La Banque de données des mutations du gène DMD
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Le gène DMD codant pour la dystrophine (OMIM 300377) a été identifié en 1986 par une approche de clonage positionnel. Localisé sur le chromosome X (Xp21.2) (Monaco et al., Koenig et al.), il constitue le plus grand gène connu. En effet, il s'étend sur un territoire génomique de 2,6 millions de paires de bases (pb) ce qui correspond à environ 0,1% du génome et approximativement 1,5% du chromosome X. Il est organisé en 79 exons séparés par des introns de taille très variable allant de 107 pb (intron 14) à plus de 200 000 pb (intron 44). Il est transcrit en un ARNm de 14 000 pb dont 11 000 pb d'ADNc codent pour une protéine de 427 kilodaltons (kDa) comportant 3685 acides aminés : la dystrophine.

Il existe de multiples promoteurs et isoformes résultant d'épissages alternatifs (Ahn and Kunkel). L'expression des isoformes les plus longues de dystrophine est controlée par trois promoteurs localisés dans la région 5' du gène (320 000 pb en amont de l'exon 2) qui sont actifs dans les neurones (promoteur du cerveau, Dp427b) (Nudel et al.), dans les muscles et les cellules gliales (promoteur M, Dp427m), et dans les cellules de Purkinje localisées dans le cerveau (promoteur P, Dp427p) (Gorecki et al.). Les ARNm transcrits à partir de ces promoteurs comportent un exon 1 spécifique raccordé aux 78 autres exons du gène.

Quatre formes tronquées de dystrophine sont transcrites à partir de promoteurs internes tissus-spécifiques. Chacun de ces promoteurs utilise un premier exon spécifique qui est rabouté, respectivement, aux exons 30, 45, 56 et 63, aboutissant à la production de protéines plus courtes nommées en fonction de leur poids moléculaire : Dp260 (rétine) (D'Souza et al.), Dp140 (cerveau, rétine et reins) (Lidov et al.), Dp116 (nerfs périphériques chez l'adulte) (Byers et al.) et Dp71 (Lederfein et al.). La Dp71 correspond à la forme majoritaire de dystrophine présente dans le cerveau et dans de nombreux tissus non-musculaires mais n'est pas exprimée dans les muscles squelettiques. Le gène DMD produit également de nombreuses autres isoformes issues d'épissages alternatifs tissus-spécifiques ou par l'utilisation d'un site alternatif de polyadénylation localisé dans l'intron 70 (isoforme Dp40) (Feener et al.). Ces différents évènements génèrent ainsi une grande diversité de protéines à l'origine d'une régulation complexe de l'expression de ce gène.

Les dystrophinopathies liées à l'X sont dues à des mutations qui conduisent à des défauts quantitatifs et/ou qualitatifs de l'expression de la dystrophine. Les dystrophinopathies incluent trois entités cliniques : la dystrophie musculaire de Duchenne (DMD; #310200), la dystrophie musculaire de Becker (BMD; #300376) et les cardiomyopathies dilatées liées à l'X (XLDCM; #302045), qui correspondent à une forme allélique rare dans laquelle l'expression et/ou la fonction de la dystrophine est principalement ou exclusivement altérée dans le tissu cardiaque (Muntoni, F). La grande taille du gène DMD contribue significativement au taux élevé de mutations spontanées ou de novo (1 pour 10,000 gamètes). Ces mutations consistent en de grandes délétions et duplications d'un ou plusieurs exons (~70%) ou de petites altérations de séquence (~30%).

Isoforme musculaire (Dp427m)


RefSeq IDs NM_004006.1
Ensembl transcript ID ENST00000357033
Swissprot ID P11532
Transcrit Dp427m
Localisation de l'isoforme Muscle
Chromosome X
Nombre d'exons 79
Brin -
Localisation de l'ATG Exon 1
Localisation de l'ATG position sur le chromosome (pb) 33 139 601

Autres isoformes


Isoforme Localisation Numéro d'acession
Dp427b Cerveau NM_000109
Dp427p Cellules de Purkinje NM_004009
Dp260 RetinRétinea NM_004011
Dp140 Système nerveux centra et reins NM_004013
Dp116 Cellules de Schwann NM_004014
Dp71 Ubiquitaire NM_004015
Dp40 Ubiquitaire NM_004019



Séquence codante du transcrit musculaire (Dp427m)

Exon # 1 Exon # 2
ATG CTT TGG TGG GAA GAA GTA GAG GAC TGT TAT GAA AGA GAA GAT GTT CAA AAG AAA ACA TTC ACA AAA TGG GTA AAT GCA CAA TTT TCT
Met
Leu
Trp
Trp
Glu
Glu
Val
Glu
Asp
Cys
Tyr
Glu
Arg
Glu
Asp
Val
Gln
Lys
Lys
Thr
Phe
Thr
Lys
Trp
Val
Asn
Ala
Gln
Phe
Ser
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30

Exon # 3
AAG TTT GGG AAG CAG CAT ATT GAG AAC CTC TTC AGT GAC CTA CAG GAT GGG AGG CGC CTC CTA GAC CTC CTC GAA GGC CTG ACA GGG CAA
Lys
Phe
Gly
Lys
Gln
His
Ile
Glu
Asn
Leu
Phe
Ser
Asp
Leu
Gln
Asp
Gly
Arg
Arg
Leu
Leu
Asp
Leu
Leu
Glu
Gly
Leu
Thr
Gly
Gln
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Exon # 3 Exon # 4 Exon # 5
AAA CTG CCA AAA GAA AAA GGA TCC ACA AGA GTT CAT GCC CTG AAC AAT GTC AAC AAG GCA CTG CGG GTT TTG CAG AAC AAT AAT GTT GAT
Lys
Leu
Pro
Lys
Glu
Lys
Gly
Ser
Thr
Arg
Val
His
Ala
Leu
Asn
Asn
Val
Asn
Lys
Ala
Leu
Arg
Val
Leu
Gln
Asn
Asn
Asn
Val
Asp
61
62
63
64
65
66
67
68
69
70
71
72
73
74
75
76
77
78
79
80
81
82
83
84
85
86
87
88
89
90
Exon # 5
TTA GTG AAT ATT GGA AGT ACT GAC ATC GTA GAT GGA AAT CAT AAA CTG ACT CTT GGT TTG ATT TGG AAT ATA ATC CTC CAC TGG CAG GTC
Leu
Val
Asn
Ile
Gly
Ser
Thr
Asp
Ile
Val
Asp
Gly
Asn
His
Lys
Leu
Thr
Leu
Gly
Leu
Ile
Trp
Asn
Ile
Ile
Leu
His
Trp
Gln
Val
91
92
93
94
95
96
97
98
99
100
101
102
103
104
105
106
107
108
109
110
111
112
113
114
115
116
117
118
119
120
Exon # 6
AAA AAT GTA ATG AAA AAT ATC ATG GCT GGA TTG CAA CAA ACC AAC AGT GAA AAG ATT CTC CTG AGC TGG GTC CGA CAA TCA ACT CGT AAT
Lys
Asn
Val
Met
Lys
Asn
Ile
Met
Ala
Gly
Leu
Gln
Gln
Thr
Asn
Ser
Glu
Lys
Ile
Leu
Leu
Ser
Trp
Val
Arg
Gln
Ser
Thr
Arg
Asn
121
122
123
124
125
126
127
128
129
130
131
132
133
134
135
136
137
138
139
140
141
142
143
144
145
146
147
148
149
150
Exon # 6 Exon # 7
TAT CCA CAG GTT AAT GTA ATC AAC TTC ACC ACC AGC TGG TCT GAT GGC CTG GCT TTG AAT GCT CTC ATC CAT AGT CAT AGG CCA GAC CTA
Tyr
Pro
Gln
Val
Asn
Val
Ile
Asn
Phe
Thr
Thr
Ser
Trp
Ser
Asp
Gly
Leu
Ala
Leu
Asn
Ala
Leu
Ile
His
Ser
His
Arg
Pro
Asp
Leu
151
152
153
154
155
156
157
158
159
160
161
162
163
164
165
166
167
168
169
170
171
172
173
174
175
176
177
178
179
180
Exon # 7
TTT GAC TGG AAT AGT GTG GTT TGC CAG CAG TCA GCC ACA CAA CGA CTG GAA CAT GCA TTC AAC ATC GCC AGA TAT CAA TTA GGC ATA GAG
Phe
Asp
Trp
Asn
Ser
Val
Val
Cys
Gln
Gln
Ser
Ala
Thr
Gln
Arg
Leu
Glu
His
Ala
Phe
Asn
Ile
Ala
Arg
Tyr
Gln
Leu
Gly
Ile
Glu
181
182
183
184
185
186
187
188
189
190
191
192
193
194
195
196
197
198
199
200
201
202
203
204
205
206
207
208
209
210
Exon # 7 Exon # 8
AAA CTA CTC GAT CCT GAA GAT GTT GAT ACC ACC TAT CCA GAT AAG AAG TCC ATC TTA ATG TAC ATC ACA TCA CTC TTC CAA GTT TTG CCT
Lys
Leu
Leu
Asp
Pro
Glu
Asp
Val
Asp
Thr
Thr
Tyr
Pro
Asp
Lys
Lys
Ser
Ile
Leu
Met
Tyr
Ile
Thr
Ser
Leu
Phe
Gln
Val
Leu
Pro
211
212
213
214
215
216
217
218
219
220
221
222
223
224
225
226
227
228
229
230
231
232
233
234
235
236
237
238
239
240
Exon # 8
CAA CAA GTG AGC ATT GAA GCC ATC CAG GAA GTG GAA ATG TTG CCA AGG CCA CCT AAA GTG ACT AAA GAA GAA CAT TTT CAG TTA CAT CAT
Gln
Gln
Val
Ser
Ile
Glu
Ala
Ile
Gln
Glu
Val
Glu
Met
Leu
Pro
Arg
Pro
Pro
Lys
Val
Thr
Lys
Glu
Glu
His
Phe
Gln
Leu
His
His
241
242
243
244
245
246
247
248
249
250
251
252
253
254
255
256
257
258
259
260
261
262
263
264
265
266
267
268
269
270
Exon # 8 Exon # 9
CAA ATG CAC TAT TCT CAA CAG ATC ACG GTC AGT CTA GCA CAG GGA TAT GAG AGA ACT TCT TCC CCT AAG CCT CGA TTC AAG AGC TAT GCC
Gln
Met
His
Tyr
Ser
Gln
Gln
Ile
Thr
Val
Ser
Leu
Ala
Gln
Gly
Tyr
Glu
Arg
Thr
Ser
Ser
Pro
Lys
Pro
Arg
Phe
Lys
Ser
Tyr
Ala
271
272
273
274
275
276
277
278
279
280
281
282
283
284
285
286
287
288
289
290
291
292
293
294
295
296
297
298
299
300
Exon # 9 Exon # 10
TAC ACA CAG GCT GCT TAT GTC ACC ACC TCT GAC CCT ACA CGG AGC CCA TTT CCT TCA CAG CAT TTG GAA GCT CCT GAA GAC AAG TCA TTT
Tyr
Thr
Gln
Ala
Ala
Tyr
Val
Thr
Thr
Ser
Asp
Pro
Thr
Arg
Ser
Pro
Phe
Pro
Ser
Gln
His
Leu
Glu
Ala
Pro
Glu
Asp
Lys
Ser
Phe
301
302
303
304
305
306
307
308
309
310
311
312
313
314
315
316
317
318
319
320
321
322
323
324
325
326
327
328
329
330
Exon # 10
GGC AGT TCA TTG ATG GAG AGT GAA GTA AAC CTG GAC CGT TAT CAA ACA GCT TTA GAA GAA GTA TTA TCG TGG CTT CTT TCT GCT GAG GAC
Gly
Ser
Ser
Leu
Met
Glu
Ser
Glu
Val
Asn
Leu
Asp
Arg
Tyr
Gln
Thr
Ala
Leu
Glu
Glu
Val
Leu
Ser
Trp
Leu
Leu
Ser
Ala
Glu
Asp
331
332
333
334
335
336
337
338
339
340
341
342
343
344
345
346
347
348
349
350
351
352
353
354
355
356
357
358
359
360
Exon # 10 Exon # 11
ACA TTG CAA GCA CAA GGA GAG ATT TCT AAT GAT GTG GAA GTG GTG AAA GAC CAG TTT CAT ACT CAT GAG GGG TAC ATG ATG GAT TTG ACA
Thr
Leu
Gln
Ala
Gln
Gly
Glu
Ile
Ser
Asn
Asp
Val
Glu
Val
Val
Lys
Asp
Gln
Phe
His
Thr
His
Glu
Gly
Tyr
Met
Met
Asp
Leu
Thr
361
362
363
364
365
366
367
368
369
370
371
372
373
374
375
376
377
378
379
380
381
382
383
384
385
386
387
388
389
390
Exon # 11
GCC CAT CAG GGC CGG GTT GGT AAT ATT CTA CAA TTG GGA AGT AAG CTG ATT GGA ACA GGA AAA TTA TCA GAA GAT GAA GAA ACT GAA GTA
Ala
His
Gln
Gly
Arg
Val
Gly
Asn
Ile
Leu
Gln
Leu
Gly
Ser
Lys
Leu
Ile
Gly
Thr
Gly
Lys
Leu
Ser
Glu
Asp
Glu
Glu
Thr
Glu
Val
391
392
393
394
395
396
397
398
399
400
401
402
403
404
405
406
407
408
409
410
411
412
413
414
415
416
417
418
419
420
Exon # 11 Exon # 12
CAA GAG CAG ATG AAT CTC CTA AAT TCA AGA TGG GAA TGC CTC AGG GTA GCT AGC ATG GAA AAA CAA AGC AAT TTA CAT AGA GTT TTA ATG
Gln
Glu
Gln
Met
Asn
Leu
Leu
Asn
Ser
Arg
Trp
Glu
Cys
Leu
Arg
Val
Ala
Ser
Met
Glu
Lys
Gln
Ser
Asn
Leu
His
Arg
Val
Leu
Met
421
422
423
424
425
426
427
428
429
430
431
432
433
434
435
436
437
438
439
440
441
442
443
444
445
446
447
448
449
450
Exon # 12
GAT CTC CAG AAT CAG AAA CTG AAA GAG TTG AAT GAC TGG CTA ACA AAA ACA GAA GAA AGA ACA AGG AAA ATG GAG GAA GAG CCT CTT GGA
Asp
Leu
Gln
Asn
Gln
Lys
Leu
Lys
Glu
Leu
Asn
Asp
Trp
Leu
Thr
Lys
Thr
Glu
Glu
Arg
Thr
Arg
Lys
Met
Glu
Glu
Glu
Pro
Leu
Gly
451
452
453
454
455
456
457
458
459
460
461
462
463
464
465
466
467
468
