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 MSD2 domain:
|
cDNA Name
|
Protein Name
|
Legacy Name
|
Region
|
Description
|
Consequence
|
|
c.488delA
|
p.Lys163ArgfsX3
|
|
|
|
|
|
c.488A>C
|
p.Lys163Thr
|
K163T
|
exon 4
|
620A>C
|
|
|
c.489G>A
|
|
621G- >A
|
exon 4
|
G to A at 621
|
mRNA splicing defect
|
|
c.490A>G
|
p.Thr164Ala
|
T164A
|
exon 5
|
622A>G
|
|
|
c.494delT
|
p.Leu165X
|
624delT
|
exon 5
|
deletion of T at 624
|
frameshift
|
|
c.494T>C
|
p.Leu165Ser
|
L165S
|
exon 5
|
T to C at 626
|
Leu to Ser at 165
|
|
c.496A>G
|
p.Lys166Glu
|
K166Q
|
exon 5
|
A to G at 628
|
Lys to Gln at 166
|
|
c.500T>G
|
p.Leu167Arg
|
|
exon 5
|
|
|
|
c.503C>T
|
p.Ser168Leu
|
|
|
|
|
|
c.508delC
|
p.Arg170ValfsX3
|
|
|
|
|
|
c.508C>T
|
p.Arg170Cys
|
R170C
|
exon 5
|
C to T at 640
|
Arg to Cys at 170
|
|
c.508C>G
|
p.Arg170Gly
|
R170G
|
exon 5
|
C to G at 640
|
Arg to Gly at 170
|
|
c.508_510delCGT
|
p.Arg170del
|
|
|
|
|
|
c.509G>A
|
p.Arg170His
|
R170H
|
exon 5
|
G to A at 641
|
Arg to His at 170
|
|
c.509G>G
|
p.Arg170Arg
|
|
|
|
|
|
c.518_522delATAAA
|
p.Ile175TyrfsX6
|
650delATAAA
|
exon 5
|
Deletion of ATAAA at 650
|
Frameshift
|
|
c.523A>G
|
p.Ile175Val
|
I175V
|
exon 5
|
A to G at 655
|
Ile to Val at 175
|
|
c.526delA
|
p.Ser176ValfsX13
|
657delA
|
exon 5
|
deletion of A at 657
|
frameshift
|
|
c.529delA
|
p.Ile177LeufsX12
|
|
|
|
|
|
c.530T>C
|
p.Ile177Thr
|
I177T
|
exon 5
|
T to C at 662
|
Ile to Thr at 177
|
|
c.531delT
|
p.Ile177MetfsX12
|
663delT
|
exon 5
|
deletion of T at 663
|
frameshift
|
|
c.531T>G
|
p.Ile177Met
|
I177M
|
exon 5
|
663T>G
|
|
|
c.531dupT
|
p.Gly178TrpfsX5
|
|
|
|
|
|
c.532G>A
|
p.Gly178Arg
|
G178R
|
exon 5
|
G to A at 664
|
Gly to Arg at 178
|
|
c.533G>A
|
p.Gly178Glu
|
G178E
|
exon 5
|
G to A at 665
|
Gly to Glu at 178
|
|
c.535C>A
|
p.Gln179Lys
|
Q179K
|
exon 5
|
C to A at 667
|
Gln to Lys at 179
|
|
c.535C>T
|
p.Gln179X
|
|
|
|
|
|
c.-530a>T
|
|
|
|
|
|
|
c.543_546delTAGT
|
p.Leu183PhefsX5
|
675del4
|
exon 5
|
deletion of TAGT from 675
|
frameshift
|
|
c.544A>G
|
p.Ser182Gly
|
676A/G
|
exon 5
|
A or G at 676
|
sequence variation
|
