Last update: 17.09.06

Nephrocystin 6 (NPHP6 / CEP290)

according to Genebank accession number AC091516 (genomic data) and NM_025114 (mRNA)

Nucleotide numbering is given in Blue

Aminoacid numbering is given in green

Colour coding of the mutations indicates the following disorders

|LCA|Joubert Syndrome|Polymorphism

-800 -790 -780 -770 -760 -750 -740

tttttgttttttccttcttacagaaggcactaccctggacgccgcttgcaaacgcctgaagagaaggcagggtgt

aaaaa caaaa aagga agaat gtctt ccgtg atggg acctg cggcg aacgt ttgcg gactt ctctt ccgtc ccaca

-730 -720 -710 -700 -690 -680 -670 -660

tcccactttttcagaatgggaccaggccctacggccccaatagcagaagcttctctaacccaggactgctcccct

agggt gaaaa agtct taccc tggtc cggga tgccg gggtt atcgt cttcg aagag attgg gtcct gacga gggga

-650 -640 -630 -620 -610 -600 -590

caattcctcccaatatgctgaccgacagctcgacctcacctgggggcggttccgccaggggatggcttaggaaaa

gttaa ggagg gttat acgac tggct gtcga gctgg agtgg acccc cgcca aggcg gtccc ctacc gaatc ctttt

-580 -570 -560 -550 -540 -530 -520 -510

cctcaggaagagcagcccagcgagtgacgccactgaaaccacagtcatggtctacctcgttcaggccaccagttt

ggagt ccttc tcgtc gggtc gctca ctgcg gtgac tttgg tgtca gtacc agatg gagca agtcc ggtgg tcaaa

-500 -490 -480 -470 -460 -450 -440

gcaggcgcctgagccgctgctcctcccgcctctcggtccttccccgccgccccggtaccgtcgcagtcttacgcg

cgtcc gcgga ctcgg cgacg aggag ggcgg agagc cagga agggg cggcg gggcc atggc agcgt cagaa tgcgc

-430 -420 -410 -400 -390 -380 -370 -360

ttgcatgccgggagcgccttacctcctcttctcagggacttcagttcccagcatgcagaagcctcaggcagaact

aacgt acggc cctcg cggaa tggag gagaa gagtc cctga agtca agggt cgtac gtctt cggag tccgt cttga

-350 -340 -330 -320 -310 -300 -290

gcactctgggATTTGAAGTCCTCGTTCCACGCCTTCTCATCATCCTGAACACCGAGCTCTGGGACTCCGGCGGAG

cgtga gaccc TAAAC TTCAG GAGCA AGGTG CGGAA GAGTA GTAGG ACTTG TGGCT CGAGA CCCTG AGGCC GCCTC

-280 -270 -260 -250 -240 -230 -220 -210

AATCTAAACGTAAAGCATCACCCACGGTCGTGAACTGTAGGCTCTCCTGGCATCCGGGATCTTATTCTGGCCTTG

TTAGA TTTGC ATTTC GTAGT GGGTG CCAGC ACTTG ACATC CGAGA GGACC GTAGG CCCTA GAATA AGACC GGAAC

-200 -190 -180 -170 -160 -150 -140

GCGGAGTTGGGGATGGTGTCGCCTAGCAGCCGCTGCCGCTTTGGCTTGCTCGGGACCATTTGGCTGGACCCAGAG

CGCCT CAACC CCTAC CACAG CGGAT CGTCG GCGAC GGCGA AACCG AACGA GCCCT GGTAA ACCGA CCTGG GTCTC

-130 -120 -110 -100 -90 -80 -70 -60

TCCGCGTGGAACCGCGATAGGGATCTGTCAGGGCCCGCGGCCGGGTCCAGCTTGGTGGTTGCGGTAGTGAGAGGC

AGGCG CACCT TGGCG CTATC CCTAG ACAGT CCCGG GCGCC GGCCC AGGTC GAACC ACCAA CGCCA TCACT CTCCG

-50 -40 -30

CTCCGCTGGTTGCCAGGCTTGGTCTAGtttttgttttttccttcttacagaaggcactaccctggacgccgcttg

GAGGC GACCA ACGGT CCGAA CCAGA TCaaa aacaa aaaag gaaga atgtc ttccg tgatg ggacc tgcgg cgaac

caaacgcctgaagagaaggcagggtgttcccactttttcagaatgggaccaggccctacggccccaatagcagaa

gtttg cggac ttctc ttccg tccca caagg gtgaa aaagt cttac cctgg tccgg gatgc cgggg ttatc gtctt

gcttctctaacccaggactgctcccctcaattcctcccaatatgctgaccgacagctcgacctcacctgggggcg

cgaag agatt gggtc ctgac gaggg gagtt aagga gggtt atacg actgg ctgtc gagct ggagt ggacc cccgc

IVS1 (+ 796 bp)

gatgattgtcggccttccacagaccctcgcgcttgccaggattagggtgttcgcgcgcattgtgggtaggggtgt

ctact aacag ccgga aggtg tctgg gagcg cgaac ggtcc taatc ccaca agcgc gcgta acacc catcc ccaca

ggaggaagggatccagaaatcttaagtattaacttagattagtgttagcaaggaagccgtcacattttatttagc

cctcc ttccc taggt cttta gaatt cataa ttgaa tctaa tcaca atcgt tcctt cggca gtgta aaata aatcg

cgggacactctgacagtttgtgccgactgctatttttgatcaaggctattttgcccacttgtctattttgtggcc

gccct gtgag actgt caaac acggc tgacg ataaa aacta gttcc gataa aacgg gtgaa cagat aaaac accgg

caattgtctgttttgctaacatcagaaagttataatgaaataatctgcaaaaaatgtaaggtgctagaaaaccaa

gttaa cagac aaaac gattg tagtc tttca atatt acttt attag acgtt tttta cattc cacga tcttt tggtt

-27 -20 -10

taatactgtgtaccttgaaaatgctaatatacacctgttttgttacagAGGTGGAGCACAGTGAAAGAATTCAAG

attat gacac atgga acttt tacga ttata tgtgg acaaa acaat gtcTC CACCT CGTGT CACTT TCTTA AGTTC

T=Cys (3)

1 15 | 30 45 60

ATGCCACCTAATATAAACTGGAAAGAAATAATGAAAGTTGACCCAGATGACCTGCCCCGTCAAGAA

TAC GGT GGA TTA TAT TTG ACC TTT CTT TAT TAC TTT CAA CTG GGT CTA CTG GAC GGG GCA GTT CTT

MetProProAsnIleAsnTrpLysGluIleMetLysValAspProAspAspLeuProArgGlnGlu

M P P N I N W K E I M K V D P D D L P R Q E

1 5 10 15 20

75 90 102

GAACTGGCAGATAATTTATTGATTTCCTTATCCAAGgtgcttaattggtcaataataatagatatatacat

CTT GAC CGT CTA TTA AAT AAC TAA AGG AAT AGG TTC cacga attaa ccagt tatta ttatc tatat atgta

GluLeuAlaAspAsnLeuLeuIleSerLeuSerLys

E L A D N L L I S L S K

25 30 34

taacttatgattaatttattaataaaatatgaatttatttttttcagggacaactataattgtcacaatctggaa

attga atact aatta aataa ttatt ttata cttaa ataaa aaaag tccct gttga tatta acagt gttag acctt

IVS 2

103

gtgttcttatattttgcttgaaggttataaaatataaaacagttgcttttctgtttacttagGTGGAAGTA

ca caaga atata aaacg aactt ccaat atttt atatt ttgtc aacga aaaga caaat gaatc CAC CTT CAT

ValGluVal

V E V

35

120 135 150 165

AATGAGCTAAAAAGTGAAAAGCAAGAAAATGTGATACACCTTTTCAGAATTACTCAGTCACTAATG

TTA CTC GAT TTT TCA CTT TTC GTT CTT TTA CAC TAT GTG GAA AAG TCT TAA TGA GTC AGT GAT TAC

AsnGluLeuLysSerGluLysGlnGluAsnValIleHisLeuPheArgIleThrGlnSerLeuMet

N E L K S E K Q E N V I H L F R I T Q S L M

40 45 50 55

t (1)

180|

AAGgtttgtatgtagtaggttttaactataggtttggctattagtggaactataaaaatctgttcttatataa

TTC caaac ataca tcatc caaaa ttgat atcca aaccg ataat cacct tgata ttttt agaca agaat atatt

Lys

K

60

ggtaatctttgtgaaaatacctggtaatatctacatcaccactaaaaaatgcaatatatttaaatgtgaattaag

ccatt agaaa cactt ttatg gacca ttata gatgt agtgg tgatt tttta cgtta tataa attta cactt aattc

tattttagtgtataaaacattgctagtttctacttaaagtttctaaaagggtgtgtaggggaaatagaatgagta

ataaa atcac atatt ttgta acgat caaag atgaa tttca aagat tttcc cacac atccc cttta tctta ctcat

IVS 3 (+ 946 bp)

tgccactgcactccagcctgggtgacaaagtgaggccctatctcaaaagcaaaaaaaacaaaaacaaaaaccaaa

acggt gacgt gaggt cggac ccact gtttc actcc gggat agagt tttcg ttttt tttgt ttttg ttttt ggttt

aactatttattcagcaaatatttactgaacgtctccatgtgccagccattgctggcactaaggatcataacaaat

ttgat aaata agtcg tttat aaatg acttg cagag gtaca cggtc ggtaa cgacc gtgat tccta gtatt gttta

aaaacagaatttttattttcagtgcttacattccagtataaaggcatattgaaataacctttttttaatgtttag

ttttg tctta aaaat aaaag tcacg aatgt aaggt catat ttccg tataa cttta ttgga aaaaa attac aaatc

