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.
19 % of the CFTR protein make up the twelve transmembrane domains (M1 - M12). These domains have been shown to be comprised of typical a-helical secondary structure. Many of the residues within these regions form the channel lining residues and have a major role in the regulation of pore function. Six positively charged residues within the transmembrane domains [K95 (M1), R134 (M2), R334 (M6), K335 (M6), R347 (M6) and R1030 (M10] that are well conserved across species. Two of these are associated with mutations causing CF, R334Q/W and R347C/H/L/P.
The mutations happenning in MSD5 domain:
|
cDNA Name
|
Protein Name
|
Legacy Name
|
Region
|
Description
|
Consequence
|
|
c.1057C>T
|
p.Gln353X
|
Q353X
|
exon 8
|
C to T at 1189
|
Gln to Stop at 353
|
|
c.1059A>C
|
p.Gln353His
|
Q353H
|
exon 8
|
A to C at 1191
|
Gln to His at 353
|
|
c.1063C>T
|
p.Pro355Ser
|
P355S
|
exon 8
|
C to T at 1195
|
Pro to Ser at 355
|
|
c.1069delG
|
p.Ala357LeufsX12
|
1199delG
|
exon 8
|
deletion of G at 1199
|
frameshift
|
|
c.1067G>C
|
p.Trp356Ser
|
W356S
|
exon 8
|
G to C at 1199
|
Tryptophan to Serine at codon 356
|
|
c.1068G>A
|
p.Trp356X
|
W356X
|
exon 8
|
G to A at 1200
|
Trp to Stop at 356
|
|
c.[1075C>A;1079C>A]
|
p.[Gln359Lys;Thr360Lys]
|
Q359K/T360K
|
exon 8
|
C to A at 1207 and C to A at 1211
|
Glu to Lys at 359 and Thr to Lys at 360
|
|
c.1076A>G
|
p.Gln359Arg
|
Q359R
|
exon 8
|
A to G at 1208
|
Gln to Arg at 359
|
|
c.1079C>G
|
p.Thr360Arg
|
T360R
|
exon 8
|
C to G at 1211
|
sequence variation? (Thr to Arg at 360)
|
|
c.1081delT
|
p.Trp361GlyfsX8
|
1213delT
|
exon 8
|
deletion of T at 1213
|
frameshift
|
|
c.1081T>A
|
p.Trp361Arg
|
W361R(T- >A)
|
exon 8
|
T to A at 1213
|
Trp to Arg at 361
|
|
c.1081T>C
|
p.Trp361Arg
|
W361R(T- >C)
|
exon 8
|
T to C at 1213
|
Trp to Arg at 361
|
|
c.1083delG
|
p.Trp361CysfsX8
|
1215delG
|
exon 8
|
deletion of G at 1215
|
frameshift
|
|
c.1083G>A
|
p.Trp361X
|
|
|
|
|
|
c.1083_1084insTATGA
|
p.Ser364MetfsX7
|
|
|
|
|
|
c.1086T>G
|
p.Tyr362X
|
|
exon 8
|
|
|
|
c.1086T>A
|
p.Tyr362X
|
|
exon 8
|
|
|
|
c.1093_1094delCT
|
p.Leu365TrpfsX16
|
1221delCT
|
exon 8
|
deletion of CT from 1221
|
frameshift
|
|
c.1089_1091delinsAAT
|
p.Asp363_Ser364delinsGluIle
|
|
exon 8
|
|
|
|
c.1090T>C
|
p.Ser364Pro
|
S364P
|
exon 8
|
T to C at 1222
|
Ser to Pro at 364
|
|
c.1092T>C
|
p.Ser364Ser
|
|
|
|
|
|
c.1094T>C
|
p.Leu365Pro
|
L365P
|
exon 8
|
T to C at 1226
|
Leu to Pro at 365
|
|
c.1101A>T
|
|
1233A/T
|
exon 8
|
A or T at 1233
|
Sequence variation
|
|
c.1111_1112ins6
|
p.Lys370_Ile371insThrLys
|
1243ins6
|
exon 8
|
insertion of ACAAAA after 1243
|
insertion of Asp and Lys after Lys370
|
|
c.1111dupA
|
p.Ile371AsnfsX11
|
|
|
|
|
|
c.1114C>T
|
p.Gln372X
|
|
|
|
|
|
c.1117G>A
|
p.Asp373Asn
|
|
|
|
|
|
c.1119T>G
|
p.Asp373Glu
|
D373E
|
exon 9
|
T to G at 1251
|
Asp to Glu a 373
|
