mutLBSgeneDB

mutLBSgeneDB
mutated Ligand Binding Site gene DataBase

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	Gene Summary
	Ligand Binding Site Mutation Information
	Protein Structure Related Information
	Gene Expression and Gene-Gene Network
	Phenotype Information
	Pharmacological Information
	Conservation Information for LBS

Gene summary for MCL1

Gene summary

Basic gene Info.	Gene symbol	MCL1
	Gene name	myeloid cell leukemia 1
	Synonyms	BCL2L3\|EAT\|MCL1-ES\|MCL1L\|MCL1S\|Mcl-1\|TM\|bcl2-L-3\|mcl1/EAT
	Cytomap	UCSC genome browser: 1q21
	Type of gene	protein-coding
	RefGenes	NM_001197320.1, NM_021960.4,NM_182763.2,
	Description	bcl-2-like protein 3bcl-2-related protein EAT/mcl1induced myeloid leukemia cell differentiation protein Mcl-1myeloid cell leukemia ESmyeloid cell leukemia sequence 1 (BCL2-related)
	Modification date	20141222
dbXrefs	MIM : 159552
	HGNC : HGNC
	Ensembl : ENSG00000143384
	HPRD : 08870
	Vega : OTTHUMG00000034867
Protein	UniProt: Q07820 go to UniProt's Cross Reference DB Table
Expression	CleanEX: HS_MCL1
	BioGPS: 4170
Pathway	NCI Pathway Interaction Database: MCL1
	KEGG: MCL1
	REACTOME: MCL1
	Pathway Commons: MCL1
Context	iHOP: MCL1
	ligand binding site mutation search in PubMed: MCL1
	UCL Cancer Institute: MCL1
Assigned class in mutLBSgeneDB	B: This gene belongs to targetable_mutLBSgenes.

Gene ontology having evidence of Inferred from Direct Assay (IDA) from Entrez

GO ID	GO Term	PubMed ID
GO:0034097	response to cytokine	9184696

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Ligand binding site mutations for MCL1

Lollipop-style diagram of mutations at LBS in amino-acid sequence.
We represented ligand binding site mutations only. (You can see big image via clicking.)

: non-synonymous mutation on LBS, Circle size denotes number of samples.

Cancer type specific mutLBS sorted by frequency

LBS	AAchange of nsSNV	Cancer type	# samples
D241	D242N	BRCA	1
K302	R303L	LUAD	1
V216,V220	D218N	PRAD	1
L290	L290F	UCEC	1

cf) Cancer type abbreviation. BLCA: Bladder urothelial carcinoma, BRCA: Breast invasive carcinoma, CESC: Cervical squamous cell carcinoma and endocervical adenocarcinoma, COAD: Colon adenocarcinoma, GBM: Glioblastoma multiforme, LGG: Brain lower grade glioma, HNSC: Head and neck squamous cell carcinoma, KICH: Kidney chromophobe, KIRC: Kidney renal clear cell carcinoma, KIRP: Kidney renal papillary cell carcinoma, LAML: Acute myeloid leukemia, LUAD: Lung adenocarcinoma, LUSC: Lung squamous cell carcinoma, OV: Ovarian serous cystadenocarcinoma, PAAD: Pancreatic adenocarcinoma, PRAD: Prostate adenocarcinoma, SKCM: Skin cutaneous melanoma, STAD: Stomach adenocarcinoma, THCA: Thyroid carcinoma, UCEC: Uterine corpus endometrial carcinoma.

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Protein structure related information for MCL1

Relative protein structure stability change (ΔΔE) using Mupro 1.1
Mupro score denotes assessment of the effect of mutations on thermodynamic stability.
(ΔΔE<0: mutation decreases stability, ΔΔE>0: mutation increases stability)

: nsSNV at non-LBS

: nsSNV at LBS

nsSNVs sorted by the relative stability change of protein structure by each mutation
Blue: mutations of positive stability change. and red : the most recurrent mutation for this gene.

LBS	AAchange of nsSNV	Relative stability change
D241	D242N	-1.0266142
L290	L290F	-0.70220771
K302	R303L	-0.52564785
V216	D218N	-0.46611231
V220	D218N	-0.46611231

(MuPro1.1: Jianlin Cheng et al., Prediction of Protein Stability Changes for Single-Site Mutations Using Support Vector Machines, PROTEINS: Structure, Function, and Bioinformatics. 2006, 62:1125-1132)

Structure image for MCL1 from PDB

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Differential gene expression and gene-gene network for MCL1

Differential gene expression between mutated and non-mutated LBS samples in all 16 major cancer types

Differential co-expressed gene network based on protein-protein interaction data (CePIN)

* Left PPI network was created from samples with mutations in the LBS of MCL1 and the right PPI network was created from samples without mutations in the LBS of MCL1. Only genes with p-value < 0.05 are shown.
Red circle: input gene. Orange circle: LBSgene. Blue circle: other gene.

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Phenotype information for MCL1

Gene level disease information (DisGeNet)

Disease ID	Disease name	# PubMed	Association type
umls:C0026764	Multiple Myeloma	39	Biomarker
umls:C0024121	Lung Neoplasms	4	AlteredExpression, Biomarker
umls:C0079773	Lymphoma, T-Cell, Cutaneous	2	Biomarker
umls:C1261473	Sarcoma	2	Biomarker
umls:C0004763	Barrett Esophagus	1	Biomarker

Mutation level pathogenic information (ClinVar annotation)

Allele ID

AA change

Clinical significance

Origin

Phenotype IDs

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Pharmacological information for MCL1

Gene expression profile of anticancer drug treated cell-lines (CCLE)
Heatmap showing the correlation between gene expression and drug response across all the cell-lines. We chose the top 20 among 138 drugs.We used Pearson's correlation coefficient.

Gene-centered drug-gene interaction network

Drug information targeting mutLBSgene (Approved drugs only)

