ADCY10 (adenylate cyclase 10)

Gene

• Entrez ID: 55811
• Gene name: Adenylate cyclase 10
• Gene symbol: ADCY10
• Synonyms (NCBI Gene): HCA2, HEL-S-7a, SAC, SACI, Sacy, hsAC
• Chromosome: 1
• Chromosome location: 1q24.2
• Summary: The protein encoded by this gene belongs to a distinct class of adenylyl cyclases that is soluble and insensitive to G protein or forskolin regulation. Activity of this protein is regulated by bicarbonate. Variation at this gene has been observed in patie

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs779944215	GT>-	Pathogenic	Coding sequence variant, frameshift variant, non coding transcript variant

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000166	Function	Nucleotide binding	IEA
GO:0000287	Function	Magnesium ion binding	IEA
GO:0003351	Process	Epithelial cilium movement involved in extracellular fluid movement	IMP	17591988
GO:0004016	Function	Adenylate cyclase activity	IBA
GO:0004016	Function	Adenylate cyclase activity	IDA	12609998, 15659711
GO:0004016	Function	Adenylate cyclase activity	IEA
GO:0004016	Function	Adenylate cyclase activity	NAS	9874775
GO:0004016	Function	Adenylate cyclase activity	TAS	9874775
GO:0005524	Function	ATP binding	IEA
GO:0005576	Component	Extracellular region	IEA
GO:0005634	Component	Nucleus	IDA	15659711
GO:0005634	Component	Nucleus	IEA
GO:0005737	Component	Cytoplasm	IBA
GO:0005737	Component	Cytoplasm	IEA
GO:0005737	Component	Cytoplasm	TAS	9874775
GO:0005739	Component	Mitochondrion	HTP	34800366
GO:0005739	Component	Mitochondrion	IEA
GO:0005829	Component	Cytosol	IEA
GO:0005829	Component	Cytosol	NAS	9874775
GO:0005856	Component	Cytoskeleton	IEA
GO:0005886	Component	Plasma membrane	IEA
GO:0005929	Component	Cilium	IEA
GO:0006007	Process	Glucose catabolic process	IEA
GO:0006171	Process	CAMP biosynthetic process	IDA	12609998, 15659711
GO:0006171	Process	CAMP biosynthetic process	IEA
GO:0006171	Process	CAMP biosynthetic process	NAS	9874775
GO:0007189	Process	Adenylate cyclase-activating G protein-coupled receptor signaling pathway	TAS	12609998
GO:0007283	Process	Spermatogenesis	IEA
GO:0007286	Process	Spermatid development	IEA
GO:0009190	Process	Cyclic nucleotide biosynthetic process	IEA
GO:0010613	Process	Positive regulation of cardiac muscle hypertrophy	IEA
GO:0010666	Process	Positive regulation of cardiac muscle cell apoptotic process	IEA
GO:0010917	Process	Negative regulation of mitochondrial membrane potential	IEA
GO:0015630	Component	Microtubule cytoskeleton	IDA	15659711
GO:0016020	Component	Membrane	IEA
GO:0016829	Function	Lyase activity	IEA
GO:0030145	Function	Manganese ion binding	IEA
GO:0030424	Component	Axon	IEA
GO:0030425	Component	Dendrite	IEA
GO:0030426	Component	Growth cone	IEA
GO:0031514	Component	Motile cilium	IDA	17591988
GO:0035556	Process	Intracellular signal transduction	IEA
GO:0042995	Component	Cell projection	IEA
GO:0043025	Component	Neuronal cell body	IEA
GO:0043065	Process	Positive regulation of apoptotic process	IEA
GO:0045177	Component	Apical part of cell	IEA
GO:0045178	Component	Basal part of cell	IEA
GO:0045773	Process	Positive regulation of axon extension	IEA
GO:0045778	Process	Positive regulation of ossification	IEA
GO:0045819	Process	Positive regulation of glycogen catabolic process	IEA
GO:0046872	Function	Metal ion binding	IEA
GO:0048471	Component	Perinuclear region of cytoplasm	IDA	15659711
GO:0048471	Component	Perinuclear region of cytoplasm	IEA
GO:0051117	Function	ATPase binding	IEA
GO:0051901	Process	Positive regulation of mitochondrial depolarization	IEA
GO:0060306	Process	Regulation of membrane repolarization	IEA
GO:0071890	Function	Bicarbonate binding	IDA	24567411
GO:0090724	Component	Central region of growth cone	IEA
GO:0097450	Component	Astrocyte end-foot	IEA
GO:0106028	Process	Neuron projection retraction	IEA
GO:0106135	Process	Negative regulation of cardiac muscle cell contraction	IEA
GO:1901524	Process	Regulation of mitophagy	IEA
GO:1903378	Process	Positive regulation of oxidative stress-induced neuron intrinsic apoptotic signaling pathway	IEA
GO:1903427	Process	Negative regulation of reactive oxygen species biosynthetic process	IEA
GO:1903428	Process	Positive regulation of reactive oxygen species biosynthetic process	IEA
GO:1903955	Process	Positive regulation of protein targeting to mitochondrion	IEA
GO:1905461	Process	Positive regulation of vascular associated smooth muscle cell apoptotic process	IEA
GO:1990138	Process	Neuron projection extension	IEA
GO:1990535	Process	Neuron projection maintenance	IEA
GO:1990544	Process	Mitochondrial ATP transmembrane transport	IEA
GO:2001171	Process	Positive regulation of ATP biosynthetic process	IEA
GO:2001244	Process	Positive regulation of intrinsic apoptotic signaling pathway	IEA

