Gene Symbol CLN5
Gene ID 1203
Chromosomal Location 13q21.1-32
Genomic RefSeqGene NG_009064.1 17594 bp
Transcript RefSeq NM_006493 2816 bp
Protein RefSeq 5729772 407 aa
No. of mutations 37
No. of sequence variations 9
Total No. of changes 46
Additional notes cln5.031& cln5.036 not assigned
Two siblings have not had their mutations characterised (Shetty et al)
Identifier Location cDNA change RNA change Genomic DNA change hg19 dbSNP Amino acid change Type of mutation Predicted functional effect NCL Phenotype or other disease Histology No. of families  Country of origin PMID References PMID 2 Patients Notes
cln5.002 B: Exon 1 c.225G>A r.(225g>a) g.77566311G>A rs104894385, CM980371 p.(Trp75*) substitution late infantile 1 Sweden 20157158 Xin et al., Neurology, 2010, also Holmberg et al., Neurology 2000 10953198 Pa-cln5.043
cln5.002 B: Exon 1 c.225G>A r.(225g>a) g.77566311G>A rs104894385, CM980371 p.(Trp75*) substitution late infantile 1 Finland 9662406 Savukoski et al., Nature Genet, 1998 Pa-cln5.019
cln5.002 B: Exon 1 c.225G>A r.(225g>a) g.77566311G>A rs104894385, CM980371 p.(Trp75*) substitution late infantile 1 Canada 21990111 Kousi et al., Hum Mut; 2012 Pa-cln5.073
cln5.012 B: Exon 1 c.4C>T r.(4c>u) g.77566090C>T rs77416795 p.(Arg2Cys) substitution sequence variant late infantile 6                      Argentina 1990111 Kousi et al., Hum Mut; 2012, also Xin et al Neurology 2010 20157158
cln5.012 B: Exon 1 c.4C>T r.(4c>u) g.77566090C>T rs77416795 p.(Arg2Cys) substitution sequence variant late infantile 13 Turkey 21990111 Kousi et al., Hum Mut; 2012 Pa-cln5.053, 054-060, Pa-cln6-064, 105, Pa-cln7.009, 059, 006
cln5.012 B: Exon 1 c.4C>T r.(4c>u) g.77566090C>T rs77416795 p.(Arg2Cys) substitution sequence variant late infantile 1 UK 21990111 Kousi et al., Hum Mut; 2012 Pa-cln5.049
cln5.012 B: Exon 1 c.4C>T r.(4c>u) g.77566090C>T rs77416795 p.(Arg2Cys) substitution sequence variant late infantile 1 Canada 21990111 Kousi et al., Hum Mut; 2012 Pa-cln5.076, 081
cln5.012 B: Exon 1 c.4C>T r.(4c>u) g.77566090C>T rs77416795 p.(Arg2Cys) substitution sequence variant late infantile n.a. Czech Republic 21990111 Kousi et al., Hum Mut; 2012
cln5.019 B: Exon 1 c.291dupC r.(291dup) g.77566377dup HI070015 p.(Ser98Leufs*13) duplication congenital 1 Argentina 20960661 Cismondi et al., Hum Genet, 2008 Pa-cln5.030
cln5.023 B: Exon 1 c.72A>G r.(72a>g) g.77566158A>G rs7987664 p.(=) substitution sequence variant 2 USA,                             Argentina 20157158 Xin et al., Neurology, 2010, Kousi et al., Hum Mut; 2011 21990111 Pa-cln5.041
cln5.024 B: Exon 1 c.234C>G r.(234c>g) g.77566320C>G rsS138037471 p.(=) substitution sequence variant 1=0.5% chr USA 20157158 Xin et al., Neurology, 2010
cln5.038 B: Exon 1 c.61C>T r.(61c>u) g.77566147C>T p.(Pro21Ser) substitution Possibly damaging 1 Turkey 21990111 Kousi et al., Hum Mut; 2012 Pa-cln5.061
cln5.038 B: Exon 1 c.61C>T r.(61c>u) g.77566147C>T p.(Pro21Ser) substitution Possibly damaging congenital GROD, CL, FP (lymphocytes and skin) 1 22727047 Staropoli et al 2012 BMC Med Genet. 13:50 Pa-cln5.084 also found as an isolated change in a teenage boy with progressive neurological decline
cln5.038 B: Exon 1 c.61C>T r.(61c>u) g.77566147C>T p.(Pro21Ser) substitution Possibly damaging Spinocerebellar ataxia   1 Brazil L Jardim (pers comm) Pa-cln5.091 2 sibs
cln5.039 B: Exon 1 c.223T>C r.(223u>c) g.77566309T>C p.(Trp75Arg) substitution Probably damaging 3 Turkey 21990111 Kousi et al., Hum Mut; 2012 Pa-cln5.060
cln5.006 C: Exon 2 c.335G>A r.(335g>a) g.77569212G>A rs104894386 p.(Arg112His) substitution Probably damaging juvenile 1 Colombia 15728307 Pineda-Trujillo et al., Neurology; 2005 Pa-cln5.022-023
cln5.006 C: Exon 2 c.335G>A r.(335g>a) g.77569212G>A rs104894386 p.(Arg112His) substitution Probably damaging juvenile 1 UK 21990111 Kousi et al., Hum Mut; 2012 Pa-cln5.051
cln5.008 C: Exon 2 c.335G>C r.(335g>c) g.77569212G>C CM050199 p.(Arg112Pro) substitution Probably damaging late infantile 1 Portugal 16814585 Bessa et al., Mol Genet Metab, 2006 Pa-cln5.024 Found on same maternal allele as p.Asp279Asn
cln5.021 C: Exon 2 c.377G>A r.(377g>a) g.77569254G>A CM063906 p.(Cys126Tyr) substitution Probably damaging adult 1 USA 20157158 Xin et al., Neurology, 2010 Pa-cln5.040
cln5.040 C: Exon 2 c.433C>T r.(433c>u) g.77569310C>T COSM196447 p.(Arg145*) substitution NA 1 UK 21990111 Kousi et al., Hum Mut; 2012 Pa-cln5.052
cln5.005  D: Exon 3 c.669dupC r.(669dup) g.77570219dup CI003728 p.(Trp224Leufs*30) duplication late infantile 1 Sweden 20157158 Xin et al., Neurology, 2010, Holmberg et al., Neurology, 2000 10953198 Pa-cln5.043 classic in combination with Y392X
cln5.005  D: Exon 3 c.669dupC r.(669dup) g.77570219dup CI003728 p.(Trp224Leufs*30) duplication late infantile 1 Finland 10953198 Holmberg et al., Neurology, 2000 Pa-cln5.021  mild in combination with Y75X
cln5.005  D: Exon 3 c.669dupC r.(669dup) g.77570219dup CI003728 p.(Trp224Leufs*30) duplication NA 1 Canada 21990111 Kousi et al., Hum Mut; 2012 Pa-cln5.073
cln5.007 D: Exon 3 c.565C>T r.(565c>u) g.77570115C>T CM063905 p.(Gln189*) substitution late infantile 1 Portugal 16814585 Bessa et al., Mol Genet Metab, 2006 Pa-cln5.024
cln5.009 D: Exon 3 c.671G>A r.(671g>a) g.77570221G>A p.(Trp224*) substitution 2 USA 20157158 Xin et al., Neurology, 2010 Pa-cln5.038, Pa-cln5.039
cln5.009 D: Exon 3 c.671G>A r.(671g>a) g.77570221G>A p.(Trp224*) substitution 1 UK 21990111 Kousi et al., Hum Mut; 2012 Pa-cln5.048
cln5.015 D: Exon 3 c.619T>C r.(619u>c) g.77570169T>C rs147065248 p.(Trp207Arg) substitution Probably damaging 1 UK 21990111 Kousi et al., Hum Mut; 2012 Pa-cln5.051
cln5.027 D: Exon 3 c.527_528insA r.(527_528insa g.77570077_77570078insA p.(Gly177Trpfs*10) insertion late infantile 1 Pakistan / USA 20157158 Xin et al., Neurology, 2010 Pa-cln5.047
cln5.029 D: Exon 3 c.575A>G r.(575a>g) g.77570125A>G p.(Asn192Ser) substitution Probably damaging 1 USA 20157158 Xin et al., Neurology, 2010 Pa-cln5.045
