AHCY: Adenosylhomocysteinase – Key Regulator of Methylation and Homocysteine Metabolism
AHCY encodes S-adenosylhomocysteine hydrolase, a critical enzyme in the methionine cycle that controls cellular methylation potential and homocysteine levels.
Gene Information Card
| Symbol | AHCY |
|---|---|
| Full Name | Adenosylhomocysteinase |
| Gene Type | Protein-coding |
| Chromosomal Location | 20q11.22 |
| NCBI Gene ID | 191 ncbi.nlm.nih.gov/gene/191 |
| Ensembl ID | ENSG00000101444 |
| UniProt ID | P23526 |
| OMIM ID | 180960 |
| HGNC ID | 343 |
| Aliases | SAHH, adoHcyase, S-adenosyl-L-homocysteine hydrolase |
Description
The AHCY gene encodes S-adenosylhomocysteine hydrolase (EC 3.13.2.1), a cytoplasmic enzyme that reversibly hydrolyzes S-adenosylhomocysteine (SAH) to adenosine and homocysteine. This reaction is essential for maintaining low intracellular SAH levels, which otherwise inhibit S-adenosylmethionine (SAM)-dependent methyltransferases. AHCY thereby regulates cellular methylation capacity and homocysteine flux. Deficiency leads to hypermethioninemia and severe developmental disorders.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Hypermethioninemia due to AHCY deficiency | Loss-of-function mutations reduce SAH hydrolysis, causing SAH accumulation and global methylation inhibition. Elevated methionine and homocysteine result. | OMIM #613752; ClinVar; PMID: 15108290 |
| Intellectual disability and developmental delay | Impaired methylation of DNA, RNA, and proteins disrupts neural development and function. | OMIM; PMID: 23033317 |
| Liver dysfunction | Accumulation of toxic metabolites (SAH, homocysteine) contributes to hepatotoxicity. | ClinVar; PMID: 15108290 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 28.5 | High |
| Kidney | 18.2 | Medium |
| Brain | 12.1 | Medium |
| Heart | 9.8 | Medium |
| Skeletal muscle | 6.4 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 | 32.1 | Hepatocellular carcinoma line; high expression |
| HEK293 | 15.4 | Embryonic kidney; moderate expression |
| SH-SY5Y | 11.2 | Neuroblastoma; moderate expression |
| K562 | 8.7 | Leukemia; low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.428C>T (p.Pro143Leu) | Missense | Rare | Reduced enzyme activity; associated with hypermethioninemia |
| c.785G>A (p.Arg262Gln) | Missense | Rare | Impaired substrate binding; loss of function |
| c.1A>G (p.Met1Val) | Start loss | Very rare | Complete loss of protein; severe phenotype |
| c.1003C>T (p.Arg335*) | Nonsense | Rare | Premature truncation; no functional enzyme |
Mutation functional classification
Loss of Function (LOF)
Most reported AHCY mutations are loss-of-function, reducing or abolishing SAH hydrolase activity, leading to SAH accumulation and methylation defects.
Gain of Function (GOF)
No gain-of-function mutations have been described for AHCY.
Dominant Negative (DN)
No dominant-negative effects reported; AHCY deficiency is autosomal recessive.
View complete mutation data：
Gene Ontology (GO)
| • GO:0004013 – adenosylhomocysteinase activity | • GO:0005515 – protein binding |
| • GO:0005829 – cytosol | • GO:0006730 – one-carbon metabolic process |
| • GO:0019280 – methionine metabolic process | • GO:0032259 – methylation |
Pathways
• KEGG hsa00270 – Cysteine and methionine metabolism
• KEGG hsa00260 – Glycine
• serine and threonine metabolism
• Reactome R-HSA-156581 – Methionine salvage pathway
• Reactome R-HSA-156590 – S-adenosylmethionine cycle
Protein Summary
S-adenosylhomocysteine hydrolase (AHCY) is a homotetrameric enzyme (each subunit ~47 kDa) that catalyzes the reversible hydrolysis of SAH. The enzyme requires NAD+ as a cofactor and is inhibited by adenosine analogs. It is ubiquitously expressed, with highest levels in liver and kidney. Structural studies reveal a conserved catalytic domain and a C-terminal domain involved in tetramerization. Post-translational modifications include phosphorylation at Ser-86 and acetylation at Lys-123, which modulate activity.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| AHCYL1 Knockout HEK293 Cell Line | EDJ-KQ6526 | Human | 10768 | Details Get a Quote |
| AHCYL2 Knockout HEK293 Cell Line | EDJ-KQ7999 | Human | 23382 | Details Get a Quote |
| AHCYL1 Knockout A-549 Cell Line | EDJ-KQ32061 | Human | 10768 | Details Get a Quote |
| AHCYL1 Knockout HCT 116 Cell Line | EDJ-KQ32062 | Human | 10768 | Details Get a Quote |
| AHCYL1 Knockout HeLa Cell Line | EDJ-KQ32063 | Human | 10768 | Details Get a Quote |
| AHCYL2 Knockout A-549 Cell Line | EDJ-KQ33745 | Human | 23382 | Details Get a Quote |
| AHCYL2 Knockout HCT 116 Cell Line | EDJ-KQ33746 | Human | 23382 | Details Get a Quote |
| AHCYL2 Knockout HeLa Cell Line | EDJ-KQ33747 | Human | 23382 | Details Get a Quote |
Displaying Records 1 To 8 Of 8 Records
