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HES4 Gene

protein-coding GIFtS: 46
GCID: GC01M000924

Hes Family BHLH Transcription Factor 4

(Previous name: hairy and enhancer of split 4 (Drosophila))

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disease database

(According to ¹HGNC, ²Entrez Gene,
³UniProtKB/Swiss-Prot, ⁴UniProtKB/TrEMBL, ⁵OMIM, ⁶GeneLoc, ⁷Ensembl, ⁸DME, ⁹miRBase, ¹⁰fRNAdb, ¹²H-InvDB, ¹³NCBI, ¹⁴NONCODE, and/or ¹⁵RNAdb)
About This Section

Aliases
Hes Family BHLH Transcription Factor 4¹ ²		hHES4² ³
Class B Basic Helix-Loop-Helix Protein 42² ³		Hairy And Enhancer Of Split 4 (Drosophila)¹
Hairy And Enhancer Of Split 4² ³		Transcription Factor HES-4²
bHLHb42² ³		BHLHB42³
BHLH Factor Hes4² ³

External Ids:	HGNC: 24149¹	Entrez Gene: 57801²	Ensembl: ENSG00000188290⁷	OMIM: 608060⁵	UniProtKB: Q9HCC6³

Export aliases for HES4 gene to outside databases

Previous GC identifers: GC01M000974 GC01M000206

(According to Entrez Gene, GeneCards, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
About This Section

GeneCards Summary for HES4 Gene:

HES4 (hes family bHLH transcription factor 4) is a protein-coding gene. GO annotations related to this gene include protein dimerization activity and transcription factor binding. An important paralog of this gene is HES5.

UniProtKB/Swiss-Prot: HES4_HUMAN, Q9HCC6

Function: Transcriptional repressor. Binds DNA on N-box motifs: 5'-CACNAG-3' (By similarity)

(According to GeneLoc and/or HGNC, and/or
Entrez Gene (NCBI build 37),
and/or miRBase,
Genomic Views according to UCSC (hg19) and Ensembl (release 75), Regulatory elements and Epigenetics data according to QIAGEN, and/or SwitchGear Genomics)
About This Section

RefSeq DNA sequence at NCBI GenBank:

NC_000001.10 NT_032977.10 NC_018912.2

Regulatory elements:

Regulatory transcription factor binding sites in the HES4 gene promoter:
CREB p53 deltaCREB MyoD
Other transcription factors

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Search Chromatin IP Primers for HES4

Epigenetics:

DNA Methylation CpG Assay Predesigned for Pyrosequencing in human, mouse, rat HES4

Genomic Location:
Genomic View: UCSC Golden Path with GeneCards custom track

Entrez Gene cytogenetic band: 1p36.33 Ensembl cytogenetic band: 1p36.33 HGNC cytogenetic band: 1p36

HES4 Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
HES4 gene location

GeneLoc information about chromosome 1 GeneLoc Exon Structure

GeneLoc location for GC01M000924: view genomic region (about GC identifiers)

Start:	934,342 bp from pter	End:	935,552 bp from pter
Size:	1,211 bases	Orientation:	minus strand

(According to ¹UniProtKB, HORDE, ²neXtProt, Ensembl, and/or Reactome, Modification sites according to PhosphoSitePlus, Specific Peptides from DME, RefSeq according to NCBI, PDB rendering according to OCA and/or Proteopedia, Recombinant Proteins from EMD Millipore, R&D Systems, GenScript, Enzo Life Sciences, OriGene, Novus Biologicals, Sino Biological, ProSpec, Cloud-Clone Corp., eBioscience, antibodies-online, and/or GeneTex,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, Cloud-Clone Corp., eBioscience, and/or antibodies-online, Antibodies by EMD Millipore, R&D Systems, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, Abcam, Cloud-Clone Corp, antibodies-online, and/or others.)
About This Section

UniProtKB/Swiss-Prot: HES4_HUMAN, Q9HCC6 (See protein sequence)

