Details for: ASMT

Gene ID: 438

Gene Type:  Protein-coding  - A gene that serves as a template for producing a messenger RNA (mRNA) molecule, which is then translated into a functional protein.

Symbol: ASMT

Ensembl ID: ENSG00000196433

Description: acetylserotonin O-methyltransferase

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

Cell Significance Index (CSI) scores for the chosen context(s)

  • basal cell of epidermis CL0002187
    CSI 4.62
    rCSI 8.19%
    PRS 98.63
  • suprabasal keratinocyte CL4033013
    CSI 4.24
    rCSI 6.93%
    PRS 99.4

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this specific cell.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.
Network Configuration

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Other Information

This section provides additional information about the gene, including a description generated by an AI language model and details about associated proteins.

## Summary [ASMT](/details-gene/438) (Acetylserotonin O-methyltransferase) is a protein-coding gene that encodes the enzyme responsible for the final, rate-limiting step in melatonin biosynthesis. This enzyme catalyzes the conversion of N-acetylserotonin to melatonin. Functionally, [ASMT](/details-gene/438) is integral to the [melatonin biosynthetic process](/details-go/GO:0030187) and the broader [Metabolism of amine-derived hormones](/details-pathway/R-HSA-209776) pathway. While classically studied for its role in the pineal gland and retina ([Link](https://pubmed.ncbi.nlm.nih.gov/8574683/)), expression data indicates its significance extends to other tissues. **Overall**, it is a highly significant marker in epidermal cells, specifically [basal cell of epidermis](/details-cell/CL0002187) and [suprabasal keratinocyte](/details-cell/CL4033013). Clinically, variations in [ASMT](/details-gene/438) have been linked to several neuropsychiatric conditions, including autism spectrum disorders ([Link](https://omim.org/entry/300015)) and bipolar disorder, suggesting its role in regulating circadian rhythms and neurodevelopment is of significant interest ([Link](https://doi.org/10.1038/sj.mp.4002016), [Link](https://doi.org/10.1093/hmg/dds227)). ## Cellular Roles and Expression Landscape The expression profile of [ASMT](/details-gene/438) highlights a prominent role in the integumentary system. **Overall**, the gene demonstrates its highest significance in cell types constituting the epidermis. It is identified as a key marker for [basal cell of epidermis](/details-cell/CL0002187) (CSI: 4.62) and [suprabasal keratinocyte](/details-cell/CL4033013) (CSI: 4.24). This strong expression signature in skin keratinocytes suggests a potential function for local melatonin synthesis within the skin, an organ known to have its own circadian clock and to be directly exposed to environmental light. While this dataset emphasizes its role in the epidermis, it is critical to note its well-established function in the pineal gland and retina, which are the primary sites of systemic melatonin production ([Link](https://pubmed.ncbi.nlm.nih.gov/8574683/)). The high expression in keratinocytes points to a perhaps underappreciated, localized role for [ASMT](/details-gene/438) beyond its central neuroendocrine functions. ## Pathways and Molecular Function [ASMT](/details-gene/438) is functionally annotated as a methyltransferase, playing a crucial role in the biosynthesis of indolalkylamines. Its molecular function is defined by its [acetylserotonin o-methyltransferase activity](/details-go/GO:0017096), which is central to the biological process of the [melatonin biosynthetic process](/details-go/GO:0030187). This is a key step within the Reactome pathway [Serotonin and melatonin biosynthesis](/details-pathway/R-HSA-209931). The enzyme is located in the [cytosol](/details-go/GO:0005829) and is known to function as a homodimer, consistent with its annotation for [protein homodimerization activity](/details-go/GO:0042803) ([Link](https://doi.org/10.1111/j.1600-079x.2012.01020.x)). The broader pathways implicated, such as [Metabolism](/details-pathway/R-HSA-1430728) and [Metabolism of amino acids and derivatives](/details-pathway/R-HSA-71291), underscore its fundamental role as a metabolic enzyme in amine hormone synthesis. ## Research Directions The association of [ASMT](/details-gene/438) with neuropsychiatric disorders, coupled with its newly highlighted expression in skin, opens several avenues for future investigation. Numerous studies have explored mutations in [ASMT](/details-gene/438) as susceptibility factors for autism spectrum disorders, bipolar disorder, and ADHD, often linking them to abnormal melatonin levels ([Link](https://doi.org/10.1038/sj.mp.4002069), [Link](https://doi.org/10.1093/hmg/dds227), [Link](https://doi.org/10.1111/j.1600-079x.2011.00902.x)). This suggests that disruptions in its enzymatic function, whether systemic or local, could have significant pathological consequences. Based on the available data, several testable hypotheses can be proposed: 1. The high expression of [ASMT](/details-gene/438) in [basal cell of epidermis](/details-cell/CL0002187) and [suprabasal keratinocyte](/details-cell/CL4033013) facilitates a local, cutaneous melatonin synthesis pathway that contributes to the skin's antioxidant defense system and protection against UV-induced DNA damage. 2. Rare, loss-of-function variants in the [ASMT](/details-gene/438) gene result in significantly reduced melatonin production, contributing to the etiology of sleep disturbances and other core symptoms observed in a subset of patients with autism spectrum disorder. 3. The expression or activity of [ASMT](/details-gene/438) in epidermal cells is regulated by the local circadian clock and UV radiation, acting as a dynamic sensor to mediate photoprotective responses. To test the first hypothesis regarding the role of [ASMT](/details-gene/438) in cutaneous photoprotection, a key experiment would involve using CRISPR-Cas9 to knock out the gene in primary human keratinocyte cultures. These [ASMT](/details-gene/438)-knockout and wild-type control cells could then be exposed to varying doses of UVA and UVB radiation. The impact of [ASMT](/details-gene/438) loss could be assessed by measuring levels of DNA damage (e.g., cyclobutane pyrimidine dimers via immunostaining), oxidative stress (e.g., reactive oxygen species assays), and apoptosis. Additionally, local melatonin and N-acetylserotonin levels in the culture medium could be quantified using mass spectrometry to confirm the disruption of the local synthesis pathway. Given its function as the final enzyme in melatonin production, [ASMT](/details-gene/438) presents a potential therapeutic target. The therapeutic strategy would likely involve **activation** rather than inhibition. For conditions linked to melatonin deficiency, such as certain neuropsychiatric or sleep disorders, developing small molecule activators or allosteric modulators to boost [ASMT](/details-gene/438) enzymatic activity could represent a novel therapeutic approach, potentially offering a more targeted alternative to exogenous melatonin supplementation.

