| 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 | ||||||||||||||||