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The official name of this gene is “dynactin 1.”
DCTN1 is the gene's official symbol. The DCTN1 gene is also known by other names, listed below.
The DCTN1 gene provides instructions for making a protein called dynactin-1. At least two different versions of this protein are produced in cells. The two versions differ in size; the larger version is called p150-glued, and the smaller version is called p135.
Both versions of the dynactin-1 protein interact with several other proteins to form a group (a complex) of proteins called dynactin. The p150-glued version of dynactin-1 is the largest component (subunit) of the dynactin complex. This complex plays a critical role in cell division and the transport of materials within cells. To carry out these roles, the complex's p150-glued subunit attaches (binds) to a protein called dynein, which acts as a motor, and also binds to a track-like system of small tubes called microtubules. The dynactin complex, dynein, and microtubules work together like a conveyer belt to move materials within cells.
Researchers believe that the dynactin complex is particularly important for the proper function of axons, which are specialized extensions of nerve cells (neurons). Axons transmit impulses from nerve to nerve and from nerves to muscles. Axons can be quite long; some are more than 3 feet in length. The dynactin complex is a critical part of a rapid transport system that supplies axons with materials to keep them healthy and functioning efficiently.
At least five mutations in the DCTN1 gene have been found to cause Perry syndrome. This progressive brain disease is characterized by a pattern of movement abnormalities known as parkinsonism, psychiatric changes, weight loss, and abnormally slow breathing (hypoventilation).
Most of the mutations that cause Perry syndrome change single protein building blocks (amino acids) in the dynactin-1 protein. These genetic changes impair the ability of the p150-glued version of dynactin-1 to bind to the dynactin complex and to microtubules. An incomplete dynactin complex has a reduced ability to transport materials within cells. Slow or abnormal transport of materials needed for the normal function of neurons causes these cells to malfunction and ultimately die. A gradual loss of neurons in areas of the brain that regulate movement, emotion, and breathing underlies the signs and symptoms of Perry syndrome.
Researchers have identified several mutations in the DCTN1 gene that may increase the risk of developing amyotrophic lateral sclerosis (ALS), a condition characterized by progressive movement problems and muscle wasting. These mutations change single amino acids in the dynactin-1 protein, which likely alter its 3-dimensional shape and impair its ability to attach to the dynactin complex. As a result, the normal function of the dynactin complex is impaired, and it cannot effectively bind with microtubules to move materials within cells.
It is unclear how DCTN1 gene mutations might increase susceptibility to ALS. Impaired formation of the dynactin complex and altered binding of the complex to microtubules may slow the transport of materials needed for the proper function of axons in the neurons that control muscle movement, which are affected in ALS.
Some people with DCTN1 gene mutations that develop ALS also develop a condition called frontotemporal dementia (FTD), which is a progressive brain disorder that affects personality, behavior, and language. Individuals who develop both conditions are diagnosed as having ALS-FTD. It is unknown why some people with ALS develop FTD and others do not.
Researchers have identified at least one DCTN1 gene mutation that causes a nervous system disorder called distal hereditary motor neuronopathy type VIIB. Signs and symptoms of this disorder first appear in early adulthood and include breathing difficulties and progressive weakness of muscles in the face and hands. Muscle weakness in the feet and legs develops later. The mutation that causes this disorder changes one of the amino acids used to make dynactin-1. Specifically, it replaces the amino acid glycine with the amino acid serine at protein position 59 (written as Gly59Ser or G59S). It is unclear how this mutation causes distal hereditary motor neuronopathy type VIIB. The altered protein may result in an abnormal dynactin complex and disturb interactions between the complex and microtubules, which would disrupt transport activities and impair the function of axons in neurons.
At least one DCTN1 gene mutation is associated with a brain disorder called frontotemporal dementia (FTD) without the features of amyotrophic lateral sclerosis (ALS). This disorder occurs in mid- to late adulthood and is characterized by changes in personality and behavior that may make it difficult for affected individuals to interact with others in a socially appropriate manner. Changes in speech and language can also occur, such as problems using the correct word and difficulty with language comprehension. The DCTN1 gene mutation associated with this disorder replaces the amino acid arginine with the amino acid lysine at protein position 1101 (written as Arg1101Lys or R1101K). It is unclear how this mutation causes FTD. This mutation likely alters the 3-dimensional shape of dynactin-1, which may impair its binding with the dynactin complex and microtubules. This impaired binding may slow the transport of materials needed for the proper function of axons and the efficient transmission of nerve impulses.
Cytogenetic Location: 2p13
Molecular Location on chromosome 2: base pairs 74,361,153 to 74,392,086
The DCTN1 gene is located on the short (p) arm of chromosome 2 at position 13.
More precisely, the DCTN1 gene is located from base pair 74,361,153 to base pair 74,392,086 on chromosome 2.
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 DCTN1 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.
acids ; amino acid ; arginine ; axons ; cell ; cell division ; dementia ; distal ; gene ; glycine ; hypoventilation ; lysine ; motor ; mutation ; nervous system ; parkinsonism ; protein ; sclerosis ; serine ; subunit ; susceptibility ; syndrome ; wasting
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.