Last update: 06.07.12
REP-1
The sequence is given according to Genebank: AL009175, NM_000390 (NG_009874.1 RefSeqGene). Sequencing at the editor’s lab has revealed two missense changes in exon 5 (A216T (676G>A) and A218S (682G>T)) in every sample sequenced and present in the homozygous state in females. This indicates T216 and S218 to be the correct amino acid at this position.Exons are taken from[1,2], personal communication with F.P.M. Cremers and H. van Bokhoven, and additional data obtained in the editors lab
Primers are given according to [1]
Nucleotide numbering
Aminoacid numbering
Sequence variations (Polymorphism,rare variant, pathogenic)
Predicted FAD-binding Domain common to REP and GDIs [3]
*: conserved residues
!: changed residues (E for G9 in REPs and GDIs)
-320 -310 -300 -290 -280 -270 -260
c taaca atttt gcttc agtat tgtca agggg tatcc aagtc tccca cattc atcct agctaacggaataaa
g attgt taaaa cgaag tcata acagt tcccc atagg ttcag agggt gtaag tagga tcgattgcct tattt
-250 -240 -230 -220 -210 -200 -190
aatct acatt tcttt cctac ttcaa ccctc caggc taaat gagct acagcattca gcctg gaaaa tgagt
ttaga tgtaa agaaa ggatg aagtt gggag gtccg attta ctcga tgtcgtaagt cggac ctttt actca
-180 -170 -160 -150 -140 -130 -120
|------
cgagc tttta actta cgtgt aaaca tttta aatat aatactgtag tcgcc tgcct ggacc ttcca cccaa
gctcg aaaat tgaat gcaca tttgt aaaat ttata ttatgacatc agcgg acgga cctgg aaggt gggtt
-110 -100 -090 -080 -070 -060 -050
------> CHM-1f
gaact acaac accca gaatg cactg ttttcttttc cgcct tccac ggagg gaatg cctaa cttga tctca
cttga tgttg tgggt cttac gtgac aaaagaaaag gcgga aggtg cctcc cttac ggatt gaact agagt
A=Ile (48) del (40)
-040 -30 -20 -10 1| 15 | 30
tttcc acaag TAATA GTCAC ATGAC ACGTT TCCCG TCAAG ATG GCG GAT ACT CTC CCT TCG GAG TTT GAT
aaagg tgttc ATTAT CAGTG TACTG TGCAA AGGGC AGTTC TAC CGC CTA TGA GAG GGA AGC CTC AAA CTA
Met Ala Asp Thr Leu Pro Ser Glu Phe Asp
M A D T L P S E F D
5 10
a (5,40)
| t (41)
45 49 | |
GTG ATC GTA ATA GGG ACG G gtatg tgtag cctgg tgctt cctgg acaaa gttta ggaag actgt cttgt
CAC TAG CAT TAT CCC TGC C catac acatc ggacc acgaa ggacc tgttt caaat ccttc tgaca gaaca
Val Ile Val Ile Gly Thr Gly <------| CHM-1r
V I V I G* T G*
15 17
ttctg ttttt tctgt cagtg gcgag ttttg ggaca aacat cgtgg gtcga
aagac aaaaa agaca gtcac cgctc aaaac cctgt ttgta gcacc cagct
IVS1 (19756 bp)
|------> CHM-2f
tgttc tatac agcaa tggca tgtat tgaac atttt atgta aaata tatat atttc tacat tctaa atgat
acaag atatg tcgtt accgt acata acttg taaaa tacat tttat atata taaag atgta agatt tacta
c (5)
|50 60 75 90
acggg tgtgt gtttt tgtag GT TTG CCT GAA TCC ATC ATT GCA GCT GCA TGT TCA AGA AGT GGC CGG
tgccc acaca caaaa acatc CA AAC GGA CTT AGG TAG TAA CGT CGA CGT ACA AGT TCT TCA CCG GCC
Gly Leu Pro Glu Ser Ile Ile Ala Ala Ala Cys Ser Arg Ser Gly Arg
G L P *E! S I I A A A C S R S G R
17 20 25 30
A=ter (30)
|a (40,42)
|t(26)
105 ||
AGA GTT CTG CAT GTT GAT TC gtaag tttat caacg atagc attaa tattt cctaa atatc tctat acagg
TCT CAA GAC GTA CAA CTA AG cattc aaata gttgc tatcg taatt ataaa ggatt tatag agata tgtcc
Arg Val Leu His Val Asp Ser <------| CHM-2r
R V L H V D S
35 39
attaa aattt acata aacac atata tgtct
taatt ttaaa tgtat ttgtg tatat acaga
IVS2 (45518 bp)
|------> CHM-3f
aa agatg gtttg ttgat gaaga tcagt gaatt gattt ttata ccatt ttctt tactt ttttt ttttt tttta
tt tctac caaac aacta cttct agtca cttaa ctaaa aatat ggtaa aagaa atgaa aaaaa aaaaa aaaat
T=ter (40) A=ter (5)
117 120 | 135 | 150 165
attgt tacag A AGA AGC TAC TAT GGA GGA AAC TGG GCC AGT TTT AGC TTT TCA GGA CTA TTG TCC
taaca atgtc T TCT TCG ATG ATA CCT CCT TTG ACC CGG TCA AAA TCG AAA AGT CCT GAT AAC AGG
Ser Arg Ser Tyr Tyr Gly Gly Asn Trp Ala Ser Phe Ser Phe Ser Gly Leu Leu Ser
S R S Y Y G G N W A S F S F S G L L S
39 40 45 50 55
a (41
180 189|
TGG CTA AAG GAA TAC CAG gtaaa gtttg tatct gacct tttaa tttgc tttgt tttat tgtat gttac atagt
ACC GAT TTC CTT ATG GTC cattt caaac ataga ctgga aaatt aaacg aaaca aaata acata caatg tatca
Trp Leu Lys Glu Tyr Gln <------| CHM-3r
W L K E Y Q
60 63
aaccc tgcac tgaag aaaac cctaa
ttggg acgtg acttc ttttg ggatt
IVS3 (2704 bp)
g (2) g (41)
|------> CHM-4f | |190 195
aaaat tgcat gtttc acact gccca ctttg attaa aactt cttat ctgtg ttttg tttag GAA AAC AGT GAC
tttta acgta caaag tgtga cgggt gaaac taatt ttgaa gaata gacac aaaac aaatc CTT TTG TCA CTG
Glu Asn Ser Asp
E N S D
64 65
T=ter (32,43) (37) Cys=T
210 225 | 240 255 |
ATT GTA AGT GAC AGT CCA GTG TGG CAA GAC CAG ATC CTT GAA AAT GAA GAA GCC ATT GCT CTT AGC
TAA CAT TCA CTG TCA GGT CAC ACC GTT CTG GTC TAG GAA CTT TTA CTT CTT CGG TAA CGA GAA TCG
Ile Val Ser Asp Ser Pro Val Trp Gln Asp Gln Ile Leu Glu Asn Glu Glu Ala Ile Ala Leu Ser
I V S D S P V W Q D Q I L E N E E A I A L S
70 75 80 85
del (7)
del (6) | G=ter (32,44)
270 285 | 300 | | 314
AGG AAG GAC AAA ACT ATT CAA CAT GTG GAA GTA TTT TGT TAT GCC AG gtatg aaaag tattt
TCC TTC CTG TTT TGA TAA GTT GTA CAC CTT CAT AAA ACA ATA CGG TC catac ttttc ataaa
Arg Lys Asp Lys Thr Ile Gln His Val Glu Val Phe Cys Tyr Ala Ser
R K D K T I Q H V E V F C Y A S
90 95 100 105
actgc aggta aacta aatta atgac ttttt cactc ttctt tagaa gaagc caaca ataaa gattt atgtg gcatt
tgacg tccat ttgat ttaat tactg aaaaa gtgag aagaa atctt cttcg gttgt tattt ctaaa tacac cgtaa
<------| CHM-4r
IVS4 (14592 bp)ins L1 repeat (98bp) at +10127 (41)
T=ter (8)
|---| del (5,26,40)
| del (40)
|------>CHM-5/1f315| |
ggggt aaggg aatat atata taaag ccctg gtgtttattat tatat ttgtt attag T CAG GAT TTG CAT
cccca ttccc ttata tatat atttc gggac cacaa taata atata aagaa taatc A GTC CTA AAC GTA
Ser Gln Asp Leu His
S Q D L H
105
G=A117A (9,26,37) del (43)
330 345 | 360 |375 390
GAA GAT GTC GAA GAA GCT GGT GCA CTG CAG AAA AAT CAT GCT CTT GTG ACA TCT GCA AAC TCC ACA
CTT CTA CAG CTT CTT CGA CCA CGT GAC GTC TTT TTA GTA CGA GAA CAC TGT AGA CGT TTG AGG TGT
Glu Asp Val Glu Glu Ala Gly Ala Leu Gln Lys Asn His Ala Leu Val Thr Ser AlaAsnSerThr
E D V E E A G A L Q K N H A L V T S A N S T
110 115 120 125 130
405 420 435 450
GAA GCT GCA GAT TCT GCC TTC CTG CCT ACG GAG GAT GAG TCA TTA AGC ACT ATG AGC TGT GAA ATG
CTT CGA CGT CTA AGA CGG AAG GAC GGA TGC CTC CTA CTC AGT AAT TCG TGA TAC TCG ACA CTT TAC
GluAlaAlaAspSerAlaPheLeuProThrGluAspGluSerAla Asn Ser Thr Glu Ala Ala Asp
E A A D S A F L P T E D E S A N S T E A A D
135 140 145 150
465 480 495 510 (48,43,33,26,2) del
|------> CHM-5/2f |-
CTC ACA GAA CAA ACT CCA AGC AGC GAT CCA GAG AAT GCG CTA GAA GTA AAT GGT GCT GAA GTG ACA
GAG TGT CTT GTT TGA GGT TCG TCG CTA GGT CTC TTA CGC GAT CTT CAT TTA CCA CGA CTT CAC TGT
CHM-5/1r <------|
Ser Ala Phe Leu Pro Thr Glu Asp Glu Ser Glu Asn Ala Leu Glu Val Asn Gly Ala Glu Val Thr
S A F L P T E D E S E N A L E V N G A E V T
155 160 165 170 175
del insAGTTTTCT (40,42)
| | del (47)
del (40) |------| || G=ter (40)
T=ter (6) | ins GA (26) |del (5)| dup A (2)
| | 540 | | 555 | ||-| | |585
GGG GAA AAA GAA AAC CAT TGT GAT GAT AAA ACT TGT GTG CCA TCA ACT TCA GCA GAA GAC ATG AGT
CCC CTT TTT CTT TTG GTA ACA CTA CTA TTT TGA ACA CAC GGT AGT TGA AGT CGT CTT CTG TAC TCA
Gly Glu Lys Glu Asn His Cys Asp Asp Lys Thr Cys Val Pro Ser Thr Ser Ala Glu Asp Met Ser
G E K E N H C D D K T C V P S T S A E D M S
180 185 190 195
T=ter (5) del (44
del (26) | ins A (38) ||(40,10,26,38) del
600 || | |630 || 645 |---|
GAA AAT GTG CCT ATA GCA GAA GAT ACC ACA GAG CAA CCA AAG AAA AAC AGA ATT ACT TAC TCA CAA
CTT TTA CAC GGA TAT CGT CTT CTA TGG TGT CTC GTT GGT TTC TTT TTG TCT TAA TGA ATG AGT GTT
