Molecule Information

General Information of the Molecule (ID: Mol01835)
Name
Guanine nucleotide-binding protein subunit alpha-11 (GNA11) ,Homo sapiens
Synonyms
Guanine nucleotide-binding protein subunit alpha-11; G alpha-11; G-protein subunit alpha-11; Guanine nucleotide-binding protein G(y) subunit alpha; GNA11; GA11
    Click to Show/Hide
Molecule Type
Protein
Gene Name
GNA11
Gene ID
2767
Location
chr19:3,094,362-3,123,999[+]
Sequence
MTLESMMACC LSDEVKESKR INAEIEKQLR RDKRDARREL KLLLLGTGES GKSTF
IKQMR IIHGAGYSEE DKRGFTKLVY QNIFTAMQAM IRAMETLKIL YKYEQNKANA
LLIREVDVEK VTTFEHQYVS AIKTLWEDPG IQECYDRRRE YQLSDSAKYY LTDV
DRIATL GYLPTQQDVL RVRVPTTGII EYPFDLENII FRMVDVGGQR SERRKWIHC
F ENVTSIMFLV ALSEYDQVLV ESDNENRMEE SKALFRTIIT YPWFQNSSVI LFL
NKKDLLE DKILYSHLVD YFPEFDGPQR DAQAAREFIL KMFVDLNPDS DKIIYSHF
TC ATDTENIRFV FAAVKDTILQ LNLKEYNLV
    Click to Show/Hide
3D-structure
PDB ID
7TRY
Classification
Signaling protein
Method
Electron microscopy
Resolution
3.70  Å
Function
Guanine nucleotide-binding proteins (G proteins) are involved as modulators or transducers in various transmembrane signaling systems. Acts as an activator of phospholipase C. Transduces FFAR4 signaling in response to long-chain fatty acids (LCFAs).
    Click to Show/Hide
Uniprot ID
GNA11_HUMAN
Ensembl ID
ENSG00000088256
HGNC ID
HGNC:4379
        Click to Show/Hide the Complete Species Lineage
Kingdom: Metazoa
Phylum: Chordata
Class: Mammalia
Order: Primates
Family: Hominidae
Genus: Homo
Species: Homo sapiens
Type(s) of Resistant Mechanism of This Molecule
  ADTT: Aberration of the Drug's Therapeutic Target
  UAPP: Unusual Activation of Pro-survival Pathway
Drug Resistance Data Categorized by Drug
Approved Drug(s)
1 drug(s) in total
Click to Show/Hide the Full List of Drugs
Trametinib
Click to Show/Hide
Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
  Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Disease Class: Uveal melanoma [ICD-11: 2D0Y.0] [1]
Sensitive Disease Uveal melanoma [ICD-11: 2D0Y.0]
 Disease Info 
Sensitive Drug Trametinib
 Drug Info 
Molecule Alteration Missense mutation
p.Q209L (c.626A>T)
Wild Type Structure Method: Electron microscopy Resolution: 3.50  Å
PDB: 6VU5
Mutant Type Structure Method: Electron microscopy Resolution: 2.90  Å
PDB: 7F6G
   Download The Information of Sequence       Download The Structure File   
RMSD: 1.91
TM score: 0.72705
Amino acid change:
Q209L
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
-
-
M
-
H
-
H
-
H
-
H
-
H
-
H
-
H
-
H
0
|
-
H
M
H
T
T
L
L
E
E
S
S
I
I
M
M
A
A
C
C
10
|
C
C
L
L
S
S
E
E
E
E
A
A
K
K
E
E
A
A
R
R
20
|
R
R
I
I
N
N
D
D
E
E
I
I
E
E
R
R
Q
Q
L
L
30
|
R
R
R
R
D
D
K
K
R
R
D
D
A
A
R
R
R
R
E
E
40
|
L
L
K
K
L
L
L
L
L
L
L
L
G
G
T
T
G
G
E
E
50
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S
S
G
G
K
K
S
S
T
T
F
F
I
I
K
K
Q
Q
M
M
60
|
R
R
I
I
I
I
H
H
G
G
S
S
G
G
Y
Y
S
S
D
D
70
|
E
E
D
D
K
K
R
R
G
G
F
F
T
T
K
K
L
L
V
V
80
|
Y
Y
Q
Q
N
N
I
I
F
F
T
T
A
A
M
M
Q
Q
A
A
90
|
M
M
I
I
R
R
A
A
M
M
D
D
T
T
L
L
K
K
I
I
100
|
P
P
Y
Y
K
K
Y
Y
E
E
H
H
N
N
K
K
A
A
H
H
110
|
A
A
Q
Q
L
L
V
V
R
R
E
E
V
V
D
D
V
V
E
E
120
|
K
K
V
V
S
S
A
A
F
F
E
E
N
N
P
P
Y
Y
V
V
130
|
D
D
A
A
I
I
K
K
S
S
L
L
W
W
N
N
D
D
P
P
140
|
G
G
I
I
Q
Q
E
E
C
C
Y
Y
D
D
R
R
R
R
R
R
150
|
E
E
Y
Y
Q
Q
L
L
S
S
D
D
S
S
T
T
K
K
Y
Y
160
|
Y
Y
L
L
N
N
D
D
L
L
D
D
R
R
V
V
A
A
D
D
170
|
P
P
A
A
Y
Y
L
L
P
P
T
T
Q
Q
Q
Q
D
D
V
V
180
|
L
L
R
R
V
V
R
Q
V
V
P
P
T
T
T
T
G
G
I
I
190
|
I
I
E
E
Y
Y
P
P
F
F
D
D
L
L
Q
Q
S
S
V
V
200
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I
I
F
F
R
R
M
M
V
V
D
D
V
V
G
G
G
G
Q
L
210
|
R
R
S
S
E
E
R
R
R
R
K
K
W
W
I
I
H
H
C
C
220
|
F
F
E
E
N
N
V
V
T
T
S
S
I
I
M
M
F
F
L
L
230
|
V
V
A
A
L
L
S
S
E
E
Y
Y
D
D
Q
Q
V
V
L
L
240
|
V
V
E
E
S
S
D
D
N
N
E
E
N
N
R
R
M
M
E
E
250
|
E
E
S
S
K
K
A
A
L
L
F
F
R
R
T
T
I
I
I
I
260
|
T
T
Y
Y
P
P
W
W
F
F
Q
Q
N
N
S
S
S
S
V
V
270
|
I
I
L
L
F
F
L
L
N
N
K
K
K
K
D
D
L
L
L
L
280
|
E
E
E
E
K
K
I
I
M
M
Y
Y
S
S
H
H
L
L
V
V
290
|
D
D
Y
Y
F
F
P
P
E
E
Y
Y
D
D
G
G
P
P
Q
Q
300
|
R
R
D
D
A
A
Q
Q
A
A
A
A
R
R
E
E
F
F
I
I
310
|
L
L
K
K
M
M
F
F
V
V
D
D
L
L
N
N
P
P
D
D
320
|
S
S
D
D
K
K
I
I
I
I
Y
Y
S
S
H
H
F
F
T
T
330
|
C
C
A
A
T
T
D
D
T
T
E
E
N
N
I
I
R
R
F
F
340
|
V
V
F
F
A
A
A
A
V
V
K
K
D
D
T
T
I
I
L
L
350
|
Q
Q
L
L
N
N
L
L
K
K
E
E
Y
Y
N
N
L
L
V
V
Click to Show/Hide the Structure
Experimental Note Revealed Based on the Cell Line Data
Experiment for
Molecule Alteration		 Western blot analysis
Experiment for
Drug Resistance		 Cell Titer-blue assay
Mechanism Description The missense mutation p.Q209L (c.626A>T) in gene GNA11 cause the sensitivity of Trametinib by unusual activation of pro-survival pathway
Clinical Trial Drug(s)
1 drug(s) in total
Click to Show/Hide the Full List of Drugs
Selumetinib
Click to Show/Hide
Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
  Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Disease Class: Melanoma [ICD-11: 2C30.0] [2]
Sensitive Disease Melanoma [ICD-11: 2C30.0]
 Disease Info 
Sensitive Drug Selumetinib
 Drug Info 
Molecule Alteration Missense mutation
p.Q209L (c.626A>T)
Wild Type Structure Method: Electron microscopy Resolution: 3.50  Å
PDB: 6VU5
Mutant Type Structure Method: Electron microscopy Resolution: 2.90  Å
PDB: 7F6G
   Download The Information of Sequence       Download The Structure File   
RMSD: 1.91
TM score: 0.72705
Amino acid change:
Q209L
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
-
-
M
-
H
-
H
-
H
-
H
-
H
-
H
-
H
-
H
0
|
-
H
M
H
T
T
L
L
E
E
S
S
I
I
M
M
A
A
C
C
10
|
C
C
L
L
S
S
E
E
E
E
A
A
K
K
E
E
A
A
R
R
20
|
R
R
I
I
N
N
D
D
E
E
I
I
E
E
R
R
Q
Q
L
L
30
|
R
R
R
R
D
D
K
K
R
R
D
D
A
A
R
R
R
R
E
E
40
|
L
L
K
K
L
L
L
L
L
L
L
L
G
G
T
T
G
G
E
E
50
|
S
S
G
G
K
K
S
S
T
T
F
F
I
I
K
K
Q
Q
M
M
60
|
R
R
I
I
I
I
H
H
G
G
S
S
G
G
Y
Y
S
S
D
D
70
|
E
E
D
D
K
K
R
R
G
G
F
F
T
T
K
K
L
L
V
V
80
|
Y
Y
Q
Q
N
N
I
I
F
F
T
T
A
A
M
M
Q
Q
A
A
90
|
M
M
I
I
R
R
A
A
M
M
D
D
T
T
L
L
K
K
I
I
100
|
P
P
Y
Y
K
K
Y
Y
E
E
H
H
N
N
K
K
A
A
H
H
110
|
A
A
Q
Q
L
L
V
V
R
R
E
E
V
V
D
D
V
V
E
E
120
|
K
K
V
V
S
S
A
A
F
F
E
E
N
N
P
P
Y
Y
V
V
130
|
D
D
A
A
I
I
K
K
S
S
L
L
W
W
N
N
D
D
P
P
140
|
G
G
I
I
Q
Q
E
E
C
C
Y
Y
D
D
R
R
R
R
R
R
150
|
E
E
Y
Y
Q
Q
L
L
S
S
D
D
S
S
T
T
K
K
Y
Y
160
|
Y
Y
L
L
N
N
D
D
L
L
D
D
R
R
V
V
A
A
D
D
170
|
P
P
A
A
Y
Y
L
L
P
P
T
T
Q
Q
Q
Q
D
D
V
V
180
|
L
L
R
R
V
V
R
Q
V
V
P
P
T
T
T
T
G
G
I
I
190
|
I
I
E
E
Y
Y
P
P
F
F
D
D
L
L
Q
Q
S
S
V
V
200
|
I
I
F
F
R
R
M
M
V
V
D
D
V
V
G
G
G
G
Q
L
210
|
R
R
S
S
E
E
R
R
R
R
K
K
W
W
I
I
H
H
C
C
220
|
F
F
E
E
N
N
V
V
T
T
S
S
I
I
M
M
F
F
L
L
230
|
V
V
A
A
L
L
S
S
E
E
Y
Y
D
D
Q
Q
V
V
L
L
240
|
V
V
E
E
S
S
D
D
N
N
E
E
N
N
R
R
M
M
E
E
250
|
E
E
S
S
K
K
A
A
L
L
F
F
R
R
T
T
I
I
I
I
260
|
T
T
Y
Y
P
P
W
W
F
F
Q
Q
N
N
S
S
S
S
V
V
270
|
I
I
L
L
F
F
L
L
N
N
K
K
K
K
D
D
L
L
L
L
280
|
E
E
E
E
K
K
I
I
M
M
Y
Y
S
S
H
H
L
L
V
V
290
|
D
D
Y
Y
F
F
P
P
E
E
Y
Y
D
D
G
G
P
P
Q
Q
300
|
R
R
D
D
A
A
Q
Q
A
A
A
A
R
R
E
E
F
F
I
I
310
|
L
L
K
K
M
M
F
F
V
V
D
D
L
L
N
N
P
P
D
D
320
|
S
S
D
D
K
K
I
I
I
I
Y
Y
S
S
H
H
F
F
T
T
330
|
C
C
A
A
T
T
D
D
T
T
E
E
N
N
I
I
R
R
F
F
340
|
V
V
F
F
A
A
A
A
V
V
K
K
D
D
T
T
I
I
L
L
350
|
Q
Q
L
L
N
N
L
L
K
K
E
E
Y
Y
N
N
L
L
V
V
Click to Show/Hide the Structure
Experimental Note Identified from the Human Clinical Data
Disease Class: Melanoma [ICD-11: 2C30.0] [2]
Sensitive Disease Melanoma [ICD-11: 2C30.0]
 Disease Info 
Sensitive Drug Selumetinib
 Drug Info 
Molecule Alteration Missense mutation
p.Q209L (c.626A>T)
Wild Type Structure Method: Electron microscopy Resolution: 3.50  Å
PDB: 6VU5
Mutant Type Structure Method: Electron microscopy Resolution: 2.90  Å
PDB: 7F6G
   Download The Information of Sequence       Download The Structure File   
RMSD: 1.91
TM score: 0.72705
Amino acid change:
Q209L
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
-
-
M
-
H
-
H
-
H
-
H
-
H
-
H
-
H
-
H
0
|
-
H
M
H
T
T
L
L
E
E
S
S
I
I
M
M
A
A
C
C
10
|
C
C
L
L
S
S
E
E
E
E
A
A
K
K
E
E
A
A
R
R
20
|
R
R
I
I
N
N
D
D
E
E
I
I
E
E
R
R
Q
Q
L
L
30
|
R
R
R
R
D
D
K
K
R
R
D
D
A
A
R
R
R
R
E
E
40
|
L
L
K
K
L
L
L
L
L
L
L
L
G
G
T
T
G
G
E
E
50
|
S
S
G
G
K
K
S
S
T
T
F
F
I
I
K
K
Q
Q
M
M
60
|
R
R
I
I
I
I
H
H
G
G
S
S
G
G
Y
Y
S
S
D
D
70
|
E
E
D
D
K
K
R
R
G
G
F
F
T
T
K
K
L
L
V
V
80
|
Y
Y
Q
Q
N
N
I
I
F
F
T
T
A
A
M
M
Q
Q
A
A
90
|
M
M
I
I
R
R
A
A
M
M
D
D
T
T
L
L
K
K
I
I
100
|
P
P
Y
Y
K
K
Y
Y
E
E
H
H
N
N
K
K
A
A
H
H
110
|
A
A
Q
Q
L
L
V
V
R
R
E
E
V
V
D
D
V
V
E
E
120
|
K
K
V
V
S
S
A
A
F
F
E
E
N
N
P
P
Y
Y
V
V
130
|
D
D
A
A
I
I
K
K
S
S
L
L
W
W
N
N
D
D
P
P
140
|
G
G
I
I
Q
Q
E
E
C
C
Y
Y
D
D
R
R
R
R
R
R
150
|
E
E
Y
Y
Q
Q
L
L
S
S
D
D
S
S
T
T
K
K
Y
Y
160
|
Y
Y
L
L
N
N
D
D
L
L
D
D
R
R
V
V
A
A
D
D
170
|
P
P
A
A
Y
Y
L
L
P
P
T
T
Q
Q
Q
Q
D
D
V
V
180
|
L
L
R
R
V
V
R
Q
V
V
P
P
T
T
T
T
G
G
I
I
190
|
I
I
E
E
Y
Y
P
P
F
F
D
D
L
L
Q
Q
S
S
V
V
200
|
I
I
F
F
R
R
M
M
V
V
D
D
V
V
G
G
G
G
Q
L
210
|
R
R
S
S
E
E
R
R
R
R
K
K
W
W
I
I
H
H
C
C
220
|
F
F
E
E
N
N
V
V
T
T
S
S
I
I
M
M
F
F
L
L
230
|
V
V
A
A
L
L
S
S
E
E
Y
Y
D
D
Q
Q
V
V
L
L
240
|
V
V
E
E
S
S
D
D
N
N
E
E
N
N
R
R
M
M
E
E
250
|
E
E
S
S
K
K
A
A
L
L
F
F
R
R
T
T
I
I
I
I
260
|
T
T
Y
Y
P
P
W
W
F
F
Q
Q
N
N
S
S
S
S
V
V
270
|
I
I
L
L
F
F
L
L
N
N
K
K
K
K
D
D
L
L
L
L
280
|
E
E
E
E
K
K
I
I
M
M
Y
Y
S
S
H
H
L
L
V
V
290
|
D
D
Y
Y
F
F
P
P
E
E
Y
Y
D
D
G
G
P
P
Q
Q
300
|
R
R
D
D
A
A
Q
Q
A
A
A
A
R
R
E
E
F
F
I
I
310
|
L
L
K
K
M
M
F
F
V
V
D
D
L
L
N
N
P
P
D
D
320
|
S
S
D
D
K
K
I
I
I
I
Y
Y
S
S
H
H
F
F
T
T
330
|
C
C
A
A
T
T
D
D
T
T
E
E
N
N
I
I
R
R
F
F
340
|
V
V
F
F
A
A
A
A
V
V
K
K
D
D
T
T
I
I
L
L
350
|
Q
Q
L
L
N
N
L
L
K
K
E
E
Y
Y
N
N
L
L
V
V
Click to Show/Hide the Structure
Experimental Note Identified from the Human Clinical Data
Disease Class: Melanoma [ICD-11: 2C30.0] [2]
Sensitive Disease Melanoma [ICD-11: 2C30.0]
 Disease Info 
Sensitive Drug Selumetinib
 Drug Info 
Molecule Alteration Missense mutation
p.Q209P (c.626A>C)
Experimental Note Identified from the Human Clinical Data
Disease Class: Melanoma [ICD-11: 2C30.0] [2]
Sensitive Disease Melanoma [ICD-11: 2C30.0]
 Disease Info 
Sensitive Drug Selumetinib
 Drug Info 
Molecule Alteration Missense mutation
p.Q209P (c.626A>C)
Experimental Note Identified from the Human Clinical Data
Preclinical Drug(s)
2 drug(s) in total
Click to Show/Hide the Full List of Drugs
AEB071/Binimetinib
Click to Show/Hide
Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
  Aberration of the Drug's Therapeutic Target (ADTT) Click to Show/Hide
Disease Class: Uveal melanoma [ICD-11: 2D0Y.0] [3]
Sensitive Disease Uveal melanoma [ICD-11: 2D0Y.0]
 Disease Info 
Sensitive Drug AEB071/Binimetinib
 Drug Info 
Molecule Alteration Missense mutation
p.Q209L (c.626A>T)
Wild Type Structure Method: Electron microscopy Resolution: 3.50  Å
PDB: 6VU5
Mutant Type Structure Method: Electron microscopy Resolution: 2.90  Å
PDB: 7F6G
   Download The Information of Sequence       Download The Structure File   
RMSD: 1.91
TM score: 0.72705
Amino acid change:
Q209L
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
-
-
M
-
H
-
H
-
H
-
H
-
H
-
H
-
H
-
H
0
|
-
H
M
H
T
T
L
L
E
E
S
S
I
I
M
M
A
A
C
C
10
|
C
C
L
L
S
S
E
E
E
E
A
A
K
K
E
E
A
A
R
R
20
|
R
R
I
I
N
N
D
D
E
E
I
I
E
E
R
R
Q
Q
L
L
30
|
R
R
R
R
D
D
K
K
R
R
D
D
A
A
R
R
R
R
E
E
40
|
L
L
K
K
L
L
L
L
L
L
L
L
G
G
T
T
G
G
E
E
50
|
S
S
G
G
K
K
S
S
T
T
F
F
I
I
K
K
Q
Q
M
M
60
|
R
R
I
I
I
I
H
H
G
G
S
S
G
G
Y
Y
S
S
D
D
70
|
E
E
D
D
K
K
R
R
G
G
F
F
T
T
K
K
L
L
V
V
80
|
Y
Y
Q
Q
N
N
I
I
F
F
T
T
A
A
M
M
Q
Q
A
A
90
|
M
M
I
I
R
R
A
A
M
M
D
D
T
T
L
L
K
K
I
I
100
|
P
P
Y
Y
K
K
Y
Y
E
E
H
H
N
N
K
K
A
A
H
H
110
|
A
A
Q
Q
L
L
V
V
R
R
E
E
V
V
D
D
V
V
E
E
120
|
K
K
V
V
S
S
A
A
F
F
E
E
N
N
P
P
Y
Y
V
V
130
|
D
D
A
A
I
I
K
K
S
S
L
L
W
W
N
N
D
D
P
P
140
|
G
G
I
I
Q
Q
E
E
C
C
Y
Y
D
D
R
R
R
R
R
R
150
|
E
E
Y
Y
Q
Q
L
L
S
S
D
D
S
S
T
T
K
K
Y
Y
160
|
Y
Y
L
L
N
N
D
D
L
L
D
D
R
R
V
V
A
A
D
D
170
|
P
P
A
A
Y
Y
L
L
P
P
T
T
Q
Q
Q
Q
D
D
V
V
180
|
L
L
R
R
V
V
R
Q
V
V
P
P
T
T
T
T
G
G
I
I
190
|
I
I
E
E
Y
Y
P
P
F
F
D
D
L
L
Q
Q
S
S
V
V
200
|
I
I
F
F
R
R
M
M
V
V
D
D
V
V
G
G
G
G
Q
L
210
|
R
R
S
S
E
E
R
R
R
R
K
K
W
W
I
I
H
H
C
C
220
|
F
F
E
E
N
N
V
V
T
T
S
S
I
I
M
M
F
F
L
L
230
|
V
V
A
A
L
L
S
S
E
E
Y
Y
D
D
Q
Q
V
V
L
L
240
|
V
V
E
E
S
S
D
D
N
N
E
E
N
N
R
R
M
M
E
E
250
|
E
E
S
S
K
K
A
A
L
L
F
F
R
R
T
T
I
I
I
I
260
|
T
T
Y
Y
P
P
W
W
F
F
Q
Q
N
N
S
S
S
S
V
V
270
|
I
I
L
L
F
F
L
L
N
N
K
K
K
K
D
D
L
L
L
L
280
|
E
E
E
E
K
K
I
I
M
M
Y
Y
S
S
H
H
L
L
V
V
290
|
D
D
Y
Y
F
F
P
P
E
E
Y
Y
D
D
G
G
P
P
Q
Q
300
|
R
R
D
D
A
A
Q
Q
A
A
A
A
R
R
E
E
F
F
I
I
310
|
L
L
K
K
M
M
F
F
V
V
D
D
L
L
N
N
P
P
D
D
320
|
S
S
D
D
K
K
I
I
I
I
Y
Y
S
S
H
H
F
F
T
T
330
|
C
C
A
A
T
T
D
D
T
T
E
E
N
N
I
I
R
R
F
F
340
|
V
V
F
F
A
A
A
A
V
V
K
K
D
D
T
T
I
I
L
L
350
|
Q
Q
L
L
N
N
L
L
K
K
E
E
Y
Y
N
N
L
L
V
V
Click to Show/Hide the Structure
Experimental Note Identified from the Human Clinical Data
In Vitro Model OMM-GN11 N.A. Mus musculus (Mouse) N.A.
OMM13 N.A. N.A. N.A.
Mel202 Eye Homo sapiens (Human) CVCL_C301
GNAQ cells N.A. N.A. N.A.
Mel270 cells Skin Homo sapiens (Human) CVCL_C302
GNA11 cells N.A. N.A. N.A.
UPMD-1 cells Skin Homo sapiens (Human) CVCL_C297
92-1 cells Bladder Homo sapiens (Human) CVCL_W909
Mel202 Eye Homo sapiens (Human) CVCL_C301
In Vivo Model C57/BL6 mouse model Mus musculus
Experiment for
Molecule Alteration		 Western blot analysis
Experiment for
Drug Resistance		 Cell proliferation assay
FR900359
Click to Show/Hide
Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
  Aberration of the Drug's Therapeutic Target (ADTT) Click to Show/Hide
Disease Class: Uveal melanoma [ICD-11: 2D0Y.0] [4]
Sensitive Disease Uveal melanoma [ICD-11: 2D0Y.0]
 Disease Info 
Sensitive Drug FR900359
 Drug Info 
Molecule Alteration Missense mutation
p.Q209L (c.626A>T)
Wild Type Structure Method: Electron microscopy Resolution: 3.50  Å
PDB: 6VU5
Mutant Type Structure Method: Electron microscopy Resolution: 2.90  Å
PDB: 7F6G
   Download The Information of Sequence       Download The Structure File   
RMSD: 1.91
TM score: 0.72705
Amino acid change:
Q209L
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
-
-
M
-
H
-
H
-
H
-
H
-
H
-
H
-
H
-
H
0
|
-
H
M
H
T
T
L
L
E
E
S
S
I
I
M
M
A
A
C
C
10
|
C
C
L
L
S
S
E
E
E
E
A
A
K
K
E
E
A
A
R
R
20
|
R
R
I
I
N
N
D
D
E
E
I
I
E
E
R
R
Q
Q
L
L
30
|
R
R
R
R
D
D
K
K
R
R
D
D
A
A
R
R
R
R
E
E
40
|
L
L
K
K
L
L
L
L
L
L
L
L
G
G
T
T
G
G
E
E
50
|
S
S
G
G
K
K
S
S
T
T
F
F
I
I
K
K
Q
Q
M
M
60
|
R
R
I
I
I
I
H
H
G
G
S
S
G
G
Y
Y
S
S
D
D
70
|
E
E
D
D
K
K
R
R
G
G
F
F
T
T
K
K
L
L
V
V
80
|
Y
Y
Q
Q
N
N
I
I
F
F
T
T
A
A
M
M
Q
Q
A
A
90
|
M
M
I
I
R
R
A
A
M
M
D
D
T
T
L
L
K
K
I
I
100
|
P
P
Y
Y
K
K
Y
Y
E
E
H
H
N
N
K
K
A
A
H
H
110
|
A
A
Q
Q
L
L
V
V
R
R
E
E
V
V
D
D
V
V
E
E
120
|
K
K
V
V
S
S
A
A
F
F
E
E
N
N
P
P
Y
Y
V
V
130
|
D
D
A
A
I
I
K
K
S
S
L
L
W
W
N
N
D
D
P
P
140
|
G
G
I
I
Q
Q
E
E
C
C
Y
Y
D
D
R
R
R
R
R
R
150
|
E
E
Y
Y
Q
Q
L
L
S
S
D
D
S
S
T
T
K
K
Y
Y
160
|
Y
Y
L
L
N
N
D
D
L
L
D
D
R
R
V
V
A
A
D
D
170
|
P
P
A
A
Y
Y
L
L
P
P
T
T
Q
Q
Q
Q
D
D
V
V
180
|
L
L
R
R
V
V
R
Q
V
V
P
P
T
T
T
T
G
G
I
I
190
|
I
I
E
E
Y
Y
P
P
F
F
D
D
L
L
Q
Q
S
S
V
V
200
|
I
I
F
F
R
R
M
M
V
V
D
D
V
V
G
G
G
G
Q
L
210
|
R
R
S
S
E
E
R
R
R
R
K
K
W
W
I
I
H
H
C
C
220
|
F
F
E
E
N
N
V
V
T
T
S
S
I
I
M
M
F
F
L
L
230
|
V
V
A
A
L
L
S
S
E
E
Y
Y
D
D
Q
Q
V
V
L
L
240
|
V
V
E
E
S
S
D
D
N
N
E
E
N
N
R
R
M
M
E
E
250
|
E
E
S
S
K
K
A
A
L
L
F
F
R
R
T
T
I
I
I
I
260
|
T
T
Y
Y
P
P
W
W
F
F
Q
Q
N
N
S
S
S
S
V
V
270
|
I
I
L
L
F
F
L
L
N
N
K
K
K
K
D
D
L
L
L
L
280
|
E
E
E
E
K
K
I
I
M
M
Y
Y
S
S
H
H
L
L
V
V
290
|
D
D
Y
Y
F
F
P
P
E
E
Y
Y
D
D
G
G
P
P
Q
Q
300
|
R
R
D
D
A
A
Q
Q
A
A
A
A
R
R
E
E
F
F
I
I
310
|
L
L
K
K
M
M
F
F
V
V
D
D
L
L
N
N
P
P
D
D
320
|
S
S
D
D
K
K
I
I
I
I
Y
Y
S
S
H
H
F
F
T
T
330
|
C
C
A
A
T
T
D
D
T
T
E
E
N
N
I
I
R
R
F
F
340
|
V
V
F
F
A
A
A
A
V
V
K
K
D
D
T
T
I
I
L
L
350
|
Q
Q
L
L
N
N
L
L
K
K
E
E
Y
Y
N
N
L
L
V
V
Click to Show/Hide the Structure
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model UM002B cells Brain Homo sapiens (Human) N.A.
Omm13 cells N.A. N.A. N.A.
Ocm3 cells Skin Homo sapiens (Human) CVCL_6937
92-1 cells Bladder Homo sapiens (Human) CVCL_W909
Experiment for
Molecule Alteration		 Sanger sequencing assay; Western blot analysis
Investigative Drug(s)
1 drug(s) in total
Click to Show/Hide the Full List of Drugs
TAK-733
Click to Show/Hide
Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
  Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Disease Class: Uveal melanoma [ICD-11: 2D0Y.0] [5]
Sensitive Disease Uveal melanoma [ICD-11: 2D0Y.0]
 Disease Info 
Sensitive Drug TAK-733
 Drug Info 
Molecule Alteration Missense mutation
p.Q209L (c.626A>T)
Wild Type Structure Method: Electron microscopy Resolution: 3.50  Å
PDB: 6VU5
Mutant Type Structure Method: Electron microscopy Resolution: 2.90  Å
PDB: 7F6G
   Download The Information of Sequence       Download The Structure File   
RMSD: 1.91
TM score: 0.72705
Amino acid change:
Q209L
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
-
-
M
-
H
-
H
-
H
-
H
-
H
-
H
-
H
-
H
0
|
-
H
M
H
T
T
L
L
E
E
S
S
I
I
M
M
A
A
C
C
10
|
C
C
L
L
S
S
E
E
E
E
A
A
K
K
E
E
A
A
R
R
20
|
R
R
I
I
N
N
D
D
E
E
I
I
E
E
R
R
Q
Q
L
L
30
|
R
R
R
R
D
D
K
K
R
R
D
D
A
A
R
R
R
R
E
E
40
|
L
L
K
K
L
L
L
L
L
L
L
L
G
G
T
T
G
G
E
E
50
|
S
S
G
G
K
K
S
S
T
T
F
F
I
I
K
K
Q
Q
M
M
60
|
R
R
I
I
I
I
H
H
G
G
S
S
G
G
Y
Y
S
S
D
D
70
|
E
E
D
D
K
K
R
R
G
G
F
F
T
T
K
K
L
L
V
V
80
|
Y
Y
Q
Q
N
N
I
I
F
F
T
T
A
A
M
M
Q
Q
A
A
90
|
M
M
I
I
R
R
A
A
M
M
D
D
T
T
L
L
K
K
I
I
100
|
P
P
Y
Y
K
K
Y
Y
E
E
H
H
N
N
K
K
A
A
H
H
110
|
A
A
Q
Q
L
L
V
V
R
R
E
E
V
V
D
D
V
V
E
E
120
|
K
K
V
V
S
S
A
A
F
F
E
E
N
N
P
P
Y
Y
V
V
130
|
D
D
A
A
I
I
K
K
S
S
L
L
W
W
N
N
D
D
P
P
140
|
G
G
I
I
Q
Q
E
E
C
C
Y
Y
D
D
R
R
R
R
R
R
150
|
E
E
Y
Y
Q
Q
L
L
S
S
D
D
S
S
T
T
K
K
Y
Y
160
|
Y
Y
L
L
N
N
D
D
L
L
D
D
R
R
V
V
A
A
D
D
170
|
P
P
A
A
Y
Y
L
L
P
P
T
T
Q
Q
Q
Q
D
D
V
V
180
|
L
L
R
R
V
V
R
Q
V
V
P
P
T
T
T
T
G
G
I
I
190
|
I
I
E
E
Y
Y
P
P
F
F
D
D
L
L
Q
Q
S
S
V
V
200
|
I
I
F
F
R
R
M
M
V
V
D
D
V
V
G
G
G
G
Q
L
210
|
R
R
S
S
E
E
R
R
R
R
K
K
W
W
I
I
H
H
C
C
220
|
F
F
E
E
N
N
V
V
T
T
S
S
I
I
M
M
F
F
L
L
230
|
V
V
A
A
L
L
S
S
E
E
Y
Y
D
D
Q
Q
V
V
L
L
240
|
V
V
E
E
S
S
D
D
N
N
E
E
N
N
R
R
M
M
E
E
250
|
E
E
S
S
K
K
A
A
L
L
F
F
R
R
T
T
I
I
I
I
260
|
T
T
Y
Y
P
P
W
W
F
F
Q
Q
N
N
S
S
S
S
V
V
270
|
I
I
L
L
F
F
L
L
N
N
K
K
K
K
D
D
L
L
L
L
280
|
E
E
E
E
K
K
I
I
M
M
Y
Y
S
S
H
H
L
L
V
V
290
|
D
D
Y
Y
F
F
P
P
E
E
Y
Y
D
D
G
G
P
P
Q
Q
300
|
R
R
D
D
A
A
Q
Q
A
A
A
A
R
R
E
E
F
F
I
I
310
|
L
L
K
K
M
M
F
F
V
V
D
D
L
L
N
N
P
P
D
D
320
|
S
S
D
D
K
K
I
I
I
I
Y
Y
S
S
H
H
F
F
T
T
330
|
C
C
A
A
T
T
D
D
T
T
E
E
N
N
I
I
R
R
F
F
340
|
V
V
F
F
A
A
A
A
V
V
K
K
D
D
T
T
I
I
L
L
350
|
Q
Q
L
L
N
N
L
L
K
K
E
E
Y
Y
N
N
L
L
V
V
Click to Show/Hide the Structure
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model Wn1366 cells Skin Homo sapiens (Human) CVCL_6789
SkMEL28 cells Skin Homo sapiens (Human) CVCL_0526
SBCL2 cells Skin Homo sapiens (Human) CVCL_D732
Experiment for
Molecule Alteration		 Western blot analysis
Experiment for
Drug Resistance		 MTS assay
Mechanism Description The missense mutation p.Q209L (c.626A>T) in gene GNA11 cause the sensitivity of TAK-733 by unusual activation of pro-survival pathway
Disease- and Tissue-specific Abundances of This Molecule
ICD Disease Classification 02
Click to Show/Hide the Resistance Disease of This Class
Melanoma [ICD-11: 2C30]
Click to Show/Hide
Differential expression of molecule in resistant diseases
The Studied Tissue Skin
The Specified Disease Melanoma
The Expression Level of Disease Section Compare with the Healthy Individual Tissue p-value: 5.69E-01; Fold-change: 3.82E-01; Z-score: 2.99E-01
Molecule expression in the diseased tissue of patients
Molecule expression in the normal tissue of healthy individuals
Disease-specific Molecule Abundances Click to View the Clearer Original Diagram
Download Molecule expression barchart for all samples
Download Molecule expression data of patients in the disease section of the tissue
Download Molecule expression data in the tissue of healthy individual
Tissue-specific Molecule Abundances in Healthy Individuals
Click to Show/Hide the Molecule Abundances
Download the Tissue-Specific Variation(s) Profile
References
Ref 1 Combination small molecule MEK and PI3K inhibition enhances uveal melanoma cell death in a mutant GNAQ- and GNA11-dependent mannerClin Cancer Res. 2012 Aug 15;18(16):4345-55. doi: 10.1158/1078-0432.CCR-11-3227. Epub 2012 Jun 25.
Ref 2 Turk J Haematol. 2016 Mar 5;33(1):41-7. doi: 10.4274/tjh.2014.0010. Epub 2014 May 21.
Ref 3 Combined PKC and MEK inhibition in uveal melanoma with GNAQ and GNA11 mutationsOncogene. 2014 Sep 25;33(39):4724-34. doi: 10.1038/onc.2013.418. Epub 2013 Oct 21.
Ref 4 Effects of Oncogenic GAlpha(q) and GAlpha(11) Inhibition by FR900359 in Uveal MelanomaMol Cancer Res. 2019 Apr;17(4):963-973. doi: 10.1158/1541-7786.MCR-18-0574. Epub 2018 Dec 19.
Ref 5 Antitumor effects of the investigational selective MEK inhibitor TAK733 against cutaneous and uveal melanoma cell linesMol Cancer. 2012 Apr 19;11:22. doi: 10.1186/1476-4598-11-22.

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