AANAT
protein-codingaralkylamine N-acetyltransferase, the group of GCN5 related N-acetyltransferases
Gene summary
The protein encoded by this gene belongs to the acetyltransferase superfamily. It is the penultimate enzyme in melatonin synthesis and controls the night/day rhythm in melatonin production in the vertebrate pineal gland. Melatonin is essential for the function of the circadian clock that influences activity and sleep. This enzyme is regulated by cAMP-dependent phosphorylation that promotes its interaction with 14-3-3 proteins and thus protects the enzyme against proteasomal degradation. This gene may contribute to numerous genetic diseases such as delayed sleep phase syndrome. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2009]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~16.8 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AD
Disease ID:MONDO:0800001
Submitter: PanelApp Australia
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to AANAT variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001088.3. 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 | 2 | 2 | 4 | |||
| missense | 40 | 8 | 1 | 49 | ||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 0 | 0 | 42 | 10 | 3 | 55 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001079.1 | 3 | MANE Select | |
| Ensembl | ENSP00000376282.2 | 3 | MANE Select | |
| RefSeq | NP_001160051.1 | 4 | Standard | |
| Ensembl | ENSP00000250615.2 | 4 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| aanat2 | Danio rerio | Structure: whole organism Quality: decreased amount abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Tryptophan metabolism - Homo sapiens (human)
- Tryptophan Metabolism
- Melatonin metabolism and effects
- Tryptophan metabolism
- Biogenic Amine Synthesis
Biological Process
- N-terminal protein amino acid acetylation
- circadian rhythm
- response to light stimulus
- photoperiodism
- response to zinc ion
Molecular Function
- aralkylamine N-acetyltransferase activity
- arylamine N-acetyltransferase activity
- protein binding
- 14-3-3 protein binding
Cellular Component
- cytoplasm
- cytosol
- perinuclear region of cytoplasm
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000250615
- Coding exons
- 4
- Length
- 16767
- Individuals with no LoFs
- 125730
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 11
- Defined
- 125741
- p
- 0.0000437
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.0909 | 154 | 157 | 0.980 | 0.0000105 | 1604 |
| Missense (PolyPhen) | 58 | 55.658 | 1.0421 | 590 | ||
| Synonymous | -0.505 | 70 | 64.8 | 1.08 | 0.00000435 | 522 |
| Loss of Function | 1.13 | 5 | 8.55 | 0.585 | 3.65e-7 | 99 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00025 | 0.00025 | 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) | 0.000018 | 0.000018 | rare |
| South Asian | 0.000065 | 0.000065 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Controls the night/day rhythm of melatonin production in the pineal gland. Catalyzes the N-acetylation of serotonin into N- acetylserotonin, the penultimate step in the synthesis of melatonin. {ECO:0000269|PubMed:11313340, ECO:0000305}.;
Recessive Scores
- pRec
- 0.211
Intolerance Scores
- LoFtool
- 0.635
- RVIS EVS
- -0.07
- RVIS percentile EVS
- 48.54
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.993
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |