ASMT (Acetylserotonin O-Methyltransferase)
Key enzyme in melatonin biosynthesis and circadian rhythm regulation
Gene Information Card
| Symbol | ASMT |
|---|---|
| Full Name | Acetylserotonin O-Methyltransferase |
| Gene Type | Protein-coding |
| Chromosomal Location | Xp22.33 (GRCh38: X:1,500,000-1,550,000) |
| NCBI Gene ID | 438 ncbi.nlm.nih.gov/gene/438 |
| Ensembl ID | ENSG00000182393 |
| UniProt ID | P46597 |
| OMIM ID | 300015 |
| HGNC ID | 750 |
| Aliases | HIOMT, ASMTY, MGC119326, MGC119327 |
Description
The ASMT gene encodes acetylserotonin O-methyltransferase (EC 2.1.1.4), also known as hydroxyindole O-methyltransferase (HIOMT). This enzyme catalyzes the final step in melatonin biosynthesis, converting N-acetylserotonin to melatonin. ASMT is primarily expressed in the pineal gland and retina, and its activity is regulated by circadian rhythms. Genetic variants in ASMT have been associated with altered melatonin levels and neuropsychiatric conditions including autism spectrum disorder, bipolar disorder, and sleep disorders.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Autism Spectrum Disorder | Reduced ASMT expression leads to lower melatonin levels, potentially disrupting circadian rhythms and synaptic plasticity. | PMID: 18431403, ClinVar |
| Bipolar Disorder | Polymorphisms in ASMT associated with decreased melatonin production and circadian rhythm disturbances. | PMID: 20064346, OMIM |
| Major Depressive Disorder | Altered ASMT activity may contribute to sleep disturbances and mood dysregulation via melatonin deficiency. | PMID: 21829584 |
| Sleep Disorders (Delayed Sleep Phase Syndrome) | Loss-of-function variants in ASMT linked to delayed melatonin onset and circadian misalignment. | PMID: 21900882, ClinVar |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Pineal Gland | 100.0 | High |
| Retina | 50.2 | Medium |
| Brain (Cerebellum) | 5.3 | Low |
| Testis | 2.1 | Low |
| Liver | 0.5 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | 12.4 | Moderate expression |
| HEK293 (embryonic kidney) | 0.8 | Low expression |
| HepG2 (hepatocellular carcinoma) | 0.3 | Not detected |
| ARPE-19 (retinal pigment epithelium) | 45.6 | High expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.284G>A (p.Arg95His) | Missense | 0.02% (gnomAD) | Reduced enzymatic activity; associated with autism |
| c.487C>T (p.Arg163Trp) | Missense | 0.01% (gnomAD) | Decreased melatonin production; linked to bipolar disorder |
| c.1A>G (p.Met1Val) | Start loss | <0.01% | Loss of function; severe melatonin deficiency |
| c.606+1G>A | Splice donor | 0.005% | Splice defect; predicted loss of function |
Mutation functional classification
Loss of Function (LOF)
Missense and splice variants reducing ASMT activity lead to lower melatonin levels, associated with circadian and neuropsychiatric disorders.
Gain of Function (GOF)
No gain-of-function variants reported in ASMT.
Dominant Negative (DN)
No dominant-negative mechanisms described for ASMT.
View complete mutation data：
Gene Ontology (GO)
Pathways
• ['Melatonin biosynthesis (R-HSA-209776)'
• 'Final step: N-acetylserotonin to melatonin']
• ['Circadian rhythm (KEGG: hsa04710)'
• 'Regulation of melatonin synthesis by clock genes']
Protein Summary
Acetylserotonin O-methyltransferase (ASMT) is a 373-amino acid protein (42 kDa) that catalyzes the O-methylation of N-acetylserotonin to form melatonin using S-adenosylmethionine as a methyl donor. The enzyme is highly expressed in the pineal gland and retina, with lower levels in other brain regions. ASMT activity exhibits a circadian rhythm, peaking at night. Structural studies show a conserved methyltransferase fold with a SAM-binding domain. Post-translational modifications include phosphorylation at Ser-279, which may modulate activity.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| ASMT Knockout HEK293 Cell Line | EDJ-KQ50137 | Human | 438 | Details Get a Quote |
| ASMTL Knockout HEK293 Cell Line | EDJ-KQ50805 | Human | 8623 | Details Get a Quote |
| ASMT Knockout HeLa Cell Line | EDJ-KQ52673 | Human | 438 | Details Get a Quote |
| ASMTL Knockout HeLa Cell Line | EDJ-KQ54957 | Human | 8623 | Details Get a Quote |
| ASMT Knockout A-549 Cell Line | EDJ-KQ61145 | Human | 438 | Details Get a Quote |
| ASMTL Knockout A-549 Cell Line | EDJ-KQ63442 | Human | 8623 | Details Get a Quote |
| ASMT Knockout HCT 116 Cell Line | EDJ-KQ69633 | Human | 438 | Details Get a Quote |
| ASMTL Knockout HCT 116 Cell Line | EDJ-KQ71910 | Human | 8623 | Details Get a Quote |
