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AHCY
adenosylhomocysteinase
The AHCY gene provides instructions for an enzyme essential in metabolising the amino acid methionine and regulating methylation processes within cells. The AHCY gene produces the S-adenosylhomocysteine hydrolase enzyme, which plays a vital role in breaking down methionine.
AHCY is located on the long (q) arm of chromosome 20, at band 20q11.22. Arm ratio per GRCh38 - banding schematic.
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Overview
The AHCY gene, also known as adenosylhomocysteinase, directs the production of the enzyme S-adenosylhomocysteine hydrolase. This enzyme is a key component in the metabolic pathway responsible for processing methionine, an essential amino acid. Beyond its role in methionine breakdown, the AHCY enzyme is critical for regulating methylation, a biochemical process where methyl groups are added to various molecules, influencing diverse cellular activities.
What the gene does
The AHCY gene's primary function is to produce the S-adenosylhomocysteine hydrolase enzyme. This enzyme participates in the breakdown of methionine, an amino acid obtained through diet. Specifically, it catalyses the conversion of S-adenosylhomocysteine into adenosine and homocysteine. This reaction is pivotal in maintaining appropriate levels of these compounds within the cell. Furthermore, the enzyme's activity directly impacts methylation reactions, which are fundamental for numerous cellular processes. Methylation is involved in controlling which parts of DNA are active, regulating protein and lipid metabolism, and influencing the function of neurotransmitters that transmit signals in the nervous system.
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Chromosome location
The AHCY gene is located on chromosome 20. Its specific position is designated as 20q11.22, which refers to the long (q) arm of chromosome 20, within region 11.22.
Protein structure
The AHCY gene encodes a protein that is 432 amino acids long. Domain architecture has not been experimentally characterised in detail for this protein.
Key variants
Genetic variations within the AHCY gene can alter the normal function of the S-adenosylhomocysteine hydrolase enzyme. These changes can affect the enzyme's efficiency in processing methionine and regulating methylation, leading to potential metabolic disruptions. Most identified variants involve single amino acid substitutions, though others may introduce premature stop signals.
Sample of pathogenic variants
9 pathogenic / likely-pathogenic variants from ClinVar, ranked by review status (expert-panel-reviewed first). This is a sample; recurrent founder variants in a specific population may not appear here - see the full ClinVar listing via the link above.
| Variant (HGVS) | Protein change | Classification | Evidence | Associated condition |
|---|---|---|---|---|
c.145C>T | p.Arg49Cys | Pathogenic/Likely pathogenic | ★★☆☆ | Inborn genetic diseases |
c.257A>G | p.Asp86Gly | Pathogenic/Likely pathogenic | ★★☆☆ | Inborn genetic diseases |
c.293C>T | p.Pro98Leu | Pathogenic/Likely pathogenic | ★★☆☆ | Inborn genetic diseases |
c.428A>G | p.Tyr143Cys | Pathogenic/Likely pathogenic | ★★☆☆ | Inborn genetic diseases |
c.145del | p.Arg49fs | Pathogenic | ★☆☆☆ | Hypermethioninemia with deficiency of S-adenosylhomocysteine hydrolase |
c.882del | p.Ile295fs | Pathogenic | ★☆☆☆ | Hypermethioninemia with deficiency of S-adenosylhomocysteine hydrolase |
c.170C>T | p.Thr57Ile | Pathogenic | - | Hypermethioninemia with deficiency of S-adenosylhomocysteine hydrolase |
c.336G>A | p.Trp112Ter | Pathogenic | - | Hypermethioninemia with deficiency of S-adenosylhomocysteine hydrolase |
c.649G>A | p.Val217Met | Pathogenic | - | Hypermethioninemia with deficiency of S-adenosylhomocysteine hydrolase |
Evidence stars indicate ClinVar review status. Individual variant interpretation should always be performed by a qualified clinical laboratory - many variants remain classified as Variants of Uncertain Significance (VUS) pending more research.
Associated conditions
Variants in the AHCY gene are associated with hypermethioninemia. This condition is characterised by elevated levels of methionine in the blood, which can arise when the S-adenosylhomocysteine hydrolase enzyme functions less efficiently due to genetic changes. Over ten different variants have been described in individuals with hypermethioninemia.
No disease links recorded for this gene in our reference set.
Inheritance pattern
Conditions caused by pathogenic AHCY variants typically follow autosomal recessive inheritance.
When both parents are carriers, each child has a 25% chance of being affected, 50% of being a carrier, and 25% of being unaffected.
UK clinical status
The AHCY gene is included in several NHS Genomic Medicine Service national test panels. It is listed as 'green' for conditions such as Foetal anomalies (R21), Foetal hydrops, Intellectual disability, Likely inborn error of metabolism (R98), and Undiagnosed metabolic disorders, indicating that there is strong evidence for its association with these conditions.
Sources: NHS GMS PanelApp · Genomics England PanelApp · NHS National Genomic Test Directory
Frequently asked questions
What is the AHCY gene responsible for?
The AHCY gene provides instructions for creating the S-adenosylhomocysteine hydrolase enzyme. This enzyme is crucial for breaking down the amino acid methionine and regulating methylation, a vital process for many cellular functions.
What happens if the AHCY gene has a variant?
Variants in the AHCY gene can lead to the enzyme working less effectively. This can result in conditions like hypermethioninemia, characterised by higher than normal levels of methionine in the blood.
What is methylation and why is it important?
Methylation is a biochemical process where small chemical tags (methyl groups) are added to molecules. It is important for controlling gene activity, regulating metabolic reactions involving proteins and fats, and influencing nerve signal transmission.
References
- Buist NR, Glenn B, Vugrek O. S-adenosylhomocysteine hydrolase deficiency in a 26-year-old man. Journal of inherited metabolic disease. 2006. PMID: 16736098
- Barić I, Cuk M, Fumić K. S-Adenosylhomocysteine hydrolase deficiency: a second patient, the younger brother of the index patient, and outcomes during therapy. Journal of inherited metabolic disease. 2005. PMID: 16435181
- Baric I, Fumic K, Glenn B. S-adenosylhomocysteine hydrolase deficiency in a human: a genetic disorder of methionine metabolism. Proceedings of the National Academy of Sciences of the United States of America. 2004. PMID: 15024124
- Turner MA, Yang X, Yin D. Structure and function of S-adenosylhomocysteine hydrolase. Cell biochemistry and biophysics. 2000. PMID: 11325033
- Smythies JR, Gottfries CG, Regland B. Disturbances of one-carbon metabolism in neuropsychiatric disorders: a review. Biological psychiatry. 1997. PMID: 9018395