ADCY3

Summary

ADCY3 (adenylate cyclase 3, HGNC:234) is a protein-coding gene on chromosome 2p23.3, encoding Adenylate cyclase type 3 (O60266). Catalyzes the formation of the signaling molecule cAMP in response to G-protein signaling.

This gene encodes adenylyl cyclase 3 which is a membrane-associated enzyme and catalyzes the formation of the secondary messenger cyclic adenosine monophosphate (cAMP). This protein appears to be widely expressed in various human tissues and may be involved in a number of physiological and pathophysiological metabolic processes. Two transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 109 — RefSeq curated summary.

At a glance

• Gene–disease (curated): body mass index quantitative trait locus 19 (Strong, GenCC)
• GWAS associations: 111
• Clinical variants (ClinVar): 599 total — 5 pathogenic, 7 likely-pathogenic
• Phenotypes (HPO): 13
• Druggable target: yes
• MANE Select transcript: NM_004036

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:234
Approved symbol	ADCY3
Name	adenylate cyclase 3
Location	2p23.3
Locus type	gene with protein product
Status	Approved
Aliases	AC3
Ensembl gene	ENSG00000138031
Ensembl biotype	protein_coding
OMIM	600291
Entrez	109

Gene structure

Transcript identifiers

Ensembl transcripts: 36 — 32 protein_coding, 2 protein_coding_CDS_not_defined, 2 retained_intron

ENST00000260600, ENST00000405392, ENST00000427849, ENST00000433852, ENST00000435135, ENST00000438445, ENST00000450524, ENST00000454027, ENST00000479517, ENST00000485887, ENST00000498288, ENST00000606682, ENST00000679454, ENST00000867857, ENST00000867858, ENST00000867859, ENST00000867860, ENST00000912210, ENST00000912211, ENST00000912212, ENST00000912213, ENST00000912214, ENST00000912215, ENST00000948874, ENST00000948875, ENST00000948876, ENST00000948877, ENST00000948878, ENST00000948879, ENST00000948880, ENST00000948881, ENST00000948882, ENST00000948883, ENST00000948884, ENST00000948885, ENST00000948886

RefSeq mRNA: 7 — MANE Select: NM_004036 NM_001320613, NM_001377128, NM_001377129, NM_001377130, NM_001377131, NM_001377132, NM_004036

CCDS: CCDS1715, CCDS82424

Canonical transcript exons

ENST00000679454 — 22 exons

Exon	Start	End
ENSE00000932298	24820724	24820848
ENSE00000932301	24823209	24823355
ENSE00000932302	24824378	24824536
ENSE00000932304	24827546	24827608
ENSE00000932308	24834485	24834646
ENSE00000932309	24834794	24834936
ENSE00001170680	24826045	24826126
ENSE00001611610	24842254	24842384
ENSE00001654747	24918313	24919184
ENSE00001780586	24872570	24872719
ENSE00001823516	24819169	24820114
ENSE00003484632	24841556	24841667
ENSE00003568430	24821517	24821640
ENSE00003571989	24822511	24822630
ENSE00003623262	24831662	24831749
ENSE00003696768	24838445	24838622
ENSE00003698786	24827902	24828161
ENSE00003699488	24836917	24837045
ENSE00003699534	24830709	24830825
ENSE00003702232	24839873	24840031
ENSE00003720336	24841259	24841386
ENSE00003912139	24919683	24920237

Expression profiles

Bgee: expression breadth ubiquitous, 281 present calls, max score 98.49.

FANTOM5 (CAGE): breadth broad, TPM avg 3.9399 / max 242.5244, expressed in 345 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
27342	9.8905	1717
27339	3.9399	345
27341	1.0894	628

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
tibial nerve	UBERON:0001323	98.49	gold quality
right ovary	UBERON:0002118	97.52	gold quality
sural nerve	UBERON:0015488	97.31	gold quality
left uterine tube	UBERON:0001303	97.25	gold quality
omental fat pad	UBERON:0010414	97.25	gold quality
peritoneum	UBERON:0002358	97.21	gold quality
endocervix	UBERON:0000458	96.88	gold quality
left ovary	UBERON:0002119	96.85	gold quality
stromal cell of endometrium	CL:0002255	96.76	gold quality
body of uterus	UBERON:0009853	96.56	gold quality
adipose tissue of abdominal region	UBERON:0007808	96.15	gold quality
ectocervix	UBERON:0012249	95.86	gold quality
mucosa of stomach	UBERON:0001199	95.33	gold quality
subcutaneous adipose tissue	UBERON:0002190	95.16	gold quality
adenohypophysis	UBERON:0002196	95.09	gold quality
right lobe of thyroid gland	UBERON:0001119	94.97	gold quality
tibial artery	UBERON:0007610	94.69	gold quality
popliteal artery	UBERON:0002250	94.68	gold quality
upper lobe of left lung	UBERON:0008952	94.64	gold quality
caudate nucleus	UBERON:0001873	94.62	gold quality
skin of leg	UBERON:0001511	94.58	gold quality
nucleus accumbens	UBERON:0001882	94.39	gold quality
right frontal lobe	UBERON:0002810	94.18	gold quality
right hemisphere of cerebellum	UBERON:0014890	94.12	gold quality
lower esophagus muscularis layer	UBERON:0035833	94.12	gold quality
lower esophagus	UBERON:0013473	94.08	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	94.06	gold quality
left coronary artery	UBERON:0001626	94.01	gold quality
upper lobe of lung	UBERON:0008948	94.00	gold quality
apex of heart	UBERON:0002098	93.95	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-ENAD-27	yes	32.12
E-GEOD-135922	yes	28.41
E-ANND-3	yes	14.37

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

70 targeting ADCY3, 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-190A-3P	100.00	80.35	5520
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-32-5P	99.98	75.21	1964
HSA-MIR-92A-3P	99.98	75.21	1960
HSA-MIR-92B-3P	99.98	75.25	1955
HSA-MIR-25-3P	99.98	74.60	1817
HSA-MIR-363-3P	99.98	74.72	1821
HSA-MIR-367-3P	99.98	74.83	1819
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-9-3P	99.96	70.88	2068
HSA-MIR-128-3P	99.95	71.17	2484
HSA-MIR-216A-3P	99.95	71.19	2505
HSA-MIR-6835-3P	99.93	70.49	2904
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-1297	99.91	73.41	3162
HSA-MIR-4731-5P	99.89	67.23	2537
HSA-MIR-3681-3P	99.88	70.46	2254
HSA-MIR-320A-3P	99.77	69.73	2107
HSA-MIR-320B	99.77	69.73	2107
HSA-MIR-320C	99.77	69.73	2107
HSA-MIR-320D	99.77	69.73	2107
HSA-MIR-4429	99.77	69.62	2111
HSA-MIR-132-3P	99.73	70.56	1424
HSA-MIR-212-3P	99.73	70.65	1424
HSA-MIR-4422	99.72	72.07	2908
HSA-MIR-4677-5P	99.70	70.09	1940
HSA-MIR-6715B-5P	99.64	69.63	1420
HSA-MIR-6126	99.62	68.09	996
HSA-MIR-451B	99.55	68.28	1380

Literature-anchored findings (GeneRIF, showing 23)

• identified AC3as the predominant AC isoform in human platelets, the activity of which may affect the extent and duration of the net aggregation response by modulating deaggregation (PMID:12623444)
• expression of nodular ADCY6, but not ADCY3, was lower than the expression of both in perinodular tissue, which may be part of the mechanisms occurring in the hyperfunctioning nodules (PMID:12782409)
• Establishment of the mature glomerular array in transgenic mice requires adenylyl cyclase 3, a key component of the odorant receptor-mediated cyclic AMP-dependent signaling cascade. (PMID:17581954)
• 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)
• This the first evidence that AC3 polymorphisms confer the risk susceptibility to obesity in Swedish men with and without type 2 diabetes. (PMID:17895882)
• These results suggest that the length of primary cilia is controlled, at least in part, by the adenylate cyclase III-cAMP signaling pathway. (PMID:19576885)
• This study suggested that the adenylate cyclase 3 (ADCY3, 2p23.3) related to major depressive disorder. (PMID:21042317)
• Data show that AC3 genetic polymorphisms are associated with decreased risk of obesity among adults but not in children in a Chinese Han population. (PMID:21079816)
• endoplasmic reticulum calcium store operated cAMP production occurred preferentially via the adenylate cyclase 3 (PMID:22681560)
• Genetically mutated serine(1076) of adenylyl cyclase III (ACIII) affects neither the cilial localization nor expression level of ACIII in olfactory sensory neurons. (PMID:23077041)
• Data demonstrate that the expression of ADCY3 is regulated through an epigenetic mechanism. (PMID:24113161)
• The association signal of height-adjusted BMI at ADCY3 appeared to be driven by a missense variant and it was strongly correlated with expression of this gene. (PMID:25044758)
• Similar results were obtained after sustained stimulation with NKH477 to directly activate adenylyl cyclase (PMID:25431134)
• In peripheral organs, AC3 is present mainly in primary cilia in cells of the mesenchymal lineage. In epithelia, the apical cilium of renal and pancreatic tubules and of ductal plate in liver is AC3-negative whereas the cilium of basal cells of stratified epithelia is AC3-positive. Using fibroblasts cell culture, we show that AC3 appears at the plasma membrane of the primary cilium as soon as this organelle develops. (PMID:28122017)
• MC4R colocalizes with ADCY3 at the primary cilia of a subset of hypothalamic neurons; obesity-associated MC4R mutations impair ciliary localization and inhibition of adenylyl cyclase signaling at the primary cilia of these neurons increases body weight. (PMID:29311635)
• An enrichment of rare ADCY3 loss-of-function variants among individuals with type 2 diabetes in trans-ancestry cohorts. (PMID:29311636)
• ADCY3 is an important mediator of energy homeostasis and an attractive pharmacological target in the treatment of obesity. (PMID:29311637)
• This study showed that subjects carrying the G allele of the rs10182181 polymorphism may benefit more in terms of weight loss and improvement of body composition measurements when undertaking a hypocaloric low-fat diet as compared to a moderately-high-protein diet. (PMID:29921800)
• ALDH2, ADCY3 and BCMO1 polymorphisms and lifestyle-induced traits are jointly associated with CAD risk in Chinese Han people. (PMID:34481002)
• Molecular modelling of novel ADCY3 variant predicts a molecular target for tackling obesity. (PMID:34821371)
• Adenylate cyclase 3: a potential genetic link between obesity and major depressive disorder. (PMID:37955134)
• Postnatal Dynamic Ciliary ARL13B and ADCY3 Localization in the Mouse Brain. (PMID:38334651)
• Cold-induced expression of a truncated adenylyl cyclase 3 acts as rheostat to brown fat function. (PMID:38684889)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	adcy3a	ENSDARG00000077145
mus_musculus	Adcy3	ENSMUSG00000020654
rattus_norvegicus	Adcy3	ENSRNOG00000003999
drosophila_melanogaster	Ac3	FBGN0023416

Paralogs (17): GUCY1B1 (ENSG00000061918), GUCY2C (ENSG00000070019), ADCY2 (ENSG00000078295), GUCY2F (ENSG00000101890), NPR3 (ENSG00000113389), ADCY7 (ENSG00000121281), ADCY4 (ENSG00000129467), GUCY2D (ENSG00000132518), GUCY1A2 (ENSG00000152402), ADCY8 (ENSG00000155897), NPR2 (ENSG00000159899), ADCY9 (ENSG00000162104), GUCY1A1 (ENSG00000164116), ADCY1 (ENSG00000164742), NPR1 (ENSG00000169418), ADCY5 (ENSG00000173175), ADCY6 (ENSG00000174233)

Protein

Protein identifiers

Adenylate cyclase type 3 — O60266 (reviewed: O60266)

Alternative names: ATP pyrophosphate-lyase 3, Adenylate cyclase type III, Adenylate cyclase, olfactive type, Adenylyl cyclase 3

All UniProt accessions (8): O60266, A0A0A0MSC1, C9J969, C9JLX3, C9JYB5, H7C1A6, U3KQ91, U3KQR1

UniProt curated annotations — full annotation on UniProt →

Function. Catalyzes the formation of the signaling molecule cAMP in response to G-protein signaling. Participates in signaling cascades triggered by odorant receptors via its function in cAMP biosynthesis: specifically activated by G alpha protein GNAL/G(olf) in olfactory epithelium. Required for normal sperm motility and normal male fertility. Plays a role in regulating insulin levels and body fat accumulation in response to a high fat diet.

Subcellular location. Cell membrane. Cytoplasm. Cell projection. Cilium. Golgi apparatus.

Tissue specificity. Detected in zona glomerulosa and zona fasciculata in the adrenal gland (at protein level). Expressed in brain, heart, kidney, liver, lung, pancreas islets, placenta, and skeletal muscle. Detected in testis.

Post-translational modifications. Sumoylated. Sumoylation is required for targeting ot olfactory cilia. N-glycosylated. Rapidly phosphorylated after stimulation by odorants or forskolin. Phosphorylation by CaMK2 at Ser-1076 down-regulates enzyme activity.

Disease relevance. Obesity (OBESITY) [MIM:601665] A condition characterized by an increase of body weight beyond the limitation of skeletal and physical requirements, as the result of excessive accumulation of body fat. Disease susceptibility is associated with variants affecting the gene represented in this entry.

Activity regulation. Specifically activated by the G alpha protein GNAL/G(olf) in signaling cascades triggered by odorant receptors. Activated by forskolin. After forskolin treatment, activity is further increased by calcium/calmodulin. In the absence of forskolin, calcium/calmodulin has little effect on enzyme activity.

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 modules have no catalytic activity, but when they are brought together, enzyme activity is restored. The active site is at the interface of the two modules.

Polymorphism. Genetic variations at the ADCY3 locus define the body mass index quantitative trait locus 19 (BMIQ19) [MIM:617885]. Variance in body mass index is a susceptibility factor for obesity.

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

Isoforms (2)

UniProt ID	Names	Canonical?
O60266-1	1	yes
O60266-2	2

RefSeq proteins (7): NP_001307542, NP_001364057, NP_001364058, NP_001364059, NP_001364060, NP_001364061, NP_004027* (*=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

Catalyzed reactions (Rhea), 1 shown:

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

UniProt features (42 total): transmembrane region 12, binding site 12, sequence variant 4, topological domain 3, modified residue 3, splice variant 3, chain 1, region of interest 1, compositionally biased region 1, glycosylation site 1, cross-link 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O60266-F1	76.86	0.36

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): 324–329; 324; 324; 325; 366–368; 368; 368; 412; 975; 1062–1064; 1069–1073; 1109

Post-translational modifications (4): 525, 580, 1076, 465

Glycosylation sites (1): 736

Function

Pathways and Gene Ontology

Reactome pathways

48 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-381753	Olfactory Signaling 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-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: 356 (showing top): VERHAAK_AML_WITH_NPM1_MUTATED_DN, GOBP_SINGLE_FERTILIZATION, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_COGNITION, GOBP_BEHAVIOR, MORF_MSH3, GOBP_CELLULAR_RESPONSE_TO_LIPID, GOBP_RESPONSE_TO_FLUID_SHEAR_STRESS, REACTOME_G_ALPHA_Z_SIGNALLING_EVENTS, GOBP_ASSOCIATIVE_LEARNING, GOBP_CELLULAR_RESPONSE_TO_FLUID_SHEAR_STRESS, MORF_BRCA1, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_UP, MORF_ATRX, GRAESSMANN_RESPONSE_TO_MC_AND_SERUM_DEPRIVATION_UP