Glu Asn Val Pro Ile Ala Glu Asp Thr Thr Glu Gln Pro Lys Lys Asn Arg Ile Thr Tyr Ser Gln
E N V P I A E D T T E Q P K K N R I A/T Y A/S Q
200 205 210 215
T=ter (48)
660 675 690 |702
ATT ATT AAA GAA GGC AGG AGA TTT AAT ATT GAT TTA GTA TCA AAG gtaag tacta atttt accca tcttt
TAA TAA TTT CTT CCG TCC TCT AAA TTA TAA CTA AAT CAT AGT TTC cattc atgat taaaa tgggt agaaa
Ile Ile Lys Glu Gly Arg Arg Phe Asn Ile Asp Leu Val Ser Lys
I I K E G R R F N I D L V S K
220 225 230 CHM-5/2r<------|
gcatt gaaaa cagta tctgg gccca taaac ccagt ttttg
cgtaa ctttt gtcat agacc cgggt atttg ggtca aaaac
IVS5 (4583 bp)
c (38)
|------> CHM-6f |705
ttgtt ttcca atttt tctac tattt caact tttat cttgt aaaat atttt ctttg tacag CTG CTG TAT TCT
aacaa aaggt taaaa agatg ataaa gttga aaata gaaca tttta taaaa gaaac atgtc GAC GAC ATA AGA
LeuLeuTyrSer
L L Y S
235 236
T=ter (26,27,31,40)
T=ter (11,40,43,28) | G=ter (10)
| del insT (40) del (12) | | del (40,42)
| |-| 735 | | | 765 | 770
CGA GGA TTA CTA ATT GAT CTT CTA ATC AAA TCT AAT GTT AGT CGA TAT GCA GAG TTT AAA AAT ATT
GCT CCT AAT GAT TAA CTA GAA GAT TAG TTT AGA TTA CAA TCA GCT ATA CGT CTC AAA TTT TTA TAA
ArgGlyLeuLeuIleAspLeuLeuIleLysSerAsnValSerArgTyrAlaGluPheLysAsnIle
R G L L I D L L I K S N V S R Y A E F K N I
240 245 250 255 260
T=ter (12,26,40,42)
| T=ter (5,25,34,40,42)
| | T=ter (41)
| | | T=ter (48)
795 | |810 | |819
ACC AGG ATT CTT GCA TTT CGA GAA GGA CGA GTG GAA CAG gtact gtgct gatca agaat tgtaa ctggg
TGG TCC TAA GAA CGT AAA GCT CTT CCT GCT CAC CTT GTC catga cacga ctagt tctta acatt gaccc
ThrArgIleLeuAlaPheArgGluGlyArg Val Glu Gln <------
T R I L A F R E G R V E Q
265 270 273
catca gctta agtta ttatg gtttg ttttg gaaag ataag caaat aagat tgtta ttttc ctcat aaagc agtaa
gtagt cgaat tcaat aatac caaac aaaac ctttc tattc gttta ttcta acaat aaaag gagta tttcg tcatt
------| CHM-6r
IVS6 (720 bp)
g (41) g (26)
| |c (45)
|------> CHM-7f | || 825
tttgg aatag ttata tcatt aggaa gcagt ttctt aactt aaaat cataa tattt ttcag GTT CCG TGT TCC
aaacc ttatc aatat agtaa tcctt cgtca aagaa ttgaa tttta gtatt ataaa aagtc CAA GGC ACA AGG
Val Pro Cys Ser
V P C S
274 275
T=ter (2,26,40,43)
840 855 870 | 885
AGA GCA GAT GTC TTT AAT AGC AAA CAA CTT ACT ATG GTA GAA AAG CGA ATG CTA ATG AAA TTT CTT
TCT CGT CTA CAG AAA TTA TCG TTT GTT GAA TGA TAC CAT CTT TTC GCT TAC GAT TAC TTT AAA GAA
Arg Ala Asp Val Phe Asn Ser Lys Gln Leu Thr Met Val Glu Lys Arg Met Leu Met Lys Phe Leu
R A D V F N S K Q L T M V E K R M L M K F L
