Encyclopedia
CLN6, transmembrane ER protein
- genes
1. Normal Function
The CLN6 gene provides instructions for making a protein whose function is not well understood. Within cells, the CLN6 protein is found in a 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. Lysosomes are compartments in the cell that digest and recycle materials. Based on this function, the CLN6 protein appears to help cells get rid of materials they no longer need.
2. Health Conditions Related to Genetic Changes
CLN6 Disease
More than 70 mutations in the CLN6 gene have been found to cause CLN6 disease. This condition impairs motor and mental development, typically starting in early to late childhood, causing gradually worsening problems with movement and a decline in intellectual function. In some cases, signs and symptoms of CLN6 disease do not appear until adulthood.
Most CLN6 gene mutations result in the production of an abnormal CLN6 protein that is quickly broken down (degraded). As a result, there is a severe reduction in the amount of functional CLN6 protein in cells. While it is not known how the loss of this protein causes the signs and symptoms of CLN6 disease, it is likely that the protein's quick degradation contributes to the childhood onset of CLN6 disease.
In the cases in which CLN6 disease develops in adulthood, CLN6 gene mutations often change single protein building blocks (amino acids), resulting in a CLN6 protein with reduced function. Research suggests that these CLN6 gene mutations allow enough functional protein to be produced so that signs and symptoms of the disorder do not develop until later in life.
CLN6 disease is characterized by the accumulation of proteins or peptides and other substances in lysosomes. These accumulations occur in cells throughout the body; however, nerve cells seem to be particularly vulnerable to their effects. The accumulations can cause cell damage leading to cell death. The progressive death of nerve cells in the brain and other tissues leads to the signs and symptoms of CLN6 disease. However, it is unclear how mutations in the CLN6 gene are involved in the buildup of substances in lysosomes in CLN6 disease. These accumulations occur in more cells throughout the body in children with CLN6 disease than in affected adults.
3. Other Names for This Gene
- ceroid-lipofuscinosis neuronal protein 6
- ceroid-lipofuscinosis, neuronal 6, late infantile, variant
- CLN4A
- CLN6_HUMAN
- FLJ20561
- HsT18960
- nclf
This entry is adapted from the peer-reviewed paper https://medlineplus.gov/genetics/gene/cln6
References
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- Canafoglia L, Gilioli I, Invernizzi F, Sofia V, Fugnanesi V, Morbin M,Chiapparini L, Granata T, Binelli S, Scaioli V, Garavaglia B, Nardocci N,Berkovic SF, Franceschetti S. Electroclinical spectrum of the neuronal ceroidlipofuscinoses associated with CLN6 mutations. Neurology. 2015 Jul28;85(4):316-24. doi: 10.1212/WNL.0000000000001784.
- Cannelli N, Garavaglia B, Simonati A, Aiello C, Barzaghi C, Pezzini F, CilioMR, 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 lipofuscinosesassociated with novel mutations in CLN6. Biochem Biophys Res Commun. 2009 Feb20;379(4):892-7. doi: 10.1016/j.bbrc.2008.12.159.
- Kay C. Same gene, surprising difference: adult neuronal ceroid lipofuscinosis linked to CLN6, mutated in variant late-infantile form. Clin Genet. 2011Dec;80(6):505-6. doi: 10.1111/j.1399-0004.2011.01761.x.
- Kurze AK, Galliciotti G, Heine C, Mole SE, Quitsch A, Braulke T. Pathogenicmutations cause rapid degradation of lysosomal storage disease-related membraneprotein CLN6. Hum Mutat. 2010 Feb;31(2):E1163-74. doi: 10.1002/humu.21184.
- Sato R, Inui T, Endo W, Okubo Y, Takezawa Y, Anzai M, Morita H, Saitsu H,Matsumoto N, Haginoya K. First Japanese variant of late infantile neuronal ceroidlipofuscinosis caused by novel CLN6 mutations. Brain Dev. 2016 Oct;38(9):852-6.doi: 10.1016/j.braindev.2016.04.007.
