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. The encoded protein has been repo... See more...

Aliases for DUX4 Gene

Aliases for DUX4 Gene

  • Double Homeobox 4 2 3 5
  • Double Homeobox Protein 10 3 4
  • Double Homeobox Protein 4 3 4
  • Double Homeobox Protein 4/10 3
  • Double Homeobox 4-Like 3
  • DUX4L 3
  • DUX10 4

External Ids for DUX4 Gene

Previous GeneCards Identifiers for DUX4 Gene

  • GC04P192017
  • GC10P134609
  • GC04P191585
  • GC04P191697
  • GC04P191683
  • GC04P191376
  • GC04P191232
  • GC04P191240
  • GC04P191251
  • GC04P191254
  • GC04P191257
  • GC04P191260
  • GC04P191005

Summaries for DUX4 Gene

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. 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 macrosatellite repeat causes autosomal dominant facioscapulohumeral muscular dystrophy (FSHD). Alternative splicing results in multiple transcript variants. [provided by RefSeq, Apr 2015]

CIViC Summary for DUX4 Gene

GeneCards Summary for DUX4 Gene

DUX4 (Double Homeobox 4) is a Protein Coding gene. Diseases associated with DUX4 include Facioscapulohumeral Muscular Dystrophy 1 and Muscular Dystrophy. Gene Ontology (GO) annotations related to this gene include transcription regulatory region sequence-specific DNA binding. An important paralog of this gene is PAX7.

UniProtKB/Swiss-Prot Summary for DUX4 Gene

  • [Isoform 1]: Transcription factor that is selectively and transiently expressed in cleavage-stage embryos (PubMed:28459457). Binds to double-stranded DNA elements with the consensus sequence 5'-TAATCTAATCA-3' (PubMed:28459457, PubMed:28459454, PubMed:29572508, PubMed:30540931, PubMed:30315230). Binds to chromatin containing histone H3 acetylated at 'Lys-27' (H3K27ac) and promotes deacetylation of H3K27ac. In parallel, binds to chromatin that lacks histone H3 acetylation at 'Lys-27' (H3K27ac) and recruits EP300 and CREBBP to promote acetylation of histone H3 at 'Lys-27' at new sites (PubMed:26951377). Involved in transcriptional regulation of numerous genes, primarily as transcriptional activator, but mediates also repression of a set of target genes (PubMed:17984056, PubMed:27378237, PubMed:26951377, PubMed:28459457, PubMed:28459454, PubMed:29618456, PubMed:30540931, PubMed:29572508). Promotes expression of ZSCAN4 and KDM4E, two proteins with essential roles during early embryogenesis (PubMed:27378237, PubMed:26951377, PubMed:28459457, PubMed:29618456). Heterologous expression in cultured embryonic stem cells mediates also transcription of HERVL retrotransposons and transcripts derived from ACRO1 and HSATII satellite repeats (PubMed:28459457). May activate expression of PITX1 (PubMed:17984056). May regulate microRNA (miRNA) expression (PubMed:24145033). Inappropriate expression can inhibit myogenesis and promote apoptosis (PubMed:26951377, PubMed:28935672, PubMed:29618456).
  • [Isoform 2]: Probably inactive as a transcriptional activator, due to the absence of the C-terminal region that is important for transcriptional activation. Can inhibit transcriptional activation mediated by isoform 1. Heterologous expression of isoform 2 has no deleterious effect on cell survival.

Additional gene information for DUX4 Gene

No data available for Tocris Summary , Gene Wiki entry , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for DUX4 Gene

Genomics for DUX4 Gene

GeneHancer (GH) Regulatory Elements for DUX4 Gene

Promoters and enhancers for DUX4 Gene
GeneHancer (GH) Identifier GH Type GH
Score
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH04J190183 Enhancer 0.2 Ensembl 0.4 +10.0 10032 0.2 RPL23AP84 DUX4
GH04J190122 Enhancer 0.2 ENCODE 0.2 -50.7 -50658 0.2 lnc-DUX4-1 DUX4
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around DUX4 on UCSC Golden Path with GeneCards custom track

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for DUX4

Genomic Locations for DUX4 Gene

Genomic Locations for DUX4 Gene
chr4:190,173,669-190,185,942
(GRCh38/hg38)
Size:
12,274 bases
Orientation:
Plus strand
chr4:191,005,267-191,007,077
(GRCh37/hg19)
Size:
1,811 bases
Orientation:
Plus strand

Genomic View for DUX4 Gene

Genes around DUX4 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
DUX4 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for DUX4 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for DUX4 Gene

Proteins for DUX4 Gene

  • Protein details for DUX4 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q9UBX2-DUX4_HUMAN
    Recommended name:
    Double homeobox protein 4
    Protein Accession:
    Q9UBX2
    Secondary Accessions:
    • E2JJS1

    Protein attributes for DUX4 Gene

    Size:
    424 amino acids
    Molecular mass:
    44940 Da
    Quaternary structure:
    • Binds DNA as a monomer (PubMed:30322619, PubMed:30540931). Interacts (via C-terminus) with EP300 and CREBBP (PubMed:26951377).
    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.

    Three dimensional structures from OCA and Proteopedia for DUX4 Gene

    Alternative splice isoforms for DUX4 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for DUX4 Gene

Post-translational modifications for DUX4 Gene

  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

Other Protein References for DUX4 Gene

No data available for DME Specific Peptides for DUX4 Gene

Domains & Families for DUX4 Gene

Gene Families for DUX4 Gene

Human Protein Atlas (HPA):
  • Disease related genes
  • Potential drug targets
  • Predicted intracellular proteins
  • Transcription factors
  • Transporters

Protein Domains for DUX4 Gene

Blocks:
  • Lambda and other repressor helix-turn-helix signature
InterPro:
ProtoNet:

Suggested Antigen Peptide Sequences for DUX4 Gene

GenScript: Design optimal peptide antigens:
  • DUX4 (C3U395_HUMAN)
  • DUX4 (C3U396_HUMAN)
  • DUX4 (C3U397_HUMAN)
  • DUX4 (C3U398_HUMAN)
  • DUX4 (C3U399_HUMAN)

Graphical View of Domain Structure for InterPro Entry

Q9UBX2

UniProtKB/Swiss-Prot:

DUX4_HUMAN :
  • The two homeobox domains are arranged in a head-to-head orientation when bound to double-stranded DNA, each domain binding to one of the two DNA strands. Together, the homeobox domains can be considered to bind DNA with the consensus sequence 5'-TAATCTAATCA-3', but due to the head-to-head orientation of the DNA-bound domains, the first homeobox domain binds to the consensus sequence 5'-TAAT-3', and the second homeobox domain binds DNA on the opposite strand, with the consensus sequence 5'-TGAT-3' (PubMed:30322619, PubMed:30540931). Both homeobox domains confer nuclear targeting (PubMed:15709750).
  • Belongs to the paired homeobox family.
Domain:
  • The two homeobox domains are arranged in a head-to-head orientation when bound to double-stranded DNA, each domain binding to one of the two DNA strands. Together, the homeobox domains can be considered to bind DNA with the consensus sequence 5'-TAATCTAATCA-3', but due to the head-to-head orientation of the DNA-bound domains, the first homeobox domain binds to the consensus sequence 5'-TAAT-3', and the second homeobox domain binds DNA on the opposite strand, with the consensus sequence 5'-TGAT-3' (PubMed:30322619, PubMed:30540931). Both homeobox domains confer nuclear targeting (PubMed:15709750).
  • The C-terminal region is required for efficient activation of transcription from target promoters (PubMed:26951377, PubMed:29618456). It mediates interaction with EP300 and CREBBP (PubMed:26951377).
Family:
  • Belongs to the paired homeobox family.
genes like me logo Genes that share domains with DUX4: view

Function for DUX4 Gene

Molecular function for DUX4 Gene

UniProtKB/Swiss-Prot Function:
[Isoform 1]: Transcription factor that is selectively and transiently expressed in cleavage-stage embryos (PubMed:28459457). Binds to double-stranded DNA elements with the consensus sequence 5'-TAATCTAATCA-3' (PubMed:28459457, PubMed:28459454, PubMed:29572508, PubMed:30540931, PubMed:30315230). Binds to chromatin containing histone H3 acetylated at 'Lys-27' (H3K27ac) and promotes deacetylation of H3K27ac. In parallel, binds to chromatin that lacks histone H3 acetylation at 'Lys-27' (H3K27ac) and recruits EP300 and CREBBP to promote acetylation of histone H3 at 'Lys-27' at new sites (PubMed:26951377). Involved in transcriptional regulation of numerous genes, primarily as transcriptional activator, but mediates also repression of a set of target genes (PubMed:17984056, PubMed:27378237, PubMed:26951377, PubMed:28459457, PubMed:28459454, PubMed:29618456, PubMed:30540931, PubMed:29572508). Promotes expression of ZSCAN4 and KDM4E, two proteins with essential roles during early embryogenesis (PubMed:27378237, PubMed:26951377, PubMed:28459457, PubMed:29618456). Heterologous expression in cultured embryonic stem cells mediates also transcription of HERVL retrotransposons and transcripts derived from ACRO1 and HSATII satellite repeats (PubMed:28459457). May activate expression of PITX1 (PubMed:17984056). May regulate microRNA (miRNA) expression (PubMed:24145033). Inappropriate expression can inhibit myogenesis and promote apoptosis (PubMed:26951377, PubMed:28935672, PubMed:29618456).
UniProtKB/Swiss-Prot Function:
[Isoform 2]: Probably inactive as a transcriptional activator, due to the absence of the C-terminal region that is important for transcriptional activation. Can inhibit transcriptional activation mediated by isoform 1. Heterologous expression of isoform 2 has no deleterious effect on cell survival.
GENATLAS Biochemistry:
double homeo box protein 4 in the partially deleted D4Z4 locus (FSHD)

