ADCY3: Adenylate Cyclase 3 - A Key Regulator of cAMP Signaling
Comprehensive gene information, expression, mutations, and clinical significance of ADCY3
Gene Information Card
| Symbol | ADCY3 |
|---|---|
| Full Name | Adenylate Cyclase 3 |
| Gene Type | protein-coding |
| Chromosomal Location | 2p23.3 |
| NCBI Gene ID | 109 ncbi.nlm.nih.gov/gene/109 |
| Ensembl ID | ENSG00000138031 |
| UniProt ID | O60266 |
| OMIM ID | 600291 |
| HGNC ID | 234 |
| Aliases | AC3, AC-III, adenylate cyclase type 3 |
Description
ADCY3 (Adenylate Cyclase 3) encodes a member of the adenylate cyclase family, which catalyzes the conversion of ATP to cyclic AMP (cAMP), a key second messenger in signal transduction. ADCY3 is predominantly expressed in olfactory epithelium, brain, and adipose tissue, and plays critical roles in olfaction, energy homeostasis, and insulin secretion. Variants in ADCY3 are associated with obesity, type 2 diabetes, and impaired olfactory function.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Obesity | Loss-of-function variants reduce cAMP signaling in hypothalamic neurons, disrupting appetite regulation and energy balance. | ClinVar, OMIM |
| Type 2 Diabetes | ADCY3 deficiency impairs insulin secretion from pancreatic beta cells via reduced cAMP levels. | ClinVar, OMIM |
| Olfactory Dysfunction | ADCY3 is essential for olfactory signal transduction; mutations lead to anosmia or hyposmia. | OMIM, NCBI |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Adipose tissue | 12.5 | Medium |
| Brain (cerebellum) | 8.3 | Medium |
| Olfactory mucosa | 45.2 | High |
| Pancreas | 6.1 | Low |
| Testis | 3.4 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 15.2 | High expression in recombinant systems |
| SH-SY5Y | 9.8 | Neuronal cell line |
| 3T3-L1 | 7.5 | Adipocyte precursor |
| HepG2 | 2.1 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1112G>A (p.Arg371His) | Missense | 0.02% (gnomAD) | Reduced catalytic activity; associated with obesity |
| c.2311C>T (p.Arg771*) | Nonsense | 0.001% | Loss of function; severe obesity |
| c.1573A>G (p.Ile525Val) | Missense | 0.1% | Benign polymorphism |
Mutation functional classification
Loss of Function (LOF)
Nonsense and missense mutations that reduce or abolish cAMP production, leading to obesity and diabetes.
Gain of Function (GOF)
Not reported in ADCY3.
Dominant Negative (DN)
Not reported in ADCY3.
View complete mutation data：
Gene Ontology (GO)
| • GO:0004016 - adenylate cyclase activity | • GO:0006171 - cAMP biosynthetic process |
| • GO:0007189 - adenylate cyclase-activating G protein-coupled receptor signaling pathway | • GO:0007608 - sensory perception of smell |
| • GO:0016021 - integral component of membrane |
Pathways
• cAMP signaling pathway (KEGG: hsa04024)
• Olfactory transduction pathway (KEGG: hsa04740)
• GPCR downstream signaling (Reactome: R-HSA-388396)
Protein Summary
ADCY3 encodes a 1144-amino acid transmembrane protein with 12 membrane-spanning domains and two cytoplasmic catalytic domains. It is a membrane-bound adenylate cyclase that synthesizes cAMP from ATP in response to G protein-coupled receptor activation. The protein is highly expressed in olfactory cilia, where it mediates odorant-induced cAMP production, and in brain and adipose tissue, where it regulates metabolic and neuroendocrine functions. Structural studies show that ADCY3 forms homodimers and is regulated by Gαs, Gαi, and calcium/calmodulin.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| ADCY3 Knockout HEK293 Cell Line | EDJ-KQ1294 | Human | 109 | Details Get a Quote |
| ADCY3 Knockout A-549 Cell Line | EDJ-KQ20700 | Human | 109 | Details Get a Quote |
| ADCY3 Knockout HCT 116 Cell Line | EDJ-KQ20701 | Human | 109 | Details Get a Quote |
| ADCY3 Knockout HeLa Cell Line | EDJ-KQ20702 | Human | 109 | Details Get a Quote |
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