ADCY8 Gene - Adenylyl Cyclase 8
Key regulator of cAMP signaling in neuronal and endocrine systems
Gene Information Card
| Symbol | ADCY8 |
|---|---|
| Full Name | Adenylyl Cyclase 8 |
| Gene Type | Protein coding |
| Chromosomal Location | 8q24.22 |
| NCBI Gene ID | 114 ncbi.nlm.nih.gov/gene/114 |
| Ensembl ID | ENSG00000155897 |
| UniProt ID | P40145 |
| OMIM ID | 103070 |
| HGNC ID | 240 |
| Aliases | AC8, ADCY3, HBAC1 |
Description
ADCY8 encodes adenylyl cyclase 8, a membrane-bound enzyme that catalyzes the conversion of ATP to cyclic AMP (cAMP). It is predominantly expressed in brain and endocrine tissues, playing a critical role in calcium- and G protein-coupled receptor signaling. Mutations in ADCY8 are associated with neurodevelopmental disorders including intellectual disability and epilepsy.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Intellectual disability, autosomal dominant 65 | Loss-of-function mutations impair cAMP synthesis, disrupting neuronal signaling | ClinVar, OMIM #619639 |
| Epileptic encephalopathy, early infantile | Biallelic variants reduce enzyme activity, leading to synaptic dysfunction | ClinVar, PubMed 31585109 |
| Bipolar disorder (susceptibility) | Altered ADCY8 expression may affect mood regulation via cAMP pathway | OMIM, GWAS studies |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain (cerebral cortex) | 12.5 | High |
| Brain (cerebellum) | 8.3 | Medium |
| Adrenal gland | 6.1 | Medium |
| Heart | 1.2 | Low |
| Liver | 0.5 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | 15.2 | Neuronal model |
| HEK293 (embryonic kidney) | 2.1 | Low endogenous expression |
| U-87 MG (glioblastoma) | 9.8 | Glial tumor line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.2074C>T (p.Arg692*) | Nonsense | <0.01% | Loss of function; truncation of catalytic domain |
| c.2536G>A (p.Gly846Arg) | Missense | 0.02% | Impaired enzyme activity; associated with intellectual disability |
| c.1123_1124del (p.Leu375fs) | Frameshift | Rare | Loss of function; epileptic encephalopathy |
Mutation functional classification
Loss of Function (LOF)
Nonsense, frameshift, and missense variants that reduce or abolish cAMP production are classified as loss-of-function.
Gain of Function (GOF)
No gain-of-function mutations have been reported in ADCY8.
Dominant Negative (DN)
Some missense variants may exert dominant-negative effects by interfering with dimerization or catalytic activity.
View complete mutation data：
Gene Ontology (GO)
| • GO:0004016 (adenylate cyclase activity) | • GO:0007189 (adenylate cyclase-activating G protein-coupled receptor signaling pathway) |
| • GO:0005886 (plasma membrane) | • GO:0035556 (intracellular signal transduction) |
| • GO:0016021 (integral component of membrane) |
Pathways
• cAMP signaling pathway (KEGG: hsa04024)
• Calcium signaling pathway (KEGG: hsa04020)
• G alpha(s) signaling events (Reactome: R-HSA-418555)
Protein Summary
ADCY8 is a 1253-amino acid transmembrane protein with 12 membrane-spanning domains and two cytoplasmic catalytic domains (C1 and C2). It is activated by G protein alpha-s subunits and calcium/calmodulin. The protein is essential for neuronal plasticity, hormone secretion, and learning. Structural studies show that mutations in the catalytic domains disrupt ATP binding and cAMP generation.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| ADCY8 Knockout HEK293 Cell Line | EDJ-KQ1298 | Human | 114 | Details Get a Quote |
| ADCY8 Knockout HeLa Cell Line | EDJ-KQ52552 | Human | 114 | Details Get a Quote |
| ADCY8 Knockout A-549 Cell Line | EDJ-KQ61034 | Human | 114 | Details Get a Quote |
| ADCY8 Knockout HCT 116 Cell Line | EDJ-KQ69510 | Human | 114 | Details Get a Quote |
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