The Sequence Is Given According to Genebank: AF039855, U20477-88, U20510

last update: 18.02.2007

RPE65

The sequence is given according to Genebank: AF039855, U20477-88, U20510.

Exons are taken from (16) and sequences were completed with additional data obtained in the editor’s lab

Primers are given according to (2) and (15)

Nucleotide numbering

Aminoacid numbering

Sequence variations (Polymorphism,rare variant, LCA2, ARRP,LCA2 or ARRP)

Mutations detectable by a mutation micro array are given in italics, and shown in grey if no reference can be allocated to these

-170 -160 -150 -140 -130 -120 -110

|------> E1-f (2)

|------> RPE65-1f (15)

gaga gctga aagca acttc tgttc cccct ccctc agctg aaggg gtggg gaagg gcctc ccaaa gccat aactc

ctct cgact ttcgt tgaag acaag gggga gggag tcgac ttccc caccc cttcc cggag ggttt cggta ttgag

Transcription start

-100 -90 -80 -70 -60 | -50 -40 -30

ctttt aaggg attta gaagg cataa aaagg cccct ggctg agaac ttcct tcttc attct gcagt tggtg ccaga

gaaaa ttccc taaat cttcc gtatt tttcc gggga ccgac tcttg aagga agaag taaga cgtca accac ggtct

C=Thr(1,14) a (2,3,13,7,17,23,24) (7) a

-20 -10 1| 11 | |

actct ggatc ctgaa ctgga agaaa ATG TCT ATC CA gtaag tatct ctggg agact ttttt aaaac acctt

tgaga cctag gactt gacct tcttt TAC AGA TAG GT cattc ataga gaccc tctga aaaaa ttttg tggaa

M S I Q

Met Ser Ile Gln

1 2 3 4

catgg attca tgata aatgt gctat ttcaa gggct cctga agaga a

gtacc taagt actat ttaca cgata acatt cccga ggact tctct t

<------ag------| RPE65-1r (15)

<------| E1-R (2)

IVS 1

|------> E2-F (2)

|------> RPE65-2f (15)

t ctatc tctgc ggact ttgag catca acatg ggctt cttcc ttatt cttcc accat ttcag

a gatag agacg cctga aactc gtagt tgtac ccgaa gaagg aataa gaagg tggta aagtc

del (5)

C=Phe (1) | C=Pro (6,25)

12 15 30 45 | |-|60 | 75

G GTT GAG CAT CCT GCT GGT GGT TAC AAG AAA CTG TTT GAA ACT GTG GAG GAA CTG TCC TCG CCG

C CAA CTC GTA GGA CGA CCA CCA ATG TTC TTT GAC AAA CTT TGA CAC CTC CTT GAC AGG AGC GGC

Q V E H P A G G Y K K L F E Thr V E E L S S P

Gln Val Glu His Pro Ala Gly Gly Tyr Lys Lys Leu Phe Glu Thr Val Glu Glu Leu Ser Ser Pro

4 5 10 15 20 25

insT (2,14)

| 94

CTC ACA GCT CAT GTA ACA G gttgg tctcg cccat cttga agcca tcctc tttta tgtca gttcc tctct

GAG TGT CGA GTA CAT TGT C caacc agagc gggta gaact tcggt aggag aaaat acagt caaggagaga

L T A H V T G <------

Leu Thr Ala His Val Thr Gly <-x------

30 32

tctct ggctt cctat tcctt ggcgt ctctc agtgc agact ccccc tgtgg gtcac aggga gaggg atcag gtggt

agaga ccgaa ggata aggaa ccgca gagag tctcg tctga ggggg acacc cagtg tccct ctccc tagtc cacca

------| RPE65-2r (15)

------| E2-R (2)

ttggg ctttt tatag caaga accca ttttc tttca ttcgc cttta cttta

aaccc gaaaa atatc gttct tgggt aaaag aaagt aagcg gaaat gaaat

IVS 2

agggc tggaa atgaa aatca ctgcc agctc tatga ggaag aagct gccca atcag gctgc tgata

tcccg acctt tactt ttagt gacgg tcgag atact ccttc ttaga cgggt tagtc agacg actat

|------> E3-F (2) (22) t

|------> RPE65-3f (15) |

tactc tgcct tacca aggac aagcc tagcc caagg caggg ataag aagca atgtt ctgtc tcccc ttcat cacag

atgag acgga atggt tcctg ttcgg atcgg gttcc gtccc tattc ttcgt tacaa gacag agggg aagta gtgtc

del (27) A=Ser (1,17,23,24)

T=Val (27) |------| | (17) A=Gln delG (13,23,24)

| 105 | | | | 135 | 150

GC AGG ATC CCC CTC TGG CTC ACC GGC AGT CTC CTT CGA TGT GGG CCA GGA CTC TTT GAA GTT GGA

CG TCC TAG GGG GAG ACC GAG TGG CCG TCA GAG GAA GCT ACA CCC GGT CCT GAG AAA CTT CAA CCT

G R I P L W L T G S L L R C G P G L F E V G

Gly Arg Ile Pro Leu Trp Leu Thr Gly Ser Leu Leu Arg Cys Gly Pro Gly Leu Phe Glu Val Gly

32 35 40 45 50

del ins tt (6)

| T=Tyr (6)

T=ter (3) | | T=Val

165 180 | 195 |-| | 225

TCT GAG CCA TTT TAC CAC CTG TTT GAT GGG CAA GCC CTC CTG CAC AAG TTT GAC TTT AAA GAA GGA

AGA CTC GGT AAA ATG GTG GAC AAA CTA CCC GTT CGG GAG GAC GTG TTC AAA CTG AAA TTT CTT CCT

S E P F Y H L F D G Q A L L H K F D F K E G

Ser Glu Pro Phe Tyr His Leu Phe Asp Gly Gln Ala Leu Leu His Lys Phe Asp Phe Lys Glu Gly

55 60 65 70 75

A=Val (17)

| C=His (14)

| | 240 245

CAT GTC ACA TAC CAC AGA AG gtaaa gcagc actcc atgcc actcc tcctc ctcaa agtag ggcct agctt

GTA CAG TGT ATG GTG TCT TC cattt cgtcg tgagg tacgg tgagg aggag gagtt tcatc ccgga tcgaa

H V T Y H R R RPE65-3r (15) <------|

His Val Thr Tyr His Arg Arg

80 82

ggctc ctcct cccat gtgag ttttc acctc tgaac tcagg aggca accta tatac ccact ttctt ctcac aatgt

ccgag gagga gggta cactc aaaag tggag acttg agtcc tccgt tggat atatg ggtga aagaa gagtg ttaca

<------| E3-R (2)

acctg ggcca gtgtg tctgc atgga tacga gggaa catta tcatg

tggac ccggt cacac agacg tacct atgct ccctt gtaat agtac

IVS 3

taata aaacc cttta ttctt catgt tgtgc attta tgatt gtgac ttgat gagga cacat agaat

attat tttgg gaaat aagaa gtaca acacg taaat actaa cactg aacta ctcct gtgta tctta

|------> E4-F (2)

|------> RP4f (15)

ggcca ttcta agctc cacat gggct gtacg gattg ctcct gtcta tactc ttccc tatgt ttcaa tgtcc ttcag

ccggt aagat tcgag gtgta cccga catgc ctaac gagga cagat atgag aaggg ataca aagtt acagg aagtc

T=Trp (1,14)

|A=Gln (8,14,23,24,17)

|G=Pro del20bp (13,14,18)

|ins A |------|

|| | ter=T (19)

A=His (14) || C=Gln (14)(23,24,1,14 Lys=A 5)

246 | 270 || | | 300 | |

G TTC ATC CGC ACT GAT GCT TAC GTA CGG GCA ATG ACT GAG AAA AGG ATC GTC ATA ACA GAA TTT

C AAG TAG GCG TGA CTA CGA ATG CAT GCC CGT TAC TGA CTC TTT TCC TAG CAG TAT TGT CTT AAA

R F I R T D A Y V R A M T E K R I V I T E F

Arg Phe Ile Arg Thr Asp Ala Tyr Val Arg Ala Met Thr Glu Lys Arg Ile Val Ile Thr Glu Phe

82 85 90 95 100

T=Val t (5)

| 315 330 345 353 |

GGC ACC TGT GCT TTC CCA GAT CCC TGC AAG AAT ATA TTT TCC AG gttac tgaac ccaaa ctgaa tgtta

CCG TGG ACA CGA AAG GGT CTA GGG ACG TTC TTA TAT AAA AGG TC caatg acttg ggttt gactt acaat

G T C A F P D P C K N I F S R

Gly Thr Cys Ala Phe Pro Asp Pro Cys Lys Asn Ile Phe Ser Arg

105 110 115 118

ctcaa gacat tttat attag ccctt tttct ctcat tttta tatta gccct ttttc tctc

gagtt ctgta aaata taatc gggaa aaaga gagta aaaat ataat cggga aaaag agag

RPE65-4r <------|

IVS 4

ter=T (14,23,24)

|------> RPE65-5f (15) 354 360 | 375

ggc ttgaa aatta ctgga ctgaa aaatt cattt gtttc tacag G TTT TTT TCT TAC TTT CGA GGA GTA

ccg aactt ttaat gacct gactt tttaa gtaaa caaag atgtc C AAA AAA AGA ATG AAA GCT CCT CAT

R F F S Y F R G V

Arg Phe Phe Ser Tyr Phe Arg Gly Val

118 120 125

(22) Asp=T

A=Thr (1,14) G=Asp(17) |

| C=Leu (1) |T=Tyr(1) |

390 | | 405 420 || 435 |

GAG GTT ACT GAC AAT GCC CTT GTT AAT GTC TAC CCA GTG GGG GAA GAT TAC TAC GCT TGC ACA GAG

CTC CAA TGA CTG TTA CGG GAA CAA TTA CAG ATG GGT CAC CCC CTT CTA ATG ATG CGA ACG TGT CTC

E V T D N A L V N V Y P V G E D Y Y A C T E

Glu Val Thr Asp Asn Ala Leu Val Asn Val Tyr Pro Val Gly Glu Asp Tyr Tyr Ala Cys Thr Glu

130 135 140 145

ins g

450 465 480 495|

ACC AAC TTT ATT ACA AAG ATT AAT CCA GAG ACC TTG GAG ACA ATT AAG CAG gtggg acaca gtgct

TGG TTG AAA TAA TGT TTC TAA TTA GGT CTC TGG AAC CTC TGT TAA TTC GTC caccc tgtgt cacga

T N F I T K I N P E T L E T I K Q

Thr Asn Phe Ile Thr Lys Ile Asn Pro Glu Thr Leu Glu Thr Ile Lys Gln

150 155 160 165

aggtg atgtt cagga attta gaatt tggaa cttaa aatta attca ccaac ataaa ttatt catgc tgcga atgta

tccac tacaa gtcct taaat cttaa acctt gaatt ttaat taagt ggttg tattt aataa gtacg acgct tacat

RPE65-5r (15) <------t-| <------

tgatt ctaac ttgat gagga cacac agaat gacca ttcca agctc caaat

actaa gattg aacta ctcct gtgtg tctta ctggt aaggt tcgag gttta

------| E5-R (2)

IVS 5

agagg gtaga atcca gagag atggg aagaa agaga agtgc actta ggatg agagt tcaag gggta gtgat

tctcc catct taggt ctctc taccc ttctt tctct tcacg tgaat cctac tctca agttc cccat cacta

|------> R6-F (2)

|------> RPE65-6f (15)

gacct cagac ctagg gacaa aggta taatg tatct tcctt ctctc aactg gagga cattc acttt acttc cgtag

ctgga gtctg gatcc ctgtt tccat attac ataga aggaa gagag ttgac ctcct gtaag tgaaa tgaag gcatc

C=Asn (22)

T=Tyr (14) T=Tyr(1,23,24,17)

498 | 510 525 540 | 555

GTT GAT CTT TGC AAC TAT GTC TCT GTC AAT GGG GCC ACT GCT CAC CCC CAC ATT GAA AAT GAT GGA

CAA CTA GAA ACG TTG ATA CAG AGA CAG TTA CCC CGG TGA CGA GTG GGG GTG TAA CTT TTA CTA CCT

V D L C N Y V S V N G A T A H P H I E N D G

Val Asp Leu Cys Asn Tyr Val Ser Val Asn Gly Ala Thr Ala His Pro His Ile Glu Asn Asp Gly

166 170 175 180 185

T=Ala (17)

| G=Ser (1)

T=Tyr (17) | |del (14)

| 585 600 | ||-|

ACC GTT TAC AAT ATT GGT AAT TGC TTT GGA AAA AAT TTT TCA ATT GCC TAC AAC ATT GTA AAG ATC

TGG CAA ATG TTA TAA CCA TTA ACG AAA CCT TTT TTA AAA AGT TAA CGG ATG TTG TAA CAT TTC TAG

T V Y N I G N C F G K N F S I A Y N I V K I

Thr Val Tyr Asn Ile Gly Asn Cys Phe Gly Lys Asn Phe Ser Ile Ala Tyr Asn Ile Val Lys Ile

190 195 200 205

c (10)

| a (14)

630 643| |

CCA CCA CTG CAA GCA G gtgag tttac caatc tgtcc tcttc tgaaa ataag tgtct atatt gtgag aaagt

GGT GGT GAC GTT CGT C cactc aaatg gttag acagg agaag acttt tattc acaga tataa cactc tttca

P P L Q A D <-

Pro Pro Leu Gln Ala Asp <------

210 215

tactg tattg tgaga aaaaa taaga ggctg ttcca aagc...

atgac ataac actct ttttt attct ccgac aaggt ttcg...

------c ----| RPE65-6r (15)

------| E6-R (2)

IVS 6

del (20) (1) t

RPE65-7f |del (20) c (20) |t

|------> || | ||

ctg ttcta aatgc tttgt attaa aaaaa aaata agagg ctgtt ccaat gcctt ttaaa accac tttat ttcag

gac aagat ttacg aaaca taatt ttttt tttat tctcc gacaa ggttt cggaa aattt tggtg aaata aagtc

G=Gly (3,14,15,25) T=ter

| 660 675 690 | 705

AC AAG GAA GAT CCA ATA AGC AAG TCA GAG ATC GTT GTA CAA TTC CCC TGC AGT GAC CGA TTC AAG

TG TTC CTT CTA GGT TAT TCG TTC AGT CTC TAG CAA CAT GTT AAG GGG ACG TCA CTG GCT AAG TTC

D K E D P I S K S E I V V Q F P C S D R F K

Asp Lys Glu Asp Pro Ile Ser Lys Ser Glu Ile Val Val Gln Phe Pro Cys Ser Asp Arg Phe Lys

215 220 225 230 235

T=Asp (23,24) g (14,17)

| 720 725 |

CCA TCT TAC GTT CAT AG gtaac ttgaa ggcct gctat gaatc ttcag gaaaa ctcaa gttta aagat ttgct

GGT AGA ATG CAA GTA TC cattg aactt ccgga cgata cttag aagtc ctttt gagtt caaat ttcta aacga

P S Y V H S <------

Pro Ser Tyr Val His Ser

240 242

ttgcc tacct

aacgg atgga

------| RPE65-7b

IVS 7

...tt gatac caatc ctgat cacaa tattt ttttg cagaa aacta aattt aaaca taatt aattt catgt aggca

...aa ctatg gttag gacta gtgtt ataaa aaaac gtctt ttgat ttaaa tttgt attaa ttaaa gtaca tccgt

RPE65-8a |------>

ctgtt gattc ttgta actga gcata ccaca tatat acaaa tttgt ctgtg gcttg agaat cagcc ctttc attca

gacaa ctaag aacat tgact cgtat ggtgt atata tgttt aaaca gacac cgaac tctta gtcgg gaaag taagt

726 735 750 765

caagc ccatt tgtgt ttctg aacag T TTT GGT CTG ACT CCC AAC TAT ATC GTT TTT GTG GAG ACA CCA

gttcg ggtaa acaca aagac ttgtc A AAA CCA GAC TGA GGG TTG ATA TAG CAA AAA CAC CTC TGT GGT

S F G L T P N Y I V F V E T P

Ser Phe Gly Leu Thr Pro Asn Tyr Ile Val Phe Val Glu Thr Pro

242 245 250 255

del (2,14)

|------| 795 810 825

GTC AAA ATT AAC CTG TTC AAG TTC CTT TCT TCA TGG AGT CTT TGG GGA GCC AAC TAC ATG GAT TGT

CAG TTT TAA TTG GAC AAG TTC AAG GAA AGA AGT ACC TCA GAA ACC CCT CGG TTG ATG TAC CTA ACA

V K I N L F K F L S S W S L W G A N Y M D C

Val Lys Ile Asn Leu Phe Lys Phe Leu Ser Ser Trp Ser Leu Trp Gly Ala Asn Tyr Met Asp Cys

260 265 270 275

a (3)

t (2,14)

| g (8)

840 855 858 | |

TTT GAG TCC AAT GAA ACC ATG GGG gtaag tctta gatat atttg tcaag tttgt gattc tgaag aagat

AAA CTC AGG TTA CTT TGG TAC CCC cattc agaat ctata taaac agttc aaaca ctaag acttc ttcta

F E S N E T M G <------

Phe Glu Ser Asn Glu Thr Met Gly

280 285 286

gtgtt taata atgta cac

cacaa attat tacat gtg

------| RPE65-8b

IVS 8

|------> RPE65-9a

gt acact ttttt ccttt ttaaa tgcat caaaa tattt tcctc atttt tcaag

ca tgtga aaaaa ggaaa aattt acgta gtttt ataaa aggag taaaa agttc

C=Thr (1,14)

| del (17)

C=Phe (13) | | del (13) T=ter (8)

| 870 | 885 | | 900 | 915

GTT TGG CTT CAT ATT GCT GAC AAA AAA AGG AAA AAG TAC CTC AAT AAT AAA TAC AGA ACT TCT CCT

CAA ACC GAA GTA TAA CGA CTG TTT TTT TCC TTT TTC ATG GAG TTA TTA TTT ATG TCT TGA AGA GGA

V W L H I A D K K R K K Y L N N K Y R T S P

Val Trp Leu His Ile Ala Asp Lys Lys Arg Lys Lys Tyr Leu Asn Asn Lys Tyr Arg Thr Ser Pro

290 295 300 305

insA (1,23,24) T=Val(1)

A=Asn |G=Lys (17,13,14,21)| (26,3)Tyr=A

930 945 | 960 || 975 | |

TTC AAC CTC TTC CAT CAC ATC AAC ACC TAT GAA GAC AAT GGG TTT CTG ATT GTG GAT CTC TGC TGC

AAG TTG GAG AAG GTA GTG TAG TTG TGG ATA CTT CTG TTA CCC AAA GAC TAA CAC CTA GAG ACG ACG

F N L F H H I N T Y E D N G F L I V D L C C

Phe Asn Leu Phe His His Ile Asn Thr Tyr Glu Asp Asn Gly Phe Leu Ile Val Asp Leu Cys Cys

310 315 320 325 330

998

TGG AAA GG gtaag aaagg acact ggaca aatgg gacac ctccc attgt tcctg gaaat tacgg ggttt ttaca

ACC TTT CC cattc tttcc tgtga cctgt ttacc ctgtg gaggg taaca aggac cttta atgcc ccaaa aatgt

