ADCY4
protein-codingadenylate cyclase 4, 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). Mouse studies show that adenylate cyclase 4, along with adenylate cyclases 2 and 3, is expressed in olfactory cilia, suggesting that several different adenylate cyclases may couple to olfactory receptors and that there may be multiple receptor-mediated mechanisms for the generation of cAMP signals. Alternative splicing results in transcript variants. [provided by RefSeq, Nov 2010]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~16.7 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 ADCY4 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001198568.2. 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 | 2 | 6 | 8 | |||
| missense | 151 | 2 | 153 | |||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 3 | 3 | ||||
| Total | 0 | 0 | 157 | 8 | 0 | 165 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001185497.1 | 25 | MANE Select | |
| Ensembl | ENSP00000393177.2 | 25 | MANE Select | |
| RefSeq | NP_001185521.1 | 25 | Standard | |
| RefSeq | NP_640340.2 | 25 | 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
- adenylate cyclase activity
- protein kinase C binding
- protein binding
- ATP binding
- metal 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
- ENST00000310677
- Coding exons
- 25
- Length
- 16745
- Individuals with no LoFs
- 125526
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 222
- Defined
- 125748
- p
- 0.000883
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.43 | 530 | 631 | 0.840 | 0.0000374 | 6838 |
| Missense (PolyPhen) | 184 | 261.97 | 0.70236 | 2753 | ||
| Synonymous | 0.485 | 263 | 273 | 0.963 | 0.0000159 | 2274 |
| Loss of Function | 2.20 | 37 | 54.6 | 0.678 | 0.00000276 | 607 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00031 | 0.00031 | rare |
| Latino/Admixed American | 0.00052 | 0.00052 | rare |
| Ashkenazi Jewish | 0.00051 | 0.00050 | rare |
| East Asian | 0.00028 | 0.00027 | rare |
| Finnish | 0.0018 | 0.0018 | notable |
| European (Non-Finnish) | 0.0011 | 0.0011 | notable |
| South Asian | 0.00072 | 0.00069 | rare |
| Other | 0.0015 | 0.0015 | notable |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Catalyzes the formation of the signaling molecule cAMP in response to G-protein signaling. {ECO:0000250|UniProtKB:P26770}.;
Recessive Scores
- pRec
- 0.165
Intolerance Scores
- LoFtool
- 0.370
- RVIS EVS
- -2.32
- RVIS percentile EVS
- 1.19
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- S
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.645
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |