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 MSD1 domain:
cDNA Name
|
Protein Name
|
Legacy Name
|
Region
|
Description
|
Consequence
|
c.376G>A
|
p.Gly126Ser
|
|
exon 4
|
|
|
c.377G>A
|
p.Gly126Asp
|
G126D
|
exon 4
|
G to A at 509
|
Gly to Asp at 126
|
c.379_381dupTTA
|
p.Leu127dup
|
L127dup
|
exon 4
|
511_513dupTTA
|
|
c.380T>G
|
p.Leu127X
|
L127X
|
exon 4
|
T to G at 512
|
Leu to Stop at 127
|
c.382T>C
|
p.Cys128Arg
|
|
exon 4
|
|
|
c.387delT
|
p.Leu130SerfsX?
|
519delT
|
exon 4
|
T deleted
|
frameshift
|
c.388C>G
|
p.Leu130Val
|
L130V
|
exon 4
|
C to G at 520
|
Leucine to Valine at 130
|
c.393delT
|
p.Phe131LeufsX3
|
525delT
|
exon 4
|
deletion of T at 525
|
frameshift
|
c.396T>G
|
p.Ile132Met
|
I132M
|
exon 4
|
T to G at 528
|
Ile to Met at 132 (sequence variation?)
|
c.400A>G
|
p.Arg134Gly
|
|
|
|
|
c.405_406dupAC
|
p.Leu136HisfsX18
|
|
exon 4
|
|
|
c.409_412delCTCC
|
p.Leu137TyrfsX15
|
541del4
|
exon 4
|
deletion of CTCC from 541
|
frameshift
|
c.409delC
|
p.Leu137SerfsX16
|
541delC
|
exon 4
|
deletion of C at 541
|
frameshift
|
c.410T>A
|
p.Leu137His
|
L137H
|
exon 4
|
T to A at 542
|
Leu to His at 137
|
c.410T>C
|
p.Leu137Pro
|
L137P
|
exon 4
|
T to C at 542
|
Leu to Pro at 137 (sequence variation?)
|
c.410T>G
|
p.Leu137Arg
|
L137R
|
exon 4
|
T to G at 542
|
Leu to Arg at 137
|
c.412_413insACT
|
p.Leu137_Leu138insThr
|
L138ins
|
exon 4
|
insertion of CTA, TAC or ACT at nucleotide 544, 545 or 546
|
insertion of leucine at 138
|
c.413T>C
|
p.Leu138Pro
|
545T/C
|
exon 4
|
T or C at 545
|
sequence variation
|
c.413_415dupTAC
|
p.Leu138dup
|
|
|
|
|
c.414_415insCTA
|
p.Leu139X
|
546insCTA
|
exon 4
|
insertion of CTA at 546
|
frameshift
|
c.415_416insGA
|
p.His139ArgfsX15
|
547insGA
|
exon 4
|
insertion of GA between nucleotides 547 and 548
|
Frameshift; a premature stop codon appears 15 codons further.
|
c.415_416insTA
|
p.His139LeufsX15
|
547insTA
|
exon 4
|
insertion of TA after 547
|
frameshift
|
c.416A>T
|
p.His139Leu
|
H139L
|
exon 4
|
A to T at 548
|
His to Leu at 139
|
c.416A>G
|
p.His139Arg
|
H139R
|
exon 4
|
A to G at 548
|
His to Arg at 139
|
c.417C>T
|
|
549C/T
|
exon 4
|
C to T at 549
|
sequence variation (His at 139 no change)
|
c.418C>T
|
p.Pro140Ser
|
P140S
|
exon 4
|
C to T at 550
|
Pro to Ser at 140
|
c.419C>T
|
p.Pro140Leu
|
P140L
|
exon 4
|
C to T at 551
|
Pro to Leu at 140
|
c.420_421insA
|
p.Ala141SerfsX18
|
552insA
|
exon 4
|
insertion of A after 552
|
frameshift
|
c.422C>A
|
p.Ala141Asp
|
A141D
|
exon 4
|
C to A at 554
|
Ala to Asp at 141
|
c.424delA
|
p.Ile142PhefsX11
|
556delA
|
exon 4
|
deletion of A at 556
|
frameshift
|
c.429delT
|
p.Phe143LeufsX10
|
557delT
|
exon 4
|
deletion of T at 557
|
frameshift
|
c.433delC
|
p.Leu145PhefsX8
|
565delC
|
exon 4
|
deletion of C at 565
|
frameshift
|
c.434T>A
|
p.Leu145His
|
L145H
|
exon 4
|
T to A at 566
|
Leu to His at 145
|
c.437A>G
|
p.His146Arg
|
H146R
|
exon 4
|
A to G at 569
|
His to Arg at 146 (CBAVD)
|
c.438_440delTCA
|
p.His147del
|
|
|
|
|