Protein-coding gene in humans
Protein CLN8 is a protein that in humans is encoded by the CLN8 gene .[ 5] [ 6]
This gene encodes a transmembrane protein that localizes to the endoplasmic reticulum (ER) and recycles between the ER and the Golgi apparatus via COPII - and COPI -coated vesicles.[ 7] [ 7] CLN6 proteins to form the EGRESS complex (E R-to-G olgi r elaying of e nzymes of the lys osomal s ystem), the functional unit responsible for the export of lysosomal enzymes from the endoplasmic reticulum .[ 8]
Mutations in this gene are associated with progressive epilepsy with mental retardation (EPMR), a subtype of neuronal ceroid lipofuscinosis (NCL). Patients with mutations in this gene have altered levels of sphingolipid and phospholipids in the brain .
^ a b c ENSG00000278220 GRCh38: Ensembl release 89: ENSG00000182372, ENSG00000278220 – Ensembl , May 2017^ a b c GRCm38: Ensembl release 89: ENSMUSG00000026317 – Ensembl , May 2017^ "Human PubMed Reference:" . National Center for Biotechnology Information, U.S. National Library of Medicine .^ "Mouse PubMed Reference:" . National Center for Biotechnology Information, U.S. National Library of Medicine .^ Ranta S, Zhang Y, Ross B, Lonka L, Takkunen E, Messer A, Sharp J, Wheeler R, Kusumi K, Mole S, Liu W, Soares MB, Bonaldo MF, Hirvasniemi A, de la Chapelle A, Gilliam TC, Lehesjoki AE (Oct 1999). "The neuronal ceroid lipofuscinoses in human EPMR and mnd mutant mice are associated with mutations in CLN8". Nat Genet . 23 (2): 233–6. doi :10.1038/13868 . PMID 10508524 . S2CID 23920094 . ^ "Entrez Gene: CLN8 ceroid-lipofuscinosis, neuronal 8 (epilepsy, progressive with mental retardation)" .^ a b di Ronza A, Bajaj L, Sharma J, Sanagasetti D, Lotfi P, Adamski CJ, Collette J, Palmieri M, Amawi A, Popp L, Chang KT, Meschini MC, Leung HE, Segatori L, Simonati A, Sifers RN, Santorelli FM, Sardiello M (2018). "CLN8 is an endoplasmic reticulum cargo receptor that regulates lysosome biogenesis" . Nature Cell Biology . 20 (12): 1370–1377. doi :10.1038/s41556-018-0228-7 . PMC 6277210 PMID 30397314 . ^ 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 (Jun 2020). "A CLN6-CLN8 complex recruits lysosomal enzymes at the ER for Golgi transfer" . J Clin Invest . 130 (8): 4118–4132. doi :10.1172/JCI130955 PMC 7410054 PMID 32597833 . Dawson G, Cho S (2000). "Batten's disease: clues to neuronal protein catabolism in lysosomes". J. Neurosci. Res . 60 (2): 133–40. doi :10.1002/(SICI)1097-4547(20000415)60:2<133::AID-JNR1>3.0.CO;2-3 . PMID 10740217 . S2CID 28786470 . Ranta S, Lehesjoki AE (2001). "Northern epilepsy, a new member of the NCL family". Neurol. Sci . 21 (3 Suppl): S43–7. doi :10.1007/s100720070039 . PMID 11073227 . S2CID 11677694 . Winter E, Ponting CP (2002). "TRAM, LAG1 and CLN8: members of a novel family of lipid-sensing domains?". Trends Biochem. Sci . 27 (8): 381–3. doi :10.1016/S0968-0004(02)02154-0 . PMID 12151215 . Ranta S, Lehesjoki AE, Hirvasniemi A, et al. (1996). "Genetic and physical mapping of the progressive epilepsy with mental retardation (EPMR) locus on chromosome 8p" . Genome Res . 6 (5): 351–60. doi :10.1101/gr.6.5.351 . PMC 6145179 PMID 8743986 . Lonka L, Kyttälä A, Ranta S, et al. (2000). "The neuronal ceroid lipofuscinosis CLN8 membrane protein is a resident of the endoplasmic reticulum" . Hum. Mol. Genet . 9 (11): 1691–7. doi :10.1093/hmg/9.11.1691 PMID 10861296 . Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "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. Bibcode :2002PNAS...9916899M . doi :10.1073/pnas.242603899 PMC 139241 PMID 12477932 . Verhoeven K, De Jonghe P, Van de Putte T, et al. (2003). "Slowed Conduction and Thin Myelination of Peripheral Nerves Associated with Mutant Rho Guanine-Nucleotide Exchange Factor 10" . Am. J. Hum. Genet . 73 (4): 926–32. doi :10.1086/378159 . PMC 1180612 PMID 14508709 . Ota T, Suzuki Y, Nishikawa T, et al. (2004). "Complete sequencing and characterization of 21,243 full-length human cDNAs" . Nat. Genet . 36 (1): 40–5. doi :10.1038/ng1285 PMID 14702039 . Ranta S, Topcu M, Tegelberg S, et al. (2004). "Variant late infantile neuronal ceroid lipofuscinosis in a subset of Turkish patients is allelic to Northern epilepsy" . Hum. Mutat . 23 (4): 300–5. doi :10.1002/humu.20018 PMID 15024724 . S2CID 34924032 . Gerhard DS, Wagner L, Feingold EA, et al. (2004). "The Status, Quality, and Expansion of the NIH Full-Length cDNA Project: The Mammalian Gene Collection (MGC)" . Genome Res . 14 (10B): 2121–7. doi :10.1101/gr.2596504 . PMC 528928 PMID 15489334 . Hermansson M, Käkelä R, Berghäll M, et al. (2005). "Mass spectrometric analysis reveals changes in phospholipid, neutral sphingolipid and sulfatide molecular species in progressive epilepsy with mental retardation, EPMR, brain: a case study" . J. Neurochem . 95 (3): 609–17. doi :10.1111/j.1471-4159.2005.03376.x PMID 16086686 . S2CID 23379785 . Kimura K, Wakamatsu A, Suzuki Y, et al. (2006). "Diversification of transcriptional modulation: Large-scale identification and characterization of putative alternative promoters of human genes" . Genome Res . 16 (1): 55–65. doi :10.1101/gr.4039406 . PMC 1356129 PMID 16344560 .