GO Biological Process (14): renal water homeostasis (GO:0003091), cAMP biosynthetic process (GO:0006171), signal transduction (GO:0007165), adenylate cyclase-activating G protein-coupled receptor signaling pathway (GO:0007189), single fertilization (GO:0007338), acrosome reaction (GO:0007340), sensory perception of smell (GO:0007608), olfactory learning (GO:0008355), flagellated sperm motility (GO:0030317), intracellular signal transduction (GO:0035556), cellular response to glucagon stimulus (GO:0071377), vascular endothelial cell response to laminar fluid shear stress (GO:0097700), cellular response to forskolin (GO:1904322), cyclic nucleotide biosynthetic process (GO:0009190)

GO Molecular Function (7): adenylate cyclase activity (GO:0004016), calmodulin binding (GO:0005516), ATP binding (GO:0005524), metal ion binding (GO:0046872), nucleotide binding (GO:0000166), lyase activity (GO:0016829), phosphorus-oxygen lyase activity (GO:0016849)

GO Cellular Component (7): cytoplasm (GO:0005737), Golgi apparatus (GO:0005794), plasma membrane (GO:0005886), cilium (GO:0005929), membrane (GO:0016020), ciliary membrane (GO:0060170), cell projection (GO:0042995)

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
Sensory Perception	1
Aquaporin-mediated transport	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
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
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
adenylate cyclase-modulating G protein-coupled receptor signaling pathway	1
adenylate cyclase activator activity	1
fertilization	1
membrane fusion involved in acrosome reaction	1
single fertilization	1
reproductive process	1
acrosomal vesicle exocytosis	1
sensory perception of chemical stimulus	1
associative learning	1
olfactory behavior	1
cilium-dependent cell motility	1
cilium movement involved in cell motility	1
sperm motility	1
signal transduction	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
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
cyclase activity	1
phosphorus-oxygen lyase activity	1
protein binding	1
adenyl ribonucleotide binding	1

Protein interactions and networks

STRING

1782 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ADCY3	CNGA2	Q16280	885
ADCY3	PROKR1	Q8TCW9	767
ADCY3	PROK1	P58294	765
ADCY3	PROKR2	Q8NFJ6	755
ADCY3	DNAJC27	Q9NZQ0	740
ADCY3	ALDH18A1	P54886	726
ADCY3	PROK2	Q9HC23	719
ADCY3	OMP	P47874	715
ADCY3	GPR83	Q9NYM4	714
ADCY3	GNAL	P38405	711
ADCY3	TMTC1	Q8IUR5	711
ADCY3	MC4R	P32245	691
ADCY3	PRKACA	P17612	675
ADCY3	RGS2	P41220	649
ADCY3	CNGA4	Q8IV77	637

IntAct

83 interactions, top by confidence:

A	B	Type	Score
KCNA5	TMEM223	psi-mi:“MI:0914”(association)	0.530
CNGA3	C2CD2L	psi-mi:“MI:0914”(association)	0.530
LGALS3	PODXL	psi-mi:“MI:0914”(association)	0.530
TCIRG1	AP3D1	psi-mi:“MI:0914”(association)	0.530
SLC30A2	RER1	psi-mi:“MI:0914”(association)	0.530
IZUMO1	ADCY3	psi-mi:“MI:0914”(association)	0.530
ANKMY2	ADCY3	psi-mi:“MI:0914”(association)	0.530
SLC30A2	ESYT2	psi-mi:“MI:0914”(association)	0.530
Dlg4	ADCY3	psi-mi:“MI:0407”(direct interaction)	0.440
IZUMO1	CNOT1	psi-mi:“MI:0914”(association)	0.350
SLC4A8	ABCC4	psi-mi:“MI:0914”(association)	0.350
ASIC4	UPK3BL1	psi-mi:“MI:0914”(association)	0.350
LGALS3	PODXL	psi-mi:“MI:0914”(association)	0.350
SLC17A2	PSMD11	psi-mi:“MI:0914”(association)	0.350
CD79B	GOLIM4	psi-mi:“MI:0914”(association)	0.350
IL17RC	C2CD2L	psi-mi:“MI:0914”(association)	0.350
PCDHGA5	MAP2K7	psi-mi:“MI:0914”(association)	0.350
ANKMY2	ADCY6	psi-mi:“MI:0914”(association)	0.350
TTMP	TMEM223	psi-mi:“MI:0914”(association)	0.350
TTYH1	TMEM223	psi-mi:“MI:0914”(association)	0.350
ZDHHC12	NBAS	psi-mi:“MI:0914”(association)	0.350
CLRN2	FAM234B	psi-mi:“MI:0914”(association)	0.350
IL17RC	TMEM131L	psi-mi:“MI:0914”(association)	0.350
RXFP1	UPK3BL1	psi-mi:“MI:0914”(association)	0.350
KCNMB3	UPK3BL1	psi-mi:“MI:0914”(association)	0.350
CHRNB4	GPR89A	psi-mi:“MI:0914”(association)	0.350

BioGRID (100): ADCY3 (Affinity Capture-MS), ADCY3 (Affinity Capture-MS), ADCY3 (Affinity Capture-MS), ADCY3 (Affinity Capture-MS), ADCY3 (Affinity Capture-MS), ADCY3 (Affinity Capture-MS), ADCY3 (Affinity Capture-MS), ADCY3 (Affinity Capture-MS), ADCY3 (Affinity Capture-MS), ADCY3 (Affinity Capture-MS), ADCY3 (Affinity Capture-MS), ADCY3 (Affinity Capture-MS), ADCY3 (Affinity Capture-MS), ADCY3 (Two-hybrid), ADCY3 (Affinity Capture-RNA)

ESM2 similar proteins: A0A125YQS6, A0A125YY03, A0A7J6K338, A1Z7R6, A4IHK6, A5K9W3, G4SDH4, J9UD11, O43306, O60266, O75387, O76269, O76343, P14773, P30804, P48768, Q01341, Q03343, Q04400, Q0C8L9, Q0VCM6, Q41706, Q4D3E8, Q4X251, Q57VW6, Q5B0V6, Q5BKX6, Q5RF58, Q5ZMT9, Q6C520, Q6CGU8, Q7Z8U2, Q8BIV7, Q8BSM7, Q8CGA3, Q8K4S3, Q8K596, Q8N370, Q93380, Q93Z75

Diamond homologs: A0A0U1RPR8, A8WPG9, A8XQC7, H2L002, N1NVB7, O02298, O02740, O16544, O16715, O19179, O54865, O60266, O60503, O62179, O64784, O75343, O88444, P0A4Y1, P11528, P16065, P16068, P18910, P19686, P19687, P19754, P20595, P21932, P22717, P23897, P25092, P26769, P26770, P32870, P33402, P40137, P40145, P40146, P51828, P51830, P51839

SIGNOR signaling

5 interactions.

A	Effect	B	Mechanism
NF1	up-regulates	ADCY3
CAMK2G	“down-regulates activity”	ADCY3	phosphorylation
ADCY3	“up-regulates quantity”	“3’,5’-cyclic AMP”	“chemical modification”
GNAL	“up-regulates activity”	ADCY3	binding
ADCY3	“up-regulates activity”	PKA	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 97 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
R-HSA-425393	6	11.8×	2e-03
Transport of small molecules	12	4.6×	2e-03

GO biological processes:

GO term	Partners	Fold	FDR
regulation of intracellular pH	5	36.3×	2e-04
transmembrane transport	7	14.2×	2e-04
monoatomic ion transport	6	11.3×	3e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	5
Likely pathogenic	7
Uncertain significance	285
Likely benign	229
Benign	27

Top pathogenic / likely-pathogenic (12)

Variant ID	HGVS	Classification
1686655	GRCh37/hg19 2p24.1-23.3(chr2:22439520-25608211)x1	Pathogenic
2427540	NC_000002.11:g.(?24443763)(26029226_?)del	Pathogenic
3391842	GRCh37/hg19 2p24.1-22.2(chr2:20938401-37327210)x3	Pathogenic
3728805	NM_004036.5(ADCY3):c.187G>T (p.Glu63Ter)	Pathogenic
4715902	NM_004036.5(ADCY3):c.2267_2268del (p.Tyr756fs)	Pathogenic
1978639	NM_004036.5(ADCY3):c.2883+1G>C	Likely pathogenic
3242601	NM_004036.5(ADCY3):c.1235G>T (p.Arg412Leu)	Likely pathogenic
3344416	NM_004036.5(ADCY3):c.1663-1G>A	Likely pathogenic
3344557	NM_004036.5(ADCY3):c.957-1G>A	Likely pathogenic
3348638	NM_004036.5(ADCY3):c.1723C>T (p.Arg575Ter)	Likely pathogenic
3350597	NM_004036.5(ADCY3):c.1318del (p.Thr440fs)	Likely pathogenic
3354510	NM_004036.5(ADCY3):c.2055+1G>C	Likely pathogenic

SpliceAI

5306 predictions. Top by Δscore:

Variant	Effect	Δscore
2:24820844:CATGC:C	acceptor_gain	1.0000
2:24820846:TGC:T	acceptor_gain	1.0000
2:24820847:GC:G	acceptor_gain	1.0000
2:24820847:GCCTA:G	acceptor_loss	1.0000
2:24820848:CC:C	acceptor_gain	1.0000
2:24820849:C:CC	acceptor_gain	1.0000
2:24821511:GCTCA:G	donor_loss	1.0000
2:24821512:CTCAC:C	donor_loss	1.0000
2:24821513:TCAC:T	donor_loss	1.0000
2:24821514:CA:C	donor_loss	1.0000
2:24821515:A:AC	donor_gain	1.0000
2:24821515:A:T	donor_loss	1.0000
2:24821516:C:CC	donor_gain	1.0000
2:24821516:C:CG	donor_loss	1.0000
2:24821637:CTTC:C	acceptor_gain	1.0000
2:24821638:TTC:T	acceptor_gain	1.0000
2:24821640:CC:C	acceptor_loss	1.0000
2:24821640:CCTG:C	acceptor_gain	1.0000
2:24821641:C:CC	acceptor_gain	1.0000
2:24821641:CTGT:C	acceptor_loss	1.0000
2:24821642:T:C	acceptor_loss	1.0000
2:24821643:G:C	acceptor_gain	1.0000
2:24821643:G:GC	acceptor_gain	1.0000
2:24821647:C:CT	acceptor_gain	1.0000
2:24821647:C:T	acceptor_gain	1.0000
2:24821648:A:T	acceptor_gain	1.0000
2:24821655:C:CT	acceptor_gain	1.0000
2:24821655:C:T	acceptor_gain	1.0000
2:24822638:C:CT	acceptor_gain	1.0000
2:24822639:A:T	acceptor_gain	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000023937 (2:24894705 T>C), RS1000050121 (2:24916020 C>G), RS1000082291 (2:24915787 C>T), RS1000099284 (2:24877481 G>A), RS1000111061 (2:24839460 C>T), RS1000127604 (2:24904446 G>A), RS1000157026 (2:24861903 C>T), RS1000166352 (2:24900494 G>C), RS1000196535 (2:24832272 G>A,C), RS1000210467 (2:24886620 A>C), RS1000252856 (2:24827071 G>A), RS1000277142 (2:24821136 G>A), RS1000280766 (2:24910243 C>T), RS1000328650 (2:24922064 G>A), RS1000331299 (2:24867493 T>A)

Disease associations

OMIM: gene MIM:600291 | disease phenotypes: MIM:615879, MIM:601665, MIM:176700

GenCC curated gene-disease

Disease	Classification	Inheritance
body mass index quantitative trait locus 19	Strong	Autosomal recessive

Mondo (5): Tatton-Brown-Rahman overgrowth syndrome (MONDO:0014382), inherited obesity (MONDO:0019182), fetal growth restriction (MONDO:0005030), autosomal dominant prognathism (MONDO:0008312), (MONDO:0054749)

Orphanet (3): Tatton-Brown-Rahman syndrome (Orphanet:404443), Genetic obesity (Orphanet:77828), Autosomal dominant prognathism (Orphanet:2964)

HPO phenotypes

13 total (13 of 13 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000458	Anosmia
HP:0000842	Hyperinsulinemia
HP:0000855	Insulin resistance
HP:0001249	Intellectual disability
HP:0001513	Obesity
HP:0002155	Hypertriglyceridemia
HP:0002591	Polyphagia
HP:0003077	Hyperlipidemia
HP:0003593	Infantile onset
HP:0004409	Hyposmia
HP:0011463	Childhood onset
HP:0031793	Increased serum leptin

GWAS associations

111 associations (top):

Study	Trait	p-value
GCST000175_18	Height	8.000000e-07
GCST000830_38	Body mass index	6.000000e-22
GCST001255_1	Type 1 diabetes	4.000000e-09
GCST001415_7	Body mass index	1.000000e-13
GCST001725_41	Inflammatory bowel disease	6.000000e-16
GCST001876_3	Pubertal anthropometrics	1.000000e-08
GCST001935_9	Body mass index in non-asthmatics	2.000000e-06
GCST001953_30	Obesity	1.000000e-17
GCST001953_54	Obesity	3.000000e-14
GCST001956_74	Height	1.000000e-13
GCST001967_2	Body mass index	4.000000e-08
GCST002461_13	Body mass index	1.000000e-10
GCST002538_1	Height adjusted BMI	4.000000e-09
GCST002783_394	Body mass index	8.000000e-26
GCST002783_481	Body mass index	9.000000e-24
GCST002783_583	Body mass index	4.000000e-21
GCST002783_79	Body mass index	6.000000e-09
GCST002894_1	Body mass index	1.000000e-11
GCST002894_2	Body mass index	1.000000e-10
GCST003177_6	Childhood body mass index	7.000000e-23
GCST004066_136	Hip circumference	2.000000e-09
GCST004066_70	Hip circumference	4.000000e-11
GCST004131_107	Inflammatory bowel disease	3.000000e-07
GCST004132_38	Crohn’s disease	9.000000e-08
GCST004280_11	Diastolic blood pressure	7.000000e-11
GCST004495_138	BMI (adjusted for smoking behaviour)	2.000000e-12
GCST004495_139	BMI (adjusted for smoking behaviour)	7.000000e-19
GCST004495_140	BMI (adjusted for smoking behaviour)	5.000000e-08
GCST004497_67	Body mass index (joint analysis main effects and smoking interaction)	1.000000e-18
GCST004497_68	Body mass index (joint analysis main effects and smoking interaction)	4.000000e-12

EFO canonical traits (20, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index
EFO:0001382	puberty
EFO:0005851	height-adjusted body mass index
EFO:0006336	diastolic blood pressure
EFO:0004318	smoking behavior
EFO:0008002	physical activity measurement
EFO:0007986	reticulocyte count
EFO:0006941	grip strength measurement
EFO:0008007	age at assessment
EFO:0008343	sex interaction measurement
EFO:0006335	systolic blood pressure
EFO:0007041	obese body mass index status
EFO:0004341	body fat distribution
EFO:0008328	chronotype measurement
EFO:0010078	dentures
EFO:0009819	comparative body size at age 10, self-reported
EFO:0007006	depressive symptom measurement
EFO:0004980	appendicular lean mass
EFO:0008039	BMI-adjusted hip circumference
EFO:0007789	BMI-adjusted waist circumference

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D005317	Fetal Growth Retardation	C12.050.703.277.370; C16.300.390; C23.550.393.450
D008313	Malocclusion, Angle Class III	C07.793.494.650

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL2097167 (PROTEIN FAMILY), CHEMBL3164 (SINGLE PROTEIN)

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — Adenylyl cyclases (ACs)

