ADCY1

Summary

ADCY1 (adenylate cyclase 1, HGNC:232) is a protein-coding gene on chromosome 7p12.3, encoding Adenylate cyclase type 1 (Q08828). Catalyzes the formation of the signaling molecule cAMP in response to G-protein signaling.

This gene encodes a member of the of adenylate cyclase gene family that is primarily expressed in the brain. This protein is regulated by calcium/calmodulin concentration and may be involved in brain development. Alternate splicing results in multiple transcript variants.

Source: NCBI Gene 107 — RefSeq curated summary.

At a glance

• Gene–disease (curated): hearing loss, autosomal recessive (Supportive, GenCC) — +2 more curated relationships
• GWAS associations: 3
• Clinical variants (ClinVar): 409 total — 6 pathogenic, 2 likely-pathogenic
• Phenotypes (HPO): 2
• Druggable target: yes — 2 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_021116

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:232
Approved symbol	ADCY1
Name	adenylate cyclase 1
Location	7p12.3
Locus type	gene with protein product
Status	Approved
Aliases	AC1
Ensembl gene	ENSG00000164742
Ensembl biotype	protein_coding
OMIM	103072
Entrez	107

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 4 protein_coding, 1 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000297323, ENST00000432715, ENST00000468353, ENST00000621543, ENST00000646653, ENST00000920696

RefSeq mRNA: 2 — MANE Select: NM_021116 NM_001281768, NM_021116

CCDS: CCDS34631, CCDS75593

Canonical transcript exons

ENST00000297323 — 20 exons

Exon	Start	End
ENSE00001087058	45710528	45710652
ENSE00001087060	45657727	45657885
ENSE00001087064	45660042	45660183
ENSE00001087066	45704518	45704616
ENSE00001087068	45685962	45686215
ENSE00001087070	45679709	45679793
ENSE00001087072	45677869	45678063
ENSE00001087073	45662059	45662214
ENSE00001087076	45684979	45685068
ENSE00001087077	45703600	45703746
ENSE00001087078	45678166	45678263
ENSE00001087080	45708350	45708464
ENSE00001138860	45648670	45648797
ENSE00001138866	45622632	45622743
ENSE00001138874	45610379	45610497
ENSE00001202433	45713693	45723116
ENSE00001212237	45574368	45575182
ENSE00001505123	45703376	45703492
ENSE00001505124	45686547	45686673
ENSE00003516486	45592759	45592908

Expression profiles

Bgee: expression breadth ubiquitous, 220 present calls, max score 98.59.

FANTOM5 (CAGE): breadth broad, TPM avg 3.7629 / max 205.6978, expressed in 531 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
78483	2.5361	512
78485	0.8668	227
78484	0.2394	142
78482	0.1206	73

Top tissues by expression

283 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
middle temporal gyrus	UBERON:0002771	98.59	gold quality
Brodmann (1909) area 23	UBERON:0013554	98.16	gold quality
orbitofrontal cortex	UBERON:0004167	97.47	gold quality
postcentral gyrus	UBERON:0002581	97.42	gold quality
parietal lobe	UBERON:0001872	97.35	gold quality
superior frontal gyrus	UBERON:0002661	96.90	gold quality
Brodmann (1909) area 46	UBERON:0006483	96.89	gold quality
endometrium epithelium	UBERON:0004811	96.34	gold quality
cortical plate	UBERON:0005343	96.09	gold quality
entorhinal cortex	UBERON:0002728	95.71	gold quality
occipital lobe	UBERON:0002021	95.30	gold quality
primary visual cortex	UBERON:0002436	95.04	gold quality
cerebellar vermis	UBERON:0004720	94.69	gold quality
frontal pole	UBERON:0002795	94.44	gold quality
paraflocculus	UBERON:0005351	94.23	gold quality
lateral nuclear group of thalamus	UBERON:0002736	93.36	gold quality
frontal cortex	UBERON:0001870	93.04	gold quality
frontal lobe	UBERON:0016525	93.04	gold quality
Brodmann (1909) area 10	UBERON:0013541	92.92	gold quality
prefrontal cortex	UBERON:0000451	92.76	gold quality
neocortex	UBERON:0001950	92.26	gold quality
CA1 field of hippocampus	UBERON:0003881	91.97	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	91.60	gold quality
cerebral cortex	UBERON:0000956	91.56	gold quality
endothelial cell	CL:0000115	91.36	gold quality
pons	UBERON:0000988	90.89	gold quality
cerebellum	UBERON:0002037	90.73	gold quality
right frontal lobe	UBERON:0002810	90.48	gold quality
cingulate cortex	UBERON:0003027	89.88	gold quality
cerebellar cortex	UBERON:0002129	89.85	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.77
E-GEOD-137537	no	532.75
E-ENAD-20	no	115.41
E-CURD-11	no	35.30

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): BMAL1, NPAS2, ZGLP1

miRNA regulators (miRDB)

404 targeting ADCY1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-188-3P	100.00	68.76	1240
HSA-MIR-4673	100.00	66.64	1490
HSA-MIR-6851-5P	100.00	65.63	1294
HSA-MIR-3689D	100.00	66.14	1181
HSA-MIR-432-3P	100.00	67.86	705
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-4455	100.00	65.48	1587
HSA-MIR-3120-5P	100.00	65.56	965
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-6758-5P	100.00	66.21	1470
HSA-MIR-6856-5P	100.00	65.47	1298
HSA-MIR-4534	99.99	66.58	1907
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-3667-3P	99.99	67.17	1636
HSA-MIR-1184	99.99	68.19	1458
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-4645-5P	99.98	65.81	1284

Literature-anchored findings (GeneRIF, showing 21)

• Tissue transglutaminase directly regulates adenylyl cyclase resulting in enhanced cAMP-response element-binding protein (CREB) activation. (PMID:12743114)
• Transgenic mice overexpressing type-1 adenylyl cyclase in the forebrain show elevated long-term potentiation (LTP), increased memory for object recognition and slower rates of extinction for contextual memory. (PMID:15133516)
• Expression of sensitization of AC1 involves Galpha(s)-adenylyl cyclase interactions. (PMID:15361543)
• Maps to 7p14.1-q11.22 between D7S2209 and marker D7S2435, maximum Lod score 5 for D7S1818. (PMID:15583425)
• These results suggest a possible role of APLP1 in regulation of alpha2A-adrenergic receptor trafficking. (PMID:16531006)
• Fully differentiated human airway epithelial cells in culture are shown to express calcium-stimulated transmembrane adenylyl cyclase (tmAC) isoforms (types 1, 3, and 8) by reverse transcription polymerase chain reaction. (PMID:17586501)
• Distinct mechanisms of regulation by Ca2+/calmodulin of type 1 and 8 adenylyl cyclases support their different physiological roles. (PMID:19029295)
• Young transgenic mice overexpressing AC1 in the forebrain (AC1+ mice) have enhanced hippocampal long-term potentiation, superior memory for novel object recognition and more persistent remote contextual memory. (PMID:19726641)
• Compartmentalized AC1-CFTR association is responsible for Ca(2+)/cAMP cross-talk. (PMID:20554763)
• AGS3 reduced D(2L)DR-mediated sensitization of AC1 and AC2. (PMID:23504261)
• Results demonstrate that ADCY1 has an evolutionarily conserved role in hearing. (PMID:24482543)
• AC1 catalytic activity can be adjusted by mediating calmodulin activation of AC1 by reversible methionine oxidation in calmodulin. (PMID:25462816)
• Increased expression of AC1 in the forebrain leads to deficits in behavioral inhibition. (PMID:25568126)
• STC1 interferes with CALCRL signaling during osteoblastogenesis via adenylate cyclase inhibition. (PMID:25591908)
• Data show that the adenylate cyclase (AC) pathway as genes relating to the antitumor activity of xanthohumol (XN) against tumor cells, and the pathway regulates various cellular functions via activating protein kinase A (PKA)-dependent phosphorylation. (PMID:28122154)
• data indicate that ST034307 is a selective small-molecule inhibitor of AC1 and suggest that selective AC1 inhibitors may be useful for managing pain. (PMID:28223412)
• Mechanistic investigations identified adenylate cyclase 1 (ADCY1) as a direct target of miR-23a-3p in mucosal melanoma, and knockdown of ADCY1 recapitulated all the phenotypic characteristics of miR-23a-3p overexpression. (PMID:30867808)
• Pancreatic cancer-derived exosomal microRNA-19a induces beta-cell dysfunction by targeting ADCY1 and EPAC2. (PMID:34512170)
• GNG7 and ADCY1 as diagnostic and prognostic biomarkers for pancreatic adenocarcinoma through bioinformatic-based analyses. (PMID:34650124)
• Circ-LTBP1 is involved in doxorubicin-induced intracellular toxicity in cardiomyocytes via miR-107/ADCY1 signal. (PMID:35076816)
• Downregulated INHBB in endometrial tissue of recurrent implantation failure patients impeded decidualization through the ADCY1/cAMP signalling pathway. (PMID:36913138)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	adcy1a	ENSDARG00000069026
danio_rerio	adcy1b	ENSDARG00000088634
mus_musculus	Adcy1	ENSMUSG00000020431
rattus_norvegicus	Adcy1	ENSRNOG00000059479

