ASMT
protein-codingacetylserotonin O-methyltransferase, the group of 7BS small molecule methyltransferases|Pseudoautosomal region 1
Gene summary
This gene belongs to the methyltransferase superfamily, and is located in the pseudoautosomal region (PAR) at the end of the short arms of the X and Y chromosomes. The encoded enzyme catalyzes the final reaction in the synthesis of melatonin, and is abundant in the pineal gland. Alternatively spliced transcript variants have been noted for this gene. [provided by RefSeq, Jan 2010]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~28.0 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 ASMT variants in ClinVar
No annotated ClinVar phenotypes.
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript . 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 | 0 | |||||
| missense | 6 | 2 | 8 | |||
| nonsense | 4 | 4 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 10 | 2 | 0 | 12 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| Ensembl | ENSP00000370639.3 | 9 | MANE Select | |
| RefSeq | NP_001164509.1 | 18 | Standard | |
| RefSeq | NP_001164510.1 | 14 | Standard | |
| RefSeq | NP_001403454.1 | 16 | Standard |
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
- translation
- aromatic compound biosynthetic process
- melatonin biosynthetic process
- methylation
- indolalkylamine biosynthetic process
Molecular Function
- O-methyltransferase activity
- S-methyltransferase activity
- S-adenosylmethionine-dependent methyltransferase activity
- acetylserotonin O-methyltransferase activity
- identical protein binding
Cellular Component
- cytosol
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000381241
- Coding exons
- 9
- Length
- 28081
- Individuals with no LoFs
- 125160
- Homozygous LoFs
- 1
- Heterozygous LoFs
- 430
- Defined
- 125591
- p
- 0.00172
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -1.70 | 268 | 200 | 1.34 | 0.0000127 | 2398 |
| Missense (PolyPhen) | 75 | 60.822 | 1.2331 | 732 | ||
| Synonymous | -2.51 | 122 | 91.5 | 1.33 | 0.00000716 | 743 |
| Loss of Function | -2.13 | 25 | 15.8 | 1.58 | 7.61e-7 | 196 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.0018 | 0.0018 | notable |
| Latino/Admixed American | 0.00055 | 0.00055 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00060 | 0.00060 | rare |
| Finnish | 0.0040 | 0.0040 | notable |
| European (Non-Finnish) | 0.0022 | 0.0022 | notable |
| South Asian | 0.00065 | 0.00065 | rare |
| Other | 0.0018 | 0.0018 | notable |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Isoform 1 catalyzes the transfer of a methyl group onto N-acetylserotonin, producing melatonin (N-acetyl-5- methoxytryptamine). Isoform 2 and isoform 3 lack enzyme activity. {ECO:0000269|PubMed:22775292}.;
Intolerance Scores
- LoFtool
- 0.969
- RVIS EVS
- 0.13
- RVIS percentile EVS
- 63.57
Essentials
- Essential (CRISPR)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.724
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |