ADCY9
protein-codingadenylate cyclase 9, the group of Adenylate cyclases
Gene summary
Adenylate cyclase is a membrane bound enzyme that catalyses the formation of cyclic AMP from ATP. It is regulated by a family of G protein-coupled receptors, protein kinases, and calcium. The type 9 adenylyl cyclase is a widely distributed adenylyl cyclase, and it is stimulated by beta-adrenergic receptor activation but is insensitive to forskolin, calcium, and somatostatin. [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 ~163.1 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 ADCY9 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001116.4. 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 | 3 | 7 | 10 | 20 | ||
| missense | 172 | 10 | 1 | 183 | ||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 175 | 17 | 11 | 203 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001107.2 | 10 | MANE Select | |
| Ensembl | ENSP00000294016.3 | 10 | MANE Select | |
| Ensembl | ENSP00000460160.1 | 2 | Standard | |
| Ensembl | ENSP00000461825.1 | 4 | 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
- signal transduction
- G protein-coupled receptor signaling pathway
- adenylate cyclase-activating G protein-coupled receptor signaling pathway
Molecular Function
- adenylate cyclase activity
- ATP binding
- metal ion binding
Cellular Component
- plasma membrane
- integral component of plasma membrane
- integral component of membrane
- axon
- dendrite
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000294016
- Coding exons
- 10
- Length
- 162799
- Individuals with no LoFs
- 125722
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 26
- Defined
- 125748
- p
- 0.000103
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.25 | 730 | 831 | 0.878 | 0.0000572 | 8882 |
| Missense (PolyPhen) | 176 | 265.52 | 0.66286 | 2941 | ||
| Synonymous | -2.93 | 457 | 384 | 1.19 | 0.0000312 | 2722 |
| Loss of Function | 5.28 | 8 | 47.2 | 0.170 | 0.00000235 | 532 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00019 | 0.00018 | rare |
| Latino/Admixed American | 0.000029 | 0.000029 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00011 | 0.00011 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000062 | 0.000062 | rare |
| South Asian | 0.00036 | 0.00036 | rare |
| Other | 0.00033 | 0.00033 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Adenylyl cyclase that catalyzes the formation of the signaling molecule cAMP in response to activation of G protein- coupled receptors (PubMed:9628827, PubMed:12972952, PubMed:15879435, PubMed:10987815). Contributes to signaling cascades activated by CRH (corticotropin-releasing factor), corticosteroids and beta-adrenergic receptors (PubMed:9628827). {ECO:0000269|PubMed:10987815, ECO:0000269|PubMed:12972952, ECO:0000269|PubMed:15879435, ECO:0000269|PubMed:9628827}.;
Recessive Scores
- pRec
- 0.179
Intolerance Scores
- LoFtool
- 0.0303
- RVIS EVS
- -1.78
- RVIS percentile EVS
- 2.28
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.563
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |