Molecule Information

General Information of the Molecule (ID: Mol00200)
Name
Cytosolic purine 5'-nucleotidase (NT5C2) ,Homo sapiens
Synonyms
Cytosolic 5'-nucleotidase II; cN-II; Cytosolic IMP/GMP-specific 5'-nucleotidase; Cytosolic nucleoside phosphotransferase 5'N; High Km 5'-nucleotidase; NT5B; NT5CP; PNT5
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Molecule Type
Protein
Gene Name
NT5C2
Gene ID
22978
Location
chr10:103087185-103277605[-]
Sequence
MSTSWSDRLQNAADMPANMDKHALKKYRREAYHRVFVNRSLAMEKIKCFGFDMDYTLAVY
KSPEYESLGFELTVERLVSIGYPQELLSFAYDSTFPTRGLVFDTLYGNLLKVDAYGNLLV
CAHGFNFIRGPETREQYPNKFIQRDDTERFYILNTLFNLPETYLLACLVDFFTNCPRYTS
CETGFKDGDLFMSYRSMFQDVRDAVDWVHYKGSLKEKTVENLEKYVVKDGKLPLLLSRMK
EVGKVFLATNSDYKYTDKIMTYLFDFPHGPKPGSSHRPWQSYFDLILVDARKPLFFGEGT
VLRQVDTKTGKLKIGTYTGPLQHGIVYSGGSSDTICDLLGAKGKDILYIGDHIFGDILKS
KKRQGWRTFLVIPELAQELHVWTDKSSLFEELQSLDIFLAELYKHLDSSSNERPDISSIQ
RRIKKVTHDMDMCYGMMGSLFRSGSRQTLFASQVMRYADLYAASFINLLYYPFSYLFRAA
HVLMPHESTVEHTHVDINEMESPLATRNRTSVDFKDTDYKRHQLTRSISEIKPPNLFPLA
PQEITHCHDEDDDEEEEEEEE
    Click to Show/Hide
3D-structure
PDB ID
6FXH
Classification
Hydrolase
Method
X-ray diffraction
Resolution
2.30  Å
Function
Broad specificity cytosolic 5'-nucleotidase that catalyzes the dephosphorylation of 6-hydroxypurine nucleoside 5'-monophosphates. In addition, possesses a phosphotransferase activity by which it can transfer a phosphate from a donor nucleoside monophosphate to an acceptor nucleoside, preferably inosine, deoxyinosine and guanosine. Has the highest activities for IMP and GMP followed by dIMP, dGMP and XMP. Could also catalyze the transfer of phosphates from pyrimidine monophosphates but with lower efficiency. Through these activities regulates the purine nucleoside/nucleotide pools within the cell.
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Uniprot ID
5NTC_HUMAN
Ensembl ID
ENSG00000076685
HGNC ID
HGNC:8022
        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 with Structure Alteration
  DISM: Drug Inactivation by Structure Modification
  UAPP: Unusual Activation of Pro-survival Pathway
Drug Resistance Data Categorized by Drug
Approved Drug(s)
2 drug(s) in total
Click to Show/Hide the Full List of Drugs
Mercaptopurine
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Drug Resistance Data Categorized by Their Corresponding Mechanisms
  Drug Inactivation by Structure Modification (DISM) Click to Show/Hide
Disease Class: Acute myeloid leukemia [ICD-11: 2A60.0] [1], [2]
Resistant Disease Acute myeloid leukemia [ICD-11: 2A60.0]
 Disease Info 
Resistant Drug Mercaptopurine
 Drug Info 
Molecule Alteration Missense mutation
p.R238W (c.c712t)
Wild Type Structure Method: X-ray diffraction Resolution: 1.70  Å
PDB: 5OPP
Mutant Type Structure Method: X-ray diffraction Resolution: 1.84  Å
PDB: 5L4Z
   Download The Information of Sequence       Download The Structure File   
RMSD: 0.41
TM score: 0.99758
Amino acid change:
R238W
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
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40
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60
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70
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80
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90
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G
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100
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L
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N
L
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110
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L
L
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V
D
D
A
A
Y
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G
G
N
N
L
L
L
L
120
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V
V
C
C
A
A
H
H
G
G
F
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N
N
F
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I
I
R
R
130
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G
G
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P
E
E
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140
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K
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D
D
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150
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T
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160
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P
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E
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L
L
A
A
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170
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D
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C
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180
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S
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C
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E
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190
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200
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210
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220
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E
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Y
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V
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D
D
230
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G
G
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L
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L
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240
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E
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G
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250
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260
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270
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280
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290
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A
A
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E
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300
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T
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310
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320
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330
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340
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410
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420
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440
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460
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A
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L
L
L
L
470
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Y
Y
Y
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P
P
F
F
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S
Y
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F
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A
A
480
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A
A
H
H
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T
490
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V
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500
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510
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520
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530
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Click to Show/Hide the Structure
Experimental Note Identified from the Human Clinical Data
Experiment for
Molecule Alteration		 Next-generation sequencing assay; Exome sequencing assay; Transcriptome sequencing assay; Whole genome sequencing assay; Sanger Sequencing assay
Experiment for
Drug Resistance		 Flow cytometry assay
Mechanism Description Several of these alterations are known to induce a more stem cell-like state (eg, IkZF1) or confer resistance directly to specific chemotherapy agents such as CREBBP and glucocorticoids and mutations in the 5-nucleotidase gene NT5C2 and nucleoside a.logs. Many relapse-acquired lesions are enriched in specific pathways, including B-cell development (IkZF1), tumor suppression (TP53),34 Ras signaling, chromatin modification (CREBBP, SETD2),17 and drug metabolism (NT5C2).
Disease Class: Acute lymphocytic leukemia [ICD-11: 2B33.0] [3]
Resistant Disease Acute lymphocytic leukemia [ICD-11: 2B33.0]
 Disease Info 
Resistant Drug Mercaptopurine
 Drug Info 
Molecule Alteration Missense mutation
p.R367Q
Wild Type Structure Method: X-ray diffraction Resolution: 2.30  Å
PDB: 6FXH
Mutant Type Structure Method: X-ray diffraction Resolution: 2.50  Å
PDB: 6DDK
   Download The Information of Sequence       Download The Structure File   
RMSD: 2.64
TM score: 0.87692
Amino acid change:
R367Q
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
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G
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S
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-10
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M
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W
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D
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R
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L
10
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N
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A
A
A
A
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D
M
M
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P
A
A
N
N
M
M
20
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D
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K
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H
A
A
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L
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K
K
K
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Y
R
R
R
R
30
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E
E
A
A
Y
Y
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H
R
R
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V
F
F
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R
40
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S
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L
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A
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M
E
E
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K
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K
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C
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F
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G
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F
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N
M
M
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Y
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T
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L
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A
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V
60
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Y
Y
K
K
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P
E
E
Y
Y
E
E
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S
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L
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G
70
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F
F
E
E
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L
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T
V
V
E
E
R
R
L
L
V
V
S
S
80
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I
I
G
G
Y
Y
P
P
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Q
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E
L
L
L
L
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S
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F
90
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A
A
Y
Y
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D
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S
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T
F
F
P
P
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T
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R
G
G
100
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L
L
V
V
F
F
D
D
T
T
L
L
Y
Y
G
G
N
N
L
L
110
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L
L
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K
V
V
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D
A
A
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Y
G
G
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N
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L
L
L
120
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V
V
C
C
A
A
H
H
G
G
F
F
N
N
F
F
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I
R
R
130
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G
G
P
P
E
E
T
T
R
R
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E
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Q
Y
Y
P
P
N
N
140
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K
K
F
F
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I
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Q
R
R
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D
D
D
T
T
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E
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R
150
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F
F
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Y
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I
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L
N
N
T
T
L
L
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F
N
N
L
L
160
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P
P
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E
T
T
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Y
L
L
L
L
A
A
C
C
L
L
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V
170
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D
D
F
F
F
F
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N
C
C
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P
R
R
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Y
T
T
180
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S
S
C
C
E
E
T
T
G
G
F
F
K
K
D
D
G
G
D
D
190
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L
L
F
F
M
M
S
S
Y
Y
R
R
S
S
M
M
F
F
Q
Q
200
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D
D
V
V
R
R
D
D
A
A
V
V
D
D
W
W
V
V
H
H
210
|
Y
Y
K
K
G
G
S
S
L
L
K
K
E
E
K
K
T
T
V
V
220
|
E
E
N
N
L
L
E
E
K
K
Y
Y
V
V
V
V
K
K
D
D
230
|
G
G
K
K
L
L
P
P
L
L
L
L
L
L
S
S
R
R
M
M
240
|
K
K
E
E
V
V
G
G
K
K
V
V
F
F
L
L
A
A
T
T
250
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N
N
S
S
D
D
Y
Y
K
K
Y
Y
T
T
D
D
K
K
I
I
260
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M
M
T
T
Y
Y
L
L
F
F
D
D
F
F
P
P
H
H
G
G
270
|
P
P
K
K
P
P
G
G
S
S
S
S
H
H
R
R
P
P
W
W
280
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Q
Q
S
S
Y
Y
F
F
D
D
L
L
I
I
L
L
V
V
D
D
290
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A
A
R
R
K
K
P
P
L
L
F
F
F
F
G
G
E
E
G
G
300
|
T
T
V
V
L
L
R
R
Q
Q
V
V
D
D
T
T
K
K
T
T
310
|
G
G
K
K
L
L
K
K
I
I
G
G
T
T
Y
Y
T
T
G
G
320
|
P
P
L
L
Q
Q
H
H
G
G
I
I
V
V
Y
Y
S
S
G
G
330
|
G
G
S
S
S
S
D
D
T
T
I
I
C
C
D
D
L
L
L
L
340
|
G
G
A
A
K
K
G
G
K
K
D
D
I
I
L
L
Y
Y
I
I
350
|
G
G
D
D
H
H
I
I
F
F
G
G
D
D
I
I
L
L
K
K
360
|
S
S
K
K
K
K
R
R
Q
Q
G
G
W
W
R
Q
T
T
F
F
370
|
L
L
V
V
I
I
P
P
E
E
L
L
A
A
Q
Q
E
E
L
L
380
|
H
H
V
V
W
W
T
T
D
D
K
K
S
S
S
S
L
L
F
F
390
|
E
E
E
E
L
L
Q
Q
S
S
L
L
D
D
I
I
F
F
L
L
400
|
A
A
E
E
L
L
Y
Y
K
K
H
H
L
L
D
D
S
S
S
S
410
|
S
S
N
N
E
E
R
R
P
P
D
D
I
I
S
S
S
S
I
I
420
|
Q
Q
R
R
R
R
I
I
K
K
K
K
V
V
T
T
H
H
D
D
430
|
M
M
D
D
M
M
C
C
Y
Y
G
G
M
M
M
M
G
G
S
S
440
|
L
L
F
F
R
R
S
S
G
G
S
S
R
R
Q
Q
T
T
L
L
450
|
F
F
A
A
S
S
Q
Q
V
V
M
M
R
R
Y
Y
A
A
D
D
460
|
L
L
Y
Y
A
A
A
A
S
S
F
F
I
I
N
N
L
L
L
L
470
|
Y
Y
Y
Y
P
P
F
F
S
S
Y
Y
L
L
F
F
R
R
A
A
480
|
A
A
H
H
V
V
L
L
M
M
P
P
H
H
E
E
S
S
T
T
490
|
V
V
E
E
H
H
T
T
H
H
V
V
D
D
I
I
N
N
E
E
500
|
M
M
E
E
S
S
P
P
L
L
A
A
T
T
R
R
N
N
R
R
510
|
T
T
S
S
V
V
D
D
F
F
K
K
D
D
T
T
D
D
Y
Y
520
|
K
K
R
R
H
H
Q
Q
L
L
T
T
R
R
S
S
I
I
S
S
530
|
E
E
I
I
K
K
P
P
P
P
N
N
L
L
F
F
P
P
L
L
540
|
A
A
P
P
Q
Q
E
E
I
I
T
T
H
H
C
C
H
H
D
D
550
|
E
E
D
D
D
D
D
D
E
E
E
E
E
E
E
E
E
E
E
E
560
|
E
E
E
E
Click to Show/Hide the Structure
Experimental Note Identified from the Human Clinical Data
Experiment for
Molecule Alteration		 Exome sequencing assay
Experiment for
Drug Resistance		 Conality analyses assay
Mechanism Description These two NT5C2 mutations (R367Q, D407V) occur as recurrent mutational hotspots in relapse-ALL and they have been functionally validated. These mutations increase the NT5C2 inosine-5-monophosphate-nucleotidase activity; and therefore lead to resistance to one of the chemotherapeutic drugs, 6-mercaptopurine.
Thioguanine
Click to Show/Hide
Drug Resistance Data Categorized by Their Corresponding Mechanisms
  Drug Inactivation by Structure Modification (DISM) Click to Show/Hide
Disease Class: Acute myeloid leukemia [ICD-11: 2A60.0] [1], [2]
Resistant Disease Acute myeloid leukemia [ICD-11: 2A60.0]
 Disease Info 
Resistant Drug Thioguanine
 Drug Info 
Molecule Alteration Missense mutation
p.R238W (c.c712t)
Wild Type Structure Method: X-ray diffraction Resolution: 1.70  Å
PDB: 5OPP
Mutant Type Structure Method: X-ray diffraction Resolution: 1.84  Å
PDB: 5L4Z
   Download The Information of Sequence       Download The Structure File   
RMSD: 0.41
TM score: 0.99758
Amino acid change:
R238W
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
-
-
M
-
G
-
S
-
S
-
H
-
H
-
H
-
H
-10
|
-
H
-
H
-
S
-
S
-
G
-
L
-
V
-
P
-
R
-
G
0
|
-
S
-
M
-
S
T
T
S
S
W
W
S
S
D
D
R
R
L
L
10
|
Q
Q
N
N
A
A
A
A
D
D
M
M
P
P
A
A
N
N
M
M
20
|
D
D
K
K
H
H
A
A
L
L
K
K
K
K
Y
Y
R
R
R
R
30
|
E
E
A
A
Y
Y
H
H
R
R
V
V
F
F
V
V
N
N
R
R
40
|
S
S
L
L
A
A
M
M
E
E
K
K
I
I
K
K
C
C
F
F
50
|
G
G
F
F
D
D
M
M
D
D
Y
Y
T
T
L
L
A
A
V
V
60
|
Y
Y
K
K
S
S
P
P
E
E
Y
Y
E
E
S
S
L
L
G
G
70
|
F
F
E
E
L
L
T
T
V
V
E
E
R
R
L
L
V
V
S
S
80
|
I
I
G
G
Y
Y
P
P
Q
Q
E
E
L
L
L
L
S
S
F
F
90
|
A
A
Y
Y
D
D
S
S
T
T
F
F
P
P
T
T
R
R
G
G
100
|
L
L
V
V
F
F
D
D
T
T
L
L
Y
Y
G
G
N
N
L
L
110
|
L
L
K
K
V
V
D
D
A
A
Y
Y
G
G
N
N
L
L
L
L
120
|
V
V
C
C
A
A
H
H
G
G
F
F
N
N
F
F
I
I
R
R
130
|
G
G
P
P
E
E
T
T
R
R
E
E
Q
Q
Y
Y
P
P
N
N
140
|
K
K
F
F
I
I
Q
Q
R
R
D
D
D
D
T
T
E
E
R
R
150
|
F
F
Y
Y
I
I
L
L
N
N
T
T
L
L
F
F
N
N
L
L
160
|
P
P
E
E
T
T
Y
Y
L
L
L
L
A
A
C
C
L
L
V
V
170
|
D
D
F
F
F
F
T
T
N
N
C
C
P
P
R
R
Y
Y
T
T
180
|
S
S
C
C
E
E
T
T
G
G
F
F
K
K
D
D
G
G
D
D
190
|
L
L
F
F
M
M
S
S
Y
Y
R
R
S
S
M
M
F
F
Q
Q
200
|
D
D
V
V
R
R
D
D
A
A
V
V
D
D
W
W
V
V
H
H
210
|
Y
Y
K
K
G
G
S
S
L
L
K
K
E
E
K
K
T
T
V
V
220
|
E
E
N
N
L
L
E
E
K
K
Y
Y
V
V
V
V
K
K
D
D
230
|
G
G
K
K
L
L
P
P
L
L
L
L
L
L
S
S
R
W
M
M
240
|
K
K
E
E
V
V
G
G
K
K
V
V
F
F
L
L
A
A
T
T
250
|
N
N
S
S
D
D
Y
Y
K
K
Y
Y
T
T
D
D
K
K
I
I
260
|
M
M
T
T
Y
Y
L
L
F
F
D
D
F
F
P
P
H
H
G
G
270
|
P
P
K
K
P
P
G
G
S
S
S
S
H
H
R
R
P
P
W
W
280
|
Q
Q
S
S
Y
Y
F
F
D
D
L
L
I
I
L
L
V
V
D
D
290
|
A
A
R
R
K
K
P
P
L
L
F
F
F
F
G
G
E
E
G
G
300
|
T
T
V
V
L
L
R
R
Q
Q
V
V
D
D
T
T
K
K
T
T
310
|
G
G
K
K
L
L
K
K
I
I
G
G
T
T
Y
Y
T
T
G
G
320
|
P
P
L
L
Q
Q
H
H
G
G
I
I
V
V
Y
Y
S
S
G
G
330
|
G
G
S
S
S
S
D
D
T
T
I
I
C
C
D
D
L
L
L
L
340
|
G
G
A
A
K
K
G
G
K
K
D
D
I
I
L
L
Y
Y
I
I
350
|
G
G
D
D
H
H
I
I
F
F
G
G
D
D
I
I
L
L
K
K
360
|
S
S
K
K
K
K
R
R
Q
Q
G
G
W
W
R
R
T
T
F
F
370
|
L
L
V
V
I
I
P
P
E
E
L
L
A
A
Q
Q
E
E
L
L
380
|
H
H
V
V
W
W
T
T
D
D
K
K
S
S
S
S
L
L
F
F
390
|
E
E
E
E
L
L
Q
Q
S
S
L
L
D
D
I
I
F
F
L
L
400
|
A
A
E
E
L
L
Y
Y
K
K
H
H
L
L
D
D
S
S
S
S
410
|
S
S
N
N
E
E
R
R
P
P
D
D
I
I
S
S
S
S
I
I
420
|
Q
Q
R
R
R
R
I
I
K
K
K
K
V
V
T
T
H
H
D
D
430
|
M
M
D
D
M
M
C
C
Y
Y
G
G
M
M
M
M
G
G
S
S
440
|
L
L
F
F
R
R
S
S
G
G
S
S
R
R
Q
Q
T
T
L
L
450
|
F
F
A
A
S
S
Q
Q
V
V
M
M
R
R
Y
Y
A
A
D
D
460
|
L
L
Y
Y
A
A
A
A
S
S
F
F
I
I
N
N
L
L
L
L
470
|
Y
Y
Y
Y
P
P
F
F
S
S
Y
Y
L
L
F
F
R
R
A
A
480
|
A
A
H
H
V
V
L
L
M
M
P
P
H
H
E
E
S
S
-
T
490
|
-
V
-
E
-
H
-
T
-
H
-
V
-
D
-
I
-
N
-
E
500
|
-
M
-
E
-
S
-
P
-
L
-
A
-
T
-
R
-
N
-
R
510
|
-
T
-
S
-
V
-
D
-
F
-
K
-
D
-
T
-
D
-
Y
520
|
-
K
-
R
-
H
-
Q
-
L
-
T
-
R
-
S
-
I
-
S
530
|
-
E
-
I
-
K
-
P
-
P
-
N
-
L
Click to Show/Hide the Structure
Experimental Note Identified from the Human Clinical Data
Experiment for
Molecule Alteration		 Next-generation sequencing assay; Exome sequencing assay; Transcriptome sequencing assay; Whole genome sequencing assay; Sanger Sequencing assay
Experiment for
Drug Resistance		 Flow cytometry assay
Mechanism Description Several of these alterations are known to induce a more stem cell-like state (eg, IkZF1) or confer resistance directly to specific chemotherapy agents such as CREBBP and glucocorticoids and mutations in the 5-nucleotidase gene NT5C2 and nucleoside a.logs. Many relapse-acquired lesions are enriched in specific pathways, including B-cell development (IkZF1), tumor suppression (TP53),34 Ras signaling, chromatin modification (CREBBP, SETD2),17 and drug metabolism (NT5C2).
Investigative Drug(s)
1 drug(s) in total
Click to Show/Hide the Full List of Drugs
Thiopurine
Click to Show/Hide
Drug Resistance Data Categorized by Their Corresponding Mechanisms
  Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Disease Class: Acute lymphocytic leukemia [ICD-11: 2B33.0] [4]
Resistant Disease Acute lymphocytic leukemia [ICD-11: 2B33.0]
 Disease Info 
Resistant Drug Thiopurine
 Drug Info 
Molecule Alteration Missense mutation
p.R238W
Wild Type Structure Method: X-ray diffraction Resolution: 1.70  Å
PDB: 5OPP
Mutant Type Structure Method: X-ray diffraction Resolution: 1.84  Å
PDB: 5L4Z
   Download The Information of Sequence       Download The Structure File   
RMSD: 0.41
TM score: 0.99758
Amino acid change:
R238W
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
-
-
M
-
G
-
S
-
S
-
H
-
H
-
H
-
H
-10
|
-
H
-
H
-
S
-
S
-
G
-
L
-
V
-
P
-
R
-
G
0
|
-
S
-
M
-
S
T
T
S
S
W
W
S
S
D
D
R
R
L
L
10
|
Q
Q
N
N
A
A
A
A
D
D
M
M
P
P
A
A
N
N
M
M
20
|
D
D
K
K
H
H
A
A
L
L
K
K
K
K
Y
Y
R
R
R
R
30
|
E
E
A
A
Y
Y
H
H
R
R
V
V
F
F
V
V
N
N
R
R
40
|
S
S
L
L
A
A
M
M
E
E
K
K
I
I
K
K
C
C
F
F
50
|
G
G
F
F
D
D
M
M
D
D
Y
Y
T
T
L
L
A
A
V
V
60
|
Y
Y
K
K
S
S
P
P
E
E
Y
Y
E
E
S
S
L
L
G
G
70
|
F
F
E
E
L
L
T
T
V
V
E
E
R
R
L
L
V
V
S
S
80
|
I
I
G
G
Y
Y
P
P
Q
Q
E
E
L
L
L
L
S
S
F
F
90
|
A
A
Y
Y
D
D
S
S
T
T
F
F
P
P
T
T
R
R
G
G
100
|
L
L
V
V
F
F
D
D
T
T
L
L
Y
Y
G
G
N
N
L
L
110
|
L
L
K
K
V
V
D
D
A
A
Y
Y
G
G
N
N
L
L
L
L
120
|
V
V
C
C
A
A
H
H
G
G
F
F
N
N
F
F
I
I
R
R
130
|
G
G
P
P
E
E
T
T
R
R
E
E
Q
Q
Y
Y
P
P
N
N
140
|
K
K
F
F
I
I
Q
Q
R
R
D
D
D
D
T
T
E
E
R
R
150
|
F
F
Y
Y
I
I
L
L
N
N
T
T
L
L
F
F
N
N
L
L
160
|
P
P
E
E
T
T
Y
Y
L
L
L
L
A
A
C
C
L
L
V
V
170
|
D
D
F
F
F
F
T
T
N
N
C
C
P
P
R
R
Y
Y
T
T
180
|
S
S
C
C
E
E
T
T
G
G
F
F
K
K
D
D
G
G
D
D
190
|
L
L
F
F
M
M
S
S
Y
Y
R
R
S
S
M
M
F
F
Q
Q
200
|
D
D
V
V
R
R
D
D
A
A
V
V
D
D
W
W
V
V
H
H
210
|
Y
Y
K
K
G
G
S
S
L
L
K
K
E
E
K
K
T
T
V
V
220
|
E
E
N
N
L
L
E
E
K
K
Y
Y
V
V
V
V
K
K
D
D
230
|
G
G
K
K
L
L
P
P
L
L
L
L
L
L
S
S
R
W
M
M
240
|
K
K
E
E
V
V
G
G
K
K
V
V
F
F
L
L
A
A
T
T
250
|
N
N
S
S
D
D
Y
Y
K
K
Y
Y
T
T
D
D
K
K
I
I
260
|
M
M
T
T
Y
Y
L
L
F
F
D
D
F
F
P
P
H
H
G
G
270
|
P
P
K
K
P
P
G
G
S
S
S
S
H
H
R
R
P
P
W
W
280
|
Q
Q
S
S
Y
Y
F
F
D
D
L
L
I
I
L
L
V
V
D
D
290
|
A
A
R
R
K
K
P
P
L
L
F
F
F
F
G
G
E
E
G
G
300
|
T
T
V
V
L
L
R
R
Q
Q
V
V
D
D
T
T
K
K
T
T
310
|
G
G
K
K
L
L
K
K
I
I
G
G
T
T
Y
Y
T
T
G
G
320
|
P
P
L
L
Q
Q
H
H
G
G
I
I
V
V
Y
Y
S
S
G
G
330
|
G
G
S
S
S
S
D
D
T
T
I
I
C
C
D
D
L
L
L
L
340
|
G
G
A
A
K
K
G
G
K
K
D
D
I
I
L
L
Y
Y
I
I
350
|
G
G
D
D
H
H
I
I
F
F
G
G
D
D
I
I
L
L
K
K
360
|
S
S
K
K
K
K
R
R
Q
Q
G
G
W
W
R
R
T
T
F
F
370
|
L
L
V
V
I
I
P
P
E
E
L
L
A
A
Q
Q
E
E
L
L
380
|
H
H
V
V
W
W
T
T
D
D
K
K
S
S
S
S
L
L
F
F
390
|
E
E
E
E
L
L
Q
Q
S
S
L
L
D
D
I
I
F
F
L
L
400
|
A
A
E
E
L
L
Y
Y
K
K
H
H
L
L
D
D
S
S
S
S
410
|
S
S
N
N
E
E
R
R
P
P
D
D
I
I
S
S
S
S
I
I
420
|
Q
Q
R
R
R
R
I
I
K
K
K
K
V
V
T
T
H
H
D
D
430
|
M
M
D
D
M
M
C
C
Y
Y
G
G
M
M
M
M
G
G
S
S
440
|
L
L
F
F
R
R
S
S
G
G
S
S
R
R
Q
Q
T
T
L
L
450
|
F
F
A
A
S
S
Q
Q
V
V
M
M
R
R
Y
Y
A
A
D
D
460
|
L
L
Y
Y
A
A
A
A
S
S
F
F
I
I
N
N
L
L
L
L
470
|
Y
Y
Y
Y
P
P
F
F
S
S
Y
Y
L
L
F
F
R
R
A
A
480
|
A
A
H
H
V
V
L
L
M
M
P
P
H
H
E
E
S
S
-
T
490
|
-
V
-
E
-
H
-
T
-
H
-
V
-
D
-
I
-
N
-
E
500
|
-
M
-
E
-
S
-
P
-
L
-
A
-
T
-
R
-
N
-
R
510
|
-
T
-
S
-
V
-
D
-
F
-
K
-
D
-
T
-
D
-
Y
520
|
-
K
-
R
-
H
-
Q
-
L
-
T
-
R
-
S
-
I
-
S
530
|
-
E
-
I
-
K
-
P
-
P
-
N
-
L
Click to Show/Hide the Structure
Experimental Note Identified from the Human Clinical Data
Experiment for
Molecule Alteration		 Whole-exome sequencing assay; Whole-genome sequencing assay
Experiment for
Drug Resistance		 Flow cytometric analysis assay; MTT assay
Mechanism Description Finally, genomic profiling of diagnostic and relapsed leukemias has identified relapse-associated mutations in the 5'-nucleotidase, cytosolic II(NT5C2) gene as drivers of resistance to thiopurine chemotherapy in about 20% of T-ALL and 5% of B-precursor ALL cases at relapse.
References
Ref 1 Relapse-specific mutations in NT5C2 in childhood acute lymphoblastic leukemia. Nat Genet. 2013 Mar;45(3):290-4. doi: 10.1038/ng.2558. Epub 2013 Feb 3.
Ref 2 The genomic landscape of acute lymphoblastic leukemia in children and young adults. Hematology Am Soc Hematol Educ Program. 2014 Dec 5;2014(1):174-80. doi: 10.1182/asheducation-2014.1.174. Epub 2014 Nov 18.
Ref 3 Mutational profiling of acute lymphoblastic leukemia with testicular relapse. J Hematol Oncol. 2017 Mar 2;10(1):65. doi: 10.1186/s13045-017-0434-y.
Ref 4 Mutational landscape, clonal evolution patterns, and role of RAS mutations in relapsed acute lymphoblastic leukemia. Proc Natl Acad Sci U S A. 2016 Oct 4;113(40):11306-11311. doi: 10.1073/pnas.1608420113. Epub 2016 Sep 21.

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