cln5.030 D: Exon 3 c.620G>C r.(620g>c) g.77570170G>C p.(Trp207Ser) substitution Probably damaging 1 China / USA 20157158 Xin et al., Neurology, 2010 Pa-cln5.044
cln5.042 D: Exon 3 c.524T>G r.(524u>g) g.77570074T>G p.(Leu175*) substitution 1 Turkey 21990111 Kousi et al., Hum Mut; 2012 Pa-cln5.067
cln5.028 D: Exon 3 c.528T>G r.(528u>g) g.77570078T>G rs34481987 p.(=) substitution sequence variant 1 Sweden 20157158 Xin et al., Neurology, 2010 Pa-cln5.043 p.Thr176Thr
cln5.028 D: Exon 3 c.528T>G r.(528u>g) g.77570078T>G rs34481987 p.(=) substitution sequence variant Argentina 21990111 Kousi et al., Hum Mut; 2012 p.Thr176Thr
cln5.043 D: Exon 3 c.593T>C r.(593u>c) g.77570143T>C p.(Leu198Pro) substitution Probably damaging 1 Turkey 21990111 Kousi et al., Hum Mut; 2012 Pa-cln7.068
cln5.044 D: Exon 3 c.613C>T r.(613c>u) g.77570163C>T p.(Pro205Ser) substitution Probably damaging 2 Canada 21990111 Kousi et al., Hum Mut; 2012 Pa-cln5.074, 075
cln5.044 D: Exon 3 c.613C>T r.(613c>u) g.77570163C>T p.(Pro205Ser) substitution Probably damaging 1 Qatar / Yemen 21447811 Al-Kowari et al., 2011 Pa-cln5.036, 037
cln5.045 D: Exon 3 c.486+139_712+2132del r.(487_712del) g.77569502_77572394del p.(Lys163Glufs*11) deletion congenital GROD, CL, FP (lymphocytes and skin) 22727047 Staropoli et al 2012 BMC Med Genet. 13:50 Pa-cln5.084 de novo mutation in patient of 2.8 kb del
cln5.046 D: Exon 3 c.694C>T r.(694c>u) g.77570244C>T p.(Gln232*) substitution 1 Serbia 23160995 Haddad et al., 2012 Pa-cln5.085
cln5.001 E: Exon 4 c.1175_1176delAT r.(1175_1176del) g.77575055_77575056delAT p.(Tyr392*) deletion late infantile 19 Finland 9662406 Savukoski et al., Nature Genet, 1998, Holmberg et al., Neurology, 2000 10953198 Pa-cln5.001-18, Pa-cln5.021 Finnish major mutation
cln5.004 E: Exon 4 c.1103A>G r.(1103a>g) g.77574983A>G rs1800209 p.(Lys368Arg) substitution sequence variant 1 USA 20157158 Xin et al., Neurology, 2010 Pa-cln5.041 A common polymorphisms
cln5.004 E: Exon 4 c.1103A>G r.(1103a>g) g.77574983A>G rs1800209 p.(Lys368Arg) substitution sequence variant n.a. Finland 9662406 Savukoski et al., Nature Genet, 1998 Pa-cln5.019 nearly 20% carrier freq in Finland, linked to FINmin mutation p.Trp75X
cln5.004 E: Exon 4 c.1103A>G r.(1103a>g) g.77574983A>G rs1800209 p.(Lys368Arg) substitution sequence variant n.a. Argentina 21990111 Kousi et al., Hum Mut; 2012
cln5.004 E: Exon 4 c.1103A>G r.(1103a>g) g.77574983A>G rs1800209 p.(Lys368Arg) substitution sequence variant 4 Turkey 21990111 Kousi et al., Hum Mut; 2012 Pa-cln5.063, Pa-cln7.066,Pa-cln5- 069-071
cln5.004 E: Exon 4 c.1103A>G r.(1103a>g) g.77574983A>G rs1800209 p.(Lys368Arg) substitution sequence variant 5 Canada 21990111 Kousi et al., Hum Mut; 2012 Pa-cln5.077, 078, 079, 080, 082
cln5.004 E: Exon 4 c.1103A>G r.(1103a>g) g.77574983A>G rs1800209 p.(Lys368Arg) substitution sequence variant 1 India 21990111 Kousi et al., Hum Mut; 2012 Pa-cln7.004
cln5.004 E: Exon 4 c.1103A>G r.(1103a>g) g.77574983A>G rs1800209 p.(Lys368Arg) substitution sequence variant 1 NA 21990111 Xin et al., 2010 Pa-cln4.041
cln5.003 E: Exon 4 c.835G>A r.(835g>a) g.77574715G>A rs28940280, CM980372 p.(Asp279Asn) substitution Probably damaging late infantile 1 The Netherlands 9662406 Savukoski et al., Nature Genet, 1998, Holmberg et al., Neurology, 2000 10953198 Pa-cln5.020
cln5.003 E: Exon 4 c.835G>A r.(835g>a) g.77574715G>A rs28940280, CM980372 p.(Asp279Asn) substitution Probably damaging late infantile 1 Portugal 16814585 Bessa et al., Mol Genet Metab, 2006 Pa-cln5.024 Found on same maternal allele as p.Arg112Pro
cln5.010 E: Exon 4 c.955_970del16 r.(955_970del) g.77574835_77574850del16 p.(Gly319Phefs*12) deletion 1 UK 21990111 Kousi et al., Hum Mut; 2012 Pa-cln5.048
cln5.011 E: Exon 4 c.772T>G r.(772u>g) g.77574652T>G CM076117 p.(Tyr258Asp) substitution Probably damaging juvenile 1 Italy 17607606 Cannelli et al., Neuropediatrics; 2007 Pa-cln5.025-026
cln5.013 E: Exon 4 c.726C>A r.(726c>a) g.77574606C>A rs138611001 p.(Asn242Lys) substitution SNP at 1.4% in European Americans 1 UK 21990111 Kousi et al., Hum Mut; 2012 Pa-cln5.049
cln5.013 E: Exon 4 c.726C>A r.(726c>a) g.77574606C>A rs138611001 p.(Asn242Lys) substitution SNP at 1.4% in European Americans 2 Turkey 21990111 Kousi et al., Hum Mut; 2012 Pa-cln5.058, 068
cln5.013 E: Exon 4 c.726C>A r.(726c>a) g.77574606C>A rs138611001 p.(Pro21Ser) substitution Spinocerebellar ataxia   1 Brazil L Jardim (pers comm) Pa-cln5.091 2 sibs
cln5.016 E: Exon 4 c.1026C>A r.(1026c>a) g.77574906C>A p.(Tyr342*) substitution 1 Czech Republic 19201763 Kousi et al., Brain; 2009 Pa-cln5.031
cln5.017 E: Exon 4 c.1054G>T r.(1054g>u g.77574934G>T rs121908292, CM083489 p.(Glu352*) substitution 1 Newfoundland / UK 18684116 Moore et al., Clin Genet; 2008 Pa-cln5.027-028
cln5.018 E: Exon 4 c.1137G>T r.(1137g>u) g.77575017G>T CM093057 p.(Trp379Cys) substitution Probably damaging 1 Afghanistan 19309691 Lebrun et al., Hum Mut; 2009 Pa-cln5.034-35
cln5.022 E: Exon 4 c.1121A>G r.(1121a>g) g.77575001A>G rs148862100 p.(Tyr374Cys) substitution Probably damaging adult 2 USA 20157158 Xin et al., Neurology, 2010 Pa-cln5.040, Pa-cln5.042 Probably milder mutation
cln5.032 E: Exon 4 c.907_1094del188 r.(907_1094del) g.77574787_77574974del188 p.(Thr303Cysfs*10) deletion 1 USA 20157158 Xin et al., Neurology, 2010 Pa-cln5.039
cln5.032 E: Exon 4 c.907_1094del188 r.(907_1094del) g.77574787_77574974del188 p.(Thr303Cysfs*10) deletion 1 USA 20157158 Xin et al., Neurology, 2010 Pa-cln5.042
cln5.033 E: Exon 4 c.919delA r.(919del) g.77574799delA p.(Arg307Glufs*29 deletion 1 Egypt / USA 20157158 Xin et al., Neurology, 2010 Pa-cln5.046
cln5.033 E: Exon 4 c.919delA r.(919del) g.77574799delA   p.(Arg307Glufs*29 deletion       1 Egypt 21990111 Kousi et al., Hum Mut; 2012   Pa-cln5.083  
cln5.034 E: Exon 4 c.1071_1072delCT r.(1071_1072del) g.77574951_77574952delCT   p.(Leu358Alafs*4) deletion       1 China / USA 20157158 Xin et al., Neurology, 2010   Pa-cln5.044  
cln5.014 E: Exon 4 c.1072_1073delTT r.(1072_1073del) g.77574952_77574953delTT CD093058 p.(Leu358Alafs*4) deletion 1 Pakistan 19309691 Lebrun et al., Hum Mut; 2009 Pa-cln5.032-33
cln5.014 E: Exon 4 c.1072_1073delTT r.(1072_1073del) g.77574952_77574953delTT CD093058 p.(Leu358Alafs*4) deletion 1 UK 21990111 Kousi et al., Hum Mut; 2012 Pa-cln5.050
cln5.020 E: Exon 4 c.1103_1106delAACA r.(1103_1106del) g.77574983_77574986delAACA HD070030 p.(Lys368Serfs*15) deletion   juvenile   1 USA 20157158 Xin et al., Neurology, 2010   Pa-cln5.038  
cln5.020 E: Exon 4 c.1103_1106delAACA r.(1103_1106del) g.77574983_77574986delAACA HD070030 p.(Lys368Serfs*15) deletion late infantile 1 Spain 20960652 Kohan et al., Hum Genet, 2008 Pa-cln5.029
cln5.025 B: Intron 1 c.320+8C>T r.(=) g.77566414C>T rs9565308 p.(=) substitution sequence variant 1 USA 20157158 Xin et al., Neurology, 2010 Pa-cln5-041
cln5.025 B: Intron 1 c.320+8C>T r.(=) g.77566414C>T rs9565308 p.(=) substitution sequence variant 4 Turkey 21990111 Kousi et al., Hum Mut; 2012 Pa-cln5.063-066
cln5.025 B: Intron 1 c.320+8C>T r.(=) g.77566414C>T rs9565308 p.(=) substitution sequence variant 1 Cook Islands 21990111 Kousi et al., Hum Mut; 2012 Pa-cln7.055
cln5.025 B: Intron 1 c.320+8C>T r.(=) g.77566414C>T rs9565308 p.(=) substitution sequence variant 4 Canada 21990111 Kousi et al., Hum Mut; 2012 Pa-cln5.077, 079, 080, 082
cln5.026 B: Intron 1 c.320+18C>T r.(=) g.77566424C>T rs112141862 p.(=) substitution sequence variant n.a. USA 20157158 Xin et al., Neurology, 2010 Pa-cln5.041
cln5.041 B: Intron 1 c.486+5G>C r.spl? g.77569368G>C p.? substitution sequence variant 1 Canada 21990111 Kousi et al., Hum Mut; 2012 Pa-cln5.076
cln5.035 E: Exon 4 c.1083delT r.(1083del) g.77574963delT p.(Phe361Leufs*4) deletion 1 USA 20157158 Xin et al., Neurology, 2010 Pa-cln5-041
cln5.037 3' UTR c.*33A>G r.(1224+33a>g) g.77575137A>G rs9573974 p.(=) substitution sequence variant 1 USA 20157158 Xin et al., Neurology, 2010 Pa-cln5.041 formerly c.1224+33A>G
cln5.047 E: Exon 4 c.935G>A r.(935g>a) p.(Ser312Asn) substitution 1 Italy 25359263 Mancini et al, J Neurol 2015 Pa-cln5.088-089
? ? 1 Pakistan 24082928 Setty et al. J. Pediatr Neurosci. 2013 Pa-cln5.086-087 Mutation in two siblings not described in this paper
cln5.048 c.741_747delinsTT p.(Trp247Cysfs*5) deletion-insertion late infantile   1 Middle East Williams (pers comm) Pa-cln5.090 Premature termination
Notes
Recommended mutation nomenclature followed (http://varnomen.hgvs.org/recommendations/general/)
Polyphen and/or SIFT used to predict functional effects
C - around birth, I -  infantile (6-18 mo), LI - late infantile (2-4 yr), vLI - variant late infantile, J - juvenile (5-10 yr), A - adult 
GROD - Granular osmiophilic deposits, CL - Curvilinear, RL- Rectilinear, FP - Fingerprint, condensed
See dbSNP for more short genetic variations
cln5.020=cln2.036
Last updated 28-Nov-17