Gene AHCY is also known as adenosylhomocysteinase.

It is the gene responsible for producing the

enzyme adenosylhomocysteinase, which plays a crucial role in the metabolism of S-
adenosylhomocysteine (SAH). SAH is a byproduct of the process of methylation, which is
important for various cellular processes such as gene expression, DNA repair, and
neurotransmitter synthesis.
The main responsibility of the AHCY gene is to produce the adenosylhomocysteinase enzyme that
catalyzes the hydrolysis of SAH into adenosine and homocysteine. This breakdown of SAH is
important to maintain a favorable ratio of S-adenosylmethionine (SAM) to SAH, which affects the
efficiency of methylation reactions in the cell.
The AHCY gene is located on chromosome 20, specifically at the locus 20q11.23.
The length of the AHCY gene is approximately 35.8 kilobases (kb).
Regarding the promoter and terminator regions of the gene, the specific details are not readily
available.
The AHCY gene consists of a total of 9 exons and 8 introns. Exons are the coding regions of a gene
that contain the instructions for protein synthesis, while introns are the non-coding regions that
are transcribed but later removed during mRNA processing.
Molecular level: At the molecular level, gene expression refers to the transcription of the AHCY
gene into mRNA and translation of mRNA into the adenosylhomocysteinase protein. Normal gene
expression occurs when the AHCY gene is actively transcribed and translated, resulting in a
functional adenosylhomocysteinase enzyme. Mutations in the gene can lead to altered or
disrupted expression, resulting in either reduced or abnormal production of the enzyme.
Cellular level: At the cellular level, AHCY gene expression determines the production and activity
of the adenosylhomocysteinase enzyme in specific cells and tissues. Normal gene expression
ensures sufficient levels of the enzyme for proper cellular functions such as methylation reactions.
Mutations or dysregulation of the AHCY gene can lead to imbalances in enzyme levels, affecting
cellular processes that rely on the methylation cycle.
Organism level: At the organism level, AHCY gene expression impacts overall health and
homeostasis. Normal gene expression ensures proper metabolic functioning, including
methylation processes, throughout the organism. Dysregulation or mutations in the AHCY gene
can lead to widespread disruptions in metabolism, potentially contributing to various diseases or
conditions at the organism level.
Known mutations in the AHCY gene have been associated with various consequences, such as
alterations in protein structure, enzyme activity, and metabolism. While I don't have access to the
specific total number of known mutations in the AHCY gene, I can provide you with an overview of
the parts of the gene that could be affected and the potential consequences.
1. Missense mutations: These mutations can lead to amino acid substitutions in the encoded
adenosylhomocysteinase protein. Depending on the specific substitution, missense mutations can
result in a non-functional or partially functional protein, leading to impaired enzyme activity and
subsequent disruptions in the methylation cycle.
2. Nonsense mutations: Nonsense mutations introduce a premature stop codon in the AHCY gene
sequence, leading to the production of a truncated and often non-functional protein. The
consequences of nonsense mutations are typically severe, as the resulting protein lacks essential
domains and regions necessary for proper function.
3. Frameshift mutations: Frameshift mutations involve the addition or deletion of nucleotides in
the AHCY gene sequence, leading to a change in the reading frame during translation. This leads
to a completely altered protein sequence and structure, often resulting in a non-functional or
unstable protein product.
4. Splice site mutations: These mutations affect the intron-exon boundaries of the AHCY gene,
impairing proper splicing during mRNA processing. Consequently, aberrant splicing can result in
the generation of abnormal mRNA transcripts, potentially leading to non-functional or partially
functional protein products.
Modifications in the metabolism can occur due to the presence of abnormal or absent
adenosylhomocysteinase protein resulting from these mutations. Adenosylhomocysteinase plays
a crucial role in the methylation cycle by catalyzing the hydrolysis of S-adenosylhomocysteine,
which is a byproduct of methylation reactions. Reduced or impaired enzyme activity can disrupt
the balance of this cycle, leading to elevated levels of S-adenosylhomocysteine. Elevated levels of
S-adenosylhomocysteine can have various consequences, such as alterations in DNA and histone
methylation patterns, impaired cellular methylation processes, and disruption of other metabolic
pathways influenced by methylation reactions.
Mutations in the AHCY gene have been associated with a few main human diseases. Here are the
main diseases caused by mutations in the AHCY gene:
1. Hypermethioninemia: Mutations in the AHCY gene can lead to hypermethioninemia, a
condition characterized by increased levels of methionine in the blood. This condition can be
caused by mutations that result in reduced adenosylhomocysteinase activity, leading to impaired
breakdown of S-adenosylhomocysteine. Hypermethioninemia can manifest with symptoms such
as intellectual disability, developmental delay, liver dysfunction, and neurological abnormalities.
2. Adenosine kinase deficiency: Although primarily associated with mutations in the ADK gene,
recent research suggests that mutations in the AHCY gene can also contribute to adenosine kinase
deficiency. Adenosine kinase is involved in the metabolism of adenosine and plays a role in purine
nucleotide synthesis. Deficiency of adenosine kinase can result in the accumulation of toxic
metabolites, leading to neurologic manifestations such as progressive psychomotor retardation,
epilepsy, and motor abnormalities.
1. Expressivity: Expressivity refers to the extent to which a genetic mutation or variant is
expressed in an individual. In the context of AHCY gene mutations, expressivity can vary among
affected individuals. For example, some individuals with mutations in the AHCY gene may exhibit