Genular Protein ID: 2640420139

Symbol: ASMT_HUMAN

Name: Acetylserotonin O-methyltransferase

UniProtKB Accession Codes:

P46597 B2RC33 Q16598 Q5JQ72 Q5JQ73

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 BRENDA 1 Bgee 1 BioCyc 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 2 CDD 1 CTD 1 ChEBI 10 ChiTaRS 1 DMDM 1 DNASU 1 DisGeNET 1 DrugBank 1 EC 1 EMBL 29 Ensembl 6 EvolutionaryTrace 1 ExpressionAtlas 1 GO 11 Gene3D 2 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 InterPro 6 KEGG 1 MANE-Select 1 MIM 2 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PDB 2 PDBsum 2 PIR 1 PIRSF 1 PRO 1 PROSITE 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 2 PharmGKB 1 Pharos 1 PhylomeDB 1 Proteomes 2 ProteomicsDB 3 RNAct 1 Reactome 1 RefSeq 3 Rhea 2 SIGNOR 1 SMR 1 STRING 1 SUPFAM 2 TreeFam 1 UCSC 1 UniPathway 1 VEuPathDB 1 eggNOG 1 neXtProt 1

Citations:

PubMed ID: 7989373

Title: Structural analysis of the human hydroxyindole-O-methyltransferase gene. Presence of two distinct promoters.

PubMed ID: 7989373

DOI: 10.1016/s0021-9258(18)31790-3

PubMed ID: 8397829

Title: Human hydroxyindole-O-methyltransferase: presence of LINE-1 fragment in a cDNA clone and pineal mRNA.

PubMed ID: 8397829

DOI: 10.1089/dna.1993.12.715

PubMed ID: 14702039

Title: Complete sequencing and characterization of 21,243 full-length human cDNAs.

PubMed ID: 14702039

DOI: 10.1038/ng1285

PubMed ID: 15772651

Title: The DNA sequence of the human X chromosome.

PubMed ID: 15772651

DOI: 10.1038/nature03440

PubMed ID: 15489334

Title: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).

PubMed ID: 15489334

DOI: 10.1101/gr.2596504

PubMed ID: 8574683

Title: Human hydroxyindole-O-methyltransferase in pineal gland, retina and Y79 retinoblastoma cells.

PubMed ID: 8574683

DOI: 10.1016/0006-8993(95)00651-6

PubMed ID: 8842389

Title: Hydroxyindole-O-methyltransferase in Y-79 cells: regulation by serum.

