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 PDHA1

Gene summary

Basic gene Info.	Gene symbol	PDHA1
	Gene name	pyruvate dehydrogenase (lipoamide) alpha 1
	Synonyms	PDHA\|PDHAD\|PDHCE1A\|PHE1A
	Cytomap	UCSC genome browser: Xp22.1
	Type of gene	protein-coding
	RefGenes	NM_000284.3, NM_001173454.1,NM_001173455.1,NM_001173456.1,
	Description	PDHE1-A type Ipyruvate dehydrogenase E1 component subunit alpha, somatic form, mitochondrialpyruvate dehydrogenase complex, E1-alpha polypeptide 1
	Modification date	20141207
dbXrefs	MIM : 300502
	HGNC : HGNC
	Ensembl : ENSG00000131828
	HPRD : 02420
	Vega : OTTHUMG00000021224
Protein	UniProt: P08559 go to UniProt's Cross Reference DB Table
Expression	CleanEX: HS_PDHA1
	BioGPS: 5160
Pathway	NCI Pathway Interaction Database: PDHA1
	KEGG: PDHA1
	REACTOME: PDHA1
	Pathway Commons: PDHA1
Context	iHOP: PDHA1
	ligand binding site mutation search in PubMed: PDHA1
	UCL Cancer Institute: PDHA1
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:0006086	acetyl-CoA biosynthetic process from pyruvate	19081061
GO:0006099	tricarboxylic acid cycle	19081061

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Ligand binding site mutations for PDHA1

Cancer type specific mutLBS sorted by frequency

LBS	AAchange of nsSNV	Cancer type	# samples
V167	V167M	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 PDHA1

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
V167	V167M	-0.28084786

(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 PDHA1 from PDB

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Differential gene expression and gene-gene network for PDHA1

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 PDHA1 and the right PPI network was created from samples without mutations in the LBS of PDHA1. 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 PDHA1

Gene level disease information (DisGeNet)

Disease ID	Disease name	# PubMed	Association type
umls:C0034345	Pyruvate Dehydrogenase Complex Deficiency Disease	27	Biomarker, GeneticVariation
umls:C0001125	Acidosis, Lactic	4	Biomarker
umls:C0242656	Disease Progression	1	Biomarker
umls:C0151744	Myocardial Ischemia	1	Biomarker
umls:C0029408	Osteoarthritis	1	Biomarker
umls:C0033578	Prostatic Neoplasms	1	Biomarker
umls:C0034350	Pyruvate Metabolism, Inborn Errors	1	Biomarker
umls:C0038356	Stomach Neoplasms	1	Biomarker

Mutation level pathogenic information (ClinVar annotation)

Allele ID

AA change

Clinical significance

Origin

Phenotype IDs

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Pharmacological information for PDHA1

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
Nutraceutical	DB00157	NADH	Small molecule

Gene-centered ligand-gene interaction network

Ligands binding to mutated ligand binding site of PDHA1 go to BioLip

Ligand ID

Ligand short name

Ligand long name

PDB ID

PDB name

mutLBS

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Conservation information for LBS of PDHA1

Multiple alignments for P08559 in multiple species

LBS	AA sequence	# species	Species
A198	LYGDGAANQGQ	7	Homo sapiens, Bos taurus, Mus musculus, Pan troglodytes, Arabidopsis thaliana, Oryza sativa subsp. japonica, Oryza sativa subsp. japonica
A198	LYGDGASNQGQ	3	Schizosaccharomyces pombe (strain 972 / ATCC 24843), Saccharomyces cerevisiae (strain ATCC 204508 / S288c), Kluyveromyces lactis (strain ATCC 8585 / CBS 2359 / DSM 70799 / NBRC 1267 / NRRL Y-1140 / WM37)
D196	LTLYGDGAANQ	4	Homo sapiens, Bos taurus, Mus musculus, Pan troglodytes
D196	FALYGDGAANQ	2	Arabidopsis thaliana, Oryza sativa subsp. japonica
D196	FALYGDGASNQ	2	Schizosaccharomyces pombe (strain 972 / ATCC 24843), Kluyveromyces lactis (strain ATCC 8585 / CBS 2359 / DSM 70799 / NBRC 1267 / NRRL Y-1140 / WM37)
D196	FDLYGDGAANQ	1	Oryza sativa subsp. japonica
D196	FTLYGDGASNQ	1	Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
G165	FYGGNGIVGAQ	7	Homo sapiens, Bos taurus, Mus musculus, Pan troglodytes, Schizosaccharomyces pombe (strain 972 / ATCC 24843), Saccharomyces cerevisiae (strain ATCC 204508 / S288c), Kluyveromyces lactis (strain ATCC 8585 / CBS 2359 / DSM 70799 / NBRC 1267 / NRRL Y-1140 /
G165	FYGGHGIVGAQ	3	Arabidopsis thaliana, Oryza sativa subsp. japonica, Oryza sativa subsp. japonica
G195	CLTLYGDGAAN	4	Homo sapiens, Bos taurus, Mus musculus, Pan troglodytes
G195	TFALYGDGAAN	2	Arabidopsis thaliana, Oryza sativa subsp. japonica
G195	TFDLYGDGAAN	1	Oryza sativa subsp. japonica
G195	TFALYGDGASN	1	Schizosaccharomyces pombe (strain 972 / ATCC 24843)
G195	SFTLYGDGASN	1	Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
G195	SFALYGDGASN	1	Kluyveromyces lactis (strain ATCC 8585 / CBS 2359 / DSM 70799 / NBRC 1267 / NRRL Y-1140 / WM37)
G197	TLYGDGAANQG	4	Homo sapiens, Bos taurus, Mus musculus, Pan troglodytes
G197	ALYGDGAANQG	2	Arabidopsis thaliana, Oryza sativa subsp. japonica
G197	ALYGDGASNQG	2	Schizosaccharomyces pombe (strain 972 / ATCC 24843), Kluyveromyces lactis (strain ATCC 8585 / CBS 2359 / DSM 70799 / NBRC 1267 / NRRL Y-1140 / WM37)
G197	DLYGDGAANQG	1	Oryza sativa subsp. japonica
G197	TLYGDGASNQG	1	Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
G228	ENNRYGMGTSV	4	Homo sapiens, Bos taurus, Mus musculus, Pan troglodytes
G228	ENNHYGMGTAE	2	Oryza sativa subsp. japonica, Oryza sativa subsp. japonica
G228	ENNKYGMGTAA	2	Saccharomyces cerevisiae (strain ATCC 204508 / S288c), Kluyveromyces lactis (strain ATCC 8585 / CBS 2359 / DSM 70799 / NBRC 1267 / NRRL Y-1140 / WM37)
G228	ENNHYGMGTAT	1	Arabidopsis thaliana
G228	ENNKYGMGTSA	1	Schizosaccharomyces pombe (strain 972 / ATCC 24843)
H292	YRYHGHSMSDP	6	Homo sapiens, Bos taurus, Mus musculus, Arabidopsis thaliana, Oryza sativa subsp. japonica, Oryza sativa subsp. japonica
H292	YRYGGHSMSDP	3	Schizosaccharomyces pombe (strain 972 / ATCC 24843), Saccharomyces cerevisiae (strain ATCC 204508 / S288c), Kluyveromyces lactis (strain ATCC 8585 / CBS 2359 / DSM 70799 / NBRC 1267 / NRRL Y-1140 / WM37)
H292	YRYHGHSMSGP	1	Pan troglodytes
I166	YGGNGIVGAQV	6	Homo sapiens, Bos taurus, Mus musculus, Pan troglodytes, Saccharomyces cerevisiae (strain ATCC 204508 / S288c), Kluyveromyces lactis (strain ATCC 8585 / CBS 2359 / DSM 70799 / NBRC 1267 / NRRL Y-1140 / WM37)
I166	YGGHGIVGAQV	2	Oryza sativa subsp. japonica, Oryza sativa subsp. japonica
I166	YGGHGIVGAQI	1	Arabidopsis thaliana
I166	YGGNGIVGAQI	1	Schizosaccharomyces pombe (strain 972 / ATCC 24843)
N225	FICENNRYGMG	4	Homo sapiens, Bos taurus, Mus musculus, Pan troglodytes
N225	LVCENNHYGMG	3	Arabidopsis thaliana, Oryza sativa subsp. japonica, Oryza sativa subsp. japonica
N225	FCCENNKYGMG	2	Saccharomyces cerevisiae (strain ATCC 204508 / S288c), Kluyveromyces lactis (strain ATCC 8585 / CBS 2359 / DSM 70799 / NBRC 1267 / NRRL Y-1140 / WM37)
N225	FACENNKYGMG	1	Schizosaccharomyces pombe (strain 972 / ATCC 24843)
Q201	DGAANQGQIFE	4	Homo sapiens, Bos taurus, Mus musculus, Pan troglodytes
Q201	DGAANQGQLFE	3	Arabidopsis thaliana, Oryza sativa subsp. japonica, Oryza sativa subsp. japonica
Q201	DGASNQGQVFE	2	Saccharomyces cerevisiae (strain ATCC 204508 / S288c), Kluyveromyces lactis (strain ATCC 8585 / CBS 2359 / DSM 70799 / NBRC 1267 / NRRL Y-1140 / WM37)
Q201	DGASNQGQAFE	1	Schizosaccharomyces pombe (strain 972 / ATCC 24843)
R119	LITAYRAHGFT	4	Homo sapiens, Bos taurus, Mus musculus, Pan troglodytes
R119	IITSYRDHCTF	1	Arabidopsis thaliana
R119	IITAYRDHCTY	1	Oryza sativa subsp. japonica
R119	IITAYRDHCAY	1	Oryza sativa subsp. japonica
R119	IITSYRCHGFA	1	Schizosaccharomyces pombe (strain 972 / ATCC 24843)
R119	IITSYRCHGFT	1	Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
R119	VITSYRCHGFT	1	Kluyveromyces lactis (strain ATCC 8585 / CBS 2359 / DSM 70799 / NBRC 1267 / NRRL Y-1140 / WM37)
V167	GGNGIVGAQVP	6	Homo sapiens, Bos taurus, Mus musculus, Pan troglodytes, Saccharomyces cerevisiae (strain ATCC 204508 / S288c), Kluyveromyces lactis (strain ATCC 8585 / CBS 2359 / DSM 70799 / NBRC 1267 / NRRL Y-1140 / WM37)
V167	GGHGIVGAQVP	2	Oryza sativa subsp. japonica, Oryza sativa subsp. japonica
V167	GGHGIVGAQIP	1	Arabidopsis thaliana
V167	GGNGIVGAQIP	1	Schizosaccharomyces pombe (strain 972 / ATCC 24843)
Y118	HLITAYRAHGF	4	Homo sapiens, Bos taurus, Mus musculus, Pan troglodytes
Y118	SIITSYRCHGF	2	Schizosaccharomyces pombe (strain 972 / ATCC 24843), Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
Y118	AIITSYRDHCT	1	Arabidopsis thaliana
Y118	SIITAYRDHCT	1	Oryza sativa subsp. japonica
Y118	AIITAYRDHCA	1	Oryza sativa subsp. japonica
Y118	TVITSYRCHGF	1	Kluyveromyces lactis (strain ATCC 8585 / CBS 2359 / DSM 70799 / NBRC 1267 / NRRL Y-1140 / WM37)
Y227	CENNRYGMGTS	4	Homo sapiens, Bos taurus, Mus musculus, Pan troglodytes
Y227	CENNHYGMGTA	3	Arabidopsis thaliana, Oryza sativa subsp. japonica, Oryza sativa subsp. japonica
Y227	CENNKYGMGTA	2	Saccharomyces cerevisiae (strain ATCC 204508 / S288c), Kluyveromyces lactis (strain ATCC 8585 / CBS 2359 / DSM 70799 / NBRC 1267 / NRRL Y-1140 / WM37)
Y227	CENNKYGMGTS	1	Schizosaccharomyces pombe (strain 972 / ATCC 24843)