Cystic Fibrosis Mutation Database: CFTR Domains

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 MSD12 domain:

cDNA Name	Protein Name	Legacy Name	Region	Description	Consequence
c.3616T>A	p.Ser1206Thr
c.3617C>G	p.Ser1206X	S1206X	exon 22	C to G at 3749	Ser to Stop at 1206
c.3617C>A	p.Ser1206X	S1206X(C>A)	exon 22	C to A at 3749	Ser to Stop at 1206
c.3618_3619delAG	p.Gly1208ProfsX56	3750delAG	exon 22	deletion of AG from 3750	frameshift
c.3618delA	p.Gly1208AlafsX3
c.3623delG	p.Gly1208AlafsX3	3755delG	exon 22	deletion of G between 3751 and 3755	frameshift
c.3627A>C	p.Gln1209His
c.3629T>A	p.Met1210Lys	M1210K	exon 22	T to A at 3761	Met to Lys at 1210
c.3630G>A	p.Met1210Ile	M1210I	exon 22	G to A at 3762	Met to Ile at 1210
c.3634G>A	p.Val1212Ile	V1212I	exon 22	G to A at 3766	Val to Ile at 1212
c.3634G>T	p.Val1212Phe		exon 22
c.3635delT	p.Val1212AlafsX16
c.3639delA	p.Asp1214IlefsX14
c.3648A>C		3780 A/C	exon 22	A to C at 3780	sequence variation
c.3657_3658insA	p.Thr1220AsnfsX45	3789insA	exon 22	insertion of A at 3789	frameshift resulting in a premature termination at 3921
c.3659C>T	p.Thr1220Ile	3791C/T	exon 22	C or T at 3791	sequence variation
c.3659delC	p.Thr1220LysfsX8	3791delC	exon 22	deletion of C at 3791	frameshift
c.3664_3665insTCAA	p.Gly1222ValfsX44		exon 22
c.3667G>A	p.Gly1223Arg
c.3674C>T	p.Ala1225Val		exon 22