Gene Ontology (GO) - Molecular Function for DUX4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000976 transcription regulatory region sequence-specific DNA binding IDA 17984056
GO:0000978 RNA polymerase II proximal promoter sequence-specific DNA binding IDA 17984056
GO:0001228 DNA-binding transcription activator activity, RNA polymerase II-specific IDA 17984056
GO:0003677 DNA binding IEA --
GO:0005515 protein binding IPI 26816005
genes like me logo Genes that share ontologies with DUX4: view

Phenotypes for DUX4 Gene

genes like me logo Genes that share phenotypes with DUX4: view

Human Phenotype Ontology for DUX4 Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Model Products

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for DUX4

No data available for Enzyme Numbers (IUBMB) , Phenotypes From GWAS Catalog , Animal Models , miRNA , Transcription Factor Targets and HOMER Transcription for DUX4 Gene

Localization for DUX4 Gene

Subcellular locations from UniProtKB/Swiss-Prot for DUX4 Gene

[Isoform 1]: Nucleus. Note=Actively transported through the nuclear pore complex (NPC). {ECO:0000305 PubMed:15709750}.
[Isoform 2]: Nucleus.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for DUX4 gene
Compartment Confidence
nucleus 5
cytosol 4
golgi apparatus 4
cytoskeleton 2
plasma membrane 1
extracellular 1
mitochondrion 1
endoplasmic reticulum 1

Subcellular locations from the

Human Protein Atlas (HPA)
  • Nucleoli (3)
  • Nucleoplasm (3)
  • Cytosol (1)
  • Golgi apparatus (1)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for DUX4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005634 nucleus IEA,IDA 17984056
GO:0005654 nucleoplasm IDA 17588759
GO:0005730 nucleolus IDA --
GO:0005794 Golgi apparatus IDA --
GO:0005829 cytosol IDA --
genes like me logo Genes that share ontologies with DUX4: view

Pathways & Interactions for DUX4 Gene

PathCards logo

SuperPathways for DUX4 Gene

No Data Available

SIGNOR curated interactions for DUX4 Gene

Activates:

Gene Ontology (GO) - Biological Process for DUX4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006915 apoptotic process IDA 17588759
GO:0007275 multicellular organism development IEA --
GO:0008285 negative regulation of cell proliferation IMP 24589735
GO:0045944 positive regulation of transcription by RNA polymerase II IDA 17984056
GO:0070317 negative regulation of G0 to G1 transition IDA 24589735
genes like me logo Genes that share ontologies with DUX4: view

No data available for Pathways by source for DUX4 Gene

Drugs & Compounds for DUX4 Gene

No Compound Related Data Available

Transcripts for DUX4 Gene

mRNA/cDNA for DUX4 Gene

5 REFSEQ mRNAs :
9 NCBI additional mRNA sequence :
6 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for DUX4

Alternative Splicing Database (ASD) splice patterns (SP) for DUX4 Gene

No ASD Table

Relevant External Links for DUX4 Gene

GeneLoc Exon Structure for
DUX4

Expression for DUX4 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for DUX4 Gene

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for DUX4

mRNA Expression by UniProt/SwissProt for DUX4 Gene:

Q9UBX2-DUX4_HUMAN
Tissue specificity: Isoform 1: Does not seem to be expressed in normal muscle, but is detected in muscle of individuals with FSHD, and also in testis (at protein level) (PubMed:21060811, PubMed:17984056). Isoform 1: Does not seem to be expressed in normal muscle, but in muscle of individuals with FSHD, where it may be toxic to cells (PubMed:21060811, PubMed:17984056). Isoform 2: Detected in skeletal muscle, fibroblasts and testis from healthy individuals (PubMed:21060811).

