAMP biosynthetic process;spermatogenesis;intracellular signal transduction;positive regulation of apoptotic process;cellular response to inorganic substance
• Cellular component: nucleus;cytoplasm;mitochondrion;cytosol;plasma membrane;microtubule cytoskeleton;dendrite;growth cone;motile cilium;neuronal cell body;apical part of cell;basal part of cell;perinuclear region of cytoplasm
• Molecular function: magnesium ion binding;adenylate cyclase activity;ATP binding;manganese ion binding;ATPase binding;bicarbonate binding