ADCY5 Gene: Adenylate Cyclase 5 - Function, Disease Associations, and Clinical Significance
Comprehensive guide to ADCY5, its role in cAMP signaling, associated disorders including familial dyskinesia, and mutation landscape.
Gene Information Card
| Symbol | ADCY5 |
|---|---|
| Full Name | Adenylate Cyclase 5 |
| Gene Type | Protein coding |
| Chromosomal Location | 3q21.1 |
| NCBI Gene ID | 111 ncbi.nlm.nih.gov/gene/111 |
| Ensembl ID | ENSG00000173175 |
| UniProt ID | O95622 |
| OMIM ID | 600293 |
| HGNC ID | 236 |
| Aliases | AC5, ADCY5, adenylate cyclase 5 |
Description
ADCY5 encodes adenylate cyclase 5, a membrane-bound enzyme that catalyzes the conversion of ATP to cyclic AMP (cAMP), a key second messenger in cellular signaling. It is highly expressed in the brain, particularly in the striatum, where it plays a critical role in dopamine and adenosine receptor signaling. Mutations in ADCY5 are associated with a spectrum of movement disorders, including familial dyskinesia with facial myokymia, and have been implicated in other neurological conditions.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Familial dyskinesia with facial myokymia (FDFM) | Gain-of-function mutations lead to increased cAMP production, causing abnormal neuronal excitability and movement disorders. | ClinVar; OMIM #606703 |
| ADCY5-related movement disorder (including paroxysmal dyskinesias) | Heterozygous missense mutations (e.g., p.Arg418Gln) result in constitutive activation or altered regulation of adenylate cyclase, leading to excessive cAMP signaling. | ClinVar; multiple case reports |
| Essential tremor (susceptibility) | Polymorphisms in ADCY5 may modulate cAMP levels in cerebellar circuits, contributing to tremor susceptibility. | GWAS studies; ClinVar |
| Dystonia (early-onset) | Rare variants affecting ADCY5 function may disrupt striatal signaling, leading to dystonic postures. | ClinVar; case reports |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain (basal ganglia) | High | High expression in caudate, putamen, and nucleus accumbens |
| Heart | Moderate | Moderate expression in cardiac muscle |
| Lung | Low | Low expression |
| Liver | Low | Low expression |
| Kidney | Low | Low expression |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | High | Neuronal-like cells; used for functional studies |
| SK-N-SH (neuroblastoma) | High | Similar to SH-SY5Y |
| HEK293 (embryonic kidney) | Moderate | Often used for recombinant expression |
| HeLa (cervical carcinoma) | Low | Low endogenous expression |
| A549 (lung carcinoma) | Low | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| p.Arg418Gln (c.1253G>A) | Missense | Recurrent; found in multiple families | Gain-of-function; increased basal cAMP activity |
| p.Arg418Trp (c.1252C>T) | Missense | Rare | Gain-of-function; similar effect to Arg418Gln |
| p.Ala726Tyr (c.2176G>T) | Missense | Rare | Likely gain-of-function; altered regulation |
| p.Leu1069Pro (c.3206T>C) | Missense | Rare | Loss-of-function?; reduced catalytic activity |
| p.Arg264His (c.791G>A) | Missense | Rare | Uncertain; possibly benign |
Mutation functional classification
Loss of Function (LOF)
Rare loss-of-function mutations may reduce cAMP production, potentially leading to altered neuronal signaling, but are less common than gain-of-function variants.
Gain of Function (GOF)
Most pathogenic mutations are gain-of-function, leading to increased basal or stimulated cAMP production, causing hyperexcitability in striatal neurons and movement disorders.
Dominant Negative (DN)
No clear dominant-negative mutations have been reported; the dominant inheritance is primarily due to gain-of-function haploinsufficiency.
View complete mutation data：
Gene Ontology (GO)
| • Adenylate cyclase activity | • cAMP biosynthetic process |
| • G protein-coupled receptor signaling pathway | • Membrane |
| • Integral component of plasma membrane | • ATP binding |
Pathways
• cAMP signaling pathway
• Dopamine receptor signaling pathway
• Adenosine receptor signaling pathway
• G alpha(s) signaling events
Protein Summary
ADCY5 is a 1261-amino acid protein with a predicted molecular mass of ~139 kDa. It contains 12 transmembrane domains, two cytoplasmic catalytic domains (C1 and C2), and is activated by G protein alpha subunits (Gs) and inhibited by Gi/o. The protein is primarily expressed in the brain and heart. Its crystal structure has not been fully resolved, but homology models based on other adenylate cyclases suggest a dimeric arrangement. Post-translational modifications include phosphorylation and glycosylation, which may regulate its activity and trafficking.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| ADCY5 Knockout HEK293 Cell Line | EDJ-KQ731 | Human | 111 | Details Get a Quote |
| ADCY5 Knockout HeLa Cell Line | EDJ-KQ52551 | Human | 111 | Details Get a Quote |
| ADCY5 Knockout A-549 Cell Line | EDJ-KQ61033 | Human | 111 | Details Get a Quote |
| ADCY5 Knockout HCT 116 Cell Line | EDJ-KQ69509 | Human | 111 | Details Get a Quote |
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