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FLASH GENE

Symbol

ARX

contributors: mct/pgu - updated : 08-02-2014

HGNC name	aristaless related homeobox
HGNC id	18060

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

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 Endocrine pancreas       highly Nervous brain forebrain cerebral cortex   highly   brain basal nuclei striatum     Reproductive female system ovary         male system testis

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Connective bone

cells

System Cell Pubmed Species Stage Rna symbol Nervous neuron

cell lineage

cell lines

fluid/secretion

at STAGE

physiological period

embryo, fetal

Text	brain, forebrain, floor plate, testis, strongly expressed in differentiating embryonic muscle

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	two independent repression domains: an N-terminal octapeptide motif/engrailed homology domain, necessary for Groucho-dependent repression activity
	a high overall GC content of 72.5p100 that codes for a multidomain protein, including the octapeptide domain, that binds DNA
	three nuclear localization sequences
	four polyalanine tracts (pA1-4)
	two repression domains, the OP and a second domain located in the C-terminus at amino acids (398-448) of the protein, termed ORD (for other repression domain)
	C-terminal Aristaless domain, a novel octapeptide motif/engrailed homology domain, and four polyalanine (polyA) tracts, and missense mutations in the ARX homeodomain represent loss-of-function mutations, which lead to a reduced or complete loss of DNA binding and as a consequence, a loss of transcriptional repression

HOMOLOGY

interspecies

ortholog to murine Arx

Homologene

FAMILY	paired homeobox family
	bicoid subfamily

CATEGORY

transcription factor

SUBCELLULAR LOCALIZATION	intracellular
	intracellular,nucleus
text	restricted to regions that are known to be rich in GABAergic neurons

basic FUNCTION	playing a role in the differentiation, radial and tangential migration and maintenance of specific neuronal subtypes in the cerebral cortex (crucial for the development of cognitive function) and a secondary role in the differentiation of the testes (controlling the function of Leydig cells)
	acting as a novel positive regulator of embryonic myogenesis by synergizing with MEF2C and MYOD1 and by establishing an activating loop with myogenin
	can function as a transcriptional repressor
	important for many developmental processes, including proper migration of GABA-ergic cortical interneurons and neuronal cell differentiation and proliferation, and for proper pancreatic endocrine cell specification through the inhibition of PAX4
	plays multiple roles in forebrain development, both dependent and independent of DLX1/2
	may play a role in controlling cell cycle exit of neural progenitors within the subpallium
	not directly involved in GABAergic cell fate specification, but having multiple and distinct cell-autonomous roles for ARX in corticogenesis
	required for the normal development of human enteroendocrine cells, and in the progenitor for enteroendocrine cell development

CELLULAR PROCESS	cell life, differentiation
	nucleotide, transcription

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

a component

INTERACTION

DNA

RNA

small molecule

protein	interacting with IPO13 (with the C-terminal nuclear localization sequences in the homeodomain of ARX is required for correct nuclear localization)
	interaction between ARX and the co-repressors Groucho and CtBP
	EBF3, LMO1 and SHOX2 are direct transcriptional targets of ARX (can bind to the putative enhancers of EBF3, LMO1 and SHOX2)
	genetic interactions between NKX2-2 and ARX within the endocrine progenitor cells that ensure the correct specification and regulation of endocrine hormone-producing cells
	LMO1 and SHOX2, are ARX targets (mutations in the ARX homeodomain disrupt repression of LMO1 and SHOX2, direct targets of ARX transcription repression)
	KDM5C is directly regulated by ARX through the binding in a conserved noncoding element (ARX transactivates the 5prime KDM5C regulatory element by binding to the two “TAAT/ATTA” boxes (BD1 and BD2)
	ARX is a direct target of NKX6.1
	LHX6 directly binds to an ARX enhancer and to an intronic CXCR7 enhancer that remains active in mature interneurons
	EBF3 is a downstream transcriptional target of aristaless-related homeobox (ARX) and is thought to be transcriptionally repressed by ARX

cell & other

REGULATION

ASSOCIATED DISORDERS

corresponding disease(s)

ISSX , PRTS , XLAG , MRX54 , EIEE1

Susceptibility

Variant & Polymorphism

Candidate gene

Marker

Therapy target

ANIMAL & CELL MODELS