ADCY10: Adenylate Cyclase 10 (Soluble)
Soluble adenylyl cyclase (sAC) – a key bicarbonate sensor and regulator of cAMP signaling
Gene Information Card
| Symbol | ADCY10 |
|---|---|
| Full Name | Adenylate Cyclase 10 (Soluble) |
| Gene Type | Protein coding |
| Chromosomal Location | 1q24.2 |
| NCBI Gene ID | 55811 ncbi.nlm.nih.gov/gene/55811 |
| Ensembl ID | ENSG00000143199 |
| UniProt ID | Q96PN6 |
| OMIM ID | 605205 |
| HGNC ID | 21285 |
| Aliases | SAC, SACH, HCA2, FLJ10718, FLJ11271 |
Description
ADCY10 encodes soluble adenylyl cyclase (sAC), a unique, bicarbonate- and calcium-regulated enzyme that catalyzes the synthesis of cyclic AMP (cAMP) from ATP. Unlike transmembrane adenylyl cyclases, sAC is not regulated by G proteins or forskolin. It acts as an intracellular bicarbonate sensor and plays critical roles in sperm capacitation, renal acid‑base balance, and cellular signaling. Mutations in ADCY10 are associated with autosomal recessive male infertility and susceptibility to idiopathic calcium nephrolithiasis.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Male infertility (spermatogenic failure) | Loss‑of‑function mutations in ADCY10 impair sAC activity, disrupting cAMP‑dependent sperm capacitation and motility. | ClinVar, OMIM #605205 |
| Idiopathic calcium nephrolithiasis | Variants in ADCY10 alter bicarbonate‑sensing in renal tubules, leading to abnormal calcium handling and stone formation. | OMIM #605205, PMID: 20041220 |
| Primary ciliary dyskinesia (atypical) | Defective sAC‑mediated cAMP signaling in ciliated epithelia may contribute to mucociliary clearance dysfunction. | OMIM #605205, limited evidence |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 28.5 | High |
| Kidney | 12.3 | Medium |
| Brain | 6.7 | Low |
| Lung | 4.1 | Low |
| Liver | 1.2 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK 293 | 15.2 | High expression in recombinant systems |
| HeLa | 8.9 | Moderate endogenous expression |
| A549 | 5.4 | Low expression |
| K562 | 2.1 | Very low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1735C>T (p.Arg579*) | Nonsense | Rare | Loss of function; truncates sAC protein |
| c.914T>C (p.Leu305Pro) | Missense | Rare | Loss of function; disrupts catalytic domain |
| c.2242G>A (p.Gly748Arg) | Missense | Rare | Likely loss of function; reduced cAMP production |
| c.1063_1064del (p.Gln355Valfs*2) | Frameshift | Rare | Loss of function; premature termination |
Mutation functional classification
Loss of Function (LOF)
Nonsense, frameshift, and missense mutations that reduce or abolish sAC catalytic activity are the primary mechanism in male infertility and nephrolithiasis.
Gain of Function (GOF)
No gain‑of‑function mutations have been reported for ADCY10.
Dominant Negative (DN)
No dominant‑negative mutations have been described; all reported pathogenic variants are recessive.
View complete mutation data：
Gene Ontology (GO)
| • GO:0004016 – adenylate cyclase activity | • GO:0005515 – protein binding |
| • GO:0005524 – ATP binding | • GO:0005737 – cytoplasm |
| • GO:0005829 – cytosol | • GO:0005886 – plasma membrane |
| • GO:0006171 – cAMP biosynthetic process | • GO:0016020 – membrane |
| • GO:0035556 – intracellular signal transduction | • GO:0048240 – sperm capacitation |
Pathways
• cAMP signaling pathway (Reactome: R-HSA-382556)
• Bicarbonate‑sensing via sAC (Reactome: R-HSA-1296067)
• Sperm motility and capacitation (KEGG: hsa04914)
Protein Summary
Soluble adenylyl cyclase (sAC) is a 187‑kDa protein encoded by ADCY10. It contains two catalytic domains (C1 and C2) that form an active site responsive to bicarbonate and calcium ions. sAC is the major source of cAMP in sperm and plays a pivotal role in pH sensing and metabolic regulation. The protein is widely expressed but most abundant in testis and kidney. Its activity is independent of G‑protein regulation, distinguishing it from transmembrane adenylyl cyclases.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| ADCY10 Knockout HEK293 Cell Line | EDC07938 | Human | 55811 | Details Get a Quote |
| ADCY10 Knockout HeLa Cell Line | EDJ-KQ56636 | Human | 55811 | Details Get a Quote |
| ADCY10 Knockout A-549 Cell Line | EDJ-KQ65142 | Human | 55811 | Details Get a Quote |
| ADCY10 Knockout HCT 116 Cell Line | EDJ-KQ73579 | Human | 55811 | Details Get a Quote |
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