severe symptoms of hypermethioninemia or adenosine kinase deficiency, while others may have
milder or even no symptoms at all. This variability in expressivity can be influenced by other
genetic and environmental factors.
2. Penetration: Penetration refers to the likelihood of a genetic mutation or variant actually
causing symptoms or a disease phenotype in individuals who carry the mutation. In the case of
AHCY gene mutations, the penetrance can be variable. Some individuals with mutations in the
AHCY gene may develop hypermethioninemia or adenosine kinase deficiency, while others may
remain unaffected carriers. Penetrance can be influenced by various factors including modifiers in
other genes or environmental exposures.
3. Pleiotropy: Pleiotropy refers to a phenomenon in which a single gene or mutation can lead to
multiple and diverse effects or phenotypes. Mutations in the AHCY gene can exhibit pleiotropy,
and the associated diseases of hypermethioninemia and adenosine kinase deficiency are
examples of this. The AHCY gene plays a role in multiple biochemical pathways, and dysfunction
caused by mutations can have effects on different systems or functions in the body, leading to
diverse clinical manifestations.
4. Genetic heterogeneity: Genetic heterogeneity refers to a situation in which mutations in
different genes can cause the same or similar phenotypic outcomes. When considering diseases
caused by gene mutations, including those associated with AHCY mutations, it is possible to
observe genetic heterogeneity. For example, while adenosine kinase deficiency is primarily
associated with mutations in the ADK gene, recent findings suggest that mutations in the AHCY
gene can also contribute to this condition. This means that different mutations in ADK or AHCY
genes can result in a similar disease phenotype.
Recommended Molecular Tests for Genetic Diagnosis of Gene AHCY:
1. DNA sequencing: Sanger sequencing or next generation sequencing (NGS) can be used to
analyze the AHCY gene and identify specific mutations or variants. This test can provide valuable
information about the genotype of affected individuals and can help confirm the presence of
AHCY gene mutations associated with diseases such as hypermethioninemia or adenosine kinase
deficiency.
2. Deletion/duplication analysis: This test can detect large deletions or duplications in the AHCY
gene that may not be identified through sequencing alone. Techniques such as multiplex ligation-
dependent probe amplification (MLPA) or array comparative genomic hybridization (aCGH) can be
used to identify these structural changes.
Indications for AHCY Gene Testing:
 - Clinical symptoms consistent with hypermethioninemia or adenosine kinase deficiency, such as
elevated methionine levels, developmental delays, neurological symptoms, or other associated
features.
- Family history of hypermethioninemia or adenosine kinase deficiency. - Carrier screening for
individuals planning to have children, particularly if there is a family history of the condition.
Limits of AHCY Gene Testing:
- Genetic testing may not identify all possible mutations in the AHCY gene, as new mutations may
be continually discovered.
- The interpretation of genetic test results may be challenging, especially if variants of uncertain
significance (VUS) are identified. VUS refers to genetic changes that have uncertain consequences
and may require further investigation or family studies to determine their significance.
- Genetic testing may not predict the severity or course of the disease accurately. Phenotypic
variability can exist even among individuals with the same underlying genetic mutation.
- Though genetic testing can provide valuable insights, clinical correlation and additional
diagnostic tests may be necessary to confirm the diagnosis and guide treatment decisions
Prophylaxis of the disease associated with AHCY gene mutations involves both primary and
secondary prevention strategies.
Primary Prophylaxis: The primary prophylaxis aims to prevent the development of the disease in
individuals at risk by addressing the underlying genetic mutation. For AHCY gene-related diseases,
primary prophylaxis options are currently limited as there are no targeted therapies available
specifically for these conditions. However, certain general measures can be taken:
1. Genetic counseling and family planning: Individuals with AHCY gene mutations or a family
history of the disease can benefit from genetic counseling. Genetic counselors can provide
information on the inheritance pattern, likelihood of passing on the mutation to offspring, and
options for family planning, such as prenatal testing or preimplantation genetic diagnosis (PGD).
2. Newborn screening: In some regions, newborn screening programs incorporate testing for
hypermethioninemia, which can be an indicator of AHCY gene mutations. Early detection through
newborn screening programs can help initiate appropriate medical management and
intervention.
Secondary Prophylaxis: Secondary prophylaxis focuses on managing and reducing the severity of
symptoms in individuals who have already been diagnosed with AHCY gene-related diseases. This
typically involves medical interventions and supportive treatments:
1. Medical management: Medical interventions aim to address the specific symptoms and
complications associated with the disease. This may include dietary modifications,
supplementation with specific nutrients, or metabolic therapies.
2. Symptom management: Various supportive measures can be employed to manage symptoms
and improve the quality of life for affected individuals. This can involve medications,
physiotherapy, occupational therapy, speech therapy, and other interventions tailored to address
the specific symptoms or complications.
3. Regular monitoring and follow-up: Regular monitoring of the affected individuals' health and
metabolic parameters is important for ensuring the timely detection of any changes or worsening
of symptoms. Close follow-up with healthcare professionals, such as metabolic specialists or
geneticists, allows for ongoing management and adjustment of treatment plans as needed.

GeneCards - AHCY (www.genecards.org/cgi-bin/carddisp.pl?gene=AHCY)

OMIM (Online Mendelian Inheritance in Man) - AHCY (www.omim.org/entry/180960)