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 MSD8 domain:
cDNA Name
|
Protein Name
|
Legacy Name
|
Region
|
Description
|
Consequence
|
c.2963C>G
|
p.Pro988Arg
|
|
exon 18
|
|
|
c.2968_2969insA
|
p.Thr990AsnfsX4
|
3100insA
|
exon 18
|
insertion of A after 3100
|
frameshift
|
c.2968A>T
|
p.Thr990Ser
|
|
exon 18
|
|
|
c.2971A>G
|
p.Ile991Val
|
I991V
|
exon 18
|
A to G at 3103
|
Ile to Val at 991
|
c.2977G>T
|
p.Asp993Tyr
|
D993Y
|
exon 18
|
G to T at 3109
|
Asp to Tyr at 993
|
c.2978A>G
|
p.Asp993Gly
|
D993G
|
exon 18
|
A to G at 3110
|
Asp to Gly at 993
|
c.2981T>G
|
p.Phe994Cys
|
F994C
|
exon 18
|
T to G at 3113
|
Phe to Cys at 994
|
c.2988G>A
|
|
3120G- >A
|
exon 18
|
G to A at 3120
|
mRNA splicing defect
|
c.2991G>C
|
p.Leu997Phe
|
L997F
|
exon 19
|
G or C at 3123
|
Leu or Phe at 997 (sequence variation)
|
c.2994_2997delATTA
|
p.Ile1000X
|
3126del4
|
exon 19
|
deletion of ATTA from 3126
|
frameshift
|
c.2997_3000delAATT
|
p.Ile1000X
|
3129del4
|
exon 19
|
deletion of 4 bp from 3129
|
frameshift
|
c.2998_3012del
|
p.Ile1000_Ile1005del
|
3130del15
|
exon 19
|
delete 15 nucleotide at 3130
|
In fram in/del
|
c.2998delA
|
p.Ile1000LeufsX2
|
3130delA
|
exon 19
|
Deletion of A at 3130
|
frameshift
|
c.2998_3012del
|
p.Val1001_Ile1005del
|
3131del15
|
exon 19
|
deletion of 15 bp from 3130, 3131, or 3132
|
deletion of Val at 1001 to Ile at 1005
|
c.3002_3003delTG
|
p.Val1001AspfsX45
|
3132delTG
|
exon 19
|
deletion of TG from 3132
|
frameshift
|
c.3000_3014delTGTGATTGGAGCTAT
|
p.Val1001_Ile1005del
|
|
|
|
|
c.3001G>A
|
p.Val1001Met
|
|
|
|
|
c.3007G>T
|
p.Gly1003X
|
G1003X
|
exon 19
|
G to T at 3139
|
Gly to Stop at 1003
|
c.3008G>A
|
p.Gly1003Glu
|
G1003E
|
exon 19
|
G to A at 3140
|
Gly to Glu at 1003
|
c.3009_3017delAGCTATAGC
|
p.Ala1004_Ala1006del
|
3141del9
|
exon 19
|
del AGCTATAGC from 3141
|
Frameshift
|
c.3014T>G
|
p.Ile1005Arg
|
I1005R
|
exon 19
|
T to G at 3146
|
Ile to Arg at 1005
|
c.3017C>A
|
p.Ala1006Glu
|
A1006E
|
exon 19
|
C to A at 3149
|
Ala to Glu at 1006
|
c.3021delT
|
p.Val1008SerfsX15
|
3152delT
|
exon 19
|
delete T at 3152
|
frameshift
|
c.3021delT
|
p.Val1008SerfsX15
|
3153delT
|
exon 19
|
deletion of T at 3153
|
frameshift
|
c.3022delG
|
p.Val1008SerfsX15
|
3154delG
|
exon 19
|
deletion of G at 3154
|
frameshift
|
c.3023T>A
|
p.Val1008Asp
|
V1008D
|
exon 19
|
T to A at 3155
|
Val to Asp at 1008
|