Paralogs (17): GUCY1B1 (ENSG00000061918), GUCY2C (ENSG00000070019), ADCY2 (ENSG00000078295), GUCY2F (ENSG00000101890), NPR3 (ENSG00000113389), ADCY7 (ENSG00000121281), ADCY4 (ENSG00000129467), GUCY2D (ENSG00000132518), ADCY3 (ENSG00000138031), GUCY1A2 (ENSG00000152402), ADCY8 (ENSG00000155897), NPR2 (ENSG00000159899), ADCY9 (ENSG00000162104), GUCY1A1 (ENSG00000164116), NPR1 (ENSG00000169418), ADCY5 (ENSG00000173175), ADCY6 (ENSG00000174233)

Protein

Protein identifiers

Adenylate cyclase type 1 — Q08828 (reviewed: Q08828)

Alternative names: ATP pyrophosphate-lyase 1, Adenylate cyclase type I, Adenylyl cyclase 1, Ca(2+)/calmodulin-activated adenylyl cyclase

All UniProt accessions (2): C9J1J0, Q08828

UniProt curated annotations — full annotation on UniProt →

Function. Catalyzes the formation of the signaling molecule cAMP in response to G-protein signaling. Mediates responses to increased cellular Ca(2+)/calmodulin levels. 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.

Subunit / interactions. Interacts with CALM.

Subcellular location. Membrane. Cell membrane. Cytoplasm. Membrane raft.

Tissue specificity. Detected in zona glomerulosa and zona fasciculata in the adrenal gland (at protein level). Brain, retina and adrenal medulla.

Post-translational modifications. N-glycosylated.

Disease relevance. Deafness, autosomal recessive, 44 (DFNB44) [MIM:610154] A form of non-syndromic deafness characterized by prelingual profound hearing loss affecting all frequencies. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. Activated by G(s) G alpha protein GNAS. Inhibited by G(i) G alpha protein GNAI1. Is further activated by the complex formed by GNB1 and GNG2. Activated by calcium/calmodulin. Inhibited by the ATP analogs adenosine, 2’-deoxyadenosine and 2’-deoxy-3’-AMP.

Cofactor. Binds 2 magnesium ions per subunit. Is also active with manganese (in vitro).

Domain organisation. The protein contains two modules with six transmembrane helices each; both are required for catalytic activity. Isolated N-terminal or C-terminal guanylate cyclase domains have no catalytic activity, but when they are brought together, enzyme activity is restored. The active site is at the interface of the two domains. Both contribute substrate-binding residues, but the catalytic metal ions are bound exclusively via the N-terminal guanylate cyclase domain.

Similarity. Belongs to the adenylyl cyclase class-4/guanylyl cyclase family.

RefSeq proteins (2): NP_001268697, NP_066939* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001054	A/G_cyclase	Domain
IPR018297	A/G_cyclase_CS	Conserved_site
IPR029787	Nucleotide_cyclase	Homologous_superfamily
IPR030672	Adcy	Family
IPR032628	AC_N	Domain

Pfam: PF00211, PF16214

Enzyme classification (BRENDA):

• EC 4.6.1.1 — adenylate cyclase (BRENDA: 120 organisms, 167 substrates, 404 inhibitors, 155 Km, 27 kcat entries)

Substrate kinetics (BRENDA)

9 substrates with measured Km, best-characterized 9. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
ATP	0.0005–8.78	135
MGATP2-	0.009–2.2	4
MNATP2-	0.067–0.086	2
ADENYLIMIDODIPHOSPHATE	0.33	1
CAMP	14	1
DATP	0.44	1
DEOXYCAMP	13	1
DIPHOSPHATE	1.9	1
GTP	1.38	1

Catalyzed reactions (Rhea), 1 shown:

• ATP = 3’,5’-cyclic AMP + diphosphate (RHEA:15389)

UniProt features (37 total): transmembrane region 12, binding site 12, topological domain 3, region of interest 3, sequence variant 3, chain 1, compositionally biased region 1, modified residue 1, glycosylation site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q08828-F1	78.34	0.43

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (12): 308–313; 308; 308; 309; 350–352; 352; 352; 396; 920; 997–999; 1004–1008; 1044

Post-translational modifications (1): 551

Glycosylation sites (1): 704

Function

Pathways and Gene Ontology

Reactome pathways

49 pathways

ID	Pathway
R-HSA-163359	Glucagon signaling in metabolic regulation
R-HSA-163615	PKA activation
R-HSA-164378	PKA activation in glucagon signalling
R-HSA-170660	Adenylate cyclase activating pathway
R-HSA-170670	Adenylate cyclase inhibitory pathway
R-HSA-418555	G alpha (s) signalling events
R-HSA-418594	G alpha (i) signalling events
R-HSA-418597	G alpha (z) signalling events
R-HSA-432040	Vasopressin regulates renal water homeostasis via Aquaporins
R-HSA-442720	CREB1 phosphorylation through the activation of Adenylate Cyclase
R-HSA-5610787	Hedgehog ‘off’ state
R-HSA-9634597	GPER1 signaling
R-HSA-9660821	ADORA2B mediated anti-inflammatory cytokines production
R-HSA-9664323	FCGR3A-mediated IL10 synthesis
R-HSA-9856530	High laminar flow shear stress activates signaling by PIEZO1 and PECAM1:CDH5:KDR in endothelial cells
R-HSA-111885	Opioid Signalling
R-HSA-111931	PKA-mediated phosphorylation of CREB
R-HSA-111933	Calmodulin induced events
R-HSA-111996	Ca-dependent events
R-HSA-111997	CaM pathway
R-HSA-112040	G-protein mediated events
R-HSA-112043	PLC beta mediated events
R-HSA-112314	Neurotransmitter receptors and postsynaptic signal transmission
R-HSA-112315	Transmission across Chemical Synapses
R-HSA-112316	Neuronal System
R-HSA-1430728	Metabolism
R-HSA-1489509	DAG and IP3 signaling
R-HSA-162582	Signal Transduction
R-HSA-163685	Integration of energy metabolism
R-HSA-1643685	Disease

MSigDB gene sets: 394 (showing top): GOBP_CIRCADIAN_RHYTHM, GOBP_MEMORY, GNF2_RTN1, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, AAGCAAT_MIR137, WANG_CLIM2_TARGETS_UP, GOBP_COGNITION, GOBP_BEHAVIOR, BIOCARTA_EDG1_PATHWAY, GOBP_INFLAMMATORY_RESPONSE, GOBP_CELLULAR_RESPONSE_TO_LIPID, GOBP_RESPONSE_TO_FLUID_SHEAR_STRESS, PEREZ_TP63_TARGETS, REACTOME_G_ALPHA_Z_SIGNALLING_EVENTS, GOBP_POSITIVE_REGULATION_OF_CREB_TRANSCRIPTION_FACTOR_ACTIVITY

GO Biological Process (18): renal water homeostasis (GO:0003091), cAMP biosynthetic process (GO:0006171), adenylate cyclase-activating G protein-coupled receptor signaling pathway (GO:0007189), axonogenesis (GO:0007409), long-term memory (GO:0007616), obsolete positive regulation of CREB transcription factor activity (GO:0032793), intracellular signal transduction (GO:0035556), regulation of circadian rhythm (GO:0042752), rhythmic process (GO:0048511), cellular response to calcium ion (GO:0071277), cellular response to glucagon stimulus (GO:0071377), vascular endothelial cell response to laminar fluid shear stress (GO:0097700), presynaptic modulation of chemical synaptic transmission (GO:0099171), neuroinflammatory response (GO:0150076), positive regulation of long-term synaptic potentiation (GO:1900273), cellular response to forskolin (GO:1904322), cyclic nucleotide biosynthetic process (GO:0009190), modulation of chemical synaptic transmission (GO:0050804)

GO Molecular Function (8): adenylate cyclase activity (GO:0004016), calmodulin binding (GO:0005516), ATP binding (GO:0005524), calcium- and calmodulin-responsive adenylate cyclase activity (GO:0008294), metal ion binding (GO:0046872), nucleotide binding (GO:0000166), lyase activity (GO:0016829), phosphorus-oxygen lyase activity (GO:0016849)

GO Cellular Component (11): cytoplasm (GO:0005737), plasma membrane (GO:0005886), membrane raft (GO:0045121), extracellular exosome (GO:0070062), Schaffer collateral - CA1 synapse (GO:0098685), hippocampal mossy fiber to CA3 synapse (GO:0098686), presynapse (GO:0098793), postsynaptic density membrane (GO:0098839), glutamatergic synapse (GO:0098978), postsynaptic density (GO:0014069), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-18 pathways:

Category	Pathways
GPCR downstream signalling	3
G-protein mediated events	2
Anti-inflammatory response favouring Leishmania parasite infection	2
Integration of energy metabolism	1
PKA-mediated phosphorylation of CREB	1
Glucagon signaling in metabolic regulation	1
Activation of GABAB receptors	1
Aquaporin-mediated transport	1
Post NMDA receptor activation events	1
Signaling by Hedgehog	1
G alpha (s) signalling events	1
Response of endothelial cells to shear stress	1
G alpha (i) signalling events	1
Calmodulin induced events	1
CaM pathway	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
synapse	3
intracellular anatomical structure	2
renal system process	1
multicellular organismal-level water homeostasis	1
purine ribonucleotide biosynthetic process	1
cyclic nucleotide biosynthetic process	1
cAMP metabolic process	1
adenylate cyclase-modulating G protein-coupled receptor signaling pathway	1
adenylate cyclase activator activity	1
cell morphogenesis involved in neuron differentiation	1
neuron projection morphogenesis	1
axon development	1
memory	1
signal transduction	1
circadian rhythm	1
regulation of biological process	1
biological_process	1
response to calcium ion	1
cellular response to metal ion	1
response to glucagon	1
cellular response to peptide hormone stimulus	1
cellular response to laminar fluid shear stress	1
vascular endothelial cell response to fluid shear stress	1
modulation of chemical synaptic transmission	1
presynapse	1
inflammatory response	1
positive regulation of synaptic transmission	1
long-term synaptic potentiation	1
regulation of long-term synaptic potentiation	1
cellular response to lipid	1
cellular response to alcohol	1
cellular response to ketone	1
response to forskolin	1
nucleotide biosynthetic process	1
cyclic nucleotide metabolic process	1
chemical synaptic transmission	1
regulation of trans-synaptic signaling	1
cyclase activity	1
phosphorus-oxygen lyase activity	1

Protein interactions and networks

STRING

1720 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ADCY1	CALML5	Q9NZT1	769
ADCY1	CALM1	P02593	768
ADCY1	CALML4	Q96GE6	765
ADCY1	CALML6	Q8TD86	763
ADCY1	CALML3	P27482	759
ADCY1	GNAS	Q5JWF2	735
ADCY1	GNB1	P04697	681
ADCY1	PLPPR3	Q6T4P5	649
ADCY1	BRD1	O95696	640
ADCY1	SLBP	Q14493	639
ADCY1	PRKACG	P22612	627
ADCY1	PLCB1	Q9NQ66	622
ADCY1	RAPGEF3	O95398	593
ADCY1	NPAS2	Q99743	569
ADCY1	GNAI3	P08754	546

IntAct

4 interactions, top by confidence:

A	B	Type	Score
ADCY1	FZD7	psi-mi:“MI:0915”(physical association)	0.370
M		psi-mi:“MI:0914”(association)	0.350
ITM2B	ILVBL	psi-mi:“MI:0914”(association)	0.350

BioGRID (7): SERTAD1 (Affinity Capture-Western), ADCY1 (Reconstituted Complex), SERTAD1 (Reconstituted Complex), ADCY1 (Biochemical Activity), ADCY1 (Affinity Capture-RNA), ADCY1 (Two-hybrid), ADCY1 (Affinity Capture-RNA)

ESM2 similar proteins: A0JMH2, A5K3F9, A6XGL0, A8IRK7, B0BNM1, B7QDG3, C3YDS7, D3ZEY4, D3ZU57, E2QRY6, E7FCP8, F6W8I0, F7DL67, F7FIH8, O14976, O88444, P16386, P51828, P52333, P52824, P53370, P70563, Q08828, Q0PIT9, Q17QN2, Q2KI13, Q2KI24, Q3TIU4, Q4R4T6, Q5GA22, Q5RAR6, Q5ZHX9, Q6AXQ5, Q6DHK1, Q6L8Q7, Q6P5E8, Q6QRN6, Q8CH40, Q8K2J9, Q8K4Z3

Diamond homologs: A0A0U1RPR8, A8WPG9, A8XQC7, B1Q257, H2L002, N1NVB7, O02298, O02740, O16544, O19179, O54865, O60503, O62026, O62179, O75343, O88444, O95622, P0A4Y1, P16066, P16068, P18293, P19686, P19687, P19754, P20595, P22717, P23897, P25092, P26769, P26770, P30803, P30804, P33402, P40144, P40145, P40146, P51828, P51829, P51830, P51839

SIGNOR signaling

15 interactions.

