DUX4 double homeobox 4 [Homo sapiens (human)] - Gene

Summary

Official Symbol: DUX4provided by HGNC
Official Full Name: double homeobox 4provided by HGNC
Primary source: HGNC:HGNC:50800
See related: Ensembl:ENSG00000260596 MIM:606009; AllianceGenome:HGNC:50800
Gene type: protein coding
RefSeq status: VALIDATED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: DUX4L
Summary: 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]
Annotation information: Note: GeneID: 22947 was previously named DUX4/double homeobox 4. GeneID: 100288687 is currently assigned the official DUX4/double homeobox 4 gene name. [19 Jun 2018]
Expression: Low expression observed in reference dataset See more
Orthologs: all
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Genomic context

Location:: 4q35.2

Exon count:: 7

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	4	NC_000004.12 (190173774..190185911)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	4	NC_060928.1 (193541579..193553139)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	Unplaced Scaffold	NT_167222.1 (112605..124171)

Chromosome 4 - NC_000004.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

DNMT3B splicing dysregulation mediated by SMCHD1 loss contributes to DUX4 overexpression and FSHD pathogenesis.
Title: DNMT3B splicing dysregulation mediated by SMCHD1 loss contributes to DUX4 overexpression and FSHD pathogenesis.
The DUX4-HIF1alpha Axis in Murine and Human Muscle Cells: A Link More Complex Than Expected.
Title: The DUX4-HIF1α Axis in Murine and Human Muscle Cells: A Link More Complex Than Expected.
DUX4-induced HSATII transcription causes KDM2A/B-PRC1 nuclear foci and impairs DNA damage response.
Title: DUX4-induced HSATII transcription causes KDM2A/B-PRC1 nuclear foci and impairs DNA damage response.
Hypoxia enhances human myoblast differentiation: involvement of HIF1alpha and impact of DUX4, the FSHD causal gene.
Title: Hypoxia enhances human myoblast differentiation: involvement of HIF1α and impact of DUX4, the FSHD causal gene.
Compromised nonsense-mediated RNA decay results in truncated RNA-binding protein production upon DUX4 expression.
Title: Compromised nonsense-mediated RNA decay results in truncated RNA-binding protein production upon DUX4 expression.
MATR3 is an endogenous inhibitor of DUX4 in FSHD muscular dystrophy.
Title: MATR3 is an endogenous inhibitor of DUX4 in FSHD muscular dystrophy.
DUX4 expression in cancer induces a metastable early embryonic totipotent program.
Title: DUX4 expression in cancer induces a metastable early embryonic totipotent program.
The transcription factor DUX4 orchestrates translational reprogramming by broadly suppressing translation efficiency and promoting expression of DUX4-induced mRNAs.
Title: The transcription factor DUX4 orchestrates translational reprogramming by broadly suppressing translation efficiency and promoting expression of DUX4-induced mRNAs.
DUX4-r exerts a neomorphic activity that depends on GTF2I in acute lymphoblastic leukemia.
Title: DUX4-r exerts a neomorphic activity that depends on GTF2I in acute lymphoblastic leukemia.
Post-Translational Modifications of the DUX4 Protein Impact Toxic Function in FSHD Cell Models.
Title: Post-Translational Modifications of the DUX4 Protein Impact Toxic Function in FSHD Cell Models.

Submit: New GeneRIF Correction See all GeneRIFs (95)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables DNA-binding transcription activator activity, RNA polymerase II-specific	IDA Inferred from Direct Assay more info	PubMed
enables DNA-binding transcription factor activity, RNA polymerase II-specific	IBA Inferred from Biological aspect of Ancestor more info
enables RNA polymerase II cis-regulatory region sequence-specific DNA binding	IDA Inferred from Direct Assay more info	PubMed
enables RNA polymerase II transcription regulatory region sequence-specific DNA binding	IBA Inferred from Biological aspect of Ancestor more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables sequence-specific double-stranded DNA binding	IDA Inferred from Direct Assay more info	PubMed
enables transcription cis-regulatory region binding	IDA Inferred from Direct Assay more info	PubMed

Process	Evidence Code	Pubs
involved_in apoptotic process	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of G0 to G1 transition	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of cell population proliferation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of transcription by RNA polymerase II	IDA Inferred from Direct Assay more info	PubMed
involved_in regulation of transcription by RNA polymerase II	IBA Inferred from Biological aspect of Ancestor more info

Component	Evidence Code	Pubs
located_in Golgi apparatus	IDA Inferred from Direct Assay more info
located_in cytosol	IDA Inferred from Direct Assay more info
located_in nuclear membrane	IDA Inferred from Direct Assay more info	PubMed
located_in nucleolus	IDA Inferred from Direct Assay more info
located_in nucleoplasm	IDA Inferred from Direct Assay more info	PubMed
located_in nucleoplasm	TAS Traceable Author Statement more info
is_active_in nucleus	IBA Inferred from Biological aspect of Ancestor more info
located_in nucleus	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: double homeobox protein 4

