Affinage

ARNT2

Aryl hydrocarbon receptor nuclear translocator 2 · UniProt Q9HBZ2

Length
717 aa
Mass
78.7 kDa
Annotated
2026-06-09
57 papers in source corpus 23 papers cited in narrative 23 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

ARNT2 is a nuclear bHLH-PAS transcription factor that functions as an obligate heterodimerization partner for multiple class I bHLH-PAS proteins, integrating developmental, neuronal, and oxygen-responsive transcriptional programs (PMID:8657146, PMID:10215907). It dimerizes with SIM1 to drive late-stage differentiation of hypothalamic neurosecretory neurons of the paraventricular and supraoptic nuclei, and Arnt2-null mice phenocopy Sim1 mutants with hypocellular PVN/SON and loss of vasopressin, oxytocin, CRH, and somatostatin neurons (PMID:10640708, PMID:11381139, PMID:11318878); this SIM1/ARNT2 dimer activates a downstream neuronal gene program including Jak2 and thyroid hormone receptor beta2 (PMID:12947113). ARNT2 also forms functional HIF-1alpha heterodimers that restore hypoxia-induced gene expression in ARNT-deficient cells and neurons (PMID:10873592, PMID:11381139), and pairs with NPAS4 and AHR, though it is essentially incapable of supporting AHR-driven xenobiotic responses owing to a single PASB Pro/His difference relative to ARNT1 (PMID:8657146, PMID:17023418, PMID:18096572). Crystal structures of NPAS4-ARNT2 heterodimers bound to DNA reveal interconnected PAS-A/PAS-B domain interfaces and ligand-accessible PAS-B pockets (PMID:36343253). Its expression is controlled epigenetically, switching from a bivalent promoter state to active expression during neuronal differentiation (PMID:23599003), and ARNT2 transcriptional output is modulated by the corepressor Necdin, which binds the bHLH domains of ARNT2 and represses ARNT2:SIM1 and ARNT2:HIF1alpha activity (PMID:17826745). In humans, a homozygous loss-of-function frameshift abolishing ARNT2 transcript and protein causes microcephaly, multiple pituitary hormone deficiency, visual impairment, and renal anomalies, establishing ARNT2 as essential for hypothalamo-pituitary axis development (PMID:24022475). ARNT2 is further required cell-autonomously in somatostatin interneurons of the anterior cingulate cortex for affective empathy behavior (PMID:39180750).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 1996 High

    Established that ARNT2 is a competent dimerization partner functionally analogous to ARNT1, capable of supporting AHR- and SIM1-based complexes and rescuing XRE-driven transcription.

    Evidence Co-IP, EMSA, yeast two-hybrid, and reporter rescue in ARNT-defective Hepa-1 c4 cells

    PMID:8657146

    Open questions at the time
    • Did not establish tissue-specific or in vivo roles
    • Functional differences from ARNT1 not yet resolved
  2. 2000 High

    Defined ARNT2 as a functional HIF partner, showing ARNT2/HIF-1alpha heterodimers can mediate oxygen-responsive transcription, broadening ARNT2 beyond developmental contexts.

    Evidence Complementation in ARNT-deficient ES cells and hepatocytes; in vivo VEGF expression

    PMID:10873592 PMID:11381139

    Open questions at the time
    • Relative contribution of ARNT2 vs ARNT1 to physiological hypoxia response unresolved
    • Cell-type specificity of HIF/ARNT2 usage not mapped
  3. 2000 High

    Identified ARNT2 as the obligate SIM1 partner for hypothalamic neuroendocrine development, linking the two genes into one genetic pathway.

    Evidence In vitro dimerization, in situ co-expression in PVN/SON, genetic loss-of-function comparison in mice

    PMID:10640708 PMID:11318878 PMID:11381139

    Open questions at the time
    • Direct target genes of the dimer not yet defined
    • Whether SIM1/ARNT2 acts at early specification or late differentiation unclear at this stage
  4. 2001 High

    Knockout established ARNT2 as essential perinatally, acting at the final differentiation step of hypothalamic neurosecretory neurons and overlapping dose-dependently with ARNT.

    Evidence Targeted knockouts, histology, hormone/Brn2 marker analysis, hypoxic gene induction in primary neurons, Arnt;Arnt2 double-heterozygote epistasis

    PMID:11318878 PMID:11381139

    Open questions at the time
    • Molecular mechanism of late differentiation arrest not defined
    • Direct transcriptional targets in vivo not yet identified
  5. 2003 Medium

    Mapped the SIM1/ARNT2 downstream transcriptional program, providing candidate effector genes for hypothalamic differentiation.

    Evidence Inducible neuronal cell system with microarray/Northern, in vivo validation in Sim1 mutant hypothalamus

    PMID:12947113

    Open questions at the time
    • Direct vs indirect target distinction not established
    • Genomic binding sites not mapped
  6. 2006 High

    Explained why ARNT2 cannot substitute for ARNT1 in xenobiotic signaling, pinpointing a single PASB His/Pro residue as the determinant while preserving HIF competence.

    Evidence Chimeric/mutant ARNT/ARNT2 constructs, reporter and endogenous CYP1A1/Glut-1 assays, site-directed mutagenesis in Hepa1-c4 cells

    PMID:17023418

    Open questions at the time
    • Structural basis of PASB residue effect not resolved at this stage
    • Whether other partners are similarly affected unknown
  7. 2007 Medium

    Identified Necdin as a direct corepressor binding ARNT2 (and HIF1alpha) bHLH domains, providing a mechanism for negative regulation of ARNT2 complexes.

    Evidence Co-IP, pulldown, GAL4 reporter, domain deletion mapping

    PMID:17826745

    Open questions at the time
    • Repression domain of NDN not identified (N-terminal fragment insufficient)
    • Single-lab interaction without reciprocal in vivo validation
  8. 2013 Medium

    Showed ARNT2 expression is controlled epigenetically, with a bivalent-to-active promoter switch during neuronal differentiation explaining reciprocal ARNT/ARNT2 usage.

    Evidence ChIP for H3K4me3/H3K27me3, bisulfite sequencing, mRNA half-life, P19 differentiation model

    PMID:23599003

    Open questions at the time
    • Upstream signals triggering the epigenetic switch unknown
    • Factors removing H3K27me3 not identified
  9. 2013 Medium

    Connected human ARNT2 missense variants to reduced NPAS4/ARNT2 activity via disrupted nuclear localization, implicating ARNT2 nuclear import in function.

    Evidence Luciferase reporter, subcellular localization, site-directed mutagenesis of R46W/R107H

    PMID:24465693

    Open questions at the time
    • NLS sequence not mapped
    • In vivo consequences of variants not tested
  10. 2013 High

    Established ARNT2 as essential for human hypothalamo-pituitary development through a complete loss-of-function patient phenotype.

    Evidence Homozygosity mapping, exome sequencing, RT-PCR/Western from patient fibroblasts, embryonic immunohistochemistry

    PMID:24022475

    Open questions at the time
    • Cell types responsible for each clinical feature not dissected
    • Partner usage underlying each defect not assigned
  11. 2014 Medium

    Demonstrated that obesity-associated SIM1 variants act partly by impairing SIM1-ARNT2 dimerization, reinforcing the dimer as the functional unit in feeding control.

    Evidence Co-IP, reporter assay, homology modeling of PAS dimerization interface

    PMID:24814368

    Open questions at the time
    • Dimerization interface not structurally confirmed
    • In vivo metabolic effect of specific variants not tested here
  12. 2018 High

    Linked an ARNT2 hypomorphic allele directly to hyperphagic obesity and metabolic dysfunction with reduced SIM1-dependent transcription, providing causal genetic-biochemical coupling.

    Evidence ENU screen, CRISPR/Cas9 knock-in (R74C), metabolic phenotyping, SIM1 co-expression transcription assay

    PMID:30563851

    Open questions at the time
    • Neural circuit mediating obesity not pinpointed
    • Target genes downstream of weakened ARNT2/SIM1 not defined
  13. 2022 High

    Provided structural mechanism for ARNT2 heterodimer assembly, showing NPAS4-ARNT2 quaternary architecture with interconnected PAS domains and ligand-accessible PAS-B pockets.

    Evidence X-ray crystallography of NPAS4-ARNT and NPAS4-ARNT2 DNA complexes, biochemical and cell-based assays

    PMID:36343253

    Open questions at the time
    • Endogenous ligands for PAS-B pockets not identified
    • Conformational dynamics in solution not resolved
  14. 2024 High

    Defined a cell-autonomous neuronal-circuit role for ARNT2 in somatostatin interneurons governing affective empathy, extending ARNT2 function to adult behavior.

    Evidence Conditional ARNT2 ablation in SST interneurons, in vivo Ca2+ imaging, electrophysiology, behavior in mice

    PMID:39180750

    Open questions at the time
    • Transcriptional targets in SST interneurons not identified
    • Dimerization partner in this context not assigned

Open questions

Synthesis pass · forward-looking unresolved questions
  • The specific DNA target repertoire and partner usage of ARNT2 across each tissue and disease context, and the identity of physiological PAS-B ligands, remain undefined.
  • No genome-wide ARNT2 occupancy map across partners
  • Endogenous PAS-B ligands unknown
  • Mechanism connecting partner choice to context-specific outputs unresolved

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 6 GO:0003677 DNA binding 4
Localization
GO:0005634 nucleus 2
Pathway
R-HSA-1266738 Developmental Biology 4 R-HSA-74160 Gene expression (Transcription) 3 R-HSA-8953897 Cellular responses to stimuli 2
Partners
AHRARNTHIF1ANCOR2NDNNPAS4SIM1
Complex memberships
ARNT2:AHR heterodimerARNT2:HIF-1alpha heterodimerARNT2:NPAS4 heterodimerARNT2:SIM1 heterodimer

Evidence

Reading pass · 23 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1996 ARNT2 interacts with AHR and SIM1 (mouse Sim) as efficiently as ARNT1, and the ARNT2-AHR complex specifically binds the xenobiotic responsive element (XRE) sequence. ARNT2 successfully rescued XRE-driven reporter gene activity in ARNT-defective Hepa-1 c4 mutant cells. Coimmunoprecipitation, gel mobility shift assay, yeast two-hybrid system, reporter gene rescue assay Molecular and cellular biology High 8657146
2000 ARNT2 forms functional HIF complexes in vivo; ARNT2 restores hypoxia-induced gene expression to ARNT-deficient ES cells and hepatocytes, demonstrating that ARNT2/HIF-1alpha heterodimers can mediate oxygen-responsive transcription. Complementation assay in ARNT-deficient ES cells and hepatocytes; in vivo teratocarcinoma VEGF expression analysis Biochemical and biophysical research communications High 10873592 11381139
2000 ARNT2 acts as the dimerization partner of SIM1 for hypothalamic development: SIM1 and ARNT2 form dimers in vitro, are co-expressed in the paraventricular nucleus (PVN) and supraoptic nucleus (SON), and loss of either gene affects the same sets of neuroendocrine cell types. In vitro dimerization assay, co-expression analysis by in situ hybridization, genetic loss-of-function comparison Mechanisms of development High 10640708 11318878 11381139
2001 Arnt2 null mice die perinatally with impaired hypothalamic development (hypocellular PVN/SON) identical to Sim1 mutant mice; cultured Arnt2-/- neurons show decreased hypoxic induction of HIF-1 target genes, demonstrating that ARNT2/HIF-1alpha complexes regulate oxygen-responsive genes. A strong genetic interaction between Arnt and Arnt2 was observed, indicating dose-dependent functional overlap before embryonic day 8.5. Targeted gene knockout, histology, immunostaining, hypoxia-responsive gene induction assay in primary neurons, genetic epistasis (Arnt;Arnt2 double heterozygotes) Proceedings of the National Academy of Sciences of the United States of America High 11381139
2001 ARNT2 is required for the final differentiation stages of secretory neurons in the hypothalamic PVN and SON (arginine vasopressin, oxytocin, CRH, and somatostatin neurons are absent in Arnt2 knockout mice); Brn2+ precursors appear but fail to express neurosecretory hormones, placing ARNT2 function at a late differentiation step. Gene targeting knockout, immunohistochemistry, in situ hybridization for hormone markers and Brn2 Genes to cells : devoted to molecular & cellular mechanisms High 11318878
2006 ARNT2 is practically incapable of supporting AHR-driven xenobiotic-responsive gene induction (XRE-reporter and CYP1A1), unlike ARNT1. This functional difference is attributed to a single His/Pro amino acid difference in the PASB domain. Conversely, ARNT and ARNT2 show similar levels of HIF-alpha-dependent hypoxia response element (HRE)-driven reporter expression. Stable and transient expression of wild-type, mutant, and chimeric ARNT/ARNT2 constructs in Hepa1-c4 cells; reporter gene assays; endogenous gene (CYP1A1, Glut-1) induction assays; site-directed mutagenesis The Journal of biological chemistry High 17023418
2007 Necdin (NDN) directly interacts with ARNT2 via separate domains and can also interact with HIF1alpha; NDN represses transcriptional activation mediated by ARNT2:SIM1 and ARNT2:HIF1alpha complexes. The N-terminal 115 residues of NDN are sufficient for interaction with the bHLH domains of ARNT2 or HIF1alpha but not for transcriptional repression. Co-immunoprecipitation, pulldown, GAL4 fusion reporter assay, domain deletion analysis Biochemical and biophysical research communications Medium 17826745
2007 In vitro, ARNT2 dimerizes equally with AHR in the presence of TCDD and can outcompete ARNT1 for AHR binding when expressed in excess. However, in Hepa-1 cell culture, ARNT2 is largely unable to induce endogenous CYP1A1 protein, and mutation of Pro352 to His in ARNT2 (mimicking ARNT1) failed to rescue AHR-mediated signaling. Expression of ARNT2 in wild-type Hepa-1 cells reduced TCDD-mediated CYP1A1 induction by ~30%. In vitro dimerization assay, co-immunoprecipitation, Western blot, site-directed mutagenesis, endogenous CYP1A1 protein induction assay Toxicological sciences : an official journal of the Society of Toxicology Medium 18096572
2000 Zebrafish ARNT2b (full-length) forms a functional heterodimer with zfAHR2 that specifically recognizes dioxin-responsive elements (XREs) in gel shift experiments and induces XRE-driven transcription in COS-7 cells treated with TCDD. In contrast, zfARNT2a (a splice variant lacking C-terminal sequences) fails to induce reporter activity, due to inefficient DNA binding of the zfARNT2a/zfAHR2 complex. Reporter gene assay, DNA gel shift (EMSA), RT-PCR tissue distribution, COS-7 cell cotransfection Biochimica et biophysica acta Medium 11072074
2003 SIM1 and ARNT2 cooperatively activate a downstream transcriptional program in neuronal cells: microarray and Northern blot analysis identified 268 potential target genes upregulated >1.7-fold by SIM1/ARNT2 in an inducible neuronal cell system, including Jak2 and thyroid hormone receptor beta2 whose expression was lost in the Sim1 mutant hypothalamus. Inducible expression system in neuronal cell line combined with microarray and Northern blot; in vivo validation by in situ hybridization in Sim1 mutant mice The Journal of biological chemistry Medium 12947113
2013 In zebrafish, Sim1a and Arnt2 transcription factors negatively regulate robo3a.1 expression; depletion of either Sim1a or Arnt2 increases robo3a.1 levels in the hypothalamus, which in turn attenuates Robo2-mediated repulsive axon guidance, displacing hypothalamo-spinal longitudinal axons toward the midline. This phenotype is suppressed in robo3 mutant embryos. Morpholino knockdown, genetic epistasis with robo3 mutant, in situ hybridization, axon tracing Development (Cambridge, England) Medium 23222439
2013 During neuronal differentiation, the Arnt2 promoter transitions from a bivalent state (H3K4me3 + H3K27me3) in P19/ES cells to loss of the repressive H3K27me3 mark, allowing high Arnt2 expression. The Arnt2 promoter is heavily methylated in hepatoma (Arnt-only) cells. mRNA half-lives of Arnt and Arnt2 are similar in both cell types, indicating that the reciprocal expression switch is transcriptionally regulated via epigenetic mechanisms. ChIP for H3K4me3/H3K27me3, bisulfite sequencing, mRNA half-life measurement, P19 neuronal differentiation model Nucleic acids research Medium 23599003
2013 A human ARNT2 variant R46W reduces transcriptional activity of the NPAS4/ARNT2 heterodimer on a reporter gene due to disruption of nuclear localization of ARNT2; a second variant R107H also significantly reduces transcriptional activity. Luciferase reporter assay, subcellular localization analysis, site-directed mutagenesis of human variants PloS one Medium 24465693
2014 Low-activity SIM1 variants found in obese humans frequently cause impaired dimerization with ARNT2. Homology modeling of the SIM1 PAS-A and PAS-B domains identified a mutational hot-spot critical for SIM1–ARNT2 dimerization. Co-immunoprecipitation, luciferase reporter assay, homology modelling of PAS domain dimerization interface The Biochemical journal Medium 24814368
2022 Crystal structures of NPAS4-ARNT and NPAS4-ARNT2 heterodimers in complex with DNA response elements reveal uniquely interconnected domain conformations: ARNT and ARNT2 PAS-A domains adopt variable conformations within these two heterodimers, and the ARNT PAS-A domain forms a distinct interface with the PAS-A and PAS-B domains of NPAS4. PAS-B domains of NPAS4, ARNT, and ARNT2 all contain ligand-accessible pockets. X-ray crystallography (quaternary heterodimer structures), biochemical assays, cell-based functional assays Proceedings of the National Academy of Sciences of the United States of America High 36343253
2018 A missense mutation Arg74Cys (R74C) in ARNT2 (a hypomorphic allele identified by ENU mutagenesis and confirmed by CRISPR/Cas9 knock-in) causes hyperphagic obesity, hepatic steatosis, and abnormal glucose homeostasis in mice. The mutant ARNT2 protein shows decreased transcriptional activity when co-expressed with SIM1. ENU mutagenesis screen, CRISPR/Cas9 recapitulation, metabolic phenotyping, co-expression transcriptional activity assay Disease models & mechanisms High 30563851
2013 Loss-of-function mutation in ARNT2 (homozygous frameshift c.1373_1374dupTC) in humans results in absence of detectable ARNT2 transcript and protein (consistent with nonsense-mediated decay), causing secondary microcephaly, multiple pituitary hormone deficiency, visual impairment, and renal anomalies, establishing ARNT2 as essential for hypothalamo-pituitary axis development in humans. Homozygosity mapping, exome sequencing, RT-PCR and Western blot from patient fibroblasts (demonstrating loss of transcript and protein), immunohistochemistry of human embryonic tissue Brain : a journal of neurology High 24022475
2019 ARNT2 forms a complex with NCoR2 that plays a dual (Yin/Yang) role in activity-dependent transcription in neurons (referenced mechanistic discovery reported by Sharma et al. 2019 as described in this commentary). Activity-dependent transcriptome analysis (as summarized in commentary) Neuron Low 30998895
2024 ARNT2 expression in somatostatin (SST)-expressing interneurons of the anterior cingulate cortex (ACC) is required for affective empathy (observational fear) in mice: selective ARNT2 ablation in SST interneurons reduces pyramidal cell excitability, increases spontaneous firing, disrupts Ca2+ dynamics and theta oscillations in the ACC, resulting in reduced vicarious freezing. Forward genetic mapping, transcriptome analysis, conditional ARNT2 ablation in SST interneurons, in vivo Ca2+ imaging, electrophysiology, behavioral testing Cell reports High 39180750
2023 In zebrafish, arnt1 and arnt2 are jointly required for hemato-vascular specification: arnt1;arnt2 double mutants (but not single mutants) lack blood cells and most endothelial cells, with absent expression of earliest endothelial/hematopoietic transcription factors etsrp and tal1. Npas4l binds both Arnt1 and Arnt2 proteins in vitro, indicating these factors form a multimeric complex to specify hemato-vascular fate. Genetic double mutant analysis, in situ hybridization for etsrp/tal1, in vitro binding assay (Npas4l with Arnt1/Arnt2) Development (Cambridge, England) Medium 37039097
2001 ARNT2 immunoreactivity is localized exclusively to nuclei of brain neurons and PC12 cells. Downregulation of ARNT2 by antisense oligonucleotides in PC12 cells prevented cell proliferation and induced apoptosis. Cell death from focal ischemia or oxidative stress was preceded by near-complete suppression of ARNT2 expression. Immunocytochemistry (subcellular localization), antisense oligonucleotide knockdown with apoptosis/proliferation readout, focal ischemia model The European journal of neuroscience Medium 10215907
2017 ARNT2 knockdown in glioblastoma stem-like cells decreased expression of SOX9, POU3F2, and OLIG2 (transcription factors implicated in GBM tumorigenicity) and repressed tumorigenic properties in vivo, positioning ARNT2 upstream of these oncogenic transcription factors in GBM. siRNA knockdown, in vivo xenograft tumorigenicity assay, ChIP for histone marks (H3K4me3/H3K27me3) to identify ARNT2 in tumorigenic signature Acta neuropathologica Medium 29149419
2025 ARNT2 directly binds the STRA6 promoter to transcriptionally upregulate STRA6, thereby reprogramming fatty acid metabolism (elevating fatty acid metabolic enzymes, lipid droplet accumulation, and triglycerides) and promoting retroperitoneal liposarcoma cell proliferation and invasion. ChIP (ARNT2 binding to STRA6 promoter), promoter reporter assay, CCK8, Transwell invasion, lipid droplet/triglyceride quantification, in vivo xenograft Journal of cancer research and clinical oncology Medium 41108418

Source papers

Stage 0 corpus · 57 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1998 Expression of ARNT, ARNT2, HIF1 alpha, HIF2 alpha and Ah receptor mRNAs in the developing mouse. Mechanisms of development 272 9545558
1996 cDNA cloning and tissue-specific expression of a novel basic helix-loop-helix/PAS factor (Arnt2) with close sequence similarity to the aryl hydrocarbon receptor nuclear translocator (Arnt). Molecular and cellular biology 220 8657146
2002 Tissue-specific expression of AHR2, ARNT2, and CYP1A in zebrafish embryos and larvae: effects of developmental stage and 2,3,7,8-tetrachlorodibenzo-p-dioxin exposure. Toxicological sciences : an official journal of the Society of Toxicology 180 12151636
2000 ARNT2 acts as the dimerization partner of SIM1 for the development of the hypothalamus. Mechanisms of development 144 10640708
2001 Targeted mutation of the murine arylhydrocarbon receptor nuclear translocator 2 (Arnt2) gene reveals partial redundancy with Arnt. Proceedings of the National Academy of Sciences of the United States of America 131 11381139
2001 Defective development of secretory neurones in the hypothalamus of Arnt2-knockout mice. Genes to cells : devoted to molecular & cellular mechanisms 94 11318878
2000 The role of ARNT2 in tumor angiogenesis and the neural response to hypoxia. Biochemical and biophysical research communications 84 10873592
2000 Developmental and tissue-specific expression of AHR1, AHR2, and ARNT2 in dioxin-sensitive and -resistant populations of the marine fish Fundulus heteroclitus. Toxicological sciences : an official journal of the Society of Toxicology 78 11006353
2000 Identification and expression of alternatively spliced aryl hydrocarbon nuclear translocator 2 (ARNT2) cDNAs from zebrafish with distinct functions. Biochimica et biophysica acta 76 11072074
1996 Cloning and selective expression in brain and kidney of ARNT2 homologous to the Ah receptor nuclear translocator (ARNT). Biochemical and biophysical research communications 76 8753765
2013 ARNT2 mutation causes hypopituitarism, post-natal microcephaly, visual and renal anomalies. Brain : a journal of neurology 50 24022475
2006 Unique and overlapping transcriptional roles of arylhydrocarbon receptor nuclear translocator (Arnt) and Arnt2 in xenobiotic and hypoxic responses. The Journal of biological chemistry 47 17023418
2003 Expression of Arnt and Arnt2 mRNA in developing murine tissues. The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society 46 12502753
1999 Functional diversity of vertebrate ARNT proteins: identification of ARNT2 as the predominant form of ARNT in the marine teleost, Fundulus heteroclitus. Archives of biochemistry and biophysics 45 9882441
2007 Analysis of Ah receptor-ARNT and Ah receptor-ARNT2 complexes in vitro and in cell culture. Toxicological sciences : an official journal of the Society of Toxicology 44 18096572
2004 ARNT2 is not required for TCDD developmental toxicity in zebrafish. Toxicological sciences : an official journal of the Society of Toxicology 39 15282404
2003 Identification of the downstream targets of SIM1 and ARNT2, a pair of transcription factors essential for neuroendocrine cell differentiation. The Journal of biological chemistry 37 12947113
2002 Identification and functional characterization of hypoxia-inducible factor 2alpha from the estuarine teleost, Fundulus heteroclitus: interaction of HIF-2alpha with two ARNT2 splice variants. The Journal of experimental zoology 36 11932946
2016 ARNT2 Regulates Tumoral Growth in Oral Squamous Cell Carcinoma. Journal of Cancer 32 27076852
2013 Reciprocal regulation of the basic helix-loop-helix/Per-Arnt-Sim partner proteins, Arnt and Arnt2, during neuronal differentiation. Nucleic acids research 30 23599003
1999 ARNT2, a transcription factor for brain neuron survival? The European journal of neuroscience 30 10215907
2022 Structures of NPAS4-ARNT and NPAS4-ARNT2 heterodimers reveal new dimerization modalities in the bHLH-PAS transcription factor family. Proceedings of the National Academy of Sciences of the United States of America 29 36343253
2018 Fine Particulate Matter (PM2.5) Promoted the Invasion of Lung Cancer Cells via an ARNT2/PP2A/STAT3/MMP2 Pathway. Journal of biomedical nanotechnology 27 30305224
2013 Sim1a and Arnt2 contribute to hypothalamo-spinal axon guidance by regulating Robo2 activity via a Robo3-dependent mechanism. Development (Cambridge, England) 25 23222439
2000 Two splice variants of the hypoxia-inducible factor HIF-1alpha as potential dimerization partners of ARNT2 in neurons. The European journal of neuroscience 25 11029639
2017 Changes in chromatin state reveal ARNT2 at a node of a tumorigenic transcription factor signature driving glioblastoma cell aggressiveness. Acta neuropathologica 24 29149419
2001 Ectopic expression of negative ARNT2 factor disrupts fish development. Biochemical and biophysical research communications 22 11401485
2014 Human variants in the neuronal basic helix-loop-helix/Per-Arnt-Sim (bHLH/PAS) transcription factor complex NPAS4/ARNT2 disrupt function. PloS one 21 24465693
2016 Hepatoprotective and antioxidant effects of dietary Glycyrrhiza polysaccharide against TCDD-induced hepatic injury and RT-PCR quantification of AHR2, ARNT2, CYP1A mRNA in Jian Carp (Cyprinus carpio var. Jian). Journal of environmental sciences (China) 18 28115129
2009 Potential roles of Arnt2 in zebrafish larval development. Zebrafish 18 19374551
2003 Identification of novel splice variants of ARNT and ARNT2 in the rat. Biochemical and biophysical research communications 18 12684048
2000 Overexpression of a Zebrafish ARNT2-like Factor Represses CYP1A Transcription in ZLE Cells. Marine biotechnology (New York, N.Y.) 18 10960127
2015 ARNT2 is downregulated and serves as a potential tumor suppressor gene in non-small cell lung cancer. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 17 25613063
2010 Molecular and functional characterization of aryl hydrocarbon receptor nuclear translocator 1 (ARNT1) and ARNT2 in chicken (Gallus gallus). Comparative biochemistry and physiology. Toxicology & pharmacology : CBP 17 21134488
1998 Physical localization of the mouse aryl hydrocarbon receptor nuclear translocator-2 (Arnt2) gene within the c112K deletion. Genomics 17 9722945
2003 ARNT gene multiplicity in amphibians: characterization of ARNT2 from the frog Xenopus laevis. Journal of experimental zoology. Part B, Molecular and developmental evolution 16 14984034
2007 Separate necdin domains bind ARNT2 and HIF1alpha and repress transcription. Biochemical and biophysical research communications 15 17826745
2002 2,3,7,8-tetrachlorodibenzo-p-dioxin causes alterations in lymphocyte development and thymic atrophy in hemopoietic chimeras generated from mice deficient in ARNT2. Toxicological sciences : an official journal of the Society of Toxicology 15 12215665
2007 Molecular characterization and tissue distribution of aryl hydrocarbon receptor nuclear translocator isoforms, ARNT1 and ARNT2, and identification of novel splice variants in common cormorant (Phalacrocorax carbo). Comparative biochemistry and physiology. Toxicology & pharmacology : CBP 14 17337252
2018 Emotion recognition associated with polymorphism in oxytocinergic pathway gene ARNT2. Social cognitive and affective neuroscience 13 29194499
2015 Genetic variant rs17225178 in the ARNT2 gene is associated with Asperger Syndrome. Molecular autism 12 25745553
2018 Molecular cloning and characterization of two ARNT (ARNT-1 and ARNT-2) genes in Atlantic croaker and their expression during coexposure to hypoxia and PCB77. Environmental toxicology 10 30334616
2020 Polymorphisms within the ARNT2 and CX3CR1 Genes Are Associated with the Risk of Developing Invasive Aspergillosis. Infection and immunity 9 31964743
2014 Characterization of human variants in obesity-related SIM1 protein identifies a hot-spot for dimerization with the partner protein ARNT2. The Biochemical journal 9 24814368
2014 Differential distribution of hypoxia-inducible factor 1-beta (ARNT or ARNT2) in mouse substantia nigra and ventral tegmental area. Journal of chemical neuroanatomy 9 25017895
2002 Aryl hydrocarbon receptor nuclear translocator 2 (ARNT2): structure, gene mapping, polymorphisms, and candidate evaluation for human orofacial clefts. Teratology 8 12210012
2018 A viable hypomorphic Arnt2 mutation causes hyperphagic obesity, diabetes and hepatic steatosis. Disease models & mechanisms 7 30563851
2024 ARNT2 controls prefrontal somatostatin interneurons mediating affective empathy. Cell reports 5 39180750
2020 Oligodendrocyte ARNT2 expression is altered in models of MS. Neurology(R) neuroimmunology & neuroinflammation 5 32439712
2025 Pan-cancer analysis of ARNT2 and its oncogenic role in cervical cancer. Journal of gynecologic oncology 3 40488594
2023 Hemato-vascular specification requires arnt1 and arnt2 genes in zebrafish embryos. Development (Cambridge, England) 3 37039097
2020 Aryl hydrocarbon receptor nuclear translocators (ARNT1, ARNT2, and ARNT3) of white sturgeon (Acipenser transmontanus): Sequences, tissue-specific expressions, and response to β-naphthoflavone. Comparative biochemistry and physiology. Toxicology & pharmacology : CBP 3 32081761
2019 The Yin and Yang of Arnt2 in Activity-Dependent Transcription. Neuron 1 30998895
2010 [Effects of ARNT2 gene on invasion and migration of human hepatocellular carcinoma HCCLM6 cell line]. Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology 1 20128965
2026 ARNT2 repression disrupts neuronal identity and promotes glioblastoma growth. Cell communication and signaling : CCS 0 42063073
2025 Identification of a Novel Gene ARNT2 for Osteogenic Differentiation of Mesenchymal Stem Cells. Calcified tissue international 0 40679635
2025 ARNT2-driven transcriptional activation of STRA6 reprograms fatty acid metabolism to promote retroperitoneal liposarcoma progression. Journal of cancer research and clinical oncology 0 41108418

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