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 MSD7 domain:
|
cDNA Name
|
Protein Name
|
Legacy Name
|
Region
|
Description
|
Consequence
|
|
c.2770G>A
|
p.Asp924Asn
|
D924N
|
exon 17
|
G to A at 2902
|
Asp to Asn at 924
|
|
c.2770G>T
|
p.Asp924Tyr
|
D924Y
|
exon 17
|
2902G>T
|
|
|
c.2775_2776delTT
|
p.Leu926AlafsX48
|
2907delTT
|
exon 17
|
deletion of TT from 2907
|
frameshift
|
|
c.2777delT
|
p.Leu926CysfsX16
|
2909delT
|
exon 17
|
deletion of T at 2909
|
frameshift
|
|
c.2778G>T
|
p.Leu926Phe
|
|
exon 17
|
|
|
|
c.2780T>C
|
p.Leu927Pro
|
L927P
|
exon 17
|
T to C at 2912
|
Leu to Pro at 927
|
|
c.2782G>C
|
p.Ala928Pro
|
|
|
|
|
|
c.2789G>A
|
p.Gly930Glu
|
|
|
|
|
|
c.2789delG
|
p.Gly930AspfsX12
|
|
|
|
|
|
c.2795T>C
|
p.Phe932Ser
|
F932S
|
exon 17
|
T to C at 2927
|
Phe to Ser at 932
|
|
c.2797A>G
|
p.Arg933Gly
|
R933G
|
exon 17
|
A to G at 2929
|
Arg to Gly at 933
|
|
c.2799A>T
|
p.Arg933Ser
|
R933S
|
exon 17
|
A to T at 2931
|
Arg to Ser at 933 (CBAVD)
|
|
c.2803_2813delCTACCACTGGT
|
p.Leu935AlafsX36
|
|
exon 17
|
|
|
|
c.2805_2810delinsTCAGA
|
p.Leu941X
|
|
exon 17
|
|
|
|
c.2806C>A
|
p.Pro936Thr
|
|
exon 17
|
|
|
|
c.2808A>G
|
|
2940A/G
|
exon 17
|
A or G at 2940
|
sequence variation
|
|
c.2810_2811insT
|
p.Val938GlyfsX37
|
2942insT
|
exon 17
|
insertion of T at 2942
|
frameshift resulting in premature termination at codon 974
|
|
c.2812G>C
|
p.Val938Leu
|
V938L
|
exon 17
|
G to C at 2944
|
Val to Leu at 938
|
|
c.2812dupG
|
p.Val938GlyfsX37
|
|
|
|
|
|
c.2813T>G
|
p.Val938Gly
|
V938G
|
exon 17
|
T to G at 2945
|
Val to Gly at 938 (CAVD)
|
|
c.2815C>G
|
p.His939Asp
|
H939D
|
exon 17
|
C to G at 2947
|
His to Asp at 939
|
|
c.2816_2817delATinsC
|
p.His439ProfsX
|
2948AT- >C
|
exon 17
|
AT to C at 2948
|
frameshift resulting in premature termination at 2953
|
|
c.2816A>G
|
p.His939Arg
|
H939R
|
exon 17
|
A to G at 2948
|
His to Arg at 939
|
|
c.2818_2819delAC
|
p.Thr940SerfsX34
|
|
|
|
|
|
c.2820T>C
|
p.Thr940Thr
|
|
exon 17
|
|
|
|
c.2825delT
|
p.Ile942ThrfsX26
|
2957delT
|
exon 17
|
2957delT
|
|
