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 MSD10 domain:
|
cDNA Name
|
Protein Name
|
Legacy Name
|
Region
|
Description
|
Consequence
|
|
c.3274T>C
|
p.Tyr1092His
|
Y1092H
|
exon 20
|
T to C at 3406
|
Tyr to His at 1092
|
|
c.3275A>G
|
p.Tyr1092Cys
|
Y1092C
|
exon 20
|
A to G at 3407
|
Tyr to Cys at 1092
|
|
c.3276C>A
|
p.Tyr1092X
|
Y1092X(C- >A)
|
exon 20
|
C to A at 3408
|
Tyr to Stop at 1092
|
|
c.3276C>G
|
p.Tyr1092X
|
Y1092X(C- >G)
|
exon 20
|
C to G at 3408
|
Tyr to Stop at 1092
|
|
c.3278T>C
|
p.Leu1093Pro
|
L1093P
|
exon 20
|
T to C at 3410
|
Leu to Pro at 1093
|
|
c.3285A>T
|
|
3417A/T
|
exon 20
|
A or T at 3417
|
sequence variation
|
|
c.3287delT
|
p.Leu1096ArgfsX6
|
3419delT
|
exon 20
|
deletion of T at 3419
|
frameshift
|
|
c.3287T>G
|
p.Leu1096Arg
|
L1096R
|
exon 20
|
T to G at 3419
|
Leu to Arg at 1096
|
|
c.3291delC
|
p.Trp1098GlyfsX4
|
3423delC
|
exon 20
|
deletion of C at 3423
|
frameshift
|
|
c.3292T>C
|
p.Trp1098Arg
|
W1098R
|
exon 20
|
T to C at 3424
|
Trp to Arg at 1098
|
|
c.3294delG
|
p.Trp1098CysfsX4
|
3425delG
|
exon 20
|
deletion of G at 3425 or 3426
|
frameshift
|
|
c.3293G>T
|
p.Trp1098Leu
|
W1098L
|
exon 20
|
G to T at 3425
|
Trp to Leu at 1098
|
|
c.3293G>A
|
p.Trp1098X
|
W1098X(TAG)
|
exon 20
|
G to A at 3425
|
Trp to Stop at 1098
|
|
c.3294G>A
|
p.Trp1098X
|
W1098X(TGA)
|
exon 20
|
G to A at 3426
|
Trp to Stop at 1098
|
|
c.3294G>C
|
p.Trp1098Cys
|
|
|
|
|
|
c.3297C>A
|
p.Phe1099Leu
|
|
|
|
|
|
c.3298C>A
|
p.Gln1100Lys
|
|
|
|
|
|
c.3299A>C
|
p.Gln1100Pro
|
Q1100P
|
exon 20
|
A to C at 3431
|
Gln to Pro at 1100
|
|
c.3302T>A
|
p.Met1101Lys
|
M1101K
|
exon 20
|
T to A at 3434
|
Met to Lys at 1101
|
|
c.3302T>G
|
p.Met1101Arg
|
M1101R
|
exon 20
|
T to G at 3434
|
Met to Arg at 1101
|
|
c.3304A>T
|
p.Arg1102X
|
R1102X
|
exon 20
|
A to T at 3436
|
Arg to Stop at 1102
|
|
c.3306A>G
|
|
3438A/G
|
exon 20
|
A or G at 3438
|
Sequence variation
|
|
c.3308T>A
|
p.Ile1103Lys
|
|
|
|
|
|
c.3310G>T
|
p.Glu1104X
|
E1104X
|
exon 20
|
G to T at 3442
|
Glu to Stop at 1104
|
|
c.3310G>A
|
p.Glu1104Lys
|
|
|
|
|
|
c.3314T>G
|
p.Met1105Arg
|
M1105R
|
exon 20
|
T to G at 3446
|
Met to Arg at 1105
|
|
c.3315delG
|
p.Met1105IlefsX16
|
3447delG
|
exon 20
|
Deleletion of G at 3447
|
Frameshift
|
|
c.3321dupT
|
p.Val1108CysfsX48
|
|
|
|
|
|
c.3322G>C
|
p.Val1108Leu
|
V1108L
|
exon 20
|
G to C at 3454
|
Val to Leu at 1108
|
