|http://ghr.nlm.nih.gov/ A service of the U.S. National Library of Medicine®|
The official name of this gene is “synuclein, alpha (non A4 component of amyloid precursor).”
SNCA is the gene's official symbol. The SNCA gene is also known by other names, listed below.
The SNCA gene provides instructions for making a small protein called alpha-synuclein. Alpha-synuclein is abundant in the brain, and smaller amounts are found in the heart, muscles, and other tissues. In the brain, alpha-synuclein is found mainly at the tips of nerve cells (neurons) in specialized structures called presynaptic terminals. Within these structures, alpha-synuclein interacts with fats (lipids) and proteins. Presynaptic terminals release chemical messengers, called neurotransmitters, from compartments known as synaptic vesicles. The release of neurotransmitters relays signals between neurons and is critical for normal brain function.
Although the function of alpha-synuclein is not well understood, studies suggest that it plays an important role in maintaining a supply of synaptic vesicles in presynaptic terminals. It may also help regulate the release of dopamine, a type of neurotransmitter that is critical for controlling the start and stop of voluntary and involuntary movements.
The SNCA gene belongs to a family of genes called PARK (Parkinson disease).
A gene family is a group of genes that share important characteristics. Classifying individual genes into families helps researchers describe how genes are related to each other. For more information, see What are gene families? (http://ghr.nlm.nih.gov/handbook/howgeneswork/genefamilies) in the Handbook.
At least 18 mutations in the SNCA gene have been found to cause Parkinson disease, a condition characterized by progressive problems with movement and balance. SNCA gene mutations are associated with the early-onset form of the disorder, which typically appears before age 50.
Researchers have described two types of alterations of the SNCA gene in people with Parkinson disease. One type changes a single protein building block (amino acid) used to make alpha-synuclein. In some cases, the amino acid alanine is replaced with the amino acid threonine at protein position 53 (written as Ala53Thr) or with the amino acid proline at position 30 (written as Ala30Pro). These mutations cause the alpha-synuclein protein to take on an incorrect 3-dimensional shape (misfold). In the other type of alteration, one of the two SNCA genes in each cell is inappropriately duplicated or triplicated. The extra copies of the SNCA gene lead to an excess of alpha-synuclein.
It is unclear how alterations in the SNCA gene cause Parkinson disease. This condition involves the selective death or impairment of neurons that produce dopamine. Misfolded or excess alpha-synuclein proteins may cluster together (aggregate) and impair the function of these neurons in specific regions of the brain. Aggregated alpha-synuclein may disrupt the regulation of dopamine, which allows dopamine to accumulate to toxic levels and eventually kill neurons. Researchers also suspect that misfolded or excess alpha-synuclein stalls or shuts down the cell machinery that removes unneeded proteins. As a result, unneeded proteins may clog neurons and impair their functions. Symptoms of Parkinson disease appear when dopamine-producing neurons become impaired or die. The loss of these cells weakens communication between the brain and muscles, and ultimately the brain becomes unable to control muscle movement.
Misfolded alpha-synuclein is also a major component of Lewy bodies, abnormal deposits that appear in certain neurons in the brain in people with Parkinson disease. The presence of Lewy bodies in a region of the brain called the substantia nigra, which controls balance and movement, are a characteristic feature of Parkinson disease. However, it is unclear whether Lewy bodies play a role in killing nerve cells or if they are part of the cells' response to the disease.
Several common variations in the SNCA gene have been found to increase the risk of multiple system atrophy, a progressive brain disorder that affects movement and balance and disrupts the function of the autonomic nervous system. The autonomic nervous system controls actions that are mostly involuntary, such as regulation of blood pressure.
The identified gene variations each change a single DNA building block (nucleotide) in the SNCA gene. Researchers are working to determine whether these changes alter the function of alpha-synuclein and how they influence the risk of developing multiple system atrophy. Variations in the SNCA gene appear to affect disease risk in people of European descent; it is unclear whether SNCA gene variations are a risk factor for this condition in people of other geographic and ethnic backgrounds. One study found that changes in this gene are not associated with multiple system atrophy in South Koreans.
Researchers have identified mutations in the SNCA gene that may lead to a loss of intellectual functions (dementia). Two mutations cause a particular disorder known as dementia with Lewy bodies, in which dementia is associated with deposits of Lewy bodies in certain areas of the brain. Although the features of this disorder are variable, symptoms typically include dementia, visual hallucinations, fluctuations in attention, and changes characteristic of Parkinson disease such as trembling or rigidity of limbs, slow movement, and impaired balance and coordination. Lewy bodies are also a feature of Parkinson disease, but these abnormal deposits tend to be more widespread in the brain in dementia with Lewy bodies.
One of the SNCA mutations responsible for dementia with Lewy bodies replaces the amino acid glutamic acid with the amino acid lysine at position 46 in the alpha-synuclein protein (written as Glu46Lys). The other mutation replaces the amino acid alanine with the amino acid threonine at position 53 (written as Ala53Thr). Both of these mutations have also been found in people with Parkinson disease.
Cytogenetic Location: 4q21
Molecular Location on chromosome 4: base pairs 90,645,249 to 90,759,446
The SNCA gene is located on the long (q) arm of chromosome 4 at position 21.
More precisely, the SNCA gene is located from base pair 90,645,249 to base pair 90,759,446 on chromosome 4.
See How do geneticists indicate the location of a gene? (http://ghr.nlm.nih.gov/handbook/howgeneswork/genelocation) in the Handbook.
You and your healthcare professional may find the following resources about SNCA helpful.
You may also be interested in these resources, which are designed for genetics professionals and researchers.
See How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.
aggregate ; amino acid ; amyloid ; atrophy ; autonomic nervous system ; cell ; dementia ; DNA ; dopamine ; gene ; hallucinations ; involuntary ; Lewy bodies ; mutation ; nervous system ; neurotransmitters ; nucleotide ; presynaptic ; protein ; substantia nigra ; synaptic vesicles ; threonine ; toxic
You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://www.ghr.nlm.nih.gov/glossary).
The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.