A	Effect	B	Mechanism
ADCY1	up-regulates	“3’,5’-cyclic AMP”	“chemical modification”
GNAS	“up-regulates activity”	ADCY1	binding
GNAI1	“down-regulates activity”	ADCY1	binding
GNAI2	“down-regulates activity”	ADCY1	binding
GNAI3	“down-regulates activity”	ADCY1	binding
ADCY1	“up-regulates activity”	PRKACA
GNAL	“up-regulates activity”	ADCY1	binding
GNB5	“down-regulates activity”	ADCY1	binding
ADCY1	“up-regulates quantity”	“3’,5’-cyclic AMP”	“chemical modification”
GNAI2	down-regulates	ADCY1	binding
GNAI3	down-regulates	ADCY1	binding
GNAZ	“down-regulates activity”	ADCY1	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

409 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	6
Likely pathogenic	2
Uncertain significance	158
Likely benign	175
Benign	46

Top pathogenic / likely-pathogenic (8)

Variant ID	HGVS	Classification
1047885	GRCh37/hg19 7p14.1-12.3(chr7:41124364-47945566)	Pathogenic
2685239	GRCh37/hg19 7p14.1-12.3(chr7:42516660-46202495)x1	Pathogenic
3063593	NC_000007.14:g.45043702_46521017delins[AGAAGGAAATTT;45310743_46521014;45043709_45310738inv]	Pathogenic
394005	GRCh37/hg19 7p14.1-12.3(chr7:40350383-47034422)x1	Pathogenic
4682689	GRCh37/hg19 7p14.3-12.3(chr7:29296048-47809018)x1	Pathogenic
58547	GRCh38/hg38 7p13-12.3(chr7:44193369-46558381)x1	Pathogenic
4682687	GRCh37/hg19 7p14.2-12.3(chr7:37166777-45983129)x3	Likely pathogenic
4845837	NM_021116.4(ADCY1):c.2410C>T (p.Gln804Ter)	Likely pathogenic

SpliceAI

3406 predictions. Top by Δscore:

Variant	Effect	Δscore
7:45575178:GGACG:G	donor_gain	1.0000
7:45575179:GACGG:G	donor_gain	1.0000
7:45592753:CTGCA:C	acceptor_loss	1.0000
7:45592754:TGCAG:T	acceptor_loss	1.0000
7:45592755:GCA:G	acceptor_loss	1.0000
7:45592756:CA:C	acceptor_loss	1.0000
7:45592757:A:AG	acceptor_gain	1.0000
7:45592757:AGCTC:A	acceptor_gain	1.0000
7:45592758:G:GA	acceptor_gain	1.0000
7:45592758:GC:G	acceptor_gain	1.0000
7:45592758:GCT:G	acceptor_gain	1.0000
7:45592758:GCTC:G	acceptor_gain	1.0000
7:45592758:GCTCG:G	acceptor_gain	1.0000
7:45592905:GCAG:G	donor_gain	1.0000
7:45592908:GGTC:G	donor_loss	1.0000
7:45592909:G:GG	donor_gain	1.0000
7:45592909:GTCA:G	donor_loss	1.0000
7:45610372:T:TA	acceptor_gain	1.0000
7:45610374:TCCAG:T	acceptor_loss	1.0000
7:45610375:CCA:C	acceptor_loss	1.0000
7:45610377:A:AG	acceptor_gain	1.0000
7:45610377:AG:A	acceptor_gain	1.0000
7:45610377:AGGAG:A	acceptor_loss	1.0000
7:45610378:G:A	acceptor_loss	1.0000
7:45610378:G:GT	acceptor_gain	1.0000
7:45610378:GG:G	acceptor_gain	1.0000
7:45610378:GGA:G	acceptor_gain	1.0000
7:45610378:GGAGC:G	acceptor_gain	1.0000
7:45610498:GTAGG:G	donor_loss	1.0000
7:45622741:ACGGT:A	donor_loss	1.0000

AlphaMissense

7242 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:45610383:G:C	R265P	1.000
7:45610386:T:C	L266P	1.000
7:45610389:T:A	L267H	1.000
7:45610389:T:C	L267P	1.000
7:45610398:T:C	L270P	1.000
7:45610401:T:A	L271Q	1.000
7:45610401:T:C	L271P	1.000
7:45610413:T:A	V275D	1.000
7:45610416:C:A	A276D	1.000
7:45610425:T:A	M279K	1.000
7:45610425:T:C	M279T	1.000
7:45610425:T:G	M279R	1.000
7:45610429:G:C	K280N	1.000
7:45610429:G:T	K280N	1.000
7:45610460:T:C	F291L	1.000
7:45610461:T:G	F291C	1.000
7:45610462:C:A	F291L	1.000
7:45610462:C:G	F291L	1.000
7:45610472:T:G	Y295D	1.000
7:45610476:T:A	I296N	1.000
7:45610496:A:C	S303R	1.000
7:45622632:C:A	S303R	1.000
7:45622632:C:G	S303R	1.000
7:45622637:T:C	L305P	1.000
7:45622639:T:C	F306L	1.000
7:45622641:T:A	F306L	1.000
7:45622641:T:G	F306L	1.000
7:45622642:G:C	A307P	1.000
7:45622643:C:A	A307D	1.000
7:45622645:G:C	D308H	1.000

dbSNP variants (sampled 300 via entrez): RS1000001511 (7:45639264 T>C), RS1000006984 (7:45575362 C>T), RS1000025786 (7:45723299 T>C,G), RS1000032033 (7:45702901 G>A), RS1000058629 (7:45720139 G>A,C), RS1000065813 (7:45620537 A>G), RS1000071551 (7:45593543 C>A,T), RS1000076947 (7:45580913 C>T), RS1000092383 (7:45670558 C>A), RS1000095107 (7:45620843 C>G,T), RS1000116140 (7:45595574 T>A,C,G), RS1000123242 (7:45713486 CTG>C), RS1000142070 (7:45635645 A>T), RS1000147669 (7:45703229 C>A,G), RS1000158330 (7:45671885 T>C)

Disease associations

OMIM: gene MIM:103072 | disease phenotypes: MIM:610154, MIM:603284

GenCC curated gene-disease

Disease	Classification	Inheritance
hearing loss, autosomal recessive	Supportive	Autosomal recessive
nonsyndromic genetic hearing loss	Limited	Autosomal recessive
autosomal recessive nonsyndromic hearing loss 44	Limited	Unknown

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
nonsyndromic genetic hearing loss	Limited	AR

Mondo (5): autosomal recessive nonsyndromic hearing loss 44 (MONDO:0012421), syndactyly (MONDO:0021002), cerebral cavernous malformation 2 (MONDO:0011304), nonsyndromic genetic hearing loss (MONDO:0019497), hearing loss, autosomal recessive (MONDO:0019588)

Orphanet (2): Rare autosomal recessive non-syndromic sensorineural deafness type DFNB (Orphanet:90636), Familial cerebral cavernous malformation (Orphanet:221061)

HPO phenotypes

2 total (3 of 2 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000399	Prelingual sensorineural hearing impairment
HP:0001159	Syndactyly

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST003160_3	Subjective response to lithium treatment in bipolar disorder	5.000000e-07
GCST003542_93	Night sleep phenotypes	1.000000e-07
GCST005081_7	Bipolar disorder lithium response (continuous) or schizophrenia	3.000000e-08

MeSH disease descriptors (5)

Descriptor	Name	Tree numbers
D013576	Syndactyly	C05.116.099.370.894.819; C05.660.585.800; C05.660.906.819; C16.131.621.585.800; C16.131.621.906.819
C566394	Cerebral Cavernous Malformations 2 (supp.)
C564609	Deafness, Autosomal Recessive (supp.)
C565716	Deafness, Autosomal Recessive 44 (supp.)
C580334	Nonsyndromic Deafness (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL2097167 (PROTEIN FAMILY), CHEMBL2899 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

2 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 40,693 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL4297305	NB-001	3	94
CHEMBL52606	COLFORSIN	2	40,599

PharmGKB: 1 entry (VIP=true, CPIC=false)

PharmGKB clinical annotations

1 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs1521470	Efficacy	3	lithium	Bipolar Disorder

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs1521470	ADCY1	3	0.00	1	lithium

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: enzyme — Adenylyl cyclases (ACs)

Most potent curated ligand interactions (2 total), top 2:

Ligand	Action	Affinity	Parameter
compound 45 [PMID: 8709105]	Activation	7.68	pIC50
ST034307	Inhibition	5.64	pIC50

ChEMBL bioactivities

263 potent at pChembl≥5 of 286 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.06	Ki	0.88	nM	CHEMBL3142312
8.77	Ki	1.7	nM	CHEMBL3142318
8.77	Ki	1.7	nM	CHEMBL3142332
8.72	Ki	1.9	nM	CHEMBL3142329
8.60	Ki	2.5	nM	CHEMBL3142331
8.59	Ki	2.6	nM	CHEMBL2369777
8.41	Ki	3.9	nM	CHEMBL2369525
8.38	Ki	4.2	nM	CHEMBL2369778
8.11	Ki	7.8	nM	CHEMBL3142313
7.85	Ki	14	nM	CHEMBL66087
7.77	Ki	17	nM	CHEMBL418135
7.70	Ki	20	nM	CHEMBL293907
7.68	IC50	21	nM	CHEMBL328689
7.54	Ki	29	nM	CHEMBL305151
7.51	IC50	31	nM	CHEMBL328561
7.50	IC50	32	nM	CHEMBL92229
7.48	Ki	33	nM	CHEMBL62123
7.44	IC50	36	nM	CHEMBL329247
7.41	IC50	39	nM	CHEMBL93009
7.39	IC50	41	nM	COLFORSIN
7.37	IC50	43	nM	CHEMBL317990
7.36	IC50	44	nM	CHEMBL432817
7.19	IC50	64	nM	CHEMBL93242
7.19	IC50	65	nM	CHEMBL93259
7.16	IC50	70	nM	CHEMBL6166043
7.16	IC50	70	nM	CHEMBL6150287
7.16	IC50	70	nM	CHEMBL6169928
7.16	Ki	69	nM	CHEMBL305151
7.15	EC50	71	nM	(R)-SKF-38393
7.14	IC50	73	nM	CHEMBL92911
7.12	IC50	76	nM	CHEMBL329916
7.12	IC50	76	nM	CHEMBL328358
7.10	IC50	80	nM	CHEMBL6133492
7.09	IC50	82	nM	CHEMBL430458
7.05	IC50	89	nM	CHEMBL93521
7.02	IC50	95	nM	CHEMBL327672
6.96	IC50	110	nM	CHEMBL6164072
6.96	IC50	110	nM	CHEMBL6164876
6.96	IC50	110	nM	CHEMBL6165758
6.96	IC50	110	nM	CHEMBL6162018
6.96	Ki	110	nM	CHEMBL62412
6.95	IC50	112	nM	CHEMBL93260
6.93	IC50	117	nM	CHEMBL92577
6.93	IC50	117	nM	CHEMBL94343
6.92	IC50	120	nM	CHEMBL6167528
6.91	IC50	123	nM	CHEMBL94313
6.89	IC50	128	nM	CHEMBL91909
6.85	IC50	140	nM	CHEMBL6162089
6.85	IC50	142	nM	CHEMBL330054
6.84	Ki	144	nM	CHEMBL64475

