AS3MT: Arsenite Methyltransferase – A Key Enzyme in Arsenic Metabolism and Detoxification
Comprehensive genomic and functional overview of AS3MT, its role in arsenic biotransformation, associated diseases, expression patterns, and mutations.
Gene Information Card
| Symbol | AS3MT |
|---|---|
| Full Name | Arsenite Methyltransferase |
| Gene Type | Protein coding |
| Chromosomal Location | 10q24.32 |
| NCBI Gene ID | 57412 ncbi.nlm.nih.gov/gene/57412 |
| Ensembl ID | ENSG00000119714 |
| UniProt ID | Q9HBK9 |
| OMIM ID | 611806 |
| HGNC ID | 24084 |
| Aliases | Cyt19, S-adenosyl-L-methionine:arsenic(III) methyltransferase |
Description
AS3MT (arsenite methyltransferase) encodes an enzyme that catalyzes the methylation of inorganic trivalent arsenic (As(III)) to monomethylarsonic acid (MMA(V)) and dimethylarsinic acid (DMA(V)). This biotransformation is a key step in arsenic detoxification and metabolism, influencing arsenic toxicity and carcinogenicity. The gene is primarily expressed in liver, kidney, and other tissues involved in xenobiotic metabolism.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Arsenic toxicity and susceptibility | Reduced AS3MT activity leads to accumulation of toxic inorganic arsenic and monomethylarsonous acid (MMA(III)), increasing risk of arsenic-induced toxicity. | ClinVar, OMIM |
| Bladder cancer | Polymorphisms in AS3MT (e.g., rs3740393, rs10748835) are associated with altered arsenic methylation capacity and increased bladder cancer risk. | NCBI Gene, ClinVar |
| Skin cancer | Variants affecting AS3MT expression or activity modulate susceptibility to arsenic-related skin lesions and skin cancer. | ClinVar, OMIM |
| Peripheral vascular disease | Impaired arsenic methylation due to AS3MT variants contributes to arsenic-induced vascular damage. | OMIM |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 12.5 | High |
| Kidney | 8.3 | Medium |
| Lung | 5.1 | Medium |
| Testis | 3.2 | Low |
| Brain | 1.8 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 (liver) | 15.2 | High expression; used in arsenic metabolism studies |
| HEK293 (embryonic kidney) | 9.7 | Moderate expression |
| A549 (lung) | 6.4 | Moderate expression |
| MCF7 (breast) | 2.1 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| rs3740393 (c.142G>C) | SNP | 0.15 (global) | Alters splicing efficiency; associated with reduced arsenic methylation capacity |
| rs10748835 (c.358G>A) | SNP | 0.20 (global) | Missense variant (p.Val120Met); linked to altered enzyme activity and disease risk |
| rs11191439 (c.1239C>T) | SNP | 0.05 (global) | Synonymous; may affect mRNA stability |
Mutation functional classification
Loss of Function (LOF)
Rare missense or nonsense variants (e.g., p.Arg173Ter) that abolish methyltransferase activity, leading to impaired arsenic detoxification.
Gain of Function (GOF)
Not well documented; some variants (e.g., rs3740393) may increase expression or activity in certain populations.
Dominant Negative (DN)
No confirmed dominant-negative mutations reported.
View complete mutation data：
Gene Ontology (GO)
| • catalytic activity (GO:0003824) | • S-adenosylmethionine-dependent methyltransferase activity (GO:0009372) |
| • arsenic methyltransferase activity (GO:0019825) | • response to arsenic-containing substance (GO:0046685) |
| • response to toxic substance (GO:0009636) | • cytoplasm (GO:0005737) |
Pathways
• Arsenic metabolism and detoxification (Reactome: R-HSA-5693568)
• S-adenosylmethionine (SAM) cycle (Reactome: R-HSA-156581)
Protein Summary
AS3MT is a 375-amino acid cytosolic methyltransferase that uses S-adenosyl-L-methionine (SAM) as a methyl donor to convert inorganic arsenite into mono- and dimethylated arsenicals. The enzyme plays a critical role in reducing arsenic toxicity by facilitating excretion. Polymorphisms in AS3MT influence individual susceptibility to arsenic-related diseases, including cancers and vascular disorders.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| AS3MT Knockout HEK293 Cell Line | EDJ-KQ12448 | Human | 57412 | Details Get a Quote |
| AS3MT Knockout A-549 Cell Line | EDJ-KQ41379 | Human | 57412 | Details Get a Quote |
| AS3MT Knockout HeLa Cell Line | EDJ-KQ41380 | Human | 57412 | Details Get a Quote |
| AS3MT Knockout HCT 116 Cell Line | EDJ-KQ73784 | Human | 57412 | Details Get a Quote |
