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GeneE
10 sources retrieved Β· Most recent: April 2026 Β· Index updated 15 days ago
β“˜GeneE is for informational purposes only. It is not a substitute for professional medical advice, diagnosis, or treatment.
ADCY6
adenylate cyclase 6
Chromosome 12 Β· 12q13.12
NCBI Gene: 112Ensembl: ENSG00000174233.13HGNC: HGNC:237UniProt: O43306
82PubMed Papers
21Diseases
0Drugs
3Pathogenic Variants
FUNCTIONAL ROLE
Hub Gene
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
cellular response to forskolinprotein kinase C bindingcellular response to catecholamine stimulusadenylate cyclase activityHypomyelination neuropathy - arthrogryposishypomyelination neuropathy-arthrogryposis syndromegenetic disorderdiabetic ketoacidosis
✦AI Summary

ADCY6 (adenylate cyclase 6) catalyzes the formation of cyclic adenosine monophosphate (cAMP), a critical second messenger in G protein-coupled receptor signaling cascades 1. The enzyme plays essential roles in multiple physiological systems, including cardiovascular function, peripheral nervous system myelination, and immune regulation. In the cardiovascular system, ADCY6 functions downstream of beta-adrenergic receptors and contributes to cardiac contractility and blood pressure regulation 2. A hyperfunctional variant (A674S) is associated with increased blood pressure and hyperdynamic cardiovascular responses 2. ADCY6 has an unexpected role in peripheral nervous system myelination, as mutations cause severe arthrogryposis multiplex congenita with axoglial defects 1. The protein appears essential for proper Schwann cell myelination through cAMP pathway activation 1. Recent studies suggest therapeutic potential, as forskolin activation of ADCY6/cAMP/PKA signaling alleviates hypertrophic cardiomyopathy 3. Additionally, ADCY6 methylation status correlates with immune cell infiltration in luminal breast cancer, where hypermethylation and downregulation associate with better prognosis 4. Disease associations include lethal congenital contracture syndrome 8, highlighting its critical developmental importance.

Sources cited
1
ADCY6 catalyzes cAMP formation and mutations cause severe arthrogryposis multiplex congenita with peripheral nervous system myelination defects
PMID: 24319099
2
ADCY6 A674S hyperfunctional variant is associated with increased blood pressure and hyperdynamic cardiovascular responses
PMID: 20732959
3
Forskolin activation of ADCY6/cAMP/PKA pathway alleviates hypertrophic cardiomyopathy
PMID: 38925286
4
ADCY6 hypermethylation and downregulation correlate with better prognosis in luminal breast cancer and immune cell infiltration
PMID: 31886586
⚠Limited data available β€” This gene has 4 indexed publications. Summary and analysis may be incomplete.
Disease Associationsβ“˜21
Hypomyelination neuropathy - arthrogryposisOpen Targets
0.72Strong
hypomyelination neuropathy-arthrogryposis syndromeOpen Targets
0.37Weak
genetic disorderOpen Targets
0.19Weak
diabetic ketoacidosisOpen Targets
0.14Weak
benign chondrogenic neoplasmOpen Targets
0.12Weak
breast cancerOpen Targets
0.08Suggestive
focal segmental glomerulosclerosisOpen Targets
0.07Suggestive
pentosuriaOpen Targets
0.07Suggestive
nephrotic syndromeOpen Targets
0.07Suggestive
familial idiopathic steroid-resistant nephrotic syndromeOpen Targets
0.07Suggestive
familial renal glucosuriaOpen Targets
0.06Suggestive
Renal glucosuriaOpen Targets
0.06Suggestive
primary hyperoxaluria type 3Open Targets
0.06Suggestive
lipoprotein glomerulopathyOpen Targets
0.06Suggestive
cystinuriaOpen Targets
0.06Suggestive
hyperprolinemia type 1Open Targets
0.06Suggestive
nephrotic syndrome, type 20Open Targets
0.06Suggestive
nephronophthisis 1Open Targets
0.06Suggestive
primary hyperoxaluria type 2Open Targets
0.06Suggestive
adenine phosphoribosyltransferase deficiencyOpen Targets
0.06Suggestive
Lethal congenital contracture syndrome 8UniProt
Pathogenic Variants3
NM_015270.5(ADCY6):c.1535+1G>APathogenic
Lethal congenital contracture syndrome 8
β˜†β˜†β˜†β˜†2021
NM_015270.5(ADCY6):c.3007G>A (p.Glu1003Lys)Pathogenic
Lethal congenital contracture syndrome 8
β˜†β˜†β˜†β˜†2021β†’ Residue 1003
NM_015270.5(ADCY6):c.3346C>T (p.Arg1116Cys)Pathogenic
Lethal congenital contracture syndrome 8
β˜†β˜†β˜†β˜†2014β†’ Residue 1116
View on ClinVar β†—
Related Genes
CALM3Protein interaction97%CALML3Protein interaction97%CALML5Protein interaction97%RAPGEF4Protein interaction97%CALML4Protein interaction97%CALML6Protein interaction97%
Tissue Expression6 tissues
Heart
100%
Ovary
40%
Liver
20%
Lung
18%
Brain
4%
Bone Marrow
4%
Gene Interaction Network
Click a node to explore
ADCY6CALM3CALML3CALML5RAPGEF4CALML4CALML6
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted Β· UniProt O43306
View on AlphaFold β†—
Constraintβ“˜
LOEUFβ“˜
0.64LoF Tolerant
pLIβ“˜
0.00Tolerant
Observed/Expected LoF0.51 [0.42–0.64]
RankingsWhere ADCY6 stands among ~20K protein-coding genes
  • #5,770of 20,598
    Most Researched82
  • #4,010of 5,498
    Most Pathogenic Variants3
  • #4,567of 17,882
    Most Constrained (LOEUF)0.64
Genes detectedADCY6
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
Phenotypic spectrum and genomics of undiagnosed arthrogryposis multiplex congenita.
PMID: 33820833
J Med Genet Β· 2022
1.00
2
A 20-year Clinical and Genetic Neuromuscular Cohort Analysis in Lebanon: An International Effort.
PMID: 34602496
J Neuromuscul Dis Β· 2022
0.90
3
Gene expression and DNA methylation analyses suggest that immune process-related ADCY6 is a prognostic factor of luminal-like breast cancer.
PMID: 31886586
J Cell Biochem Β· 2020
0.80
4
Mutations in CNTNAP1 and ADCY6 are responsible for severe arthrogryposis multiplex congenita with axoglial defects.
PMID: 24319099
Hum Mol Genet Β· 2014
0.70
5
Increased blood pressure and hyperdynamic cardiovascular responses in carriers of a common hyperfunctional variant of adenylyl cyclase 6.
PMID: 20732959
J Pharmacol Exp Ther Β· 2010
0.60