Analysis of p.Gly194Arg 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.
There is no gap in the alignment.
The wild-type residue G194 is highly conserved among the CFTR orthologs: 90% (45 / 50 CFTR orthologs)The variant G194R 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 194). 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
|
|
|
194
|
|
Homo sapiens
R
V
L
D
K
I
S
I
G
Q
L
V
S
L
L
S
N
N
L
N
K
F
D
E
G
L
A
L
A
H
F
V
W
I
A
P
L
Q
V
A
L
L
M
G
L
I
W
E
L
L
Pan troglodytes
R
V
L
D
K
I
S
I
G
Q
L
V
S
L
L
S
N
N
L
N
K
F
D
E
G
L
A
L
A
H
F
V
W
I
A
P
L
Q
V
A
L
L
M
G
L
I
W
E
L
L
Pongo pygmaeus
R
V
L
D
K
I
S
I
G
Q
L
V
S
L
L
S
N
N
L
N
K
F
D
E
G
L
A
L
A
H
F
V
W
I
A
P
L
Q
V
A
L
L
M
G
L
I
W
E
L
L
Gorilla gorilla
R
V
L
D
K
I
S
I
G
Q
L
V
S
L
L
S
N
N
L
N
K
F
D
E
G
L
A
L
A
H
F
V
W
I
A
P
L
Q
V
A
L
L
M
G
L
I
W
E
L
L
Nomascus leucogenys
R
V
L
D
K
I
S
I
G
Q
L
V
S
L
L
S
N
N
L
N
K
F
D
E
G
L
A
L
A
H
F
V
W
I
A
P
L
Q
V
A
L
L
M
G
L
I
W
E
L
L
Macaca mulatta
R
V
L
D
K
I
S
I
G
Q
L
V
S
L
L
S
N
N
L
N
K
F
D
E
G
L
A
L
A
H
F
V
W
I
V
P
L
Q
V
A
L
L
M
G
L
I
W
E
L
L
Macaca nemestrina
R
V
L
D
K
I
S
I
G
Q
L
V
S
L
L
S
N
N
L
N
K
F
D
E
G
L
A
L
A
H
F
V
W
I
V
P
L
Q
V
A
L
L
M
G
L
I
W
E
L
L
Macaca fascicularis
R
V
L
D
K
I
S
I
G
Q
L
V
S
L
L
S
N
N
L
N
K
F
D
E
G
L
A
L
A
H
F
V
W
I
V
P
L
Q
V
A
L
L
M
G
L
I
W
E
L
L
Papio anubis
R
V
L
D
K
I
S
I
G
Q
L
V
S
L
L
S
N
N
L
N
K
F
D
E
G
L
A
L
A
H
F
V
W
I
V
P
L
Q
V
A
L
L
M
G
L
I
W
E
L
L
Callithrix jacchus
R
V
L
D
K
I
S
I
G
Q
L
V
S
L
L
S
N
N
L
N
K
F
D
E
G
L
A
L
A
H
F
V
W
I
A
P
L
Q
V
A
L
L
M
G
L
I
W
E
L
L
Chlorocebus aethiops
R
V
L
D
K
I
S
I
G
Q
L
V
S
L
L
S
N
N
L
N
K
F
D
E
G
L
A
L
A
H
F
V
W
I
V
P
L
Q
V
A
L
L
M
G
L
I
W
E
L
L
Colobus guereza
R
V
L
D
K
I
S
I
G
Q
L
V
S
F
L
S
N
N
L
N
K
F
D
E
G
L
A
L
A
H
F
V
W
I
V
P
L
Q
V
A
L
L
M
G
L
I
W
E
L
L
Ateles geoffroyi
R
V
L
D
K
I
S
I
G
Q
L
V
S
L
L
S
N
N
L
N
K
F
D
E
G
L
A
L
A
H
F
V
W
I
A
P
L
Q
V
A
L
L
M
G
L
I
W
E
L
L
Plecturocebus moloch
R
V
L
D
K
I
S
I
G
Q
L
V
S
L
L
S
N
N
L
N
K
F
D
E
G
L
A
L
A
H
F
V
W
I
A
P
L
Q
V
A
L
L
M
G
L
I
W
E
L
L
Saimiri boliviensis
R
V
L
D
K
I
S
I
G
Q
L
V
S
L
L
S
N
N
L
N
K
F
D
E
G
L
A
L
A
H
F
V
W
I
A
P
L
Q
V
A
L
L
M
G
L
I
W
E
L
L
Aotus nancymaae
R
V
L
D
K
I
S
I
G
Q
L
V
S
L
L
S
N
N
L
N
K
F
D
E
G
L
A
L
A
H
F
V
W
I
A
P
L
Q
V
A
L
L
M
G
L
I
W
E
L
L
Otolemur garnettii
R
V
L
D
K
I
S
I
G
Q
L
V
S
L
L
S
N
N
L
N
K
F
D
E
G
L
A
L
A
H
F
V
W
I
A
P
L
Q
V
T
L
L
M
G
L
L
W
E
L
L
Microcebus murinus
R
V
L
D
K
I
S
I
G
Q
L
V
S
L
L
S
N
N
L
N
K
F
D
E
G
L
A
L
A
H
F
V
W
I
A
P
L
Q
V
M
L
L
M
G
L
L
W
E
L
L
Vicugna pacos
R
V
L
D
K
I
S
I
G
Q
L
I
S
L
L
S
N
N
L
N
K
F
D
E
G
L
A
L
A
H
F
V
W
I
A
P
L
Q
V
T
L
L
M
G
L
L
W
E
L
L
Sus scrofa
R
V
L
D
K
I
S
I
G
Q
L
V
S
L
L
S
N
N
L
N
K
F
D
E
G
L
A
L
A
H
F
V
W
I
A
P
L
Q
V
T
L
L
M
G
L
L
W
E
L
L
Bos taurus
R
V
L
D
K
I
S
I
G
Q
L
V
S
L
L
S
N
N
L
N
K
F
D
E
G
L
A
L
A
H
F
V
W
I
A
P
L
Q
V
T
L
L
M
G
L
L
W
E
L
L
Muntiacus reevesi
R
V
L
D
K
I
S
I
G
Q
L
V
S
L
L
S
N
N
L
N
K
F
D
E
G
L
A
L
A
H
F
V
W
I
A
P
L
Q
V
T
L
L
M
G
L
L
W
E
L
L
Muntiacus muntjak
R
V
L
D
K
I
S
I
G
Q
L
V
S
L
L
S
N
N
L
N
K
F
D
E
G
L
A
L
A
H
F
V
W
I
A
P
L
Q
V
T
L
L
M
G
L
L
W
E
L
L
Ovis aries
R
V
L
D
K
I
S
I
G
Q
L
V
S
L
L
S
N
N
L
N
K
F
D
E
G
L
A
L
A
H
F
V
W
I
A
P
L
Q
V
T
L
L
M
G
L
L
W
D
L
L
Equus caballus
R
V
L
D
K
I
S
I
G
Q
L
V
S
L
L
S
N
N
L
N
K
F
D
E
G
L
A
L
A
H
F
V
W
I
A
P
L
Q
V
T
L
L
M
G
L
L
W
D
L
L
Canis familiaris
R
V
L
D
K
I
S
I
G
Q
L
V
S
L
L
S
N
N
L
N
K
F
D
E
G
L
A
L
A
H
F
V
W
I
A
P
L
Q
V
T
L
L
M
G
L
L
W
D
L
L
Loxodonta africana
R
V
L
D
K
I
S
I
G
Q
L
V
S
L
L
S
N
N
L
N
K
F
D
E
G
L
A
L
A
H
F
V
W
I
A
P
L
Q
V
T
L
L
M
G
L
I
W
D
L
L
Mustela furo
R
V
L
D
K
I
S
I
G
Q
L
V
S
L
L
S
N
N
L
N
K
F
D
E
G
L
A
L
A
H
F
V
W
I
A
P
L
Q
V
T
L
L
M
G
L
L
W
D
L
L
Oryctolagus cuniculus
R
V
L
D
K
I
S
I
G
Q
L
I
S
L
L
S
N
N
L
N
K
F
D
E
G
L
A
L
A
H
F
V
W
I
S
P
L
Q
V
T
L
L
M
G
L
L
W
E
L
L
Atelerix albiventris
R
V
L
D
K
I
S
I
G
Q
L
I
S
L
L
S
N
N
L
N
K
F
D
E
G
L
A
L
A
H
F
V
W
I
V
P
L
Q
V
T
L
L
M
G
L
L
W
E
L
L
Dasypus novemcinctus
R
V
L
D
K
I
S
I
G
Q
L
V
S
L
L
S
N
N
L
N
K
F
D
E
G
L
A
L
A
H
F
V
W
I
A
P
L
Q
V
T
L
L
M
G
L
L
W
D
L
L
Rhinolophus ferrumequinum
R
V
L
D
K
I
S
I
G
Q
L
V
S
L
L
S
N
N
L
N
K
F
D
E
G
L
A
L
A
H
F
V
W
I
A
P
L
Q
V
M
L
L
M
G
L
L
W
E
L
L
Cavia porcellus
R
V
L
D
K
I
S
I
G
Q
L
V
S
L
L
S
N
N
L
N
K
F
D
E
G
L
A
L
A
H
F
V
W
I
A
P
L
Q
V
T
L
L
M
G
L
L
W
D
L
L
Monodelphis domestica
R
V
L
D
K
I
S
T
G
Q
L
I
S
L
L
S
N
N
L
N
K
F
D
E
G
L
A
L
A
H
F
V
W
I
V
P
L
Q
V
V
L
L
M
G
L
L
W
D
L
L
Ornithorhynchus anatinus
R
V
L
D
K
I
S
T
G
Q
L
V
S
L
L
S
N
N
L
N
K
F
D
E
G
L
A
L
A
H
F
V
W
I
A
P
L
Q
V
M
L
L
M
G
L
L
W
D
L
L
Didelphis virginiana
R
V
L
D
K
I
S
T
G
Q
L
I
S
L
L
S
N
N
L
N
K
F
D
E
G
L
A
L
A
H
F
V
W
I
V
P
L
Q
V
V
L
L
M
G
L
L
W
D
L
L
Trichosurus vulpecula
R
V
L
D
K
I
S
T
G
Q
L
I
S
L
L
S
N
N
L
N
K
F
D
E
G
L
A
L
A
H
F
V
W
I
A
P
L
Q
V
V
L
L
M
G
L
L
W
D
L
L
Carollia perspicillata
R
V
L
D
K
I
S
I
G
Q
L
V
S
L
L
S
N
N
L
N
K
F
D
E
G
L
A
L
A
H
F
V
W
I
A
P
L
Q
V
T
L
L
M
G
L
L
W
E
L
L
Mus musculus
R
V
L
D
K
I
S
I
G
Q
L
V
S
L
L
S
N
N
L
N
K
F
D
E
G
L
A
L
A
H
F
I
W
I
A
P
L
Q
V
T
L
L
M
G
L
L
W
D
L
L
Rattus norvegicus
R
V
L
D
K
I
S
I
G
Q
L
I
S
L
L
S
N
N
L
N
K
F
D
E
G
L
A
L
A
H
F
I
W
I
A
P
L
Q
V
V
L
L
M
G
L
L
W
D
L
L
Gallus gallus
K
V
L
D
K
I
S
T
G
Q
L
V
S
L
L
S
N
N
L
N
K
F
D
E
G
L
A
L
A
H
F
V
W
I
A
P
L
Q
V
A
L
L
M
G
L
L
W
D
M
L
Taeniopygia guttata
R
V
L
D
K
I
S
T
G
Q
L
V
S
L
L
S
N
N
L
N
K
F
D
E
G
L
A
L
A
H
F
V
W
I
A
P
L
Q
V
A
L
L
M
G
L
L
W
D
M
L
Xenopus tropicalis
R
V
L
D
K
I
S
T
G
Q
L
V
S
L
L
S
N
N
L
N
K
F
D
E
G
L
A
L
A
H
F
V
W
I
A
P
L
Q
V
L
L
L
M
G
L
L
W
D
L
L
Xenopus laevis
K
V
L
D
K
I
S
T
G
Q
L
V
S
L
L
S
N
N
L
N
K
F
D
E
G
L
A
L
A
H
F
V
W
I
A
P
L
Q
V
L
L
L
M
G
L
L
W
D
L
L
Squalus acanthias
R
V
L
D
K
I
D
T
G
Q
L
V
S
L
L
S
N
N
L
N
K
F
D
E
G
V
A
V
A
H
F
V
W
I
A
P
V
Q
V
V
L
L
M
G
L
I
W
N
E
L
Danio rerio
R
V
L
D
K
I
S
T
G
Q
L
V
S
L
M
S
A
N
L
G
K
F
D
Q
S
L
G
M
A
H
F
I
W
I
S
P
L
Q
C
I
L
C
T
G
L
I
W
E
L
I
Oryzias latipes
K
V
L
D
K
I
T
T
G
Q
L
V
S
L
M
S
A
H
L
N
K
L
D
E
S
L
G
L
A
H
F
V
W
I
T
P
L
Q
C
M
L
C
A
G
L
V
W
E
L
I
Takifugu rubripes
R
V
L
D
K
I
S
T
D
Q
L
V
S
L
M
S
A
H
L
N
K
L
D
E
S
L
G
L
A
H
F
I
W
I
T
P
L
Q
C
I
L
C
V
G
L
I
W
E
L
I
Tetraodon nigroviridis
R
V
L
D
N
I
S
T
D
Q
L
V
S
L
M
S
A
H
L
N
K
L
D
E
S
L
G
L
A
H
F
I
W
I
T
P
L
Q
C
I
L
C
V
G
L
I
W
E
L
I
Caenorhabditis elegans
T
S
L
F
E
T
N
S
G
Q
I
I
Q
L
L
N
T
D
A
A
K
L
E
Q
A
F
L
F
A
H
Y
V
W
L
C
P
L
L
M
F
F
Y
A
Y
I
L
W
S
M
F
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 domain MSD1 of CF Transmembrane conductance Regulator has been shown to interact with:
is the membrane-spanning domain 1, composed of six transmembrane helices (TM1-TM6). Four of the six TMs protrude into the cytosol to form the intracellular loops ICL1 (between TM2 and TM3) and ICL2 (between TM4 and TM5). ICL1 contacts NBD1 at the level of the ATP-binding site, while ICL2 binds in a groove located at the surface of NBD2.
MSD1: is the membrane-spanning domain 1, composed of six transmembrane helices (TM1-TM6). Four of the six TMs protrude into the cytosol to form the intracellular loops ICL1 (between TM2 and TM3) and ICL2 (between TM4 and TM5). ICL1 contacts NBD1 at the level of the ATP-binding site, while ICL2 binds in a groove located at the surface of NBD2.
MSD1 of CF Transmembrane conductance Regulator domain alignment including p.Gly194 residue.
***AAPID: Alignment Average Percentage Identity of the Domain (positions are indicated). !AAPIR: Alignment Average Percentage Identity of the Region (20 residues surrounding position 194). 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.
A - 22.84%
F - 13.75%
I - 5.13%
L - 15.85%
M - 1.86%
N - 0.23%
S - 11.89%
T - 1.17%
V - 8.86%
Y - 2.80%
The wild-type residue G194 belongs to the MSD1 domain and is conserved at 15.15% among the MSD1 homologs (65 / 429 MSD1 homologs)
The variant G194R has never been found among the MSD1 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 MSD1 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.
