CLN5 explained

Ceroid-lipofuscinosis neuronal protein 5 is a protein that in humans is encoded by the CLN5 gene.^{[1] [2] [3]}

The neuronal ceroid lipofuscinoses (CLN or NCL) are a group of autosomal recessive, progressive encephalopathies in children. They are characterized by psychomotor deterioration, visual failure, and the accumulation of autofluorescent lipopigment in neurons and other cell types. The main childhood forms are the infantile type (Santavuori-Haltia disease; MIM 256730), the late infantile type (Jansky–Bielschowsky disease; MIM 204500), and the juvenile type (Batten disease; MIM 204200) based on the age of onset, clinical course, neurologic and ophthalmologic findings, and ultrastructural analysis (Carpenter et al., 1977 [PubMed 193610]).[supplied by OMIM]^[3]

A human clinical trial of gene therapy for the CLN5 form of Batten disease began in 2022 through the University of Rochester, using vectors developed by the Hughes research lab in New Zealand.^[4]

Further reading

• Mole SE, Mitchison HM, Munroe PB . Molecular basis of the neuronal ceroid lipofuscinoses: mutations in CLN1, CLN2, CLN3, and CLN5 . Hum. Mutat. . 14 . 3 . 199–215 . 1999 . 10477428 . 10.1002/(SICI)1098-1004(1999)14:3<199::AID-HUMU3>3.0.CO;2-A . free.
• 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.
• Vesa J, Peltonen L . Mutated genes in juvenile and variant late infantile neuronal ceroid lipofuscinoses encode lysosomal proteins . Curr. Mol. Med. . 2 . 5 . 439–44 . 2003 . 12125809 . 10.2174/1566524023362311.
• Mole SE . The genetic spectrum of human neuronal ceroid-lipofuscinoses . Brain Pathol. . 14 . 1 . 70–6 . 2004 . 14997939 . 10.1111/j.1750-3639.2004.tb00500.x . 8095883.
• Carpenter S, Karpati G, Andermann F . The ultrastructural characteristics of the abnormal cytosomes in Batten-Kufs' disease . Brain . 100 Pt 1 . 137–56 . 1977 . 193610 . 10.1093/brain/100.1.137 . etal.
• Savukoski M, Klockars T, Holmberg V . CLN5, a novel gene encoding a putative transmembrane protein mutated in Finnish variant late infantile neuronal ceroid lipofuscinosis . Nat. Genet. . 19 . 3 . 286–8 . 1998 . 9662406 . 10.1038/975 . 23745986 . etal.
• Heinonen O, Salonen T, Jalanko A . CLN-1 and CLN-5, genes for infantile and variant late infantile neuronal ceroid lipofuscinoses, are expressed in the embryonic human brain . J. Comp. Neurol. . 426 . 3 . 406–12 . 2000 . 10992246 . 10.1002/1096-9861(20001023)426:3<406::AID-CNE5>3.0.CO;2-5 . 37672531 . etal.
• 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.
• Isosomppi J, Vesa J, Jalanko A, Peltonen L . Lysosomal localization of the neuronal ceroid lipofuscinosis CLN5 protein . Hum. Mol. Genet. . 11 . 8 . 885–91 . 2003 . 11971870 . 10.1093/hmg/11.8.885 . free.
• Vesa J, Chin MH, Oelgeschläger K . Neuronal Ceroid Lipofuscinoses Are Connected at Molecular Level: Interaction of CLN5 Protein with CLN2 and CLN3 . Mol. Biol. Cell . 13 . 7 . 2410–20 . 2003 . 12134079 . 10.1091/mbc.E02-01-0031 . 117323 . etal.
• Pineda-Trujillo N, Cornejo W, Carrizosa J . A CLN5 mutation causing an atypical neuronal ceroid lipofuscinosis of juvenile onset . Neurology . 64 . 4 . 740–2 . 2005 . 15728307 . 10.1212/01.WNL.0000151974.44980.F1 . 43644394 . etal.
• Bessa C, Teixeira CA, Mangas M . Two novel CLN5 mutations in a Portuguese patient with vLINCL: insights into molecular mechanisms of CLN5 deficiency . Mol. Genet. Metab. . 89 . 3 . 245–53 . 2006 . 16814585 . 10.1016/j.ymgme.2006.04.010 . etal.
• Ewing RM, Chu P, Elisma F . Large-scale mapping of human protein–protein interactions by mass spectrometry . Mol. Syst. Biol. . 3 . 1 . 89 . 2007 . 17353931 . 10.1038/msb4100134 . 1847948 . etal.
• Cannelli N, Nardocci N, Cassandrini D . Revelation of a novel CLN5 mutation in early juvenile neuronal ceroid lipofuscinosis . Neuropediatrics . 38 . 1 . 46–9 . 2007 . 17607606 . 10.1055/s-2007-981449 . 260241788 . etal.

External links

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

Notes and References

1. Savukoski M, Kestila M, Williams R, Jarvela I, Sharp J, Harris J, Santavuori P, Gardiner M, Peltonen L . Defined chromosomal assignment of CLN5 demonstrates that at least four genetic loci are involved in the pathogenesis of human ceroid lipofuscinoses . Am J Hum Genet . 55 . 4 . 695–701 . Oct 1994 . 7942847 . 1918303 .
2. Klockars T, Savukoski M, Isosomppi J, Laan M, Jarvela I, Petrukhin K, Palotie A, Peltonen L . Efficient construction of a physical map by fiber-FISH of the CLN5 region: refined assignment and long-range contig covering the critical region on 13q22 . Genomics . 35 . 1 . 71–8 . Sep 1996 . 8661106 . 10.1006/geno.1996.0324 . free .
3. Web site: Entrez Gene: CLN5 ceroid-lipofuscinosis, neuronal 5.
4. Web site: Biochemistry . Department of . 2022-08-02 . Trial of world-first gene therapy for Batten disease . 2024-04-13 . www.otago.ac.nz . en.