W K G <------| RPE65-9b

Trp Lys Gly

333

gaggt tttta cagag ctgct gcact caatc tgaat cacat ctaaa acagc aagag ttatg tgaga gtcaa aaatg

ctcca aaaat gtctc gacga cgtga gttag actta gtgta gattt tgtcg ttctc aatac actct cagtt tttac

taatt ggaaa agcag tagga agttt aggta atctg aacat caaaa ctatg attaa tgatt gaaaa ctaat cgggt

attaa ccttt tcgtc atcct tcaaa tccat tagac ttgta gtttt gatac taatt actaa ctttt gatta gccca

ccacg aaccc cacct gaaaa caaaa gattc tgtga cctga gaggt gaact atttc aactg tttt

ggtgc ttggg gtgga ctttt gtttt ctaag acact ggact ctcca cttga taaag ttgac aaaa

IVS 9

|------> RPE65-10a

agaat catct ctcta aaatt atttg

tctta gtaga gagat tttaa taaac

(1)Ser=C

999 1005 1020 |

tcatt gcctg tgctc atgtt tgact tttta tttt tgcag A TTT GAG TTT GTT TAT AAT TAC TTA TAT TTA

agtaa cggac acgag tacaa actga aaaat aaaa acgtc T AAA CTC AAA CAA ATA TTA ATG AAT ATA AAT

G F E F V Y N Y L Y L

Gly Phe Glu Phe Val Tyr Asn Tyr Leu Tyr Leu

333 335 340

insTGG (6)

| G=Glu (15)

| | A=Glu (1,17)

| | | del (3,14,15)

| | | | ins1bp (13,23,24)

1035 |1050 | | | | | | 1095

GCC AAT TTA CGT GAG AAC TGG GAA GAG GTG AAA AAA AAT GCC AGA AAG GCT CCC CAA CCT GAA GTT

CGG TTA AAT GCA CTC TTG ACC CTT CTC CAC TTT TTT TTA CGG TCT TTC CGA GGG GTT GGA CTT CAA

A N L R E N W E E V K K N A R K A P Q P E V

Ala Asn Leu Arg Glu Asn Trp Glu Glu Val Lys Lys Asn Ala Arg Lys Ala Pro Gln Pro Glu Val

345 350 355 360 365

C=His (4,14)

|G=Cys del (11,25)

|| 1110 | 1128

AGG AGA TAT GTA CTT CCT TTG AAT ATT GAC AAG gtaac ctgct tctct gtaga tttca gattt aacca

TCC TCT ATA CAT GAA GGA AAC TTA TAA CTG TTC cattg gacga agaga catct aaagt ctaaa ttggt

R R Y V L P L N I D K <--

Arg Arg Tyr Val Leu Pro Leu Asn Ile Asp Lys

370 375 376

|------> RPE65-11a

gaatg tttca tctct ctcag IVS10 gttt gaatt ctttc ctgct cactg aggtt tctgt tatct tctct cctag

cttac aaagt agaga gagtc caaa cttaa gaaag gacga gtgac tccaa agaca ataga agaga ggatc

------| RPE65-10b

A=Thr (1,17) G=Gly (13,23,24)

1131 1140 | 1170 | 1185

GCT GAC ACA GGC AAG AAT TTA GTC ACG CTC CCC AAT ACA ACT GCC ACT GCA ATT CTG TGC AGT GAC

CGA CTG TGT CCG TTC TTA AAT CAG TGC GAG GGG TTA TGT TGA CGG TGA CGT TAA GAC ACG TCA CTG

A D T G K N L V T L P N T T A T A I L C S D

Ala Asp Thr Gly Lys Asn Leu Val Thr Leu Pro Asn Thr Thr Ala Thr Ala Ile Leu Cys Ser Asp

377 380 385 390 395

T=Pro C=Ala (1)

dup (1) | C=Pro

1200 || | 1215 | | 1230 1243

GAG ACT ATC TGG CTG GAG CCT GAA GTT CTC TTT TCA GGG CCT CGT CAA G gtgag atgat ctaga gaaaa

CTC TGA TAG ACC GAC CTC GGA CTT CAA GAG AAA AGT CCC GGA GCA GTT C cactc tacta gatct ctttt