469
470
471
472
473
474
475
476
477
478
479
480
Exon # 12 Exon # 13
CCT GAT CTT GAA GAC CTA AAA CGC CAA GTA CAA CAA CAT AAG GTG CTT CAA GAA GAT CTA GAA CAA GAA CAA GTC AGG GTC AAT TCT CTC
Pro
Asp
Leu
Glu
Asp
Leu
Lys
Arg
Gln
Val
Gln
Gln
His
Lys
Val
Leu
Gln
Glu
Asp
Leu
Glu
Gln
Glu
Gln
Val
Arg
Val
Asn
Ser
Leu
481
482
483
484
485
486
487
488
489
490
491
492
493
494
495
496
497
498
499
500
501
502
503
504
505
506
507
508
509
510
Exon # 13 Exon # 14
ACT CAC ATG GTG GTG GTA GTT GAT GAA TCT AGT GGA GAT CAC GCA ACT GCT GCT TTG GAA GAA CAA CTT AAG GTA TTG GGA GAT CGA TGG
Thr
His
Met
Val
Val
Val
Val
Asp
Glu
Ser
Ser
Gly
Asp
His
Ala
Thr
Ala
Ala
Leu
Glu
Glu
Gln
Leu
Lys
Val
Leu
Gly
Asp
Arg
Trp
511
512
513
514
515
516
517
518
519
520
521
522
523
524
525
526
527
528
529
530
531
532
533
534
535
536
537
538
539
540
Exon # 14 Exon # 15
GCA AAC ATC TGT AGA TGG ACA GAA GAC CGC TGG GTT CTT TTA CAA GAC ATC CTT CTC AAA TGG CAA CGT CTT ACT GAA GAA CAG TGC CTT
Ala
Asn
Ile
Cys
Arg
Trp
Thr
Glu
Asp
Arg
Trp
Val
Leu
Leu
Gln
Asp
Ile
Leu
Leu
Lys
Trp
Gln
Arg
Leu
Thr
Glu
Glu
Gln
Cys
Leu
541
542
543
544
545
546
547
548
549
550
551
552
553
554
555
556
557
558
559
560
561
562
563
564
565
566
567
568
569
570
Exon # 15
TTT AGT GCA TGG CTT TCA GAA AAA GAA GAT GCA GTG AAC AAG ATT CAC ACA ACT GGC TTT AAA GAT CAA AAT GAA ATG TTA TCA AGT CTT
Phe
Ser
Ala
Trp
Leu
Ser
Glu
Lys
Glu
Asp
Ala
Val
Asn
Lys
Ile
His
Thr
Thr
Gly
Phe
Lys
Asp
Gln
Asn
Glu
Met
Leu
Ser
Ser
Leu
571
572
573
574
575
576
577
578
579
580
581
582
583
584
585
586
587
588
589
590
591
592
593
594
595
596
597
598
599
600
Exon # 15 Exon # 16
CAA AAA CTG GCC GTT TTA AAA GCG GAT CTA GAA AAG AAA AAG CAA TCC ATG GGC AAA CTG TAT TCA CTC AAA CAA GAT CTT CTT TCA ACA
Gln
Lys
Leu
Ala
Val
Leu
Lys
Ala
Asp
Leu
Glu
Lys
Lys
Lys
Gln
Ser
Met
Gly
Lys
Leu
Tyr
Ser
Leu
Lys
Gln
Asp
Leu
Leu
Ser
Thr
601
602
603
604
605
606
607
608
609
610
611
612
613
614
615
616
617
618
619
620
621
622
623
624
625
626
627
628
629
630
Exon # 16
CTG AAG AAT AAG TCA GTG ACC CAG AAG ACG GAA GCA TGG CTG GAT AAC TTT GCC CGG TGT TGG GAT AAT TTA GTC CAA AAA CTT GAA AAG
Leu
Lys
Asn
Lys
Ser
Val
Thr
Gln
Lys
Thr
Glu
Ala
Trp
Leu
Asp
Asn
Phe
Ala
Arg
Cys
Trp
Asp
Asn
Leu
Val
Gln
Lys
Leu
Glu
Lys
631
632
633
634
635
636
637
638
639
640
641
642
643
644
645
646
647
648
649
650
651
652
653
654
655
656
657
658
659
660
Exon # 16 Exon # 17
AGT ACA GCA CAG ATT TCA CAG GCT GTC ACC ACC ACT CAG CCA TCA CTA ACA CAG ACA ACT GTA ATG GAA ACA GTA ACT ACG GTG ACC ACA
Ser
Thr
Ala
Gln
Ile
Ser
Gln
Ala
Val
Thr
Thr
Thr
Gln
Pro
Ser
Leu
Thr
Gln
Thr
Thr
Val
Met
Glu
Thr
Val
Thr
Thr
Val
Thr
Thr
661
662
663
664
665
666
667
668
669
670
671
672
673
674
675
676
677
678
679
680
681
682
683
684
685
686
687
688
689
690
Exon # 17
AGG GAA CAG ATC CTG GTA AAG CAT GCT CAA GAG GAA CTT CCA CCA CCA CCT CCC CAA AAG AAG AGG CAG ATT ACT GTG GAT TCT GAA ATT
Arg
Glu
Gln
Ile
Leu
Val
Lys
His
Ala
Gln
Glu
Glu
Leu
Pro
Pro
Pro
Pro
Pro
Gln
Lys
Lys
Arg
Gln
Ile
Thr
Val
Asp
Ser
Glu
Ile
691
692
693
694
695
696
697
698
699
700
701
702
703
704
705
706
707
708
709
710
711
712
713
714
715
716
717
718
719
720
Exon # 17 Exon # 18
AGG AAA AGG TTG GAT GTT GAT ATA ACT GAA CTT CAC AGC TGG ATT ACT CGC TCA GAA GCT GTG TTG CAG AGT CCT GAA TTT GCA ATC TTT
Arg
Lys
Arg
Leu
Asp
Val
Asp
Ile
Thr
Glu
Leu
His
Ser
Trp
Ile
Thr
Arg
Ser
Glu
Ala
Val
Leu
Gln
Ser
Pro
Glu
Phe
Ala
Ile
Phe
721
722
723
724
725
726
727
728
729
730
731
732
733
734
735
736
737
738
739
740
741
742
743
744
745
746
747
748
749
750
Exon # 18 Exon # 19
CGG AAG GAA GGC AAC TTC TCA GAC TTA AAA GAA AAA GTC AAT GCC ATA GAG CGA GAA AAA GCT GAG AAG TTC AGA AAA CTG CAA GAT GCC
Arg
Lys
Glu
Gly
Asn
Phe
Ser
Asp
Leu
Lys
Glu
Lys
Val
Asn
Ala
Ile
Glu
Arg
Glu
Lys
Ala
Glu
Lys
Phe
Arg
Lys
Leu
Gln
Asp
Ala
751
752
753
754
755
756
757
758
759
760
761
762
763
764
765
766
767
768
769
770
771
772
773
774
775
776
777
778
779
780
Exon # 19 Exon # 20
AGC AGA TCA GCT CAG GCC CTG GTG GAA CAG ATG GTG AAT GAG GGT GTT AAT GCA GAT AGC ATC AAA CAA GCC TCA GAA CAA CTG AAC AGC
Ser
Arg
Ser
Ala
Gln
Ala
Leu
Val
Glu
Gln
Met
Val
Asn
Glu
Gly
Val
Asn
Ala
Asp
Ser
Ile
Lys
Gln
Ala
Ser
Glu
Gln
Leu
Asn
Ser
781
782
783
784
785
786
787
788
789
790
791
792
793
794
795
796
797
798
799
800
801
802
803
804
805
806
807
808
809
810
Exon # 20
CGG TGG ATC GAA TTC TGC CAG TTG CTA AGT GAG AGA CTT AAC TGG CTG GAG TAT CAG AAC AAC ATC ATC GCT TTC TAT AAT CAG CTA CAA
Arg
Trp
Ile
Glu
Phe
Cys
Gln
Leu
Leu
Ser
Glu
Arg
Leu
Asn
Trp
Leu
Glu
Tyr
Gln
Asn
Asn
Ile
Ile
Ala
Phe
Tyr
Asn
Gln
Leu
Gln
811
812
813
814
815
816
817
818
819
820
821
822
823
824
825
826
827
828
829
830
831
832
833
834
835
836
837
838
839
840
Exon # 20
CAA TTG GAG CAG ATG ACA ACT ACT GCT GAA AAC TGG TTG AAA ATC CAA CCC ACC ACC CCA TCA GAG CCA ACA GCA ATT AAA AGT CAG TTA
Gln
Leu
Glu
Gln
Met
Thr
Thr
Thr
Ala
Glu
Asn
Trp
Leu
Lys
Ile
Gln
Pro
Thr
Thr
Pro
Ser
Glu
Pro
Thr
Ala
Ile
Lys
Ser
Gln
Leu
841
842
843
844
845
846
847
848
849
850
851
852
853
854
855
856
857
858
859
860
861
862
863
864
865
866
867
868
869
870
Exon # 20 Exon # 21
AAA ATT TGT AAG GAT GAA GTC AAC CGG CTA TCA GAT CTT CAA CCT CAA ATT GAA CGA TTA AAA ATT CAA AGC ATA GCC CTG AAA GAG AAA
Lys
Ile
Cys
Lys
Asp
Glu
Val
Asn
Arg
Leu
Ser
Asp
Leu
Gln
Pro
Gln
Ile
Glu
Arg
Leu
Lys
Ile
Gln
Ser
Ile
Ala
Leu
Lys
Glu
Lys
871
872
873
874
875
876
877
878
879
880
881
882
883
884
885
886
887
888
889
890
891
892
893
894
895
896
897
898
899
900
Exon # 21
GGA CAA GGA CCC ATG TTC CTG GAT GCA GAC TTT GTG GCC TTT ACA AAT CAT TTT AAG CAA GTC TTT TCT GAT GTG CAG GCC AGA GAG AAA
Gly
Gln
Gly
Pro
Met
Phe
Leu
Asp
Ala
Asp
Phe
Val
Ala
Phe
Thr
Asn
His
Phe
Lys
Gln
Val
Phe
Ser
Asp
Val
Gln
Ala
Arg
Glu
Lys
901
902
903
904
905
906
907
908
909
910
911
912
913
914
915
916
917
918
919
920
921
922
923
924
925
926
927
928
929
930
Exon # 21 Exon # 22
GAG CTA CAG ACA ATT TTT GAC ACT TTG CCA CCA ATG CGC TAT CAG GAG ACC ATG AGT GCC ATC AGG ACA TGG GTC CAG CAG TCA GAA ACC
Glu
Leu
Gln
Thr
Ile
Phe
Asp
Thr
Leu
Pro
Pro
Met
Arg
Tyr
Gln
Glu
Thr
Met
Ser
Ala
Ile
Arg
Thr
Trp
Val
Gln
Gln
Ser
Glu
Thr
931
932
933
934
935
936
937
938
939
940
941
942
943
944
945
946
947
948
949
950
951
952
953
954
955
956
957
958
959
960
Exon # 22 Exon # 23
AAA CTC TCC ATA CCT CAA CTT AGT GTC ACC GAC TAT GAA ATC ATG GAG CAG AGA CTC GGG GAA TTG CAG GCT TTA CAA AGT TCT CTG CAA
Lys
Leu
Ser
Ile
Pro
Gln
Leu
Ser
Val
Thr
Asp
Tyr
Glu
Ile
Met
Glu
Gln
Arg
Leu
Gly
Glu
Leu
Gln
Ala
Leu
Gln
Ser
Ser
Leu
Gln
961
962
963
964
965
966
967
968
969
970
971
972
973
974
975
976
977
978
979
980
981
982
983
984
985
986
987
988
989
990
Exon # 23
GAG CAA CAA AGT GGC CTA TAC TAT CTC AGC ACC ACT GTG AAA GAG ATG TCG AAG AAA GCG CCC TCT GAA ATT AGC CGG AAA TAT CAA TCA
Glu
Gln
Gln
Ser
Gly
Leu
Tyr
Tyr
Leu
Ser
Thr
Thr
Val
Lys
Glu
Met
Ser
Lys
Lys
Ala
Pro
Ser
Glu
Ile
Ser
Arg
Lys
Tyr
Gln
Ser
991
992
993
994
995
996
997
998
999
1000
1001
1002
1003
1004
1005
1006
1007
1008
1009
1010
1011
1012
1013
1014
1015
1016
1017
1018
1019
1020
Exon # 23
GAA TTT GAA GAA ATT GAG GGA CGC TGG AAG AAG CTC TCC TCC CAG CTG GTT GAG CAT TGT CAA AAG CTA GAG GAG CAA ATG AAT AAA CTC
Glu
Phe
Glu
Glu
Ile
Glu
Gly
Arg
Trp
Lys
Lys
Leu
Ser
Ser
Gln
Leu
Val
Glu
His
Cys
Gln
Lys
Leu
Glu
Glu
Gln
Met
Asn
Lys
Leu
1021
1022
1023
1024
1025
1026
1027
1028
1029
1030
1031
1032
1033
1034
1035
1036
1037
1038
1039
1040
1041
1042
1043
1044
1045
1046
1047
1048
1049
1050
Exon # 23 Exon # 24
CGA AAA ATT CAG AAT CAC ATA CAA ACC CTG AAG AAA TGG ATG GCT GAA GTT GAT GTT TTT CTG AAG GAG GAA TGG CCT GCC CTT GGG GAT
Arg
Lys
Ile
Gln
Asn
His
Ile
Gln
Thr
Leu
Lys
Lys
Trp
Met
Ala
Glu
Val
Asp
Val
Phe
Leu
Lys
Glu
Glu
Trp
Pro
Ala
Leu
Gly
Asp
1051
1052
1053
1054
1055
1056
1057
1058
1059
1060
1061
1062
1063
1064
1065
1066
1067
1068
1069
1070
1071
1072
1073
1074
1075
1076
1077
1078
1079
1080
Exon # 24 Exon # 25
TCA GAA ATT CTA AAA AAG CAG CTG AAA CAG TGC AGA CTT TTA GTC AGT GAT ATT CAG ACA ATT CAG CCC AGT CTA AAC AGT GTC AAT GAA
Ser
Glu
Ile
Leu
Lys
Lys
Gln
Leu
Lys
Gln
Cys
Arg
Leu
Leu
Val
Ser
Asp
Ile
Gln
Thr
Ile
Gln
Pro
Ser
Leu
Asn
Ser
Val
Asn
Glu
1081
1082
1083
1084
1085
1086
1087
1088
1089
1090
1091
1092
1093
1094
1095
1096
1097
1098
1099
1100
1101
1102
1103
1104
1105
1106
1107
1108
1109
1110
Exon # 25
GGT GGG CAG AAG ATA AAG AAT GAA GCA GAG CCA GAG TTT GCT TCG AGA CTT GAG ACA GAA CTC AAA GAA CTT AAC ACT CAG TGG GAT CAC
Gly
Gly
Gln
Lys
Ile
Lys
Asn
Glu
Ala
Glu
Pro
Glu
Phe
Ala
Ser
Arg
Leu
Glu
Thr
Glu
Leu
Lys
Glu
Leu
Asn
Thr
Gln
Trp
Asp
His
1111
1112
1113
1114
1115
1116
1117
1118
1119
1120
1121
1122
1123
1124
1125
1126
1127
1128
1129
1130
1131
1132
1133
1134
1135
1136
1137
1138
1139
1140
Exon # 25 Exon # 26
ATG TGC CAA CAG GTC TAT GCC AGA AAG GAG GCC TTG AAG GGA GGT TTG GAG AAA ACT GTA AGC CTC CAG AAA GAT CTA TCA GAG ATG CAC
Met
Cys
Gln
Gln
Val
Tyr
Ala
Arg
Lys
Glu
Ala
Leu
Lys
Gly
Gly
Leu
Glu
Lys
Thr
Val
Ser
Leu
Gln
Lys
Asp
Leu
Ser
Glu
Met
His
1141
1142
1143
1144
1145
1146
1147
1148
1149
1150
1151
1152
1153
1154
1155
1156
1157
1158
1159
1160
1161
1162
1163
1164
1165
1166
1167
1168
1169
1170
Exon # 26
GAA TGG ATG ACA CAA GCT GAA GAA GAG TAT CTT GAG AGA GAT TTT GAA TAT AAA ACT CCA GAT GAA TTA CAG AAA GCA GTT GAA GAG ATG
Glu
Trp
Met
Thr
Gln
Ala
Glu
Glu
Glu
Tyr
Leu
Glu
Arg
Asp
Phe
Glu
Tyr
Lys
Thr
Pro
Asp
Glu
Leu
Gln
Lys
Ala
Val
Glu
Glu
Met
1171
1172
1173
1174
1175
1176
1177
1178
1179
1180
1181
1182
1183
1184
1185
1186
1187
1188
1189
1190
1191
1192
1193
1194
1195
1196
1197
1198
1199
1200

Exon # 27
AAG AGA GCT AAA GAA GAG GCC CAA CAA AAA GAA GCG AAA GTG AAA CTC CTT ACT GAG TCT GTA AAT AGT GTC ATA GCT CAA GCT CCA CCT
Lys
Arg
Ala
Lys
Glu
Glu
Ala
Gln
Gln
Lys
Glu
Ala
Lys
Val
Lys
Leu
Leu
Thr
Glu
Ser
Val
Asn
Ser
Val
Ile
Ala
Gln
Ala
Pro
Pro
1201
1202
1203
1204
1205
1206
1207
1208
1209
1210
1211
1212
1213
1214
1215
1216
1217
1218
1219
1220
1221
1222
1223
1224
1225
1226
1227
1228
1229
1230
Exon # 27
GTA GCA CAA GAG GCC TTA AAA AAG GAA CTT GAA ACT CTA ACC ACC AAC TAC CAG TGG CTC TGC ACT AGG CTG AAT GGG AAA TGC AAG ACT
Val
Ala
Gln
Glu
Ala
Leu
Lys
Lys
Glu
Leu
Glu
Thr
Leu
Thr
Thr
Asn
Tyr
Gln
Trp
Leu
Cys
Thr
Arg
Leu
Asn
Gly
Lys
Cys
Lys
Thr
1231
1232
1233
1234
1235
1236
1237
1238
1239
1240
1241
1242
1243
1244
1245
1246
1247
1248
1249
1250
1251
1252
1253
1254
1255
1256
1257
1258
1259
1260
Exon # 27 Exon # 28
TTG GAA GAA GTT TGG GCA TGT TGG CAT GAG TTA TTG TCA TAC TTG GAG AAA GCA AAC AAG TGG CTA AAT GAA GTA GAA TTT AAA CTT AAA
Leu
Glu
Glu
Val
Trp
Ala
Cys
Trp
His
Glu
Leu
Leu
Ser
Tyr
Leu
Glu
Lys
Ala
Asn
Lys
Trp
Leu
Asn
Glu
Val
Glu
Phe
Lys
Leu
Lys
1261
1262
1263
1264
1265
1266
1267
1268
1269
1270
1271
1272
1273
1274
1275
1276
1277
1278
1279
1280
1281
1282
1283
1284
1285
1286
1287
1288
1289
1290
Exon # 28 Exon # 29
ACC ACT GAA AAC ATT CCT GGC GGA GCT GAG GAA ATC TCT GAG GTG CTA GAT TCA CTT GAA AAT TTG ATG CGA CAT TCA GAG GAT AAC CCA
Thr
Thr
Glu
Asn
Ile
Pro
Gly
Gly
Ala
Glu
Glu
Ile
Ser
Glu
Val
Leu
Asp
Ser
Leu
Glu
Asn
Leu
Met
Arg
His
Ser
Glu
Asp
Asn
Pro
1291
1292
1293
1294
1295
1296
1297
1298
1299
1300
1301
1302
1303
1304
1305
1306
1307
1308
1309
1310
1311
1312
1313
1314
1315
1316
1317
1318
1319
1320
Exon # 29
AAT CAG ATT CGC ATA TTG GCA CAG ACC CTA ACA GAT GGC GGA GTC ATG GAT GAG CTA ATC AAT GAG GAA CTT GAG ACA TTT AAT TCT CGT
Asn
Gln
Ile
Arg
Ile
Leu
Ala
Gln
Thr
Leu
Thr
Asp
Gly
Gly
Val
Met
Asp
Glu
Leu
Ile
Asn
Glu
Glu
Leu
Glu
Thr
Phe
Asn
Ser
Arg
1321
1322
1323
1324
1325
1326
1327
1328
1329
1330
1331
1332
1333
1334
1335
1336
1337
1338
1339
1340
1341
1342
1343
1344
1345
1346
1347
1348
1349
1350
Exon # 29 Exon # 30
TGG AGG GAA CTA CAT GAA GAG GCT GTA AGG AGG CAA AAG TTG CTT GAA CAG AGC ATC CAG TCT GCC CAG GAG ACT GAA AAA TCC TTA CAC
Trp
Arg
Glu
Leu
His
Glu
Glu
Ala
Val
Arg
Arg
Gln
Lys
Leu
Leu
Glu
Gln
Ser
Ile
Gln
Ser
Ala
Gln
Glu
Thr
Glu
Lys
Ser
Leu
His
1351
1352
1353
1354
1355
1356
1357
1358
1359
1360
1361
1362
1363
1364
1365
1366
1367
1368
1369
1370
1371
1372
1373
1374
1375
1376
1377
1378
1379
1380
Exon # 30
TTA ATC CAG GAG TCC CTC ACA TTC ATT GAC AAG CAG TTG GCA GCT TAT ATT GCA GAC AAG GTG GAC GCA GCT CAA ATG CCT CAG GAA GCC
Leu
Ile
Gln
Glu
Ser
Leu
Thr
Phe
Ile
Asp
Lys
Gln
Leu
Ala
Ala
Tyr
Ile
Ala
Asp
Lys
Val
Asp
Ala
Ala
Gln
Met
Pro
Gln
Glu
Ala
1381
1382
1383
1384
1385
1386
1387
1388
1389
1390
1391
1392
1393
1394
1395
1396
1397
1398
1399
1400
1401
1402
1403
1404
1405
1406
1407
1408
1409
1410

Exon # 31
CAG AAA ATC CAA TCT GAT TTG ACA AGT CAT GAG ATC AGT TTA GAA GAA ATG AAG AAA CAT AAT CAG GGG AAG GAG GCT GCC CAA AGA GTC
Gln
Lys
Ile
Gln
Ser
Asp
Leu
Thr
Ser
His
Glu
Ile
Ser
Leu
Glu
Glu
Met
Lys
Lys
His
Asn
Gln
Gly
Lys
Glu
Ala
Ala
Gln
Arg
Val
1411
1412
1413
1414
1415
1416
1417
1418
1419
1420
1421
1422
1423
1424
1425
1426
1427
1428
1429
1430
1431
1432
1433
1434
1435
1436
1437
1438
1439
1440
Exon # 31 Exon # 32
CTG TCT CAG ATT GAT GTT GCA CAG AAA AAA TTA CAA GAT GTC TCC ATG AAG TTT CGA TTA TTC CAG AAA CCA GCC AAT TTT GAG CAG CGT
Leu
Ser
Gln
Ile
Asp
Val
Ala
Gln
Lys
Lys
Leu
Gln
Asp
Val
Ser
Met
Lys
Phe
Arg
Leu
Phe
Gln
Lys
Pro
Ala
Asn
Phe
Glu
Gln
Arg
1441
1442
1443
1444
1445
1446
1447
1448
1449
1450
1451
1452
1453
1454
1455
1456
1457
1458
1459
1460
1461
1462
1463
1464
1465
1466
1467
1468
1469
1470
Exon # 32
CTA CAA GAA AGT AAG ATG ATT TTA GAT GAA GTG AAG ATG CAC TTG CCT GCA TTG GAA ACA AAG AGT GTG GAA CAG GAA GTA GTA CAG TCA
Leu
Gln
Glu
Ser
Lys
Met
Ile
Leu
Asp
Glu
Val
Lys
Met
His
Leu
Pro
Ala
Leu
Glu
Thr
Lys
Ser
Val
Glu
Gln
Glu
Val
Val
Gln
Ser
1471
1472
1473
1474
1475
1476
1477
1478
1479
1480
1481
1482
1483
1484
1485
1486
1487
1488
1489
1490
1491
1492
1493
1494
1495
1496
1497
1498
1499
1500
Exon # 32 Exon # 33
CAG CTA AAT CAT TGT GTG AAC TTG TAT AAA AGT CTG AGT GAA GTG AAG TCT GAA GTG GAA ATG GTG ATA AAG ACT GGA CGT CAG ATT GTA
Gln
Leu
Asn
His
Cys
Val
Asn
Leu
Tyr
Lys
Ser
Leu
Ser
Glu
Val
Lys
Ser
Glu
Val
Glu
Met
Val
Ile
Lys
Thr
Gly
Arg
Gln
Ile
Val
1501
1502
1503
1504
1505
1506
1507
1508
1509
1510
1511
1512
1513
1514
1515
1516
1517
1518
1519
1520
1521
1522
1523
1524
1525
1526
1527
1528
1529
1530
Exon # 33 Exon # 34
CAG AAA AAG CAG ACG GAA AAT CCC AAA GAA CTT GAT GAA AGA GTA ACA GCT TTG AAA TTG CAT TAT AAT GAG CTG GGA GCA AAG GTA ACA
Gln
Lys
Lys
Gln
Thr
Glu
Asn
Pro
Lys
Glu
Leu
Asp
Glu
Arg
Val
Thr
Ala
Leu
Lys
Leu
His
Tyr
Asn
Glu
Leu
Gly
Ala
Lys
Val
Thr
1531
1532
1533
1534
1535
1536
1537
1538
1539
1540
1541
1542
1543
1544
1545
1546
1547
1548
1549
1550
1551
1552
1553
1554
1555
1556
1557
1558
1559
1560
Exon # 34
GAA AGA AAG CAA CAG TTG GAG AAA TGC TTG AAA TTG TCC CGT AAG ATG CGA AAG GAA ATG AAT GTC TTG ACA GAA TGG CTG GCA GCT ACA
Glu
Arg
Lys
Gln
Gln
Leu
Glu
Lys
Cys
Leu
Lys
Leu
Ser
Arg
Lys
Met
Arg
Lys
Glu
Met
Asn
Val
Leu
Thr
Glu
Trp
Leu
Ala
Ala
Thr
1561
1562
1563
1564
1565
1566
1567
1568
1569
1570
1571
1572
1573
1574
1575
1576
1577
1578
1579
1580
1581
1582
1583
1584
1585
1586
1587
1588
1589
1590
Exon # 34 Exon # 35
GAT ATG GAA TTG ACA AAG AGA TCA GCA GTT GAA GGA ATG CCT AGT AAT TTG GAT TCT GAA GTT GCC TGG GGA AAG GCT ACT CAA AAA GAG
Asp
Met
Glu
Leu
Thr
Lys
Arg
Ser
Ala
Val
Glu
Gly
Met
Pro
Ser
Asn
Leu
Asp
Ser
Glu
Val
Ala
Trp
Gly
Lys
Ala
Thr
Gln
Lys
Glu
1591
1592
1593
1594
1595
1596
1597
1598
1599
1600
1601
1602
1603
1604
1605
1606
1607
1608
1609
1610
1611
1612
1613
1614
1615
1616
1617
1618
1619
1620
Exon # 35
ATT GAG AAA CAG AAG GTG CAC CTG AAG AGT ATC ACA GAG GTA GGA GAG GCC TTG AAA ACA GTT TTG GGC AAG AAG GAG ACG TTG GTG GAA
Ile
Glu
Lys
Gln
Lys
Val
His
Leu
Lys
Ser
Ile
Thr
Glu
Val
Gly
Glu
Ala
Leu
Lys
Thr
Val
Leu
Gly
Lys
Lys
Glu
Thr
Leu
Val
Glu
1621
1622
1623
1624
1625
1626
1627
1628
1629
1630
1631
1632
1633
1634
1635
1636
1637
1638
1639
1640
1641
1642
1643
1644
1645
1646
1647
1648
1649
1650
Exon # 35 Exon # 36
GAT AAA CTC AGT CTT CTG AAT AGT AAC TGG ATA GCT GTC ACC TCC CGA GCA GAA GAG TGG TTA AAT CTT TTG TTG GAA TAC CAG AAA CAC
Asp
Lys
Leu
Ser
Leu
Leu
Asn
Ser
Asn
Trp
Ile
Ala
Val
Thr
Ser
Arg
Ala
Glu
Glu
Trp
Leu
Asn
Leu
Leu
Leu
Glu
Tyr
Gln
Lys
His
1651
1652
1653
1654
1655
1656
1657
1658
1659
1660
1661
1662
1663
1664
1665
1666
1667
1668
1669
1670
1671
1672
1673
1674
1675
1676
1677
1678
1679
1680
Exon # 36
ATG GAA ACT TTT GAC CAG AAT GTG GAC CAC ATC ACA AAG TGG ATC ATT CAG GCT GAC ACA CTT TTG GAT GAA TCA GAG AAA AAG AAA CCC
Met
Glu
Thr
Phe
Asp
Gln
Asn
Val
Asp
His
Ile
Thr
Lys
Trp
Ile
Ile
Gln
Ala
Asp
Thr
Leu
Leu
Asp
Glu
Ser
Glu
Lys
Lys
Lys
Pro
1681
1682
1683
1684
1685
1686
1687
1688
1689
1690
1691
1692
1693
1694
1695
1696
1697
1698
1699
1700
1701
1702
1703
1704
1705
1706
1707
1708
1709
1710
Exon # 36 Exon # 37
CAG CAA AAA GAA GAC GTG CTT AAG CGT TTA AAG GCA GAA CTG AAT GAC ATA CGC CCA AAG GTG GAC TCT ACA CGT GAC CAA GCA GCA AAC
Gln
Gln
Lys
Glu
Asp
Val
Leu
Lys
Arg
Leu
Lys
Ala
Glu
Leu
Asn
Asp
Ile
Arg
Pro
Lys
Val
Asp
Ser
Thr
Arg
Asp
Gln
Ala
Ala
Asn
1711
1712
1713
1714
1715
1716
1717
1718
1719
1720
1721
1722
1723
1724
1725
1726
1727
1728
1729
1730
1731
1732
1733
1734
1735
1736
1737
1738
1739
1740
Exon # 37
TTG ATG GCA AAC CGC GGT GAC CAC TGC AGG AAA TTA GTA GAG CCC CAA ATC TCA GAG CTC AAC CAT CGA TTT GCA GCC ATT TCA CAC AGA
Leu
Met
Ala
Asn
Arg
Gly
Asp
His
Cys
Arg
Lys
Leu
Val
Glu
Pro
Gln
Ile
Ser
Glu
Leu
Asn
His
Arg
Phe
Ala
Ala
Ile
Ser
His
Arg
1741
1742
1743
1744
1745
1746
1747
1748
1749
1750
1751
1752
1753
1754
1755
1756
1757
1758
1759
1760
1761
1762
1763
1764
1765
1766
1767
1768
1769
1770
Exon # 37 Exon # 38
ATT AAG ACT GGA AAG GCC TCC ATT CCT TTG AAG GAA TTG GAG CAG TTT AAC TCA GAT ATA CAA AAA TTG CTT GAA CCA CTG GAG GCT GAA
Ile
Lys
Thr
Gly
Lys
Ala
Ser
Ile
Pro
Leu
Lys
Glu
Leu
Glu
Gln
Phe
Asn
Ser
Asp
Ile
Gln
Lys
Leu
Leu
Glu
Pro
Leu
Glu
Ala
Glu
1771
1772
1773
1774
1775
1776
1777
1778
1779
1780
1781
1782
1783
1784
1785
1786
1787
1788
1789
1790
1791
1792
1793
1794
1795
1796
1797
1798
1799
1800
Exon # 38 Exon # 39
ATT CAG CAG GGG GTG AAT CTG AAA GAG GAA GAC TTC AAT AAA GAT ATG AAT GAA GAC AAT GAG GGT ACT GTA AAA GAA TTG TTG CAA AGA
Ile
Gln
Gln
Gly
Val
Asn
Leu
Lys
Glu
Glu
Asp
Phe
Asn
Lys
Asp
Met
Asn
Glu
Asp
Asn
Glu
Gly
Thr
Val
Lys
Glu
Leu
Leu
Gln
Arg
1801
1802
1803
1804
1805
1806
1807
1808
1809
1810
1811
1812
1813
1814
1815
1816
1817
1818
1819
1820
1821
1822
1823
1824
1825
1826
1827
1828
1829
1830
Exon # 39
GGA GAC AAC TTA CAA CAA AGA ATC ACA GAT GAG AGA AAG CGA GAG GAA ATA AAG ATA AAA CAG CAG CTG TTA CAG ACA AAA CAT AAT GCT
Gly
Asp
Asn
Leu
Gln
Gln
Arg
Ile
Thr
Asp
Glu
Arg
Lys
Arg
Glu
Glu
Ile
Lys
Ile
Lys
Gln
Gln
Leu
Leu
Gln
Thr
Lys
His
Asn
Ala
1831
1832
1833
1834
1835
1836
1837
1838
1839
1840
1841
1842
1843
1844
1845
1846
1847
1848
1849
1850
1851
1852
1853
1854
1855
1856
1857
1858
1859
1860
Exon # 39 Exon # 40
CTC AAG GAT TTG AGG TCT CAA AGA AGA AAA AAG GCT CTA GAA ATT TCT CAT CAG TGG TAT CAG TAC AAG AGG CAG GCT GAT GAT CTC CTG
Leu
Lys
Asp
Leu
Arg
Ser
Gln
Arg
Arg
Lys
Lys
Ala
Leu
Glu
Ile
Ser
His
Gln
Trp
Tyr
Gln
Tyr
Lys
Arg
Gln
Ala
Asp
Asp
Leu
Leu
1861
1862
1863
1864
1865
1866
1867
1868
1869
1870
1871
1872
1873
1874
1875
1876
1877
1878
1879
1880
1881
1882
1883
1884
1885
1886
1887
1888
1889
1890
Exon # 40 Exon # 41
AAA TGC TTG GAT GAC ATT GAA AAA AAA TTA GCC AGC CTA CCT GAG CCC AGA GAT GAA AGG AAA ATA AAG GAA ATT GAT CGG GAA TTG CAG
Lys
Cys
Leu
Asp
Asp
Ile
Glu
Lys
Lys
Leu
Ala
Ser
Leu
Pro
Glu
Pro
Arg
Asp
Glu
Arg
Lys
Ile
Lys
Glu
Ile
Asp
Arg
Glu
Leu
Gln
1891
1892
1893
1894
1895
1896
1897
1898
1899
1900
1901
1902
1903
1904
1905
1906
1907
1908
1909
1910
1911
1912
1913
1914
1915
1916
1917
1918
1919
1920
Exon # 41
AAG AAG AAA GAG GAG CTG AAT GCA GTG CGT AGG CAA GCT GAG GGC TTG TCT GAG GAT GGG GCC GCA ATG GCA GTG GAG CCA ACT CAG ATC
Lys
Lys
Lys
Glu
Glu
Leu
Asn
Ala
Val
Arg
Arg
Gln
Ala
Glu
Gly
Leu
Ser
Glu
Asp
Gly
Ala
Ala
Met
Ala
Val
Glu
Pro
Thr
Gln
Ile
1921
1922
1923
1924
1925
1926
1927
1928
1929
1930
1931
1932
1933
1934
1935
1936
1937
1938
1939
1940
1941
1942
1943
1944
1945
1946
1947
1948
1949
1950
Exon # 41 Exon # 42
CAG CTC AGC AAG CGC TGG CGG GAA ATT GAG AGC AAA TTT GCT CAG TTT CGA AGA CTC AAC TTT GCA CAA ATT CAC ACT GTC CGT GAA GAA
Gln
Leu
Ser
Lys
Arg
Trp
Arg
Glu
Ile
Glu
Ser
Lys
Phe
Ala
Gln
Phe
Arg
Arg
Leu
Asn
Phe
Ala
Gln
Ile
His
Thr
Val
Arg
Glu
Glu
1951
1952
1953
1954
1955
1956
1957
1958
1959
1960
1961
1962
1963
1964
1965
1966
1967
1968
1969
1970
1971
1972
1973
1974
1975
1976
1977
1978
1979
1980
Exon # 42
ACG ATG ATG GTG ATG ACT GAA GAC ATG CCT TTG GAA ATT TCT TAT GTG CCT TCT ACT TAT TTG ACT GAA ATC ACT CAT GTC TCA CAA GCC
Thr
Met
Met
Val
Met
Thr
Glu
Asp
Met
Pro
Leu
Glu
Ile
Ser
Tyr
Val
Pro
Ser
Thr
Tyr
Leu
Thr
Glu
Ile
Thr
His
Val
Ser
Gln
Ala
1981
1982
1983
1984
1985
1986
1987
1988
1989
1990
1991
1992
1993
1994
1995
1996
1997
1998
1999
2000
2001
2002
2003
2004
2005
2006
2007
2008
2009
2010
Exon # 42
CTA TTA GAA GTG GAA CAA CTT CTC AAT GCT CCT GAC CTC TGT GCT AAG GAC TTT GAA GAT CTC TTT AAG CAA GAG GAG TCT CTG AAG AAT
Leu
Leu
Glu
Val
Glu
Gln
Leu
Leu
Asn
Ala
Pro
Asp
Leu
Cys
Ala
Lys
Asp
Phe
Glu
Asp
Leu
Phe
Lys
Gln
Glu
Glu
Ser
Leu
Lys
Asn
2011
2012
2013
2014
2015
2016
2017
2018
2019
2020
2021
2022
2023
2024
2025
2026
2027
2028
2029
2030
2031
2032
2033
2034
2035
2036
2037
2038
2039
2040
Exon # 43
ATA AAA GAT AGT CTA CAA CAA AGC TCA GGT CGG ATT GAC ATT ATT CAT AGC AAG AAG ACA GCA GCA TTG CAA AGT GCA ACG CCT GTG GAA
Ile
Lys
Asp
Ser
Leu
Gln
Gln
Ser
Ser
Gly
Arg
Ile
Asp
Ile
Ile
His
Ser
Lys
Lys
Thr
Ala
Ala
Leu
Gln
Ser
Ala
Thr
Pro
Val
Glu
2041
2042
2043
2044
2045
2046
2047
2048
2049
2050
2051
2052
2053
2054
2055
2056
2057
2058
2059
2060
2061
2062
2063
2064
2065
2066
2067
2068
2069
2070
Exon # 43 Exon # 44
AGG GTG AAG CTA CAG GAA GCT CTC TCC CAG CTT GAT TTC CAA TGG GAA AAA GTT AAC AAA ATG TAC AAG GAC CGA CAA GGG CGA TTT GAC
Arg
Val
Lys
Leu
Gln
Glu
Ala
Leu
Ser
Gln
Leu
Asp
Phe
Gln
Trp
Glu
Lys
Val
Asn
Lys
Met
Tyr
Lys
Asp
Arg
Gln
Gly
Arg
Phe
Asp
2071
2072
2073
2074
2075
2076
2077
2078
2079
2080
2081
2082
2083
2084
2085
2086
2087
2088
2089
2090
2091
2092
2093
2094
2095
2096
2097
2098
2099
2100
Exon # 44
AGA TCT GTT GAG AAA TGG CGG CGT TTT CAT TAT GAT ATA AAG ATA TTT AAT CAG TGG CTA ACA GAA GCT GAA CAG TTT CTC AGA AAG ACA
Arg
Ser
Val
Glu
Lys
Trp
Arg
Arg
Phe
His
Tyr
Asp
Ile
Lys
Ile
Phe
Asn
Gln
Trp
Leu
Thr
Glu
Ala
Glu
Gln
Phe
Leu
Arg
Lys
Thr
2101
2102
2103
2104
2105
2106
2107
2108
2109
2110
2111
2112
2113
2114
2115
2116
2117
2118
2119
2120
2121
2122
2123
2124
2125
2126
2127
2128
2129
2130
Exon # 44 Exon # 45
CAA ATT CCT GAG AAT TGG GAA CAT GCT AAA TAC AAA TGG TAT CTT AAG GAA CTC CAG GAT GGC ATT GGG CAG CGG CAA ACT GTT GTC AGA
Gln
Ile
Pro
Glu
Asn
Trp
Glu
His
Ala
Lys
Tyr
Lys
Trp
Tyr
Leu
Lys
Glu
Leu
Gln
Asp
Gly
Ile
Gly
Gln
Arg
Gln
Thr
Val
Val
Arg
2131
2132
2133
2134
2135
2136
2137
2138
2139
2140
2141
2142
2143
2144
2145
2146
2147
2148
2149
2150
2151
2152
2153
2154
2155
2156
2157
2158
2159
2160
Exon # 45
ACA TTG AAT GCA ACT GGG GAA GAA ATA ATT CAG CAA TCC TCA AAA ACA GAT GCC AGT ATT CTA CAG GAA AAA TTG GGA AGC CTG AAT CTG
Thr
Leu
Asn
Ala
Thr
Gly
Glu
Glu
Ile
Ile
Gln
Gln
Ser
Ser
Lys
Thr
Asp
Ala
Ser
Ile
Leu
Gln
Glu
Lys
Leu
Gly
Ser
Leu
Asn
Leu
2161
2162
2163
2164
2165
2166
2167
2168
2169
2170
2171
2172
2173
2174
2175
2176
2177
2178
2179
2180
2181
2182
2183
2184
2185
2186
2187
2188
2189
2190
Exon # 45 Exon # 46
CGG TGG CAG GAG GTC TGC AAA CAG CTG TCA GAC AGA AAA AAG AGG CTA GAA GAA CAA AAG AAT ATC TTG TCA GAA TTT CAA AGA GAT TTA
Arg
Trp
Gln
Glu
Val
Cys
Lys
Gln
Leu
Ser
Asp
Arg
Lys
Lys
Arg
Leu
Glu
Glu
Gln
Lys
Asn
Ile
Leu
Ser
Glu
Phe
Gln
Arg
Asp
Leu
2191
2192
2193
2194
2195
2196
2197
2198
2199
2200
2201
2202
2203
2204
2205
2206
2207
2208
2209
2210
2211
2212
2213
2214
2215
2216
2217
2218
2219
2220
Exon # 46
AAT GAA TTT GTT TTA TGG TTG GAG GAA GCA GAT AAC ATT GCT AGT ATC CCA CTT GAA CCT GGA AAA GAG CAG CAA CTA AAA GAA AAG CTT
Asn
Glu
Phe
Val
Leu
Trp
Leu
Glu
Glu
Ala
Asp
Asn
Ile
Ala
Ser
Ile
Pro
Leu
Glu
Pro
Gly
Lys
Glu
Gln
Gln
Leu
Lys
Glu
Lys
Leu
2221
2222
2223
2224
2225
2226
2227
2228
2229
2230
2231
2232
2233
2234
2235
2236
2237
2238
2239
2240
2241
2242
2243
2244
2245
2246
2247
2248
2249
2250
Exon # 46 Exon # 47
GAG CAA GTC AAG TTA CTG GTG GAA GAG TTG CCC CTG CGC CAG GGA ATT CTC AAA CAA TTA AAT GAA ACT GGA GGA CCC GTG CTT GTA AGT
Glu
Gln
Val
Lys
Leu
Leu
Val
Glu
Glu
Leu
Pro
Leu
Arg
Gln
Gly
Ile
Leu
Lys
Gln
Leu
Asn
Glu
Thr
Gly
Gly
Pro
Val
Leu
Val
Ser
2251
2252
2253
2254
2255
2256
2257
2258
2259
2260
2261
2262
2263
2264
2265
2266
2267
2268
2269
2270
2271
2272
2273
2274
2275
2276
2277
2278
2279
2280
Exon # 47 Exon # 48
GCT CCC ATA AGC CCA GAA GAG CAA GAT AAA CTT GAA AAT AAG CTC AAG CAG ACA AAT CTC CAG TGG ATA AAG GTT TCC AGA GCT TTA CCT
Ala
Pro
Ile
Ser
Pro
Glu
Glu
Gln
Asp
Lys
Leu
Glu
Asn
Lys
Leu
Lys
Gln
Thr
Asn
Leu
Gln
Trp
Ile
Lys
Val
Ser
Arg
Ala
Leu
Pro
2281
2282
2283
2284
2285
2286
2287
2288
2289
2290
2291
2292
2293
2294
2295
2296
2297
2298
2299
2300
2301
2302
2303
2304
2305
2306
2307
2308
2309
2310
Exon # 48
GAG AAA CAA GGA GAA ATT GAA GCT CAA ATA AAA GAC CTT GGG CAG CTT GAA AAA AAG CTT GAA GAC CTT GAA GAG CAG TTA AAT CAT CTG