Recommended Name: Transcription factor HES-4

Size: 221 amino acids; 23523 Da

Subunit: Transcription repression requires formation of a complex with a corepressor protein of the Groucho/TLE

family (By similarity)

Secondary accessions: Q5SVA5

Explore the universe of human proteins at neXtProt for HES4: NX_Q9HCC6

Explore proteomics data for HES4 at MOPED

See HES4 Protein Expression from SPIRE MOPED, PaxDB, and MaxQB

REFSEQ proteins (2 alternative transcripts):

NP_001135939.1 NP_066993.1

ENSEMBL proteins:

ENSP00000393198 ENSP00000304595 ENSP00000425085

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(According to HGNC, IUPHAR, InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GenesLikeMe)
About This Section

HGNC Gene Families:

bHLH: Basic helix-loop-helix proteins

3 InterPro protein domains:

IPR018352 Orange_subgr

IPR003650 Orange

IPR011598 bHLH_dom

Graphical View of Domain Structure for InterPro Entry Q9HCC6

ProtoNet protein and cluster: Q9HCC6

2 Blocks protein domains:

IPB001092 Basic helix-loop-helix dimerization domain bHLH

IPB003650 Orange

UniProtKB/Swiss-Prot: HES4_HUMAN, Q9HCC6

Domain: Has a particular type of basic domain (presence of a helix-interrupting proline) that binds to the N-box

(CACNAG), rather than the canonical E-box (CANNTG) (By similarity)

Domain: The C-terminal WRPW motif is a transcriptional repression domain necessary for the interaction with

Groucho/TLE family members, transcriptional corepressors recruited to specific target DNA by Hairy-related

proteins (By similarity)

Similarity: Contains 1 bHLH (basic helix-loop-helix) domain

Similarity: Contains 1 Orange domain

Find genes that share domains with HES4 About GenesLikeMe

(According to ¹UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or ²DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013, genOway,
transcription factor targeting from QIAGEN and/or HOMER, miRNA Gene Targets from miRTarBase, shRNA from OriGene, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, SwitchGear Genomics, Gene Editing from DNA2.0, Clones from OriGene, GenScript, Sino Biological, DNA2.0, Vector BioLabs and/or Addgene, Cell Lines from GenScript, ESI BIO, In Situ Hybridization Assays from Advanced Cell Diagnostics, Flow cytometry from eBioscience, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene, Sets of similar genes according to GenesLikeMe)
About This Section

Molecular Function:

UniProtKB/Swiss-Prot Summary: HES4_HUMAN, Q9HCC6

Function: Transcriptional repressor. Binds DNA on N-box motifs: 5'-CACNAG-3' (By similarity)

Gene Ontology (GO): 3 molecular function terms: About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0003677	DNA binding	IEA	--
GO:0008134	transcription factor binding	NAS	17611704
GO:0046983	protein dimerization activity	IEA	--

Find genes that share ontologies with HES4 About GenesLikeMe

Phenotypes:
1 GenomeRNAi human phenotype for HES4:

Decreased Hepatitis C virus re

Animal Models:

genOway: Develop your customized and physiologically relevant rodent model for HES4

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(According to UniProtKB, COMPARTMENTS Subcellular localization database, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene, Sets of similar genes according to GenesLikeMe)
About This Section

Subcellular locations from UniProtKB/Swiss-Prot

HES4_HUMAN, Q9HCC6: Nucleus (By similarity)

Subcellular locations from COMPARTMENTS:

Compartment	Confidence
nucleus	3

About this image

Gene Ontology (GO): 1 cellular component term: About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0005634	nucleus	IEA	--

Find genes that share ontologies with HES4 About GenesLikeMe

(SuperPaths according to PathCards, Pathways according to R&D Systems, Cell Signaling Technology, KEGG, PharmGKB, BioSystems, Sino Biological, Reactome, Tocris Bioscience, GeneGo (Thomson Reuters), QIAGEN, and/or UniProtKB, Sets of similar genes according to GenesLikeMe, Interaction Networks according to QIAGEN, and/or STRING, Interactions according to ¹UniProtKB, ²MINT, ³I2D, and/or ⁴STRING, with links to IntAct and Ensembl, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene, Sets of similar genes according to GenesLikeMe)
About This Section

Custom Pathway & Disease-focused RT² Profiler PCR Arrays for HES4
Interactions:

Search GeneGlobe Interaction Network for HES4

STRING Interaction Network Preview (showing 5 interactants - click image to see 23)

Selected Interacting proteins for HES4 (Q9HCC6³ ENSP00000393198⁴) via UniProtKB, MINT, STRING, and/or I2D (see all 33)

Interactant		Interaction Details
GeneCard	External ID(s)	Interaction Details
PCBD1	P61457³, ENSP00000299299⁴	I2D: score=1 STRING: ENSP00000299299
PCBD2	Q9H0N5³, ENSP00000254908⁴	I2D: score=1 STRING: ENSP00000254908
ATP13A4	Q4VNC1³	I2D: score=1
CMSS1	Q9BQ75³	I2D: score=1
COPG2	Q9UBF2³	I2D: score=1

About this table

Gene Ontology (GO): 4 biological process terms: About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0006351	transcription, DNA-templated	IEA	--
GO:0006355	regulation of transcription, DNA-templated	IEA	--
GO:0007399	nervous system development	IEA	--
GO:0030154	cell differentiation	IEA	--

Find genes that share ontologies with HES4 About GenesLikeMe

(Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience, ApexBio, HMDB, BitterDB, and/or Novoseek, Ligands according to IUPHAR, and Drugs according to DrugBank, Enzo Life Sciences, and/or PharmGKB, Sets of similar genes according to GenesLikeMe)
About This Section

Browse Small Molecules at EMD Millipore

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(Secondary structures according to fRNAdb,
GenBank/EMBL/DDBJ Accessions according to
Unigene (Build 236 Homo sapiens; Apr 25 2013) or GenBank,
RefSeq according to Entrez Gene,
DOTS (version 10), and/or AceView, transcript ids from Ensembl with links to UCSC,
exon structure from GeneLoc, alternative splicing isoforms according to ASD and/or ECgene,
siRNAs from OriGene, QIAGEN, shRNA from OriGene, microRNA from QIAGEN, SwitchGear Genomics,
Tagged/untagged cDNA clones from OriGene, GenScript, DNA2.0, Vector BioLabs, and/or Addgene, Primers from OriGene, and/or QIAGEN, Flow cytometry from eBioscience )
About This Section

REFSEQ mRNAs for HES4 gene (3 alternative transcripts):

NM_001142467.1 NM_021170.3 XM_005244771.2

Unigene Cluster for HES4:

Hairy and enhancer of split 4 (Drosophila)

Hs.154029 [show with all ESTs]

Unigene Representative Sequence: BM543941

4 Ensembl transcripts including schematic representations, and UCSC links where relevant:

ENST00000428771(uc001aci.2 uc010nyc.1) ENST00000304952 ENST00000481869

ENST00000484667

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Additional mRNA sequence:

AB048791.1 BC012351.1

8 DOTS entries:

DT.75101873 DT.100860764 DT.92421458 DT.97795287 DT.100830033 DT.121366989 DT.100860763 DT.95374160

Selected AceView cDNA sequences (see all 65):

BM789724 BU634310 BU622703 BU741558 CB241590 AW630809 BQ072399 BM747954

BM127944 BQ013563 BM727881 BI763672 AW161193 BF001624 BG325949 BX281754

BM713553 BM128269 BF001578 BI602134 BX455241 BU633915 BC012351 BI834315

GeneLoc Exon Structure

3 Alternative Splicing Database (ASD) splice patterns (SP) for HES4 About this scheme

ExUns:	1a	·	1b	^	2a	·	2b	^	3	^	4a	·	4b
SP1:					-
SP2:					-		-
SP3:

ECgene alternative splicing isoforms for HES4

(RNA expression data according to H-InvDB, NONCODE, miRBase, and RNAdb, Expression images according to data from BioGPS, Illumina Human BodyMap, and CGAP SAGE, Sets of similar genes according to GenesLikeMe, in vivo and in vitro expression data from LifeMap Discovery™, Protein expression images according to data from SPIRE ¹MOPED, ²PaxDb, and ³MaxQB, plus additional links to SOURCE, and/or BioGPS, and/or UniProtKB,
PCR Arrays from QIAGEN, Primers from OriGene, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
About This Section

HES4 expression in normal human tissues (normalized intensities)
See probesets specificity/sensitivity at GeneAnnot
About this imageBioGPS <intensity>^2/3
CGAP TAG: GAGAAGCGGC

About this image

HES4 expression in embryonic tissues and stem cells About this table

Data from LifeMap, the Embryonic Development and Stem Cells Database
selected tissues (see all 3) fully expand


Endoderm (Gastrulation Derivatives)
Definitive endoderm-like cells

Blood (Hematopoietic System)
Granulocytes Peripheral Blood

Brain (Nervous System)
N2/LSB induced-cells

HES4 Protein expression data from MOPED¹, PaxDb² and MaxQB³:

About this image

HES4 Protein Expression

SOURCE GeneReport for Unigene cluster: Hs.154029

Custom PCR Arrays for HES4

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In Situ
Assay Products:

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(Orthologs according to ^1,2HomoloGene (²older version, for species not in ¹newer version), ³euGenes, ⁴SGD , ⁵MGI Mar 06 2013, with possible further links to Flybase and/or WormBase, and/or ⁶Ensembl pan taxonomic compara , Gene Trees according to Ensembl and TreeFam)
About This Section

This gene was present in the common ancestor of animals.

Orthologs for HES4 gene from Selected species (see all 9) About this table

Organism	Taxonomic classification	Gene	Description	Human Similarity	Orthology Type	Details
dog (Canis familiaris)	Mammalia	HES4⁶	hes family bHLH transcription factor 4	83(a)	1 ↔ 1	5(55972417-56226772)
chicken (Gallus gallus)	Aves	--	Uncharacterized protein	38(a)	many ↔ many	9(12410467-12423754)
lizard (Anolis carolinensis)	Reptilia	--	--	49(a)	many ↔ many	GL343334.1(1036941-1044433)
zebrafish (Danio rerio)	Actinopterygii	her6⁶	hairy-related 6	47(a)	many ↔ many	6(36329655-36331416) ENSDARG00000006514
fruit fly (Drosophila melanogaster)	Insecta	h⁶ dpn⁶ (see all 3)	deadpan (see all 3)	25(a) 22(a) (see all 3)	many ↔ many many ↔ many (see all 3)	3L(8668859-8672353) 2R(4116476-4119832)

ENSEMBL Gene Tree for HES4 (if available)
TreeFam Gene Tree for HES4 (if available)

(Paralogs according to ¹HomoloGene,
²Ensembl, and ³SIMAP, Pseudogenes according to ⁴Pseudogene.org Build 68,Sets of similar genes according to GenesLikeMe)
About This Section

Paralogs for HES4 gene

HES5² HES6² HES2² HES1²

4 SIMAP similar genes for HES4 using alignment to 3 protein entries: HES4_HUMAN (see all proteins):

HES1 HEYL HES6 HES3

Find genes that share paralogs with HES4 About GenesLikeMe

(SNPs/Variants according to the ¹NCBI SNP Database, ²Ensembl, ³PupaSUITE, ⁴UniProtKB, and DNA2.0, Linkage Disequilibrium by HapMap, Structural Variations(CNVs/InDels/Inversions) from the Database of Genomic Variants, Mutations from the Human Gene Mutation Database (HGMD), the Human Cytochrome P450 Allele Nomenclature Database, and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers, Cancer Mutation PCR Arrays and Assays, and Copy Number PCR Arrays from QIAGEN)
About This Section

SNP ID	Valid	Clinical significance	Chr 1 pos	Sequence	#	AA Chg	Type	More	#	Allele freq	Pop	Total sample	More
Genomic Data					Transcription Related Data				Allele Frequencies
				--	--	--		--	--
rs145897528^1,2	C	--	934144(+)	`GGAGC-/GGAGG GGAGG`	2	--	ds500¹		0	--	--	--	--

HapMap Linkage Disequilibrium report for HES4 (934342 - 935552 bp)

Structural Variations
Database of Genomic Variants (DGV) Selected variations for HES4 (see all 17): About this table

Variant ID	Type	Subtype	PubMed ID
dgv9n71	CNV	Loss	21882294
dgv12n71	CNV	Loss	21882294
dgv10n71	CNV	Loss	21882294
dgv13n71	CNV	Loss	21882294
dgv11n71	CNV	Loss	21882294
nsv871483	CNV	Loss	21882294
nsv871547	CNV	Loss	21882294
nsv428334	CNV	Gain	18775914
nsv832980	CNV	Gain	17160897
dgv2n67	CNV	Gain	20364138

Site Specific Mutation Identification with PCR Assays

SeqTarget long-range PCR primers for resequencing HES4

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(in which this Gene is Involved, According to MalaCards, OMIM, UniProtKB, the University of Copenhagen DISEASES database, Genatlas, GeneTests, GAD, HuGE Navigator, and/or TGDB, Sets of similar genes according to GenesLikeMe)
About This Section

OMIM gene information: 608060 OMIM disorders: --

Find genes that share disorders with HES4 About GenesLikeMe

Export disorders for HES4 gene to outside databases

(in PubMed. Associations of this gene to articles via ¹Entrez Gene, ²UniProtKB/Swiss-Prot, ³HGNC, ⁴GAD, ⁵PharmGKB, ⁶HMDB, ⁷DrugBank, ⁸UniProtKB/TrEMBL, ⁹ Novoseek, and/or ¹⁰fRNAdb)
About This Section

PubMed articles for HES4 gene, integrated from 10 sources (see all 11):
(articles sorted by number of sources associating them with HES4)

Hes7: a bHLH-type repressor gene regulated by Notch and expressed in the presomitic mesoderm. (PubMed id 11260262)^{1, 2, 3} Bessho Y.... Kageyama R. (Genes Cells 2001)
The DNA sequence and biological annotation of human chromosome 1. (PubMed id 16710414)^{1, 2} Gregory S.G.... Bentley D.R. (Nature 2006)
The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). (PubMed id 15489334)^{1, 2} Gerhard D.S.... Malek J. (Genome Res. 2004)
Identification and characterization of human HES2, HES3, and HES5 genes in silico. (PubMed id 15254753)^{1, 3} Katoh M. and Katoh M. (Int. J. Oncol. 2004)
The proteomic analysis of endogenous FAT10 substrates identifies p62/SQSTM1 as a substrate of FAT10ylation. (PubMed id 22797925)¹ Aichem A....Groettrup M. (J. Cell. Sci. 2012)
Effects of chronic ascariasis and trichuriasis on cytokine production and gene expression in human blood: a cross-sectional study. (PubMed id 21666788)¹ Reina Ortiz M....Cooper P.J. (PLoS Negl Trop Dis 2011)
A comprehensive resource of interacting protein regions for refining human transcription factor networks. (PubMed id 20195357)¹ Miyamoto-Sato E....Yanagawa H. (PLoS ONE 2010)
An atlas of combinatorial transcriptional regulation in mouse and man. (PubMed id 20211142)¹ Ravasi T....Hayashizaki Y. (Cell 2010)
Integrative genomic analyses on HES/HEY family: Notch-independent HES1, HES3 transcription in undifferentiated ES cells, and Notch-dependent HES1, HES5, HEY1, HEY2, HEYL transcription in fetal tissues, adult tissues, or cancer. (PubMed id 17611704)¹ Katoh M. and Katoh M. (Int. J. Oncol. 2007)
Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. (PubMed id 12477932)¹ Strausberg R.L....Marra M.A. (Proc. Natl. Acad. Sci. U.S.A. 2002)

(in PubMed, OMIM, and NCBI Bookshelf)
About This Section

		AND	OR
Aliases
Free Text

Query String		PubMed OMIM NCBI Bookshelf
	(Note: In FireFox, select the above section and copy using Ctrl-C)

(According to Entrez Gene, HGNC, AceView, euGenes, Ensembl, miRBase, ECgene, Kegg, and/or H-InvDB)
About This Section

Entrez Gene: 57801	HGNC: 24149	AceView: Hes4	Ensembl:ENSG00000188290	euGenes: HUgn57801
ECgene: HES4	H-InvDB: HES4

(According to HUGE)
About This Section

(According to PharmGKB, ATLAS, HORDE, IMGT, LEIDEN, UniProtKB/Swiss-Prot, UniProtKB/TrEMBL, and/or others, e.g. Wikipedia and GeneReviews, via UniProtKB/Swiss-Prot)
About This Section

Name	Description
PharmGKB entry for HES4	Pharmacogenomics, SNPs, Pathways

Intellectual Property for HES4 gene
(Patent information from GeneIP, Licensable technologies from WIS Yeda, Salk, Tufts, IP news from LifeMap Sciences, Inc.)

About This Section

Patent Information for HES4 gene:
Search GeneIP for patents involving HES4

GeneCards and IP:
Japan Patent Office Licenses GeneCards European Patent Office Licenses GeneCards Improving the IP Search

(Antibodies, recombinant proteins, and assays from EMD Millipore, R&D Systems, OriGene, QIAGEN, GenScript, Cell Signaling Technology, Novus Biologicals, Sino Biological, Enzo Life Sciences, Abcam, ProSpec, Cloud-Clone Corp., Thermo Fisher Scientific, eBioscience, antibodies-online, GeneTex, and/or others, Gene Editing from DNA2.0. Clones from OriGene, GenScript, Sino Biological, DNA2.0, SwitchGear Genomics, Vector BioLabs, Addgene, Cell lines from GenScript, and ESI BIO, Flow cytometery from eBioscience, PCR Arrays from QIAGEN, Drugs and/or compounds from EMD Millipore, Tocris Bioscience, Enzo Life Sciences, and/or ApexBio, In Situ Hybridization Assays from
Advanced Cell Diagnostics, Animal models from genOway)
About This Section


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	DNA Methylation CpG Assay Predesigned for Pyrosequencing in human, mouse, rat HES4		Predesigned siRNA for gene silencing in human, mouse, rat HES4
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Hot genes Disease genes HES4 gene at Home site.

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HES4 Gene

Hes Family BHLH Transcription Factor 4

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Export list of displayed genes

HES4 Gene

Hes Family BHLH Transcription Factor 4

Aliasesfor HES4 gene

Summariesfor HES4 gene

Genomic Viewsfor HES4 gene

Proteinsfor HES4 gene

HES4 Human Recombinant Protein Products:

HES4 Antibody Products:

HES4 Assay Products:

Domains /Familiesfor HES4 gene

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Localizationfor HES4 gene

Pathways & Interactionsfor HES4 gene

Drugs & Compoundsfor HES4 gene

Transcriptsfor HES4 gene

Expression for HES4 gene

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Genomic Variantsfor HES4 gene

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Genome Databases showing HES4 gene

Other Databases showing HES4 gene

Specialized Databases showing HES4 gene

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for HES4 gene

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for HES4 gene

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for HES4 gene

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for HES4 gene

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for HES4 gene

Function
for HES4 gene

Localization
for HES4 gene

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for HES4 gene

Drugs & Compounds
for HES4 gene

Transcripts
for HES4 gene

Expression
for HES4 gene

Orthologs
for HES4 gene

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for HES4 gene

Genomic Variants
for HES4 gene

Disorders / Diseases
for HES4 gene

Publications
for HES4 gene

Intellectual Property
for HES4 gene

Products
for HES4 gene