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DUX4 Gene

protein-coding GIFtS: 41
GCID: GC04P191005

Double Homeobox 4

See DUX4-related diseases
at

MalaCards

(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
Double Homeobox 4¹ ²
Double Homeobox Protein 10² ³
Double Homeobox Protein 4/10² ³
DUX10² ³
Double Homeobox Protein 4²

External Ids:	HGNC: 3082¹	Entrez Gene: 22947²	Ensembl: ENSG00000258389⁷	OMIM: 606009⁵	UniProtKB: Q9UBX2³

Export aliases for DUX4 gene to outside databases

Previous GC identifers: GC04P192017 GC10P134609 GC04P191585 GC04P191697 GC04P191683 GC04P191376 GC04P191232 GC04P191240 GC04P191251 GC04P191254 GC04P191257 GC04P191260

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

Entrez Gene summary for DUX4 Gene:

This gene is located within a D4Z4 repeat array in the subtelomeric region of chromosome 4q. The D4Z4 repeat is

polymorphic in length; a similar D4Z4 repeat array has been identified on chromosome 10. Each D4Z4 repeat unit

has an open reading frame (named DUX4) that encodes two homeoboxes; the repeat-array and ORF is conserved in

other mammals. There is no evidence for transcription of this gene from standard cDNA libraries, however, RT-PCR

and in vitro expression experiments indicate that the ORF is transcribed. The encoded protein has been reported

to function as a transcriptional activator of paired-like homeodomain transcription factor 1 (PITX1; GeneID

5307). Contraction of the microsatellite repeat causes autosomal dominant facioscapulohumeral muscular dystrophy

(FSHD). (provided by RefSeq, May 2013)

GeneCards Summary for DUX4 Gene:

DUX4 (double homeobox 4) is a protein-coding gene. Diseases associated with DUX4 include facioscapulohumeral muscular dystrophy, and embryonal rhabdomyosarcoma. GO annotations related to this gene include transcription regulatory region sequence-specific DNA binding and sequence-specific DNA binding transcription factor activity. An important paralog of this gene is DUX4L3.

UniProtKB/Swiss-Prot: DUX4_HUMAN, Q9UBX2

Function: Involved in transcriptional regulation. May regulate microRNA (miRNA) expression

(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_000004.11 NT_016354.20

Regulatory elements:

Search for regulatory transcription factor binding sites for DUX4
Other transcription factors

Browse SwitchGear Promoter luciferase reporter plasmids

Search Chromatin IP Primers for DUX4

Epigenetics:

DNA Methylation CpG Assay Predesigned for Pyrosequencing in human, mouse, rat DUX4

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

Entrez Gene cytogenetic band: 4q35 Ensembl cytogenetic band: 4q35.2 HGNC cytogenetic band: 4q35.2

DUX4 Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
DUX4 gene location

GeneLoc information about chromosome 4 GeneLoc Exon Structure

GeneLoc location for GC04P191005: view genomic region (about GC identifiers)

Start:	191,005,267 bp from pter	End:	191,007,077 bp from pter
Size:	1,811 bases	Orientation:	plus strand

1 alternative location:

Chr4+,NW_003571034 177,042-178,658

(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,
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About This Section

UniProtKB/Swiss-Prot: DUX4_HUMAN, Q9UBX2 (See protein sequence)

Recommended Name: Double homeobox protein 4

Size: 424 amino acids; 44940 Da

Subunit: May exist as a monomer or a dimer

Miscellaneous: DUX genes are present in 3.3-kilobase elements, a tandem repeat family scattered in the genome

found on the short arms of all acrocentric chromosomes as well as on several other chromosomes

Explore the universe of human proteins at neXtProt for DUX4: NX_Q9UBX2

Post-translational modifications:

Modification sites at neXtProt

Modification sites at PhosphoSitePlus

REFSEQ proteins: NP_149418.4

ENSEMBL proteins:

ENSP00000473851 ENSP00000451207 ENSP00000451304

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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:

PRD: Homeoboxes / PRD class

3 InterPro protein domains:

IPR000047 HTH_motif

IPR001356 Homeobox_dom

IPR009057 Homeodomain-like

Graphical View of Domain Structure for InterPro Entry Q9UBX2

ProtoNet protein and cluster: Q9UBX2

1 Blocks protein domain: IPB000047 Lambda and other repressor helix-turn-helix signature

UniProtKB/Swiss-Prot: DUX4_HUMAN, Q9UBX2

Domain: Both homeobox domains confer nuclear targeting

Similarity: Belongs to the paired homeobox family

Similarity: Contains 2 homeobox DNA-binding domains

Find genes that share domains with DUX4 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: DUX4_HUMAN, Q9UBX2

Function: Involved in transcriptional regulation. May regulate microRNA (miRNA) expression

Genatlas biochemistry entry for DUX4:

double homeo box protein 4 in the partially deleted D4Z4 locus (FSHD)

Gene Ontology (GO): 4 molecular function terms: About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0000976	transcription regulatory region sequence-specific DNA binding	IEA	--
GO:0003677	DNA binding	--	--
GO:0003700	sequence-specific DNA binding transcription factor activity	IEA	--
GO:0043565	sequence-specific DNA binding	--	--

Find genes that share ontologies with DUX4 About GenesLikeMe

Phenotypes:
1 GenomeRNAi human phenotype for DUX4:

Increased HPV18 LCR reporter a

Animal Models:

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In Situ Assay
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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

DUX4_HUMAN, Q9UBX2: Nucleus. Note=Actively transported through the nuclear pore complex (NPC)

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 DUX4 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 DUX4
Interactions:

GeneGlobe Interaction Network for DUX4

Gene Ontology (GO): 2 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	--	--

Find genes that share ontologies with DUX4 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 DUX4 gene:

NM_033178.4

Unigene Cluster for DUX4:

Double homeobox 4

Hs.553518

Unigene Representative Sequence: NM_033178

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

ENST00000605758 ENST00000554285 ENST00000556625(uc010ist.1)

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1 AceView cDNA sequence:

NM_033178

GeneLoc Exon Structure

(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

DUX4 expression in normal human tissues (normalized intensities)
See probesets specificity/sensitivity at GeneAnnot
About this imageBioGPS <intensity>^2/3
CGAP TAG: --

About this image

DUX4 Protein expression data from MOPED¹, PaxDb² and MaxQB³:

--

SOURCE GeneReport for Unigene cluster: Hs.553518

UniProtKB/Swiss-Prot: DUX4_HUMAN, Q9UBX2

Tissue specificity: Does not seem to be expressed in normal muscle, but in muscle of individuals with FSHD, where

it may be toxic to cells

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In Situ
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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

--

ENSEMBL Gene Tree for DUX4 (if available)
TreeFam Gene Tree for DUX4 (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 DUX4 gene

DUX4L2¹ ² DUX4L6¹ ² DUX4L3¹ ² DUX4L5¹ ² DUX4L7¹ ² DUX2 DUX4L4¹ ² LOC102723538

LOC102723495 LOC102723449 LOC102723472 LOC102723423 LOC102723518 LOC100287823 ENSG00000214325² DUXA²

Selected SIMAP similar genes for DUX4 using alignment to 25 protein entries: DUX4_HUMAN (see all proteins) (see all similar genes):

DUX4L2 DUX4L3 DUX4L5 DUX4L6 DUX4L7 DUX4L4

DUX4L9 DUX2 DUX5 DUX1 DUX3 HPX-2

CIC/DUX4 fusion LHX3 MSX1 PITX2 TPRX2P MNX1

Find genes that share paralogs with DUX4 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

Structural Variations
Database of Genomic Variants (DGV) Selected variations for DUX4 (see all 11): About this table

Variant ID	Type	Subtype	PubMed ID
dgv4n31	CNV	Duplication	19718026
nsv471357	CNV	Duplication	19718026
nsv471487	CNV	Duplication	19718026
nsv10641	CNV	Loss	18304495
nsv428243	CNV	Gain	18775914
nsv896428	CNV	Gain	21882294
nsv482152	CNV	Gain	20164927
esv23426	CNV	Gain+Loss	19812545
esv28562	CNV	Gain+Loss	19812545
nsv8752	CNV	Gain+Loss	18304495

Human Gene Mutation Database (HGMD): DUX4

Site Specific Mutation Identification with PCR Assays

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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: 606009 OMIM disorders: --

UniProtKB/Swiss-Prot: DUX4_HUMAN, Q9UBX2

Facioscapulohumeral muscular dystrophy 1 (FSHD1) [MIM:158900]: A degenerative muscle disease

characterized by slowly progressive weakness of the muscles of the face, upper-arm, and shoulder girdle. The

onset of symptoms usually occurs in the first or second decade of life. Affected individuals usually present with

impairment of upper extremity elevation. This tends to be followed by facial weakness, primarily involving the

orbicularis oris and orbicularis oculi muscles. Note=The gene represented in this entry is involved in disease

pathogenesis. The disease is caused by deletion of an integral number of units of a 3.3-kb tandem repeats, termed

D4Z4 macrosatellite, located on chromosome 4q35. In unaffected subjects, the D4Z4 array consists of 11-150

repeats, while in FSHD1 patients, the array is reduced to 1-10 repeats (PubMed:19320656). DUX4 is located in D4Z4

macrosatellite which is epigenetically repressed in somatic tissues. D4Z4 chromatin relaxation in FSHD1 results

in inefficient epigenetic repression of DUX4 and a variegated pattern of DUX4 protein expression in a subset of

skeletal muscle nuclei. Ectopic expression of DUX4 in skeletal muscle activates the expression of stem cell and

germline genes, and, when overexpressed in somatic cells, DUX4 can ultimately lead to cell death

2 diseases for DUX4:
About MalaCards

facioscapulohumeral muscular dystrophy embryonal rhabdomyosarcoma

Find genes that share disorders with DUX4 About GenesLikeMe

Genetic Association Database (GAD): DUX4
Human Genome Epidemiology (HuGE) Navigator: DUX4 (1 document)

Export disorders for DUX4 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 DUX4 gene, integrated from 10 sources (see all 48):
(articles sorted by number of sources associating them with DUX4)

Intracellular trafficking and dynamics of double homeodomain proteins. (PubMed id 15709750)^{1, 2, 9} Oestlund C.... Worman H.J. (Biochemistry 2005)
Polymorphism of the D4Z4 locus associated with facioscapulohumeral muscular dystrophy 1A in Shanghai population. (PubMed id 16086272)^{1, 4} Zhang Y.Z....Urtizberea J.A. (Zhonghua Yi Xue Yi Chuan Xue Za Zhi 2005)
Nucleotide sequence of the partially deleted D4Z4 locus in a patient with FSHD identifies a putative gene within each 3.3 kb element. (PubMed id 10433963)^{1, 2} Gabrieels J.... Belayew A. (Gene 1999)
DUX4, a candidate gene of facioscapulohumeral muscular dystrophy, encodes a transcriptional activator of PITX1. (PubMed id 17984056)^{1, 9} Dixit M....Chen Y.W. (Proc. Natl. Acad. Sci. U.S.A. 2007)
Intrinsic epigenetic regulation of the D4Z4 macrosatellite repeat in a transgenic mouse model for FSHD. (PubMed id 23593020)¹ Krom Y.D....van der Maarel S.M. (PLoS Genet. 2013)
A focal domain of extreme demethylation within D4Z4 in FSHD2. (PubMed id 23284062)¹ Hartweck L.M....Kyba M. (Neurology 2013)
Expression of the human FSHD-linked DUX4 gene induces neurogenesis during differentiation of murine embryonic stem cells. (PubMed id 23560660)¹ Dandapat A....Kyba M. (Stem Cells Dev. 2013)
Defective regulation of microRNA target genes in myoblasts from facioscapulohumeral dystrophy patients. (PubMed id 24145033)² Dmitriev P.... Vassetzky Y.S. (J. Biol. Chem. 2013)
DUX4 differentially regulates transcriptomes of human rhabdomyosarcoma and mouse C2C12 cells. (PubMed id 23717650)¹ Sharma V....Chen Y.W. (PLoS ONE 2013)
DUX4 expression in FSHD muscle cells: how could such a rare protein cause a myopathy? (PubMed id 23206257)¹ Tassin A....Belayew A. (J. Cell. Mol. Med. 2013)

(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: 22947	HGNC: 3082	AceView: DUX4	Ensembl:ENSG00000258389	euGenes: HUgn22947
ECgene: DUX4	H-InvDB: DUX4

(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 DUX4	Pharmacogenomics, SNPs, Pathways

Intellectual Property for DUX4 gene
(Patent information from GeneIP, Licensable technologies from WIS Yeda, Salk, Tufts, IP news from LifeMap Sciences, Inc.)

About This Section

Patent Information for DUX4 gene:
Search GeneIP for patents involving DUX4

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

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Advanced Cell Diagnostics, Animal models from genOway)
About This Section

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GeneCards Home - Full update: 7 May 2014 - Incrementals: 9 May 2014 , 2 Jun 2014 , 26 Jun 2014 , 30 Jun 2014 , 21 Aug 2014 , 8 Sep 2014 , 2 Nov 2014 , 8 Jan 2015 , 3 Feb 2015

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Hot genes Disease genes DUX4 gene at Home site.

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DUX4 Gene

Double Homeobox 4

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GeneCards Suite

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Export list of displayed genes

DUX4 Gene

Double Homeobox 4

Aliasesfor DUX4 gene

Summariesfor DUX4 gene

Genomic Viewsfor DUX4 gene

Proteinsfor DUX4 gene

DUX4 Human Recombinant Protein Products:

DUX4 Antibody Products:

DUX4 Assay Products:

Domains /Familiesfor DUX4 gene

Functionfor DUX4 gene

Localizationfor DUX4 gene

Pathways & Interactionsfor DUX4 gene

Drugs & Compoundsfor DUX4 gene

Transcriptsfor DUX4 gene

Expression for DUX4 gene

Orthologsfor DUX4 gene

Paralogsfor DUX4 gene

Genomic Variantsfor DUX4 gene

Disorders / Diseasesfor DUX4 gene

Publicationsfor DUX4 gene

External Searches for DUX4 gene

Genome Databases showing DUX4 gene

Other Databases showing DUX4 gene

Specialized Databases showing DUX4 gene

Intellectual Propertyfor DUX4 gene

Productsfor DUX4 gene

View Random Gene

Aliases
for DUX4 gene

Summaries
for DUX4 gene

Genomic Views
for DUX4 gene

Proteins
for DUX4 gene

Domains /
Families
for DUX4 gene

Function
for DUX4 gene

Localization
for DUX4 gene

Pathways & Interactions
for DUX4 gene

Drugs & Compounds
for DUX4 gene

Transcripts
for DUX4 gene

Expression
for DUX4 gene

Orthologs
for DUX4 gene

Paralogs
for DUX4 gene

Genomic Variants
for DUX4 gene

Disorders / Diseases
for DUX4 gene

Publications
for DUX4 gene

Intellectual Property
for DUX4 gene

Products
for DUX4 gene