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

No. of sequence variations

Total No. of changes

Additional notes

cln5.031& cln5.036 no longer used

Identifier

Location

cDNA change

RNA change

Genomic DNA change hg19

dbSNP

Protein change

Type of mutation

Predicted functional effect

Phenotype

Histology

No. of families

Country of origin

PMID

References

Patients

Notes

cln5.002

B: Exon 1

c.225G>A

r.(225g>a)

g.77566311G>A

rs104894385, CM980371

p.(Trp75*)

Nonsense

classic

Sweden

20157158 , 10953198

Xin et al., Neurology, 2010, Holmberg et al., Neurology, 2000

Pa-cln5.043

cln5.002

B: Exon 1

c.225G>A

r.(225g>a)

g.77566311G>A

rs104894385, CM980371

p.(Trp75*)

Nonsense

classic

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*)

Nonsense

classic

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)

Sequence variant

classic

n.a., Argentina

20157158 , 21990111

Kousi et al., Hum Mut; 2012

cln5.012

B: Exon 1

c.4C>T

r.(4c>u)

g.77566090C>T

rs77416795

p.(Arg2Cys)

Sequence variant

classic

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)

Sequence variant

classic

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)

Sequence variant

classic

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)

Sequence variant

classic

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)

1-bp insertion

early onset (4 mo)

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.(=)

Sequence variant

USA, Argentina

20157158 21990111

Xin et al., Neurology, 2010, Kousi et al., Hum Mut; 2011

Pa-cln5.041

cln5.024

B: Exon 1

c.234C>G

r.(234c>g)

g.77566320C>G

rsS138037471

p.(=)

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)

Missense

Possibly damaging

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)

Missense

Possibly damaging

congenital/infantile

GROD, CL, FP (lymphocytes and skin)

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

cln5.039

B: Exon 1

c.223T>C

r.(223u>c)

g.77566309T>C

p.(Trp75Arg)

Missense

Probably damaging

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)

Missense

Probably damaging

later onset

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)

Missense

Probably damaging

later onset

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)

Missense

Probably damaging

classic

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)

Missense

Probably damaging

Late onset (age 17)

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*)

Nonsense

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)

1-bp insertion

classic

Sweden

20157158 10953198

Xin et al., Neurology, 2010, Holmberg et al., Neurology, 2000

Pa-cln5.043

classic in combination with Y392X

cln5.005

D: Exon 3

c.669dupC

r.(669dup)

g.77570219dup

CI003728

p.(Trp224Leufs*30)

1-bp insertion

mild

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)

1-bp insertion

classic/mild

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*)

Nonsense

classic

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*)

Nonsense

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*)

Nonsense

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)

Missense

Probably damaging

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)

1-bp insertion

vLINCL

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)

Missense

Probably damaging

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)

Missense

Probably damaging

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*)

Nonsense

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.(=)

Sequence variant

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.(=)

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)

Missense

Probably damaging

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)

Missense

Probably damaging

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)

Missense

Probably damaging

Arab (Qatar and 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)

Frameshift

congenital/infantile

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*)

Nonsense

Serbia

n.a.

Boustany pers comm to NCL mutation database 2012

Pa-cln5.085

cln5.001

E: Exon 4

c.1175_1176delAT

r.(1175_1176del)

g.77575055_77575056delAT

p.(Tyr392*)

2-bp deletion

classic

Finland

9662406 10953198

Savukoski et al., Nature Genet, 1998, Holmberg et al., Neurology, 2000

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)

Sequence variant

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)

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)

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)

Sequence variant

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)

Sequence variant

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)

Sequence variant

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)

Sequence variant

Hispanic

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)

Missense

Probably damaging

classic

The Netherlands

9662406 10953198

Savukoski et al., Nature Genet, 1998, Holmberg et al., Neurology, 2000

Pa-cln5.020

cln5.003

E: Exon 4

c.835G>A

r.(835g>a)

g.77574715G>A

rs28940280, CM980372

p.(Asp279Asn)

Missense

Probably damaging

classic

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)

16-bp del

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)

Missense

Probably damaging

vJNCL, seizures lateer

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)

Missense

Probably damaging

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)

Missense

Probably damaging

Turkey

21990111

Kousi et al., Hum Mut; 2012

Pa-cln5.058, 068

cln5.016

E: Exon 4

c.1026C>A

r.(1026c>a)

g.77574906C>A

p.(Tyr342*)

Nonsense

Roma from the former Czechoslovakia

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*)

Nonsense

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)

Missense

Probably damaging

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)

Missense

Probably damaging

Late onset (age 17)

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

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

USA

20157158

Xin et al., Neurology, 2010

Pa-cln5.042

cln5.033

E: Exon 4

c.919delA

r.(919del)

g.77574799delA

p.(Arg307Glufs*29

1-bp deletion

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

1-bp deletion

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)

2-bp deletion

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)

2-bp deletion

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)

2-bp deletion

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)

4-bp deletion

vLINCL, vJNCL

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)

4-bp deletion

vLINCL, vJNCL

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.(=)

Sequence variant

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.(=)

Sequence variant

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.(=)

Sequence variant

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.(=)

Sequence variant

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.(=)

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.?

Sequence variant

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)

1-bp deletion

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.(=)

Sequence variant

USA

20157158

Xin et al., Neurology, 2010

Pa-cln5.041

formerly c.1224+33A>G

Notes

Recommended mutation nomenclature followed (http://www.hgvs.org/rec.html)

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