Gene Symbol CLN8
Gene ID 2055
Chromosomal Location 8p23
Genomic RefSeqGene NG_008656.2 37793 bp
Transcript RefSeq NM_018941.3 7185 b
Protein RefSeq NP_061764.2 286 aa
No. of mutations 34
No. of sequence variations 2
Total No. of changes 36
Additional Notes
Identifier Location cDNA change RNA change Genomic DNA change hg19 dbSNP Protein change Type of mutation Predicted functional effect Phenotype Progression Histology No. of families Country of origin PMID References Patients Notes
cln8.001 C: Exon 2 c.70C>G r.(70c>g) g.1719290C>G rs104894064, CM992146 p.(Arg24Gly) Missense Possibly damaging EPMR 22 patients Finland 10508524 Ranta et al., Nat Genet; 1999 Pa-cln8.001-Pa-cln8.022 Founder effect for EPMR in Finland.  carrier freq in Finland 1:1135; 1:146 in Kalnuu
cln8.001 C: Exon 2 c.70C>G r.(70c>g) g.1719290C>G rs104894064, CM992146 p.(Arg24Gly) Missense Possibly damaging EPMR 1 Finland 16828266 Siintola et al., 2006a Pa-cln8.034 Finnish patient: In association with p.Gly237Arg = EPMR or even milder
cln8.002 C: Exon 2 c.507C>T r.(507c>u) g.1719727C>T p.(=) sequence variation EPMR ? Finland 10508524 Ranta et al., Nat Genet; 1999 p.Ser169Ser, probable polymorphism
cln8.003 C: Exon 2 c.464C>T r.(464c>u) g.1719684C>T p.(Ala155Val) sequence variation EPMR ? Finland 10508524 Ranta et al., Nat Genet; 1999  probable polymorphism
cln8.004 C: Exon 2 c.88delG r.(88delg) g.1719308delG CD040881 p.(Ala30Leufs*20) frameshift Frameshift after V29 and truncated protein late infantile 1 Turkey 15024724 Ranta et al., Hum Mut; 2004 Pa-cln8.033
cln8.005 C: Exon 2 c.[46C>A;509C>T] r.[46c>a; 509c>u] g.[1719266C>A; 1719729C>T] CM040701 p.[Leu16Met;Thr170Met] Missense late infantile 1 Turkey 15024724 Ranta et al., Hum Mut; 2004 Pa-cln8.031; Pa-cln8.032 siblings; p.Leu16Met predicted benign
cln8.006 D: Exon 3 c.610C>T r.(610c>u) g.1728482C>T rs104894060, CM040703 p.(Arg204Cys) Missense Probably damaging late infantile 4 Turkey 15024724, 21990111 Ranta et al, Hum. Mutat 2004, Kousi et al, Hum. Mutat 2012 Pa-cln8.026; Pa-cln8.029; Pa-cln8.030; Pa-cln8.058
cln8.006 D: Exon 3 c.610C>T r.(610c>u) g.1728482C>T rs104894060, CM040703 p.(Arg204Cys) Missense Probably damaging late infantile 2 Turkey 15024724 Ranta et al., Hum Mut; 2004 Pa-cln8.027; Pa-cln8.028
cln8.006 D: Exon 3 c.610C>T r.(610c>u) g.1728482C>T rs104894060, CM040703 p.(Arg204Cys) Missense Probably damaging late infantile 2 UK 21990111 Kousi et al., 2011 Pa-cln8.051; Pa-cln8.064
cln8.007 D: Exon 3 c.789G>C r.(789g>c) g.1728661G>C rs28940569, CM040704 p.(Trp263Cys) Missense Possibly damaging late infantile mild 3 Turkey 15024724 Ranta et al., Hum Mut; 2004 Pa-cln8.023; Pa-cln8.024; Pa-cln8.025 (later age of onset and protracted)
cln8.007 D: Exon 3 c.789G>C r.(789g>c) g.1728661G>C rs28940569, CM040704 p.(Trp263Cys) Missense Possibly damaging late infantile mild 1 Turkey 15024724 Ranta et al., Hum Mut; 2004 Pa-cln8.027 (later age of onset and protracted)
cln8.007 D: Exon 3 c.789G>C r.(789g>c) g.1728661G>C rs28940569, CM040704 p.(Trp263Cys) Missense Possibly damaging late infantile mild 1 Middle East 21990111 Kousi et al., 2011 Pa-cln8.065 (later age of onset and protracted)
cln8.008 C: Exon 2 c.66delG r.(66delg) g.1719286delG CD067158 p.(Ile23Serfs*5)5 frameshift late infantile 2 Italy 16570191 Cannelli et al., Neurogenetics; 2006 Pa-cln8.035; Pa-cln8.036 both het with different mutations
cln8.009 C: Exon 2 c.88G>C r.(88g>c) g.1719308G>C rs137852883, CM066760 p.(Ala30Pro) Missense Possibly damaging late infantile 1 Italy 16570191 Cannelli et al., Neurogenetics; 2006 Pa-cln8.037
cln8.010 C: Exon 2 c.473A>G r.(473a>g) g.1719693A>G CM066761 p.(Tyr158Cys) Missense Probably damaging late infantile 1 Italy 16570191 Cannelli et al., Neurogenetics; 2006 Pa-cln8.036
cln8.010 C: Exon 2 c.473A>G r.(473a>g) g.1719693A>G CM066761 p.(Tyr158Cys) Missense Probably damaging late infantile 2 Pakistan 21990111 Kousi et al., 2011 Pa-cln8.056; Pa-cln8.057
cln8.010 C: Exon 2 c.473A>G r.(473a>g) g.1719693A>G CM066761 p.(Tyr158Cys) Missense Probably damaging late infantile 1 Canada 21990111 Kousi et al., 2011 Pa-cln8.066; Pa-cln8.067 siblings
cln8.010 C: Exon 2 c.473A>G r.(473a>g) g.1719693A>G CM066761 p.(Tyr158Cys) Missense Probably damaging late infantile none 1 Asia N.A. A. Dobbie, pers comm Pa-cln8.071
cln8.011 D: Exon 3 c.581A>G r.(581a>g) g.1728453A>G CM066759 p.(Gln194Arg) Missense Possibly damaging late infantile 1 Italy 16570191 Cannelli et al., Neurogenetics; 2006 Pa-cln8.035 Slightly more severe phenotype
cln8.012 D: Exon 3 c.709G>A r.(709g>a) g.1728581G>A p.(Gly237Arg) Missense Possibly damaging late infantile 1 Finland 16828266 Siintola et al., Biochim Biophys Acta; 2006 Pa-cln8.034 Finnish patient: In association with c.70C>G = EPMR or even milder
cln8.012 D: Exon 3 c.709G>A r.(709g>a) g.1728581G>A p.(Gly237Arg) Missense Possibly damaging late infantile 1 Pakistan 19807737 Reinhardt et al., Clin Genet; 2010 Pa-cln8.042
cln8.012 D: Exon 3 c.709G>A r.(709g>a) g.1728581G>A p.(Gly237Arg) Missense Possibly damaging late infantile 1 Turkey 19201763 Kousi et al., Brain, 2009 Pa-cln8.045
cln8.012 D: Exon 3 c.709G>A r.(709g>a) g.1728581G>A p.(Gly237Arg) Missense Possibly damaging late infantile 1 UK 21990111 Kousi et al., 2011 Pa-cln8.050
cln8.012 D: Exon 3 c.709G>A r.(709g>a) g.1728581G>A p.(Gly237Arg) Missense Possibly damaging late infantile 1 Turkey 21990111 Kousi et al., 2011 Pa-cln8.060; Pa-cln8.061
cln8.012 D: Exon 3 c.709G>A r.(709g>a) g.1728581G>A p.(Gly237Arg) Missense Possibly damaging late infantile 1 Albania 21990111 Kousi et al., 2011 Pa-cln8.063
cln8.013 D: Exon 3 c.766C>G r.(766c>g) g.1728638C>G CM072954 p.(Gln256Glu) Missense Possibly damaging late infantile 1 Israel 22964447 Zelnik et al., Pediatr Neurol. 2007;Mahajnah and Zelnik 2012 Pa-cln8.038, Pa-cln8.069-070 Different disease course in same extended family
cln8.014 C: Exon 2 c.470A>G r.(470a>g) g.1719690A>G rs149308952, CM091906 p.(His157Arg) Missense Probably damaging late infantile 1 Turkey 19201763 Kousi et al., Brain, 2009 Pa-cln8.040
cln8.014 C: Exon 2 c.470A>G r.(470a>g) g.1719690A>G rs149308952, CM091906 p.(His157Arg) Missense Probably damaging 1 Norway   Helland (pers comm) Pa-cln-081
cln8.015 C: Exon 2 c.180_182delGAA r.(180_182delgaa) g.1719400_1719402delGAA CD093843 p.(Lys61del) deletion late infantile 1 Italy 19431184 Vantaggiato et al., Hum Mut; 2009 Pa-cln8.039 Maternal Uniparental Disomy
cln8.016 C: Intron 2-Exon 3 c.544-2566_590del2613 r.0 g.1725850_1728462del2613 p.0 deletion probably mRNA instability since no transcripts detected or a truncated protein late infantile rapid 1 Turkey 19807737 Reinhardt et al., Clin Genet; 2010 Pa-cln8.043 - Pa-cln8.044 siblings; rapid progression; predicted p.(Ala182Aspfs*49) but no transcipts or mutated alleles produced
cln8.017 D: Exon 3 c.611G>T r.(611g>u) g.1728483G>T p.(Arg204Leu) Missense Probably damaging 1 Germany 19807737 Reinhardt et al., Clin Genet; 2010 Pa-cln8.041
cln8.018 D: Exon 3 c.685C>G r.(685c>g) g.1728557C>G rs150047904 p.(Pro229Ala) Missense Possibly damaging 1 Mexico 21990111 Kousi et al., 2011 Pa-cln8.046
cln8.018 D: Exon 3 c.685C>G r.(685c>g) g.1728557C>G rs150047904 p.(Pro229Ala) Missense Possibly damaging 1 Argentina 21990111 Kousi et al., 2011 Pa-cln8.047
cln8.019 C: Exon 2 c.209G>A r.(209g>a) g.1719429G>A p.(Arg70His) Missense Possibly damaging 1 India 21990111 Kousi et al., 2011 Pa-cln8.048
cln8.019 C: Exon 2 c.209G>A r.(209g>a) g.1719429G>A p.(Arg70His) Missense Possibly damaging 1 Pakistan 21990111 Kousi et al., 2011 Pa-cln8.049
cln8.019 C: Exon 2 c.209G>A r.(209g>a) g.1719429G>A p.(Arg70His) Missense Possibly damaging 1 New Zealand 21990111 Kousi et al., 2011 Pa-cln8.052
cln8.020 C: Exon 2 c.227A>G r.(227a>g) g.1719447A>G p.(Gln76Arg) Missense Possibly damaging 1 Turkey 21990111 Kousi et al., 2011 Pa-cln8.053
cln8.021 C: Exon 2 c.320T>G r.(320u>g) g.1719540T>G p.(Ile107Ser) Missense Possibly damaging 1 Turkey 21990111 Kousi et al., 2011 Pa-cln8.054
cln8.022 C: Exon 2 c.374A>G r.(374a>g) g.1719594A>G rs142269885 p.(Asn125Ser) Missense Possibly damaging 1 Turkey 21990111 Kousi et al., 2011 Pa-cln8.055
cln8.023 C: Exon 2 c.415C>T r.(415c>u) g.1719635C>T p.(His139Tyr) Missense Benign 1 New Zealand 21990111 Kousi et al., 2011 Pa-cln8.052
cln8.024 D: Exon 3 c.637_639delTGG r.(637_639delugg) g.1728509_1728511delTGG p.(Trp213del) deletion 1 Turkey 21990111 Kousi et al., 2011 Pa-cln8.053
cln8.025 D: Exon 3 c.661G>A r.(661g>a) g.1728533G>A p.(Gly221Ser) Missense Benign 1 Turkey 21990111 Kousi et al., 2011 Pa-cln8.059
cln8.026 D: Exon 3 c.806A>T r.(806a>u) g.1728678A>T rs139003032 p.(Glu269Val) Missense Benign 1 Turkey 21990111 Kousi et al., 2011 Pa-cln8.062
cln8.027 D: Exon 3 c.562_563delCT r.(562_563delcu) g.1728434_1728435delCT p.(Leu188Valfs*58) deletion 1 Ireland 22220808 Allen et al 2012 Clin Genet 81:602-4 Pa-cln8.068
cln8.028 n.a. c.(?_-305)_*144635289del r.0 g.1711870-?_146364022del p.0 chr deletion late infantile 1 Ireland 22220808 Allen et al 2012 Clin Genet 81:602-4 Pa-cln8.068 de novo  8p23.3 terminal  deletion
cln8.029 c.208C>T splice site? 1 Italy   A. Simonati, pers comm Pa-cln8.072
cln8.030 D: Exon 3 c.763C>T p.(Gln255*) Nonsense late infantile 1 UK   R. Williams pers comm Pa-cln8.073
cln8.031 del 8p23.3  deletion late infantile 1 UK   R. Williams pers comm Pa-cln8.073 maternal 8p23.3 235 Kb deletion
cln8.032 D: Exon 3 c.728T>C p.(Leu243Pro) Missense late infantile 1 UK   R. Williams pers comm Pa-cln8.074
cln8.033 del 54Kb deletion late infantile 1 UK   R. Williams pers comm Pa-cln8.074
cln8.034 D: Exon 3 c.620T>G p.(Leu207Arg) Missense late infantile 1 Japan 26443629 Katata et al. Brain&Dev (2016) Pa-cln8-075
cln8.035 D: Exon 3 c.677T>C p. (Leu226Pro)  Missense EPMR 1 Turkey 27844444 Sahin et al. Acta Neurol Belg (2017) Pa-cln8-076, Pa-cln8-077, Pa-cln8-078, Pa-cln8-079, Pa-cln8-080 5 siblings
cln8.036 C: Exon 2 p.(Trp102Cys) juvenile Norway   i. Helland (pers comm) Pa-cln8-081
Notes
Recommended Mutation nomenclature followed (http://www.hgvs.org/rec.html)
Polyphen and/or SIFT used to predict functional effects
C around birth,  infantile (6-18 mo)I, LI late infantile (2-4 yr), vLI (varaint late infantile), J Juvenile (5-10 yr), A Adult 
GROD, CL, RL, FP, condensed
Coloured boxes are identical mutations separated due to a different country or origin
See dbSNP for more short genetic variations