Gene Symbol CLN6
Gene ID 54982
Chromosomal Location 15q23
Genomic RefSeqGene NG_008764.1 29751 bp
Transcript RefSeq NM_017882.2 2258 bp
Protein RefSeq NP_060352.1 311 aa
No. of mutations 68
No. of sequence variations 4
No. of changes 72
Additional notes
Identifier Location Nucleotide change Amino acid change Type of mutation Predicted functional effect Phenotype Histology No. of families  Country of origin PMID Reference Patients Notes
cln6.019 5' upstream c.1-194_1-185dupCTCCGCTCCG upstream Polymorphism n.a. n.a. 12815591 Sharp et al., Hum Mut; 2003 Not known; N.A.
cln6.060 5' upstream c.1-214_1-195insCTCCGCTCCGCCCCGCCTCC upstream n.a. n.a. N.A. Kousi et al., unpublished data N.A
cln6.001 Exon 1 c.7delG p.Ala3Argfs*30 1 bp deletion vLINCL 1 Greece 11727201 Wheeler et al., Am J Hum Genet., 2002 Pa-cln6-001
cln6.020 Exon 1 c.13C>T p.Arg5Trp Missense Probably damaging 1 USA 21990111 Kousi et al., Hum Mut; 2012 Pa-cln6.118
cln6.047 Exon 1 c.17G>C p.Arg6Thr Missense Benign Kufs type A 1 Italy 21549341 Arsov et al., Am J Hum Genet; 2011 Pa-cln6.078
cln6.061 Exon 1 c.34G>A p.Ala12Thr Missense Benign 1 Turkey 21990111 Kousi et al., Hum Mut; 2012 Pa-cln6.095
cln6.062 Exon 1 c.49G>A p.Gly17Ser Missense Benign 1 Turkey 21990111 Kousi et al., Hum Mut; 2012 Pa-cln6.096
cln6.041 Intron 1 - Intron 3 c.83+?_297+?del splice defect Intragenic deletion (undefined) vLINCL 1 Saudi Arabia 19520283 Al-Muhaizea et al., Pediatr Neurol; 2009 Pa-cln6.046-047
cln6.008 Exon 2 c.185G>A p.Arg62His Missense Probably damaging vLINCL 1 Italy/                 Portugal 12815591 Sharp et al., Hum Mut; 2003 Pa-cln6.041
cln6.027 Exon 2 c.184C>T p.Arg62Cys Missense Probably damaging vLINCL 1 Italy 19135028 Cannelli et al., Biochim Biophys Res Comm; 2009 Pa-cln6.058-059
cln6.048 Exon 2 c.100G>A p.Ala34Thr Polymorphism Kufs type B 1 Italy 21549341 Arsov et al., Am J Hum Genet; 2011 Pa-cln6.085
cln6.049 Exon 2 c.139C>T p.Leu47Phe Missense Benign Kufs type A 1 Italy 21549341 Arsov et al., Am J Hum Genet; 2011 Pa-cln6.077
cln6.050 Exon 2 c.150C>G p.Tyr50X Nonsense ANCL 1 USA 21549341 Arsov et al., Am J Hum Genet; 2011 Pa-cln6.084
cln6.009 Intron 2 c.198+2dupT splice defect 1 bp insertion at splice site vLINCL 1 Italy / Portugal 12815591 Sharp et al., Hum Mut; 2003 Pa-cln6.041
cln6.042 Intron 2 c.198+104T>C intronic polymorphism Polymorphism LINCL n.a. Argentina 21990111 Kousi et al., Hum Mut; 2012 Pa-cln6.086
cln6.042 Intron 2 c.198+104T>C intronic polymorphism Polymorphism n.a. UK 21990111 Kousi et al., Hum Mut; 2012 N.A
cln6.002 Exon 3 c.214G>T p.Glu72X Nonsense vLINCL 19 Costa Rica 11727201, 11791207 Wheeler et al., Am J Hum Genet., 2002; Gao et al., Am J Hum Genet, 2002 Pa-cln6-002-007; Pa-cln6.016-028
cln6.002 Exon 3 c.214G>T p.Glu72X Nonsense vLINCL 1 Costa Rica 11727201, 12815591 Wheeler et al., Am J Hum Genet., 2002; Sharp et al., Hum Mut; 2003 Pa-cln6.008
cln6.015 Exon 3 c.214G>C p.Glu72Gln Missense Benign vLINCL 1 India 12815591 Sharp et al., Hum Mut; 2003 Pa-cln6.042
cln6.016 Exon 3 c.268_271dupAACG p.Val91GlufsX42 4 bp insertion/duplication vLINCL 1 USA 12673792 Teixeira et al., Hum Mutat, 2003 Pa-cln6.030
cln6.016 Exon 3 c.268_271dupAACG p.Val91GlufsX42 4 bp insertion/duplication vLINCL 5 Newfoundland 18684116 Moore et al., Clin Genet, 2008 Pa-cln6.065-071
cln6.021 Exon 3 c.247G>C p.Asp83His Missense 1 USA 21990111 Kousi et al., Hum Mut; 2012 Pa-cln6.118
cln6.028 Exon 3 c.248A>T p.Asp83Val Missense Probably damaging 1 USA 21990111 Kousi et al., Hum Mut; 2012 Pa-cln6.120
cln6.034 Exon 3 c.251delA p.Tyr84SerfsX32 1 bp deletion 1 China 21990111 Kousi et al., Hum Mut; 2012 Pa-cln6.112
cln6.043 Exon 3 c.209C>T p.Pro70Leu Missense Probably damaging 1 Canada 21990111 Kousi et al., Hum Mut; 2012 Pa-cln6.119
cln6.051 Exon 3 c.200T>C p.Leu67Pro Missense Probably damaging Kufs type A 1 Italy 21549341 Arsov et al., Am J Hum Genet; 2011 Pa-cln6.075-076 
cln6.052 Exon 3 c.231C>G p.Asn77Lys Missense Probably damaging ANCL 1 USA 21549341 Arsov et al., Am J Hum Genet; 2011 Pa-cln6.084
cln6.056 Exon 3 c.308G>A p.Arg103Gln Missense Probably damaging Kufs 1 Italy 21549341 Arsov et al., Am J Hum Genet; 2011 Pa-cln6.075-076 
cln6.056 Exon 3 c.308G>A p.Arg103Gln Missense Probably damaging Kufs 1 UK 21990111 Armour pers comm Pa-cln6.119
cln6.058 Exon 3 c.278C>T p.Thr93Met Missense Probably damaging ANCL 1 USA N.A. K Sims pers comm Pa-cln6.122
cln6.070 Exon 3 c.270C>G p.Asn90Lys Missense Probably damaging vLINCL 1 India 21990111 Kousi et al., Hum Mut; 2012 Pa-cln6.110
cln6.064 Intron 3 c.298-13C>T splice defect?? 1 Canada 21990111 Kousi et al., Hum Mut; 2012 Pa-cln6.114
cln6.065 Intron 3 c.298-6C>T splice defect?? 1 Turkey 21990111 Kousi et al., Hum Mut; 2012 Pa-cln6.097
cln6.065 Intron 3 c.298-6C>T splice defect?? 1 Canada 21990111 Kousi et al., Hum Mut; 2012 Pa-cln6.116
cln6.003 Exon 4 c.368G>A p.Gly123Asp Missense Probably damaging vLINCL 1 Costa Rica 11727201 Wheeler et al., Am J Hum Genet., 2002 Pa-cln6-012
cln6.004 Exon 4 c.316dupC p.Arg106ProfsX26 1-bp insertion vLINCL 2 Pakistan 11727201 Wheeler et al., Am J Hum Genet., 2002 Pa-cln6.010-011
cln6.004 Exon 4 c.316dupC p.Arg106ProfsX26 1-bp insertion vLINCL 1 Pakistan 11727201 Wheeler et al., Am J Hum Genet., 2002 Pa-cln6-009
cln6.004 Exon 4 c.316dupC p.Arg106ProfsX26 1-bp insertion 1 UK 21990111 Kousi et al., Hum Mut; 2012 Pa-cln6.094
cln6.005 Exon 4 c.395_396delCT p.Ser132CysfsX18 2-bp deletion vLINCL 1 India 11727201 Wheeler et al., Am J Hum Genet., 2002 Pa-cln6-013
cln6.005 Exon 4 c.395_396delCT p.Ser132CysfsX18 2-bp deletion vLINCL 1 Saudi Arabia 19520283 Al-Muhaizea et al., Pediatr Neurol; 2009 Pa-cln6.048
cln6.005 Exon 4 c.395_396delCT p.Ser132CysfsX18 2-bp deletion vLINCL 3 Italy 19135028 Cannelli et al., Biochim Biophys Res Comm; 2009 Pa-cln6.053-054, Pa-cln6.057, Pa-cln6.060
cln6.005 Exon 4 c.395_396delCT p.Ser132CysfsX18 2-bp deletion 1 UK 21990111 Kousi et al., Hum Mut; 2012 Pa-cln6.091
cln6.006 Exon 4 c.460_462delATC p.Ile154del 3-bp deletion vLINCL 7 Portugal 11727201                             12673792 Wheeler et al., Am J Hum Genet., 2002; Teixeira et al., Hum Mutat, 2003 Pa-cln6-014, Pa-cln6-035-040
cln6.006 Exon 4 c.460_462delATC p.Ile154del 3-bp deletion vLINCL 1 Portugal 11727201                             12815591                              12673792 Wheeler et al., Am J Hum Genet., 2002; Sharp et al., Hum Mut; 2003; Teixeira et al., Hum Mutat, 2003 Pa-cln6-015, Pa-cln6.033
cln6.006 Exon 4 c.460_462delATC p.Ile154del 3-bp deletion 1 Arabic origin 21990111 Kousi et al., Hum Mut; 2012 Pa-cln6.113
cln6.024 Exon 4 c.406C>T p.Arg136Cys Missense Probably damaging vLINCL 1 Italy 19135028 Cannelli et al., Biochim Biophys Res Comm; 2009 Pa-cln6.051-052
cln6.024 Exon 4 c.406C>T p.Arg136Cys Missense Probably damaging 1 Turkey 21990111 Kousi et al., Hum Mut; 2012 Pa-cln6.098
cln6.025 Exon 4 c.426C>G p.Tyr142X Nonsense vLINCL 1 Italy 19135028 Cannelli et al., Biochim Biophys Res Comm; 2009 Pa-cln6.051-052
cln6.026 Exon 4 c.485T>G p.Leu162Arg Missense Probably damaging vLINCL 1 Italy 19135028 Cannelli et al., Biochim Biophys Res Comm; 2009 Pa-cln6.056
cln6.026 Exon 4 c.485T>G p.Leu162Arg Missense Probably damaging 1 Czech Republic 21990111 Kousi et al., Hum Mut; 2012 Pa-cln6.087
cln6.029 Exon 4 c.360_361insATC p.Ile119_Phe120insIle 3 bp insertion 1 USA 21990111 K Sims pers comm Pa-cln6.121 Referred to as c.357_358 insATC in former database but c.358_360insATC p.Phe120dup in Kousi et al 2012 
cln6.031 Exon 4 c.445C>T p.Arg149Cys Missense Probably damaging 1 Canada 21990111 Kousi et al., Hum Mut; 2012 Pa-cln6.115
cln6.032 Exon 4 c.307C>T p.Arg103Trp Missense Probably damaging vLINCL 1 Argentina 18846690 Cismondi et al 2008 Hum Genet  Pa-cln6.063
cln6.040 Exon 4 c.476C>T p.Pro159Leu Missense Probably damaging LINCL 1 Turkey 19201763 Kousi et al., Brain, 2009 Pa-cln6.064
cln6.044 Exon 4 c.311C>T p.Ser104Phe Missense Possibly damaging vLINCL 1 Czech Republic 21990111 Kousi et al., Hum Mut; 2012 Pa-cln6.088
cln6.053 Exon 4 c.446G>A p.Arg149His Missense Probably damaging Kufs 1 Ireland 21549341 Arsov et al., Am J Hum Genet; 2011 Pa-cln6.082-083 
cln6.059 Exon 4 c.382C>G p.Leu128Val Missense Benign ANCL 1 USA N.A. K Sims pers comm Pa-cln6.122
cln6.017 Intron 4 c.486+1G>T splice defect Splice site vLINCL 1 India 12673792 Teixeira et al., Hum Mutat, 2003 Pa-cln6.031-032
cln6.035 Intron 4 c.486+8C>T splice defect Aberrant splicing LINCL 1 Argentina 21990111 Kousi et al., Hum Mut; 2012 Pa-cln6.086
cln6.035 Intron 4 c.486+8C>T splice defect Aberrant splicing 1 UK 21990111 Kousi et al., Hum Mut; 2012 Pa-cln6.092
cln6.035 Intron 4 c.486+8C>T splice defect Aberrant splicing 1 Canada 21990111 Kousi et al., Hum Mut; 2012 Pa-cln6.117
cln6.007 Exon 5 c.510_512delCTA p.Tyr172del 3 bp deletion vLINCL 1 Venezuela 11791207 Gao et al., Am J Hum Genet, 2002 Pa-cln6-029
cln6.037 Exon 5 c.519delT p.Asp173GlufsX33 1 bp deletion vLINCL 1 Italy 19135028 Cannelli et al., Biochim Biophys Res Comm; 2009 Pa-cln6.055
cln6.045 Exon 5 c.506T>C p.Leu169Pro Missense Probably damaging vLINCL 1 Czech Republic 21990111 Kousi et al., Hum Mut; 2012 Pa-cln6.088
cln6.067 Exon 5 c.516T>A p.Tyr172X Nonsense 1 Turkey 21990111 Kousi et al., Hum Mut; 2012 Pa-cln6.099
cln6.022 Intron 5 c.542+5G>T splice defect (confirmed by RT-PCR) Aberrant splicing vLINCL 1 Turkey 15996215 Siintola et al., Clin Gen, 2005 Pa-cln6.074
cln6.010 Exon 6 c.662A>C p.Tyr221Ser Missense Possibly damaging vLINCL 1 Argentina 12815591 Sharp et al., Hum Mut; 2003 Pa-cln6.043
cln6.010 Exon 6 c.662A>C p.Tyr221Ser Missense Possibly damaging 2 Turkey 21990111 Kousi et al., Hum Mut; 2012 Pa-cln6.101-102
cln6.023 Exon 6 c.663C>G p.Tyr221X Nonsense vLINCL 1 Turkey 15996215 Siintola et al., Clin Gen, 2005 Pa-cln6.072-073
cln6.023 Exon 6 c.663C>G p.Tyr221X Nonsense 1 Turkey 21990111 Kousi et al., Hum Mut; 2012 Pa-cln6.103
cln6.033 Exon 6 c.552dupC p.Phe185LeufsX17 1 bp insertion.  vLINCL 1 Argentina 18846690 Cismondi et al 2008 Hum Genet  Pa-cln6.063
cln6.033 Exon 6 c.552dupC p.Phe185LeufsX17 1 bp insertion.  1 UK 21990111 Kousi et al., Hum Mut; 2012 Pa-cln6.092
cln6.057 Exon 6 c.662A>G p.Tyr221Cys Missense Probably damaging vLINCL 2 Italy 19135028 Cannelli et al., Biochim Biophys Res Comm; 2009 Pa-cln6.050
cln6.069 Exon 6 c.557T>C p.Phe186Ser Missense Probably damaging LINCL 1 India 21990111 Kousi et al., Hum Mut; 2012 Pa-cln6.100
cln6.011 Exon 7 c.722T>C p.Met241Thr Missense Possibly damaging vLINCL 1 Costa Rica 11727201      12815590 Wheeler et al., Am J Hum Genet., 2002; Sharp et al., Hum Mut; 2003 Pa-cln6-008
cln6.012 Exon 7 c.794_796delCCT p.Ser265del 3bp deletion vLINCL 1 Sudan 12815591 Sharp et al., Hum Mut; 2003 Pa-cln6.044 This mutation has previously been referred to as c.793_795delTCC
cln6.012 Exon 7 c.794_796delCCT p.Ser265del 3bp deletion vLINCL 1 Saudi Arabia 19520283 Al-Muhaizea et al., Pediatr Neurol; 2009 Pa-cln6.049 This mutation has previously been referred to as c.793_795delTCC
cln6.012 Exon 7 c.794_796delCCT p.Ser265del 3bp deletion vLINCL 1 Italy 19135028 Cannelli et al., Biochim Biophys Res Comm; 2009 Pa-cln6.056 This mutation has previously been referred to as c.793_795delTCC
cln6.012 Exon 7 c.794_796delCCT p.Ser265del 3bp deletion 1 Czech Republic 21990111 Kousi et al., Hum Mut; 2012 Pa-cln6.087 This mutation has previously been referred to as c.793_795delTCC
cln6.012 Exon 7 c.794_796delCCT p.Ser265del 3bp deletion 1 UK 21990111 Kousi et al., Hum Mut; 2012 Pa-cln6-093 This mutation has previously been referred to as c.793_795delTCC
cln6.012 Exon 7 c.794_796delCCT p.Ser265del 3bp deletion 3 Turkey 21990111 Kousi et al., Hum Mut; 2012 Pa-cln6.104-106 This mutation has previously been referred to as c.793_795delTCC
