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 ACLY

Gene summary

Basic gene Info.	Gene symbol	ACLY
	Gene name	ATP citrate lyase
	Synonyms	ACL\|ATPCL\|CLATP
	Cytomap	UCSC genome browser: 17q21.2
	Type of gene	protein-coding
	RefGenes	NM_001096.2, NM_198830.1,
	Description	ATP citrate synthaseATP-citrate (pro-S-)-lyaseATP-citrate synthasecitrate cleavage enzyme
	Modification date	20141207
dbXrefs	MIM : 108728
	HGNC : HGNC
	Ensembl : ENSG00000131473
	HPRD : 00155
	Vega : OTTHUMG00000133507
Protein	UniProt: P53396 go to UniProt's Cross Reference DB Table
Expression	CleanEX: HS_ACLY
	BioGPS: 47
Pathway	NCI Pathway Interaction Database: ACLY
	KEGG: ACLY
	REACTOME: ACLY
	Pathway Commons: ACLY
Context	iHOP: ACLY
	ligand binding site mutation search in PubMed: ACLY
	UCL Cancer Institute: ACLY
Assigned class in mutLBSgeneDB	C: This gene just belongs to mutLBSgenes.

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

GO ID	GO Term	PubMed ID
GO:0008610	lipid biosynthetic process	23932781

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Ligand binding site mutations for ACLY

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
N203	I202F	BRCA	1
R66	R66C	COAD	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 ACLY

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
N203	I202F	-1.2753649
R66	R66C	-0.60645005

(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 ACLY from PDB

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Differential gene expression and gene-gene network for ACLY

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 ACLY and the right PPI network was created from samples without mutations in the LBS of ACLY. 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 ACLY

Gene level disease information (DisGeNet)

Disease ID	Disease name	# PubMed	Association type
umls:C2239176	Carcinoma, Hepatocellular	1	Biomarker
umls:C0028754	Obesity	1	Biomarker

Mutation level pathogenic information (ClinVar annotation)

Allele ID

AA change

Clinical significance

Origin

Phenotype IDs

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Pharmacological information for ACLY

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.

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 ACLY go to BioLip

Ligand ID	Ligand short name	Ligand long name	PDB ID	PDB name	mutLBS
MG		MAGNESIUM(2+)	3pff	A	N203
ADP		ADP	3pff	A	R66 N203

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Conservation information for LBS of ACLY

Multiple alignments for P53396 in multiple species

LBS	AA sequence	# species	Species
A262	-----------	5	Oryza sativa subsp. japonica, Arabidopsis thaliana, Arabidopsis thaliana, Schizosaccharomyces pombe (strain 972 / ATCC 24843), Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987)
A262	DAKSGASLKLT	3	Homo sapiens, Rattus norvegicus, Bos taurus
A262	DAKTGASLKLT	1	Caenorhabditis elegans
A310	-----------	5	Oryza sativa subsp. japonica, Arabidopsis thaliana, Arabidopsis thaliana, Schizosaccharomyces pombe (strain 972 / ATCC 24843), Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987)
A310	GEYSGAPSEQQ	3	Homo sapiens, Rattus norvegicus, Bos taurus
A310	GEYSGDPSESQ	1	Caenorhabditis elegans
A345	-----------	5	Oryza sativa subsp. japonica, Arabidopsis thaliana, Arabidopsis thaliana, Schizosaccharomyces pombe (strain 972 / ATCC 24843), Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987)
A345	IGGSIANFTNV	4	Homo sapiens, Caenorhabditis elegans, Rattus norvegicus, Bos taurus
D216	-----------	5	Oryza sativa subsp. japonica, Arabidopsis thaliana, Arabidopsis thaliana, Schizosaccharomyces pombe (strain 972 / ATCC 24843), Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987)
D216	GVYVLDLAAKV	2	Homo sapiens, Bos taurus
D216	QIHVLDLAARL	1	Caenorhabditis elegans
D216	GVYILDLAAKV	1	Rattus norvegicus
D257	-----------	5	Oryza sativa subsp. japonica, Arabidopsis thaliana, Arabidopsis thaliana, Schizosaccharomyces pombe (strain 972 / ATCC 24843), Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987)
D257	YIADLDAKSGA	3	Homo sapiens, Rattus norvegicus, Bos taurus
D257	YISEMDAKTGA	1	Caenorhabditis elegans
E118	-----------	5	Oryza sativa subsp. japonica, Arabidopsis thaliana, Arabidopsis thaliana, Schizosaccharomyces pombe (strain 972 / ATCC 24843), Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987)
E118	HSQAEEFYVCI	2	Homo sapiens, Rattus norvegicus
E118	HTEKDEMYIAI	1	Caenorhabditis elegans
E118	HTQEEEFYVCI	1	Bos taurus
F110	-----------	5	Oryza sativa subsp. japonica, Arabidopsis thaliana, Arabidopsis thaliana, Schizosaccharomyces pombe (strain 972 / ATCC 24843), Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987)
F110	FLIEPFVPHSQ	2	Homo sapiens, Rattus norvegicus
F110	FIVEPFCAHTE	1	Caenorhabditis elegans
F110	FLIEPFVPHTQ	1	Bos taurus
F347	-----------	5	Oryza sativa subsp. japonica, Arabidopsis thaliana, Arabidopsis thaliana, Schizosaccharomyces pombe (strain 972 / ATCC 24843), Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987)
F347	GSIANFTNVAA	3	Homo sapiens, Rattus norvegicus, Bos taurus
F347	GSIANFTNVAK	1	Caenorhabditis elegans
G261	-----------	5	Oryza sativa subsp. japonica, Arabidopsis thaliana, Arabidopsis thaliana, Schizosaccharomyces pombe (strain 972 / ATCC 24843), Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987)
G261	LDAKSGASLKL	3	Homo sapiens, Rattus norvegicus, Bos taurus
G261	MDAKTGASLKL	1	Caenorhabditis elegans
G309	-----------	5	Oryza sativa subsp. japonica, Arabidopsis thaliana, Arabidopsis thaliana, Schizosaccharomyces pombe (strain 972 / ATCC 24843), Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987)
G309	YGEYSGAPSEQ	3	Homo sapiens, Rattus norvegicus, Bos taurus
G309	YGEYSGDPSES	1	Caenorhabditis elegans
G67	-----------	5	Oryza sativa subsp. japonica, Arabidopsis thaliana, Arabidopsis thaliana, Schizosaccharomyces pombe (strain 972 / ATCC 24843), Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987)
G67	LIKRRGKLGLV	3	Homo sapiens, Caenorhabditis elegans, Rattus norvegicus
G67	LIKRRGKLGLI	1	Bos taurus
H113	-----------	5	Oryza sativa subsp. japonica, Arabidopsis thaliana, Arabidopsis thaliana, Schizosaccharomyces pombe (strain 972 / ATCC 24843), Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987)
H113	EPFVPHSQAEE	2	Homo sapiens, Rattus norvegicus
H113	EPFCAHTEKDE	1	Caenorhabditis elegans
H113	EPFVPHTQEEE	1	Bos taurus
K58	-----------	5	Oryza sativa subsp. japonica, Arabidopsis thaliana, Arabidopsis thaliana, Schizosaccharomyces pombe (strain 972 / ATCC 24843), Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987)
K58	SL-VVKPDQLI	2	Rattus norvegicus, Bos taurus
K58	NL-VVKPDQLI	1	Homo sapiens
K58	NKGVIKPDQLI	1	Caenorhabditis elegans