Names: double homeobox protein 10; double homeobox protein 4/10

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_034189.3 RefSeqGene

Range

1701..3772

Download

GenBank, FASTA, Sequence Viewer (Graphics), LRG_1075

mRNA and Protein(s)

NM_001293798.3 → NP_001280727.1 double homeobox protein 4 isoform DUX4-fl

See identical proteins and their annotated locations for NP_001280727.1

Status: VALIDATED

Description

Transcript Variant: This variant (2) lacks an alternate segment in the 3' UTR compared to variant 1. Both variants 1 and 2 encode the same isoform (DUX4-fl).

Source sequence(s)

AC215524, HQ266760

Consensus CDS

CCDS77990.1

UniProtKB/Swiss-Prot

E2JJS1, P0CJ85, P0CJ86, P0CJ88, P0CJ89, P0CJ90, Q9UBX2

UniProtKB/TrEMBL

C3U3A0

Related

ENSP00000456539.1, ENST00000569241.5

Conserved Domains (2) summary

pfam00046
Location:97 → 149

Homeobox; Homeobox domain

cl26386
Location:141 → 319

DNA_pol3_gamma3; DNA polymerase III subunits gamma and tau domain III
NM_001306068.3 → NP_001292997.1 double homeobox protein 4 isoform DUX4-fl

See identical proteins and their annotated locations for NP_001292997.1

Status: VALIDATED

Description

Transcript Variant: This variant (1) represents the longest transcript and encodes the longer isoform (DUX4-fl). Both variants 1 and 2 encode the same isoform.

Source sequence(s)

AC215524, HQ266761, HQ266762

Consensus CDS

CCDS77990.1

UniProtKB/Swiss-Prot

E2JJS1, P0CJ85, P0CJ86, P0CJ88, P0CJ89, P0CJ90, Q9UBX2

UniProtKB/TrEMBL

C3U3A0

Related

ENSP00000458065.1, ENST00000565211.1

Conserved Domains (2) summary

pfam00046
Location:97 → 149

Homeobox; Homeobox domain

cl26386
Location:141 → 319

DNA_pol3_gamma3; DNA polymerase III subunits gamma and tau domain III
NM_001363820.2 → NP_001350749.1 double homeobox protein 4 isoform DUX4-s

Status: VALIDATED

Description

Transcript Variant: This variant (4) lacks a large portion of the coding region compared to variant 1. The resulting isoform (DUX4-s) has a shorter and distinct C-terminus compared to isoform DUX4-fl.

Source sequence(s)

AC215524

Consensus CDS

CCDS93681.1

UniProtKB/TrEMBL

I0EZ61

Related

ENSP00000455112.1, ENST00000570263.5

Conserved Domains (2) summary

cd00086
Location:25 → 78

homeodomain; Homeodomain; DNA binding domains involved in the transcriptional regulation of key eukaryotic developmental processes; may bind to DNA as monomers or as homo- and/or heterodimers, in a sequence-specific manner.

pfam00046
Location:97 → 149

Homeobox; Homeobox domain

RNA

NR_137167.1 RNA Sequence

Status: VALIDATED

Description

Transcript Variant: This variant (3) has multiple differences in the 3' end compared to variant 1, including a distinct 3' terminus. This variant is represented as non-coding because the use of the 5'-most expected translational start codon renders the transcript a candidate for nonsense-mediated mRNA decay (NMD).

Source sequence(s)

HQ266760, HQ266765

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000004.12 Reference GRCh38.p14 Primary Assembly

Range

190173774..190185911

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GenBank, FASTA, Sequence Viewer (Graphics)

Reference GRCh38.p14 PATCHES

Genomic

NW_015495300.1 Reference GRCh38.p14 PATCHES

Range

200222..211788

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GenBank, FASTA, Sequence Viewer (Graphics)

Alternate T2T-CHM13v2.0

Genomic

NC_060928.1 Alternate T2T-CHM13v2.0

Range

193541579..193553139

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GenBank, FASTA, Sequence Viewer (Graphics)

Suppressed Reference Sequence(s)

The following Reference Sequences have been suppressed. Explain

NM_001205218.1: Suppressed sequence

Description

NM_001205218.1: This RefSeq was permanently suppressed because it is a nonsense-mediated mRNA decay (NMD) candidate.
NM_001278056.1: Suppressed sequence

Description

NM_001278056.1: This RefSeq was permanently suppressed because it is now thought that this gene does not encode a protein.
NR_038191.1: Suppressed sequence

Description

NR_038191.1: This RefSeq was temporarily suppressed because currently there is not sufficient data to support this transcript.