PubChem BioAssay actives

235 with measured affinity, of 451 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
(4R,7S,10S,13S,16S)-N-[(2R)-1-[[(2R)-1-amino-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]-7-(2-amino-2-oxoethyl)-13-benzyl-20,20-dicyclopentyl-16-[(4-ethoxyphenyl)methyl]-6,9,12,15,18-pentaoxo-10-propan-2-yl-1,2-dithia-5,8,11,14,17-pentazacycloicosane-4-carboxamide	34311: Compound was evaluated for the inhibition constant for inhibition of 8-lysine-vasopressin stimulated adenylate cyclase of pig kidney medullary membrane	ki	0.0009	uM
(4R,7S,10S,13S,16S)-N-[(2S)-1-[[(2S)-1-amino-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]-7-(2-amino-2-oxoethyl)-13-benzyl-20,20-dicyclopentyl-16-[(4-ethoxyphenyl)methyl]-6,9,12,15,18-pentaoxo-10-propan-2-yl-1,2-dithia-5,8,11,14,17-pentazacycloicosane-4-carboxamide	34311: Compound was evaluated for the inhibition constant for inhibition of 8-lysine-vasopressin stimulated adenylate cyclase of pig kidney medullary membrane	ki	0.0017	uM
(4R,7S,10S,13S,16S)-N-[(2S)-1-[[(2R)-1-amino-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]-7-(2-amino-2-oxoethyl)-13-benzyl-20,20-dicyclopentyl-16-[(4-ethoxyphenyl)methyl]-6,9,12,15,18-pentaoxo-10-propan-2-yl-1,2-dithia-5,8,11,14,17-pentazacycloicosane-4-carboxamide	34311: Compound was evaluated for the inhibition constant for inhibition of 8-lysine-vasopressin stimulated adenylate cyclase of pig kidney medullary membrane	ki	0.0017	uM
(4R,7S,10S,13S,16S)-N-[(2R)-1-[[(2S)-1-amino-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]-7-(2-amino-2-oxoethyl)-13-benzyl-20,20-dicyclopentyl-16-[(4-ethoxyphenyl)methyl]-6,9,12,15,18-pentaoxo-10-propan-2-yl-1,2-dithia-5,8,11,14,17-pentazacycloicosane-4-carboxamide	34311: Compound was evaluated for the inhibition constant for inhibition of 8-lysine-vasopressin stimulated adenylate cyclase of pig kidney medullary membrane	ki	0.0019	uM
(4R,7S,10S,13S,16S)-N-[(2S)-1-amino-5-(diaminomethylideneamino)-1-oxopentan-2-yl]-7-(2-amino-2-oxoethyl)-13-benzyl-20,20-dicyclopentyl-16-[(4-ethoxyphenyl)methyl]-6,9,12,15,18-pentaoxo-10-propan-2-yl-1,2-dithia-5,8,11,14,17-pentazacycloicosane-4-carboxamide	34312: Compound was evaluated for the inhibition constant for inhibition of 8-lysine-vasopressin stimulated adenylate cyclase of pig kidney medullary membrane	ki	0.0025	uM
(4R,7S,10S,13S,16R)-7-(2-amino-2-oxoethyl)-13-benzyl-20,20-dicyclopentyl-N-[(2S)-5-(diaminomethylideneamino)-1-[[(2S)-1,6-diamino-1-oxohexan-2-yl]amino]-1-oxopentan-2-yl]-16-[(4-ethoxyphenyl)methyl]-6,9,12,15,18-pentaoxo-10-propan-2-yl-1,2-dithia-5,8,11,14,17-pentazacycloicosane-4-carboxamide	34311: Compound was evaluated for the inhibition constant for inhibition of 8-lysine-vasopressin stimulated adenylate cyclase of pig kidney medullary membrane	ki	0.0026	uM
(2S)-N-[(2S)-1-amino-5-(diaminomethylideneamino)-1-oxopentan-2-yl]-1-[(4R,7S,10S,13S,16R)-7-(2-amino-2-oxoethyl)-13-benzyl-20,20-dicyclopentyl-16-[(4-ethoxyphenyl)methyl]-6,9,12,15,18-pentaoxo-10-propan-2-yl-1,2-dithia-5,8,11,14,17-pentazacycloicosane-4-carbonyl]pyrrolidine-2-carboxamide	34311: Compound was evaluated for the inhibition constant for inhibition of 8-lysine-vasopressin stimulated adenylate cyclase of pig kidney medullary membrane	ki	0.0039	uM
(4R,7S,10S,13S,16R)-N-[(2S)-6-amino-1-[[(2S)-1-amino-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-1-oxohexan-2-yl]-7-(2-amino-2-oxoethyl)-13-benzyl-20,20-dicyclopentyl-16-[(4-ethoxyphenyl)methyl]-6,9,12,15,18-pentaoxo-10-propan-2-yl-1,2-dithia-5,8,11,14,17-pentazacycloicosane-4-carboxamide	34311: Compound was evaluated for the inhibition constant for inhibition of 8-lysine-vasopressin stimulated adenylate cyclase of pig kidney medullary membrane	ki	0.0042	uM
(2S)-2-[[(2S)-2-[[(4R,7S,10S,13S,16S)-7-(2-amino-2-oxoethyl)-13-benzyl-20,20-dicyclopentyl-16-[(4-ethoxyphenyl)methyl]-6,9,12,15,18-pentaoxo-10-propan-2-yl-1,2-dithia-5,8,11,14,17-pentazacycloicosane-4-carbonyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-5-(diaminomethylideneamino)pentanoic acid	34311: Compound was evaluated for the inhibition constant for inhibition of 8-lysine-vasopressin stimulated adenylate cyclase of pig kidney medullary membrane	ki	0.0078	uM
3-[[4-[1-[4-(2,4-dichlorophenyl)anilino]-1-oxooctan-2-yl]oxybenzoyl]amino]propanoic acid	34294: In vitro inhibitory activity against glucagon induced human adenylate cyclase	ki	0.0140	uM
3-[[4-[1-[4-(1-benzofuran-2-yl)anilino]-1-oxooctan-2-yl]oxybenzoyl]amino]propanoic acid	34294: In vitro inhibitory activity against glucagon induced human adenylate cyclase	ki	0.0170	uM
3-[[4-[2-[[4-(1-benzofuran-2-yl)phenyl]carbamoyl]octyl]benzoyl]amino]propanoic acid	34294: In vitro inhibitory activity against glucagon induced human adenylate cyclase	ki	0.0200	uM
[(3R,4aR,5S,6S,6aS,10S,10aR,10bS)-3-ethenyl-10,10b-dihydroxy-3,4a,7,7,10a-pentamethyl-1-oxo-6-(2-pyridin-2-ylethylcarbamoyloxy)-5,6,6a,8,9,10-hexahydro-2H-benzo[f]chromen-5-yl] acetate	34749: Inhibition of [125 I]6-IHPP-forskolin binding to adenylate cyclase 1	ic50	0.0210	uM
3-[[4-[3-[4-(1-benzofuran-2-yl)anilino]-2-(4-tert-butylphenyl)-3-oxopropyl]benzoyl]amino]propanoic acid	34296: In vitro inhibitory activity against glucagon induced human adenylate cyclase	ki	0.0290	uM
[(3R,4aR,5S,6S,6aS,10S,10aR,10bS)-6-(2-aminoethylcarbamoyloxy)-3-ethenyl-10,10b-dihydroxy-3,4a,7,7,10a-pentamethyl-1-oxo-5,6,6a,8,9,10-hexahydro-2H-benzo[f]chromen-5-yl] acetate	34749: Inhibition of [125 I]6-IHPP-forskolin binding to adenylate cyclase 1	ic50	0.0310	uM
[(3R,4aR,5S,6S,6aS,10S,10aR,10bS)-3-ethenyl-10,10b-dihydroxy-6-(2-methoxyethylcarbamoyloxy)-3,4a,7,7,10a-pentamethyl-1-oxo-5,6,6a,8,9,10-hexahydro-2H-benzo[f]chromen-5-yl] acetate	34749: Inhibition of [125 I]6-IHPP-forskolin binding to adenylate cyclase 1	ic50	0.0320	uM
3-[[4-[2-(4-tert-butylphenyl)-3-[4-(2,4-dichlorophenyl)anilino]-3-oxopropyl]benzoyl]amino]propanoic acid	34296: In vitro inhibitory activity against glucagon induced human adenylate cyclase	ki	0.0330	uM
[(3R,4aR,5S,6S,6aS,10S,10aR,10bS)-3-ethenyl-10,10b-dihydroxy-3,4a,7,7,10a-pentamethyl-1-oxo-6-(2-phenylethylcarbamoyloxy)-5,6,6a,8,9,10-hexahydro-2H-benzo[f]chromen-5-yl] acetate	34749: Inhibition of [125 I]6-IHPP-forskolin binding to adenylate cyclase 1	ic50	0.0360	uM
[(3R,4aR,5S,6S,6aS,10S,10aR,10bS)-6-[2-(4-aminophenyl)ethylcarbamoyloxy]-3-ethenyl-10,10b-dihydroxy-3,4a,7,7,10a-pentamethyl-1-oxo-5,6,6a,8,9,10-hexahydro-2H-benzo[f]chromen-5-yl] acetate	34749: Inhibition of [125 I]6-IHPP-forskolin binding to adenylate cyclase 1	ic50	0.0390	uM
[(3R,4aR,5S,6S,6aS,10S,10aR,10bS)-3-ethenyl-6,10,10b-trihydroxy-3,4a,7,7,10a-pentamethyl-1-oxo-5,6,6a,8,9,10-hexahydro-2H-benzo[f]chromen-5-yl] acetate	34749: Inhibition of [125 I]6-IHPP-forskolin binding to adenylate cyclase 1	ic50	0.0410	uM
[(3R,4aR,5S,6S,6aS,10S,10aR,10bS)-3-ethenyl-6,10,10b-trihydroxy-3,4a,7,7,10a-pentamethyl-1-oxo-5,6,6a,8,9,10-hexahydro-2H-benzo[f]chromen-5-yl] N-(2-hydroxyethyl)carbamate	34749: Inhibition of [125 I]6-IHPP-forskolin binding to adenylate cyclase 1	ic50	0.0430	uM
ethyl 3-[[(3R,4aR,5S,6S,6aS,10S,10aR,10bS)-5-acetyloxy-3-ethenyl-10,10b-dihydroxy-3,4a,7,7,10a-pentamethyl-1-oxo-5,6,6a,8,9,10-hexahydro-2H-benzo[f]chromen-6-yl]oxycarbonylamino]propanoate	34749: Inhibition of [125 I]6-IHPP-forskolin binding to adenylate cyclase 1	ic50	0.0440	uM
[(3R,4aR,5S,6S,6aS,10S,10aR,10bS)-3-ethenyl-6,10,10b-trihydroxy-3,4a,7,7,10a-pentamethyl-1-oxo-5,6,6a,8,9,10-hexahydro-2H-benzo[f]chromen-5-yl] N-[2-(4-aminophenyl)ethyl]carbamate	34749: Inhibition of [125 I]6-IHPP-forskolin binding to adenylate cyclase 1	ic50	0.0640	uM
[(3R,4aR,5S,6S,6aS,10S,10aR,10bS)-3-ethenyl-5,10,10b-trihydroxy-3,4a,7,7,10a-pentamethyl-1-oxo-5,6,6a,8,9,10-hexahydro-2H-benzo[f]chromen-6-yl] N-(2-phenylethyl)carbamate	34749: Inhibition of [125 I]6-IHPP-forskolin binding to adenylate cyclase 1	ic50	0.0650	uM
(5R)-5-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine-7,8-diol	34592: Compound was tested for the adenylate cyclase stimulation	ec50	0.0710	uM
[(3R,4aR,5S,6S,6aS,10S,10aR,10bS)-6-[2-(dimethylamino)ethylcarbamoyloxy]-3-ethenyl-10,10b-dihydroxy-3,4a,7,7,10a-pentamethyl-1-oxo-5,6,6a,8,9,10-hexahydro-2H-benzo[f]chromen-5-yl] acetate	34749: Inhibition of [125 I]6-IHPP-forskolin binding to adenylate cyclase 1	ic50	0.0730	uM
[(3R,4aR,5S,6S,6aS,10S,10aR,10bS)-3-ethenyl-10,10b-dihydroxy-3,4a,7,7,10a-pentamethyl-1-oxo-6-(propylcarbamoyloxy)-5,6,6a,8,9,10-hexahydro-2H-benzo[f]chromen-5-yl] acetate	34749: Inhibition of [125 I]6-IHPP-forskolin binding to adenylate cyclase 1	ic50	0.0760	uM
[(3R,4aR,5S,6S,6aS,10S,10aR,10bS)-3-ethenyl-10,10b-dihydroxy-3,4a,7,7,10a-pentamethyl-1-oxo-6-(prop-2-enylcarbamoyloxy)-5,6,6a,8,9,10-hexahydro-2H-benzo[f]chromen-5-yl] acetate	34749: Inhibition of [125 I]6-IHPP-forskolin binding to adenylate cyclase 1	ic50	0.0760	uM
[(3R,4aR,5S,6S,6aS,10S,10aR,10bS)-3-ethenyl-10,10b-dihydroxy-3,4a,7,7,10a-pentamethyl-1-oxo-6-(2-piperidin-1-ylethylcarbamoyloxy)-5,6,6a,8,9,10-hexahydro-2H-benzo[f]chromen-5-yl] acetate	34749: Inhibition of [125 I]6-IHPP-forskolin binding to adenylate cyclase 1	ic50	0.0820	uM
[(3R,4aR,5S,6S,6aS,10S,10aR,10bS)-3-ethenyl-6,10,10b-trihydroxy-3,4a,7,7,10a-pentamethyl-1-oxo-5,6,6a,8,9,10-hexahydro-2H-benzo[f]chromen-5-yl] N-propylcarbamate	34749: Inhibition of [125 I]6-IHPP-forskolin binding to adenylate cyclase 1	ic50	0.0890	uM
[(3R,4aR,5S,6S,6aS,10S,10aR,10bS)-3-ethenyl-6,10,10b-trihydroxy-3,4a,7,7,10a-pentamethyl-1-oxo-5,6,6a,8,9,10-hexahydro-2H-benzo[f]chromen-5-yl] N-[2-(4-hydroxyphenyl)ethyl]carbamate	34749: Inhibition of [125 I]6-IHPP-forskolin binding to adenylate cyclase 1	ic50	0.0950	uM
3-[[4-[2-(4-tert-butylphenyl)-3-oxo-3-[4-(trifluoromethoxy)anilino]propyl]benzoyl]amino]propanoic acid	34296: In vitro inhibitory activity against glucagon induced human adenylate cyclase	ki	0.1100	uM
[(3R,4aR,5S,6S,6aS,10S,10aR,10bS)-3-ethenyl-6,10,10b-trihydroxy-3,4a,7,7,10a-pentamethyl-1-oxo-5,6,6a,8,9,10-hexahydro-2H-benzo[f]chromen-5-yl] N-(2-methylpropyl)carbamate	34749: Inhibition of [125 I]6-IHPP-forskolin binding to adenylate cyclase 1	ic50	0.1120	uM
[(3R,4aR,5S,6S,6aS,10S,10aR,10bS)-3-ethenyl-5,10,10b-trihydroxy-3,4a,7,7,10a-pentamethyl-1-oxo-5,6,6a,8,9,10-hexahydro-2H-benzo[f]chromen-6-yl] N-(2-pyridin-2-ylethyl)carbamate	34749: Inhibition of [125 I]6-IHPP-forskolin binding to adenylate cyclase 1	ic50	0.1170	uM
[(3R,4aR,5S,6S,6aS,10S,10aR,10bS)-6-(cyclohexylmethylcarbamoyloxy)-3-ethenyl-10,10b-dihydroxy-3,4a,7,7,10a-pentamethyl-1-oxo-5,6,6a,8,9,10-hexahydro-2H-benzo[f]chromen-5-yl] acetate	34749: Inhibition of [125 I]6-IHPP-forskolin binding to adenylate cyclase 1	ic50	0.1170	uM
[(3R,4aR,5S,6S,6aS,10S,10aR,10bS)-3-ethenyl-5,10,10b-trihydroxy-3,4a,7,7,10a-pentamethyl-1-oxo-5,6,6a,8,9,10-hexahydro-2H-benzo[f]chromen-6-yl] N-(2-piperidin-1-ylethyl)carbamate	34749: Inhibition of [125 I]6-IHPP-forskolin binding to adenylate cyclase 1	ic50	0.1230	uM
[(3R,4aR,5S,6S,6aS,10S,10aR,10bS)-3-ethenyl-6,10,10b-trihydroxy-3,4a,7,7,10a-pentamethyl-1-oxo-5,6,6a,8,9,10-hexahydro-2H-benzo[f]chromen-5-yl] N-(2-aminoethyl)carbamate	34749: Inhibition of [125 I]6-IHPP-forskolin binding to adenylate cyclase 1	ic50	0.1280	uM
[(3R,4aR,5S,6S,6aS,10S,10aR,10bS)-3-ethenyl-10,10b-dihydroxy-6-(2-hydroxyethylcarbamoyloxy)-3,4a,7,7,10a-pentamethyl-1-oxo-5,6,6a,8,9,10-hexahydro-2H-benzo[f]chromen-5-yl] acetate	34749: Inhibition of [125 I]6-IHPP-forskolin binding to adenylate cyclase 1	ic50	0.1420	uM
[(3R,4aR,5S,6S,6aS,10S,10aR,10bS)-3-ethenyl-6,10,10b-trihydroxy-3,4a,7,7,10a-pentamethyl-1-oxo-5,6,6a,8,9,10-hexahydro-2H-benzo[f]chromen-5-yl] N-(2-pyridin-2-ylethyl)carbamate	34749: Inhibition of [125 I]6-IHPP-forskolin binding to adenylate cyclase 1	ic50	0.1430	uM
3-[[4-[1-(4-tert-butylphenyl)-2-oxo-2-(4-phenylanilino)ethoxy]benzoyl]amino]propanoic acid	34294: In vitro inhibitory activity against glucagon induced human adenylate cyclase	ki	0.1440	uM
[(3R,4aR,5S,6S,6aS,10S,10aR,10bS)-3-ethenyl-6,10,10b-trihydroxy-3,4a,7,7,10a-pentamethyl-1-oxo-5,6,6a,8,9,10-hexahydro-2H-benzo[f]chromen-5-yl] N-prop-2-enylcarbamate	34749: Inhibition of [125 I]6-IHPP-forskolin binding to adenylate cyclase 1	ic50	0.1570	uM
[(3R,4aR,5S,6S,6aS,10S,10aR,10bS)-3-ethenyl-5,10,10b-trihydroxy-3,4a,7,7,10a-pentamethyl-1-oxo-5,6,6a,8,9,10-hexahydro-2H-benzo[f]chromen-6-yl] N-[2-(4-aminophenyl)ethyl]carbamate	34749: Inhibition of [125 I]6-IHPP-forskolin binding to adenylate cyclase 1	ic50	0.1620	uM
[(3R,4aR,5S,6S,6aS,10S,10aR,10bS)-3-ethenyl-10,10b-dihydroxy-3,4a,7,7,10a-pentamethyl-6-(2-methylpropylcarbamoyloxy)-1-oxo-5,6,6a,8,9,10-hexahydro-2H-benzo[f]chromen-5-yl] acetate	34749: Inhibition of [125 I]6-IHPP-forskolin binding to adenylate cyclase 1	ic50	0.1670	uM
ethyl 3-[[(3R,4aR,5S,6S,6aS,10S,10aR,10bS)-3-ethenyl-5,10,10b-trihydroxy-3,4a,7,7,10a-pentamethyl-1-oxo-5,6,6a,8,9,10-hexahydro-2H-benzo[f]chromen-6-yl]oxycarbonylamino]propanoate	34749: Inhibition of [125 I]6-IHPP-forskolin binding to adenylate cyclase 1	ic50	0.1710	uM
[(3R,4aR,5S,6S,6aS,10S,10aR,10bS)-3-ethenyl-6,10,10b-trihydroxy-3,4a,7,7,10a-pentamethyl-1-oxo-5,6,6a,8,9,10-hexahydro-2H-benzo[f]chromen-5-yl] N-(2-methoxyethyl)carbamate	34749: Inhibition of [125 I]6-IHPP-forskolin binding to adenylate cyclase 1	ic50	0.1740	uM
[(3R,4aR,5S,6S,6aS,10S,10aR,10bS)-3-ethenyl-6,10,10b-trihydroxy-3,4a,7,7,10a-pentamethyl-1-oxo-5,6,6a,8,9,10-hexahydro-2H-benzo[f]chromen-5-yl] N-(2-piperidin-1-ylethyl)carbamate	34749: Inhibition of [125 I]6-IHPP-forskolin binding to adenylate cyclase 1	ic50	0.1840	uM
ethyl 3-[[(3R,4aR,5S,6S,6aS,10S,10aR,10bS)-3-ethenyl-6,10,10b-trihydroxy-3,4a,7,7,10a-pentamethyl-1-oxo-5,6,6a,8,9,10-hexahydro-2H-benzo[f]chromen-5-yl]oxycarbonylamino]propanoate	34749: Inhibition of [125 I]6-IHPP-forskolin binding to adenylate cyclase 1	ic50	0.1850	uM
[(3R,4aR,5S,6S,6aS,10S,10aR,10bS)-3-ethenyl-5,10,10b-trihydroxy-3,4a,7,7,10a-pentamethyl-1-oxo-5,6,6a,8,9,10-hexahydro-2H-benzo[f]chromen-6-yl] N-(2-aminoethyl)carbamate	34749: Inhibition of [125 I]6-IHPP-forskolin binding to adenylate cyclase 1	ic50	0.1920	uM
[(3R,4aR,5S,6S,6aS,10S,10aR,10bS)-3-ethenyl-6,10,10b-trihydroxy-3,4a,7,7,10a-pentamethyl-1-oxo-5,6,6a,8,9,10-hexahydro-2H-benzo[f]chromen-5-yl] N-[2-(dimethylamino)ethyl]carbamate	34749: Inhibition of [125 I]6-IHPP-forskolin binding to adenylate cyclase 1	ic50	0.2280	uM
[(3R,4aR,5S,6S,6aS,10S,10aR,10bS)-3-ethenyl-5,10,10b-trihydroxy-3,4a,7,7,10a-pentamethyl-1-oxo-5,6,6a,8,9,10-hexahydro-2H-benzo[f]chromen-6-yl] N-(2-hydroxyethyl)carbamate	34749: Inhibition of [125 I]6-IHPP-forskolin binding to adenylate cyclase 1	ic50	0.2300	uM

CTD chemical–gene interactions

44 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, decreases expression, affects expression, increases expression	6
bisphenol A	decreases methylation, increases expression	2
sodium arsenite	increases expression	2
bisphenol S	increases expression, affects cotreatment	2
Benzo(a)pyrene	affects methylation, increases methylation	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
ammonium 2,3,3,3-tetrafluoro-2-(heptafluoropropoxy)-propanoate	affects cotreatment, affects expression	1
methylmercuric chloride	decreases expression	1
trichostatin A	decreases expression	1
perfluorooctanoic acid	affects cotreatment, affects expression	1
benzo(e)pyrene	decreases methylation, increases methylation	1
aflatoxin B2	decreases methylation, increases methylation	1
S-(1,2-dichlorovinyl)cysteine	affects cotreatment, decreases expression	1
perfluorooctane sulfonic acid	affects cotreatment, affects expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
obeticholic acid	increases expression	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
perfluorobutanesulfonic acid	affects expression, affects cotreatment	1
1-(2-trifluoromethoxyphenyl)-2-nitroethanone	decreases expression	1
Rosiglitazone	decreases expression	1
Sunitinib	decreases expression	1
Vorinostat	decreases expression	1
Cisplatin	increases expression	1
Dexamethasone	affects cotreatment, increases expression	1
Diethylstilbestrol	increases expression	1
Doxorubicin	decreases expression	1
Estradiol	increases expression	1
Ibuprofen	decreases expression	1
Indomethacin	affects cotreatment, increases expression	1

ChEMBL screening assays

47 unique, capped per target: 34 binding, 12 functional, 1 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3284336	Binding	Agonist activity at adenylyl cyclase (unknown origin) at 1.35 x 10’-4 M	Synthesis of a fragment of human parathyroid hormore, hPTH-(44-68). — J Med Chem
CHEMBL645298	Functional	In vitro antagonist activity was measured by inhibition of vasopressin-stimulated adenylate cyclase in renal medullary preparation in pig	Dicarbavasopressin antagonist analogues exhibit reduced in vivo agonist activity. — J Med Chem
CHEMBL4685440	ADMET	Agonist activity at recombinant human AC1 expressed in HEK293 cells assessed as increase in cAMP level at 50 uM measured after 30 mins by LANCE Ultra cAMP Detection kit method	The discovery, design and synthesis of potent agonists of adenylyl cyclase type 2 by virtual screening combining biological evaluation. — Eur J Med Chem

Cellosaurus cell lines

1 cell lines: 1 transformed cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_D8YS	Ubigene HEK293 ADCY1 KO	Transformed cell line	Female

Clinical trials (associated diseases)

6 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT04564430	PHASE4	UNKNOWN	Clonidine for Tourniquet-related Pain in Children
NCT01802190	Not specified	TERMINATED	Prevalence of POU4F3 and SLC17A8 Mutations
NCT03107546	Not specified	COMPLETED	Comparison of Scar Formation in Syndactyly Release Surgery With Full Thickness Skin Graft Versus Skin Graft Substitute
NCT06239064	Not specified	ACTIVE_NOT_RECRUITING	Early Genetic Identification of Obesity
NCT07596862	Not specified	COMPLETED	Remote Assesment of Functional Sequelae in Patients Operated for Congenital Syndactyly
NCT03652181	Not specified	COMPLETED	CASH (Cavernous Angiomas With Symptomatic Hemorrhage) Trial Readiness