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

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The Database was last updated at Apr 25, 2011