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Genetics Home Reference: your guide to understanding genetic conditions
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CLN6

Reviewed September 2013

What is the official name of the CLN6 gene?

The official name of this gene is “ceroid-lipofuscinosis, neuronal 6, late infantile, variant.”

CLN6 is the gene's official symbol. The CLN6 gene is also known by other names, listed below.

What is the normal function of the CLN6 gene?

The CLN6 gene provides instructions for making a protein whose function is not well understood. The CLN6 protein is found within a cell structure called the endoplasmic reticulum, which is involved in protein processing and transport. Research suggests that the CLN6 protein regulates the transportation of certain proteins and fats from the endoplasmic reticulum to lysosomes. Based on this function, the CLN6 protein appears to help in the process of ridding cells of materials they no longer need.

How are changes in the CLN6 gene related to health conditions?

Kufs disease - caused by mutations in the CLN6 gene

Mutations in the CLN6 gene are the most common cause of Kufs disease type A. This condition is a type of neuronal ceroid lipofuscinosis (NCL) characterized by seizures, progressive problems with movement, and a decline in intellectual function beginning in adulthood. Most of the CLN6 gene mutations that cause Kufs disease type A change single protein building blocks (amino acids), resulting in a CLN6 protein with reduced function.

In Kufs disease, fatty substances called lipopigments accumulate in the lysosomes of nerve cells (neurons) in the brain. These accumulations can result in cell dysfunction and eventually cause cell death. The progressive death of neurons contributes to the signs and symptoms of Kufs disease. However, it is unclear how mutations in the CLN6 gene are involved in the buildup of lipopigments and the features of Kufs disease. Research suggests that CLN6 gene mutations that cause Kufs disease allow enough functional protein to be produced so that signs and symptoms of the disorder do not develop until adulthood. The presence of other proteins that compensate for the lack of CLN6 protein could also play a role in the appearance of symptoms in adulthood.

late-infantile neuronal ceroid lipofuscinosis - caused by mutations in the CLN6 gene

More than 60 mutations in the CLN6 gene have been found to cause late-infantile NCL. This condition impairs motor and mental development beginning in early childhood, causing movement disorders and a decline in intellectual function. In addition, affected children often develop recurrent seizures (epilepsy) and vision impairment. Certain CLN6 gene mutations have been found to cause most cases of late-infantile NCL in Costa Rica, Portugal, and the Canadian island of Newfoundland. Most CLN6 gene mutations result in the production of abnormal CLN6 proteins that are quickly broken down. This rapid degradation of CLN6 protein results in a severe reduction of functional protein and contributes to the childhood appearance of symptoms in people with late-infantile NCL.

Lipopigments accumulate in the lysosomes of people with late-infantile NCL. Unlike in Kufs disease (described above), these accumulations occur in cells throughout the body and can result in cell dysfunction and eventually cause cell death. Neurons are particularly vulnerable to damage caused by lipopigments and more susceptible to cell death. The progressive death of neurons contributes to the signs and symptoms of late-infantile NCL. However, it is unclear how mutations in the CLN6 gene are involved in the buildup of lipopigments and the signs and symptoms of late-infantile NCL.

Where is the CLN6 gene located?

Cytogenetic Location: 15q23

Molecular Location on chromosome 15: base pairs 68,206,991 to 68,229,741

The CLN6 gene is located on the long (q) arm of chromosome 15 at position 23.

The CLN6 gene is located on the long (q) arm of chromosome 15 at position 23.

More precisely, the CLN6 gene is located from base pair 68,206,991 to base pair 68,229,741 on chromosome 15.

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 CLN6?

You and your healthcare professional may find the following resources about CLN6 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 CLN6 gene or gene products?

  • ceroid-lipofuscinosis neuronal protein 6
  • CLN4A
  • CLN6_HUMAN
  • FLJ20561
  • HsT18960
  • nclf

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 CLN6?

acids ; cell ; ceroid ; degradation ; endoplasmic reticulum ; epilepsy ; gene ; motor ; protein

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

References

  • Arsov T, Smith KR, Damiano J, Franceschetti S, Canafoglia L, Bromhead CJ, Andermann E, Vears DF, Cossette P, Rajagopalan S, McDougall A, Sofia V, Farrell M, Aguglia U, Zini A, Meletti S, Morbin M, Mullen S, Andermann F, Mole SE, Bahlo M, Berkovic SF. Kufs disease, the major adult form of neuronal ceroid lipofuscinosis, caused by mutations in CLN6. Am J Hum Genet. 2011 May 13;88(5):566-73. doi: 10.1016/j.ajhg.2011.04.004. Epub 2011 May 5. (http://www.ncbi.nlm.nih.gov/pubmed/21549341?dopt=Abstract)
  • Cannelli N, Garavaglia B, Simonati A, Aiello C, Barzaghi C, Pezzini F, Cilio MR, Biancheri R, Morbin M, Dalla Bernardina B, Granata T, Tessa A, Invernizzi F, Pessagno A, Boldrini R, Zibordi F, Grazian L, Claps D, Carrozzo R, Mole SE, Nardocci N, Santorelli FM. Variant late infantile ceroid lipofuscinoses associated with novel mutations in CLN6. Biochem Biophys Res Commun. 2009 Feb 20;379(4):892-7. doi: 10.1016/j.bbrc.2008.12.159. Epub 2009 Jan 7. (http://www.ncbi.nlm.nih.gov/pubmed/19135028?dopt=Abstract)
  • OMIM: CLN6 GENE (http://omim.org/entry/606725)
  • Kousi M, Lehesjoki AE, Mole SE. Update of the mutation spectrum and clinical correlations of over 360 mutations in eight genes that underlie the neuronal ceroid lipofuscinoses. Hum Mutat. 2012 Jan;33(1):42-63. doi: 10.1002/humu.21624. Epub 2011 Nov 16. Review. (http://www.ncbi.nlm.nih.gov/pubmed/21990111?dopt=Abstract)
  • Kurze AK, Galliciotti G, Heine C, Mole SE, Quitsch A, Braulke T. Pathogenic mutations cause rapid degradation of lysosomal storage disease-related membrane protein CLN6. Hum Mutat. 2010 Feb;31(2):E1163-74. doi: 10.1002/humu.21184. (http://www.ncbi.nlm.nih.gov/pubmed/20020536?dopt=Abstract)
  • NCBI Gene (http://www.ncbi.nlm.nih.gov/gene/54982)

 

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: September 2013
Published: February 23, 2015