Affinage

Showing BMAL2 — ARNTL2 is a alias.

BMAL2

Basic helix-loop-helix ARNT-like protein 2 · UniProt Q8WYA1

Length
636 aa
Mass
70.9 kDa
Annotated
2026-06-09
44 papers in source corpus 27 papers cited in narrative 27 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

BMAL2 (ARNTL2) is a bHLH-PAS transcription factor that heterodimerizes with CLOCK, NPAS2/MOP4, and HIF1α to drive E-box-dependent transcription of circadian and clock-controlled genes, functioning as a core but dose-sensitive component of the molecular clock (PMID:10864977, PMID:11554928). It is structurally related to BMAL1 and is sufficient to substitute for it: constitutive BMAL2 expression rescues the circadian locomotor and metabolic defects of Bmal1-knockout mice, establishing functional redundancy between the two paralogs (PMID:20153195). Its transcriptional output is tuned at multiple levels — alternative splicing generates isoforms of graded activity, high BMAL2 levels switch it from an activator to a repressor of E-box transcription, and PER2 binds and inhibits CLOCK:BMAL2 more potently than CLOCK:BMAL1 while CRY2 preferentially inhibits CLOCK:BMAL1 (PMID:12055078, PMID:11554928, PMID:19605937). Genetic deletion in mice shortens free-running period and disrupts SCN metabolic gene rhythms, food-anticipatory activity, and energy balance, producing increased adiposity, hepatic steatosis, and insulin resistance (PMID:38531632, PMID:40983272). BMAL2 expression is itself regulated by inflammatory and nutrient signaling, including NF-κB-driven induction downstream of TNF and stabilization by mTOR/MAPK signaling, and it feeds back to restrain adipogenesis by promoting BMAL1 degradation and suppressing the MAPK–C/EBPβ and KLF15 programs (PMID:30210560, PMID:36329012). In cancer, BMAL2 acts as a direct promoter-binding transcriptional regulator of metabolic and survival genes — it transactivates ACOT7, MRPL15, SLC7A11, SLC31A1/ENO1, and ANXA2 to support glycolysis and suppress ferroptosis, represses AMOTL2 to enhance YAP nuclear activity, stabilizes HIF1A while destabilizing HIF2A downstream of KRAS, and sustains RAD51-dependent homologous recombination repair (PMID:37003979, PMID:41075325, PMID:40753759, PMID:39147318, PMID:41243277, PMID:38956029, PMID:36993718, PMID:41933240). In immune cells it binds the Il21 and PD-L1 promoters to control IL-21 production, thymocyte apoptosis, and macrophage endotoxin tolerance (PMID:24520124, PMID:27671790, PMID:38938563). BMAL2 protein is targeted for ubiquitin-proteasome degradation by melatonin and by a high-affinity small-molecule ligand, providing pharmacological handles on its activity (PMID:40753759, PMID:41933240).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 2000 Medium

    Established BMAL2 as a bHLH-PAS factor that partners with circadian and hypoxia transcription factors, defining its molecular identity and candidate partners.

    Evidence Heterodimer formation and transcriptional activity assays with CLOCK, NPAS2, HIF1α; SCN co-expression; cDNA cloning and tissue expression analysis

    PMID:10864977 PMID:10964693

    Open questions at the time
    • Endogenous target genes not yet defined
    • Functional consequence of HIF1α partnership not tested in vivo
  2. 2002 Medium

    Showed that CLOCK:BMAL2 transcriptional amplitude is tunable by alternative splicing and by BMAL2 dosage, indicating bidirectional regulatory behavior rather than a simple activator role.

    Evidence RT-PCR splice variant identification and luciferase reporter assays on Per1, vasopressin, PAI-1 promoters; chicken ortholog overexpression in pineal cells

    PMID:11554928 PMID:12055078

    Open questions at the time
    • Physiological splice-isoform abundance unknown
    • Mechanism of dose-dependent repression not resolved
  3. 2003 Medium

    Demonstrated that CLOCK:BMAL2 contributes additively with CLOCK:BMAL1 to E-box-driven promoter activity and is suppressed redox-independently by PER/CRY, positioning it within the clock feedback loop.

    Evidence Luciferase reporter assays with E-box mutants in endothelial cells (PAI-1 promoter); antisense BMAL2 cell-cycle and colony assays

    PMID:12738229 PMID:12917632

    Open questions at the time
    • Endogenous occupancy of PAI-1 E-boxes not shown
    • Proliferation phenotype mechanism uncharacterized
  4. 2009 High

    Resolved paralog-specific repression: PER2 preferentially binds and inhibits BMAL2, while CRY2 preferentially inhibits BMAL1, and BMAL2 knockdown blunts cellular clock rhythms.

    Evidence Co-immunoprecipitation, luciferase reporter assays, siRNA with Bmal1-promoter bioluminescence rhythm monitoring

    PMID:19605937

    Open questions at the time
    • Structural basis of differential PER2/CRY2 binding unknown
    • Cell-type generality of rhythm contribution untested
  5. 2010 High

    Proved BMAL1/BMAL2 functional redundancy by genetic rescue, reframing BMAL2 as a bona fide core clock and metabolic regulator rather than an accessory factor.

    Evidence Transgenic constitutive BMAL2 rescue of Bmal1-knockout mice with locomotor and metabolic phenotyping

    PMID:20153195

    Open questions at the time
    • Endogenous tissue-specific roles of BMAL2 not separated from BMAL1
    • Whether redundancy is reciprocal in all tissues unknown
  6. 2014 Medium

    Identified a direct immunoregulatory target, showing ARNTL2 binds the Il21 promoter allele-specifically and represses IL-21 to control T-cell numbers.

    Evidence ChIP at Il21 promoter, transcriptome analysis, T-cell quantification in congenic mice

    PMID:24520124

    Open questions at the time
    • Whether repression requires CLOCK heterodimer not addressed
    • Direct vs indirect effect on T-cell subsets unresolved
  7. 2016 High

    Established BMAL2 as a driver of cancer metastasis and immune phenotypes, linking its transcriptional output to a pro-metastatic secretome and to thymocyte apoptosis via IL-21 epistasis.

    Evidence In vivo lung adenocarcinoma metastasis assays, CLOCK Co-IP, SMOC2 validation; Arntl2-knockout thymocyte assays with IL-21 rescue

    PMID:27150038 PMID:27671790

    Open questions at the time
    • Direct promoter targets of the secretome program not mapped
    • Upstream signals activating BMAL2 in tumors not defined here
  8. 2017 Medium

    Connected inflammatory signaling to BMAL2 regulation, showing TNF drives NF-κB-dependent ARNTL2/NPAS2 induction and nuclear localization, while the ARNTL2/NPAS2 dimer is a weaker clock-gene inducer than ARNTL1/NPAS2.

    Evidence Reporter assays in HEK293, immunofluorescence, RT-qPCR with IKK-2 inhibitor in human fibroblasts

    PMID:30210560

    Open questions at the time
    • In vivo relevance of TNF–ARNTL2 axis untested
    • Functional outcome of weaker clock-gene induction unclear
  9. 2022 Medium

    Defined a feedback role in adipogenesis whereby ARNTL2 destabilizes BMAL1 and suppresses MAPK–C/EBPβ/KLF15, with its own stability set by mTOR/MAPK signaling.

    Evidence Overexpression, siRNA, Western blot, gene expression in human adipose stem/progenitor cells

    PMID:36329012

    Open questions at the time
    • Mechanism of BMAL1 degradation not detailed
    • Direct transcriptional targets vs signaling effects not separated
  10. 2023 Medium

    Began mapping direct cancer target promoters, showing ARNTL2 transactivates ACOT7 to drive fatty acid synthesis and suppress ferroptosis in NSCLC.

    Evidence Dual luciferase, ChIP-qPCR, gain/loss-of-function, ferroptosis/apoptosis assays

    PMID:37003979

    Open questions at the time
    • Requirement for CLOCK heterodimer at ACOT7 not tested
    • Whether circadian timing modulates ACOT7 regulation unknown
  11. 2024 High

    Through a dedicated knockout, established BMAL2 as a non-redundant regulator of period length, SCN metabolic gene rhythms, food-anticipatory activity, and systemic energy balance.

    Evidence Bmal2-knockout mice with locomotor, feeding, and metabolic phenotyping and SCN/hypothalamic gene expression

    PMID:38531632

    Open questions at the time
    • Direct SCN target genes underlying period change not identified
    • Cell-autonomous vs circuit-level contributions unresolved
  12. 2024 Medium

    Expanded the direct-target repertoire across cancers, showing BMAL2 represses AMOTL2 to activate YAP, upregulates SLC31A1/ENO1 glycolysis, enhances HIF1A-driven aerobic glycolysis, and is itself epigenetically activated at its promoter and induced via TREM-1 to drive PD-L1.

    Evidence ChIP, luciferase, glycolysis/invasion assays, xenografts (NPC, bladder, AML/NSCLC); LINC01232/p300 RIP-ChIP; CRISPR activation with BIAcore PD-L1 binding

    PMID:38660843 PMID:38938563 PMID:38956029 PMID:39147318 PMID:39268727

    Open questions at the time
    • HIF1A link (idx 18) is Low-confidence and single-study
    • Direct vs cofactor-dependent binding at several promoters not fully resolved
  13. 2025 High

    Consolidated BMAL2 as a multi-target transcriptional driver of cancer metabolism, ferroptosis resistance, and DNA repair, and identified druggable degradation as a therapeutic strategy.

    Evidence ChIP/luciferase for SLC7A11, MRPL15, ANXA2; HIF1A/HIF2A stability in PDAC (preprint); RAD51/HR and DNA-damage assays with small-molecule degrader; melatonin-induced ubiquitin-proteasome degradation; Bmal2-KO obesity phenotyping

    PMID:36993718 PMID:40753759 PMID:40983272 PMID:41075325 PMID:41243277 PMID:41933240

    Open questions at the time
    • Whether a single DNA-binding mode unifies these diverse targets is unknown
    • Mechanism distinguishing HIF1A stabilization from HIF2A destabilization not defined
    • Degrader specificity over BMAL1 not established

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unknown how BMAL2 selects between activator and repressor modes and between its circadian, metabolic, immune, and oncogenic target genes, and whether these cancer targets require CLOCK/NPAS2 heterodimerization and circadian timing.
  • No genome-wide endogenous BMAL2 occupancy map across contexts
  • Structural determinants of paralog-specific cofactor binding undefined
  • Causal Mendelian disease link not established in the corpus

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 12 GO:0003677 DNA binding 7 GO:0140097 catalytic activity, acting on DNA 1
Localization
GO:0005634 nucleus 1
Pathway
R-HSA-1643685 Disease 8 R-HSA-74160 Gene expression (Transcription) 6 R-HSA-1430728 Metabolism 5 R-HSA-9909396 Circadian clock 4 R-HSA-168256 Immune System 3 R-HSA-73894 DNA Repair 1
Partners
BMAL1CLOCKCRY2HIF1ANPAS2PER2

Evidence

Reading pass · 27 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2000 BMAL2 (MOP9) forms transcriptionally active heterodimers with CLOCK, MOP4/NPAS2, and HIF1α, and is co-expressed with CLOCK in the suprachiasmatic nucleus, consistent with a role as a biologically relevant partner of these circadian and hypoxia factors. Heterodimer formation and transcriptional activity assays; co-expression analysis in brain regions The Journal of neuroscience Medium 10864977
2000 BMAL2 encodes a bHLH-PAS transcription factor with 49% overall identity to BMAL1; its mRNA expression is restricted to fetal brain and adult liver in humans, distinct from BMAL1 expression in brain and skeletal muscle. cDNA cloning, RNA analysis, FISH chromosomal localization Biochemical and biophysical research communications Medium 10964693
2001 Chicken BMAL2 forms heterodimers with cCLOCK and activates E-box-dependent transcription; co-expression of cCLOCK, cBMAL1 and cBMAL2 cooperatively activates E-box transcription, but higher levels of cBMAL2 inhibit this activation, suggesting BMAL2 acts as a bidirectional regulator. cBMAL2 overexpression also disrupts circadian melatonin rhythms in pineal cells. In vitro heteromer formation assays, luciferase reporter assays, overexpression in cultured pineal cells measuring melatonin rhythms Genes to cells Medium 11554928
2002 Alternative splicing of BMAL2 generates multiple isoforms with high, medium, low, or no transcriptional activity when assayed as CLOCK:BMAL2 heterodimers on Per1, vasopressin, and PAI-1 promoters, indicating that alternative splicing regulates the amplitude of CLOCK:BMAL2-driven transcription. Identification of splice variants by RT-PCR, luciferase reporter gene assays with three different promoters American journal of physiology. Cell physiology Medium 12055078
2003 Both CLOCK:BMAL1 and CLOCK:BMAL2 heterodimers activate the human PAI-1 promoter through proximal and distal E-box enhancers in transfected endothelial cells. CLOCK:BMAL1 and CLOCK:BMAL2 make additive contributions. Period and cryptochrome proteins inhibit both heterodimers equivalently, and this inhibition is redox independent. Transfection-based luciferase reporter assays in endothelial cells, E-box mutational analysis Journal of molecular and cellular cardiology Medium 12738229
2003 Antisense overexpression of BMAL2 in 293EBNA cells reduces cell cycle time, increases colony formation in soft agar, diminishes TNF-α-induced caspase-3 activity, and shifts cells from G2 to S phase, indicating BMAL2 normally suppresses cell proliferation. Antisense RNA overexpression, cell cycle analysis, soft agar colony assay, caspase-3 activity assay Oncogene Medium 12917632
2009 PER2 preferentially inhibits BMAL2-CLOCK-mediated E-box transcription more strongly than BMAL1-CLOCK. PER2 shows greater binding affinity for BMAL2 than for BMAL1 by co-immunoprecipitation. CRY2 inhibits BMAL1-CLOCK more strongly than BMAL2-CLOCK. BMAL2 siRNA knockdown blunts cellular circadian rhythms as monitored by Bmal1 promoter-driven bioluminescence. Co-immunoprecipitation, luciferase reporter assays, RNA interference with bioluminescence rhythm monitoring The Journal of biological chemistry High 19605937
2010 Constitutive expression of BMAL2 from a non-circadian promoter rescues the clock and metabolic phenotypes of Bmal1-knockout mice, including rhythmic locomotor activity, rhythmic metabolism, low body weight, and enhanced fat deposition, demonstrating that BMAL2 and BMAL1 are functionally redundant. Bmal1 knockout downregulates Bmal2, effectively creating a functional double knockout. Transgenic rescue of Bmal1-knockout mice using constitutive BMAL2 expression; locomotor activity monitoring; metabolic phenotype analysis Current biology : CB High 20153195
2014 ARNTL2 binds in an allele-specific manner to the RNA polymerase binding site of the Il21 promoter and inhibits IL21 expression; mice with C3H alleles at Idd6.3 carrying higher ARNTL2 produce lower numbers of CD4+IL21+, CD4+, and CD8+ T cells compared to NOD allele carriers. Transcriptome analysis, chromatin immunoprecipitation (ChIP) for ARNTL2 at Il21 promoter, T-cell quantification in congenic mice Diabetes Medium 24520124
2016 Arntl2 is required for metastatic ability of lung adenocarcinoma cells in vivo and for clonal growth in cell culture. Arntl2 drives metastatic self-sufficiency by orchestrating expression of a pro-metastatic secretome; CLOCK is identified as an Arntl2 binding partner in this context; Smoc2 is validated as a pro-metastatic secreted factor downstream of Arntl2. In vivo metastasis assays, clonal growth assays, co-immunoprecipitation of CLOCK, functional validation of SMOC2 Cancer cell High 27150038
2016 Arntl2 knockout (B6 allele) decreases thymocyte apoptosis and proliferation. ARNTL2 (C3H and B6 alleles) inhibits transcription of Il21; IL-21 injection abolishes the B6 allele-mediated decrease in apoptosis/proliferation and increases thymic Th17 cells, placing ARNTL2 upstream of IL-21 in thymocyte apoptosis control. Arntl2-/- mouse generation, thymocyte apoptosis and proliferation assays, IL-21 rescue experiment, Th17 quantification Mammalian genome High 27671790
2017 The ARNTL2/NPAS2 dimer is a weaker inducer of PER3 and DBP expression than the ARNTL1/NPAS2 dimer. TNF promotes ARNTL2 nuclear localization and upregulates ARNTL2 and NPAS2 expression via NF-κB (blocked by IKK-2 inhibitor IMD-0354) in human fibroblasts. Transfection of cloned ARNTL2/NPAS2 into HEK293 cells with reporter assays; immunofluorescence for nuclear localization; RT-qPCR with NF-κB inhibitor Journal of circadian rhythms Medium 30210560
2022 ARNTL2 protein is induced during adipogenic differentiation and inhibits adipogenesis by facilitating degradation of ARNTL1, inhibiting KLF15 gene expression, and downregulating the MAPK-C/EBPβ axis. ARNTL2 protein stability is maintained cooperatively by mTOR and MAPK signaling, and ARNTL2 itself inhibits both pathways, forming a feedback mechanism. Ectopic overexpression, siRNA knockdown, Western blot, gene expression analysis in human adipose stem/progenitor cells Cell death discovery Medium 36329012
2023 ARNTL2 directly binds to the ACOT7 gene promoter (validated by dual luciferase and ChIP-qPCR) and potentiates ACOT7 transcription; ACOT7 upregulation by ARNTL2 promotes fatty acid synthesis and suppresses lipid peroxidation, thereby inhibiting ferroptosis and apoptosis to support NSCLC cell proliferation. Dual luciferase assay, ChIP-qPCR, gain/loss-of-function experiments, ferroptosis and apoptosis assays BMC molecular and cell biology Medium 37003979
2024 BMAL2 deletion in mice (B2KO) produces shorter free-running circadian period (−14 min/cycle), loss of rhythmicity of metabolic regulators (Lipoprotein lipase, Uncoupling protein 2) in SCN, altered bimodal feeding pattern, increased adiposity, fasted hyperinsulinemia, and near-complete prevention of food-anticipatory activity, with downregulation of orexigenic neuropeptides (NPY, AgRP) in mediobasal hypothalamus. Bmal2 knockout mouse model, locomotor activity recording, metabolic phenotyping, gene expression analysis, feeding behavior analysis The Journal of neuroscience High 38531632
2024 ARNTL2 negatively regulates AMOTL2 transcription by directly binding to the AMOTL2 promoter, reducing AMOTL2 recruitment to LATS1/2 kinases, thereby enhancing YAP nuclear translocation through suppression of LATS-dependent YAP phosphorylation, promoting NPC invasion and metastasis. ChIP assay, luciferase reporter assay, loss/gain-of-function experiments, in vivo xenograft metastasis models, rescue with AMOTL2 inhibition Cell death & disease Medium 38956029
2024 ARNTL2 promotes bladder cancer glycolysis and proliferation by upregulating SLC31A1 and ENO1, with SLC31A1 enhancing ENO1 enzymatic activity; ARNTL2 drives transcription of SLC31A1 and ENO1 as shown by luciferase assay. Luciferase reporter assay, Western blot, glycolysis measurement, ENO1 activity assay, xenograft models Life sciences Medium 39147318
2024 eCIRP upregulates BMAL2 expression via TREM-1 in macrophages; BMAL2 induction correlates with increased PD-L1 expression; computational modeling and BIAcore binding assay identified a putative BMAL2 binding region in the PD-L1 promoter, suggesting BMAL2 drives PD-L1 transcription to promote macrophage endotoxin tolerance. CRISPR activation of BMAL2, BIAcore binding assay, PCR array, TREM-1 knockout macrophages, ELISA Frontiers in immunology Medium 38938563
2024 In NSCLC/AML cells, BMAL2 promotes aerobic glycolysis by enhancing HIF1A expression, and BMAL2 knockdown reduces glucose uptake and lactate production. shRNA knockdown, RT-PCR, Western blot, glucose uptake assay, lactate production assay in AML cell lines Zhongguo shi yan xue ye xue za zhi Low 38660843
2024 LINC01232 interacts with p300 to enhance H3K27ac levels at the ARNTL2 promoter, promoting ARNTL2 transcriptional activity; ARNTL2 overexpression reverses the pro-ferroptotic effect of LINC01232 knockdown in colorectal cancer cells. ChIP assay, RNA immunoprecipitation, chromatin immunoprecipitation, knockdown/overexpression experiments Epigenomics Medium 39268727
2025 ARNTL2 directly binds to the SLC7A11 promoter (ChIP assay) and enhances its transcription; ARNTL2 also influences SLC7A11 mRNA stability through PHGDH. This ARNTL2-SLC7A11 axis promotes resistance to 5-FU by suppressing ferroptosis in colon cancer. Melatonin degrades ARNTL2 via the ubiquitination-proteasome pathway. ChIP assay, luciferase reporter assay, in vitro and in vivo loss/gain-of-function experiments, ubiquitination/proteasome assay Redox biology Medium 40753759
2025 BMAL2 depletion in OCCC cells reduces RAD51 expression (a core HR pathway enzyme), leading to DNA double-strand break accumulation, decreased cell viability, and reduced tumor growth. GW833972A (cannabinoid receptor agonist) binds BMAL2 with high affinity and facilitates its protein degradation, reducing RAD51 and accumulating DNA damage. BMAL2 knockdown, RAD51 expression analysis, DNA damage assays (DSB accumulation), xenograft tumor growth, small molecule binding and degradation assay EMBO molecular medicine High 41933240
2025 BMAL2 promotes NSCLC tumorigenesis by directly binding to the MRPL15 promoter (luciferase reporter and ChIP-qPCR) and enhancing MRPL15 transcription; MRPL15 upregulation accelerates cell cycle progression and inhibits ferroptosis and apoptosis. Luciferase reporter assay, ChIP-qPCR, overexpression and knockdown experiments, ferroptosis/apoptosis assays Translational oncology Medium 41075325
2025 ARNTL2 (with CLOCK) is recruited to the ANXA2 promoter (ChIP and dual-luciferase assay) and activates ANXA2 transcription; ANXA2 protein binds the 3'UTR of C-MYC mRNA (RIP and RNA pulldown) and stabilizes C-MYC protein, promoting esophageal cancer malignant phenotypes. ChIP, dual-luciferase reporter assay, RIP, RNA pulldown, in vivo xenograft Cancer biology & therapy Medium 41243277
2025 BMAL2 is required for stabilization of HIF1A under hypoxic conditions while simultaneously destabilizing HIF2A in PDAC cells; BMAL2 knockout reduces cancer cell viability, invasion, and glycolysis, particularly under hypoxia, and impairs in vivo xenograft tumor growth. BMAL2 acts downstream of KRAS signaling. BMAL2 knockout in multiple PDAC cell lines, HIF1A/HIF2A protein stability assays, glycolysis assays, invasion assays, in vivo xenograft, regulatory network analysis bioRxivpreprint Medium 36993718
2025 Bmal2 deletion in mice leads to increased body weight gain during diet-induced obesity, increased Tnfα expression, modified adipocyte progenitor fate, reduced lipid storage in WAT, increased ectopic liver storage, hepatic steatosis, and insulin resistance in liver and WAT. Bmal2 knockout mouse model with diet-induced obesity, adipose tissue histology, metabolic phenotyping, gene expression analysis Metabolism: clinical and experimental High 40983272
2024 ARNTL2/E2F1 axis-mediated cellular glycolysis activates the PI3K/AKT signaling pathway, sensitizing pancreatic cancer cells to erlotinib treatment; ARNTL2 inhibition reduces erlotinib efficacy while ARNTL2 overexpression improves sensitivity, validated in patient-derived xenograft models. In vitro gain/loss-of-function experiments, in vivo PDX models, PI3K/AKT pathway analysis Molecular cancer Medium 38459558

Source papers

Stage 0 corpus · 44 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2003 Regulation of the PAI-1 promoter by circadian clock components: differential activation by BMAL1 and BMAL2. Journal of molecular and cellular cardiology 136 12738229
2010 Circadian clock gene Bmal1 is not essential; functional replacement with its paralog, Bmal2. Current biology : CB 120 20153195
2011 ARNTL2 and SERPINE1: potential biomarkers for tumor aggressiveness in colorectal cancer. Journal of cancer research and clinical oncology 112 22198637
2016 An Arntl2-Driven Secretome Enables Lung Adenocarcinoma Metastatic Self-Sufficiency. Cancer cell 95 27150038
2000 The basic helix-loop-helix-PAS protein MOP9 is a brain-specific heterodimeric partner of circadian and hypoxia factors. The Journal of neuroscience : the official journal of the Society for Neuroscience 91 10864977
2001 Chicken pineal clock genes: implication of BMAL2 as a bidirectional regulator in circadian clock oscillation. Genes to cells : devoted to molecular & cellular mechanisms 76 11554928
2017 CLIF-C ACLF score is a better mortality predictor than MELD, MELD-Na and CTP in patients with Acute on chronic liver failure admitted to the ward. Revista espanola de enfermedades digestivas 54 28467096
2002 Alternative splicing yields novel BMAL2 variants: tissue distribution and functional characterization. American journal of physiology. Cell physiology 52 12055078
2009 Preferential inhibition of BMAL2-CLOCK activity by PER2 reemphasizes its negative role and a positive role of BMAL2 in the circadian transcription. The Journal of biological chemistry 50 19605937
2000 cDNA cloning of a novel bHLH-PAS transcription factor superfamily gene, BMAL2: its mRNA expression, subcellular distribution, and chromosomal localization. Biochemical and biophysical research communications 49 10964693
2011 Decreased expression of Bmal2 in patients with Parkinson's disease. Neuroscience letters 44 21658431
2016 The Circadian Rhythm Gene Arntl2 Is a Metastasis Susceptibility Gene for Estrogen Receptor-Negative Breast Cancer. PLoS genetics 43 27656887
2020 ARNTL2 promotes pancreatic ductal adenocarcinoma progression through TGF/BETA pathway and is regulated by miR-26a-5p. Cell death & disease 39 32826856
2014 Polymorphisms in the circadian expressed genes PER3 and ARNTL2 are associated with diurnal preference and GNβ3 with sleep measures. Journal of sleep research 39 24635757
2024 Activation of the PI3K/AKT signaling pathway by ARNTL2 enhances cellular glycolysis and sensitizes pancreatic adenocarcinoma to erlotinib. Molecular cancer 34 38459558
2006 Identification of the transcription factor ARNTL2 as a candidate gene for the type 1 diabetes locus Idd6. Human molecular genetics 34 16893914
2020 ARNTL2 knockdown suppressed the invasion and migration of colon carcinoma: decreased SMOC2-EMT expression through inactivation of PI3K/AKT pathway. American journal of translational research 30 32355542
2003 Antisense overexpression of BMAL2 enhances cell proliferation. Oncogene 26 12917632
2023 ARNTL2 upregulation of ACOT7 promotes NSCLC cell proliferation through inhibition of apoptosis and ferroptosis. BMC molecular and cell biology 22 37003979
2013 Increased sensitivity of the circadian system to temporal changes in the feeding regime of spontaneously hypertensive rats - a potential role for Bmal2 in the liver. PloS one 21 24086613
2015 Association between brain-muscle-ARNT-like protein-2 (BMAL2) gene polymorphism and type 2 diabetes mellitus in obese Japanese individuals: A cross-sectional analysis of the Japan Multi-institutional Collaborative Cohort Study. Diabetes research and clinical practice 19 26497775
2017 DEC2 Blocks the Effect of the ARNTL2/NPAS2 Dimer on the Expression of PER3 and DBP. Journal of circadian rhythms 14 30210560
2014 Linking the circadian rhythm gene Arntl2 to interleukin 21 expression in type 1 diabetes. Diabetes 14 24520124
2024 ARNTL2 facilitates bladder cancer progression through potentiating ENO1-mediated glycolysis in a SLC31A1-independent and -dependent manner. Life sciences 13 39147318
2024 The circadian gene ARNTL2 promotes nasopharyngeal carcinoma invasiveness and metastasis through suppressing AMOTL2-LATS-YAP pathway. Cell death & disease 12 38956029
2010 Downregulation of the circadian rhythm related gene Arntl2 suppresses diabetes protection in Idd6 NOD.C3H congenic mice. Clinical and experimental pharmacology & physiology 11 20880188
2016 The circadian gene Arntl2 on distal mouse chromosome 6 controls thymocyte apoptosis. Mammalian genome : official journal of the International Mammalian Genome Society 10 27671790
2024 Deletion of the Clock Gene Bmal2 Leads to Alterations in Hypothalamic Clocks, Circadian Regulation of Feeding, and Energy Balance. The Journal of neuroscience : the official journal of the Society for Neuroscience 8 38531632
2025 Ras-dependent activation of BMAL2 regulates hypoxic metabolism in pancreatic cancer. bioRxiv : the preprint server for biology 6 36993718
2024 BMAL2 promotes eCIRP-induced macrophage endotoxin tolerance. Frontiers in immunology 6 38938563
2022 The circadian transcription factor ARNTL2 is regulated by weight-loss interventions in human white adipose tissue and inhibits adipogenesis. Cell death discovery 6 36329012
2024 Adaptive changes in BMAL2 with increased locomotion associated with the evolution of unihemispheric slow-wave sleep in mammals. Sleep 5 38289699
2025 ARNTL2: a key player in promoting tumor aggressiveness in papillary thyroid cancer. Translational cancer research 4 39974412
2025 Clock gene ARNTL2 enhances 5-fluorouracil resistance in colon cancer by upregulating SLC7A11 to suppress ferroptosis. Redox biology 4 40753759
2024 LINC01232 promotes ARNTL2 transcriptional activation and inhibits ferroptosis of CRC cells through p300/H3K27ac. Epigenomics 4 39268727
2023 Determination of specific autoantibodies in patients with systemic lupus erythematosus by Line immunoassay, ELISA and CLIF assay. Asian Pacific journal of allergy and immunology 3 32170924
2014 The polymorphism of ARNTL2 (BMAL2) gene rs2306074 C>T is associated with susceptibility of Alzheimer disease in Chinese population. Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology 2 24847962
2025 BMAL2 controls adipose tissue inflammation and metabolic adaptation during obesity. Metabolism: clinical and experimental 1 40983272
2025 The oncogenic role of BMAL2 in non-small cell lung cancer: MRPL15-mediated regulation of apoptosis and ferroptosis. Translational oncology 1 41075325
2025 ARNTL2 regulated the oncogene c-myc and promoted the progression of esophageal cancer through activating transcription. Cancer biology & therapy 1 41243277
2026 Association of circadian rhythms, MTNR1B, BMAL1, BMAL2, and CRY2 gene polymorphisms and their interactions with type 2 diabetes in coal miners. Frontiers in endocrinology 0 41847453
2026 BMAL2 is a druggable target for ovarian clear cell carcinoma (OCCC). EMBO molecular medicine 0 41933240
2025 Analysis of the expression of ARNTL2 and miR-204-5p and their correlation with clinical pathological features in NSCLC patients. American journal of clinical and experimental immunology 0 41567727
2024 [Effects of BMAL2 on Aerobic Glycolysis and Cell Proliferation in Acute Myeloid Leukemia Cells]. Zhongguo shi yan xue ye xue za zhi 0 38660843

Missed literature

Know a paper Affinage missed for BMAL2? Flag it for the maintainers and the community.

No submissions yet.