280 285 290 295
del (46)
del (40) G=ter (41) | a (26,40)
900 | 915 | 930 |-----|
ACA TTT TGT ATG GAA TAT GAG AAA TAT CCT GAT GAA TAT AAA G gtatt ttttt catta agtag tgctc
TGT AAA ACA TAC CTT ATA CTC TTT ATA GGA CTA CTT ATA TTT C cataa aaaaa gtaat tcatc acgag
Thr Phe Cys Met Glu Tyr Glu Lys Tyr Pro Asp Glu Tyr Lys Gly <------
T F C M E Y E K Y P D E Y K G
300 305 310 314
tccaa ttatt tgaca tttct
aggtt aataa actgt aaaga
----|CHM-7r
IVS7 (1372 bp)
g (41)
|------> CHM-8f | 945
ggtgg tttta aatag aagtt tagtt ctgat tttaa gtgat aaaat ttcat ctttt catag GA TAT GAA GAG
ccacc aaaat ttatc ttcaa atcaa gacta aaatt cacta tttta aagta gaaaa gtatc CT ATA CTT CTC
Gly Tyr Glu Glu
G Y E E
314 315
del (40) T=ter (12)
960 975 | 990 | 1005
ATC ACA TTT TAT GAA TAT TTA AAG ACT CAA AAA TTA ACC CCC AAC CTC CAA TAT ATT GTC ATG CAT
TAG TGT AAA ATA CTT ATA AAT TTC TGA GTT TTT AAT TGG GGG TTG GAG GTT ATA TAA CAG TAC GTA
Ile Thr Phe Tyr Glu Tyr Leu Lys Thr Gln Lys Leu Thr Pro Asn Leu Gln Tyr Ile Val Met His
I T F Y E Y L K T Q K L T P N L Q Y I V M H
320 325 330 335
A=ter (13,38,40) G=ter (5)
| 1032 | 1050 1065 1080
TCA ATT GCA ATG ACA TCA GAG ACA GCC AGC ACC ATA GAT GGT CTC AAA GCT ACC AAA AGC AAC TTT
AGT TAA CGT TAC TGT AGT CTC TGT CGG TCG TCG TGG TAT CTA CCA GAG TTT CGA TGG TTT TTG AAA
Ser Ile Ala Met Thr Ser Glu Thr Ala Ser Ser Thr Ile Asp Gly Leu Lys Ala Thr Lys Asn Phe
S I A M T S E T A S S T I D G L K A T K N F
340 345 350 355 360
A=ter (36)
A=Gln (37) | ins AAT (8)
| | | T=ter (42)
1095 | 1110 1125 | | |
CTT CAC TGT CTT GGG CGG TAT GGC AAC ACT CCA TTT TTG TTT CCT TTA TAT GGC CAA GGA GAA CTC
GAA GTG ACA GAA CCC GCC ATA CCG TTG TGA GGT AAA AAC AAA GGA AAT ATA CCG GTT CCT CTT GAG
Leu His Cys Leu Gly Arg Tyr Gly Asn Thr Pro Phe Leu Phe Pro Leu Tyr Gly Gln Gly Glu Leu
L H C L G R Y G N T P F L F P L Y G Q G E L
365 370 375 380
ins C (2)
| 1166
CCC CAG TGT TTC TGC AG gtaa gtttg ccatt gattt tcttg tccct tctaa aagtg atact tgaat aacag
GGG GTC ACA AAG ACG TC catt caaac ggtaa ctaaa agaac aggga agatt ttcac tatga actta ttgtc
Pro Gln Cys Phe Cys Arg <------|- CHM-8r
P Q C F C R
385 389
atgaa aatta ggcag gcaaa aatga gattt attca agatt tagta tatgc aaa
tactt ttaat ccgtc cgttt ttact ctaaa taagt tctaa atcat atacg ttt
IVS8 (4466 bp)
|------> CHM-9f 1167 1185
tt ttcaa cccaa ttacc ctaat tctta ttttt ctgtt ctctt tctag G ATG TGT GCT GTG TTT GGT GGA
aa aagtt gggtt aatgg gatta agaat aaaaa gacaa gagaa agatc C TAC ACA CGA GAC AAA CCA CCT
