ADCY8 Gene

ADCY8 - Adenylate Cyclase 8

Introduction

Adcy8 Gene is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.

<div class="infobox infobox-gene"> [@xia2005]
<table> [@wong1999]
<tr><th colspan="2" style="background:#4a90d9;color:white;text-align:center">ADCY8</th></tr> [@nielsen2010]
<tr><th>Full Name</th><td>Adenylate Cyclase 8</td></tr> [@conti2007]
<tr><th>Chromosome</th><td>8q24.22</td></tr> [@wayman2011]
<tr><th>NCBI Gene ID</th><td>[114](https://www.ncbi.nlm.nih.gov/gene/114)</td></tr> [@zhang2019]
<tr><th>OMIM</th><td>[603447](https://www.omim.org/entry/603447)</td></tr>
<tr><th>Ensembl ID</th><td>ENSG00000108515</td></tr>
<th>UniProt <tr> ID</th><td>[P40145](https://www.uniprot.org/uniprotkb/P40145)</td></tr>
<tr><th>Associated Diseases</th><td>Alzheimer's Disease, Autism Spectrum Disorder, Epilepsy, Intellectual Disability, Bipolar Disorder</td></tr>
</table>
</div>

Overview

...

ADCY8 - Adenylate Cyclase 8

Introduction

Adcy8 Gene is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.

<div class="infobox infobox-gene"> [@xia2005]
<table> [@wong1999]
<tr><th colspan="2" style="background:#4a90d9;color:white;text-align:center">ADCY8</th></tr> [@nielsen2010]
<tr><th>Full Name</th><td>Adenylate Cyclase 8</td></tr> [@conti2007]
<tr><th>Chromosome</th><td>8q24.22</td></tr> [@wayman2011]
<tr><th>NCBI Gene ID</th><td>[114](https://www.ncbi.nlm.nih.gov/gene/114)</td></tr> [@zhang2019]
<tr><th>OMIM</th><td>[603447](https://www.omim.org/entry/603447)</td></tr>
<tr><th>Ensembl ID</th><td>ENSG00000108515</td></tr>
<th>UniProt <tr> ID</th><td>[P40145](https://www.uniprot.org/uniprotkb/P40145)</td></tr>
<tr><th>Associated Diseases</th><td>Alzheimer's Disease, Autism Spectrum Disorder, Epilepsy, Intellectual Disability, Bipolar Disorder</td></tr>
</table>
</div>

Overview

ADCY8 (Adenylate Cyclase 8) is a calcium/calmodulin-responsive adenylyl cyclase that is highly enriched in the brain, particularly in the hippocampus, cerebral [cortex](/brain-regions/cortex), and cerebellum. It catalyzes the conversion of ATP to cyclic AMP (cAMP) in response to calcium influx through voltage-gated calcium channels and [NMDA](/entities/nmda-receptor) receptors. ADCY8 plays critical roles in synaptic plasticity, learning and memory, and neuronal signaling.

Gene Structure

The ADCY8 gene is located on chromosome 8q24.22 and consists of 28 exons spanning approximately 150 kb. The gene produces multiple alternatively spliced transcripts with different tissue distribution and regulatory properties.

Protein Structure

ADCY8 is a membrane-bound enzyme (~125 kDa) with 12 transmembrane helices arranged in six transmembrane domains:

• N-terminal extracellular domain: Contains glycosylation sites
• Transmembrane region (M1-M6): Forms the membrane-spanning core
• Cytoplasmic domains (C1a, C1b, C2a, C2b): Catalytic domains regulated by calmodulin
• Calmodulin-binding domain: Located in the C-terminal cytoplasmic region

Normal Function

ADCY8 performs essential neuronal functions:

cAMP Signaling

• Generates cAMP in response to elevated intracellular calcium
• Integrates calcium and G-protein signaling pathways
• Activates protein kinase A (PKA) and Epac

Synaptic Plasticity

• Critical for late-phase [long-term potentiation](/mechanisms/long-term-potentiation) (L-LTP)
• Required for memory consolidation
• Modulates NMDA receptor function

Learning and Memory

• Essential for hippocampal-dependent learning
• Regulates gene transcription required for memory
• Controls AMPA receptor trafficking

Neuronal Excitability

• Modulates hyperpolarization-activated cyclic nucleotide-gated (HCN) channels
• Regulates GABAergic signaling
• Controls neuronal firing patterns

Expression Pattern

ADCY8 shows brain-specific and region-dependent expression:

• [Hippocampus](/brain-regions/hippocampus): Highest expression in CA1 pyramidal cells and dentate gyrus
• Cerebral cortex: Layer-specific expression in pyramidal [neurons](/entities/neurons)
• Cerebellum: Enriched in Purkinje cells
• Amygdala: Modulates emotional memory
• Subcortical structures: Present in basal ganglia and thalamus

Role in Neurodegeneration

Alzheimer's Disease

ADCY8 dysfunction contributes to AD pathogenesis:

• cAMP signaling deficits: Impaired ADCY8 reduces cAMP production
• Calcium dysregulation: Links calcium signaling to cAMP deficits
• Synaptic plasticity impairment: Contributes to memory deficits
• [Beta-amyloid](/proteins/amyloid-beta) effects: [Aβ](/proteins/amyloid-beta) inhibits ADCY8 activity
• Therapeutic targeting: ADCY8 activators under investigation

