ADCY5 (adenylate cyclase 5)

Gene

• Entrez ID: 111
• Gene name: Adenylate cyclase 5
• Gene symbol: ADCY5
• Synonyms (NCBI Gene): AC5, DSKOD, FDFM
• Chromosome: 3
• Chromosome location: 3q21.1
• Summary: This gene encodes a member of the membrane-bound adenylyl cyclase enzymes. Adenylyl cyclases mediate G protein-coupled receptor signaling through the synthesis of the second messenger cAMP. Activity of the encoded protein is stimulated by the Gs alpha sub

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs61734561	C>G,T	Conflicting-interpretations-of-pathogenicity, likely-benign	Coding sequence variant, synonymous variant, missense variant
rs548282891	C>T	Uncertain-significance, conflicting-interpretations-of-pathogenicity	Missense variant, genic upstream transcript variant, coding sequence variant
rs746547282	C>T	Likely-pathogenic	Splice donor variant
rs757156390	G>A,C	Pathogenic	Missense variant, synonymous variant, coding sequence variant
rs765349480	C>G,T	Likely-pathogenic	Coding sequence variant, missense variant
rs796065306	C>T	Pathogenic	Missense variant, coding sequence variant
rs797045002	C>A,T	Pathogenic	Splice donor variant
rs864309483	G>A	Conflicting-interpretations-of-pathogenicity, pathogenic	Missense variant, coding sequence variant, 5 prime UTR variant
rs864309484	A>T	Pathogenic	Missense variant, coding sequence variant
rs864309515	C>T	Pathogenic	Missense variant, coding sequence variant, 5 prime UTR variant
rs910314734	G>C,T	Likely-pathogenic	Missense variant, coding sequence variant
rs1057520218	G>A	Likely-pathogenic	Missense variant, coding sequence variant
rs1085308027	C>A	Likely-pathogenic	Missense variant, coding sequence variant
rs1215504032	AGCCGCCGCCGCCG>-	Pathogenic	Coding sequence variant, genic upstream transcript variant, frameshift variant
rs1553718964	G>T	Pathogenic	Missense variant, stop gained, coding sequence variant
rs1553726054	T>A,C	Likely-pathogenic	Missense variant, stop gained, coding sequence variant
rs1553732126	->G	Likely-pathogenic	Frameshift variant, 5 prime UTR variant, coding sequence variant
rs1553751151	G>T	Pathogenic	Stop gained, genic upstream transcript variant, coding sequence variant
rs1553751262	GCCGAGCCGCCGCCGCCGCC>-,GCC	Likely-pathogenic	Frameshift variant, genic upstream transcript variant, coding sequence variant
rs1576526285	T>G	Likely-pathogenic	Missense variant, coding sequence variant
rs1576606182	T>A,C	Likely-pathogenic	Missense variant, coding sequence variant
rs1576606282	G>A	Likely-pathogenic	5 prime UTR variant, coding sequence variant, missense variant
rs1576704514	AG>-	Likely-pathogenic	Frameshift variant, coding sequence variant, genic upstream transcript variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT720875	hsa-miR-4753-5p	HITS-CLIP	19536157
MIRT720874	hsa-miR-4717-5p	HITS-CLIP	19536157
MIRT720873	hsa-miR-3922-5p	HITS-CLIP	19536157
MIRT720872	hsa-miR-6832-3p	HITS-CLIP	19536157
MIRT720871	hsa-miR-4287	HITS-CLIP	19536157
MIRT720870	hsa-miR-4685-3p	HITS-CLIP	19536157
MIRT720869	hsa-miR-204-5p	HITS-CLIP	19536157
MIRT720868	hsa-miR-211-5p	HITS-CLIP	19536157
MIRT720867	hsa-miR-718	HITS-CLIP	19536157
MIRT720866	hsa-miR-1273h-5p	HITS-CLIP	19536157
MIRT720875	hsa-miR-4753-5p	HITS-CLIP	19536157
MIRT720874	hsa-miR-4717-5p	HITS-CLIP	19536157
MIRT720873	hsa-miR-3922-5p	HITS-CLIP	19536157
MIRT720872	hsa-miR-6832-3p	HITS-CLIP	19536157
MIRT720871	hsa-miR-4287	HITS-CLIP	19536157
MIRT720870	hsa-miR-4685-3p	HITS-CLIP	19536157
MIRT720869	hsa-miR-204-5p	HITS-CLIP	19536157
MIRT720868	hsa-miR-211-5p	HITS-CLIP	19536157
MIRT720867	hsa-miR-718	HITS-CLIP	19536157
MIRT720866	hsa-miR-1273h-5p	HITS-CLIP	19536157
MIRT768008	hsa-miR-4455	CLIP-seq
MIRT768009	hsa-miR-510	CLIP-seq
MIRT768010	hsa-miR-512-5p	CLIP-seq
MIRT768011	hsa-miR-603	CLIP-seq
MIRT768012	hsa-miR-633	CLIP-seq
MIRT768013	hsa-miR-1263	CLIP-seq
MIRT768014	hsa-miR-1271	CLIP-seq
MIRT768015	hsa-miR-182	CLIP-seq
MIRT768016	hsa-miR-2392	CLIP-seq
MIRT768017	hsa-miR-298	CLIP-seq
MIRT768018	hsa-miR-3148	CLIP-seq
MIRT768019	hsa-miR-3194-3p	CLIP-seq
MIRT768020	hsa-miR-3200-3p	CLIP-seq
MIRT768021	hsa-miR-323-5p	CLIP-seq
MIRT768022	hsa-miR-3978	CLIP-seq
MIRT768023	hsa-miR-4299	CLIP-seq
MIRT768024	hsa-miR-4436b-5p	CLIP-seq
MIRT768025	hsa-miR-4452	CLIP-seq
MIRT768026	hsa-miR-4456	CLIP-seq
MIRT768027	hsa-miR-4521	CLIP-seq
MIRT768028	hsa-miR-4534	CLIP-seq
MIRT768029	hsa-miR-4642	CLIP-seq
MIRT768030	hsa-miR-4680-3p	CLIP-seq
MIRT768031	hsa-miR-4778-5p	CLIP-seq
MIRT768032	hsa-miR-548q	CLIP-seq
MIRT768033	hsa-miR-876-3p	CLIP-seq
MIRT768034	hsa-miR-888	CLIP-seq
MIRT768035	hsa-miR-96	CLIP-seq
MIRT1926528	hsa-miR-1226	CLIP-seq
MIRT1926529	hsa-miR-3692	CLIP-seq
MIRT1926530	hsa-miR-4443	CLIP-seq
MIRT2443219	hsa-miR-1913	CLIP-seq
MIRT2443220	hsa-miR-214	CLIP-seq
MIRT2443221	hsa-miR-216a	CLIP-seq
MIRT768018	hsa-miR-3148	CLIP-seq
MIRT2443222	hsa-miR-3152-5p	CLIP-seq
MIRT2443223	hsa-miR-3173-5p	CLIP-seq
MIRT2443224	hsa-miR-324-3p	CLIP-seq
MIRT2443225	hsa-miR-3619-5p	CLIP-seq
MIRT2443226	hsa-miR-3691-3p	CLIP-seq
MIRT2443227	hsa-miR-3909	CLIP-seq
MIRT2443228	hsa-miR-4291	CLIP-seq
MIRT2443229	hsa-miR-4307	CLIP-seq
MIRT2443230	hsa-miR-4313	CLIP-seq
MIRT2443231	hsa-miR-4655-3p	CLIP-seq
MIRT2443232	hsa-miR-4734	CLIP-seq
MIRT2443233	hsa-miR-503	CLIP-seq
MIRT2443234	hsa-miR-567	CLIP-seq
MIRT2443235	hsa-miR-761	CLIP-seq
MIRT2443236	hsa-miR-922	CLIP-seq
MIRT2443220	hsa-miR-214	CLIP-seq
MIRT2443221	hsa-miR-216a	CLIP-seq
MIRT768018	hsa-miR-3148	CLIP-seq
MIRT2443225	hsa-miR-3619-5p	CLIP-seq
MIRT2443226	hsa-miR-3691-3p	CLIP-seq
MIRT2443228	hsa-miR-4291	CLIP-seq
MIRT2443233	hsa-miR-503	CLIP-seq
MIRT2443235	hsa-miR-761	CLIP-seq
MIRT2443236	hsa-miR-922	CLIP-seq

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000166	Function	Nucleotide binding	IEA
GO:0001973	Process	G protein-coupled adenosine receptor signaling pathway	IEA
GO:0004016	Function	Adenylate cyclase activity	IBA
GO:0004016	Function	Adenylate cyclase activity	IDA	15385642, 24700542
GO:0004016	Function	Adenylate cyclase activity	IEA
GO:0004016	Function	Adenylate cyclase activity	IMP	24740569
GO:0005524	Function	ATP binding	IEA
GO:0005886	Component	Plasma membrane	IBA
GO:0005886	Component	Plasma membrane	IEA
GO:0005886	Component	Plasma membrane	ISS
GO:0005886	Component	Plasma membrane	TAS
GO:0005929	Component	Cilium	IEA
GO:0005929	Component	Cilium	ISS
GO:0006171	Process	CAMP biosynthetic process	IBA
GO:0006171	Process	CAMP biosynthetic process	IDA	15385642, 24700542
GO:0006171	Process	CAMP biosynthetic process	IEA
GO:0006171	Process	CAMP biosynthetic process	IMP	24740569
GO:0007189	Process	Adenylate cyclase-activating G protein-coupled receptor signaling pathway	IBA
GO:0007189	Process	Adenylate cyclase-activating G protein-coupled receptor signaling pathway	IEA
GO:0007189	Process	Adenylate cyclase-activating G protein-coupled receptor signaling pathway	IMP	24700542
GO:0007191	Process	Adenylate cyclase-activating dopamine receptor signaling pathway	IEA
GO:0007195	Process	Adenylate cyclase-inhibiting dopamine receptor signaling pathway	IEA
GO:0007204	Process	Positive regulation of cytosolic calcium ion concentration	IMP	24740569
GO:0007626	Process	Locomotory behavior	IEA
GO:0008179	Function	Adenylate cyclase binding	IEA
GO:0008179	Function	Adenylate cyclase binding	ISS
GO:0009190	Process	Cyclic nucleotide biosynthetic process	IEA
GO:0016020	Component	Membrane	IDA	15385642
GO:0016020	Component	Membrane	IEA
GO:0016829	Function	Lyase activity	IEA
GO:0016849	Function	Phosphorus-oxygen lyase activity	IEA
GO:0035556	Process	Intracellular signal transduction	IEA
GO:0042995	Component	Cell projection	IEA
GO:0046872	Function	Metal ion binding	IEA
GO:0050885	Process	Neuromuscular process controlling balance	IEA
GO:0061178	Process	Regulation of insulin secretion involved in cellular response to glucose stimulus	IMP	24740569
GO:0097110	Function	Scaffold protein binding	IEA
GO:1904322	Process	Cellular response to forskolin	IDA	15385642, 24700542

Other IDs

• MIM: 600293
• HGNC: 236
• e!Ensembl: ENSG00000173175

Protein

• UniProt ID: O95622
• Protein name: Adenylate cyclase type 5 (EC 4.6.1.1) (ATP pyrophosphate-lyase 5) (Adenylate cyclase type V) (Adenylyl cyclase 5) (AC5)
• Protein function: Catalyzes the formation of the signaling molecule cAMP in response to G-protein signaling (PubMed:15385642, PubMed:24700542, PubMed:26206488). Mediates signaling downstream of ADRB1 (PubMed:24700542). Regulates the increase of free cytosolic Ca(
• PDB: 8SL3, 8SL4
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF16214	AC_N	1 → 458	Adenylyl cyclase N-terminal extracellular and transmembrane region	Family
  PF00211	Guanylate_cyc	460 → 642	Adenylate and Guanylate cyclase catalytic domain	Domain
  PF06327	DUF1053	668 → 761	Domain of Unknown Function (DUF1053)	Family
  PF00211	Guanylate_cyc	1062 → 1256	Adenylate and Guanylate cyclase catalytic domain	Domain

• Tissue specificity: TISSUE SPECIFICITY: Detected in pancreas islets (at protein level). Expressed in the brain, with high expression in the corpus striatum (PubMed:26085604). {ECO:0000269|PubMed:24740569, ECO:0000269|PubMed:26085604}.
• Sequence:

  MSGSKSVSPPGYAAQKTAAPAPRGGPEHRSAWGEADSRANGYPHAPGGSARGSTKKPGGA
  VTPQQQQRLASRWRSDDDDDPPLSGDDPLAGGFGFSFRSKSAWQERGGDDCGRGSRRQRR
  GAASGGSTRAPPAGGGGGSAAAAASAGGTEVRPRSVEVGLEERRGKGRAADELEAGAVEG
  GEGSGDGGSSADSGSGAGPGAVLSLGACCLALLQIFRSKKFPSDKLERLYQRYFFRLNQS
  SLTMLMAVLVLVCLVMLAFHAARPPLQLPYLAVLAAAVGVILIMAVLCNRAAFHQDHMGL
  ACYALIAVVLAVQVVGLLLPQPRSASEGIWWTVFFIYTIYTLLPVRMRAAVLSGVLLSAL
  HLAIALRTNAQDQFLLKQLVSNVLIFSCTNIVGVCTHYPAEVSQRQAFQETRECIQARLH
  SQRENQQQERLLLSVLPRHVAMEMKADINAKQEDMMFHKIYIQKHDNVSILFADIEGFTS
  LASQCTAQELVMTLNELFARFDKLAAENHCLRIKILGDCYYCVSGLPEARADHAHCCVEM
  GMDMIEAISLVREVTGVNVNMRVGIHSGRVHCGVLGLRKWQFDVWSNDVTLANHMEAGGK
  AGRIHITKATLNYLNGDYEVEPGCGGERNAYLKEHSIETFLILRCTQKRKEEKAMIAKMN
  RQRTNSIGHNPPHWGAERPFYNHLGGNQVSKEMKRMGFEDPKDKNAQESANPEDEVDEFL
  GRAIDARSIDRLRSEHVRKFLLTFREPDLEKKYSKQVDDRFGAYVACASLVFLFICFVQI
  TIVPHSIFMLSFYLTCSLLLTLVVFVSVIYSCVKLFPSPLQTLSRKIVRSKMNSTLVGVF
  TITLVFLAAFVNMFTCNSRDLLGCLAQEHNISASQVNACHVAESAVNYSLGDEQGFCGSP
  WPNCNFPEYFTYSVLLSLLACSVFLQISCIGKLVLMLAIELIYVLIVEVPGVTLFDNADL
  LVTANAIDFFNNGTSQCPEHATKVALKVVTPIIISVFVLALYLHAQQVESTARLDFLWKL
  QATEEKEEMEELQAYNRRLLHNILPKDVAAHFLARERRNDELYYQSCECVAVMFASIANF
  SEFYVELEANNEGVECLRLLNEIIADFDEIISEDRFRQLEKIKTIGSTYMAASGLNDSTY
  DKVGKTHIKALADFAMKLMDQMKYINEHSFNNFQMKIGLNIGPVVAGVIGARKPQYDIWG
  NTVNVASRMDSTGVPDRIQVTTDMYQVLAANTYQLECRGVVKVKGKGEMMTYFLNGGPPL
  S

• Sequence length: 1261

Pathways

KEGG:

Purine metabolism
Metabolic pathways
Endocrine resistance
Rap1 signaling pathway
cGMP-PKG signaling pathway
cAMP signaling pathway
Chemokine signaling pathway
Phospholipase D signaling pathway
Hormone signaling
Oocyte meiosis
Longevity regulating pathway
Longevity regulating pathway - multiple species
Adrenergic signaling in cardiomyocytes
Vascular smooth muscle contraction
Apelin signaling pathway
Gap junction
Platelet activation
Circadian entrainment
Thermogenesis
Retrograde endocannabinoid signaling
Glutamatergic synapse
Cholinergic synapse
Serotonergic synapse
GABAergic synapse
Dopaminergic synapse
Inflammatory mediator regulation of TRP channels
Insulin secretion
GnRH signaling pathway
Ovarian steroidogenesis
Progesterone-mediated oocyte maturation
Estrogen signaling pathway
Melanogenesis
Thyroid hormone synthesis
Oxytocin signaling pathway
Regulation of lipolysis in adipocytes
Renin secretion
Aldosterone synthesis and secretion
Relaxin signaling pathway
Cortisol synthesis and secretion
Parathyroid hormone synthesis, secretion and action
Cushing syndrome
Growth hormone synthesis, secretion and action
Salivary secretion
Gastric acid secretion
Pancreatic secretion
Bile secretion
Parkinson disease
Cocaine addiction
Amphetamine addiction
Morphine addiction
Alcoholism
Human cytomegalovirus infection
Human T-cell leukemia virus 1 infection
Pathways in cancer
Chemical carcinogenesis - receptor activation
Dilated cardiomyopathy

Reactome:

Glucagon signaling in metabolic regulation
PKA activation
PKA activation in glucagon signalling
Adenylate cyclase activating pathway
Adenylate cyclase inhibitory pathway
Glucagon-like Peptide-1 (GLP1) regulates insulin secretion
Adrenaline,noradrenaline inhibits insulin secretion
G alpha (s) signalling events
G alpha (z) signalling events
Vasopressin regulates renal water homeostasis via Aquaporins
Hedgehog 'off' state
ADORA2B mediated anti-inflammatory cytokines production
FCGR3A-mediated IL10 synthesis

Associated diseases

Causal
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession
ADCY5-related disorder	Likely pathogenic	rs1553751019	RCV003387603
Dyskinesia with orofacial involvement, autosomal dominant	Pathogenic; Likely pathogenic	rs2108372267, rs1007363034, rs2107658582, rs1576526285, rs1941427629, rs1553724606, rs864309484, rs796065306, rs864309483, rs2472988765, rs1553718863, rs797045002, rs864309515, rs910314734, rs1576704514, rs1553726054, rs1576606182, rs1576606282	RCV001548757 RCV001789712 RCV001789713 RCV002248962 RCV002248963 RCV002249230 RCV000202493 RCV000030679 RCV000202545 RCV002466312 RCV002468889 RCV000190498 RCV000202586 RCV000202572 RCV000987316 RCV000987319 RCV000987320 RCV000995686 RCV000995687 RCV000995688
Dyskinesia with orofacial involvement, autosomal recessive	Likely pathogenic; Pathogenic	rs2108390731, rs1365372289, rs1553751262	RCV001789714 RCV001789708 RCV001789709
Neurodevelopmental delay	Pathogenic	rs864309515	RCV002273986
Neurodevelopmental disorder with hyperkinetic movements and dyskinesia	Pathogenic; Likely pathogenic	rs2108148749, rs2108384208, rs756172692, rs1553751262	RCV001789715 RCV001789716 RCV004596501 RCV004596385
See cases	Pathogenic	rs864309515	RCV003128395

Unknown
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession
Cervical cancer	Benign	rs377556468	RCV005921412
Distal myopathy with posterior leg and anterior hand involvement	Uncertain significance	rs1286137967	RCV000714607
Dysarthria	Uncertain significance	rs1057518757	RCV000414975
Gastric cancer	Benign	rs13081065	RCV005916709
Hereditary ataxia	Conflicting classifications of pathogenicity	rs373748121	RCV005626712
Language disorder	Uncertain significance	rs1057518757	RCV000414975
Malignant tumor of esophagus	Benign	rs13081065	RCV005916708
Morphological central nervous system abnormality	Conflicting classifications of pathogenicity	rs2472794733	RCV005622197
Parkinsonian disorder	Uncertain significance	rs1057518757	RCV000414975
Thymoma	Benign	rs9870651	RCV005917942
Uterine carcinosarcoma	Benign	rs13081065, rs9870651	RCV005916710 RCV005917941

Associations from Text Mining
Disease Name	Relationship Type	References
Adenocarcinoma of Lung	Associate	35567329
Apraxia oculomotor Cogan type	Associate	27061943
Breast Neoplasms	Inhibit	35697697
Breast Neoplasms	Associate	36705562
Carcinoma Intraductal Noninfiltrating	Associate	35697697
Cardiomyopathy Dilated	Associate	27427220
Cerebral Palsy	Associate	28511835, 32647899
Chorea	Associate	26085604, 26537056, 27061943, 28511835, 36054588
Choreoathetosis Hypothyroidism And Neonatal Respiratory Distress	Associate	27061943
Colorectal Neoplasms	Associate	35545337
Diabetes Mellitus	Associate	25375650, 34801028
Diabetes Mellitus Type 2	Associate	20081857, 20081858, 20490451, 21712988, 21949744, 23193118, 23202124, 23462794, 24740569, 26168825, 27896934, 28684635, 29412141, 30089489, 31123324, 32163478
Diabetes Mellitus Type 2	Stimulate	27896934, 30089489
Dyskinesia Drug Induced	Associate	22782511, 24700542, 26085604, 26537056, 27061943, 28229249, 30772269, 32647899
Dyskinesia Familial with Facial Myokymia	Associate	22782511, 24700542
Dystonia	Associate	26085604, 26537056, 27061943, 28511835, 31731261, 35041927
Dystonia Focal Task Specific	Associate	26537056
Episodic Ataxia	Associate	26537056
Facial Nerve Diseases	Associate	22782511, 24700542, 26085604, 27061943
Glucose Metabolism Disorders	Associate	21712988, 21789219, 26168825
Head and Neck Neoplasms	Associate	28511835
Hyperglycemia	Associate	33513366
Hyperkinesis	Associate	26537056, 28511835, 32647899, 36054588
Hypertriglyceridemia	Associate	36233117
Hypoplastic Left Heart Syndrome	Associate	24793904
Hypoxia	Associate	38188159
Hypoxia Brain	Associate	38188159
Insulin Resistance	Associate	21789219, 32163478
Intellectual Disability	Associate	27061943
Leukemia Lymphocytic Chronic B Cell	Associate	20484983
Movement Disorders	Associate	22782511, 24700542, 28511835, 32647899
Multiple Sulfatase Deficiency Disease	Associate	39931922
Muscle Hypertonia	Associate	26537056
Muscle Hypotonia	Associate	26537056, 27061943
Muscular Diseases	Associate	28511835
Myoclonic dystonia	Associate	28229249
Myoclonus	Associate	26537056, 27061943, 28511835
Neoplasms	Associate	23544068
Obesity	Associate	21789219
Pneumonia Lipid	Associate	36233117
Polycystic Kidney Autosomal Dominant	Associate	22952279
Prostatic Neoplasms	Associate	23193118
Reperfusion Injury	Associate	38188159
Speech Disorders	Associate	39931922
Wolfram Like Syndrome Autosomal Dominant	Associate	26168825