Arg Met Cys AlaVal Phe Gly Gly
R M C A V F G G
389 390 395
G=ter (5)
| A=ter (8,28,40,42)
1200 | 1215 | 1230
ATT TAT TGT CTT CGC CAT TCA GTA CAG TGC CTT GTA GTG GAC
TAA ATA ACA GAA GCG GTA AGT CAT GTC ACG GAA CAT CAC CTG
Ile Tyr Cys Leu Arg His Ser Val Gln Cys Leu Val Val Asp
I Y C L R H S V Q C L V V D
400 405 410
a (12,40)
1244 |
AAA GAA TCC AGA AA gtaag gatga tataa gtaac cttca tatatatata tatat atatt catat
TTT CTT AGG TCT TT cattc ctact atatt cattg gaagt atatatatat atata tataa gtata
Lys Glu Ser Arg Lys <------| CHM-9r
K E S R K
415
IVS9 (9969 bp)
|------> CHM-10f 1245 1260
taatc attaa tatga acttt tatgg tatgc ttatc ttctt tatag A TGT AAA GCA ATT ATA GAT CAG
attag taatt atact tgaaa atacc atacg aatag aagaa atatc T ACA TTT CGT TAA TAT CTA GTC
Lys Cys Lys Ala Ile Ile Asp Gln
K C K A I I D Q
415 420
del (6)del (40) del (26)
1275 || | 1305 |---| 1320
TTT GGT CAG AGA ATA ATC TCT GAG CAT TTC CTC GTG GAG GAC AGT TAC TTT CCT GAG AAC ATG TGC
AAA CCA GTC TCT TAT TAG AGA CTC GTA AAG GAG CAC CTC CTG TCA ATG AAA GGA CTC TTG TAC ACG
Phe Gly Gln Arg Ile Ile Ser Glu His Phe Leu Val Glu Asp Ser Tyr Phe Pro Glu Asn Met Cys
F G Q R I I S E H F L V E D S Y F P E N M C
425 430 435 440
ins C (5)
| ins ggt (12,40)
1335 | 1349 |
TCA CGT GTG CAA TAC AG gtaag gcccc ctcca ccacc catta gcaag cgaag gtaat tttat tgaca ttcct
AGT GCA CAC GTT ATG TC cattc cgggg gaggt ggtgg gtaat cgttc gcttc catta aaata actgt aagga
Ser Asn Val Gln Tyr Arg <------|CHM-10r
S R V Q Y R
445 450
IVS10 (270 bp)
g (40) delCCinsG (12,41)
| a (26,40) || del (8,40)
|------> CHM-11f | | || |
cga aactt atcca tggaa tcaga attac tgctt cactg ttttg tgcat tacag G CAG ATC TCC AGG GCA GTG
gct ttgaa taggt acctt agtct taatg acgaa gtgac aaaac acgta atgtc C GTC TAG AGG TCC CGT CAC
Arg Gln Ile Ser Arg Ala Val
R Q I S R A V
450 455
G=ter (25)
| T=ter (28)
| |T=Leu (14)
1380 1395 | ||
CTG ATT ACA GAT AGA TCT GTC CTA AAA ACA GAT TCA GAT CAA CAG gtaaa ttcag tccta tatat
GAC TAA TGT CTA TCT AGA CAG GAT TTT TGT CTA AGT CTA GTT GTC cattt aagtc aggat atata
Leu Ile Thr Asp Arg Ser Val Leu Lys Thr Asp Ser Asp Gln Gln
L I T D R S V L K T D S D Q Q
460 465 471
tttta ataaa agttg tatat atgaa gatgt ttcgg tatat atata catgg tgaac taatc actac accgg
aaaat tattt tcaac atata tactt ctaca aagcc atata tatat gtacc acttg attag tgatg tggcc
CHM-11r <------
IVS11 (6237 bp)
g (4)
| a (15)
|------> CHM-12f ||1416 1425 1440
cg atcta acagc tgtgt ctgat acttt atttt tgctt tttag ATT TCC ATT TTG ACA GTG CCA GCA GAG