Affinage

ADCY5

Adenylate cyclase type 5 · UniProt O95622

Length
1261 aa
Mass
138.9 kDa
Annotated
2026-04-28
74 papers in source corpus 16 papers cited in narrative 16 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

ADCY5 encodes adenylyl cyclase 5, a membrane-anchored enzyme that converts ATP to cAMP and serves as a central signal integrator in striatal neurons, pancreatic β-cells, juxtaglomerular cells, and cardiomyocytes. Its catalytic activity is stimulated by Gαs and conditionally modulated by Gβγ binding to a coiled-coil domain linking its transmembrane helices to the catalytic core, while calcium inhibits the enzyme through its Mg²⁺-binding catalytic sites; scaffolding by AKAP79/150 via the AC5 N-terminus organizes it into signalosomes with PKA and AMPA receptors (PMID:38589608, PMID:12065575, PMID:20231277). In striatal medium spiny neurons, AC5 is the obligate effector downstream of mu/delta opioid and D2 dopamine Gαi-coupled receptors, and in pancreatic β-cells it specifically couples glucose metabolism to cAMP generation and insulin secretion, with a type 2 diabetes risk variant reducing ADCY5 expression from an intronic enhancer (PMID:16537460, PMID:24740569, PMID:28684635). Gain-of-function mutations at the Gβγ-binding interface (notably R418W) increase Gαs-stimulated cAMP while impairing Gαi-mediated inhibition, causing familial dyskinesia with chorea (PMID:24700542, PMID:30772269).

Mechanistic history

Synthesis pass · year-by-year structured walk · 11 steps
  1. 2002 High

    Defining how calcium inhibits AC5 resolved the long-standing question of which catalytic determinants confer calcium sensitivity: both high- and low-affinity Ca²⁺ inhibition operate through the Mg²⁺-binding sites in the catalytic domain itself, not through auxiliary domains.

    Evidence Site-directed mutagenesis, AC5/AC2 chimeric constructs, and in vitro enzyme assays with divalent cation titrations

    PMID:12065575

    Open questions at the time
    • Structural basis of Ca²⁺ vs Mg²⁺ competition at the active site not resolved at atomic level
    • Whether Ca²⁺ inhibition is modulated by scaffolding context in vivo was untested
  2. 2006 High

    Knockout studies established AC5 as the specific adenylyl cyclase isoform coupling mu/delta opioid receptors and Gαi to cAMP suppression in the striatum, explaining isoform selectivity of opioid signaling and revealing AC5 as essential for morphine-induced behaviors including reward and dependence.

    Evidence AC5 knockout mice; striatal membrane adenylyl cyclase assays with selective opioid agonists; morphine behavioral pharmacology

    PMID:16537460

    Open questions at the time
    • Whether AC5 loss is compensated by other AC isoforms over time was not assessed
    • Mechanism of kappa receptor sparing in AC5 KO striatum remained unexplained
  3. 2006 High

    Parallel work showed AC5 (together with AC6) mediates calcium-dependent suppression of cAMP and renin secretion in juxtaglomerular cells, extending AC5's role as a calcium-inhibited cyclase to a non-neuronal physiological context.

    Evidence siRNA knockdown of AC5/AC6 in primary juxtaglomerular cells and As4.1 line; cAMP rescue with membrane-permeable analogs; isolated perfused kidneys

    PMID:17068292

    Open questions at the time
    • Relative contribution of AC5 vs AC6 to renin regulation in vivo not genetically separated
  4. 2010 High

    Mapping the AC5–AKAP79/150 interaction revealed how AC5 is scaffolded into signaling complexes: the AC5 N-terminus binds AKAP79 residues 77–108, and disruption of this scaffold uncouples PKA-mediated feedback inhibition of AC activity, establishing the spatial organization principle for AC5 signaling at synapses.