Drug status

DrugBank ID

Name

Type

Drug structure

Gene-centered ligand-gene interaction network

Ligands binding to mutated ligand binding site of MCL1 go to BioLip

Ligand ID	Ligand short name	Ligand long name	PDB ID	PDB name	mutLBS
ZN		ZINC(2+)	3kj2	A	D241
ZN		ZINC(2+)	3kz0	B	D241
3M6		(2S)-2-[(2S,3R)-10-{[(4-FLUOROPHENYL)SULFONYL]AMINO}-3- METHYL-2-[(METHYL{[4-(TRIFLUOROMETHYL) PHENYL]CARBAMOYL}AMINO)METHYL]-6-OXO-3,4-DIHYDRO-2H-1, 5-BENZOXAZOCIN-5(6H)-YL]PROPANOIC ACID	4wgi	A	K302
LC6		7-(4-{[(4-{[(2R)-4-(DIMETHYLAMINO)-1-(PHENYLSULFANYL) BUTAN-2-YL]AMINO}-3-NITROPHENYL)SULFONYL]CARBAMOYL}-2- METHYLPHENYL)-3-[3-(NAPHTHALEN-1-YLOXY) PROPYL]PYRAZOLO[1,5-A]PYRIDINE-2-CARBOXYLIC ACID	3wiy	D	L290
LC6		7-(4-{[(4-{[(2R)-4-(DIMETHYLAMINO)-1-(PHENYLSULFANYL) BUTAN-2-YL]AMINO}-3-NITROPHENYL)SULFONYL]CARBAMOYL}-2- METHYLPHENYL)-3-[3-(NAPHTHALEN-1-YLOXY) PROPYL]PYRAZOLO[1,5-A]PYRIDINE-2-CARBOXYLIC ACID	3wiy	F	L290
2UU		4-(4-METHYLNAPHTHALEN-1-YL)-2-{[(4-PHENOXYPHENYL) SULFONYL]AMINO}BENZOIC ACID	4oq5	A	L290
2UU		4-(4-METHYLNAPHTHALEN-1-YL)-2-{[(4-PHENOXYPHENYL) SULFONYL]AMINO}BENZOIC ACID	4oq5	B	L290
2UU		4-(4-METHYLNAPHTHALEN-1-YL)-2-{[(4-PHENOXYPHENYL) SULFONYL]AMINO}BENZOIC ACID	4oq5	C	L290
2UU		4-(4-METHYLNAPHTHALEN-1-YL)-2-{[(4-PHENOXYPHENYL) SULFONYL]AMINO}BENZOIC ACID	4oq5	D	L290
2UU		4-(4-METHYLNAPHTHALEN-1-YL)-2-{[(4-PHENOXYPHENYL) SULFONYL]AMINO}BENZOIC ACID	4oq5	E	L290
2UU		4-(4-METHYLNAPHTHALEN-1-YL)-2-{[(4-PHENOXYPHENYL) SULFONYL]AMINO}BENZOIC ACID	4oq5	F	L290
4M7		(1R)-7-[3-(NAPHTHALEN-1-YLOXY)PROPYL]-3,4-DIHYDRO-2H- [1,4]THIAZEPINO[2,3,4-HI]INDOLE-6-CARBOXYLIC ACID 1- OXIDE	4zbf	I	L290
4M6		1-[3-(NAPHTHALEN-1-YLOXY)PROPYL]-5,6-DIHYDRO-4H- PYRROLO[3,2,1-IJ]QUINOLINE-2-CARBOXYLIC ACID	4zbi	B	L290
4M6		1-[3-(NAPHTHALEN-1-YLOXY)PROPYL]-5,6-DIHYDRO-4H- PYRROLO[3,2,1-IJ]QUINOLINE-2-CARBOXYLIC ACID	4zbi	K	L290
4M6		1-[3-(NAPHTHALEN-1-YLOXY)PROPYL]-5,6-DIHYDRO-4H- PYRROLO[3,2,1-IJ]QUINOLINE-2-CARBOXYLIC ACID	4zbi	L	L290
III		Peptide ligand (ALA,SER,THR,LYS,LYS,LEU,SER,GLU,CYS,LEU,LYS,ARG,ILE,GLY,ASP,GLU,LEU,ASP,SER,ASN,MET,GLU,LEU,GLN,ARG,MET,ILE)	3pk1	A	V216
III		Peptide ligand (ALA,SER,THR,LYS,LYS,LEU,SER,GLU,CYS,LEU,LYS,ARG,ILE,GLY,ASP,GLU,LEU,ASP,SER,ASN,MET,GLU,LEU,GLN,ARG,MET,ILE)	3pk1	C	V216
III		Peptide ligand (GLY,ARG,PRO,GLU,ILE,TRP,ILE,ALA,GLN,GLU,LEU,ARG,ARG,ILE,GLY,ASP,GLU,PHE,ASN,ALA,TYR,TYR,ALA)	2pqk	A	V216 V220
III		Peptide ligand (ARG,PRO,GLU,ILE,TRP,ALA,ALA,GLN,GLU,LEU,ARG,ARG,ILE,GLY,ASP,GLU,PHE,ASN,ALA,TYR,TYR,ARG)	3kj1	A	V216 V220
III		Peptide ligand (ARG,PRO,GLU,ILE,TRP,ILE,ALA,GLN,GLU,LEU,ARG,ARG,ILE,GLY,ASP,GLU,GLU,ASN,ALA,TYR,TYR,ARG)	3kj2	A	V216 V220
III		Peptide ligand (ARG,PRO,GLU,ILE,TRP,ILE,ALA,GLN,GLU,TYR,ARG,ARG,ILE,GLY,ASP,GLU,PHE,ASN,ALA,TYR,TYR,ALA,ARG)	3io9	A	V220
III		Peptide ligand (GLY,ARG,PRO,GLU,ILE,TRP,TYR,ALA,GLN,GLU,LEU,ARG,ARG,ILE,GLY,ASP,GLU,PHE,ASN,ALA,TYR,TYR,ALA,ARG)	3kj0	A	V220
III		Peptide ligand (ARG,PRO,GLU,ILE,TRP,ALA,ALA,GLN,GLU,ILE,ARG,ARG,ILE,GLY,ASP,GLU,ASN,ASN,ALA,TYR,TYR,ALA,ARG)	3kz0	A	V220
III		Peptide ligand (ARG,PRO,GLU,ILE,TRP,ALA,ALA,GLN,GLU,ILE,ARG,ARG,ILE,GLY,ASP,GLU,ASN,ASN,ALA,TYR,TYR,ALA,ARG)	3kz0	B	V220
III		Peptide ligand (ACE,ALA,LEU,GLU,THR,LEU,ARG,ARG,VAL,GLY,ASP,GLY,VAL,GLN,ARG,ASN,HIS,NH2)	4hw4	A	V220
III		Peptide ligand (ACE,ALA,LEU,GLU,THR,LEU,ARG,ARG,VAL,GLY,ASP,GLY,VAL,GLN,ARG,ASN,HIS,NH2)	4hw4	B	V220
III		Peptide ligand (ALA,GLU,GLU,ILE,GLY,ALA,GLN,LEU,ARG,ARG,MET,ALA,ASP,ASP,LEU,ASN,ALA,GLN,TYR)	4bpi	A	V220

