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DDC
dopa decarboxylase
The DDC gene provides instructions for making the aromatic L-amino acid decarboxylase (AADC) enzyme, which is crucial for the production of neurotransmitters like dopamine and serotonin in the brain and nervous system. The DDC gene plays a vital role in neurological function by encoding an enzyme essential for neurotransmitter synthesis.
DDC is located on the short (p) arm of chromosome 7, at band 7p12.2-p12.1. Arm ratio per GRCh38 - banding schematic.
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Overview
The DDC gene, also known as dopa decarboxylase, is responsible for producing the aromatic L-amino acid decarboxylase (AADC) enzyme. This enzyme is an important component of the nervous system, where it facilitates the creation of chemical messengers called neurotransmitters. Neurotransmitters are essential for transmitting signals between nerve cells and other cells throughout the body.
Inherited changes in the DDC gene can reduce the activity of the AADC enzyme, leading to a deficiency that impacts neurological development and function.
What the gene does
The AADC enzyme, produced from the DDC gene, performs a critical role in the synthesis of several key neurotransmitters, including dopamine and serotonin. This enzyme acts in the final step of their production pathways. For dopamine, the AADC enzyme converts L-dopa by removing a carboxyl group, which is a specific molecular structure. This process is part of a two-step mechanism where the amino acid tyrosine is first converted to L-dopa, and then L-dopa is processed into dopamine.
Similarly, for serotonin production, the AADC enzyme removes a carboxyl group from 5-hydroxytryptophan, which is derived from the amino acid tryptophan. Dopamine itself is also a precursor for other neurotransmitters, including norepinephrine and epinephrine, further highlighting the widespread impact of the AADC enzyme on nervous system signalling.
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Chromosome location
The DDC gene is situated on the short (p) arm of chromosome 7, specifically in the region designated 7p12.2-p12.1. This genomic location specifies where the DDC gene can be found within the human genome.
Protein structure
The AADC enzyme, encoded by the DDC gene, has a length of 480 amino acids. Its protein structure includes two approximate tandem repeats, spanning amino acids 58-178. These repeats are further delineated into two distinct repeat regions: one from amino acids 58-115, and another from amino acids 118-178.
Key variants
Variants in the DDC gene can alter the production or function of the aromatic L-amino acid decarboxylase (AADC) enzyme. These genetic changes can lead to reduced enzyme activity, impairing the synthesis of critical neurotransmitters. Such variants are associated with specific inherited conditions.
Sample of pathogenic variants
10 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.1041+1G>A | - | Pathogenic/Likely pathogenic | ★★☆☆ | Deficiency of aromatic-L-amino-acid decarboxylase |
c.1123C>T | p.Gln375Ter | Pathogenic/Likely pathogenic | ★★☆☆ | Deficiency of aromatic-L-amino-acid decarboxylase |
c.1241dup | p.Ser416fs | Pathogenic/Likely pathogenic | ★★☆☆ | Inborn genetic diseases |
c.128del | p.Pro43fs | Pathogenic/Likely pathogenic | ★★☆☆ | Inborn genetic diseases |
c.1339C>T | p.Arg447Cys | Pathogenic/Likely pathogenic | ★★☆☆ | Deficiency of aromatic-L-amino-acid decarboxylase |
c.1340G>A | p.Arg447His | Pathogenic | ★★☆☆ | Deficiency of aromatic-L-amino-acid decarboxylase |
c.140C>A | p.Pro47His | Pathogenic/Likely pathogenic | ★★☆☆ | Deficiency of aromatic-L-amino-acid decarboxylase |
c.175G>A | p.Asp59Asn | Pathogenic/Likely pathogenic | ★★☆☆ | Deficiency of aromatic-L-amino-acid decarboxylase |
c.201+5G>C | - | Pathogenic/Likely pathogenic | ★★☆☆ | Deficiency of aromatic-L-amino-acid decarboxylase |
c.710T>C | p.Phe237Ser | Pathogenic/Likely pathogenic | ★★☆☆ | Deficiency of aromatic-L-amino-acid decarboxylase |
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 DDC gene are known to cause Aromatic L-amino acid decarboxylase deficiency, an inherited condition. This disorder affects the nervous system, particularly how neurons transmit information, and can result in neurological problems typically appearing early in life. The reduced activity of the AADC enzyme, due to DDC gene variants, leads to lower levels of dopamine and serotonin.
Inheritance pattern
Conditions caused by pathogenic DDC 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 DDC gene is recognised within the NHS Genomic Medicine Service, featuring on several NHS England National Genomic Test Directory panels. It has a 'green' status on the DDG2P panel, indicating its strong clinical evidence. Additionally, DDC is included in panels for 'Dystonia, chorea or related movement disorder, childhood onset' (R57), 'Early onset dystonia', 'Early onset or syndromic epilepsy', 'Intellectual disability', 'Likely inborn error of metabolism' (R98), 'Neurotransmitter disorders', and 'Undiagnosed metabolic disorders', all with a 'green' status.
Sources: NHS GMS PanelApp · Genomics England PanelApp · NHS National Genomic Test Directory
Frequently asked questions
What does the DDC gene do?
The DDC gene provides instructions for making the aromatic L-amino acid decarboxylase (AADC) enzyme, which is essential for producing neurotransmitters like dopamine and serotonin in the brain and nervous system. These neurotransmitters are crucial for nerve cell communication.
What is Aromatic L-amino acid decarboxylase deficiency?
Aromatic L-amino acid decarboxylase deficiency is an inherited condition caused by variants in the DDC gene. It results in reduced activity of the AADC enzyme, leading to lower levels of dopamine and serotonin, which affects neurological development and function from an early age.
How is the DDC gene relevant to carrier screening?
The DDC gene is associated with an autosomal recessive inherited condition, meaning an individual must inherit two copies of a variant DDC gene (one from each parent) to be affected. Carrier screening identifies individuals who carry one copy of a DDC gene variant, who typically show no symptoms themselves but could pass the variant on to their children.
References
- Brun L, Ngu LH, Keng WT. Clinical and biochemical features of aromatic L-amino acid decarboxylase deficiency. Neurology. 2010. PMID: 20505134
- Verbeek MM, Geurtz PB, Willemsen MA. Aromatic L-amino acid decarboxylase enzyme activity in deficient patients and heterozygotes. Molecular genetics and metabolism. 2007. PMID: 17240182
- Hyland K. Inherited disorders affecting dopamine and serotonin: critical neurotransmitters derived from aromatic amino acids. The Journal of nutrition. 2007. PMID: 17513427
- Pearl PL, Taylor JL, Trzcinski S. The pediatric neurotransmitter disorders. Journal of child neurology. 2007. PMID: 17690069
- Yu Y, Panhuysen C, Kranzler HR. Intronic variants in the dopa decarboxylase (DDC) gene are associated with smoking behavior in European-Americans and African-Americans. Human molecular genetics. 2006. PMID: 16740595
- Zhang H, Ye Y, Wang X. DOPA decarboxylase gene is associated with nicotine dependence. Pharmacogenomics. 2006. PMID: 17184203
- Pearl PL, Capp PK, Novotny EJ. Inherited disorders of neurotransmitters in children and adults. Clinical biochemistry. 2005. PMID: 16298354