    Evidence Co-immunoprecipitation, FRET in live cells, AC activity assays in AKAP150-knockout mouse brain membranes

    PMID:20231277

    Open questions at the time
    • Structural details of the AC5-AKAP interface at atomic resolution were lacking
    • Whether AKAP scaffolding modulates Gαi-mediated inhibition of AC5 was not tested
  5. 2012 Medium

    D2 receptor-mediated heterologous sensitization of AC5 was shown to require Gαs–AC5 interaction and vesicular trafficking for signalosome assembly, but not Gαs palmitoylation or Gβγ interaction, separating the trafficking requirements for sensitization from acute activation.

    Evidence Gαs mutant expression in Gαs-null cells; dominant-negative trafficking inhibitors; cAMP assays

    PMID:22523680

    Open questions at the time
    • Vesicular trafficking mechanism delivering AC5 to the signalosome not molecularly defined
    • Single-lab finding without independent replication
  6. 2014 High

    Functional characterization of ADCY5 mutations (R418W, A726T) directly demonstrated that familial dyskinesia is caused by gain-of-function increases in Gαs-stimulated cAMP production, establishing the first genotype-to-mechanism link for ADCY5-related movement disorders.

    Evidence cAMP accumulation assays in transfected cells with wild-type and mutant ADCY5; whole-exome sequencing of affected families

    PMID:24700542

    Open questions at the time
    • Why different mutations in distinct domains converge on gain-of-function was structurally unexplained
    • In vivo neuronal consequences of specific mutants were not assessed
  7. 2014 High

    In parallel, ADCY5 was identified as the specific adenylyl cyclase coupling glucose metabolism to cAMP, calcium transients, and β-cell functional connectivity in human islets—distinct from the GLP-1 pathway—directly linking the GWAS T2D risk locus to a defined secretory mechanism.

    Evidence siRNA knockdown in human islets; in situ cAMP, ATP, and calcium imaging; functional connectivity analysis

    PMID:24740569

    Open questions at the time
    • Whether reduced ADCY5 expression in risk-allele carriers quantitatively accounts for diabetes susceptibility remained unresolved
    • Downstream effectors of AC5-generated cAMP in β-cells not fully delineated
  8. 2017 High

    The T2D risk variant rs11708067-A was shown to reduce enhancer activity at an intronic element, decreasing ADCY5 transcription and insulin secretion, providing a causal regulatory mechanism connecting non-coding genetic variation to AC5 expression and β-cell function.

    Evidence ChIP-seq for H3K27ac, luciferase reporters in β-cell lines, CRISPR enhancer deletion with insulin secretion readout

    PMID:28684635

    Open questions at the time
    • Identity of transcription factors binding the risk vs protective allele not determined
    • Effect validated in rodent β-cell lines but not in human β-cells with endogenous genotype
  9. 2019 High

    Systematic characterization of four dyskinesia mutations in a clean genetic background showed that gain-of-function mutants share a dual defect—enhanced Gαs stimulation and reduced Gαi (D2 receptor) inhibition—and that P-site inhibitors preferentially suppress overactive mutants, opening a pharmacological strategy.

    Evidence CRISPR-Cas9 AC-null HEK cells reconstituted with WT or mutant AC5; membrane and whole-cell cAMP assays; neuronal transcription reporters

    PMID:30772269

    Open questions at the time
    • Whether P-site inhibitors achieve selectivity in vivo without affecting other AC isoforms was untested
    • Circuit-level consequences of reduced Gαi sensitivity in MSNs were unexplored
  10. 2019 Medium

    A BiFC interaction screen in striatal MSNs identified PP2A catalytic subunit (PPP2CB) and NAPA as novel AC5 interactors, with PP2A knockdown reducing both acute and sensitized cAMP output, revealing phosphatase-mediated regulation of AC5.

    Evidence Bimolecular fluorescence complementation in D1/D2 MSNs from CAMPER mice; genetic knockdown; cAMP assays

    PMID:31752385

    Open questions at the time
    • Direct physical binding of PP2A to AC5 not confirmed by reciprocal co-IP or structural data
    • Phosphorylation site(s) on AC5 regulated by PP2A not identified
  11. 2024 High

    Cryo-EM structures of AC5 in complex with Gβγ revealed that Gβγ binds a coiled-coil domain connecting the transmembrane region to the catalytic core and to the C1b regulatory hub, and that dyskinesia mutations (including R418W) map precisely to this interface, providing the atomic-level explanation for how they disrupt Gβγ-dependent conditional regulation and cause disease.

    Evidence Cryo-EM structures of AC5–Gβγ complex; mutagenesis; cell-based cAMP assays

    PMID:38589608

    Open questions at the time
    • Full-length AC5 structure with Gαs and Gαi simultaneously bound not yet obtained
    • How the C1b hub integrates Gβγ, Ca²⁺, and PKA feedback structurally remains incomplete

Open questions

Synthesis pass · forward-looking unresolved questions
  • A unified structural model of AC5 incorporating simultaneous regulation by Gαs, Gαi, Gβγ, Ca²⁺, and AKAP scaffolding is still lacking, and no selective AC5 inhibitor has been validated in vivo for movement disorders or metabolic disease.
  • No full-length AC5 structure with all regulators simultaneously resolved
  • No AC5-selective pharmacological tool validated in animal models of dyskinesia
  • Relative contributions of AC5 versus AC6 in shared tissues (heart, kidney) not genetically resolved in humans

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0009975 cyclase activity 4 GO:0140657 ATP-dependent activity 3
Localization
GO:0005886 plasma membrane 2
Pathway
R-HSA-162582 Signal Transduction 4 R-HSA-112316 Neuronal System 3 R-HSA-1643685 Disease 2
Partners
AKAP5GNAI1GNASGNB1GNG2NAPAPPP2CB
Complex memberships
AKAP79/150-AC5-PKA signalosome

