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 HRH1

Gene summary

Basic gene Info.	Gene symbol	HRH1
	Gene name	histamine receptor H1
	Synonyms	H1-R\|hisH1
	Cytomap	UCSC genome browser: 3p25
	Type of gene	protein-coding
	RefGenes	NM_000861.3, NM_001098211.1,NM_001098212.1,NM_001098213.1,
	Description	H1RHH1Rhistamine H(1) receptorhistamine H1 receptorhistamine receptor, subclass H1
	Modification date	20141207
dbXrefs	MIM : 600167
	HGNC : HGNC
	Ensembl : ENSG00000196639
	HPRD : 02544
	Vega : OTTHUMG00000129719
Protein	UniProt: P35367 go to UniProt's Cross Reference DB Table
Expression	CleanEX: HS_HRH1
	BioGPS: 3269
Pathway	NCI Pathway Interaction Database: HRH1
	KEGG: HRH1
	REACTOME: HRH1
	Pathway Commons: HRH1
Context	iHOP: HRH1
	ligand binding site mutation search in PubMed: HRH1
	UCL Cancer Institute: HRH1
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

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Ligand binding site mutations for HRH1

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
K179	E177K	BLCA	1
W158	L157M	COAD	1
D107	M106I	LUAD	1
D107	S105F	SKCM	1
F435	V437I	SKCM	1
D107	S105Y	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 HRH1

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
W158	L157M	-1.7812806
K179	E177K	-1.3645105
F435	V437I	-0.63451313
D107	S105Y	-0.60935363
D107	S105F	-0.57855455
D107	M106I	-0.51216151

(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 HRH1 from PDB

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Differential gene expression and gene-gene network for HRH1

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 HRH1 and the right PPI network was created from samples without mutations in the LBS of HRH1. 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 HRH1

Gene level disease information (DisGeNet)

Disease ID	Disease name	# PubMed	Association type
umls:C0036341	Schizophrenia	4	Biomarker, GeneticVariation
umls:C0004153	Atherosclerosis	2	Biomarker
umls:C0035455	Rhinitis	2	Biomarker
umls:C0030193	Pain	2	Biomarker
umls:C0020649	Hypotension	1	Biomarker
umls:C0033774	Pruritus	1	Biomarker
umls:C0035228	Respiratory Hypersensitivity	1	Biomarker
umls:C0038587	Substance Withdrawal Syndrome	1	Biomarker

Mutation level pathogenic information (ClinVar annotation)

Allele ID

AA change

Clinical significance

Origin

Phenotype IDs

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Pharmacological information for HRH1

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
Approved	DB00215	Citalopram	Small molecule
Approved	DB00245	Benzatropine	Small molecule
Approved	DB00246	Ziprasidone	Small molecule
Approved	DB00283	Clemastine	Small molecule
Approved	DB00321	Amitriptyline	Small molecule
Approved\|investigational	DB00334	Olanzapine	Small molecule
Approved	DB00341	Cetirizine	Small molecule
Withdrawn	DB00342	Terfenadine	Small molecule
Approved	DB00354	Buclizine	Small molecule
Approved	DB00363	Clozapine	Small molecule
Approved\|vet_approved	DB00366	Doxylamine	Small molecule
Approved	DB00370	Mirtazapine	Small molecule
Approved	DB00405	Dexbrompheniramine	Small molecule
Approved	DB00408	Loxapine	Small molecule
Approved\|vet_approved	DB00420	Promazine	Small molecule
Approved	DB00427	Triprolidine	Small molecule
Approved	DB00434	Cyproheptadine	Small molecule
Approved	DB00455	Loratadine	Small molecule
Approved	DB00458	Imipramine	Small molecule
Approved\|vet_approved	DB00477	Chlorpromazine	Small molecule
Approved	DB00540	Nortriptyline	Small molecule
Approved	DB00543	Amoxapine	Small molecule
Approved	DB00557	Hydroxyzine	Small molecule
Approved	DB00568	Cinnarizine	Small molecule
Approved\|withdrawn	DB00637	Astemizole	Small molecule
Approved\|investigational	DB00656	Trazodone	Small molecule
Approved	DB00667	Histamine Phosphate	Small molecule
Approved	DB00719	Azatadine	Small molecule
Approved	DB00726	Trimipramine	Small molecule
Approved\|investigational	DB00734	Risperidone	Small molecule
Approved	DB00737	Meclizine	Small molecule
Approved	DB00748	Carbinoxamine	Small molecule
Approved\|investigational	DB00751	Epinastine	Small molecule
Withdrawn	DB00767	Benzquinamide	Small molecule
Approved	DB00768	Olopatadine	Small molecule
Approved	DB00777	Propiomazine	Small molecule
Approved\|vet_approved	DB00792	Tripelennamine	Small molecule
Approved\|vet_approved	DB00797	Tolazoline	Small molecule
Approved	DB00835	Brompheniramine	Small molecule
Approved	DB00902	Methdilazine	Small molecule
Approved	DB00920	Ketotifen	Small molecule
Approved	DB00934	Maprotiline	Small molecule
Approved	DB00950	Fexofenadine	Small molecule
Approved\|investigational	DB00967	Desloratadine	Small molecule
Approved	DB00972	Azelastine	Small molecule
Approved	DB00985	Dimenhydrinate	Small molecule
Approved	DB01069	Promethazine	Small molecule
Approved	DB01071	Mequitazine	Small molecule
Approved	DB01075	Diphenhydramine	Small molecule
Approved	DB01084	Emedastine	Small molecule
Approved	DB01106	Levocabastine	Small molecule
Approved	DB01114	Chlorphenamine	Small molecule
Approved	DB01142	Doxepin	Small molecule
Approved	DB01146	Diphenylpyraline	Small molecule
Approved	DB01151	Desipramine	Small molecule
Approved	DB01173	Orphenadrine	Small molecule
Approved\|investigational	DB01175	Escitalopram	Small molecule
Approved	DB01176	Cyclizine	Small molecule
Approved	DB01224	Quetiapine	Small molecule
Approved	DB01237	Bromodiphenhydramine	Small molecule
Approved\|investigational	DB01238	Aripiprazole	Small molecule
Approved\|withdrawn	DB01239	Chlorprothixene	Small molecule
Approved\|vet_approved	DB01246	Alimemazine	Small molecule
Approved	DB01267	Paliperidone	Small molecule
Approved	DB01403	Methotrimeprazine	Small molecule
Approved	DB01615	Aceprometazine	Small molecule
Approved	DB01619	Phenindamine	Small molecule
Approved	DB01620	Pheniramine	Small molecule
Approved\|investigational	DB01624	Zuclopenthixol	Small molecule
Approved\|withdrawn	DB04837	Clofedanol	Small molecule
Approved	DB04841	Flunarizine	Small molecule
Approved	DB04890	Bepotastine	Small molecule
Investigational	DB04905	Tesmilifene	Small molecule
Approved	DB04946	Iloperidone	Small molecule
Investigational	DB05079	HY10275	Small molecule
Investigational	DB05080	OBE101	Small molecule
Investigational	DB05345	SO-101	Small molecule
Investigational	DB05492	Epicept NP-1	Small molecule
Approved	DB06016	Cariprazine	Small molecule
Approved	DB06148	Mianserin	Small molecule
Approved	DB06216	Asenapine	Small molecule
Approved	DB06282	Levocetirizine	Small molecule
Investigational	DB06678	Esmirtazapine	Small molecule
Approved\|vet_approved	DB06691	Mepyramine	Small molecule
Approved	DB06698	Betahistine	Small molecule
Approved	DB06766	Alcaftadine	Small molecule
Approved	DB08799	Antazoline	Small molecule
Approved	DB08800	Chloropyramine	Small molecule
Approved	DB08801	Dimetindene	Small molecule
Approved	DB08802	Isothipendyl	Small molecule
Approved	DB08936	Chlorcyclizine	Small molecule
Approved	DB09016	Butriptyline	Small molecule
Approved	DB11591	Bilastine	Small molecule

