Analysis of p.Glu826Lys variant, CFTR gene, CF Transmembrane conductance Regulator protein (1480 residues)
Data provided and calculated by CYSMA must be considered as predictions.
They are meant for educational purposes only and are provided with NO WARRANTY with respect to their biological reliability.
The mutant residue cannot be found in the alignment.
Following species have a gap at the position:
Caenorhabditis elegans
The wild-type residue E826 is highly conserved among the CFTR orthologs: 96% (48 / 50 CFTR orthologs)The variant E826K has never been found among the CFTR orthologs
*AAPI: Alignment Average Percentage Identity
**AAPIR: Alignment Average Percentage Identity of the Region (20 residues surrounding position 826). AAPIR appears in green if it is more than 10% compared to AAPI, in red if less than 10%. Click here for more details on the alignment.
Divergencies show the amino acids which have been selected in the evolution.
If you find your variant among them with a high occurrence, there are good chances that your variant will most likely either have a small impact or no impact at all on the CFTR function.
Please note that CYSMA does not consider splicing alterations.
Refer to the Help page for more details.
CYSMA's visualizing modules for Ortholog conservation:
⬇ Download the region alignment (50 residues, Fasta format)
⬇ Download the CFTR phylogenic tree
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826
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Homo sapiens
L
T
E
L
D
I
Y
S
R
R
L
S
Q
E
T
G
L
E
I
S
E
E
I
N
E
E
D
L
K
E
C
F
F
D
D
M
E
S
I
P
A
V
T
T
W
N
T
Y
L
R
Pan troglodytes
L
T
E
L
D
I
Y
S
R
R
L
S
Q
E
T
G
L
E
I
S
E
E
I
N
E
E
D
L
K
E
C
F
F
D
D
M
E
S
I
P
A
V
T
T
W
N
T
Y
L
R
Pongo pygmaeus
L
T
E
L
D
I
Y
S
R
R
L
S
Q
E
T
G
L
E
I
S
E
E
I
N
E
E
D
L
K
E
C
F
F
D
D
M
E
S
I
P
A
V
T
T
W
N
T
Y
L
R
Gorilla gorilla
L
T
E
L
D
I
Y
S
R
R
L
S
Q
E
T
G
L
E
I
S
E
E
I
N
E
E
D
L
K
E
C
F
F
D
D
M
E
S
I
P
A
V
T
T
W
N
T
Y
L
R
Nomascus leucogenys
L
T
E
L
D
I
Y
S
R
R
L
S
Q
E
T
G
L
E
I
S
E
E
I
N
E
E
D
L
K
E
C
F
F
D
D
M
E
S
I
P
A
V
T
T
W
N
T
Y
L
R
Macaca mulatta
L
T
E
L
D
I
Y
S
R
R
L
S
Q
E
T
G
L
E
I
S
E
E
I
N
E
E
D
L
K
E
C
F
F
D
D
M
E
S
I
P
A
V
T
T
W
N
T
Y
L
R
Macaca nemestrina
L
T
E
L
D
I
Y
S
R
R
L
S
Q
E
T
G
L
E
I
S
E
E
I
N
E
E
D
L
K
E
C
F
F
D
D
M
E
S
I
P
A
V
T
T
W
N
T
Y
L
R
Macaca fascicularis
L
T
E
L
D
I
Y
S
R
R
L
S
Q
E
T
G
L
E
I
S
E
E
I
N
E
E
D
L
K
E
C
F
F
D
D
M
E
S
I
P
A
V
T
T
W
N
T
Y
L
R
Papio anubis
L
T
E
L
D
I
Y
S
R
R
L
S
Q
E
T
G
L
E
I
S
E
E
I
N
E
E
D
L
K
E
C
F
F
D
D
M
E
S
I
P
A
V
T
T
W
N
T
Y
L
R
Callithrix jacchus
L
T
E
L
D
I
Y
S
R
R
L
S
Q
E
T
G
L
E
I
S
E
E
I
N
E
E
D
L
K
E
C
F
F
D
D
M
E
S
I
P
A
V
T
T
W
N
T
Y
L
R
Chlorocebus aethiops
L
T
E
L
D
I
Y
S
R
R
L
S
Q
E
T
G
L
E
I
S
E
E
I
N
E
E
D
L
K
E
C
F
F
D
D
M
E
S
I
P
A
V
T
T
W
N
T
Y
L
R
Colobus guereza
L
T
E
L
D
I
Y
S
R
R
L
S
Q
E
T
G
L
E
I
S
E
E
I
N
E
E
D
L
K
E
C
F
F
D
D
M
E
S
I
P
A
V
T
T
W
N
T
Y
L
R
Ateles geoffroyi
L
T
E
L
D
I
Y
S
R
R
L
S
Q
E
T
G
L
E
I
S
E
E
I
N
E
E
D
L
K
E
C
F
F
D
N
M
E
S
I
P
A
V
T
T
W
N
T
Y
L
R
Plecturocebus moloch
L
T
E
L
D
I
Y
S
R
R
L
S
Q
E
T
G
L
E
I
S
E
E
I
N
E
E
D
L
K
E
C
F
F
D
D
M
E
S
I
P
A
V
T
T
W
N
T
Y
L
R
Saimiri boliviensis
L
T
E
L
D
I
Y
S
R
R
L
S
Q
E
T
G
L
E
I
S
E
E
I
N
E
E
D
L
K
E
C
F
F
D
D
M
E
S
I
P
A
V
T
T
W
N
T
Y
L
R
Aotus nancymaae
L
T
E
L
D
I
Y
S
R
R
L
S
Q
E
T
G
L
E
I
S
E
E
I
N
E
E
D
L
K
E
C
F
F
D
D
M
E
S
I
P
A
V
T
T
W
N
T
Y
L
R
Otolemur garnettii
L
T
E
M
D
I
Y
S
R
R
L
S
Q
E
S
S
L
E
I
S
E
E
I
N
E
E
Y
L
K
E
C
F
C
D
D
V
E
N
I
P
A
V
T
T
W
N
T
Y
L
R
Microcebus murinus
L
T
E
M
D
I
Y
S
R
R
L
S
Q
E
S
S
L
E
I
S
E
E
I
N
E
E
D
L
K
E
C
F
F
D
D
A
E
N
I
P
A
V
T
T
W
N
T
Y
L
R
Vicugna pacos
L
T
E
I
D
I
Y
S
R
R
L
S
Q
D
I
G
L
E
I
S
E
E
I
N
E
E
D
L
R
E
C
F
F
D
D
V
E
N
I
P
A
V
T
T
W
N
T
Y
L
R
Sus scrofa
L
T
E
I
D
I
Y
S
R
R
L
S
Q
D
T
G
L
E
I
S
E
E
I
N
E
E
D
L
R
E
C
F
F
D
D
V
E
S
I
P
T
V
T
T
W
N
T
Y
L
R
Bos taurus
L
A
E
I
D
I
Y
S
R
R
L
S
Q
D
T
G
L
E
I
S
E
E
I
N
E
E
D
L
R
D
C
F
F
D
D
V
E
N
I
P
A
V
T
T
W
N
T
Y
L
R
Muntiacus reevesi
L
A
E
I
D
I
Y
S
R
R
L
S
Q
D
T
G
L
E
I
S
E
E
I
N
E
E
D
L
R
D
C
F
F
D
D
V
E
N
I
P
A
V
T
T
W
N
T
Y
L
R
Muntiacus muntjak
L
A
E
I
D
I
Y
S
R
R
L
S
Q
D
T
G
L
E
I
S
E
E
I
N
E
E
D
L
R
D
C
F
F
D
D
V
E
N
I
P
A
V
T
T
W
N
T
Y
L
R
Ovis aries
L
A
E
I
D
I
Y
S
R
R
L
S
Q
D
T
G
L
E
I
S
E
E
I
N
E
E
D
L
R
D
C
F
F
D
D
V
E
N
I
P
A
V
T
T
W
N
T
Y
L
R
Equus caballus
L
T
E
M
D
I
Y
S
R
R
L
S
Q
D
S
G
L
E
I
S
E
E
I
N
E
D
D
L
K
E
C
F
F
D
D
V
E
S
I
P
T
V
T
T
W
N
T
Y
L
R
Canis familiaris
L
T
E
M
D
I
Y
S
R
R
L
S
Q
D
S
G
L
E
I
S
E
E
I
N
E
E
D
L
K
E
C
F
F
D
D
V
E
S
I
P
P
V
T
T
W
N
T
Y
L
R
Loxodonta africana
L
T
E
M
D
I
Y
S
R
R
L
S
Q
D
S
G
L
E
I
S
E
E
I
N
E
E
D
L
K
E
C
F
F
D
D
V
E
N
M
P
P
V
T
T
W
N
T
Y
L
R
Mustela furo
L
T
E
M
D
I
Y
S
R
R
L
S
Q
D
S
G
L
E
I
S
E
E
I
N
E
E
D
L
K
E
C
F
I
D
D
V
E
S
I
P
P
V
T
T
W
N
T
Y
L
R
Oryctolagus cuniculus
L
T
E
M
D
I
Y
S
R
R
L
S
Q
E
S
G
L
E
I
S
E
E
I
N
E
E
D
L
K
E
C
F
I
D
D
V
D
S
I
P
T
V
T
T
W
N
T
Y
L
R
Atelerix albiventris
F
T
E
M
D
I
Y
S
R
R
L
S
Q
D
S
G
L
E
I
S
E
E
I
N
E
E
D
L
K
E
C
F
F
D
D
V
E
N
I
P
A
V
T
T
W
N
T
Y
L
R
Dasypus novemcinctus
L
V
E
M
D
I
Y
S
R
R
L
S
Q
D
S
G
L
E
I
S
E
E
I
N
E
E
D
L
K
E
C
F
L
D
D
V
E
S
I
P
A
V
T
T
W
N
T
Y
L
R
Rhinolophus ferrumequinum
F
T
E
M
D
I
Y
S
R
R
L
S
Q
D
N
G
L
E
I
S
E
E
I
N
E
E
D
L
K
E
C
L
F
D
D
L
E
S
I
P
A
V
T
T
W
N
T
Y
L
R
Cavia porcellus
L
T
E
M
D
I
Y
S
R
R
L
S
Q
D
S
S
L
E
I
N
E
E
I
N
E
E
D
L
K
E
C
F
F
D
D
V
E
N
I
P
T
V
T
T
W
N
T
Y
L
R
Monodelphis domestica
L
S
E
I
D
I
Y
S
R
R
L
S
Q
D
S
G
M
D
I
S
D
E
I
N
E
E
D
L
K
E
W
F
F
D
D
V
E
N
I
P
A
V
T
T
W
N
T
Y
L
R
Ornithorhynchus anatinus
M
S
E
M
D
I
Y
S
R
R
L
S
K
D
S
G
L
E
I
S
E
E
I
N
E
E
D
L
K
E
C
F
I
D
D
I
E
S
T
T
S
V
T
T
W
N
T
Y
L
R
Didelphis virginiana
L
S
E
I
D
I
Y
S
R
R
L
S
Q
D
S
G
M
D
I
S
D
E
I
N
E
E
D
L
K
E
W
F
F
D
D
V
E
N
I
P
A
V
T
T
W
N
T
Y
L
R
Trichosurus vulpecula
L
S
E
I
D
I
Y
S
R
R
L
S
R
D
S
G
M
D
I
S
D
E
I
N
E
E
D
L
K
E
W
F
F
D
D
V
E
N
I
P
A
V
T
T
W
N
T
Y
L
R
Carollia perspicillata
L
A
E
M
D
I
Y
S
R
R
L
S
Q
G
S
G
L
E
I
S
E
E
I
N
E
E
D
L
K
E
C
F
F
D
D
M
E
S
I
P
T
V
T
T
W
N
T
Y
L
R
Mus musculus
L
N
E
V
D
V
Y
S
R
R
L
S
Q
D
S
T
L
N
I
T
E
E
I
N
E
E
D
L
K
E
C
F
L
D
D
V
I
K
I
P
P
V
T
T
W
N
T
Y
L
R
Rattus norvegicus
L
K
E
E
D
I
Y
S
R
R
L
S
Q
D
S
T
L
N
I
T
E
E
I
N
E
E
D
L
K
E
C
F
F
D
D
M
V
K
I
P
T
V
T
T
W
N
T
Y
L
R
Gallus gallus
L
S
E
I
D
I
Y
T
R
R
L
S
R
D
S
I
L
D
I
T
D
E
I
N
E
E
D
L
K
E
C
F
T
D
D
A
E
S
M
G
T
V
T
T
W
N
T
Y
F
R
Taeniopygia guttata
L
S
E
I
D
I
Y
N
R
R
V
S
R
D
S
V
L
D
I
T
D
E
I
S
E
E
D
L
K
E
C
F
S
D
D
A
E
S
M
G
T
V
T
T
W
N
T
Y
F
R
Xenopus tropicalis
S
S
E
V
D
I
Y
N
R
R
L
S
Q
D
S
I
L
E
V
S
E
E
I
N
E
E
D
L
K
E
C
F
L
D
D
T
D
S
P
S
P
T
T
T
W
N
T
Y
I
R
Xenopus laevis
S
S
D
L
D
I
Y
N
R
R
L
S
Q
D
S
I
L
E
V
S
E
E
I
N
E
E
D
L
K
E
C
F
L
D
D
T
D
S
Q
S
P
T
T
T
W
N
T
Y
L
R
Squalus acanthias
F
S
E
I
D
I
Y
S
R
R
L
S
E
D
G
S
F
E
I
S
E
E
I
N
E
E
D
L
K
E
C
F
A
D
E
E
E
I
Q
N
V
T
T
T
W
S
T
Y
L
R
Danio rerio
L
A
E
L
D
I
Y
T
R
R
L
S
-
D
S
T
Y
D
M
T
G
I
L
E
E
E
N
I
E
A
C
L
T
D
E
I
E
E
T
F
E
T
T
K
W
N
T
Y
V
R
Oryzias latipes
L
A
E
L
D
I
Y
A
R
R
L
S
K
D
S
V
F
E
I
T
E
E
V
E
E
E
D
M
E
Q
C
F
A
D
E
R
E
N
V
F
V
T
T
S
W
S
T
Y
L
R
Takifugu rubripes
L
A
E
L
D
I
Y
A
R
R
L
S
K
D
S
V
Y
D
I
S
E
D
V
D
T
E
D
M
E
Q
C
F
A
D
D
R
D
N
T
F
E
T
T
S
W
S
T
Y
L
R
Tetraodon nigroviridis
L
A
E
L
D
I
Y
A
R
R
L
S
K
D
S
V
Y
D
I
S
E
D
V
D
E
E
D
M
E
Q
C
F
A
D
D
R
E
N
T
F
E
T
T
S
W
S
T
Y
L
R
Caenorhabditis elegans
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
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K
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Species color legend (basic classification):
Great apes | Other monkeys | Prosimians | Other mammals | Lizards | Birds | Amphibians | Fishes | Insects | Nematods | Tunicates | Echinoderms
Ortholog sequences have been selected from the Ensembl(1) and
NCBI websites. Alignment has been performed with
ClustalW(2), version 1.83 or 2.0.7.
Trees have been built using Phylogeny.fr(3), based on the alignments.
Software used is PhyML 3.0 aLRT with default parameters. Pictures of trees have been made using Phylip at Mobyle.
AAPI and AAPIR have been calculated thanks to Bioperl.
Domain conservation:
The residue p.Glu826 belongs to the domain R.
650
842
the regulatory (R) domain links the two transporter halves (MSD1-NBD1 and MSD2-NBD2). It is a highly flexible region and it contains multiple phosphorylation sites, which are the target of Protein Kinase A and B (PKA and PKC), and control the gating and traffiking of the chloride chanel.
R: the regulatory (R) domain links the two transporter halves (MSD1-NBD1 and MSD2-NBD2). It is a highly flexible region and it contains multiple phosphorylation sites, which are the target of Protein Kinase A and B (PKA and PKC), and control the gating and traffiking of the chloride chanel.
R of CF Transmembrane conductance Regulator domain alignment including p.Glu826 residue.
***AAPID: Alignment Average Percentage Identity of the Domain (positions are indicated). !AAPIR: Alignment Average Percentage Identity of the Region (20 residues surrounding position 826). AAPIR appears in green if it is more than 10% compared to AAPID, in red if less than 10%.
Divergencies
Residues present in more than 10% of the sequences are highlighted in blue.
T - 2.13%
The wild-type residue E826 belongs to the R domain and is conserved at 97.87% among the R homologs (46 / 47 R homologs)
The variant E826K has never been found among the R homologs
Divergencies show the amino acids which have been selected in the evolution. Residues present in more than 10% of the sequences are highlighted in blue.
Please note that CYSMA does not consider splicing alterations.
Refer to the Help page for more details.
CYSMA's visualizing modules for R domain conservation:
Sequence alignments for NBDs have all been extracted from Prosite(4). Sequence alignments for MSDs have been extracted using the PSI-BLAST web server.
Sequences alignments have been manually re-aligned using a structural alignment including the human CFTR and bacterian ABC transporters with know 3D structures (for MSDs and NBDs domains).
Predictions of secondary structures have been made with PsiPred(9)
, version 2.5, using Protein Multiple Sequences Alignments as input, in order to increase the accuracy of the prediction.
Amino acid frequencies have been calculated from a non redondant set defined by the RCSB.
The Help page will tell you more about it.