Evidence

Reading pass · 16 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2024 Cryo-EM structures of AC5 in complex with Gβγ reveal that Gβγ binds to a coiled-coil domain linking the AC5 transmembrane region to its catalytic core and to the C1b regulatory hub; gain-of-function dyskinesia mutations in AC5 are located at the AC5-Gβγ interface and show reduced conditional activation by Gβγ, establishing a molecular mechanism for how these mutations cause disease. Cryo-electron microscopy, purified protein binding assays, cell-based cAMP assays, mutagenesis Nature structural & molecular biology High 38589608
2014 Gain-of-function missense mutations in ADCY5 (p.R418W in C1 domain; p.A726T in first membrane-spanning domain) cause significantly increased β-adrenergic receptor agonist-stimulated intracellular cAMP accumulation, establishing that ADCY5 mutations cause familial dyskinesia through increased adenylyl cyclase activity. cAMP accumulation assay in transfected cells with wild-type and mutant ADCY5 constructs; whole exome sequencing Annals of neurology High 24700542
2019 AC5 gain-of-function mutants (R418W, R418Q, A726T, M1029K) exhibit enhanced Gαs-mediated cAMP stimulation in membrane and cell-based assays, increased downstream gene transcription in neuronal models, and significantly reduced inhibition following D2 dopamine receptor (Gαi-coupled) activation; the P-site inhibitor SQ22536 preferentially inhibits overactive AC5 mutants. CRISPR-Cas9 knockout of endogenous adenylyl cyclases in HEK cells; membrane-based and cell-based cAMP assays; neuronal transcription reporter assays; pharmacological inhibition Biochemical pharmacology High 30772269
2014 ADCY5 silencing in human islets impairs glucose-induced cAMP increases and blocks glucose metabolism toward ATP at >8 mmol/L glucose, and sharply inhibits calcium transient generation and functional connectivity between β-cells at all glucose concentrations; GLP-1-induced calcium rises are unaffected, demonstrating that ADCY5 specifically couples glucose (but not GLP-1) to insulin secretion. siRNA knockdown of ADCY5 in human islets; in situ imaging of cAMP and ATP probes; calcium imaging; functional connectivity analysis Diabetes High 24740569
2010 AKAP79/150 scaffolds AC5 (and AC6) to synaptic AMPA receptors; the N-terminal region of AC5 mediates binding to residues 77–108 of AKAP79; deletion of this AKAP79 region abolishes AC5-AKAP79 interaction in living cells; the AKAP79(77-153) polypeptide fragment uncouples AC5/6 from AKAP and prevents PKA-mediated inhibition of AC activity; loss of AKAP150 in mice reduces AMPA receptor-associated AC activity. Co-immunoprecipitation, pulldown, FRET (intensity- and lifetime-based) in living cells, AC activity assays in brain membranes from AKAP150-/- mice The Journal of biological chemistry High 20231277
2006 AC5 is an essential mediator of mu and delta (but not kappa) opioid receptor signaling in the striatum: AC5 knockout mice lack mu/delta opioid receptor agonist-induced suppression of adenylyl cyclase activity in striatum, and all major behavioral effects of morphine (locomotor activation, analgesia, tolerance, reward, physical dependence/withdrawal) are attenuated. AC5 knockout mice; biochemical adenylyl cyclase activity assay in striatal membranes; behavioral pharmacology with selective opioid receptor agonists Proceedings of the National Academy of Sciences of the United States of America High 16537460
2006 Calcium inhibits renin exocytosis from juxtaglomerular cells by inhibiting AC5 and AC6: siRNA-mediated knockdown of AC5 and/or AC6 prevented calcium-dependent inhibition of intracellular cAMP levels and renin release; clamping cAMP with membrane-permeable analogs bypassed calcium suppression of renin secretion. siRNA knockdown in primary JG cells and As4.1 renin-producing cell line; cAMP measurements; renin secretion assays; isolated perfused mouse kidneys Circulation research High 17068292
2002 Both high and low affinity Ca2+ inhibition of AC5 are exerted through the Mg2+-binding sites in the catalytic domain: Mg2+ activation reduces absolute high-affinity inhibition without changing Ki, while decreasing the Ki for low-affinity inhibition; forskolin (acting by a different mechanism) does not modify Ca2+ inhibition; chimeric constructs confirmed that the catalytic domain alone is responsible for high-affinity Ca2+ inhibition. Site-directed mutagenesis of AC5, domain deletion mutants, AC5/AC2 chimeric constructs, in vitro adenylyl cyclase activity assays with Ca2+, Mg2+, Sr2+, Ba2+ The Journal of biological chemistry High 12065575
2014 AC5 overexpression in transgenic mice creates a proarrhythmic substrate by inducing SR Ca2+ overload, increasing SERCA2a levels, causing oxidative CaMKII activation, and hyperphosphorylation of ryanodine receptors at the CaMKII site, leading to spontaneous Ca2+ waves, afterdepolarizations, and triggered action potentials upon isoproterenol stimulation. AC5 transgenic mice; intracellular Ca2+ imaging (fluo-4 AM); action potential recordings; Western blotting for SERCA2a, phospho-RyR, oxidized CaMKII; ROS measurements; in vivo arrhythmia assays American journal of physiology. Heart and circulatory physiology High 25485900
2012 Dopamine D2 receptor-mediated heterologous sensitization of AC5 requires Gαs-AC5 interactions and proper signalosome assembly: neither Gαs palmitoylation nor Gαs-Gβγ interactions were required for sensitization, but βARKct-CD8 or dominant-negative Sar1(H79G) blocked sensitization, implicating vesicular trafficking in assembly of the AC5 signalosome. Expression of Gαs mutants in Gαs-deficient Gnas(E2-/E2-) cells; cAMP assays; dominant-negative trafficking inhibitors Journal of signal transduction Medium 22523680
2019 Bimolecular fluorescence complementation (BiFC) screening in striatal medium spiny neurons identified PP2A catalytic subunit (PPP2CB) and NAPA as novel AC5 interactors/modulators; PPP2CB knockdown reduced both acute and sensitized adenylyl cyclase activity, establishing PP2A as a persistent regulator of AC5 activity in D1 and D2 MSNs. BiFC protein-protein interaction screening, genetic knockdown, cAMP assays in D1/D2 MSNs from CAMPER mice Cells Medium 31752385
2020 AC5 is required for stress-induced suppression of GluA1 protein synthesis in Bergmann glial cells: deletion of adenylyl cyclase 5 prevented stress-induced GluA1 suppression, placing AC5 downstream of β-adrenergic receptor activation and upstream of CPEB3-dependent GluA1 mRNA regulation and glial process retraction. AC5 knockout mice; immunofluorescence and Western blotting for GluA1; electrophysiology; genetic epistasis with CPEB3 knockout and β-adrenergic blocker The Journal of neuroscience Medium 32229518
2022 In zebrafish, Adcy3a and Adcy5 double mutants show defective melanosome dispersion (but not melanoblast differentiation); AC5-mediated cAMP-PKA signaling regulates melanosome dispersion by activating kinesin-1 and inhibiting cytoplasmic dynein-1; in adults, Adcy5 regulates Mitfa expression and melanin synthesis enzyme levels (Tyr, Dct, Trp1b), and loss of Adcy5 reduces pigmented melanocyte numbers. CRISPR/Cas9 knockout zebrafish; PKA activator rescue experiments; epistasis analysis of motor proteins International journal of molecular sciences Medium 36430661
2017 A type 2 diabetes risk allele at rs11708067-A in an intronic enhancer of ADCY5 reduces H3K27ac marks, shows lower transcriptional activity in reporter assays in rodent β-cells, and increased nuclear protein binding; homozygous deletion of the orthologous enhancer in 832/13 cells reduces Adcy5 expression by 64% and insulin secretion by 39%. ChIP-seq, luciferase reporter assays, CRISPR enhancer deletion, insulin secretion assay Diabetes High 28684635
2021 miR-18a-3p directly targets ADCY5 mRNA (confirmed by dual luciferase reporter and RNA pulldown); miR-18a-3p mimic inhibits osteogenic differentiation of hBMSCs, while ADCY5 overexpression promotes calcium deposition and osteoblast marker expression (OSX, ALP, RUNX2), and partially reverses miR-18a-3p-mediated inhibition. Dual luciferase reporter assay, RNA pulldown, overexpression and mimic transfection in hBMSCs, ALP activity and calcium deposition assays Biochemical and biophysical research communications Medium 33684620
2023 Caffeine, theophylline, and istradefylline all reduce cAMP production by ADCY5-overexpressing cells, with more pronounced effects on the gain-of-function R418W mutant than wild-type ADCY5, consistent with preferential inhibition of overactive AC5. cAMP measurement in ADCY5 wild-type and R418W mutant overexpressing cell lines treated with purine derivatives PloS one Medium 36867608

