The cystic fibrosis transmembrane conductance regulator (CFTR) is a 1480 amino acid membrane bound glycoprotein with a molecular mass of 170,000. It is a member of the ATP binding cassette (ABC)superfamily of proteins. The protein is comprised of two, six span membrane bound regions each connected to a nuclear binding factor which binds ATP. Between these two units is an R-domain which is comprised of many charged amino acids. The R-domain is a unique feature of CFTR within the ABC superfamily.

Put your mouse over the domain region in the following graph to view the summary of that domain, click to view the details.

Many of the mutations identified in CF occur in the first nuclear binding domain (NBF1), while very few occur in NBF2. This is a common feature of the ABC superfamily and indicates a separate role for the two binding domains. The most common mutation in CF DF508 occurs in NBF1. This results in a 3 bp deletion and the loss of a phenylalanine residue. The deletion causes a protein trafficking defect. If this defect is overcome then the protein can form a functional channel. This can be brought about by overexpression of CFTR or by culturing cells at > 30 oC. The NBFs contain a number of highly conserved motifs predicted to bind and hydrolyse ATP. Site directed mutagenesis at these motifs have indicated that ATP binds to both NBFs to control the gating of the channel.

The mutations happenning in NBD2 domain:

cDNA Name Protein Name Legacy Name Region Description Consequence
c.3787A>G p.Thr1263Ala T1263A exon 23 A to G at 3919 Thr to Ala at 1263
c.3788C>T p.Thr1263Ile T1263I exon 23 C to T at 3920 Thr to Ile at 1263
c.3790_3799delGAAGGAGAAA p.Glu1264SerfsX11 3922del10- >C exon 23 deletion of 10 bp from 3922 and replacement with 3921 deletion of Glu1264 to Glu1266
c.3793G>A p.Gly1265Arg
c.3800T>A p.Ile1267Asn exon 23
c.3803A>G p.Gln1268Arg Q1268R exon 23 A to G at 3935 Gln to Arg at 1268
c.3806T>A p.Ile1269Asn I1269N exon 23 T to A at 3938 Ile to Asn at 1269
c.3807C>T 3939C/T exon 23 C or T at 3939 sequence variation
c.3808G>A p.Asp1270Asn D1270N exon 23 G to A at 3940 Asp to Asn at 1270
c.3808G>T p.Asp1270Tyr D1270Y exon 23 G to T at 3940 Asp to Tyr at 1270
c.3816_3817delGT p.Ser1273LeufsX28 3944delGT exon 23 deletion of GT from 3944 frameshift
c.3815_3816delTG p.Ser1273LeufsX28
c.3822G>A p.Trp1274X W1274X exon 23 G to A at 3954 Trp to Stop at 1274
c.3825T>C p.Asp1275Asp exon 23
c.3829delA p.Ile1277X 3960- 3961delA exon 23 Deletion of A at 3960- 3961 Frameshift
c.3835_3836delTT p.Leu1279AlafsX22 exon 23
c.3837G>A p.Leu1279Leu exon 23
c.3841C>T p.Gln1281X Q1281X exon 23 C to T at 3973 Gln to Stop at 1281
c.3844T>G p.Trp1282Gly W1282G exon 23 T to G at 3976 Trp to Gly at 1282
c.3844T>C p.Trp1282Arg W1282R exon 23 T to C at 3976 Trp to Arg at 1282
c.3846G>T p.Trp1282Cys W1282C exon 23 G to T at 3978 Trp to Cys at 1282
c.3846G>A p.Trp1282X W1282X exon 23 G to A at 3978 Trp to Stop at 1282
c.3847A>G p.Arg1283Gly exon 23
c.3848G>A p.Arg1283Lys R1283K exon 23 G to A at 3980 Arg to Lys at 1283
c.3848G>T p.Arg1283Met R1283M exon 23 G to T at 3980 Arg to Met at 1283
c.3854C>T p.Ala1285Val A1285V exon 23 3986C>T
c.3855delC p.Phe1286LeufsX3 exon 23
c.3854C>T p.Ala1285Val exon 23
c.3857T>C p.Phe1286Ser F1286S exon 23 T to C at 3989 Phe to Ser at 1286
c.3868C>T p.Pro1290Ser P1290S exon 23 C to T at 4000 Pro to Ser at 1290
c.3868C>A p.Pro1290Thr P1290T exon 23 C to A at 4000 Pro to Thr at 1290
c.3870A>G P1290P (4002A/G) exon 23 A or G at 4002 sequence variation
c.3871C>T p.Gln1291X Q1291X exon 23 C to T at 4003 Gln to Stop at 1291
c.3872A>G p.Gln1291Arg Q1291R exon 23 A to G at 4004 Gln to Arg at 1291
c.3873G>C p.Gln1291His Q1291H exon 23 G to C at 4005 Gln to His at 1291; mRNA splicing defect (?)
c.3876delA p.Val1293TyrfsX35 4006delA exon 24 deletion of A at 4006 frameshift
c.3877G>A p.Val1293Ile V1293I exon 24 G to A at 4009 Val to Ile at 1293
c.3882_3885delTATT p.Ile1295PhefsX32 4010del4 exon 24 deletion of TATT from 4010 frameshift
c.3883delA p.Ile1295PhefsX33 4015delA exon 24 deletion of A at 4015 frameshift
c.3884_3885insT p.Ser1297PhefsX5 4016insT exon 24 insertion of T at 4016 frameshift
c.3890_3891insT p.Gly1298TrpfsX4 4022insT exon 24 insertion of T at 4022 Frameshift.
c.3892G>T p.Gly1298X
c.3893G>C p.Gly1298Ala G1298A exon 24 4025G>C
c.3893G>T p.Gly1298Val
c.3896C>T p.Thr1299Ile T1299I exon 24 C to T at 4028 Thr to Ile at 1299
c.3897A>G 4029A/G exon 24 A or G at 4029 sequence variation
c.3897A>G p.Thr1299Thr
c.3898T>C p.Phe1300Leu F1300L exon 24 T to C at 4030 Phe to Leu at 1300
c.3905A>G p.Lys1302Arg K1302R exon 24 A to G at 4037 (AAA- >AGA) Lys to Arg at 1302
c.3907A>C p.Asn1303His N1303H exon 24 A to C at 4039 Asn to His at 1303
c.3908delA p.Asn1303ThrfsX25 4040delA exon 24 deletion of A at 4040 frameshift
c.3908A>T p.Asn1303Ile N1303I exon 24 A to T at 4040 Asn to Ile at 1303
c.3908dupA p.Asn1303LysfsX6 exon 24
c.3909_3914del6insTGT p.Leu1304_Asp1305delinsVal1304 4041_4046del6insTGT exon 24 Deletion of nucleotides 4041 to 4046 and insertion of TGT deletion of Leu at 1304 and Asp at 1305, insertion of Val at 1304
c.3909C>G p.Asn1303Lys N1303K exon 24 C to G at 4041 Asn to Lys at 1303
c.3910T>A p.Leu1304Met exon 24
c.3915T>A p.Asp1305Glu D1305E exon 24 T to A at 4047 Asp to Glu at 1305
c.3916_3917insCC p.Tyr1307ProfsX22 4048insCC exon 24 insertion of CC after 4048 frameshift
c.3918C>T P1306P (4050C/T) exon 24 C or T at 4050 sequence variation
c.3920A>G p.Tyr1307Cys Y1307C exon 24 A to G at 4052 Tyr to Cys at 1307
c.3921T>A p.Tyr1307X Y1307X exon 24 T to A at 4053 Tyr to Stop at 1307
c.3922G>T p.Glu1308X E1308X exon 24 G to T at 4054 Glu to Stop at 1308
c.3925C>T p.Gln1309X
c.3925C>G p.Gln1309Glu exon 24
c.3927G>T p.Gln1309His Q1309H exon 24 G to T at 4059 Gln to His at 1309
c.3929G>A p.Trp1310X W1310X exon 24 G to A at 4061 Trp to Stop at 1310
c.3931A>G p.Ser1311Gly S1311R exon 24 A to C at 4063 or T to A or G at 4065 Ser to Arg at 1311
c.3932G>A p.Ser1311Asn exon 24
c.3932_3933delinsAATATG p.Ser1311LysfsX12 exon 24
c.3935A>G p.Asp1312Gly D1312G exon 24 A to G at 4067 Asp to Gly at 1312
c.3937C>A p.Gln1313Lys Q1313K exon 24 C to A at 4069 Gln to Lys at 1313
c.3937C>T p.Gln1313X Q1313X exon 24 C to T at 4069 Gln to Stop at 1313
c.3947G>A p.Trp1316X W1316X exon 24 G to A at 4079 Trp to Stop at 1316
c.3951delA p.Val1318LeufsX10
c.3953T>C p.Val1318Ala V1318A exon 24 T to C at 4085 Val to Ala at 1318
c.3953T>G p.Val1318Gly
c.3954T>C 4086T/C exon 24 T or C at 4086 sequence variation
c.3956C>A p.Ala1319Glu A1319E exon 24 C to A at 4088 Ala to Glu at 1319
c.3957_3958insAGGG p.Asp1320ArgfsX3 4089ins4 exon 24 4089ins4
c.3961G>C p.Glu1321Gln E1321Q exon 24 G to C at 4093 Glu to Gln at 1321
c.3971T>C p.Leu1324Pro L1324P exon 25 T to C at 4103 Leu to Pro at 1324
c.3976delT p.Ser1326LeufsX2 4108delT exon 25 deletion of T at 4108 frameshift
c.3982_3984delATAinsTT p.Ile1328LeufsX? 4114ATA- >TT exon 25 ATA to TT from 4114 Ile to Leu at 1328 and frameshift
c.3985G>C p.Glu1329Gln exon 25
c.3986A>T p.Glu1329Val
c.3997G>T p.Gly1333Trp G1333W exon 25 4129G>T
c.4003C>T p.Leu1335Phe L1335F exon 25 C to T at 4135 Leu to Phe at 1335
c.4004T>C p.Leu1335Pro L1335P exon 25 T to C at 4136 Leu to Pro at 1335
c.4009T>G p.Phe1337Val F1337V exon 25 T to G at 4141 Phe to Val at 1337 (CBAVD)
c.4015C>T p.Leu1339Phe L1339F exon 25 C to T at 4147 Leu to Phe at 1339
c.4027G>A p.Gly1343Ser exon 25
c.4025_4028dupGGGG p.Cys1344GlyfsX16 exon 25
c.4036_4042del p.Leu1346MetfsX6 4168delCTAAGCC exon 25 Deletion of CTAAGCC at 4168
c.4035_4038dupCCTA p.Ser1347ProfsX13 exon 25
c.4039_4040insA p.Ser1347LysfsX12 4171insA exon 25 insertion of A at 4171 Frameshift a premature stop codon appears 12 codons further.
c.4040_4041delGC p.Ser1347ThrfsX11 4172delGC exon 25 deletion of GC from 4172 frameshift
c.4042delC p.His1348MetfsX6 4173delC exon 25 deletion of C at 4173 frameshift
c.4045G>A p.Gly1349Ser G1349S exon 25 G to A at 4177 Gly to Ser at 1349
c.4046G>A p.Gly1349Asp G1349D exon 25 G to A at 4178 Gly to Asp at 1349
c.4051A>G p.Lys1351Glu K1351E exon 25 A to G at 4183 Lys to Glu at 1351 (CBAVD)
c.4054C>G p.Gln1352Glu Q1352E exon 25 C to G at 4186 Gln to Glu at 1352
c.4056G>C p.Gln1352His Q1352H(G- >C) exon 25 G to C at 4188 Gln to His at 1352
c.4056G>T p.Gln1352His Q1352H(G- >T) exon 25 G to T at 4188 Gln to His at 1352
c.4058delT p.Leu1353X
c.4064G>T p.Cys1355Phe
c.4071_4073delTAGinsAA p.Ala1357LeufsX? 4203TAG- >AA exon 25 TAG to AA at 4203 frameshift
c.4074A>T p.Arg1358Ser R1358S exon 25 A to T at 4206 Arg to Ser at 1358
c.4077_4080delTGTTinsAA p.Val1360delfsX? 4209TGTT- >AA exon 25 TGTT to AA from 4209 Frame shift
c.4086_4087insT p.Lys1363X 4218insT exon 25 insertion of T after 4218 frameshift
c.4091C>T p.Ala1364Val A1364V exon 25 C to T at 4223 Ala to Val at 1364 CBAVD
c.4097T>C p.Ile1366Thr I1366T exon 25 T to C at 4229 Ile to Thr at 1366
c.4097T>A p.Ile1366Asn
c.4105_4110delinsAGAA p.Ile1384X exon 25
c.4111G>T p.Glu1371X E1371X exon 25 G to T at 4243 Glu to Stop at 1371
c.4111_4113dupGAA p.Glu1371dup exon 25
c.4114C>A p.Pro1372Thr P1372T exon 25 C to A 4246 Pro to Thr at 1372
c.4115C>T p.Pro1372Leu P1372 L exon 25 C to T at 4247 Pro to Leu at 1732
c.4123C>A p.His1375Asn exon 25
c.4124A>C p.His1375Pro H1375P exon 25 A to C at 4256 His to Pro at 1375
c.4127_4131delTGGAT p.Leu1376SerfsX8 exon 25
c.4129G>C p.Asp1377His D1377H exon 25 G to C at 4261 Asp to His at 1377
c.4139delC p.Thr1380AsnfsX4 4271delC exon 26 deletion of C at 4271 frameshift
c.4140delA p.Tyr1381ThrfsX3 4272delA exon 26 Deletion of nucleotide A at 4272 position Frameshift
c.4141T>C p.Tyr1381His Y1381H exon 26 T to C at 4273 Tyr to His at 1381
c.4143C>A p.Tyr1381X Y1381X exon 26 C to A at 4275 Tyr to Stop at 1381
c.4144C>T p.Gln1382X Q1382X exon 26 C to T at 4276 Gln to Stop at 1382
c.4147_4148insA p.Ile1383AsnfsX3 4279insA exon 26 insertion of A after 4279 frameshift
c.4162C>G p.Leu1388Val L1388V exon 26 C to G at 4294 Leu to Val at 1388
c.4163T>A p.Leu1388Gln L1388Q exon 26 T to A at 4295 Leu to Gln at 1388 (CBAVD)
c.4168C>T p.Gln1390X Q1390X exon 26 4300 C to T Gln to stop at 1390
c.4170delA p.Ala1391HisfsX7 4301(4302?)delA exon 26 deletion of A at 4301 or 4302 frameshift
c.4182T>C p.Asp1394Asp exon 26
c.4190T>A p.Val1397Glu V1397E exon 26 T to A at 4322 Val to Glu at 1397
c.4193T>G p.Ile1398Ser I1398S exon 26 T to G at 4325 Ile to Ser at 1398
c.4196_4197delTC p.Cys1400X 4326delTC exon 26 deletion of TC from 4326 frameshift
c.4196_4197delTC p.Cys1400X 4326delTC exon 26 Deletion of TC from 4326 to 4327 FrameShift
c.4197C>G 4329C/G exon 26 C or G at 4329 Sequence Variation
c.4197C>G p.Leu1399Leu exon 26
c.4200_4201delTG p.Cys1400X 4332delTG exon 26 deletion of TG at 4332 framshift
c.4201dupG p.Glu1401GlyfsX61 exon 26
c.4201G>A p.Glu1401Lys E1401K exon 26 G to A at 4333 Glu to Lys at 1401
c.4201G>T p.Glu1401X E1401X exon 26 G to T at 4333 Glu to Stop at 1401
c.4202A>C p.Glu1401Ala E1401A exon 26 A to C at 4334 Glu to Ala at 1401
c.4202A>G p.Glu1401Gly E1401G exon 26 A to G at 4334 Glu to Gly at 1401
c.4207A>G p.Arg1403Gly
c.4220T>C p.Met1407Thr M1407T exon 26 T to C at 4352 Met to Thr at 1407
c.4224G>A 4356G/A exon 26 G or A at 4356 sequence variation
c.4225G>A p.Glu1409Lys E1409K exon 26 G to A at 4357 Glu to Lys at 1409
c.4226A>T p.Glu1409Val E1409V exon 26 A to T at 4358 Glu to Val at 1409
c.4231C>T p.Gln1411X Q1411X exon 26 C to T at 4363 Gln to Stop at 1411
c.4232A>C p.Gln1411Pro
c.4234C>T p.Gln1412X Q1412X exon 26 C to T at 4366 Gln to Stop at 1412
c.4241T>C p.Leu1414Ser L1414S exon 26 T to C at 4373 Leu to Ser at 1414
c.4242_4242+1delGGinsTT p.Leu1414Phe 4374_4374+ 1GG>TT exon 26 - intron 26 4374_4374+ 1GG>TT mRNA splicing defect
c.4243_4244insCTGT p.Val1415AlafsX48
c.4251delA p.Glu1418ArgfsX14 4382delA exon 27 deletion of A at 4382 frameshift
c.4252G>T p.Glu1418X E1418X exon 27 G to T at 4384 (GAG- >TAG) Glu to Stop at 1418
c.4264C>T p.Arg1422Trp R1422W exon 27 C to T at 4396 Arg to Trp at 1422
c.4272C>T 4404C/T exon 27 C or T at 4404 sequence variation
c.4272C>A p.Tyr1424X exon 27
c.4272C>G p.Tyr1424X
c.4276T>C p.Ser1426Pro S1426P exon 27 T to C at 4408 Ser to Pro at 1426
c.4277C>T p.Ser1426Phe S1426F exon 27 C to T at 4409 Ser to Phe at 1426

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The Database was last updated at Apr 25, 2011