Other IDs

• MIM: 605205
• HGNC: 21285
• e!Ensembl: ENSG00000143199

Protein

• UniProt ID: Q96PN6
• Protein name: Adenylate cyclase type 10 (EC 4.6.1.1) (AH-related protein) (Adenylate cyclase homolog) (Germ cell soluble adenylyl cyclase) (hsAC) (sAC) (Testicular soluble adenylyl cyclase)
• Protein function: Catalyzes the formation of the signaling molecule cAMP (PubMed:12609998, PubMed:15659711, PubMed:24567411, PubMed:24616449, PubMed:25040695). May function as sensor that mediates responses to changes in cellular bicarbonate and CO(2) levels (Pub
• PDB: 4CLF, 4CLK, 4CLL, 4CLP, 4CLS, 4CLT, 4CLU, 4CLW, 4CLY, 4CLZ, 4CM0, 4CM2, 4OYA, 4OYB, 4OYI, 4OYM, 4OYO, 4OYP, 4OYW, 4OYX, 4OYZ, 4OZ2, 4OZ3, 4UST, 4USU, 4USV, 4USW, 5D0R, 5IV3, 5IV4, 7OVD, 8B75, 8CNH, 8CO7, 8COJ, 8COT, 8IL7
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00211	Guanylate_cyc	37 → 219	Adenylate and Guanylate cyclase catalytic domain	Domain
  PF00211	Guanylate_cyc	285 → 463	Adenylate and Guanylate cyclase catalytic domain	Domain

• Tissue specificity: TISSUE SPECIFICITY: Detected in airway epithelial cells and testis (at protein level) (PubMed:17591988). Weakly expressed in multiple tissues. Expressed in brain, heart, kidney, liver, lung, pancreas, peripheral blood leukocytes, placenta, skeletal muscle
• Sequence:

  MNTPKEEFQDWPIVRIAAHLPDLIVYGHFSPERPFMDYFDGVLMFVDISGFTAMTEKFSS
  AMYMDRGAEQLVEILNYHISAIVEKVLIFGGDILKFAGDALLALWRVERKQLKNIITVVI
  KCSLEIHGLFETQEWEEGLDIRVKIGLAAGHISMLVFGDETHSHFLVIGQAVDDVRLAQN
  MAQMNDVILSPNCWQLCDRSMIEIESVPDQRAVKVNFLKPPPNFNFDEFFTKCTTFMHYY
  PSGEHKNLLRLACTLKPDPELEMSLQKYVMESILKQIDNKQLQGYLSELRPVTIVFVNLM
  FEDQDKAEEIGPAIQDAYMHITSVLKIFQGQINKVFMFDKGCSFLCVFGFPGEKVPDELT
  HALECAMDIFDFCSQVHKIQTVSIGVASGIVFCGIVGHTVRHEYTVIGQKVNLAARMMMY
  YPGIVTCDSVTYNGSNLPAYFFKELPKKVMKGVADSGPLYQYWGRTEKVMFGMACLICNR
  KEDYPLLGRNKEINYFMYTMKKFLISNSSQVLMYEGLPGYGKSQILMKIEYLAQGKNHRI
  IAISLNKISFHQTFYTIQMFMANVLGLDTCKHYKERQTNLRNKVMTLLDEKFYCLLNDIF
  HVQFPISREISRMSTLKKQKQLEILFMKILKLIVKEERIIFIIDEAQFVDSTSWRFMEKL
  IRTLPIFIIMSLCPFVNIPCAAARAVIKNRNTTYIVIGAVQPNDISNKICLDLNVSCISK
  ELDSYLGEGSCGIPFYCEELLKNLEHHEVLVFQQTESEEKTNRTWNNLFKYSIKLTEKLN
  MVTLHSDKESEEVCHLTSGVRLKNLSPPTSLKEISLIQLDSMRLSHQMLVRCAAIIGLTF
  TTELLFEILPCWNMKMMIKTLATLVESNIFYCFRNGKELQKALKQNDPSFEVHYRSLSLK
  PSEGMDHGEEEQLRELENEVIECHRIRFCNPMMQKTAYELWLKDQRKAMHLKCARFLEED
  AHRCDHCRGRDFIPYHHFTVNIRLNALDMDAIKKMAMSHGFKTEEKLILSNSEIPETSAF
  FPENRSPEEIREKILNFFDHVLTKMKTSDEDIIPLESCQCEEILEIVILPLAHHFLALGE
  NDKALYYFLEIASAYLIFCDNYMAYMYLNEGQKLLKTLKKDKSWSQTFESATFYSLKGEV
  CFNMGQIVLAKKMLRKALKLLNRIFPYNLISLFLHIHVEKNRHFHYVNRQAQESPPPGKK
  RLAQLYRQTVCLSLLWRIYSYSYLFHCKYYAHLAVMMQMNTALETQNCFQIIKAYLDYSL
  YHHLAGYKGVWFKYEVMAMEHIFNLPLKGEGIEIVAYVAETLVFNKLIMGHLDLAIELGS
  RALQMWALLQNPNRHYQSLCRLSRCLLLNSRYPQLIQVLGRLWELSVTQEHIFSKAFFYF
  VCLDILLYSGFVYRTFEECLEFIHQYENNRILKFHSGLLLGLYSSVAIWYARLQEWDNFY
  KFSNRAKNLLPRRTMTLTYYDGISRYMEGQVLHLQKQIKEQSENAQASGEELLKNLENLV
  AQNTTGPVFCPRLYHLMAYVCILMGDGQKCGLFLNTALRLSETQGNILEKCWLNMNKESW
  YSTSELKEDQWLQTILSLPSWEKIVAGRVNIQDLQKNKFLMRANTVDNHF

• Sequence length: 1610

Pathways

KEGG:

Purine metabolism
Metabolic pathways
cAMP signaling pathway
Apelin signaling pathway
Circadian entrainment
Thermogenesis
Growth hormone synthesis, secretion and action

Reactome:

Hedgehog 'off' state

Associated diseases

Evidence Score:

• ★☆☆☆☆  Gene-disease association found in Text Mining only
• ★★☆☆☆  Found in Text Mining and Unknown/Other Associations
• ★★★☆☆  Reported in Unknown/Other Associations across ≥2 Sources
• ★★★★☆  ClinVar: Pathogenic/Likely Pathogenic (<5 Variants)
• ★★★★★  ClinVar: Pathogenic/Likely Pathogenic (≥5 Variants)