Source papers

Stage 0 corpus · 74 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2014 ADCY5 couples glucose to insulin secretion in human islets. Diabetes 122 24740569
2016 Phenotypic insights into ADCY5-associated disease. Movement disorders : official journal of the Movement Disorder Society 103 27061943
2015 ADCY5-related dyskinesia: Broader spectrum and genotype-phenotype correlations. Neurology 101 26537056
2014 Gain-of-function ADCY5 mutations in familial dyskinesia with facial myokymia. Annals of neurology 101 24700542
2010 AKAP79 interacts with multiple adenylyl cyclase (AC) isoforms and scaffolds AC5 and -6 to alpha-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate (AMPA) receptors. The Journal of biological chemistry 95 20231277
2006 Adenylyl cyclase type 5 (AC5) is an essential mediator of morphine action. Proceedings of the National Academy of Sciences of the United States of America 94 16537460
2015 The AC5 protein encoded by Mungbean yellow mosaic India virus is a pathogenicity determinant that suppresses RNA silencing-based antiviral defenses. The New phytologist 80 26010321
2011 The effect of including Lactobacillus reuteri KUB-AC5 during post-hatch feeding on the growth and ileum microbiota of broiler chickens. Poultry science 72 22080014
2015 ADCY5 mutations are another cause of benign hereditary chorea. Neurology 70 26085604
2017 ADCY5-related movement disorders: Frequency, disease course and phenotypic variability in a cohort of paediatric patients. Parkinsonism & related disorders 64 28511835
2006 The calcium paradoxon of renin release: calcium suppresses renin exocytosis by inhibition of calcium-dependent adenylate cyclases AC5 and AC6. Circulation research 64 17068292
2014 A de novo ADCY5 mutation causes early-onset autosomal dominant chorea and dystonia. Movement disorders : official journal of the Movement Disorder Society 63 25545163
2017 A Type 2 Diabetes-Associated Functional Regulatory Variant in a Pancreatic Islet Enhancer at the ADCY5 Locus. Diabetes 51 28684635
2021 An Update on the Phenotype, Genotype and Neurobiology of ADCY5-Related Disease. Movement disorders : official journal of the Movement Disorder Society 44 33934385
2022 Efficacy of Caffeine in ADCY5-Related Dyskinesia: A Retrospective Study. Movement disorders : official journal of the Movement Disorder Society 39 35384065
2019 ADCY5-Related Dyskinesia: Improving Clinical Detection of an Evolving Disorder. Movement disorders clinical practice 38 31538084
2002 A critical interplay between Ca2+ inhibition and activation by Mg2+ of AC5 revealed by mutants and chimeric constructs. The Journal of biological chemistry 38 12065575
2019 Functional characterization of AC5 gain-of-function variants: Impact on the molecular basis of ADCY5-related dyskinesia. Biochemical pharmacology 37 30772269
2016 Treatment of ADCY5-Associated Dystonia, Chorea, and Hyperkinetic Disorders With Deep Brain Stimulation: A Multicenter Case Series. Journal of child neurology 37 27052971
2012 Aluminum carboxymethyl cellulose-rice bran microcapsules: enhancing survival of Lactobacillus reuteri KUB-AC5. Carbohydrate polymers 37 24751013
2019 Identification of Novel Adenylyl Cyclase 5 (AC5) Signaling Networks in D1 and D2 Medium Spiny Neurons using Bimolecular Fluorescence Complementation Screening. Cells 35 31752385
2018 Protective effect of Lactobacillus reuteri KUB-AC5 against Salmonella Enteritidis challenge in chickens. Beneficial microbes 33 30406695
2018 PDE10A and ADCY5 mutations linked to molecular and microstructural basal ganglia pathology. Movement disorders : official journal of the Movement Disorder Society 30 30345538
2017 ADCY5-related dyskinesia presenting as familial myoclonus-dystonia. Neurogenetics 30 28229249
2010 Mice lacking adenylyl cyclase type 5 (AC5) show increased ethanol consumption and reduced ethanol sensitivity. Psychopharmacology 26 21193983
2020 Deep brain stimulation reduces (nocturnal) dyskinetic exacerbations in patients with ADCY5 mutation: a case series. Journal of neurology 22 32647899
2019 Autosomal recessive ADCY5-Related dystonia and myoclonus: Expanding the genetic spectrum of ADCY5-Related movement disorders. Parkinsonism & related disorders 22 30975617
2014 Overexpression of adenylyl cyclase type 5 (AC5) confers a proarrhythmic substrate to the heart. American journal of physiology. Heart and circulatory physiology 21 25485900
2023 Scoping Review on ADCY5-Related Movement Disorders. Movement disorders clinical practice 20 37476318
2020 Polymorphic variants of bovine ADCY5 gene identified in GWAS analysis were significantly associated with ovarian morphological related traits. Gene 19 32949694
2005 Probing the reorganization of the nicotinic acetylcholine receptor during desensitization by time-resolved covalent labeling using [3H]AC5, a photoactivatable agonist. Molecular pharmacology 18 16269537
2024 Structure of adenylyl cyclase 5 in complex with Gβγ offers insights into ADCY5-related dyskinesia. Nature structural & molecular biology 17 38589608
2020 Emotional Stress Induces Structural Plasticity in Bergmann Glial Cells via an AC5-CPEB3-GluA1 Pathway. The Journal of neuroscience : the official journal of the Society for Neuroscience 16 32229518
2014 Enhancement of Lactobacillus reuteri KUB-AC5 survival in broiler gastrointestinal tract by microencapsulation with alginate-chitosan semi-interpenetrating polymer networks. Journal of applied microbiology 16 24712513
2017 Facial twitches in ADCY5-associated disease - Myokymia or myoclonus? An electromyography study. Parkinsonism & related disorders 14 28442302
2018 The group I alphabaculovirus-specific protein, AC5, is a novel component of the occlusion body but is not associated with ODVs or the PIF complex. The Journal of general virology 13 29465345
2022 Probing Genome-Scale Model Reveals Metabolic Capability and Essential Nutrients for Growth of Probiotic Limosilactobacillus reuteri KUB-AC5. Biology 12 35205160
2018 Depression and psychosis in ADCY5-related dyskinesia-part of the phenotypic spectrum? Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia 12 30172639
2017 Combined effects of holy basil essential oil and inlet temperature on lipid peroxidation and survival of Lactobacillus reuteri KUB-AC5 during spray drying. Food research international (Ottawa, Ont.) 12 28873688
2023 Development of high cell density Limosilactobacillus reuteri KUB-AC5 for cell factory using oxidative stress reduction approach. Microbial cell factories 11 37120528
2021 ADCY5, CAPN10 and JAZF1 Gene Polymorphisms and Placental Expression in Women with Gestational Diabetes. Life (Basel, Switzerland) 11 34440550
2022 AC5 protein encoded by squash leaf curl China virus is an RNA silencing suppressor and a virulence determinant. Frontiers in microbiology 9 36060769
2021 Effects of Whole-Body Adenylyl Cyclase 5 (Adcy5) Deficiency on Systemic Insulin Sensitivity and Adipose Tissue. International journal of molecular sciences 9 33919448
2011 Absence of birth-weight lowering effect of ADCY5 and near CCNL, but association of impaired glucose-insulin homeostasis with ADCY5 in Asian Indians. PloS one 9 21712988
2023 Effects of theophylline on ADCY5 activation-From cellular studies to improved therapeutic options for ADCY5-related dyskinesia patients. PloS one 8 36867608
2020 Common genetic variants in ADCY5 and gestational glycemic traits. PloS one 8 32163478
2020 Efficacy of Istradefylline for the Treatment of ADCY5-Related Disease. Movement disorders clinical practice 8 33043083
2012 Dopamine D(2) Receptor-Mediated Heterologous Sensitization of AC5 Requires Signalosome Assembly. Journal of signal transduction 8 22523680
2023 DNA methylation alterations of ADCY5, MICAL2, and PLEKHG2 during the developmental stage of cryptogenic hepatocellular carcinoma. Hepatology research : the official journal of the Japan Society of Hepatology 7 37906571
