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 MSD6 domain:
|
cDNA Name
|
Protein Name
|
Legacy Name
|
Region
|
Description
|
Consequence
|
|
c.1125A>C
|
p.Leu375Phe
|
L375F
|
exon 9
|
A to C at 1257
|
Leu to Phe at 375 (CUAVD)
|
|
c.1127_1128insA
|
p.Gln378AlafsX4
|
1259insA
|
exon 9
|
insertion of A after 1259
|
frameshift
|
|
c.1132C>T
|
p.Gln378X
|
|
|
|
|
|
c.1133A>G
|
p.Gln378Arg
|
Q378R
|
exon 9
|
A to G at 1265
|
Gln to Arg at 378
|
|
c.1135G>A
|
p.Glu379Lys
|
E379K
|
exon 9
|
G to A at 1267
|
Glu to Lys at 379
|
|
c.1135G>T
|
p.Glu379X
|
E379X
|
exon 9
|
G to T at 1267
|
Glu to Stop at 379
|
|
c.1141_1142delAA
|
p.Lys381AspfsX5
|
|
|
|
|
|
c.1148T>C
|
p.Leu383Ser
|
L383S
|
exon 9
|
T to C at 1280
|
Leu to Ser at 383
|
|
c.1149G>A
|
|
L383L (1281G/A)
|
exon 9
|
G or A at 1281
|
sequence variation
|
|
c.1149G>T
|
p.Leu383Phe
|
|
|
|
|
|
c.1152delA
|
p.Glu384AspfsX4
|
1283delA
|
exon 9
|
deletion of A at 1283
|
frameshift
|
|
c.1153_1154insAT
|
p.Asn386IlefsX3
|
1288insTA
|
exon 9
|
Insertion of TA at 1285 Or Insertion of AT at 1284
|
Frameshift
|
|
c.1157_1158insTA
|
p.Leu387ThrfsX2
|
1289insTA
|
exon 9
|
Insertion of TA at 1289
|
Frameshift
|
|
c.1159_1160delTT
|
p.Leu387AsnfsX23
|
1291delTT
|
exon 9
|
delete TT from 1291
|
Frame shift
|
|
c.1162_1168delACGACTA
|
p.Thr388GlnfsX3
|
1294del7
|
exon 9
|
deletion of 7 bp from 1294
|
frameshift
|
|
c.1162_1163delACinsTA
|
p.Thr388X
|
T388X
|
exon 9
|
AC to TA at 1294
|
Thr to Stop at 388
|
|
c.1163C>T
|
p.Thr388Met
|
T388M
|
exon 9
|
C to T at 1295
|
Thr to Met at 388 (sequence variation?)
|
|
c.1164G>T
|
|
1296G/T
|
exon 9
|
G to T at 1296
|
sequence variation (Thr at 388 no change)
|
|
c.1175T>C
|
p.Val392Ala
|
V392A
|
exon 9
|
T to C at 1307
|
Val to Ala at 392 CAVD
|
|
c.1175T>G
|
p.Val392Gly
|
V392G
|
exon 9
|
T to G at 1307
|
Val to Gly at 392
|
|
c.1177delG
|
p.Val393X
|
1309delG
|
exon 9
|
deletion of G at 1309
|
frameshift
|
|
c.1181T>G
|
p.Met394Arg
|
M394R
|
exon 9
|
T to G at 1313
|
Met to Arg at 394
|