Gene-centered ligand-gene interaction network

Ligands binding to mutated ligand binding site of HRH1 go to BioLip

Ligand ID	Ligand short name	Ligand long name	PDB ID	PDB name	mutLBS
5EH		(3E)-3-(DIBENZO[B,E]OXEPIN-11(6H)-YLIDENE)-N,N-DIMETHYLPROPAN-1-AMINE	3rze	A	D107 W158 F435
D7V		(3Z)-3-(DIBENZO[B,E]OXEPIN-11(6H)-YLIDENE)-N,N-DIMETHYLPROPAN-1-AMINE	3rze	A	D107 W158 F435
PO4		PHOSPHATE ION	3rze	A	K179 F435

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Conservation information for LBS of HRH1

Multiple alignments for P35367 in multiple species

LBS	AA sequence	# species	Species
D107	FWLSMDYVAST	4	Homo sapiens, Pan troglodytes, Mus musculus, Rattus norvegicus
F424	FIMAAFILCWI	3	Homo sapiens, Pan troglodytes, Rattus norvegicus
F424	CIMAAFILCWI	1	Mus musculus
F432	CWIPYFIFFMV	4	Homo sapiens, Pan troglodytes, Mus musculus, Rattus norvegicus
F435	PYFIFFMVIAF	4	Homo sapiens, Pan troglodytes, Mus musculus, Rattus norvegicus
H450	CNEHLHMFTIW	2	Homo sapiens, Pan troglodytes
H450	CSEPVHMFTIW	1	Mus musculus
H450	CSEPMHMFTIW	1	Rattus norvegicus
I115	ASTASIFSVFI	4	Homo sapiens, Pan troglodytes, Mus musculus, Rattus norvegicus
K179	VRREDKCETDF	2	Homo sapiens, Pan troglodytes
K179	ELREDKCETDF	2	Mus musculus, Rattus norvegicus
K191	DVTWFKVMTAI	2	Homo sapiens, Pan troglodytes
K191	NVTWFKIMTAI	2	Mus musculus, Rattus norvegicus
N198	MTAIINFYLPT	4	Homo sapiens, Pan troglodytes, Mus musculus, Rattus norvegicus
S111	MDYVASTASIF	4	Homo sapiens, Pan troglodytes, Mus musculus, Rattus norvegicus
T112	DYVASTASIFS	4	Homo sapiens, Pan troglodytes, Mus musculus, Rattus norvegicus
W158	FLSFLWVIPIL	3	Homo sapiens, Pan troglodytes, Mus musculus
W158	FFSFLWVIPIL	1	Rattus norvegicus
W428	AFILCWIPYFI	4	Homo sapiens, Pan troglodytes, Mus musculus, Rattus norvegicus
Y108	WLSMDYVASTA	4	Homo sapiens, Pan troglodytes, Mus musculus, Rattus norvegicus
Y431	LCWIPYFIFFM	4	Homo sapiens, Pan troglodytes, Mus musculus, Rattus norvegicus
Y458	TIWLGYINSTL	4	Homo sapiens, Pan troglodytes, Mus musculus, Rattus norvegicus