ADCY3
protein-codingadenylate cyclase 3, the group of Adenylate cyclases
Gene summary
This gene encodes adenylyl cyclase 3 which is a membrane-associated enzyme and catalyzes the formation of the secondary messenger cyclic adenosine monophosphate (cAMP). This protein appears to be widely expressed in various human tissues and may be involved in a number of physiological and pathophysiological metabolic processes. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Feb 2016]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~101.1 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AR
Disease ID:MONDO:0054749
Submitter: PanelApp Australia
Inheritance Pattern: AR
Disease ID:MONDO:0054749
Submitter: Labcorp Genetics (formerly Invitae)
Clinical Genomic Database (CGD)
Manifestation: Endocrine
Intervention: General
Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to ADCY3 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_004036.5. 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 | 6 | 222 | 8 | 236 | ||
| missense | 1 | 395 | 12 | 1 | 409 | |
| nonsense | 2 | 4 | 5 | 11 | ||
| start loss | 1 | 1 | ||||
| frameshift | 1 | 13 | 7 | 21 | ||
| splice donor/acceptor (+/-2bp) | 7 | 9 | 16 | |||
| Total | 3 | 25 | 423 | 234 | 9 | 694 |
Highest pathogenic variant AF is 0.000009577128
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_004027.2 | 21 | MANE Select | |
| Ensembl | ENSP00000505261.1 | 21 | MANE Select | |
| RefSeq | NP_001307542.1 | 21 | Standard | |
| RefSeq | NP_001364057.1 | 22 | 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
- calmodulin binding
- ATP binding
- metal ion binding
Cellular Component
- cytoplasm
- Golgi apparatus
- plasma membrane
- integral component of plasma membrane
- cilium
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000260600
- Coding exons
- 21
- Length
- 100671
- Individuals with no LoFs
- 125703
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 45
- Defined
- 125748
- p
- 0.000179
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 2.57 | 541 | 738 | 0.733 | 0.0000483 | 7508 |
| Missense (PolyPhen) | 152 | 287.6 | 0.52852 | 2936 | ||
| Synonymous | -0.938 | 334 | 313 | 1.07 | 0.0000219 | 2275 |
| Loss of Function | 3.47 | 27 | 54.7 | 0.494 | 0.00000293 | 585 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00044 | 0.00043 | rare |
| Latino/Admixed American | 0.00015 | 0.00014 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00027 | 0.00027 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.00019 | 0.00018 | rare |
| South Asian | 0.00020 | 0.00020 | rare |
| Other | 0.00016 | 0.00016 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Catalyzes the formation of the signaling molecule cAMP in response to G-protein signaling. Participates in signaling cascades triggered by odorant receptors via its function in cAMP biosynthesis. Required for the perception of odorants. Required for normal sperm motility and normal male fertility. Plays a role in regulating insulin levels and body fat accumulation in response to a high fat diet. {ECO:0000250|UniProtKB:Q8VHH7}.;
- Disease
- DISEASE: Obesity (OBESITY) [MIM:601665]: A condition characterized by an increase of body weight beyond the limitation of skeletal and physical requirements, as the result of excessive accumulation of body fat. {ECO:0000269|PubMed:29311636, ECO:0000269|PubMed:29311637}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.;
Recessive Scores
- pRec
- 0.177
Intolerance Scores
- LoFtool
- 0.244
- RVIS EVS
- -2.17
- RVIS percentile EVS
- 1.42
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.489
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |