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Genetics Home Reference: your guide to understanding genetic conditions
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TARDBP

Reviewed August 2012

What is the official name of the TARDBP gene?

The official name of this gene is “TAR DNA binding protein.”

TARDBP is the gene's official symbol. The TARDBP gene is also known by other names, listed below.

What is the normal function of the TARDBP gene?

The TARDBP gene provides instructions for making a protein called transactive response DNA binding protein 43 kDa (TDP-43). This protein is found within the cell nucleus in most tissues and is involved in many of the steps of protein production. The TDP-43 protein attaches (binds) to DNA and regulates an activity called transcription, which is the first step in the production of proteins from genes. This protein can also bind to RNA, a chemical cousin of DNA, to ensure the RNA's stability. The TDP-43 gene is involved in processing molecules called messenger RNA (mRNA), which serve as genetic blueprints for making proteins. By cutting and rearranging mRNA molecules in different ways, the TDP-43 protein controls the production of different versions of certain proteins. This process is known as alternative splicing. The TDP-43 can influence various functions of a cell by regulating protein production.

The TARDBP gene is particularly active (expressed) during early development before birth when new tissues are forming. Many of the proteins whose production is influenced by the TDP-43 protein are involved in neuronal and organ development.

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

amyotrophic lateral sclerosis - caused by mutations in the TARDBP gene

At least 50 mutations in the TARDBP gene have been found to cause amyotrophic lateral sclerosis (ALS), a condition characterized by progressive movement problems and muscle wasting. Most mutations change single protein building blocks (amino acids) in the TDP-43 protein. The majority of these changes affect the region of the protein involved in RNA processing, likely disrupting subsequent production of other proteins. Changes to the TDP-43 protein cause the protein to misfold and form protein clumps (aggregates) within nerve cells that control muscle movement (motor neurons). It is unknown how these disruptions cause ALS. Motor neurons die off in people with ALS; however it is unclear whether a buildup of TDP-43 aggregates are the cause of cell death or a byproduct of a dying cell.

Some people with ALS caused by TARDBP gene mutations also develop a condition called frontotemporal dementia (FTD), which is a progressive brain disorder that affects personality, behavior, and language. It is unclear why some people with TARDBP gene mutations develop FTD and others do not. Individuals who develop both conditions are diagnosed as having ALS-FTD.

other disorders - caused by mutations in the TARDBP gene

Mutations in the TARDBP gene have been found to cause frontotemporal dementia (FTD) without features of amyotrophic lateral sclerosis (ALS). FTD caused by TARDBP gene mutations is characterized by a gradual loss of problem-solving skills and language comprehension. Affected individuals often have changes in personality and behavior that may make it difficult to interact with others in a socially appropriate manner. Most TARDBP gene mutations that cause FTD change single amino acids in the TDP-43 protein. These mutations are thought to affect only part of the protein, leaving other parts of the protein functional. Because the TARDBP gene mutation results in a protein with some residual function, the features of the condition tend to appear later in life, in one's late sixties or early seventies. Some people who inherit the altered TARDBP gene never develop FTD, a situation known as reduced penetrance.

Where is the TARDBP gene located?

Cytogenetic Location: 1p36.22

Molecular Location on chromosome 1: base pairs 11,012,621 to 11,025,491

The TARDBP gene is located on the short (p) arm of chromosome 1 at position 36.22.

The TARDBP gene is located on the short (p) arm of chromosome 1 at position 36.22.

More precisely, the TARDBP gene is located from base pair 11,012,621 to base pair 11,025,491 on chromosome 1.

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 TARDBP?

You and your healthcare professional may find the following resources about TARDBP 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 TARDBP gene or gene products?

  • ALS10
  • TADBP_HUMAN
  • TAR DNA-binding protein 43
  • TAR DNA-binding protein-43
  • TDP-43

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 TARDBP?

acids ; alternative splicing ; cell ; cell nucleus ; dementia ; DNA ; expressed ; gene ; inherit ; messenger RNA ; motor ; mRNA ; mutation ; nucleus ; penetrance ; protein ; RNA ; sclerosis ; splicing ; transcription ; wasting

You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://www.ghr.nlm.nih.gov/glossary).

References

  • Borroni B, Archetti S, Del Bo R, Papetti A, Buratti E, Bonvicini C, Agosti C, Cosseddu M, Turla M, Di Lorenzo D, Pietro Comi G, Gennarelli M, Padovani A. TARDBP mutations in frontotemporal lobar degeneration: frequency, clinical features, and disease course. Rejuvenation Res. 2010 Oct;13(5):509-17. doi: 10.1089/rej.2010.1017. Epub 2010 Jul 20. (http://www.ncbi.nlm.nih.gov/pubmed/20645878?dopt=Abstract)
  • Budini M, Baralle FE, Buratti E. Regulation of gene expression by TDP-43 and FUS/TLS in frontotemporal lobar degeneration. Curr Alzheimer Res. 2011 May;8(3):237-45. Review. (http://www.ncbi.nlm.nih.gov/pubmed/21222602?dopt=Abstract)
  • Budini M, Baralle FE, Buratti E. Regulation of gene expression by TDP-43 and FUS/TLS in frontotemporal lobar degeneration. Curr Alzheimer Res. 2011 May;8(3):237-45. Review. (http://www.ncbi.nlm.nih.gov/pubmed/21222602?dopt=Abstract)
  • Buratti E, Baralle FE. Multiple roles of TDP-43 in gene expression, splicing regulation, and human disease. Front Biosci. 2008 Jan 1;13:867-78. Review. (http://www.ncbi.nlm.nih.gov/pubmed/17981595?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)
  • NCBI Gene (http://www.ncbi.nlm.nih.gov/gene/23435)
  • OMIM: TAR DNA-BINDING PROTEIN (http://omim.org/entry/605078)
  • Tollervey JR, Curk T, Rogelj B, Briese M, Cereda M, Kayikci M, König J, Hortobágyi T, Nishimura AL, Zupunski V, Patani R, Chandran S, Rot G, Zupan B, Shaw CE, Ule J. Characterizing the RNA targets and position-dependent splicing regulation by TDP-43. Nat Neurosci. 2011 Apr;14(4):452-8. doi: 10.1038/nn.2778. Epub 2011 Feb 27. (http://www.ncbi.nlm.nih.gov/pubmed/21358640?dopt=Abstract)
  • Warraich ST, Yang S, Nicholson GA, Blair IP. TDP-43: a DNA and RNA binding protein with roles in neurodegenerative diseases. Int J Biochem Cell Biol. 2010 Oct;42(10):1606-9. doi: 10.1016/j.biocel.2010.06.016. Epub 2010 Jun 25. Review. (http://www.ncbi.nlm.nih.gov/pubmed/20601083?dopt=Abstract)

 

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: July 21, 2014