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FLASH GENE

Symbol

DUX4

contributors: mct/npt - updated : 22-09-2016

HGNC name	double homeobox, 4
HGNC id	3082

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed DUX4S - splicing - - - in muscles 2012 22798623 splice form of DUX4 encoding only the N-terminal portion NM_001293798 3 - 1574 NP_001280727 - 424 - 2012 22798623 expression of DUX4-fl mRNA or protein, though likely necessary for FSHD pathogenesis, is clearly not a sufficient condition (PMID: 22798623) NM_001306068 2 - 1710 NP_001292997 - 424 - 2012 22798623

EXPRESSION

Type	restricted

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Reproductive female system placenta     specific Homo sapiens   male system testis     highly Homo sapiens

cell lineage

cell lines

fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains

two helix-turn-helix (homeo) domains

HOMOLOGY

Homologene

FAMILY

DUX paired homeobox family

CATEGORY

transcription factor

SUBCELLULAR LOCALIZATION	intracellular
	intracellular,cytoplasm,organelle,Golgi
	intracellular,cytoplasm,cytosolic
	intracellular,nucleus,nucleoplasm
	intracellular,nucleus,nucleolus
	intracellular,nuclear envelope

basic FUNCTION	involved in regulation of transcription, DNA-dependent
	DUX4-mediated cell death contributes to the pathogenic pathway in FSHD (Kowaljow 2007)
	DUX4 originated from retrotransposition of a processed transcript, most probably DUXC
	initiates a large transcription deregulation cascade leading to muscle atrophy and oxidative stress, which are FSHMD1A key features
	role for DUX4 and repetitive elements in mammalian germline evolution and in FSHD muscular dystrophy
	expression of DUX4 accounts for the majority of the gene expression changes in FSHD skeletal muscle together with an immune cell infiltration
	DUX4, is responsible for driving gene expression signatures known as zygotic gene activation (ZGA) at the cleavage stage of totipotent zygotes

CELLULAR PROCESS

nucleotide, transcription

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

a component

part of subtelomeric macrosatellite D4Z4 that has 11–150 repeats, each containing a copy of the intronless DUX4 gene

INTERACTION

DNA

RNA

small molecule

protein	transcription activator of PITX1
	PITX1 protein can further diffuse to additional myonuclei and expand the transcriptional deregulation cascade initiated by DUX4 in FSHMD1A
	DUX4 might potentially induce proliferation inhibition and G1 phase arrest through upregulation of CDKN1A
	LMCD1 is a DUX4 partner

cell & other

REGULATION

repressed by

Wnt/CTNNB signaling is important for transcriptional repression of DUX4

ASSOCIATED DISORDERS

corresponding disease(s)

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function constitutional       gain of function in patient myoblasts at both mRNA and protein level in FSHMD1A, attributable to the stabilized distal DUX4 transcript ( constitutional     --over   induces cell death, induces caspase 3/7 activity and alters emerin distribution at the nuclear envelope (Kowaljow 2007) constitutional     --other   in FSHMD1A, the combination of inefficient chromatin silencing of the D4Z4 repeat and inappropriate DUX4 protein expression in muscle cells tumoral fusion       to CIC as a result of a recurrent chromosomal translocation t(4;19)(q35;q13) in Ewing-like sarcomas constitutional     --other   expressed in FSHMD1A myotubes constitutional     --over   over ten-fold in FSHMD1A myoblasts and myotubes with short telomeres, and its expression is inversely proportional to telomere length

Susceptibility

Variant & Polymorphism

Candidate gene

Marker

Therapy target

ANIMAL & CELL MODELS