CLN6 explained

Ceroid-lipofuscinosis neuronal protein 6 is a protein that in humans is encoded by the CLN6 gene.^{[1] [2] [3]}

The CLN6 protein is part of the EGRESS complex (ER-to-Golgi relaying of enzymes of the lysosomal system), which recruits lysosomal enzymes at the endoplasmic reticulum to promote their transfer to the Golgi complex.^[4] The EGRESS complex is composed of CLN6 and CLN8 proteins.^[4] Loss-of-function mutations in CLN6 result in inefficient export of lysosomal enzymes from the endoplasmic reticulum and diminished levels of the enzymes at the lysosome.^[4]

See also

• Batten disease

Further reading

• Dawson G, Cho S . Batten's disease: clues to neuronal protein catabolism in lysosomes. . J. Neurosci. Res. . 60 . 2 . 133–40 . 2000 . 10740217 . 10.1002/(SICI)1097-4547(20000415)60:2<133::AID-JNR1>3.0.CO;2-3 . 28786470.
• Holopainen JM, Saarikoski J, Kinnunen PK, Järvelä I . Elevated lysosomal pH in neuronal ceroid lipofuscinoses (NCLs). . Eur. J. Biochem. . 268 . 22 . 5851–6 . 2001 . 11722572 . 10.1046/j.0014-2956.2001.02530.x . free.
• Gao H, Boustany RM, Espinola JA . Mutations in a novel CLN6-encoded transmembrane protein cause variant neuronal ceroid lipofuscinosis in man and mouse. . Am. J. Hum. Genet. . 70 . 2 . 324–35 . 2002 . 11791207 . 10.1086/338190 . 384912 . etal.
• Strausberg RL, Feingold EA, Grouse LH . Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. . Proc. Natl. Acad. Sci. U.S.A. . 99 . 26 . 16899–903 . 2003 . 12477932 . 10.1073/pnas.242603899 . 139241 . 2002PNAS...9916899M . etal . free.
• Teixeira CA, Espinola J, Huo L . Novel mutations in the CLN6 gene causing a variant late infantile neuronal ceroid lipofuscinosis. . Hum. Mutat. . 21 . 5 . 502–8 . 2003 . 12673792 . 10.1002/humu.10207 . 27128687 . etal .
• Sharp JD, Wheeler RB, Parker KA . Spectrum of CLN6 mutations in variant late infantile neuronal ceroid lipofuscinosis. . Hum. Mutat. . 22 . 1 . 35–42 . 2003 . 12815591 . 10.1002/humu.10227 . 25698616 . etal . free.
• Ota T, Suzuki Y, Nishikawa T . Complete sequencing and characterization of 21,243 full-length human cDNAs. . Nat. Genet. . 36 . 1 . 40–5 . 2004 . 14702039 . 10.1038/ng1285 . etal . free.
• Heine C, Koch B, Storch S . Defective endoplasmic reticulum-resident membrane protein CLN6 affects lysosomal degradation of endocytosed arylsulfatase A. . J. Biol. Chem. . 279 . 21 . 22347–52 . 2004 . 15010453 . 10.1074/jbc.M400643200 . etal . free.
• Mole SE, Michaux G, Codlin S . CLN6, which is associated with a lysosomal storage disease, is an endoplasmic reticulum protein. . Exp. Cell Res. . 298 . 2 . 399–406 . 2004 . 15265688 . 10.1016/j.yexcr.2004.04.042 . etal.
• Gerhard DS, Wagner L, Feingold EA . The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). . Genome Res. . 14 . 10B . 2121–7 . 2004 . 15489334 . 10.1101/gr.2596504 . 528928 . etal.
• Siintola E, Topcu M, Kohlschütter A . Two novel CLN6 mutations in variant late-infantile neuronal ceroid lipofuscinosis patients of Turkish origin. . Clin. Genet. . 68 . 2 . 167–73 . 2005 . 15996215 . 10.1111/j.1399-0004.2005.00471.x . 40168289 . etal.
• Otsuki T, Ota T, Nishikawa T . Signal sequence and keyword trap in silico for selection of full-length human cDNAs encoding secretion or membrane proteins from oligo-capped cDNA libraries. . DNA Res. . 12 . 2 . 117–26 . 2007 . 16303743 . 10.1093/dnares/12.2.117 . etal . free.
• Teixeira CA, Lin S, Mangas M . Gene expression profiling in vLINCL CLN6-deficient fibroblasts: Insights into pathobiology. . Biochim. Biophys. Acta . 1762 . 7 . 637–46 . 2006 . 16857350 . 10.1016/j.bbadis.2006.06.002 . etal . free.
• Olsen JV, Blagoev B, Gnad F . Global, in vivo, and site-specific phosphorylation dynamics in signaling networks. . Cell . 127 . 3 . 635–48 . 2006 . 17081983 . 10.1016/j.cell.2006.09.026 . etal . free.
• Heine C, Quitsch A, Storch S . Topology and endoplasmic reticulum retention signals of the lysosomal storage disease-related membrane protein CLN6. . Mol. Membr. Biol. . 24 . 1 . 74–87 . 2007 . 17453415 . 10.1080/09687860600967317 . 35490146 . etal.

External links

• GeneReviews/NIH/NCBI/UW entry on Neuronal Ceroid-Lipofuscinoses

Notes and References

1. Sharp JD, Wheeler RB, Lake BD, Savukoski M, Jarvela IE, Peltonen L, Gardiner RM, Williams RE . Loci for classical and a variant late infantile neuronal ceroid lipofuscinosis map to chromosomes 11p15 and 15q21-23 . Hum Mol Genet . 6 . 4 . 591–5 . Jul 1997 . 9097964 . 10.1093/hmg/6.4.591 . free .
2. Wheeler RB, Sharp JD, Schultz RA, Joslin JM, Williams RE, Mole SE . The gene mutated in variant late-infantile neuronal ceroid lipofuscinosis (CLN6) and in nclf mutant mice encodes a novel predicted transmembrane protein . Am J Hum Genet . 70 . 2 . 537–42 . Jan 2002 . 11727201 . 384927 . 10.1086/338708 .
3. Web site: Entrez Gene: CLN6 ceroid-lipofuscinosis, neuronal 6, late infantile, variant.
4. Bajaj L, Sharma J, di Ronza A, Zhang P, Eblimit A, Pal R, Roman D, Collette JR, Booth C, Chang KT, Sifers RN, Jung SY, Weimer JM, Chen R, Schekman RW, Sardiello M . A CLN6-CLN8 complex recruits lysosomal enzymes at the ER for Golgi transfer . J Clin Invest . Jun 2020 . 130 . 8 . 4118–4132 . 32597833 . 10.1172/JCI130955 . 7410054 . free .