181 195 210 225 240

ATGAAAGCTCAAGAAGTGGAGCTGGCTTTGGAAGAAGTAGAAAAAGCTGGAGAAGAACAAGCAAAA

TAC TTT CGA GTT CTT CAC CTC GAC CGA AAC CTT CTT CAT CTT TTT CGA CCT CTT CTT GTT CGT TTT

MetLysAlaGlnGluValGluLeuAlaLeuGluGluValGluLysAlaGlyGluGluGlnAlaLys

M K A Q E V E L A L E E V E K A G E E Q A K

61 65 70 75 80

250

TTTGgtaagcaccttggaaaaagtttattatggtattaaataatgaattccatttgttcattaaactgtagaaa

AAA C cattc gtgga acctt tttca aataa tacca taatt tatta cttaa ggtaa acaag taatt tgaca tcttt

PheGlu

F E

84

attaaattatattctataaaatatatatattcagtttatttttaatatataacatttaataataaatatttctag

taatt taata taaga tattt tatat atata agtca aataa aaatt atata ttgta aatta ttatt tataa agatc

actcctattttatggatctgccatataatactttttgttaccttataatcatgatggactcttttaaaagaatta

tgagg ataaa atacc tagac ggtat attat gaaaa acaat ggaat attag tacta cctga gaaaa ttttc ttaat

IVS 4

attttgttattgaaatttatttaaaagtttgttttgtggtaactaatcaattaaaacgtttttcttttttttt

taa aacaa taact ttaaa taaat tttca aacaa aacac cattg attag ttaat tttgc aaaaa gaaaa aaaaa

insA (1)

251 255 | 270 285 297

aaaaaaatagAAAATCAATTAAAAACTAAAGTAATGAAACTGGAAAATGAACTGGAGgtatg tcttt

ttttt ttatc TT TTA GTT AAT TTT TGA TTT CAT TAC TTT GAC CTT TTA CTT GAC CTC catac agaaa

GluAsnGlnLeuLysThrLysValMetLysLeuGluAsnGluLeuGlu

E N Q L K T K V M K L E N E L E

84 85 90 95 99

ttgta ttccc tagga tgtaa ttgtc attaa tttta ttttg aattg ttttc aaatt ttaaa attat tgttg gctgg

aacat aaggg atcct acatt aacag taatt aaaat aaaac ttaac aaaag tttaa aattt taata acaac cgacc

aaaaa ttata aggat gattg taatc atggt tattt gttta ttctg tatat gttct acatg cctat tatgt gcctt

ttttt aatat tccta ctaac attag tacca ataaa caaat aagac atata caaga tgtac ggata ataca cggaa

atata gtact aagga ctgag catat ggttg tgaac aaaat aagaa gttaa ctgct ggatg gagct tatag tcttg

tatat catga ttcct gactc gtata ccaac acttg tttta ttctt caatt gacga cctac ctcga atatc agaac

IVS 5(+ 1898 bp)

gcatc tctgg gtggc tcagg aaaaa tttaa ggagt tatta gctgt gaact aacct taagt aagtt aaatt aaaaa

cgtag agacc caccg agtcc ttttt aaatt cctca ataat cgaca cttga ttgga attca ttcaa tttaa ttttt

aaaaa aagtt cttaa gctaa tatga tttta aatat ctgca ctgaa gtata atgca aattt aaatt cagca taatt

ttttt ttcaa gaatt cgatt atact aaaat ttata gacgt gactt catat tacgt ttaaa tttaa gtcgt attaa

atttg cttgt tgttg actca tttga acctc aaaat ataat gggat taatt tatac tttgg gttta ttact ttaag

taaac gaaca acaac tgagt aaact tggag tttta tatta cccta attaa atatg aaacc caaat aatga aattc

298 315 330 345 360

ATGGCTCAGCAGTCTGCAGGTGGACGAGATACTCGGTTTTTACGTAATGAAATTTGCCAACTTGAA

TAC CGA GTC GTC AGA CGT CCA CCT GCT CTA TGA GCC AAA AAT GCA TTA CTT TAA ACG GTT GAA CTT

MetAlaGlnGlnSerAlaGlyGlyArgAspThrArgPheLeuArgAsnGluIleCysGlnLeuGlu

M A Q Q S A G G R D T R F L R N E I C Q L E

100 105 110 115 120

375 390 405 420

AAACAATTAGAACAAAAAGATAGAGAATTGGAGGACATGGAAAAGGAGTTGGAGAAAGAGAAGAAA

TTT GTT AAT CTT GTT TTT CTA TCT CTT AAC CTC CTG TAC CTT TTC CTC AAC CTC TTT CTC TTC TTT

LysGlnLeuGluGlnLysAspArgGluLeuGluAspMetGluLysGluLeuGluLysGluLysLys

K Q L E Q K D R E L E D M E K E L E K E K K

125 130 135 140

435 441

GTTAATGAGCAA gtaaagcactttttttttccatgaatcttcactgttcaagttacctggctttttattatt

CAA TTA CTC GTT cattt cgtga aaaaa aaagg tactt agaag tgaca agttc aatgg accga aaaat aataa

ValAsnGluGln

V N E Q

145 147

attggtaacaatatcaatttttatattgtatgttatatttgaaaaatgatgtacacttatctctaaggttttata

taacc attgt tatag ttaaa aatat aacat acaat ataaa ctttt tacta catgt gaata gagat tccaa aatat

tcactgttcattttgtcatcaccaattttaaaatataatggtacttctagtgaatatgacttgaagattaattct

agtga caagt aaaac agtag tggtt aaaat tttat attac catga agatc actta tactg aactt ctaat taaga

ttatatttggaagtacatttttctcaggacatcaaacttgttacctaaaattaatgcttttgtctggaagattgg

aatat aaacc ttcat gtaaa aagag tcctg tagtt tgaac aatgg atttt aatta cgaaa acaga ccttc taacc

IVS 6 (+4914 bp)

taaaaatacaaaaattagccagttatggtaatgcatgccagtaattccagctactcggtaggctgaggtgggaga

atttt tatgt tttta atcgg tcaat accat tacgt acggt catta aggtc gatga gccat ccgac tccac cctct

attgcttgaaccgggaggcagaggttgcagtgagccgagatcgcaccactgtactccagcctaggcgacaaagac

taacg aactt ggccc tccgt ctcca acgtc actcg gctct agcgt ggtga catga ggtcg gatcc gctgt ttctg

tttgtctcaaaaaaaaaaaaaattactgctgaattttatcttcttcttatttattttttttttttactattttag

aaaca gagtt ttttt ttttt ttaat gacga cttaa aatag aagaa gaata aataa aaaaa aaaaa tgata aaatc

442 450 465 480 495

TTGGCTCTTCGAAATGAGGAGGCAGAAAATGAAAACAGCAAATTAAGAAGAGAGgtaaaaaattttagt

AAC CGA GAA GCT TTA CTC CTC CGT CTT TTA CTT TTG TCG TTT AAT TCT TCT CTC cattt tttaa aatca

LeuAlaLeuArgAsnGluGluAlaGluAsnGluAsnSerLysLeuArgArgGlu

L A L R N E E A E N E N S K L R R E

148 150 155 160 165

agttgtggtggttcaacaaaggtacttattaaaataagtacctaagtttacataaatttatattttaaccaggac

tcaac accac caagt tgttt ccatg aataa tttta ttcat ggatt caaat gtatt taaat ataaa attgg tcctg

tggagtcttctaagtaactgatgttttcagactgattttatggtatgactttgtctcagggaaatagaaaacaaa

acctc agaag attca ttgac tacaa aagtc tgact aaaat accat actga aacag agtcc cttta tcttt tgttt

gcaaaatgtgaggccattaagtattacattcatctcaggtctatgcgggtaaatctttttttgttgttttataag

cgttt tacac tccgg taatt cataa tgtaa gtaga gtcca gatac gccca tttag aaaaa aacaa caaaa tattc

IVS 7

ataagccattctttgctagttttctaattgaatagatgactggatttctattcttatttctcttacccagaatc

tatt cggta agaaa cgatc aaaag attaa cttat ctact gacct aaaga taaga ataaa gagaa tgggt cttag

ctttaaaattttttgttacttgtggaatcttataaattctgattatcatttggttctactgagccaaataatgtt

gaaat tttaa aaaac aatga acacc ttaga atatt taaga ctaat agtaa accaa gatga ctcgg tttat tacaa

tgtacattgtttattctgatagaagttcttaagtttctaacataattgaaatattatttgttttggtagataatt

acatg taaca aataa gacta tcttc aagaa ttcaa agatt gtatt aactt tataa taaac aaaac catct attaa

agtattctttctttggttattcaagataatatgcatcattttcccaaaatttttttgttttctttagtttctgat

tcata agaaa gaaac caata agttc tatta tacgt agtaa aaggg tttta aaaaa acaaa agaaa tcaaa gacta

496

tattatttttaattatgtattacctttctcatttctaattaccgttttcctgtccttttctgtagAACAAACGT

ataat aaaaa ttaat acata atgga aagag taaag attaa tggca aaagg acagg aaaag acatc TTG TTT GCA

AsnLysArg

N K R

166

510 516

CTAAAGAAAAAGgtgaggctttaagtgtggtgaaatcttgggaatttaaaatatgttgtgagagcactattt

GAT TTC TTT TTC cactc cgaaa ttcac accac tttag aaccc ttaaa tttta tacaa cactc tcgtg ataaa

LeuLysLysLys

L K K K

170 172

IVS 8

517 525

agaggatatgattttgttattctgaatagttttgtaattgaatgttgtgtttggttaccttcagAATGAACAA

tctc ctata ctaaa acaat aagac ttatc aaaac attaa cttac aacac aaacc aatgg aagtc TTA CTT GTT

AsnGluGln

N E Q

173 175

540 555 570 585

CTTTGTCAGGATATTATTGACTACCAGAAACAAATAGATTCACAGAAAGAAACACTTTTATCAAGA

GAA ACA GTC CTA TAA TAA CTG ATG GTC TTT GTT TAT CTA AGT GTC TTT CTT TGT GAA AAT AGT TCT

LeuCysGlnAspIleIleAspTyrGlnLysGlnIleAspSerGlnLysGluThrLeuLeuSerArg

L C Q D I I D Y Q K Q I D S Q K E T L L S R

180 185 190 195

600 615 630 645

AGAGGGGAAGACAGTGACTACCGATCACAGTTGTCTAAAAAAAACTATGAGCTTATCCAATATCTT

TCT CCC CTT CTG TCA CTG ATG GCT AGT GTC AAC AGA TTT TTT TTG ATA CTC GAA TAG GTT ATA GAA

ArgGlyGluAspSerAspTyrArgSerGlnLeuSerLysLysAsnTyrGluLeuIleGlnTyrLeu

R G E D S D Y R S Q L S K K N Y E L I Q Y L

200 205 210 215

660 669

GATGAAATTCAGgtaaaatggctagaagtcaattcagagcaatggttcctaaaaactttaatttcattacaa

CTA CTT TAA GTC cattt taccg atctt cagtt aagtc tcgtt accaa ggatt tttga aatta aagta atgtt

AspGluIleGln

D E I Q

220 223

tgtaaatataatatttagccctacatgtaaattccctggtataaatctgtcactatgtacttgtaaaatgtgaaa

acatt tatat tataa atcgg gatgt acatt taagg gacca tattt agaca gtgat acatg aacat tttac acttt

taaattacatctttgaagttgcaactttttagccatttttatatttgcctgtcttggtcattaagaacaattgag

attta atgta gaaac ttcaa cgttg aaaaa tcggt aaaaa tataa acgga cagaa ccagt aattc ttgtt aactc

IVS 9

gtccttatgtactattttcttgattcaatttgatttaattggtcaatgccaattagtaaaggtctataaag

c aggaa tacat gataa aagaa ctaag ttaaa ctaaa ttaac cagtt acggt taatc atttc cagat atttc

aattctctttttttctagaggacacttatggctgcgtttaattttaatttggtttaaatttcagtttttttaaaa

ttaag agaaa aaaag atctc ctgtg aatac cgacg caaat taaaa ttaaa ccaaa tttaa agtca aaaaa atttt

del (1)

670 675 || 690 705

ttactttttaattatagtgtctttaacttttttagACTTTAACAGAAGCTAATGAGAAAATTGAAGTTCAG

aatga aaaat taata tcaca gaaat tgaaa aaatc TGA AAT TGT CTT CGA TTA CTC TTT TAA CTT CAA GTC

ThrLeuThrGluAlaAsnGluLysIleGluValGln

T L T E A N E K I E V Q

224225 230 235

720 735 750 765

AATCAAGAAATGAGAAAAAATTTAGAAGAGTCTGTACAGGAAATGGAGAAGATGACTGATGAATAT

TTA GTT CTT TAC TCT TTT TTA AAT CTT CTC AGA CAT GTC CTT TAC CTC TTC TAC TGA CTA CTT ATA

AsnGlnGluMetArgLysAsnLeuGluGluSerValGlnGluMetGluLysMetThrAspGluTyr

N Q E M R K N L E E S V Q E M E K M T D E Y

240 245 250 255

780 795 810 825

AATAGAATGAAAGCTATTGTGCATCAGACAGATAATGTAATAGATCAGTTAAAAAAAGAAAACGAT

TTA TCT TAC TTT CGA TAA CAC GTA GTC TGT CTA TTA CAT TAT CTA GTC AAT TTT TTT CTT TTG CTA

AsnArgMetLysAlaIleValHisGlnThrAspAsnValIleAspGlnLeuLysLysGluAsnAsp

N R M K A I V H Q T D N V I D Q L K K E N D

260 265 270 275

840 852

CATTATCAACTTCAAgtaagaattacttttagaataacttatttattcagacttcatattatctcattac

GTA ATA GTT GAA GTT cattc ttaat gaaaa tctta ttgaa taaat aagtc tgaag tataa tagag taatg

HisTyrGlnLeuGln

H Y Q L Q

280 284

tatttatttgacactagaaagtactttttctaggatgtgaatttttgtctgtctttttaatagtgtaatatcttg

ataaa taaac tgtga tcttt catga aaaag atcct acact taaaa acaga cagaa aaatt atcac attat agaac

tcatgttggtatatttgtccatatgtgtttctccaatcacctcacaaacactaatttttgcaatttaggatatat

agtac aacca tataa acagg tatac acaaa gaggt tagtg gagtg tttgt gatta aaaac gttaa atcct atata

aaatg atact tgaat gaatg tgtag atagc agtca ttatg gggtt ttcta taaaa gacta ctgaa aatcc tgtgg

tttac tatga actta cttac acatc tatcg tcagt aatac cccaa aagat atttt ctgat gactt ttagg acacc

IVS 10 (+153 bp)

ataagatgcagaaactattaaatgtcacctataattccaggatgacttcaatgataaatacacatatgtaatgta

tattc tacgt ctttg ataat ttaca gtgga tatta aggtc ctact gaagt tacta tttat gtgta tacat tacat

atgtatccgtatgtatgtgtatataagtatgaatacgtatgtgtgtgtatgtagatatatttatatatataatgt

tacat aggca tacat acaca tatat tcata cttat gcata cacac acata catct atata aatat atata ttaca

atatgtaaatatgcacaggtgtaaatatatgttacatcagtttgcaacaactcttgaaataactttgtcttttag

tatac attta tacgt gtcca cattt atata caatg tagtc aaacg ttgtt gagaa cttta ttgaa acaga aaatc

853 870 885 900 915

GTGCAGGAGCTTACAGATCTTCTGAAATCAAAAAATGAAGAAGATGATCCAATTATGGTAGCTGTC

CAC GTC CTC GAA TGT CTA GAA GAC TTT AGT TTT TTA CTT CTT CTA CTA GGT TAA TAC CAT CGA CAG

ValGlnGluLeuThrAspLeuLeuLysSerLysAsnGluGluAspAspProIleMetValAlaVal

V Q E L T D L L K S K N E E D D P I M V A V

285 290 295 300 305

930 942

AATGCAAAAGTAGAAGAATGGAAGgtattttttttcaattgacataataactttttctttttgtatttt

TTA CGT TTT CAT CTT CTT ACC TTC cataa aaaaa agtta actgt attat tgaaa aagaa aaaca taaaa

AsnAlaLysValGluGluTrpLys

N A K V E E W K

310 314

agatttaaattttagtcttatttttctttaaatgtcttatactggtttataacacgtttattagggtttttaaac

tctaa attta aaatc agaat aaaaa gaaat ttaca gaata tgacc aaata ttgtg caaat aatcc caaaa atttg

ataagtttattttatttattggttagaaaagctctagaactgtcctttttgatctctagctaatttgttattgaa

tattc aaata aaata aataa ccaat ctttt cgaga tcttg acagg aaaaa ctaga gatcg attaa acaat aactt

tgacctctttcacatcaatgagtttaactttaaactttttgatagaagtctaactccaaaatatatttggcatct

actgg agaaa gtgta gttac tcaaa ttgaa atttg aaaaa ctatc ttcag attga ggttt tatat aaacc gtaga

IVS 11 (+2012 bp)

aaaagaaaattcggtatatattttaaaatcattttctatttgaatttcaggttgtatatacaaaaggaacagaga

ttttc tttta agcca tatat aaaat tttag taaaa gataa actta aagtc caaca tatat gtttt ccttg tctct

ttatgccagtagttgctcatactttctcatttcaaataatttttattttctgtatcataaatctactaacggtgt

aatac ggtca tcaac gagta tgaaa gagta aagtt tatta aaaat aaaag acata gtatt tagat gattg ccaca

ttattatttatgataatgaagaatgttttattaactttccttttgcataacagattctattgtgtttatttctag

aataa taaat actat tactt cttac aaaat aattg aaagg aaaac gtatt gtcta agata acaca aataa agatc

943 960 975 990 1005

CTAATTTTGTCTTCTAAAGATGATGAAATTATTGAGTATCAGCAAATGTTACATAACCTAAGGGAG

GAT TAA AAC AGA AGA TTT CTA CTA CTT TAA TAA CTC ATA GTC GTT TAC AAT GTA TTG GAT TCC CTC

LeuIleLeuSerSerLysAspAspGluIleIleGluTyrGlnGlnMetLeuHisAsnLeuArgGlu

L I L S S K D D E I I E Y Q Q M L H N L R E

315 320 325 330 335

1020 1035 1050 1065

AAACTTAAGAATGCTCAGCTTGATGCTGATAAAAGTAATGTTATGGCTCTACAGCAGgtaaaatctt

TTT GAA TTC TTA CGA GTC GAA CTA CGA CTA TTT TCA TTA CAA TAC CGA GAT GTC GTC cattt tagaa

LysLeuLysAsnAlaGlnLeuAspAlaAspLysSerAsnValMetAlaLeuGlnGln

K L K N A Q L D A D K S N V M A L Q Q

340 345 350 355

aacagaattttgtttatcaaccagttttattacagttggaactctgaacgatgtcttttatttattatatcatca

ttgtc ttaaa acaaa tagtt ggtca aaata atgtc aacct tgaga cttgc tacag aaaat aaata atata gtagt

gtgcctagtgtagcggctggtactaccaagtgtataataatgtcttttgaaatttcttctaccacctggtcccaa

cacgg atcac atcgc cgacc atgat ggttc acata ttatt acaga aaact ttaaa gaaga tggtg gacca gggtt

taaaaaattagaattaagtttagatcacggattagacttagaactagagttactgtgtttatttttctatgttta

atttt ttaat cttaa ttcaa atcta gtgcc taatc tgaat cttga tctca atgac acaaa taaaa agata caaat

IVS 12 (+486 bp)

ttccagagtgttagccattatatccatctttcagtattggagtaacagcagtgtacctatcattgtgtattacag

aaggt ctcac aatcg gtaat atagg tagaa agtca taacc tcatt gtcgt cacat ggata gtaac acata atgtc

ttgaagtgtacaaaatggtaaaaggcatacttgtacccacaagaaaatatgttctacagtcttgttgaaaaaaat

aactt cacat gtttt accat tttcc gtatg aacat gggtg ttctt ttata caaga tgtca gaaca acttt tttta

cagacgtacttttttccttacctttttaggttaatattcatgaagggatatatattgttttaaaatattttatag

gtctg catga aaaaa ggaat ggaaa aatcc aatta taagt acttc cctat atata acaaa atttt ataaa atatc

1066 1080 1095 1110 1125

GGTATACAGGAACGAGACAGTCAAATTAAGATGCTCACCGAACAAGTAGAACAATATACAAAAGAA

CCA TAT GTC CTT GCT CTG TCA GTT TAA TTC TAC GAG TGG CTT GTT CAT CTT GTT ATA TGT TTT CTT

GlyIleGlnGluArgAspSerGlnIleLysMetLeuThrGluGlnValGluGlnTyrThrLysGlu

G I Q E R D S Q I K M L T E Q V E Q Y T K E

356 360 365 370 375

1140 1155 1170 1185 1189

ATGGAAAAGAATACTTGTATTATTGAAGATTTGAAAAATGAGCTCCAAAGAAACAAAGgtatttttat

TAC CTT TTC TTA TGA ACA TAA TAA CTT CTA AAC TTT TTA CTC GAG GTT TCT TTG TTT C cataa aaata

MetGluLysAsnThrCysIleIleGluAspLeuLysAsnGluLeuGlnArgAsnLysGly

M E K N T C I I E D L K N E L Q R N K G

380 385 390 395 397

aaatatatagttattttatatacaattatgtttttaacgactttatttttattaaaataaaatgtcaagtcaata

tttat atatc aataa aatat atgtt aatac aaaaa ttgct gaaat aaaaa taatt ttatt ttaca gttca gttat

ttgagttttctccatttgaattttatattttcaaaaaattgtacaagatatttattattatacttatattactag

aactc aaaag aggta aactt aaaat ataaa agttt tttaa catgt tctat aaata ataat atgaa tataa tgatc

tgcttacatttgtaaatgatggatgcattttctattatttttctcctctggtgaaaattacattaacgtt tatta

acgaa tgtaa acatt tacta cctac gtaaa agata ataaa aagag gagac cactt ttaat gtaat tgcaa ataat

IVS 13 (+ 3619 bp)

ttaaaatccataccccttcagctaagaaggttttactgaacttcagttttttagtaaattgtattagtaaaacca

aattt taggt atggg gaagt cgatt cttcc aaaat gactt gaagt caaaa aatca tttaa cataa tcatt ttggt

aaacaaaactttcatcttacaaatataaaatgacaactttaaaggatttttttttaatggcataccacttttctt

tttgt tttga aagta gaatg tttat atttt actgt tgaaa tttcc taaaa aaaaa ttacc gtatg gtgaa aagaa

gccaccatgttgggatcactgatttgaaggaataagtagtcaattcaattcatgatttttgtttttactctgtag

cggtg gtaca accct agtga ctaaa cttcc ttatt catca gttaa gttaa gtact aaaaa caaaa atgag acatc

