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 MSD4 domain:
|
cDNA Name
|
Protein Name
|
Legacy Name
|
Region
|
Description
|
Consequence
|
|
c.803delA
|
p.Asn268IlefsX17
|
935delA
|
exon 7
|
deletion of A at 935
|
frameshift
|
|
c.805_806delAT
|
p.Ile269ProfsX4
|
936delTA
|
exon 7
|
deletion of TA from 936
|
frameshift
|
|
c.812C>G
|
p.Ser271Cys
|
|
|
|
|
|
c.825C>G
|
p.Tyr275X
|
|
exon 7
|
|
|
|
c.827_828delinsAA
|
p.Cys276X
|
|
|
|
|
|
c.828C>A
|
p.Cys276X
|
C276X
|
exon 7
|
C to A at 960
|
Cys to Stop at 276
|
|
c.829T>A
|
p.Trp277Arg
|
W277R
|
exon 7
|
T to A at 961
|
Trp to Arg at 277
|
|
c.830G>A
|
p.Trp277X
|
|
|
|
|
|
c.836_838delAAG
|
p.Glu279del
|
E278del
|
exon 7
|
deletion of AAG from 965
|
deletion of Glu at 278
|
|
c.-236a>T
|
|
|
promoter
|
|
|
|
c.837A>T
|
p.Glu279Asp
|
E279D
|
exon 7
|
A to T at 969
|
Glu to Asp at 279
|
|
c.837A>T
|
p.Glu279Asp
|
E279D
|
exon 7
|
A to T at 969
|
Glu to Asp at 279
|
|
c.842T>C
|
p.Met281Thr
|
M281T
|
exon 7
|
T to C at 974
|
Met to Thr at 281
|
|
c.845_846insA
|
p.Met284AsnfsX3
|
977insA
|
exon 7
|
insertion of A after 977
|
frameshift
|
|
c.846A>T
|
p.Glu282Asp
|
E282D
|
exon 7
|
978A>T
|
|
|
c.853A>T
|
p.Ile285Phe
|
I285F
|
exon 7
|
A to T at 985
|
Ile to Phe at 285
|
|
c.857_858insA
|
p.Asn287LysfsX21
|
989- 992insA
|
exon 7
|
Insertion of A at 989- 992
|
Frameshift
|
|
c.859_863delAACTT
|
p.Asn287LysfsX19
|
991del5
|
exon 7
|
deletion AACTT from 991 or CTTAA from 993
|
frameshift
|
|
c.859A>T
|
p.Asn287Tyr
|
N287Y
|
exon 7
|
A to T at 991
|
Asn to Tyr at 287
|
|
c.861C>G
|
p.Asn287Lys
|
|
exon 7
|
|
|