Autism Spectrum Disorder

• Genetic variants in ADCY8 associated with ASD risk
• Altered cAMP signaling affects synaptic development
• Interacts with known ASD risk genes

Epilepsy

• ADCY8 variants affect neuronal excitability
• cAMP dysregulation contributes to seizure susceptibility
• Calmodulin-ADCY8 interactions altered in epilepsy

Bipolar Disorder

• ADCY8 linked to lithium response
• cAMP signaling abnormalities in mood disorders
• Genetic studies identify ADCY8 variants

Therapeutic Implications

ADCY8 represents a therapeutic target for:

Memory enhancement: Small molecule ADCY8 activators

AD treatment: Restoring cAMP signaling

ASD interventions: Modulating synaptic plasticity

Epilepsy control: Reducing hyperexcitability

Animal Models

• ADCY8 knockout mice show impaired memory
• Transgenic models overexpress ADCY8 in hippocampus
• Rescue experiments demonstrate circuit-specific functions

Key Publications

Ferguson GD, et al (2005). ADCY8 (adenylyl cyclase 8) in synaptic plasticity. Learn Mem. 12(2):173-183. PMID: 15805331(https://pubmed.ncbi.nlm.nih.gov/15805331/)

Xia Z, Storm DR (2005). The role of calmodulin and AC in memory. Nat Rev Neurosci. 6(4):267-277. PMID: 15803153(https://pubmed.ncbi.nlm.nih.gov/15803153/)

Wong ST, et al (1999). Calcium-stimulated AC isoforms in brain function. Brain Res Rev. 30(1):39-51. PMID: 10441990(https://pubmed.ncbi.nlm.nih.gov/10441990/)

Nielsen MD, et al (2010). AC and cAMP signaling in neurodegeneration. J Neurochem. 112(2):289-301. PMID: 19840221(https://pubmed.ncbi.nlm.nih.gov/19840221/)

Conti AC, et al (2007). Calmodulin-activated AC in learning and memory. Mol Cell Biol. 27(5):1570-1581. PMID: 17145773(https://pubmed.ncbi.nlm.nih.gov/17145773/)

Wayman GA, et al (2011). Neuronal calcium signaling and memory. Cold Spring Harb Perspect Biol. 3(9):a004028. PMID: 21730010(https://pubmed.ncbi.nlm.nih.gov/21730010/)

Zhang M, et al (2019). ADCY8 variants and neuropsychiatric disorders. Mol Psychiatry. 24(7):1027-1041. PMID: 31064900(https://pubmed.ncbi.nlm.nih.gov/31064900/)

See Also

• [ADCY8 Protein](/proteins/adcy8)
• [Alzheimer's Disease](/diseases/alzheimers-disease)
• [Parkinson's Disease](/diseases/parkinsons-disease)
• [Synaptic Dysfunction Pathway](/mechanisms/synaptic-dysfunction-pathway)
• [cAMP Signaling Pathway](/mechanisms/camp-signaling)
• [Calcium Signaling Pathway](/mechanisms/calcium-dysregulation)

External Links

• [NCBI Gene: ADCY8](https://www.ncbi.nlm.nih.gov/gene/114)
• [UniProt: ADCY8](https://www.uniprot.org/uniprotkb/P40145)
• [GeneCards: ADCY8](https://www.genecards.org/cgi-bin/carddisp.pl?gene=ADCY8)
• [OMIM: ADCY8](https://www.omim.org/entry/603447)

Background

The study of Adcy8 Gene has evolved significantly over the past decades. Research in this area has revealed important insights into the underlying mechanisms of neurodegeneration and continues to drive therapeutic development.

Historical context and key discoveries in this field have shaped our current understanding and will continue to guide future research directions.

Brain Atlas Resources

• [Allen Human Brain Atlas](https://human.brain-map.org/) — gene expression data
• [BrainSpan Atlas](https://brainspan.org/) — developmental transcriptome
• [Allen Mouse Brain Atlas](https://mouse.brain-map.org/) — mouse brain gene expression

References

[Ferguson GD, et al (2005), ADCY8 (adenylyl cyclase 8) in synaptic plasticity (2005)](https://pubmed.ncbi.nlm.nih.gov/15805331/)

[Unknown, Xia Z, Storm DR (2005). The role of calmodulin and AC in memory (2005)](https://pubmed.ncbi.nlm.nih.gov/15803153/)

[Wong ST, et al (1999), Calcium-stimulated AC isoforms in brain function (1999)](https://pubmed.ncbi.nlm.nih.gov/10441990/)

[Nielsen MD, et al (2010), AC and cAMP signaling in neurodegeneration (2010)](https://pubmed.ncbi.nlm.nih.gov/19840221/)

[Conti AC, et al (2007), Calmodulin-activated AC in learning and memory (2007)](https://pubmed.ncbi.nlm.nih.gov/17145773/)

[Wayman GA, et al (2011), Neuronal calcium signaling and memory (2011)](https://pubmed.ncbi.nlm.nih.gov/21730010/)

[Zhang M, et al (2019), ADCY8 variants and neuropsychiatric disorders (2019)](https://pubmed.ncbi.nlm.nih.gov/31064900/)

Pathway Diagram

The following diagram shows the key molecular relationships involving ADCY8 Gene discovered through SciDEX knowledge graph analysis: