mutLBSgeneDB

mutLBSgeneDB
mutated Ligand Binding Site gene DataBase

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Bioinformatics and Systems Medicine Laboratory Bioinformatics and Systems Medicine Laboratory

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 HDAC4
Gene summary
Basic gene Info.Gene symbolHDAC4
Gene namehistone deacetylase 4
SynonymsAHO3|BDMR|HA6116|HD4|HDAC-4|HDAC-A|HDACA
CytomapUCSC genome browser: 2q37.3
Type of geneprotein-coding
RefGenesNM_006037.3,
Descriptionhistone deacetylase A
Modification date20141219
dbXrefs MIM : 605314
HGNC : HGNC
Ensembl : ENSG00000068024
HPRD : 05610
Vega : OTTHUMG00000133344
ProteinUniProt: P56524
go to UniProt's Cross Reference DB Table
ExpressionCleanEX: HS_HDAC4
BioGPS: 9759
PathwayNCI Pathway Interaction Database: HDAC4
KEGG: HDAC4
REACTOME: HDAC4
Pathway Commons: HDAC4
ContextiHOP: HDAC4
ligand binding site mutation search in PubMed: HDAC4
UCL Cancer Institute: HDAC4
Assigned class in mutLBSgeneDBB: This gene belongs to targetable_mutLBSgenes.

Gene ontology having evidence of Inferred from Direct Assay (IDA) from Entrez
GO IDGO TermPubMed ID
GO:0000122negative regulation of transcription from RNA polymerase II promoter10869435
GO:0006338chromatin remodeling18850004
GO:0016575histone deacetylation10869435
GO:0033235positive regulation of protein sumoylation17696781
GO:0034983peptidyl-lysine deacetylation18614528
GO:0045892negative regulation of transcription, DNA-templated10869435
GO:0070932histone H3 deacetylation12590135
GO:0070933histone H4 deacetylation12590135


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Ligand binding site mutations for HDAC4
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
LBSAAchange of nsSNVCancer type# samples
R681R681KLUSC1
P942P942HSKCM1
D934F933LSKCM1
G975D977NSTAD1
H665L663VSTAD1
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 HDAC4
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.
LBSAAchange of nsSNVRelative stability change
P942P942H-1.4575842
H665L663V-1.1832811
D934F933L-1.0853421
R681R681K-0.96707605
G975D977N-0.16414282
(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 HDAC4 from PDB

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Differential gene expression and gene-gene network for HDAC4
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 HDAC4 and the right PPI network was created from samples without mutations in the LBS of HDAC4. 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 HDAC4
Gene level disease information (DisGeNet)
Disease IDDisease name# PubMedAssociation type
umls:C2931817Chromosome 2q37 deletion syndrome5Biomarker
umls:C3714756Intellectual Disability2Biomarker
umls:C0221357Brachydactyly1Biomarker
umls:C0236736Cocaine-Related Disorders1Therapeutic
umls:C0005695Urinary Bladder Neoplasms1Biomarker

Mutation level pathogenic information (ClinVar annotation)
Allele IDAA changeClinical significanceOriginPhenotype IDs

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Pharmacological information for HDAC4
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 statusDrugBank IDNameTypeDrug structure
Approved|investigationalDB06176RomidepsinSmall molecule
Approved|investigationalDB06603PanobinostatSmall molecule
ExperimentalDB07879N-hydroxy-5-[(3-phenyl-5,6-dihydroimidazo[1,2-a]pyrazin-7(8H)-yl)carbonyl]thiophene-2-carboxamideSmall molecule
ExperimentalDB086132,2,2-TRIFLUORO-1-{5-[(3-PHENYL-5,6-DIHYDROIMIDAZO[1,2-A]PYRAZIN-7(8H)-YL)CARBONYL]THIOPHEN-2-YL}ETHANE-1,1-DIOLSmall molecule

Gene-centered ligand-gene interaction network

Ligands binding to mutated ligand binding site of HDAC4 go to BioLip
Ligand IDLigand short nameLigand long namePDB IDPDB namemutLBS
9F4(1R,2R,3R)-2-[4-(5-FLUORANYLPYRIMIDIN-2-YL) PHENYL]-N-OXIDANYL-3-PHENYL-CYCLOPROPANE-1- CARBOXAMIDE4cbtAD934
ZNZINC(2+)4cbtAD934
ZNZINC(2+)4cbtBD934
ZNZINC(2+)4cbtCD934
ZNZINC(2+)4cbyAD934
ZNZINC(2+)4cbyBD934
KEE(1R,2R,3R)-2-[4-(1,3-OXAZOL-5-YL)PHENYL]-N- OXIDANYL-3-PHENYL-CYCLOPROPANE-1-CARBOXAMIDE4cbyCD934
ZNZINC(2+)4cbyCD934
ZNZINC(2+)4cbyDD934
KEE(1R,2R,3R)-2-[4-(1,3-OXAZOL-5-YL)PHENYL]-N- OXIDANYL-3-PHENYL-CYCLOPROPANE-1-CARBOXAMIDE4cbyAR681 D934
KEE(1R,2R,3R)-2-[4-(1,3-OXAZOL-5-YL)PHENYL]-N- OXIDANYL-3-PHENYL-CYCLOPROPANE-1-CARBOXAMIDE4cbyBR681 D934
KEE(1R,2R,3R)-2-[4-(1,3-OXAZOL-5-YL)PHENYL]-N- OXIDANYL-3-PHENYL-CYCLOPROPANE-1-CARBOXAMIDE4cbyDR681 D934
9F4(1R,2R,3R)-2-[4-(5-FLUORANYLPYRIMIDIN-2-YL) PHENYL]-N-OXIDANYL-3-PHENYL-CYCLOPROPANE-1- CARBOXAMIDE4cbtCR681 D934 P942
9F4(1R,2R,3R)-2-[4-(5-FLUORANYLPYRIMIDIN-2-YL) PHENYL]-N-OXIDANYL-3-PHENYL-CYCLOPROPANE-1- CARBOXAMIDE4cbtBR681 D934 P942 G975


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Conservation information for LBS of HDAC4
Multiple alignments for P56524 in multiple species
LBSAA sequence# speciesSpecies
C667MLKHQCTCGNT3Gallus gallus, Mus musculus, Rattus norvegicus
C667MLKHQCTCGSS1Homo sapiens
C669KHQCTCGNTNS3Gallus gallus, Mus musculus, Rattus norvegicus
C669KHQCTCGSSSS1Homo sapiens
C751FVRLPCGGVGV4Homo sapiens, Gallus gallus, Mus musculus, Rattus norvegicus
D840LIVDWDVHHGN4Homo sapiens, Gallus gallus, Mus musculus, Rattus norvegicus
D934VSSGFDAVEGH4Homo sapiens, Gallus gallus, Mus musculus, Rattus norvegicus
E677TNSHPEHAGRI3Gallus gallus, Mus musculus, Rattus norvegicus
E677SSSHPEHAGRI1Homo sapiens
E973IVLALEGGHDL2Homo sapiens, Rattus norvegicus
E973VVLALEGGHDL1Gallus gallus
E973LVLALEGGHDL1Mus musculus
F812STPMGFCYFNS4Homo sapiens, Gallus gallus, Mus musculus, Rattus norvegicus
F871DDGNFFPGSGA4Homo sapiens, Gallus gallus, Mus musculus, Rattus norvegicus
G811ESTPMGFCYFN4Homo sapiens, Gallus gallus, Mus musculus, Rattus norvegicus
G974VLALEGGHDLT4Homo sapiens, Gallus gallus, Mus musculus, Rattus norvegicus
G975LALEGGHDLTA4Homo sapiens, Gallus gallus, Mus musculus, Rattus norvegicus
H665TLMLKHQCTCG4Homo sapiens, Gallus gallus, Mus musculus, Rattus norvegicus
H675GNTNSHPEHAG3Gallus gallus, Mus musculus, Rattus norvegicus
H675GSSSSHPEHAG1Homo sapiens
H678NSHPEHAGRIQ3Gallus gallus, Mus musculus, Rattus norvegicus
H678SSHPEHAGRIQ1Homo sapiens
H802VRPPGHHAEES4Homo sapiens, Gallus gallus, Mus musculus, Rattus norvegicus
H803RPPGHHAEEST4Homo sapiens, Gallus gallus, Mus musculus, Rattus norvegicus
H842VDWDVHHGNGT4Homo sapiens, Gallus gallus, Mus musculus, Rattus norvegicus
L943GHPTPLGGYNL4Homo sapiens, Gallus gallus, Mus musculus, Rattus norvegicus
P676NTNSHPEHAGR3Gallus gallus, Mus musculus, Rattus norvegicus
P676SSSSHPEHAGR1Homo sapiens
P800AVVRPPGHHAE4Homo sapiens, Gallus gallus, Mus musculus, Rattus norvegicus
P942EGHPTPLGGYN4Homo sapiens, Gallus gallus, Mus musculus, Rattus norvegicus
R681PEHAGRIQSIW4Homo sapiens, Gallus gallus, Mus musculus, Rattus norvegicus


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