1190 1200 1215 1230 1245

GTGCTTCAACCCTTTCTCAACAGACTCATATGAAAATTCAGTCAACGTTAGACATTTTAAAAGAG

CA CGA AGT TGG GAA AGA GTT GTC TGA GTA TAC TTT TAA GTC AGT TGC AAT CTG TAA AAT TTT CTC

GlyAlaSerThrLeuSerGlnGlnThrHisMetLysIleGlnSerThrLeuAspIleLeuLysGlu

G A S T L S Q Q T H M K I Q S T L D I L K E

397 400 405 410 415

1260 1275 1290 1305 1320

AAAACTAAAGAGGCTGAGAGAACAGCTGAACTGGCTGAGGCTGATGCTAGGGAAAAGGATAAAGAA

TTT TGA TTT CTC CGA CTC TCT TGT CGA CTT GAC CGA CTC CGA CTA CGA TCC CTT TTC CTA TTT CTT

LysThrLysGluAlaGluArgThrAlaGluLeuAlaGluAlaAspAlaArgGluLysAspLysGlu

K T K E A E R T A E L A E A D A R E K D K E

420 425 430 435 440

1335 1350 1359

TTAGTTGAGGCTCTGAAGAGGTTAAAAGATTATGAATCGgtatgtatttttatcttgtcattcaaggag

AAT CAA CTC CGA GAC TTC TCC AAT TTT CTA ATA CTT AGC catac ataaa aatag aacag taagt tcctc

LeuValGluAlaLeuLysArgLeuLysAspTyrGluSer

L V E A L K R L K D Y E S

445 450 453

cttagaattattcttgccattcacagactattctgtgctatttactgcataccatttaaaaaacattccataagt

gaatc ttaat aagaa cggta agtgt ctgat aagac acgat aaatg acgta tggta aattt tttgt aaggt attca

atcttttgataaagattatcctcattaatttatactaaactattgaaacctttgagcatttactttttgccagaa

tagaa aacta tttct aatag gagta attaa atatg atttg ataac tttgg aaact cgtaa atgaa aaacg gtctt

ttgttttcaaacttttgatcacagtgatttgtccaaataatcagttttggtgaagcagcaggattactttttttt

aacaa aagtt tgaaa actag tgtca ctaaa caggt ttatt agtca aaacc acttc gtcgt cctaa tgaaa aaaaa

IVS 14 (+ 240 bp )

actttgcctttaggatattatactggaaagttttaactgttgcatattacatcattattattactggatttggtt

tgaaa cggaa atcct ataat atgac ctttc aaaat tgaca acgta taatg tagta ataat aatga cctaa accaa

tataaaagcacaataaaaaaccagtgtaatgatataaattataggcatatgtacattttcctttagacttagtaa

atatt ttcgt gttat ttttt ggtca catta ctata tttaa tatcc gtata catgt aaaag gaaat ctgaa tcatt

aaaaaaaatcatgaacttgataaatttattcaagtaaaccatgttatattttaaattaaattggatatttttcag

ttttt tttag tactt gaact attta aataa gttca tttgg tacaa tataa aattt aattt aacct ataaa aagtc

1360 1365 1380 1395 1410 1425

GGAGTATATGGTTTAGAAGATGCTGTCGTTGAAATAAAGAATTGTAAAAACCAAATTAAAATAAGA

CCT CAT ATA CCA AAT CTT CTA CGA CAG CAA CTT TAT TTC TTA ACA TTT TTG GTT TAA TTT TAT TCT

GlyValTyrGlyLeuGluAspAlaValValGluIleLysAsnCysLysAsnGlnIleLysIleArg

G V Y G L E D A V V E I K N C K N Q I K I R

454 455 460 465 470 475

1440 1455 1470 1485

GATCGAGAGATTGAAATATTAACAAAGGAAATCAATAAACTTGAATTGAAGATCAGTGATTTCCTT

CTA GCT CTC TAA CTT TAT AAT TGT TTC CTT TAG TTA TTT GAA CTT AAC TTC TAG TCA CTA AAG GAA

AspArgGluIleGluIleLeuThrLysGluIleAsnLysLeuGluLeuLysIleSerAspPheLeu

D R E I E I L T K E I N K L E L K I S D F L

480 485 490 495

1500 1515 1522

GATGAAAATGAGGCACTTAGAGAGCGTGTGGgtaagccatgttttaagttacatagtttgcgcaacctgat

CTA CTT TTA CTC CGT GAA TCT CTC GCA CAC C cattc ggtac aaaat tcaat gtatc aaacg cgttg gacta

AspGluAsnGluAlaLeuArgGluArgValGly

D E N E A L R E R V G

500 505 508

ttacaagtctttttttttaatttaaattttgtttattattatttattaagtagtttaatgcttttttcaaatgct

aatgt tcaga aaaaa aaatt aaatt taaaa caaat aataa taaat aattc atcaa attac gaaaa aagtt tacga

tttataaaacatttaatacaaataaaagtggagctaacctgattgaagtggaatcagattttatggggttggagt

aaata ttttg taaat tatgt ttatt ttcac ctcga ttgga ctaac ttcac cttag tctaa aatac cccaa cctca