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Genetics Home Reference: your guide to understanding genetic conditions
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VAPB

Reviewed August 2012

What is the official name of the VAPB gene?

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.

What is the normal function of the VAPB gene?

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.

How are changes in the VAPB gene related to health conditions?

amyotrophic lateral sclerosis - caused by mutations in the VAPB gene

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.

spinal muscular atrophy - caused by mutations in the VAPB gene

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.

Where is the VAPB gene located?

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.

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.

Where can I find additional information about VAPB?

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.

What other names do people use for the VAPB gene or gene products?

  • ALS8
  • VAMP-B
  • VAMP-C
  • VAP-B
  • VAPB_HUMAN
  • VAP-C

See How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.

What glossary definitions help with understanding VAPB?

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 (/glossary).

References

  • Andersen PM, Al-Chalabi A. Clinical genetics of amyotrophic lateral sclerosis: what do we really know? Nat Rev Neurol. 2011 Oct 11;7(11):603-15. doi: 10.1038/nrneurol.2011.150. Review. (http://www.ncbi.nlm.nih.gov/pubmed/21989245?dopt=Abstract)
  • Ferraiuolo L, Kirby J, Grierson AJ, Sendtner M, Shaw PJ. Molecular pathways of motor neuron injury in amyotrophic lateral sclerosis. Nat Rev Neurol. 2011 Nov;7(11):616-30. doi: 10.1038/nrneurol.2011.152. Review. (http://www.ncbi.nlm.nih.gov/pubmed/22051914?dopt=Abstract)
  • Gkogkas C, Middleton S, Kremer AM, Wardrope C, Hannah M, Gillingwater TH, Skehel P. VAPB interacts with and modulates the activity of ATF6. Hum Mol Genet. 2008 Jun 1;17(11):1517-26. doi: 10.1093/hmg/ddn040. Epub 2008 Feb 8. (http://www.ncbi.nlm.nih.gov/pubmed/18263603?dopt=Abstract)
  • Kanekura K, Nishimoto I, Aiso S, Matsuoka M. Characterization of amyotrophic lateral sclerosis-linked P56S mutation of vesicle-associated membrane protein-associated protein B (VAPB/ALS8). J Biol Chem. 2006 Oct 6;281(40):30223-33. Epub 2006 Aug 4. (http://www.ncbi.nlm.nih.gov/pubmed/16891305?dopt=Abstract)
  • Marques VD, Barreira AA, Davis MB, Abou-Sleiman PM, Silva WA Jr, Zago MA, Sobreira C, Fazan V, Marques W Jr. Expanding the phenotypes of the Pro56Ser VAPB mutation: proximal SMA with dysautonomia. Muscle Nerve. 2006 Dec;34(6):731-9. (http://www.ncbi.nlm.nih.gov/pubmed/16967488?dopt=Abstract)
  • NCBI Gene (http://www.ncbi.nlm.nih.gov/gene/9217)
  • Nishimura AL, Al-Chalabi A, Zatz M. A common founder for amyotrophic lateral sclerosis type 8 (ALS8) in the Brazilian population. Hum Genet. 2005 Dec;118(3-4):499-500. Epub 2005 Sep 27. (http://www.ncbi.nlm.nih.gov/pubmed/16187141?dopt=Abstract)
  • Nishimura AL, Mitne-Neto M, Silva HC, Richieri-Costa A, Middleton S, Cascio D, Kok F, Oliveira JR, Gillingwater T, Webb J, Skehel P, Zatz M. A mutation in the vesicle-trafficking protein VAPB causes late-onset spinal muscular atrophy and amyotrophic lateral sclerosis. Am J Hum Genet. 2004 Nov;75(5):822-31. Epub 2004 Sep 15. (http://www.ncbi.nlm.nih.gov/pubmed/15372378?dopt=Abstract)
  • OMIM: VESICLE-ASSOCIATED MEMBRANE PROTEIN-ASSOCIATED PROTEIN B (http://omim.org/entry/605704)

 

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.

 
Reviewed: August 2012
Published: May 4, 2015