L215	-----------	5	Oryza sativa subsp. japonica, Arabidopsis thaliana, Arabidopsis thaliana, Schizosaccharomyces pombe (strain 972 / ATCC 24843), Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987)
L215	DGVYVLDLAAK	2	Homo sapiens, Bos taurus
L215	NQIHVLDLAAR	1	Caenorhabditis elegans
L215	DGVYILDLAAK	1	Rattus norvegicus
N203	-----------	5	Oryza sativa subsp. japonica, Arabidopsis thaliana, Arabidopsis thaliana, Schizosaccharomyces pombe (strain 972 / ATCC 24843), Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987)
N203	TYLEINPLVVT	3	Homo sapiens, Rattus norvegicus, Bos taurus
N203	TYLEINPFVLL	1	Caenorhabditis elegans
N346	-----------	5	Oryza sativa subsp. japonica, Arabidopsis thaliana, Arabidopsis thaliana, Schizosaccharomyces pombe (strain 972 / ATCC 24843), Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987)
N346	GGSIANFTNVA	4	Homo sapiens, Caenorhabditis elegans, Rattus norvegicus, Bos taurus
P109	-----------	5	Oryza sativa subsp. japonica, Arabidopsis thaliana, Arabidopsis thaliana, Schizosaccharomyces pombe (strain 972 / ATCC 24843), Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987)
P109	NFLIEPFVPHS	2	Homo sapiens, Rattus norvegicus
P109	TFIVEPFCAHT	1	Caenorhabditis elegans
P109	NFLIEPFVPHT	1	Bos taurus
P204	-----------	5	Oryza sativa subsp. japonica, Arabidopsis thaliana, Arabidopsis thaliana, Schizosaccharomyces pombe (strain 972 / ATCC 24843), Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987)
P204	YLEINPLVVTK	3	Homo sapiens, Rattus norvegicus, Bos taurus
P204	YLEINPFVLLN	1	Caenorhabditis elegans
R379	-----------	5	Oryza sativa subsp. japonica, Arabidopsis thaliana, Arabidopsis thaliana, Schizosaccharomyces pombe (strain 972 / ATCC 24843), Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987)
R379	TIFVRRGGPNY	4	Homo sapiens, Caenorhabditis elegans, Rattus norvegicus, Bos taurus
R65	-----------	5	Oryza sativa subsp. japonica, Arabidopsis thaliana, Arabidopsis thaliana, Schizosaccharomyces pombe (strain 972 / ATCC 24843), Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987)
R65	DQLIKRRGKLG	4	Homo sapiens, Caenorhabditis elegans, Rattus norvegicus, Bos taurus
R66	-----------	5	Oryza sativa subsp. japonica, Arabidopsis thaliana, Arabidopsis thaliana, Schizosaccharomyces pombe (strain 972 / ATCC 24843), Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987)
R66	QLIKRRGKLGL	4	Homo sapiens, Caenorhabditis elegans, Rattus norvegicus, Bos taurus
S260	-----------	5	Oryza sativa subsp. japonica, Arabidopsis thaliana, Arabidopsis thaliana, Schizosaccharomyces pombe (strain 972 / ATCC 24843), Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987)
S260	DLDAKSGASLK	3	Homo sapiens, Rattus norvegicus, Bos taurus
S260	EMDAKTGASLK	1	Caenorhabditis elegans
S308	-----------	5	Oryza sativa subsp. japonica, Arabidopsis thaliana, Arabidopsis thaliana, Schizosaccharomyces pombe (strain 972 / ATCC 24843), Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987)
S308	NYGEYSGAPSE	3	Homo sapiens, Rattus norvegicus, Bos taurus
S308	NYGEYSGDPSE	1	Caenorhabditis elegans
T348	-----------	5	Oryza sativa subsp. japonica, Arabidopsis thaliana, Arabidopsis thaliana, Schizosaccharomyces pombe (strain 972 / ATCC 24843), Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987)
T348	SIANFTNVAAT	3	Homo sapiens, Rattus norvegicus, Bos taurus
T348	SIANFTNVAKT	1	Caenorhabditis elegans
V111	-----------	5	Oryza sativa subsp. japonica, Arabidopsis thaliana, Arabidopsis thaliana, Schizosaccharomyces pombe (strain 972 / ATCC 24843), Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987)
V111	LIEPFVPHSQA	2	Homo sapiens, Rattus norvegicus
V111	IVEPFCAHTEK	1	Caenorhabditis elegans
V111	LIEPFVPHTQE	1	Bos taurus
V140	-----------	5	Oryza sativa subsp. japonica, Arabidopsis thaliana, Arabidopsis thaliana, Schizosaccharomyces pombe (strain 972 / ATCC 24843), Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987)
V140	HHEGGVDVGDV	3	Homo sapiens, Rattus norvegicus, Bos taurus
V140	YEQGGVDIGDV	1	Caenorhabditis elegans
V56	-----------	5	Oryza sativa subsp. japonica, Arabidopsis thaliana, Arabidopsis thaliana, Schizosaccharomyces pombe (strain 972 / ATCC 24843), Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987)
V56	SQSL-VVKPDQ	2	Rattus norvegicus, Bos taurus
V56	SQNL-VVKPDQ	1	Homo sapiens
V56	RDNKGVIKPDQ	1	Caenorhabditis elegans