ChEMBL bioactivities

24 potent at pChembl≥5 of 24 total, top 24 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
7.54	Ki	29	nM	CHEMBL305151
7.48	Ki	33	nM	CHEMBL62123
7.16	Ki	69	nM	CHEMBL305151
7.15	EC50	71	nM	(R)-SKF-38393
6.96	Ki	110	nM	CHEMBL62412
6.84	Ki	144	nM	CHEMBL64475
6.59	Ki	254	nM	CHEMBL62444
6.52	Ki	300	nM	CHEMBL62892
6.50	Ki	317	nM	CHEMBL64646
6.21	Ki	610	nM	CHEMBL418468
6.00	Ki	1000	nM	CHEMBL64955
5.28	EC50	5200	nM	CHEMBL57873

PubChem BioAssay actives

24 with measured affinity, of 76 total; 23 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
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
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
(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
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
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
3-[[4-[[(4-tert-butylcyclohexyl)-[[4-(trifluoromethoxy)phenyl]carbamoyl]amino]methyl]benzoyl]amino]propanoic acid	34294: In vitro inhibitory activity against glucagon induced human adenylate cyclase	ki	0.2540	uM
3-[[4-[2-(4-tert-butylphenyl)-3-oxo-3-(4-phenylanilino)propyl]benzoyl]amino]propanoic acid	34296: In vitro inhibitory activity against glucagon induced human adenylate cyclase	ki	0.3000	uM
4-[1-(4-tert-butylphenyl)-2-oxo-2-(4-phenylanilino)ethoxy]-N-(2H-tetrazol-5-yl)benzamide	34294: In vitro inhibitory activity against glucagon induced human adenylate cyclase	ki	0.3170	uM
3-[[4-[2-(4-tert-butylphenyl)-3-oxo-3-(quinolin-3-ylamino)propyl]benzoyl]amino]propanoic acid	34294: In vitro inhibitory activity against glucagon induced human adenylate cyclase	ki	0.6100	uM
3-[[4-[2-(4-tert-butylphenyl)-3-[4-(hydroxymethyl)anilino]-3-oxopropyl]benzoyl]amino]propanoic acid	34294: In vitro inhibitory activity against glucagon induced human adenylate cyclase	ki	1.0000	uM
2,3,4,5-tetrahydro-1H-3-benzazepine-7,8-diol	34592: Compound was tested for the adenylate cyclase stimulation	ec50	5.2000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases methylation, affects cotreatment, increases expression	2
sodium arsenite	increases abundance, increases expression, decreases expression, affects cotreatment	2
cobaltous chloride	decreases expression	2
(+)-JQ1 compound	decreases expression	2
Air Pollutants	affects cotreatment, increases abundance, increases oxidation, affects expression	2
Arsenic	increases expression, affects methylation, affects cotreatment, increases abundance	2
Benzo(a)pyrene	affects methylation, decreases methylation, increases expression	2
Copper	affects binding, increases expression	2
Estradiol	increases expression, increases reaction	2
Valproic Acid	affects expression, increases methylation	2
Vitamin K 3	affects expression, decreases expression	2
Particulate Matter	affects cotreatment, affects expression, increases abundance, increases expression	2
aristolochic acid I	decreases expression	1
FR900359	decreases phosphorylation	1
ammonium 2,3,3,3-tetrafluoro-2-(heptafluoropropoxy)-propanoate	affects cotreatment, affects expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
butyraldehyde	decreases expression	1
perfluorooctanoic acid	affects cotreatment, affects expression	1
manganese chloride	affects cotreatment, increases abundance, increases expression	1
benzo(e)pyrene	increases methylation	1
aflatoxin B2	decreases methylation	1
methacrylaldehyde	affects cotreatment, increases oxidation, increases abundance	1
beta-methylcholine	affects expression	1
perfluorooctane sulfonic acid	affects expression, affects cotreatment	1
ICG 001	increases expression	1
abrine	decreases expression	1
2-(1H-indazol-4-yl)-6-(4-methanesulfonylpiperazin-1-ylmethyl)-4-morpholin-4-ylthieno(3,2-d)pyrimidine	decreases expression, increases response to substance	1
perfluorobutanesulfonic acid	affects expression, affects cotreatment	1
Leflunomide	decreases expression	1