2022 Type 2 diabetes is more closely associated with risk of colorectal cancer based on elevated DNA methylation levels of ADCY5. Oncology letters 7 35720494
2019 Antimicrobial peptide presenting potential strain-specific real time polymerase chain reaction assay for detecting the probiotic Lactobacillus reuteri KUB-AC5 in chicken intestine. Poultry science 7 32416839
2025 Treatment Efficacy of Theophylline in ADCY5-Related Dyskinesia: A Retrospective Case Series Study. Movement disorders : official journal of the Movement Disorder Society 6 40079709
2024 Probiotic Limosilactobacillus reuteri KUB-AC5 decreases urothelial cell invasion and enhances macrophage killing of uropathogenic Escherichia coli in vitro study. Frontiers in cellular and infection microbiology 6 39091675
2021 By inhibiting ADCY5, miR-18a-3p promotes osteoporosis and possibly contributes to spinal fracture. Biochemical and biophysical research communications 6 33684620
2021 Homozygous ADCY5 mutation causes early-onset movement disorder with severe intellectual disability. Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology 6 33704598
2019 Hyperphosphorylated Tau, Increased Adenylate Cyclase 5 (ADCY5) Immunoreactivity, but No Neuronal Loss in ADCY5-Dyskinesia. Movement disorders clinical practice 6 31970214
2022 Requirement of Zebrafish Adcy3a and Adcy5 in Melanosome Dispersion and Melanocyte Stripe Formation. International journal of molecular sciences 4 36430661
2024 ADCY5-related dyskinesia - case series with literature review. Neurologia i neurochirurgia polska 3 38230756
2022 Early-life low-level lead exposure alters anxiety-like behavior, voluntary alcohol consumption and AC5 protein content in adult male and female C57BL/6 J mice. Neurotoxicology and teratology 3 36539102
2021 Integrative growth physiology and transcriptome profiling of probiotic Limosilactobacillus reuteri KUB-AC5. PeerJ 3 34707932
2025 ADCY5 Gene Affects Seasonal Reproduction in Dairy Goats by Regulating Ovarian Granulosa Cells Steroid Hormone Synthesis. International journal of molecular sciences 2 40004085
2024 ADCY5 act as a putative tumor suppressor in glioblastoma: An integrated analysis. Heliyon 2 39319137
2022 ADCY5 gene mutation: a case report. Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology 1 36112278
2020 [ADCY5-associated dyskinesia in young children: a case report of a family and an updated review]. Revista de neurologia 1 32627162
2015 ADCY5 Mutations and Benign Hereditary Chorea. Pediatric neurology briefs 1 26933606
1999 Accumulation of ζ-carotene in Chlamydomonas reinhardtii under control of the ac5 nuclear gene. Plant cell reports 1 30754756
2026 Nocturnal Ballistic Bouts in ADCY5-Related Movement Disorder. Cureus 0 41705003
2026 [Autosomal dominant dyskinesia associated with the ADCY5 gene]. Zhurnal nevrologii i psikhiatrii imeni S.S. Korsakova 0 41782543
2026 Mixed Movement Disorder Caused by ADCY5 Pathogenic Variant Successfully Treated With Caffeine: A Case From Ukraine. Case reports in neurological medicine 0 41799247
2025 Generation of an induced pluripotent stem cell line (UCLi026-A) from a patient with ADCY5-related disease carrying the heterozygous variant c.1253G > A; (p. Arg418Gln). Stem cell research 0 39919432
2025 Pearls & Oy-sters: ADCY5-Related Dyskinesia: From a Longstanding Misdiagnosis of Drug-Resistant Epilepsy. Neurology 0 40300124
2025 Artemisinin alleviates Parkinson's disease by targeting Adcy5-Gch1 axis to trigger a cascade generation of BH4 and dopamine in rats. Genome biology 0 40908481
2024 A Single-Arm, Prospective Study of a Proprietary Synthetic Acellular Self-Assembling Peptide Wound Matrix, AC5® Advanced Wound System, for Treatment of Hard-to-Heal Wounds. Surgical technology international 0 39546632
2023 Case report: Diagnosis of ADCY5-related dyskinesia explaining the entire phenotype in a patient with atypical citrullinemia type I. Frontiers in neurology 0 38020658