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Conservation information for LBS of MCL1

Multiple alignments for Q07820 in multiple species

LBS	AA sequence	# species	Species
A227	RNHETAFQGML	3	Homo sapiens, Mus musculus, Rattus norvegicus
C286	INQESCIEPLA	2	Homo sapiens, Rattus norvegicus
C286	VNQESFIEPLA	1	Mus musculus
D236	MLRKLDIKNED	2	Homo sapiens, Rattus norvegicus
D236	MLRKLDIKNEG	1	Mus musculus
D241	DIKNEDDVKSL	1	Homo sapiens
D241	DIKNEGDVKSF	1	Mus musculus
D241	DIKNEDDVKSF	1	Rattus norvegicus
D256	IHVFSDGVTNW	1	Homo sapiens
D256	VHVFKDGVTNW	1	Mus musculus
D256	THVFKDGVTNW	1	Rattus norvegicus
D313	KQRGWDGFVEF	3	Homo sapiens, Mus musculus, Rattus norvegicus
E240	LDIKNEDDVKS	2	Homo sapiens, Rattus norvegicus
E240	LDIKNEGDVKS	1	Mus musculus
E288	QESCIEPLAES	2	Homo sapiens, Rattus norvegicus
E288	QESFIEPLAET	1	Mus musculus
E292	IEPLAESITDV	2	Homo sapiens, Rattus norvegicus
E292	IEPLAETITDV	1	Mus musculus
E317	WDGFVEFFHVQ	2	Mus musculus, Rattus norvegicus
E317	WDGFVEFFHVE	1	Homo sapiens
E39	RLLATEKEASA	1	Homo sapiens
E39	ARLVAE-EAKA	1	Mus musculus
E39	TRLAAE-EAKA	1	Rattus norvegicus
F228	NHETAFQGMLR	3	Homo sapiens, Mus musculus, Rattus norvegicus
F254	VMIHVFSDGVT	1	Homo sapiens
F254	VMVHVFKDGVT	1	Mus musculus
F254	VMTHVFKDGVT	1	Rattus norvegicus
F270	VTLISFGAFVA	3	Homo sapiens, Mus musculus, Rattus norvegicus
F318	DGFVEFFHVQD	2	Mus musculus, Rattus norvegicus
F318	DGFVEFFHVED	1	Homo sapiens
F319	GFVEFFHVQDL	2	Mus musculus, Rattus norvegicus
F319	GFVEFFHVEDL	1	Homo sapiens
G230	ETAFQGMLRKL	3	Homo sapiens, Mus musculus, Rattus norvegicus
G262	GVTNWGRIVTL	3	Homo sapiens, Mus musculus, Rattus norvegicus
G271	TLISFGAFVAK	3	Homo sapiens, Mus musculus, Rattus norvegicus
H224	GVQRNHETAFQ	3	Homo sapiens, Mus musculus, Rattus norvegicus
H252	SRVMIHVFSDG	1	Homo sapiens
H252	SRVMVHVFKDG	1	Mus musculus
H252	SRVMTHVFKDG	1	Rattus norvegicus
H277	AFVAKHLKTIN	1	Homo sapiens
H277	AFVAKHLKSVN	1	Mus musculus
H277	AFVAKHLKSIN	1	Rattus norvegicus
H320	FVEFFHVQDLE	2	Mus musculus, Rattus norvegicus
H320	FVEFFHVEDLE	1	Homo sapiens
I264	TNWGRIVTLIS	3	Homo sapiens, Mus musculus, Rattus norvegicus
I294	PLAESITDVLV	2	Homo sapiens, Rattus norvegicus
I294	PLAETITDVLV	1	Mus musculus
K234	QGMLRKLDIKN	3	Homo sapiens, Mus musculus, Rattus norvegicus
K302	VLVRTKRDWLV	3	Homo sapiens, Mus musculus, Rattus norvegicus
L235	GMLRKLDIKNE	3	Homo sapiens, Mus musculus, Rattus norvegicus
L246	DDVKSLSRVMI	1	Homo sapiens
L246	GDVKSFSRVMV	1	Mus musculus
L246	DDVKSFSRVMT	1	Rattus norvegicus
L267	GRIVTLISFGA	3	Homo sapiens, Mus musculus, Rattus norvegicus
L290	SCIEPLAESIT	2	Homo sapiens, Rattus norvegicus
L290	SFIEPLAETIT	1	Mus musculus
M231	TAFQGMLRKLD	3	Homo sapiens, Mus musculus, Rattus norvegicus
M250	SLSRVMIHVFS	1	Homo sapiens
M250	SFSRVMVHVFK	1	Mus musculus
M250	SFSRVMTHVFK	1	Rattus norvegicus
N260	KDGVTNWGRIV	2	Mus musculus, Rattus norvegicus
N260	SDGVTNWGRIV	1	Homo sapiens
Q229	HETAFQGMLRK	3	Homo sapiens, Mus musculus, Rattus norvegicus
R215	LETLRRVGDGV	3	Homo sapiens, Mus musculus, Rattus norvegicus
R248	VKSLSRVMIHV	1	Homo sapiens
R248	VKSFSRVMVHV	1	Mus musculus
R248	VKSFSRVMTHV	1	Rattus norvegicus
R263	VTNWGRIVTLI	3	Homo sapiens, Mus musculus, Rattus norvegicus
R310	WLVKQRGWDGF	3	Homo sapiens, Mus musculus, Rattus norvegicus
S245	EDDVKSLSRVM	1	Homo sapiens
S245	EGDVKSFSRVM	1	Mus musculus
S245	EDDVKSFSRVM	1	Rattus norvegicus
S255	MIHVFSDGVTN	1	Homo sapiens
S255	MVHVFKDGVTN	1	Mus musculus
S255	MTHVFKDGVTN	1	Rattus norvegicus
T226	QRNHETAFQGM	3	Homo sapiens, Mus musculus, Rattus norvegicus
T259	FKDGVTNWGRI	2	Mus musculus, Rattus norvegicus
T259	FSDGVTNWGRI	1	Homo sapiens
T266	WGRIVTLISFG	3	Homo sapiens, Mus musculus, Rattus norvegicus
V216	ETLRRVGDGVQ	3	Homo sapiens, Mus musculus, Rattus norvegicus
V220	RVGDGVQRNHE	3	Homo sapiens, Mus musculus, Rattus norvegicus
V249	KSLSRVMIHVF	1	Homo sapiens
V249	KSFSRVMVHVF	1	Mus musculus
V249	KSFSRVMTHVF	1	Rattus norvegicus
V253	RVMIHVFSDGV	1	Homo sapiens
V253	RVMVHVFKDGV	1	Mus musculus
V253	RVMTHVFKDGV	1	Rattus norvegicus
V258	VFKDGVTNWGR	2	Mus musculus, Rattus norvegicus
V258	VFSDGVTNWGR	1	Homo sapiens
V265	NWGRIVTLISF	3	Homo sapiens, Mus musculus, Rattus norvegicus
V316	GWDGFVEFFHV	3	Homo sapiens, Mus musculus, Rattus norvegicus
V9	LRRNAVIGLNL	2	Mus musculus, Rattus norvegicus
V9	LKRNAVIGLNL	1	Homo sapiens
W261	DGVTNWGRIVT	3	Homo sapiens, Mus musculus, Rattus norvegicus