Causal
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession	Evidence Score
Abnormal sperm morphology	Pathogenic	rs779944215	RCV000714269	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Familial idiopathic hypercalciuria	Likely pathogenic; Pathogenic	rs1407377211, rs763059448, rs754094260	RCV001535865 RCV006249791 RCV004555403	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Reduced sperm motility	Pathogenic	rs779944215	RCV000714269	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
Acute myeloid leukemia	Benign; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
ADCY10-related disorder	Likely benign; Benign; Uncertain significance; Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Cervical cancer	Benign; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Cholangiocarcinoma	Benign; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Clear cell carcinoma of kidney	Benign; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Colorectal cancer	Benign; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Gastric cancer	Benign; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Hepatocellular carcinoma	Benign; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
HYPERCALCIURIA, ABSORPTIVE, 2	—	CTD, GWAS catalog CTD, GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
IDIOPATHIC HYPERCALCIURIA	—	Disgenet, Orphanet Disgenet, Orphanet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
IDIOPATHIC INHERITED HYPERCALCIURIA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Lung cancer	Benign; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MAJOR DEPRESSIVE DISORDER	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Male infertility	Uncertain significance	ClinVar Disgenet	★★★☆☆ Reported in Unknown/Other Associations (≥2 sources)
Malignant lymphoma, large B-cell, diffuse	Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Malignant tumor of esophagus	Benign; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Melanoma	Benign; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Sarcoma	Benign; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
TERATOZOOSPERMIA	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Thymoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Uterine carcinosarcoma	Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Adenocarcinoma	Adenocarcinoma	BEFREE	31280048		★☆☆☆☆ Found in Text Mining only
Angioedemas Hereditary	Angioedema	Pubtator	2723063	Associate	★☆☆☆☆ Found in Text Mining only
Aortic Aneurysm, Abdominal	Aortic Aneurysm	BEFREE	25993294		★☆☆☆☆ Found in Text Mining only
Arteriosclerosis	Arteriosclerosis	BEFREE	30270326		★☆☆☆☆ Found in Text Mining only
Asthenozoospermia	Asthenozoospermia	BEFREE	31119281		★☆☆☆☆ Found in Text Mining only
Asthenozoospermia	Asthenozoospermia	CLINVAR_DG	31119281		★☆☆☆☆ Found in Text Mining only
Asthma	Asthma	BEFREE	30732486		★☆☆☆☆ Found in Text Mining only
Atherosclerosis	Atherosclerosis	BEFREE	30270326		★☆☆☆☆ Found in Text Mining only
Burkitt Lymphoma	Burkitt lymphoma	Pubtator	3035497	Associate	★☆☆☆☆ Found in Text Mining only
Carcinoma	Carcinoma	BEFREE	26009897		★☆☆☆☆ Found in Text Mining only
Chronic Lymphocytic Leukemia	Lymphocytic Leukemia	BEFREE	30601084		★☆☆☆☆ Found in Text Mining only
Congestive heart failure	Congestive Heart Failure	BEFREE	30998392, 31023122		★☆☆☆☆ Found in Text Mining only
Dehydrated Hereditary Stomatocytosis Pseudohyperkalemia and Perinatal Edema	Hereditary xerocytosis	Pubtator	29221444	Associate	★☆☆☆☆ Found in Text Mining only
Diabetes Mellitus, Insulin-Dependent	Diabetes Mellitus	BEFREE	15642486		★☆☆☆☆ Found in Text Mining only
Diabetic Retinopathy	Diabetic Retinopathy	BEFREE	24215154		★☆☆☆☆ Found in Text Mining only
Esophageal Squamous Cell Carcinoma	Esophageal squamous cell carcinoma	Pubtator	16832412	Associate	★☆☆☆☆ Found in Text Mining only
Familial idiopathic hypercalciuria	Hypercalciuria	GENOMICS_ENGLAND_DG	11932268		★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Familial idiopathic hypercalciuria	Hypercalciuria	CTD_human_DG			★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Fibroid Tumor	Leiomyoma	BEFREE	29308311		★☆☆☆☆ Found in Text Mining only
Glaucoma	Glaucoma	BEFREE	28161252, 28728897, 28887000, 29462772, 29571155, 31237458, 31539777		★☆☆☆☆ Found in Text Mining only
Glioma	Glioma	BEFREE	22022424		★☆☆☆☆ Found in Text Mining only
Heart failure	Heart Failure	BEFREE	30998392, 31023122		★☆☆☆☆ Found in Text Mining only
Hypercalciuria Absorptive 2	Hypercalciuria	Pubtator	15659711	Associate	★☆☆☆☆ Found in Text Mining only
Hyperglycinemia Nonketotic	Hyperglycemia	Pubtator	1671321	Associate	★☆☆☆☆ Found in Text Mining only
Hypertriglyceridemia	Hypertriglyceridemia	Pubtator	2989400	Associate	★☆☆☆☆ Found in Text Mining only
Hypogonadism	Hypogonadism	Pubtator	33574797	Associate	★☆☆☆☆ Found in Text Mining only
Idiopathic hypercalciuria	Hypercalciuria	ORPHANET_DG	11932268		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Idiopathic hypercalciuria	Hypercalciuria	Orphanet			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Infertility	Infertility	Pubtator	33574797	Associate	★☆☆☆☆ Found in Text Mining only
Infertility Male	Male infertility	Pubtator	33574797	Associate	★☆☆☆☆ Found in Text Mining only
Intracranial Aneurysm	Intracranial Aneurysm	BEFREE	28834890		★☆☆☆☆ Found in Text Mining only
Kidney Diseases	Kidney disease	Pubtator	2880682	Associate	★☆☆☆☆ Found in Text Mining only
Malignant Neoplasms	Malignant Neoplasm	BEFREE	24724894, 28456097, 31280048		★☆☆☆☆ Found in Text Mining only
Metabolic Bone Disorder	Metabolic Bone Disorder	BEFREE	18189416, 19415900		★☆☆☆☆ Found in Text Mining only
Neoplasms	Neoplasms	BEFREE	18836307, 24156017, 28802125, 28965419, 28971310, 29981145		★☆☆☆☆ Found in Text Mining only
NEPHROLITHIASIS, CALCIUM OXALATE	Nephronophthisis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Obesity	Obesity	BEFREE	30270326		★☆☆☆☆ Found in Text Mining only
Osteopenia	Osteopenia	BEFREE	24116140		★☆☆☆☆ Found in Text Mining only
Osteopenia	Osteopenia	HPO_DG			★☆☆☆☆ Found in Text Mining only
OSTEOPETROSIS, AUTOSOMAL RECESSIVE 3	Osteopetrosis	BEFREE	15327960, 18189416, 19415900		★☆☆☆☆ Found in Text Mining only
Osteoporosis	Osteoporosis	Pubtator	22957024	Associate	★☆☆☆☆ Found in Text Mining only
Osteoporosis	Osteoporosis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Pancreatic Neoplasms	Pancreatic neoplasm	Pubtator	26854454	Associate	★☆☆☆☆ Found in Text Mining only
Pseudohypoparathyroidism	Pseudohypoparathyroidism	Pubtator	2829196	Associate	★☆☆☆☆ Found in Text Mining only
Retinal Diseases	Retinal Diseases	BEFREE	24215154		★☆☆☆☆ Found in Text Mining only
Septicemia	Septicemia	BEFREE	30951370		★☆☆☆☆ Found in Text Mining only
Syringomyelia	Syringomyelia	BEFREE	30952036		★☆☆☆☆ Found in Text Mining only
Teratozoospermia	Teratozoospermia	CLINVAR_DG	31119281		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Uterine Fibroids	Uterine Fibroids	BEFREE	29308311		★☆☆☆☆ Found in Text Mining only