ADCY2
protein-codingadenylate cyclase 2, the group of Adenylate cyclases
Gene summary
This gene encodes a member of the family of adenylate cyclases, which are membrane-associated enzymes that catalyze the formation of the secondary messenger cyclic adenosine monophosphate (cAMP). This enzyme is insensitive to Ca(2+)/calmodulin, and is stimulated by the G protein beta and gamma subunit complex. [provided by RefSeq, Jul 2008]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~433.9 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to ADCY2 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_020546.3. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 5 | 3 | 1 | 9 | ||
| missense | 79 | 3 | 82 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 1 | 1 | ||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 85 | 6 | 1 | 92 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_065433.2 | 25 | MANE Select | |
| Ensembl | ENSP00000342952.4 | 25 | MANE Select | |
| Ensembl | ENSP00000426196.1 | 3 | Standard | |
| Ensembl | ENSP00000425069.1 | 3 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Inflammatory mediator regulation of TRP channels - Homo sapiens (human)
- Platelet activation - Homo sapiens (human)
- Cortisol synthesis and secretion - Homo sapiens (human)
- Relaxin signaling pathway - Homo sapiens (human)
- Aldosterone synthesis and secretion - Homo sapiens (human)
Biological Process
- renal water homeostasis
- cAMP biosynthetic process
- G protein-coupled receptor signaling pathway
- adenylate cyclase-modulating G protein-coupled receptor signaling pathway
- adenylate cyclase-activating G protein-coupled receptor signaling pathway
Molecular Function
- magnesium ion binding
- adenylate cyclase activity
- ATP binding
- adenylate cyclase binding
- manganese ion binding
Cellular Component
- cytoplasm
- plasma membrane
- integral component of plasma membrane
- membrane
- dendrite
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000338316
- Coding exons
- 25
- Length
- 433874
- Individuals with no LoFs
- 123681
- Homozygous LoFs
- 52
- Heterozygous LoFs
- 2015
- Defined
- 125748
- p
- 0.00825
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 4.25 | 343 | 647 | 0.530 | 0.0000374 | 7160 |
| Missense (PolyPhen) | 46 | 204.7 | 0.22471 | 2266 | ||
| Synonymous | 0.867 | 248 | 266 | 0.932 | 0.0000174 | 2109 |
| Loss of Function | 5.89 | 8 | 55.2 | 0.145 | 0.00000267 | 654 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.0056 | 0.0049 | notable |
| Latino/Admixed American | 0.011 | 0.011 | notable |
| Ashkenazi Jewish | 0.017 | 0.016 | notable |
| East Asian | 0.0032 | 0.0030 | notable |
| Finnish | 0.0055 | 0.0054 | notable |
| European (Non-Finnish) | 0.0072 | 0.0070 | notable |
| South Asian | 0.014 | 0.014 | notable |
| Other | 0.013 | 0.013 | notable |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Catalyzes the formation of the signaling molecule cAMP in response to G-protein signaling (PubMed:15385642). Down-stream signaling cascades mediate changes in gene expression patterns and lead to increased IL6 production. Functions in signaling cascades downstream of the muscarinic acetylcholine receptors (By similarity). {ECO:0000250|UniProtKB:P26769, ECO:0000269|PubMed:15385642}.;
Recessive Scores
- pRec
- 0.665
Intolerance Scores
- LoFtool
- 0.104
- RVIS EVS
- 0.12
- RVIS percentile EVS
- 62.17
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.831
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |