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Genetics Home Reference: your guide to understanding genetic conditions
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HTT

Reviewed October 2008

What is the official name of the HTT gene?

The official name of this gene is “huntingtin.”

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

What is the normal function of the HTT gene?

The HTT gene provides instructions for making a protein called huntingtin. Although the exact function of this protein is unknown, it appears to play an important role in nerve cells (neurons) in the brain and is essential for normal development before birth. Huntingtin is found in many of the body's tissues, with the highest levels of activity in the brain. Within cells, this protein may be involved in chemical signaling, transporting materials, attaching (binding) to proteins and other structures, and protecting the cell from self-destruction (apoptosis).

One region of the HTT gene contains a particular DNA segment known as a CAG trinucleotide repeat. This segment is made up of a series of three DNA building blocks (cytosine, adenine, and guanine) that appear multiple times in a row. Normally, the CAG segment is repeated 10 to 35 times within the gene.

Does the HTT gene share characteristics with other genes?

The HTT gene belongs to a family of genes called endogenous ligands (endogenous ligands).

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.

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

Huntington disease - caused by mutations in the HTT gene

The inherited mutation that causes Huntington disease is known as a CAG trinucleotide repeat expansion. This mutation increases the size of the CAG segment in the HTT gene. People with Huntington disease have 36 to more than 120 CAG repeats. People with 36 to 39 CAG repeats may or may not develop the signs and symptoms of Huntington disease, while people with 40 or more repeats almost always develop the disorder.

The expanded CAG segment leads to the production of an abnormally long version of the huntingtin protein. The elongated protein is cut into smaller, toxic fragments that bind together and accumulate in neurons, disrupting the normal functions of these cells. This process particularly affects regions of the brain that help coordinate movement and control thinking and emotions (the striatum and cerebral cortex). The dysfunction and eventual death of neurons in these areas of the brain underlie the signs and symptoms of Huntington disease.

As the altered HTT gene is passed from one generation to the next, the size of the CAG trinucleotide repeat often increases in size. A larger number of repeats is usually associated with an earlier onset of signs and symptoms. This phenomenon is called anticipation. People with the adult-onset form of Huntington disease (which appears in mid-adulthood) typically have 40 to 50 CAG repeats in the HTT gene, while people with the less common, juvenile form of the disorder (which appears in childhood or adolescence) tend to have more than 60 CAG repeats.

Individuals who have 27 to 35 CAG repeats in the HTT gene do not develop Huntington disease, but they are at risk of having children who will develop the disorder. As the gene is passed from parent to child, the size of the CAG trinucleotide repeat may lengthen into the range associated with Huntington disease (36 repeats or more).

Where is the HTT gene located?

Cytogenetic Location: 4p16.3

Molecular Location on chromosome 4: base pairs 3,074,680 to 3,243,959

The HTT gene is located on the short (p) arm of chromosome 4 at position 16.3.

The HTT gene is located on the short (p) arm of chromosome 4 at position 16.3.

More precisely, the HTT gene is located from base pair 3,074,680 to base pair 3,243,959 on chromosome 4.

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 HTT?

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

  • HD
  • HD_HUMAN
  • huntingtin (Huntington disease)
  • Huntington's disease protein
  • IT15

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 HTT?

adenine ; aggregate ; anticipation ; apoptosis ; cell ; cerebral cortex ; cytosine ; DNA ; gene ; guanine ; inherited ; juvenile ; mutation ; protein ; striatum ; toxic ; trinucleotide repeat

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

References

  • Bates G. Huntingtin aggregation and toxicity in Huntington's disease. Lancet. 2003 May 10;361(9369):1642-4. Review. (http://www.ncbi.nlm.nih.gov/pubmed/12747895?dopt=Abstract)
  • Borrell-Pagès M, Zala D, Humbert S, Saudou F. Huntington's disease: from huntingtin function and dysfunction to therapeutic strategies. Cell Mol Life Sci. 2006 Nov;63(22):2642-60. Review. (http://www.ncbi.nlm.nih.gov/pubmed/17041811?dopt=Abstract)
  • Cattaneo E. Dysfunction of wild-type huntingtin in Huntington disease. News Physiol Sci. 2003 Feb;18:34-7. Review. (http://www.ncbi.nlm.nih.gov/pubmed/12531930?dopt=Abstract)
  • Gárdián G, Vécsei L. Huntington's disease: pathomechanism and therapeutic perspectives. J Neural Transm. 2004 Oct;111(10-11):1485-94. Review. (http://www.ncbi.nlm.nih.gov/pubmed/15480847?dopt=Abstract)
  • Imarisio S, Carmichael J, Korolchuk V, Chen CW, Saiki S, Rose C, Krishna G, Davies JE, Ttofi E, Underwood BR, Rubinsztein DC. Huntington's disease: from pathology and genetics to potential therapies. Biochem J. 2008 Jun 1;412(2):191-209. doi: 10.1042/BJ20071619. Review. (http://www.ncbi.nlm.nih.gov/pubmed/18466116?dopt=Abstract)
  • Jones L, Hughes A. Pathogenic mechanisms in Huntington's disease. Int Rev Neurobiol. 2011;98:373-418. doi: 10.1016/B978-0-12-381328-2.00015-8. Review. (http://www.ncbi.nlm.nih.gov/pubmed/21907095?dopt=Abstract)
  • Landles C, Bates GP. Huntingtin and the molecular pathogenesis of Huntington's disease. Fourth in molecular medicine review series. EMBO Rep. 2004 Oct;5(10):958-63. Review. (http://www.ncbi.nlm.nih.gov/pubmed/15459747?dopt=Abstract)
  • Li SH, Li XJ. Huntingtin and its role in neuronal degeneration. Neuroscientist. 2004 Oct;10(5):467-75. Review. (http://www.ncbi.nlm.nih.gov/pubmed/15359012?dopt=Abstract)
  • MacDonald ME. Huntingtin: alive and well and working in middle management. Sci STKE. 2003 Nov 4;2003(207):pe48. Review. (http://www.ncbi.nlm.nih.gov/pubmed/14600292?dopt=Abstract)
  • NCBI Gene (http://www.ncbi.nlm.nih.gov/gene/3064)
  • Rangone H, Humbert S, Saudou F. Huntington's disease: how does huntingtin, an anti-apoptotic protein, become toxic? Pathol Biol (Paris). 2004 Jul;52(6):338-42. Review. (http://www.ncbi.nlm.nih.gov/pubmed/15261377?dopt=Abstract)
  • Slow EJ, Graham RK, Hayden MR. To be or not to be toxic: aggregations in Huntington and Alzheimer disease. Trends Genet. 2006 Aug;22(8):408-11. Epub 2006 Jun 27. (http://www.ncbi.nlm.nih.gov/pubmed/16806565?dopt=Abstract)
  • van Dellen A, Grote HE, Hannan AJ. Gene-environment interactions, neuronal dysfunction and pathological plasticity in Huntington's disease. Clin Exp Pharmacol Physiol. 2005 Dec;32(12):1007-19. Review. (http://www.ncbi.nlm.nih.gov/pubmed/16445565?dopt=Abstract)
  • Young AB. Huntingtin in health and disease. J Clin Invest. 2003 Feb;111(3):299-302. Review. (http://www.ncbi.nlm.nih.gov/pubmed/12569151?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: October 2008
Published: December 16, 2014