cln6.013 Exon 7 c.829_837delinsCCTG p.Val277ProfsX5 9 bp deletion + 4 bp insertion vLINCL 1 Portugal 12673792 Teixeira et al., Hum Mutat, 2003 Pa-cln6-015, 033
cln6.014 Exon 7 c.896C>T p.Pro299Leu Missense Probably damaging vLINCL 1 Italy 12815591 Sharp et al., Hum Mut; 2003 Pa-cln6.045
cln6.014 Exon 7 c.896C>T p.Pro299Leu Missense Probably damaging vLINCL 4 Italy 19135028 Cannelli et al., Biochim Biophys Res Comm; 2009 Pa-cln6.055, Pa-cln6.057, Pa-cln6.060, Pa-cln6.062
cln6.014 Exon 7 c.896C>T p.Pro299Leu Missense Probably damaging vLINCL 1 Italy/Libya 21990111 Kousi et al., Hum Mut; 2012 Pa-cln6.090
cln6.018 Exon 7 c.898T>C p.Trp300Arg Missense Possibly damaging vLINCL 1 USA 12673792 Teixeira et al., Hum Mutat, 2003 Pa-cln6.030
cln6.030 Exon 7 c.890delC p.Pro297LeufsX53 1-bp deletion Kufs 1 Ireland 21549341 Arsov et al., Am J Hum Genet; 2011 Pa-cln6.082-083 
cln6.030 Exon 7 c.890delC p.Pro297LeufsX53 1-bp deletion 1 USA 21990111 Kousi et al., Hum Mut; 2012 Pa-cln6.122
cln6.036 Exon 7 c.755G>A p.Arg252His Missense Probably damaging LINCL 1 Argentina 21990111 Kousi et al., Hum Mut; 2012 Pa-cln6.086
cln6.036 Exon 7 c.755G>A p.Arg252His Missense Probably damaging 1 UK 21990111 Kousi et al., Hum Mut; 2012 Pa-cln6.092
cln6.038 Exon 7 c.715_718delTTCG p.Phe239ProfsX29 Nonsense vLINCL 1 Italy 19135028 Cannelli et al., Biochim Biophys Res Comm; 2009 Pa-cln6.053-054
cln6.039 Exon 7 c.776G>T p.Gly259Val Missense Probably damaging vLINCL 1 Italy 19135028 Cannelli et al., Biochim Biophys Res Comm; 2009 Pa-cln6.061
cln6.046 Exon 7 c.889C>A p.Pro297Thr Missense Probably damaging vLINCL 1 Pakistan 21990111 Kousi et al., Hum Mut; 2012 Pa-cln6.111
cln6.054 Exon 7 c.712_713delinsAC p.Phe238Thr 2 bp deletion + 2 bp insertion Benign Kufs type A 1 Malta 21549341 Arsov et al., Am J Hum Genet; 2011 Pa-cln6.079-080
cln6.054 Exon 7 c.712_713delinsAC p.Phe238Thr 2 bp deletion + 2 bp insertion Benign Kufs 1 Italy 21549341 Arsov et al., Am J Hum Genet; 2011 Pa-cln6.081
cln6.055 Exon 7 c.923G>C p.Ser308Thr Polymorphism Kufs 1 USA 21549341 Arsov et al., Am J Hum Genet; 2011 Pa-cln6.084
cln6.063 Exon 7 c.829_837delinsCCTG p.Val277ProfsX5 Nonsense 1 Portugal 12815591 Sharp et al., Hum Mut; 2003 Pa-cln6.034
cln6.066 Exon 7 c.727delG p.Ala243ProfsX26 Nonsense vLINCL 1 Italy/Lybia 21990111 Kousi et al., Hum Mut; 2012 Pa-cln6.090
cln6.068 Exon 7 c.700T>C p.Phe234Leu Missense Possibly damaging vLINCL 1 Italy 21990111 Kousi et al., Hum Mut; 2012 Pa-cln6.089
cln6.071 Exon 7 c.775G>A p.Gly259Ser Missense Probably damaging vLINCL 1 India 21990111 Kousi et al., Hum Mut; 2012 Pa-cln6.107-109 Discrepancy:  c.775G>A is p.Arg252His; c.797G>A is p.Gly259Ser.
cln6.072 Exon 7 c.768C>G p.Asp256Glu Missense teenage NCL 1 Afghanistan 22883287 Andrade et al., Ped Neurol 2012 Pa-cln6.123-125
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