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The official name of this gene is “VAMP (vesicle-associated membrane protein)-associated protein B and C.”
VAPB is the gene's official symbol. The VAPB gene is also known by other names, listed below.
The VAPB gene provides instructions for making a protein that is found in cells throughout the body. Little is known about the function of the VAPB protein. Research indicates that this protein is associated with the membrane that surrounds the endoplasmic reticulum, a specialized structure within cells. Among its many functions, the endoplasmic reticulum folds newly formed proteins and prepares them for transport within the cell or to the cell surface. To function efficiently, the endoplasmic reticulum relies on a system that detects a buildup of unfolded or misfolded proteins. The cell's process for preventing or correcting a buildup of abnormal proteins is called the unfolded protein response. Researchers suggest that the VAPB protein plays an important role in the unfolded protein response.
Researchers have identified at least two VAPB gene mutations in people with amyotrophic lateral sclerosis (ALS), a condition characterized by progressive movement problems and muscle wasting. Both mutations change single protein building blocks (amino acids) used to make the VAPB protein. In one mutation the amino acid proline is replaced with the amino acid serine at position 56 in the VAPB protein (written as Pro56Ser or P56S). This mutation can cause ALS in some people and spinal muscular atrophy (discussed below) in others. It is not known how the same mutation causes different conditions. The other mutation replaces the amino acid threonine with the amino acid isoleucine at position 56 in the VAPB protein (written as Thr46Ile or T46I).
The abnormal VAPB proteins cannot turn on (activate) the unfolded protein response. As a result, abnormal proteins form clumps (aggregates) in cells, leading to cell death. It is unclear why nerve cells that control muscle movement seem to be particularly affected. The progressive loss of these nerve cells underlies the signs and symptoms of ALS.
Researchers have identified one VAPB gene mutation in people with an adult-onset form of spinal muscular atrophy. This type of spinal muscular atrophy is characterized by muscle weakness and abnormal muscle movement that typically begin in early to mid-adulthood. The mutation that causes this condition replaces the amino acid proline with the amino acid serine at position 56 in the VAPB protein (written as Pro56Ser or P56S). The P56S mutation can cause amyotrophic lateral sclerosis (described above) in some people and spinal muscular atrophy in others. It is not known how the same mutation causes different conditions.
The abnormal VAPB protein cannot turn on (activate) the unfolded protein response. As a result, abnormal proteins form clumps (aggregates) in cells, resulting in cell death. Nerve cells that control muscle movement appear to be particularly vulnerable to cell death due to protein aggregates. The progressive loss of these nerve cells underlies the signs and symptoms of spinal muscular atrophy.
Cytogenetic Location: 20q13.33
Molecular Location on chromosome 20: base pairs 58,389,118 to 58,451,100
The VAPB gene is located on the long (q) arm of chromosome 20 at position 13.33.
More precisely, the VAPB gene is located from base pair 58,389,118 to base pair 58,451,100 on chromosome 20.
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 VAPB 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 ; atrophy ; cell ; endoplasmic reticulum ; gene ; isoleucine ; mutation ; proline ; protein ; sclerosis ; serine ; threonine ; vesicle ; wasting
You may find definitions for these and many other terms in the Genetics Home Reference 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.