PubMed ID: 8842389

DOI: 10.1016/0006-8993(96)00359-9

PubMed ID: 8752109

Title: Retinoic acid increases hydroxyindole-O-methyltransferase activity and mRNA in human Y-79 retinoblastoma cells.

PubMed ID: 8752109

DOI: 10.1046/j.1471-4159.1996.67031032.x

PubMed ID: 22775292

Title: Crystal structure and functional mapping of human ASMT, the last enzyme of the melatonin synthesis pathway.

PubMed ID: 22775292

DOI: 10.1111/j.1600-079x.2012.01020.x

PubMed ID: 17957233

Title: Is ASMT a susceptibility gene for autism spectrum disorders? A replication study in European populations.

PubMed ID: 17957233

DOI: 10.1038/sj.mp.4002069

PubMed ID: 17505466

Title: Abnormal melatonin synthesis in autism spectrum disorders.

PubMed ID: 17505466

DOI: 10.1038/sj.mp.4002016

PubMed ID: 21251267

Title: Mutation screening of ASMT, the last enzyme of the melatonin pathway, in a large sample of patients with intellectual disability.

PubMed ID: 21251267

DOI: 10.1186/1471-2350-12-17

PubMed ID: 21615493

Title: Genetic variations of the melatonin pathway in patients with attention-deficit and hyperactivity disorders.

PubMed ID: 21615493

DOI: 10.1111/j.1600-079x.2011.00902.x

PubMed ID: 22694957

Title: Genetic and functional abnormalities of the melatonin biosynthesis pathway in patients with bipolar disorder.

PubMed ID: 22694957

DOI: 10.1093/hmg/dds227

PubMed ID: 23349736

Title: Sequencing ASMT identifies rare mutations in Chinese Han patients with autism.

PubMed ID: 23349736

DOI: 10.1371/journal.pone.0053727

Sequence Information:

  • Length: 345
  • Mass: 38453
  • Checksum: 187A375E1E2940B7
  • Sequence:
    • MGSSEDQAYR LLNDYANGFM VSQVLFAACE LGVFDLLAEA PGPLDVAAVA AGVRASAHGT 
ELLLDICVSL KLLKVETRGG KAFYRNTELS SDYLTTVSPT SQCSMLKYMG RTSYRCWGHL 
ADAVREGRNQ YLETFGVPAE ELFTAIYRSE GERLQFMQAL QEVWSVNGRS VLTAFDLSVF 
PLMCDLGGGA GALAKECMSL YPGCKITVFD IPEVVWTAKQ HFSFQEEEQI DFQEGDFFKD 
PLPEADLYIL ARVLHDWADG KCSHLLERIY HTCKPGGGIL VIESLLDEDR RGPLLTQLYS 
LNMLVQTEGQ ERTPTHYHML LSSAGFRDFQ FKKTGAIYDA ILARK

Genular Protein ID: 2331626421

Symbol: X5D784_HUMAN

Name: N/A

UniProtKB Accession Codes:

X5D784

Database IDs:

ARBA 8 AlphaFoldDB 1 Antibodypedia 1 BioGRID-ORCS 1 CTD 1 ChiTaRS 1 DNASU 1 DisGeNET 1 EMBL 2 ExpressionAtlas 1 GO 3 Gene3D 2 HOGENOM 1 InterPro 6 NCBI Taxonomy 1 OrthoDB 1 PANTHER 2 PIRSF 1 PIRSR 1 PROSITE 1 Pfam 4 RefSeq 1 SMR 1 SUPFAM 2 UCSC 1 VEuPathDB 1

Citations:

PubMed ID: 24722188

Title: Protein interaction network of alternatively spliced isoforms from brain links genetic risk factors for autism.

PubMed ID: 24722188

Sequence Information:

  • Length: 298
  • Mass: 33192
  • Checksum: AAFC60D1F8D70E5A
  • Sequence:
    • MGSSEDQAYR LLNDYANGFM VSQVLFAACE LGVFDLLAEA PGPLDVAAVA AGVRASAHGT 
ELLLDICVSL KLLKVETRGG KAFYRNTELS SDYLTTVSPT SQCSMLKYMG RTSYRCWGHL 
ADAVREGRNQ YLETFGVPAE ELFTAIYRSE GERLQFMQAL QEVWSVNGRS VLTAFDLSVF 
PLMCDLGGDF FKDPLPEADL YILARVLHDW ADGKCSHLLE RIYHTCKPGG GILVIESLLD 
EDRRGPLLTQ LYSLNMLVQT EGQERTPTHY HMLLSSAGFR DFQFKKTGAI YDAILARK