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AHCY
adenosylhomocysteinase
The AHCY gene provides instructions for creating the enzyme S-adenosylhomocysteine hydrolase, which is critical for methionine metabolism and the regulation of cellular methylation processes. AHCY encodes S-adenosylhomocysteine hydrolase, an enzyme central to breaking down the amino acid 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 produces the S-adenosylhomocysteine hydrolase enzyme, which plays a key role in the body's metabolic pathways. This enzyme is involved in the breakdown of methionine, an essential amino acid. Proper functioning of the AHCY gene is therefore important for maintaining normal cellular metabolism and regulating critical biological processes like methylation.
What the gene does
The primary function of the AHCY gene is to provide instructions for the S-adenosylhomocysteine hydrolase enzyme. This enzyme is involved in a multi-step process that metabolises the amino acid methionine. Specifically, S-adenosylhomocysteine hydrolase facilitates the conversion of S-adenosylhomocysteine into adenosine and homocysteine. This particular enzymatic reaction is crucial not only for methionine breakdown but also for regulating methylation, a fundamental cellular process involving the addition of methyl groups to various compounds. Methylation plays a broad role in cell biology, including gene expression regulation, protein and lipid processing, and the control of neurotransmitter signalling in the nervous system.
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Chromosome location
The AHCY gene is situated on chromosome 20 at band 20q11.22. This chromosomal location specifies the gene's precise position within the human genome.
Protein structure
Domain architecture has not been experimentally characterised in detail for this protein.
Key variants
Genetic changes, known as variants, within the AHCY gene can alter the function of the S-adenosylhomocysteine hydrolase enzyme. These variants can range from single amino acid substitutions to other changes that impact enzyme efficiency or production. The specific effect of a variant depends on its nature and location within the gene.
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 | ★★☆☆ | AHCY-related disorder |
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 have been linked to hypermethioninaemia. This condition is characterised by elevated levels of methionine in the blood, often resulting from the S-adenosylhomocysteine hydrolase enzyme processing methionine less efficiently due to genetic changes. Most reported variants associated with this condition involve single amino acid changes, but others can lead to premature termination of protein production.
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. These panels cover conditions such as Foetal anomalies, Foetal hydrops, Intellectual disability, Likely inborn error of metabolism, and Undiagnosed metabolic disorders, indicating its recognised clinical importance within the UK healthcare system.
Sources: NHS GMS PanelApp · Genomics England PanelApp · NHS National Genomic Test Directory
Frequently asked questions
What does the AHCY gene do?
The AHCY gene provides instructions for making the S-adenosylhomocysteine hydrolase enzyme. This enzyme is essential for breaking down the amino acid methionine and for regulating methylation, a crucial cellular process affecting gene expression and other biological functions.
What condition is associated with AHCY gene variants?
Variants in the AHCY gene are associated with hypermethioninaemia, a condition characterised by abnormally high levels of methionine in the blood. This typically occurs when the S-adenosylhomocysteine hydrolase enzyme does not function correctly.
Is AHCY included in NHS genetic testing?
Yes, the AHCY gene is part of several NHS Genomic Medicine Service national test panels. These panels include testing for conditions such as Foetal anomalies, Intellectual disability, and metabolic disorders.
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