Evidence on tissue expression from TISSUES for DUX4 Gene

  • Muscle(2.3)

Phenotype-based relationships between genes and organs from Gene ORGANizer for DUX4 Gene

Germ Layers:
  • ectoderm
  • endoderm
  • mesoderm
Systems:
  • digestive
  • integumentary
  • nervous
  • respiratory
  • skeletal muscle
  • skeleton
Regions:
Head and neck:
  • brain
  • cranial nerve
  • eye
  • eyelid
  • face
  • head
  • mouth
  • tongue
Thorax:
  • clavicle
  • lung
  • scapula
Abdomen:
  • abdominal wall
Pelvis:
  • pelvis
Limb:
  • arm
  • humerus
  • lower limb
  • shin
  • shoulder
  • upper limb
General:
  • hair
  • peripheral nervous system
  • skin
  • spinal column
  • vertebrae
genes like me logo Genes that share expression patterns with DUX4: view

Primer Products

No data available for mRNA expression in embryonic tissues and stem cells from LifeMap Discovery , mRNA differential expression in normal tissues , Protein differential expression in normal tissues , Protein expression and Protein tissue co-expression partners for DUX4 Gene

Orthologs for DUX4 Gene

Evolution for DUX4 Gene

ENSEMBL:
Gene Tree for DUX4 (if available)
TreeFam:
Gene Tree for DUX4 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for DUX4: view image

No data available for Orthologs for DUX4 Gene

Paralogs for DUX4 Gene

(20) SIMAP similar genes for DUX4 Gene using alignment to 25 proteins:

  • DUX4_HUMAN
  • C3U395_HUMAN
  • C3U396_HUMAN
  • C3U397_HUMAN
  • C3U398_HUMAN
  • C3U399_HUMAN
  • C3U3A0_HUMAN
  • E0YLM6_HUMAN
  • E0Z3E7_HUMAN
  • E0Z3E8_HUMAN
  • E0Z3E9_HUMAN
  • E0Z3F0_HUMAN
  • E0Z3F1_HUMAN
  • E0Z3F3_HUMAN
  • E0Z3F7_HUMAN
  • E0Z3G4_HUMAN
  • E0Z3H0_HUMAN
  • E0Z3H2_HUMAN
  • E0Z3H5_HUMAN
  • E2JJS1_HUMAN
  • F8QWT8_HUMAN
  • F8QWU0_HUMAN
  • F8QWU1_HUMAN
  • F8QWU2_HUMAN
  • Q14333_HUMAN
genes like me logo Genes that share paralogs with DUX4: view

Variants for DUX4 Gene

Additional dbSNP identifiers (rs#s) for DUX4 Gene

Additional Variant Information for DUX4 Gene

SNPedia medical, phenotypic, and genealogical associations of SNPs for
DUX4

SNP Genotyping and Copy Number Assay Products

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot , Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP , Structural Variations from Database of Genomic Variants (DGV) and Variation tolerance for DUX4 Gene

Disorders for DUX4 Gene

MalaCards: The human disease database

(10) MalaCards diseases for DUX4 Gene - From: Orphanet, DISEASES, and GeneCards

Disorder Aliases PubMed IDs
facioscapulohumeral muscular dystrophy 1
  • fmd
muscular dystrophy
  • muscular dystrophies
embryonal rhabdomyosarcoma
  • botryoid rhabdomyosarcoma
retinal telangiectasia
ewing sarcoma
  • es
- elite association - COSMIC cancer census association via MalaCards
Search DUX4 in MalaCards View complete list of genes associated with diseases

UniProtKB/Swiss-Prot

DUX4_HUMAN
  • 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. {ECO:0000269 PubMed:10433963, ECO:0000269 PubMed:19320656}. 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. {ECO:0000269 PubMed:19320656}.

Additional Disease Information for DUX4

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
genes like me logo Genes that share disorders with DUX4: view

No data available for Genatlas for DUX4 Gene

Publications for DUX4 Gene

  1. DUX4HD2-DNAERG structure reveals new insight into DUX4-Responsive-Element. (PMID: 30315230) Dong X … Meng G (Leukemia 2019) 3 4 54
  2. Crystal Structure of the Double Homeodomain of DUX4 in Complex with DNA. (PMID: 30540931) Lee JK … Aihara H (Cell reports 2018) 3 4 54
  3. Structural basis for multiple gene regulation by human DUX4. (PMID: 30322619) Li Y … Gan J (Biochemical and biophysical research communications 2018) 3 4 54
  4. The DUX4 homeodomains mediate inhibition of myogenesis and are functionally exchangeable with the Pax7 homeodomain. (PMID: 28935672) Bosnakovski D … Kyba M (Journal of cell science 2017) 3 4 54
  5. Conservation and innovation in the DUX4-family gene network. (PMID: 28459454) Whiddon JL … Tapscott SJ (Nature genetics 2017) 3 4 54

Products for DUX4 Gene

Sources for DUX4 Gene