Glu
Lys
Gln
Gly
Glu
Ile
Glu
Ala
Gln
Ile
Lys
Asp
Leu
Gly
Gln
Leu
Glu
Lys
Lys
Leu
Glu
Asp
Leu
Glu
Glu
Gln
Leu
Asn
His
Leu
2311
2312
2313
2314
2315
2316
2317
2318
2319
2320
2321
2322
2323
2324
2325
2326
2327
2328
2329
2330
2331
2332
2333
2334
2335
2336
2337
2338
2339
2340
Exon # 48 Exon # 49
CTG CTG TGG TTA TCT CCT ATT AGG AAT CAG TTG GAA ATT TAT AAC CAA CCA AAC CAA GAA GGA CCA TTT GAC GTT AAG GAA ACT GAA ATA
Leu
Leu
Trp
Leu
Ser
Pro
Ile
Arg
Asn
Gln
Leu
Glu
Ile
Tyr
Asn
Gln
Pro
Asn
Gln
Glu
Gly
Pro
Phe
Asp
Val
Lys
Glu
Thr
Glu
Ile
2341
2342
2343
2344
2345
2346
2347
2348
2349
2350
2351
2352
2353
2354
2355
2356
2357
2358
2359
2360
2361
2362
2363
2364
2365
2366
2367
2368
2369
2370
Exon # 49
GCA GTT CAA GCT AAA CAA CCG GAT GTG GAA GAG ATT TTG TCT AAA GGG CAG CAT TTG TAC AAG GAA AAA CCA GCC ACT CAG CCA GTG AAG
Ala
Val
Gln
Ala
Lys
Gln
Pro
Asp
Val
Glu
Glu
Ile
Leu
Ser
Lys
Gly
Gln
His
Leu
Tyr
Lys
Glu
Lys
Pro
Ala
Thr
Gln
Pro
Val
Lys
2371
2372
2373
2374
2375
2376
2377
2378
2379
2380
2381
2382
2383
2384
2385
2386
2387
2388
2389
2390
2391
2392
2393
2394
2395
2396
2397
2398
2399
2400
Exon # 50
AGG AAG TTA GAA GAT CTG AGC TCT GAG TGG AAG GCG GTA AAC CGT TTA CTT CAA GAG CTG AGG GCA AAG CAG CCT GAC CTA GCT CCT GGA
Arg
Lys
Leu
Glu
Asp
Leu
Ser
Ser
Glu
Trp
Lys
Ala
Val
Asn
Arg
Leu
Leu
Gln
Glu
Leu
Arg
Ala
Lys
Gln
Pro
Asp
Leu
Ala
Pro
Gly
2401
2402
2403
2404
2405
2406
2407
2408
2409
2410
2411
2412
2413
2414
2415
2416
2417
2418
2419
2420
2421
2422
2423
2424
2425
2426
2427
2428
2429
2430
Exon # 50 Exon # 51
CTG ACC ACT ATT GGA GCC TCT CCT ACT CAG ACT GTT ACT CTG GTG ACA CAA CCT GTG GTT ACT AAG GAA ACT GCC ATC TCC AAA CTA GAA
Leu
Thr
Thr
Ile
Gly
Ala
Ser
Pro
Thr
Gln
Thr
Val
Thr
Leu
Val
Thr
Gln
Pro
Val
Val
Thr
Lys
Glu
Thr
Ala
Ile
Ser
Lys
Leu
Glu
2431
2432
2433
2434
2435
2436
2437
2438
2439
2440
2441
2442
2443
2444
2445
2446
2447
2448
2449
2450
2451
2452
2453
2454
2455
2456
2457
2458
2459
2460
Exon # 51
ATG CCA TCT TCC TTG ATG TTG GAG GTA CCT GCT CTG GCA GAT TTC AAC CGG GCT TGG ACA GAA CTT ACC GAC TGG CTT TCT CTG CTT GAT
Met
Pro
Ser
Ser
Leu
Met
Leu
Glu
Val
Pro
Ala
Leu
Ala
Asp
Phe
Asn
Arg
Ala
Trp
Thr
Glu
Leu
Thr
Asp
Trp
Leu
Ser
Leu
Leu
Asp
2461
2462
2463
2464
2465
2466
2467
2468
2469
2470
2471
2472
2473
2474
2475
2476
2477
2478
2479
2480
2481
2482
2483
2484
2485
2486
2487
2488
2489
2490
Exon # 51 Exon # 52
CAA GTT ATA AAA TCA CAG AGG GTG ATG GTG GGT GAC CTT GAG GAT ATC AAC GAG ATG ATC ATC AAG CAG AAG GCA ACA ATG CAG GAT TTG
Gln
Val
Ile
Lys
Ser
Gln
Arg
Val
Met
Val
Gly
Asp
Leu
Glu
Asp
Ile
Asn
Glu
Met
Ile
Ile
Lys
Gln
Lys
Ala
Thr
Met
Gln
Asp
Leu
2491
2492
2493
2494
2495
2496
2497
2498
2499
2500
2501
2502
2503
2504
2505
2506
2507
2508
2509
2510
2511
2512
2513
2514
2515
2516
2517
2518
2519
2520
Exon # 52
GAA CAG AGG CGT CCC CAG TTG GAA GAA CTC ATT ACC GCT GCC CAA AAT TTG AAA AAC AAG ACC AGC AAT CAA GAG GCT AGA ACA ATC ATT
Glu
Gln
Arg
Arg
Pro
Gln
Leu
Glu
Glu
Leu
Ile
Thr
Ala
Ala
Gln
Asn
Leu
Lys
Asn
Lys
Thr
Ser
Asn
Gln
Glu
Ala
Arg
Thr
Ile
Ile
2521
2522
2523
2524
2525
2526
2527
2528
2529
2530
2531
2532
2533
2534
2535
2536
2537
2538
2539
2540
2541
2542
2543
2544
2545
2546
2547
2548
2549
2550
Exon # 52 Exon # 53
ACG GAT CGA ATT GAA AGA ATT CAG AAT CAG TGG GAT GAA GTA CAA GAA CAC CTT CAG AAC CGG AGG CAA CAG TTG AAT GAA ATG TTA AAG
Thr
Asp
Arg
Ile
Glu
Arg
Ile
Gln
Asn
Gln
Trp
Asp
Glu
Val
Gln
Glu
His
Leu
Gln
Asn
Arg
Arg
Gln
Gln
Leu
Asn
Glu
Met
Leu
Lys
2551
2552
2553
2554
2555
2556
2557
2558
2559
2560
2561
2562
2563
2564
2565
2566
2567
2568
2569
2570
2571
2572
2573
2574
2575
2576
2577
2578
2579
2580
Exon # 53
GAT TCA ACA CAA TGG CTG GAA GCT AAG GAA GAA GCT GAG CAG GTC TTA GGA CAG GCC AGA GCC AAG CTT GAG TCA TGG AAG GAG GGT CCC
Asp
Ser
Thr
Gln
Trp
Leu
Glu
Ala
Lys
Glu
Glu
Ala
Glu
Gln
Val
Leu
Gly
Gln
Ala
Arg
Ala
Lys
Leu
Glu
Ser
Trp
Lys
Glu
Gly
Pro
2581
2582
2583
2584
2585
2586
2587
2588
2589
2590
2591
2592
2593
2594
2595
2596
2597
2598
2599
2600
2601
2602
2603
2604
2605
2606
2607
2608
2609
2610
Exon # 53 Exon # 54
TAT ACA GTA GAT GCA ATC CAA AAG AAA ATC ACA GAA ACC AAG CAG TTG GCC AAA GAC CTC CGC CAG TGG CAG ACA AAT GTA GAT GTG GCA
Tyr
Thr
Val
Asp
Ala
Ile
Gln
Lys
Lys
Ile
Thr
Glu
Thr
Lys
Gln
Leu
Ala
Lys
Asp
Leu
Arg
Gln
Trp
Gln
Thr
Asn
Val
Asp
Val
Ala
2611
2612
2613
2614
2615
2616
2617
2618
2619
2620
2621
2622
2623
2624
2625
2626
2627
2628
2629
2630
2631
2632
2633
2634
2635
2636
2637
2638
2639
2640
Exon # 54
AAT GAC TTG GCC CTG AAA CTT CTC CGG GAT TAT TCT GCA GAT GAT ACC AGA AAA GTC CAC ATG ATA ACA GAG AAT ATC AAT GCC TCT TGG
Asn
Asp
Leu
Ala
Leu
Lys
Leu
Leu
Arg
Asp
Tyr
Ser
Ala
Asp
Asp
Thr
Arg
Lys
Val
His
Met
Ile
Thr
Glu
Asn
Ile
Asn
Ala
Ser
Trp
2641
2642
2643
2644
2645
2646
2647
2648
2649
2650
2651
2652
2653
2654
2655
2656
2657
2658
2659
2660
2661
2662
2663
2664
2665
2666
2667
2668
2669
2670
Exon # 54 Exon # 55
AGA AGC ATT CAT AAA AGG GTG AGT GAG CGA GAG GCT GCT TTG GAA GAA ACT CAT AGA TTA CTG CAA