Affinage

ARX

Homeobox protein ARX · UniProt Q96QS3

Length
562 aa
Mass
58.2 kDa
Annotated
2026-06-09
100 papers in source corpus 28 papers cited in narrative 28 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

ARX is a paired-type homeodomain transcription factor that orchestrates cell-fate specification and migration in two distinct developmental contexts: the forebrain and the pancreatic islet (PMID:12379852, PMID:14561778). In the developing telencephalon, ARX is required cell-autonomously for tangential migration of ganglionic-eminence-derived GABAergic interneurons, cortical progenitor proliferation, and cholinergic neuron formation, acting downstream of Dlx2 and Lhx6, which bind ultraconserved forebrain enhancers in the ARX locus to drive its expression (PMID:18923043, PMID:18509041, PMID:17460091, PMID:24742460). It functions principally as a sequence-specific transcriptional repressor, directly silencing Lmo1, Ebf3, Shox2, and the cell-cycle inhibitor Cdkn1c; de-repression of Ebf3 in ARX-deficient cells blocks interneuron migration, while loss of Cdkn1c repression causes premature progenitor cell-cycle exit (PMID:18799476, PMID:22194193, PMID:19627984, PMID:23968833). Loss of ARX function specifically in cortical interneurons produces seizures and infantile-spasm-like events, and postnatal ARX in parvalbumin interneurons further tunes their excitability (PMID:19439424, PMID:33490907). In the pancreas, ARX is necessary and sufficient to instruct alpha/PP-cell fate while suppressing beta- and delta-cell identity through mutually repressive antagonism with PAX4; in beta cells, the ARX locus is held silent by Dnmt1-dependent DNA methylation, MeCP2 binding, and PRMT6-mediated H3R2 methylation, and combined loss of ARX and Dnmt1 converts alpha cells into functional insulin-secreting beta-like cells (PMID:14561778, PMID:17404619, PMID:15930104, PMID:21497756, PMID:28215845). Disease mechanisms are stratified by mutation class: homeodomain missense mutations abolish DNA binding and repression (lissencephaly), polyalanine expansions reduce ARX protein abundance and target repression (interneuronopathy and epilepsy), and NLS mutations sequester the import receptor IPO13 to disrupt nuclear distribution (PMID:22194193, PMID:20148114, PMID:24122442). ARX can also act as a context-dependent activator, cooperating with FoxA2 to induce Shh at a floor-plate enhancer (PMID:24968361).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 2002 High

    Established ARX as essential for forebrain development by defining its requirement for GABAergic interneuron migration and neuronal proliferation, framing it as the molecular basis of a human brain malformation syndrome.

    Evidence Knockout mouse phenotypic analysis with human mutation identification

    PMID:12379852

    Open questions at the time
    • Direct transcriptional targets not yet identified
    • Upstream regulators of Arx expression unknown
  2. 2003 High

    Extended ARX function beyond brain to the pancreatic islet, showing it specifies alpha-cell fate through mutual transcriptional repression with PAX4.

    Evidence Gene-targeted knockout mouse, immunohistology, multiplex RT-PCR

    PMID:14561778

    Open questions at the time
    • Direct binding to the Pax4 locus not demonstrated
    • Cofactors mediating repression unknown
  3. 2005 High

    Resolved the combinatorial logic of islet fate allocation by showing Arx and Pax4 together gate alpha/beta versus delta-cell identity, and conserved ARX neuronal function in an invertebrate.

    Evidence Mouse double-mutant genetic epistasis; C. elegans alr-1/lin-11 genetics

    PMID:15790968 PMID:15930104

    Open questions at the time
    • Mechanism of somatostatin-cell default fate not defined
    • Direct vs indirect cross-repression unresolved
  4. 2007 High

    Demonstrated ARX is sufficient, not merely necessary, to instruct alpha/PP fate, and revealed a separate role promoting embryonic myoblast differentiation via Mef2C.

    Evidence Conditional gain-of-function mouse with lineage tracing; C2C12 overexpression and Co-IP with Mef2C

    PMID:17404619 PMID:17932502

    Open questions at the time
    • Muscle role rests on single lab
    • Whether activation vs repression underlies myogenic effect unclear
  5. 2008 High

    Placed ARX within a transcriptional hierarchy downstream of Dlx2 via ultraconserved enhancers and defined cell-autonomous progenitor proliferation and migration roles, plus its first direct repression targets.

    Evidence Enhancer functional characterization, Dlx gain/loss-of-function, in utero electroporation, genome-wide expression screen

    PMID:17460091 PMID:18509041 PMID:18799476 PMID:18923043

    Open questions at the time
    • Repressive cofactor complexes not identified
    • Direct binding for most dysregulated genes not confirmed
  6. 2009 High

    Causally linked ARX loss in interneurons to epilepsy and identified Ebf3 de-repression as a migration-blocking mechanism rescuable by Ebf3 silencing.

    Evidence Dlx5/6-CRE conditional knockout with EEG; ectopic-expression and epistasis rescue

    PMID:19439424 PMID:19627984

    Open questions at the time
    • Full set of seizure-relevant targets unresolved
    • Circuit-level mechanism of spasms not defined
  7. 2010 Medium

    Defined a nuclear-import disease mechanism in which NLS mutations sequester IPO13, and identified TUBA1A interaction with a mitotic accumulation phenotype.

    Evidence Co-immunoprecipitation, immunofluorescence, cell-cycle analysis

    PMID:20148114

    Open questions at the time
    • TUBA1A interaction not reciprocally validated
    • Functional consequence of mitotic accumulation in vivo unknown
  8. 2011 High

    Established the epigenetic logic silencing Arx in beta cells (Dnmt1-MeCP2-PRMT6), mapped upstream activators (Isl-1) and a genome-wide ARX regulatory network, and identified KDM5C as a target linking ARX to histone methylation.

    Evidence Conditional Dnmt1 KO with ChIP and lineage tracing; Isl-1 ChIP and mutagenesis; ChIP-chip in neuroblastoma/brain; KDM5C reporter and H3K4me3 assays

    PMID:21388963 PMID:21497756 PMID:21966449 PMID:23246292

    Open questions at the time
    • Direct ARX targets among ChIP-chip bound promoters mostly unvalidated
    • Generality of epigenetic silencing model beyond beta cells unclear
  9. 2012 High

    Defined ARX biochemically as a repressor whose DNA-binding specificity depends on homeodomain-flanking residues, mechanistically explaining how homeodomain missense mutations cause disease.

    Evidence In vitro DNA-binding and luciferase repression assays with mutant analysis

    PMID:22194193 PMID:22252899

    Open questions at the time
    • Structural basis of flanking-residue contribution not resolved
    • Genome-wide binding motif not derived
  10. 2013 Medium

    Mechanistically separated polyalanine-expansion pathology (reduced protein abundance impairing Lmo1 repression) from earlier aggregation models, identified Cdkn1c as a direct proliferation target, and established Arx inhibition alone as sufficient to trigger alpha-to-beta cell regeneration.

    Evidence Knock-in mouse models with western blot; cortex-specific conditional KO with profiling; conditional alpha-cell loss-of-function with lineage tracing

    PMID:23968833 PMID:24122442 PMID:24204325

    Open questions at the time
    • Reconciliation of aggregation vs abundance-loss models incomplete
    • Cdkn1c regulation rests on single lab
  11. 2014 Medium

    Placed ARX downstream of Lhx6 in interneuron fate, revealed a context-dependent activator role with FoxA2 at the Shh floor-plate enhancer, and showed early target normalization (by estradiol) yields lasting seizure rescue.

    Evidence In vivo ChIP and MGE complementation; chick/mouse Shh enhancer perturbation; pharmacological E2 rescue with target qRT-PCR

    PMID:24452264 PMID:24742460 PMID:24968361

    Open questions at the time
    • Switch between repressor and activator modes mechanistically undefined
    • Cofactors converting ARX to an activator unknown
  12. 2017 High

    Demonstrated that combined ARX and Dnmt1 loss produces functional beta-like cells and that this conversion occurs in human type 1 diabetes islets, establishing translational relevance of ARX-controlled cell identity.

    Evidence Lineage tracing, scRNA-seq, electrophysiology, GSIS, human tissue immunostaining

    PMID:28215845

    Open questions at the time
    • Stability and durability of converted cells unresolved
    • Therapeutic targeting strategy not established
  13. 2020 High

    Showed ARX has an ongoing postnatal role tuning parvalbumin interneuron excitability and identifying synaptic/ECM target pathways, extending its function beyond developmental specification.

    Evidence Postnatal PV-Cre conditional knockout, EEG, FACS-RNA-seq, patch-clamp

    PMID:33490907

    Open questions at the time
    • Direct vs indirect regulation of synaptic/ECM targets unconfirmed
    • Mechanism linking ARX loss to PVI hypoexcitability undefined

Open questions

Synthesis pass · forward-looking unresolved questions
  • How ARX switches between transcriptional repression and context-dependent activation, and which cofactor complexes mediate each mode at specific loci, remains unresolved.
  • No structure of ARX bound to DNA or cofactors
  • Identity of corepressor/coactivator complexes unknown
  • Genome-wide direct target set across tissues incompletely defined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 8 GO:0003677 DNA binding 5
Localization
GO:0005634 nucleus 2 GO:0005654 nucleoplasm 1
Pathway
R-HSA-1266738 Developmental Biology 6 R-HSA-74160 Gene expression (Transcription) 6 R-HSA-112316 Neuronal System 2 R-HSA-4839726 Chromatin organization 2
Partners
DLX2FOXA2IPO13ISL1LHX6MEF2CPAX4TUBA1A

Evidence

Reading pass · 28 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2002 ARX loss-of-function causes suppressed forebrain neuronal proliferation and aberrant migration/differentiation of GABAergic interneurons in the ganglionic eminence and neocortex, establishing ARX as essential for interneuron development and forebrain formation. Knockout mouse phenotypic analysis (loss-of-function); human mutation identification Nature genetics High 12379852
2003 Arx is required for pancreatic alpha-cell fate acquisition; Arx-deficient mice lose mature alpha cells with concomitant increase in beta- and delta-cell numbers. Arx and Pax4 act as transcriptional repressors of each other's expression, with antagonistic functions in islet cell specification. Gene targeting/knockout in mouse ES cells; immunohistology; multiplex RT-PCR Genes & development High 14561778
2007 Arx gain-of-function (misexpression) in embryonic or adult beta cells promotes conversion to glucagon- or PP-producing cells, confirming Arx is not only necessary but sufficient to instruct alpha/PP cell fate and suppress beta- and delta-cell identity. Conditional gain-of-function mouse; lineage tracing; quantitative RT-PCR The Journal of clinical investigation High 17404619
2005 Combined loss of Arx and Pax4 results in near-exclusive generation of somatostatin-producing cells at the expense of alpha- and beta-cells, and both proteins act as transcriptional repressors controlling each other's expression levels to mediate proper endocrine fate allocation. Double-mutant mouse genetic epistasis; immunohistology; molecular analysis Development (Cambridge, England) High 15930104
2008 Arx is a direct transcriptional target of Dlx2: Dlx overexpression induces ectopic Arx expression through a GABAergic enhancer element, loss of Dlx reduces Arx expression, and Arx is necessary (but not sufficient) for the Dlx-dependent promotion of interneuron tangential migration. Ultraconserved enhancer modules downstream of the Arx coding region, partially within introns of PolA1, control its forebrain expression. Enhancer isolation; functional characterization; Dlx gain/loss-of-function; combined mutant analysis The Journal of neuroscience High 18923043
2008 Arx plays cell-autonomous roles in cortical development: ARX knockdown causes premature cell-cycle exit of cortical progenitors and impairs multipolar morphology and radial/tangential migration; ARX overexpression increases cell-cycle length and promotes tangential processes. ARX level is critical for tangential migration of GABAergic interneurons but is not directly required for GABAergic cell fate specification. In utero electroporation with RNAi knockdown and overexpression; live imaging; cell morphology analysis The Journal of neuroscience High 18509041
2008 Arx inactivation in the ventral telencephalon causes periventricular accumulation of immature neurons due to cell-autonomous defects in neuronal migration, impairs cholinergic neuron formation, and disrupts thalamocortical projections. Arx mutant neurons retain differentiation potential in vitro but show deficits in morphology and migration. Arx mutant mouse analysis; in vitro neuronal culture; immunohistochemistry The Journal of neuroscience High 17460091
2008 ARX directly represses transcription of Lmo1, Ebf3, and Shox2 in the developing basal forebrain; genome-wide expression screen identified 84 dysregulated genes in the Arx-deficient subpallium enriched for cell migration, axonal guidance, and neurogenesis. Genome-wide expression screen; chromatin analysis; validation of direct repression Human molecular genetics Medium 18799476
2009 Conditional deletion of Arx from ganglionic eminence-derived neurons (via Dlx5/6-CRE) causes multiple seizure types including infantile spasm-like events, demonstrating that Arx function specifically in cortical interneurons underlies epilepsy pathogenesis. Heterozygous females with single mutant Arx allele also develop seizures. Conditional knockout (Cre-lox); EEG recordings; behavioral analysis Brain : a journal of neurology High 19439424
2004 Polyalanine tract expansions in ARX lead to intranuclear protein aggregation forming filamentous nuclear inclusions, increased cell death, ubiquitination of inclusions, and recruitment of Hsp70. Co-expression of Hsp70 decreases inclusion formation. Mutant Arx also forms nuclear inclusions in mouse brain slices. Cell culture transfection; brain slice electroporation; immunofluorescence; ubiquitin staining; Hsp70 co-expression rescue The Journal of cell biology High 15533998
2011 In pancreatic beta cells, the Arx locus is methylated and repressed via Dnmt1-dependent propagation of DNA methylation; the methylated region is bound by MeCP2 which recruits PRMT6, an enzyme that methylates histone H3R2 to repress Arx. Loss of Dnmt1 leads to Arx de-repression and beta-to-alpha cell conversion. Conditional Dnmt1 knockout; bisulfite sequencing; ChIP; lineage tracing Developmental cell High 21497756
2011 ARX homeodomain missense mutations causing brain malformations and infantile spasms abolish DNA binding and reduce transcriptional repression activity; the milder P353L mutation retains partial DNA binding and repression. Wild-type ARX represses endogenous targets LMO1 and SHOX2 by direct DNA binding confirmed by EMSA and ChIP. Luciferase reporter assays; EMSA; ChIP; qRT-PCR of endogenous targets Human molecular genetics High 22194193
2009 Arx acts as a regional key selector gene in the ventral telencephalon primarily through transcriptional repression. Ectopic expression of Ebf3 in ganglionic eminences prevents tangential migration; Arx directly represses Ebf3, and Ebf3 silencing in Arx mutants partially rescues tangential migration. Arx mutant mice; ectopic expression studies; epistasis rescue experiment Developmental biology High 19627984
2010 Missense mutations in the nuclear localization sequences (NLS) flanking the ARX homeodomain disrupt nuclear accumulation. These mutations do not abolish binding to Importin 13 (IPO13); instead, mutant ARX sequesters endogenous IPO13 even in RanGTP-rich nuclear environments, preventing normal ARX distribution. ARX also interacts with TUBA1A (α-tubulin), and cells expressing mutant ARX accumulate in mitosis. Co-immunoprecipitation; immunofluorescence; cell cycle analysis PathoGenetics Medium 20148114
2013 Selective inhibition of Arx in adult pancreatic alpha-cells is sufficient to promote their conversion into functional beta-like cells; this conversion induces mobilization of duct-lining precursor cells to adopt glucagon+ fate which then convert to beta-like cells. Pax4 is dispensable for this regeneration process, identifying Arx as the primary trigger. Conditional loss-of-function; lineage tracing; functional beta-cell characterization PLoS genetics High 24204325
2013 ARX directly regulates Cdkn1c transcription in cortical progenitors; loss of Arx causes Cdkn1c overexpression which inhibits cell cycle progression, reducing intermediate progenitor cell expansion and upper-layer neuron formation. Cortex-specific conditional knockout; transcriptional profiling; direct regulatory relationship validated Cerebral cortex Medium 23968833
2014 Lhx6 directly binds in vivo to an Arx enhancer (and a CXCR7 intronic enhancer) to regulate their expression. Arx rescues cell-fate but not laminar positioning defects in Lhx6-null MGE cells, establishing Lhx6→Arx as a direct transcriptional hierarchy for interneuron fate specification. In vivo ChIP at Arx enhancer; MGE transplantation/complementation assay; conditional genetics Neuron High 24742460
2014 Arx, in conjunction with FoxA2, directly induces Shh expression by binding to the Shh floor plate enhancer (SFPE2). FoxA2 induces Arx transcription while Nkx2.2 (induced by Shh) suppresses Arx, forming a feedback loop. Arx functions as a context-dependent transcriptional activator at this locus. In ovo chick electroporation (gain-of-function); Arx-deficient mouse (loss-of-function); enhancer binding assay Developmental biology Medium 24968361
2011 Islet-1 (Isl-1) directly activates Arx transcription in pancreatic alpha-cells through binding to two conserved noncoding regulatory regions (Re1 at +5.6-6.1 kb and Re2 at +23.6-24 kb) in the Arx locus; loss of Isl-1 reduces Arx-positive cell numbers and Arx mRNA levels. ChIP; cell transfection reporter assays; Isl-1 knockdown and overexpression; site-directed mutagenesis The Journal of biological chemistry High 21388963
2011 ARX directly regulates KDM5C transcription by binding a conserved noncoding element in the KDM5C regulatory region. ARX polyalanine expansion mutations show decreased trans-activity and reduced binding to this element, correlating with reduced Kdm5c mRNA in Arx-knockout neural stem cells and altered H3K4me3 levels during neuronal differentiation. Reporter assays with ARX binding; qRT-PCR in Arx-KO cells; H3K4me3 measurement American journal of human genetics Medium 23246292
2012 ARX functions primarily as a transcriptional repressor: missense mutations in the homeodomain reduce or abolish DNA binding and transcriptional repression. DNA-binding preferences of ARX are influenced by amino acid sequences flanking the homeodomain; mutations affecting DNA binding also reduce repression of Arx target genes. In vitro DNA binding assays; luciferase repression reporter assays; deletion and missense mutant analysis Neurogenetics Medium 22252899
2013 Polyalanine expansion mutations in ARX cause a marked reduction in Arx protein abundance in the developing forebrain without detectable protein aggregates; this reduced protein level correlates with impaired repression of target gene Lmo1, with greater loss of Lmo1 repression in the more severe PA1 (GCG7) expansion model than the PA2 (dup24) model. Knock-in mouse models; western blot; qRT-PCR of target gene expression Human molecular genetics Medium 24122442
2007 Arx is strongly expressed in differentiating embryonic (but not fetal) skeletal muscle downstream of myogenic bHLH genes; it co-immunoprecipitates with Mef2C, enhances myogenic differentiation when overexpressed in C2C12 cells, stimulates Myogenin promoter activity and E-box-driven transcription with MyoD and Mef2C, and its absence causes delayed embryonic myoblast differentiation in vivo. Co-immunoprecipitation; C2C12 overexpression; reporter/promoter assays; Arx-deficient embryo analysis Cell death and differentiation Medium 17932502
2017 Combined loss of Arx and Dnmt1 in mouse alpha-cells drives extensive conversion of alpha cells into progeny resembling native beta cells, with converted cells acquiring beta-cell electrophysiology and glucose-stimulated insulin secretion. In human T1D patients, subsets of glucagon-expressing cells show loss of DNMT1 and ARX and produce insulin. Lineage tracing; single-cell RNA sequencing; electrophysiology; GSIS assays; human tissue immunostaining Cell metabolism High 28215845
2020 Postnatal Arx expression in parvalbumin interneurons (PVIs) regulates their functional properties; conditional postnatal ablation of Arx from PVIs increases theta oscillations, causes occasional seizures, elevated anxiety, and PVI hypoexcitability. Genome-wide sequencing of sorted PVIs identified Arx target genes associated with synaptic and extracellular matrix pathways. Conditional knockout (postnatal, PV-Cre); EEG recording; FACS-sorted cell RNA-seq; whole-cell patch-clamp recordings iScience High 33490907
2011 Chromatin immunoprecipitation combined with microarray analysis identified ~1006 gene promoters bound by Arx in neuroblastoma cells and mouse embryonic brain; ~24% of bound genes showed expression changes on Arx overexpression or knockdown, defining a broad ARX gene regulatory network. ChIP-chip (chromatin immunoprecipitation with microarray); mRNA expression microarray; Arx overexpression and knockdown PloS one Medium 21966449
2005 The C. elegans Arx ortholog alr-1 acts in a pathway with the LIM-homeodomain protein lin-11 (LIM1 ortholog) to regulate chemosensory neuron development, and alr-1 is required for differentiation of a GABAergic motoneuron subtype, demonstrating conservation of ARX function in GABAergic and sensory neuron development. C. elegans genetics; double mutant epistasis; neuronal cell fate analysis Development (Cambridge, England) Medium 15790968
2014 Neonatal estradiol (E2) administration prevents spasms and seizures in Arx(GCG)10+7 mice by altering mRNA levels of three Arx downstream targets (Shox2, Ebf3, and Lgi1) and restoring depleted interneuron populations, establishing that early transcriptional changes downstream of Arx are sufficient for lasting disease modification. Pharmacological treatment (E2) in Arx mutant mice; EEG; interneuron counts; qRT-PCR of Arx targets Science translational medicine Medium 24452264

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2002 Mutation of ARX causes abnormal development of forebrain and testes in mice and X-linked lissencephaly with abnormal genitalia in humans. Nature genetics 526 12379852
2003 Opposing actions of Arx and Pax4 in endocrine pancreas development. Genes & development 454 14561778
2002 ARX, a novel Prd-class-homeobox gene highly expressed in the telencephalon, is mutated in X-linked mental retardation. Human molecular genetics 233 11971879
2004 Mutations of ARX are associated with striking pleiotropy and consistent genotype-phenotype correlation. Human mutation 232 14722918
2013 The inactivation of Arx in pancreatic α-cells triggers their neogenesis and conversion into functional β-like cells. PLoS genetics 213 24204325
2011 Pancreatic β cell identity is maintained by DNA methylation-mediated repression of Arx. Developmental cell 210 21497756
2007 Embryonic endocrine pancreas and mature beta cells acquire alpha and PP cell phenotypes upon Arx misexpression. The Journal of clinical investigation 204 17404619
2005 The simultaneous loss of Arx and Pax4 genes promotes a somatostatin-producing cell fate specification at the expense of the alpha- and beta-cell lineages in the mouse endocrine pancreas. Development (Cambridge, England) 175 15930104
2017 Converting Adult Pancreatic Islet α Cells into β Cells by Targeting Both Dnmt1 and Arx. Cell metabolism 171 28215845
2009 Targeted loss of Arx results in a developmental epilepsy mouse model and recapitulates the human phenotype in heterozygous females. Brain : a journal of neurology 158 19439424
2002 Infantile spasms, dystonia, and other X-linked phenotypes caused by mutations in Aristaless related homeobox gene, ARX. Brain & development 152 12142061
1997 Expression of a novel aristaless related homeobox gene 'Arx' in the vertebrate telencephalon, diencephalon and floor plate. Mechanisms of development 151 9256348
2009 A triplet repeat expansion genetic mouse model of infantile spasms syndrome, Arx(GCG)10+7, with interneuronopathy, spasms in infancy, persistent seizures, and adult cognitive and behavioral impairment. The Journal of neuroscience : the official journal of the Society for Neuroscience 138 19587282
2007 A longer polyalanine expansion mutation in the ARX gene causes early infantile epileptic encephalopathy with suppression-burst pattern (Ohtahara syndrome). American journal of human genetics 133 17668384
2010 ARX spectrum disorders: making inroads into the molecular pathology. Human mutation 129 20506206
1997 Expression patterns of Brx1 (Rieg gene), Sonic hedgehog, Nkx2.2, Dlx1 and Arx during zona limitans intrathalamica and embryonic ventral lateral geniculate nuclear formation. Mechanisms of development 121 9347917
2008 Arx is a direct target of Dlx2 and thereby contributes to the tangential migration of GABAergic interneurons. The Journal of neuroscience : the official journal of the Society for Neuroscience 120 18923043
2007 Expansion of the first PolyA tract of ARX causes infantile spasms and status dystonicus. Neurology 115 17664401
2007 Inactivation of Arx, the murine ortholog of the X-linked lissencephaly with ambiguous genitalia gene, leads to severe disorganization of the ventral telencephalon with impaired neuronal migration and differentiation. The Journal of neuroscience : the official journal of the Society for Neuroscience 114 17460091
2008 Identification of Arx transcriptional targets in the developing basal forebrain. Human molecular genetics 110 18799476
2006 ARX: a gene for all seasons. Current opinion in genetics & development 109 16650978
2003 The ARX story (epilepsy, mental retardation, autism, and cerebral malformations): one gene leads to many phenotypes. Current opinion in pediatrics 105 14631200
2014 Lhx6 directly regulates Arx and CXCR7 to determine cortical interneuron fate and laminar position. Neuron 102 24742460
2008 Cell-autonomous roles of ARX in cell proliferation and neuronal migration during corticogenesis. The Journal of neuroscience : the official journal of the Society for Neuroscience 97 18509041
2005 Arx homeobox gene is essential for development of mouse olfactory system. Development (Cambridge, England) 94 15677725
2002 Variable expression of mental retardation, autism, seizures, and dystonic hand movements in two families with an identical ARX gene mutation. American journal of medical genetics 94 12376946
2010 Mutations in ARX Result in Several Defects Involving GABAergic Neurons. Frontiers in cellular neuroscience 90 20300201
2004 Monogenic X-linked mental retardation: is it as frequent as currently estimated? The paradox of the ARX (Aristaless X) mutations. European journal of human genetics : EJHG 83 15319782
2012 The homeodomain-containing transcription factors Arx and Pax4 control enteroendocrine subtype specification in mice. PloS one 78 22570716
2002 X-linked myoclonic epilepsy with spasticity and intellectual disability: mutation in the homeobox gene ARX. Neurology 77 12177367
2004 Neuroanatomical distribution of ARX in brain and its localisation in GABAergic neurons. Brain research. Molecular brain research 75 14992814
2013 Pancreatic α-cell specific deletion of mouse Arx leads to α-cell identity loss. PloS one 74 23785486
2004 A polyalanine tract expansion in Arx forms intranuclear inclusions and results in increased cell death. The Journal of cell biology 74 15533998
2006 The role of ARX in cortical development. The European journal of neuroscience 71 16519652
2009 Three human ARX mutations cause the lissencephaly-like and mental retardation with epilepsy-like pleiotropic phenotypes in mice. Human molecular genetics 70 19605412
2004 Mouse orthologue of ARX, a gene mutated in several X-linked forms of mental retardation and epilepsy, is a marker of adult neural stem cells and forebrain GABAergic neurons. Developmental dynamics : an official publication of the American Association of Anatomists 70 15376319
2003 ARX mutations in X-linked lissencephaly with abnormal genitalia. Neurology 63 12874405
2012 Arx is required for normal enteroendocrine cell development in mice and humans. Developmental biology 62 22387004
2002 Cell-wall proteinases PrtS and PrtB have a different role in Streptococcus thermophilus/Lactobacillus bulgaricus mixed cultures in milk. Microbiology (Reading, England) 62 12427933
2012 Interneuron, interrupted: molecular pathogenesis of ARX mutations and X-linked infantile spasms. Current opinion in neurobiology 58 22565167
2009 The Xenopus Irx genes are essential for neural patterning and define the border between prethalamus and thalamus through mutual antagonism with the anterior repressors Fezf and Arx. Developmental biology 57 19268445
2014 Neonatal estradiol stimulation prevents epilepsy in Arx model of X-linked infantile spasms syndrome. Science translational medicine 56 24452264
2013 Aristaless related homeobox gene, Arx, is implicated in mouse fetal Leydig cell differentiation possibly through expressing in the progenitor cells. PloS one 55 23840809
2004 Three new families with X-linked mental retardation caused by the 428-451dup(24bp) mutation in ARX. Clinical genetics 55 15200506
2002 Human ARX gene: genomic characterization and expression. Molecular genetics and metabolism 55 12359145
2013 ARX regulates cortical intermediate progenitor cell expansion and upper layer neuron formation through repression of Cdkn1c. Cerebral cortex (New York, N.Y. : 1991) 54 23968833
2004 Screening of the ARX gene in 682 retarded males. European journal of human genetics : EJHG 49 15199382
2011 Identification of Arx targets unveils new candidates for controlling cortical interneuron migration and differentiation. Frontiers in cellular neuroscience 47 22355284
2009 Arx acts as a regional key selector gene in the ventral telencephalon mainly through its transcriptional repression activity. Developmental biology 47 19627984
2011 The fast milk acidifying phenotype of Streptococcus thermophilus can be acquired by natural transformation of the genomic island encoding the cell-envelope proteinase PrtS. Microbial cell factories 46 21995822
2012 An epilepsy-related ARX polyalanine expansion modifies glutamatergic neurons excitability and morphology without affecting GABAergic neurons development. Cerebral cortex (New York, N.Y. : 1991) 41 22628459
2005 Screening of ARX in mental retardation families: Consequences for the strategy of molecular diagnosis. Neurogenetics 41 16235064
2016 Developmental interneuron subtype deficits after targeted loss of Arx. BMC neuroscience 40 27287386
2011 Nkx2.2 and Arx genetically interact to regulate pancreatic endocrine cell development and endocrine hormone expression. Developmental biology 40 21856296
2012 A regulatory path associated with X-linked intellectual disability and epilepsy links KDM5C to the polyalanine expansions in ARX. American journal of human genetics 38 23246292
2005 Regulation of chemosensory and GABAergic motor neuron development by the C. elegans Aristaless/Arx homolog alr-1. Development (Cambridge, England) 36 15790968
2012 Analysis of transcriptional codes for zebrafish dopaminergic neurons reveals essential functions of Arx and Isl1 in prethalamic dopaminergic neuron development. Developmental biology 34 22728160
2011 High-throughput analysis of promoter occupancy reveals new targets for Arx, a gene mutated in mental retardation and interneuronopathies. PloS one 34 21966449
2014 Conditional Loss of Arx From the Developing Dorsal Telencephalon Results in Behavioral Phenotypes Resembling Mild Human ARX Mutations. Cerebral cortex (New York, N.Y. : 1991) 33 24794919
2011 Islet-1 regulates Arx transcription during pancreatic islet alpha-cell development. The Journal of biological chemistry 33 21388963
2010 A novel ARX phenotype: rapid neurodegeneration with Ohtahara syndrome and a dyskinetic movement disorder. Developmental medicine and child neurology 33 19747203
2010 Mutations in the nuclear localization sequence of the Aristaless related homeobox; sequestration of mutant ARX with IPO13 disrupts normal subcellular distribution of the transcription factor and retards cell division. PathoGenetics 33 20148114
2015 The Role of ARX in Human Pancreatic Endocrine Specification. PloS one 32 26633894
2019 The maternal immune activation model uncovers a role for the Arx gene in GABAergic dysfunction in schizophrenia. Brain, behavior, and immunity 29 31175998
2010 Frameshift mutations of the ARX gene in familial Ohtahara syndrome. Epilepsia 29 20384723
2006 The ARX mutations: a frequent cause of X-linked mental retardation. American journal of medical genetics. Part A 29 16523516
2007 The homeobox gene Arx is a novel positive regulator of embryonic myogenesis. Cell death and differentiation 28 17932502
2005 The phenotypic spectrum of ARX mutations. Developmental medicine and child neurology 28 15707237
2022 NanoDam identifies Homeobrain (ARX) and Scarecrow (NKX2.1) as conserved temporal factors in the Drosophila central brain and visual system. Developmental cell 27 35483359
2019 Assessment of ARX expression, a novel biomarker for metastatic risk in pancreatic neuroendocrine tumors, in endoscopic ultrasound fine-needle aspiration. Diagnostic cytopathology 27 31846235
2011 ARX polyalanine expansions are highly implicated in familial cases of mental retardation with infantile epilepsy and/or hand dystonia. American journal of medical genetics. Part A 27 21204215
2009 Ohtahara syndrome in a family with an ARX protein truncation mutation (c.81C>G/p.Y27X). European journal of human genetics : EJHG 27 19738637
2008 Expansion of the ARX spectrum. Clinical neurology and neurosurgery 27 18462864
2008 Combination of infantile spasms, non-epileptic seizures and complex movement disorder: a new case of ARX-related epilepsy. Epilepsy research 27 18468866
2014 Arx together with FoxA2, regulates Shh floor plate expression. Developmental biology 25 24968361
2011 Arx and Nkx2.2 compound deficiency redirects pancreatic alpha- and beta-cell differentiation to a somatostatin/ghrelin co-expressing cell lineage. BMC developmental biology 25 21880149
1994 X-linked mental retardation with dystonic movements of the hands (PRTS): revisited. American journal of medical genetics 24 7943040
2011 Screening and cell-based assessment of mutations in the Aristaless-related homeobox (ARX) gene. Clinical genetics 23 21496008
2011 ARX homeodomain mutations abolish DNA binding and lead to a loss of transcriptional repression. Human molecular genetics 23 22194193
2022 Multifunctional Bioactive Scaffolds from ARX-g-(Zn@rGO)-HAp for Bone Tissue Engineering: In Vitro Antibacterial, Antitumor, and Biocompatibility Evaluations. ACS applied bio materials 22 36215135
2011 A novel mutation in the aristaless domain of the ARX gene leads to Ohtahara syndrome, global developmental delay, and ambiguous genitalia in males and neuropsychiatric disorders in females. Epilepsia 22 21426321
2010 Familial Ohtahara syndrome due to a novel ARX gene mutation. American journal of medical genetics. Part A 22 21108397
2008 Disruption of the IQSEC2 transcript in a female with X;autosome translocation t(X;20)(p11.2;q11.2) and a phenotype resembling X-linked infantile spasms (ISSX) syndrome. Molecular medicine reports 22 21479374
2007 Mutation screening of the ARX gene in patients with autism. American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics 22 17044103
2020 Streptococcus thermophilus growth in soya milk: Sucrose consumption, nitrogen metabolism, soya protein hydrolysis and role of the cell-wall protease PrtS. International journal of food microbiology 21 33065381
2013 Reduced polyalanine-expanded Arx mutant protein in developing mouse subpallium alters Lmo1 transcriptional regulation. Human molecular genetics 21 24122442
2010 Partial loss of pancreas endocrine and exocrine cells of human ARX-null mutation: consideration of pancreas differentiation. Differentiation; research in biological diversity 21 20538404
2005 XLMR in MRX families 29, 32, 33 and 38 results from the dup24 mutation in the ARX (Aristaless related homeobox) gene. BMC medical genetics 20 15850492
2005 Maternal mosaicism for mutations in the ARX gene in a family with X linked mental retardation. Human genetics 20 16078051
2019 Arsenite Oxidation by a Newly Isolated Betaproteobacterium Possessing arx Genes and Diversity of the arx Gene Cluster in Bacterial Genomes. Frontiers in microbiology 19 31191509
2018 A new mouse model of ARX dup24 recapitulates the patients' behavioral and fine motor alterations. Human molecular genetics 19 29659809
2003 X-linked mental retardation and epilepsy: pathogenetic significance of ARX mutations. Brain & development 19 12689693
2012 Distinct DNA binding and transcriptional repression characteristics related to different ARX mutations. Neurogenetics 18 22252899
2016 Redifferentiation of expanded human islet β cells by inhibition of ARX. Scientific reports 17 26856418
2006 Genotype-phenotype associations for ARX gene duplication in X-linked mental retardation. Neurology 17 17082467
2016 Embryonic forebrain transcriptome of mice with polyalanine expansion mutations in the ARX homeobox gene. Human molecular genetics 16 27798109
2002 The Xenopus arx gene is expressed in the developing rostral forebrain. Development genes and evolution 16 12536326
2020 Postnatal Arx transcriptional activity regulates functional properties of PV interneurons. iScience 15 33490907
2015 Unraveling the pathogenesis of ARX polyalanine tract variants using a clinical and molecular interfacing approach. Molecular genetics & genomic medicine 15 26029707
2010 The aristaless (Arx) gene: one gene for many "interneuronopathies". Frontiers in bioscience (Elite edition) 15 20036914

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