ChEMBL screening assays

17 unique, capped per target: 15 binding, 2 functional

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

Cellosaurus cell lines

3 cell lines: 3 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B1J3	Abcam HeLa ADCY3 KO	Cancer cell line	Female
CVCL_SB67	HAP1 ADCY3 (-) 1	Cancer cell line	Male
CVCL_XL04	HAP1 ADCY3 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00347867	PHASE4	UNKNOWN	Viagra for the Treatment of IUGR
NCT00909974	PHASE4	COMPLETED	Effect of Prenatal Nutritional Supplementation on Birth Outcome in Hounde District, Burkina Faso
NCT01352234	PHASE4	COMPLETED	Comparison of Doses of Acetylsalicylic Acid in Women With Previous History of Preeclampsia
NCT01390051	PHASE4	COMPLETED	Can Low Molecular Weight Heparin During Pregnancy With Intrauterine Growth Restriction Increase Birth Weight?
NCT01695070	PHASE4	COMPLETED	Melatonin to Prevent Brain Injury in Unborn Growth Restricted Babies
NCT03674606	PHASE4	COMPLETED	Trial of Early Screening Test for Pre-eclampsia and Growth Restriction
NCT04051567	PHASE4	UNKNOWN	Low-dose Aspirin for Prevention of Adverse Pregnancy Outcomes in Twin Pregnancies
NCT05029778	PHASE4	UNKNOWN	Arginine + Citrulline as a Supplement for Weight Gain in Fetus With a Decrease in Their Growth Curve
NCT05800938	PHASE4	COMPLETED	The Effect of Oral Isosorbide Mononitrate Therapy on Umbilical Artery Doppler Resistance Index in Pregnancies With Intrauterine Growth Restriction: Prospective Randomized Control Trial
NCT07171086	PHASE4	NOT_YET_RECRUITING	AI-POCUS for Maternal and Neonatal Health in Ethiopia
NCT05093634	PHASE3	ACTIVE_NOT_RECRUITING	EMANATE: A Study of Setmelanotide in Patients With Specific Gene Variants in the MC4R Pathway
NCT07220772	PHASE3	RECRUITING	A Study Evaluating Mibavademab Treatment of Obesity Due to Leptin (LEP) Gene Mutations in Children, Adolescents and Adults
NCT00174252	PHASE3	COMPLETED	Study Aimed At Improving Height With Genotonorm In Children Born Little And/Or Light With Growth Retardation At The Age
NCT00197340	PHASE3	COMPLETED	Antepartum Chronic Epidural Therapy (ACET) to Improve Blood Flow to the Uterus, Placenta and Baby in Pre-Eclampsia and Intrauterine Growth Restriction
NCT00452491	PHASE3	COMPLETED	MAXOMAT ® in the Treatment of Severe Early Onset Intrauterine Growth Retardation on Pre-pubertal Children
NCT01073605	PHASE3	COMPLETED	Genotropin Treatment in Short Prepubertal Children With Intra-Uterine Growth Retardation
NCT02336243	PHASE3	UNKNOWN	A Randomized Trial of Docosahexaenoic Acid Supplementation During Pregnancy to Prevent Deep Placentation Disorders
NCT02590536	PHASE3	COMPLETED	A Trial Evaluating the Role of Sildenafil in the Treatment of Fetal Growth Restriction
NCT02672566	PHASE3	COMPLETED	Low-molecular-weight Heparin in Constituted Vascular Intrauterine Growth Restriction
NCT03177824	PHASE3	UNKNOWN	Sildenafil Citrate for Treatment of Growth-restricted Fetuses
NCT03230162	PHASE3	UNKNOWN	Sildenafil Versus Low Molecular Weight Heparin in Fetal Growth Restriction Treatment
NCT03324139	PHASE3	COMPLETED	Treatment of Intrauterine Growth Restriction With Low Molecular Heparin.
NCT03669185	PHASE3	UNKNOWN	Pentaerithrityl Tetranitrate (PETN) for Secondary Prevention of Intrauterine Growth Restriction
NCT04084990	PHASE3	TERMINATED	Sleep Apnea and Fetal Growth Restriction
NCT04356326	PHASE3	RECRUITING	Chronic Hypertension and Acetyl Salicylic Acid in Pregnancy
NCT04557475	PHASE3	WITHDRAWN	Transplacental Aspirin Therapy for Early Onset Fetal Growth Restriction
NCT04762992	PHASE3	ENROLLING_BY_INVITATION	LMWH for Treatment of Early Fetal Growth Restriction (HepaGrowth)
NCT05253781	PHASE3	COMPLETED	Low Dose Aspirin for Preventing Intrauterine Growth Restriction and Preeclampsia in Sickle Cell Pregnancy (PIPSICKLE)
NCT05651347	PHASE3	RECRUITING	Antenatal Melatonin Supplementation for Neuroprotection in Fetal Growth Restriction
NCT05774236	PHASE3	COMPLETED	Cook´s Balloon Versus Dinoprostone for Labor Induction of Term Pregnancies With Fetal Growth Restriction
NCT06497959	PHASE3	RECRUITING	Study of Placental Vascularization Using Contrast Ultrasound
NCT03013543	PHASE2	COMPLETED	Setmelanotide Phase 2 Treatment Trial in Participants With Rare Genetic Disorders of Obesity
NCT04963231	PHASE2	COMPLETED	DAYBREAK: A Study of Setmelanotide in Participants With Specific Gene Variants in the Melanocortin-4 Receptor (MC4R) Pathway
NCT02280031	PHASE2	COMPLETED	Effect of Low Dose Aspirin on Birthweight in Twins: The GAP Trial.
NCT02425436	PHASE2	COMPLETED	Role of Ginkgo Biloba Extract in IUGR
NCT02678221	PHASE2	UNKNOWN	Sildenafil Citrate for the Management of Asymmetrical Intrauterine Growth Restriction
NCT02696577	PHASE2	COMPLETED	The Effect of Omega 3 on Pregnancy Complicated by Asymmetrical Intrauterine Growth Restriction
NCT07098975	PHASE2	RECRUITING	Statin Intervention for Severe Early-Onset Placental Insufficiency. (STATIN-PRE Trial)
NCT04508751	PHASE1	COMPLETED	PED NEONAT 20-000599 Fetal Body Composition
NCT06565728	PHASE1	COMPLETED	Vitamin D Versus Sildenafil Citrate in Fetal Growth Restriction