Affinage

ASXL1

Polycomb group protein ASXL1 · UniProt Q8IXJ9

Length
1541 aa
Mass
165.4 kDa
Annotated
2026-04-28
100 papers in source corpus 30 papers cited in narrative 30 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

ASXL1 is a chromatin scaffolding protein that orchestrates multiple histone modifications to regulate gene expression in hematopoiesis, development, and metabolism. Its DEUBAD domain activates the deubiquitinase BAP1 within the PR-DUB complex, conferring specificity for H2AK119Ub removal at Polycomb target genes through direct nucleosome contacts revealed by cryo-EM, while its N-terminal ASXH domain recruits HP1 and LSD1 to demethylate H3K4 at retinoic acid-responsive promoters, and its association with PRC2 supports H3K27 trimethylation (PMID:26739236, PMID:37556531, PMID:19880879, PMID:22897849). ASXL1 is stabilized by OGT-mediated O-GlcNAcylation within an ASXL1–HCFC1–OGT complex that promotes H3K4 methylation and myeloid differentiation, and its C-terminal intrinsically disordered region drives phase separation required for paraspeckle formation (PMID:29556021, PMID:34433054). Recurrent C-terminal truncation mutations in myeloid malignancies produce stable gain-of-function proteins that hyperactivate BAP1, globally redistribute H2AK119Ub, acquire a novel BRD4 interaction via an exposed ET-domain binding motif, lose FOXK1/2 and BMI1 binding, and activate AKT through BAP1-mediated deubiquitination, collectively driving clonal hematopoiesis and leukemic transcriptional programs (PMID:35122023, PMID:38359087, PMID:34536441, PMID:33758188, PMID:29967380).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 2006 High

    Establishing that ASXL1 is a nuclear receptor coregulator answered how a mammalian Asx homolog participates in transcription: ASXL1 directly contacts RAR via a C-terminal NR box and cooperates with SRC-1 to increase histone H3 acetylation at RA-responsive promoters.

    Evidence GST pulldown, co-IP, ChIP, luciferase reporter in mammalian cells

    PMID:16606617

    Open questions at the time
    • Whether coactivation extends to other nuclear receptors beyond RAR in vivo
    • Structural basis of NR box–RAR AF-2 interaction unresolved
  2. 2009 High

    Demonstrating that ASXL1 also represses RAR targets resolved an apparent paradox — the same protein acts as both coactivator and corepressor — by showing the N-terminal region recruits HP1 and LSD1 to remove H3K4 methylation, establishing ASXL1 as a context-dependent transcriptional switch.

    Evidence GST pulldown, co-IP, ChIP, siRNA knockdown, transcription assays

    PMID:19880879

    Open questions at the time
    • How the switch between coactivation and corepression is regulated at specific loci
    • Whether the ASXL1-HP1-LSD1 complex has genome-wide targets beyond RAR
  3. 2012 High

    Linking ASXL1 to PRC2-mediated H3K27me3 established its role as a Polycomb co-factor and explained how ASXL1 loss derepresses HOXA genes to cooperate with oncogenic RAS in myeloid leukemogenesis.

    Evidence Co-IP of ASXL1–PRC2, ChIP-Seq, in vivo NRAS-G12D mouse model

    PMID:22897849

    Open questions at the time
    • Whether ASXL1 is a stable PRC2 subunit or a transient recruiter
    • Mechanism by which ASXL1 facilitates PRC2 catalytic activity
  4. 2013 High

    In vivo knockout studies and truncation mutant mouse models demonstrated that ASXL1 loss and C-terminal truncation produce overlapping yet distinct epigenomic consequences — both reduce H3K27me3 and derepress Hoxa9/miR-125a, establishing the MDS-initiating mechanism.

    Evidence Conditional KO mice, knock-in of truncation mutant, ChIP-Seq, RNA-Seq, bone marrow transplantation

    PMID:24216483 PMID:24218140

    Open questions at the time
    • Relative contributions of PRC2 loss versus PR-DUB gain-of-function in truncation mutants
    • Cell-intrinsic versus microenvironmental contributions to MDS phenotype
  5. 2015 High

    Biochemical reconstitution revealed that ASXL1's DEUBAD domain directly activates BAP1 by increasing its affinity for ubiquitin on H2AK119, and that truncation mutations produce stable proteins with enhanced BAP1 deubiquitinase activity that globally erases H2AK119Ub — reframing truncations as gain-of-function rather than simple loss-of-function.

    Evidence In vitro deubiquitinase reconstitution, mutagenesis, nucleosome binding assays, mass spectrometry detection of truncated protein, genome-wide histone ChIP

    PMID:26095772 PMID:26700326 PMID:26739236

    Open questions at the time
    • Structural basis of how truncation enhances BAP1 activity was unknown at this stage
    • Whether enhanced activity is dosage-dependent in vivo
  6. 2017 High

    Identification of a neomorphic BRD4 interaction specific to truncated ASXL1 — mediated by an ET-domain binding motif exposed by truncation — explained how mutant ASXL1 opens chromatin at leukemogenic loci and established BET inhibitor sensitivity as a therapeutic vulnerability.

    Evidence LC-MS/MS, co-IP, ATAC-seq, RNA-seq, transgenic mouse model, ITC/SPR binding quantification

    PMID:29113963 PMID:34536441

    Open questions at the time
    • Whether BRD4 interaction and enhanced BAP1 activity act synergistically or independently
    • Genome-wide sites of aberrant BRD4 recruitment by truncated ASXL1
  7. 2018 High

    Discovery of the ASXL1–HCFC1–OGT complex showed that OGT-mediated O-GlcNAcylation stabilizes ASXL1 protein and promotes H3K4 methylation, while the finding that truncated ASXL1 loses BMI1 interaction placed PRC1-mediated H2AK119Ub at the p16Ink4a locus as a key senescence checkpoint disrupted by mutation.

    Evidence Co-IP, mass spectrometry, O-GlcNAcylation assay, ChIP, knock-in mouse with p16Ink4a genetic rescue

    PMID:29556021 PMID:29967380

    Open questions at the time
    • Whether OGT stabilization is disrupted by truncation mutations
    • How H3K4me3 reduction and H2AK119Ub loss cooperate at individual loci
  8. 2018 High

    Physiological knock-in of Asxl1 truncation revealed that mutant protein reduces H3K4me3 and H2AK119Ub without significantly reducing H3K27me3 — distinguishing gain-of-function truncation from loss-of-function and demonstrating opposing epigenomic effects of wild-type versus mutant at specific loci.

    Evidence Conditional knock-in mice, genome-wide ChIP-Seq, competitive transplantation

    PMID:29643185

    Open questions at the time
    • Locus-specific rules governing which marks are affected remain incompletely defined
    • Whether the epigenomic signature changes during disease progression
  9. 2020 High

    Genome-wide PR-DUB mapping showed that ASXL proteins and FOXK1/2 are both required for BAP1 chromatin recruitment and H2AK119Ub removal, while truncated ASXL1 loses FOXK1/2 interaction, clarifying how the full complex is assembled and how truncation rewires its targeting.

    Evidence ChIP-seq, genetic knockouts in ESCs, proteomics, allele-specific CRISPR deletion in leukemia cells

    PMID:32683582 PMID:32747411

    Open questions at the time
    • How PR-DUB target selection differs between ASXL1, ASXL2, and ASXL3
    • Whether FOXK1/2 loss fully explains aberrant PR-DUB targeting in mutant cells
  10. 2021 High

    Truncated ASXL1 cooperates with BAP1 to deubiquitinate and activate AKT, establishing a non-histone substrate for the hyperactive PR-DUB complex and connecting mutant ASXL1 to mTOR signaling; rapamycin rescue validated therapeutic targeting of this axis.

    Evidence Biochemical AKT deubiquitination assay, conditional knock-in mice, rapamycin treatment

    PMID:33758188

    Open questions at the time
    • Full repertoire of non-histone PR-DUB substrates is unknown
    • Whether AKT deubiquitination contributes to leukemogenesis independently of chromatin effects
  11. 2021 Medium

    Discovery that ASXL1's C-terminal IDR drives phase separation supporting paraspeckle formation via NONO–NEAT1 interactions revealed a non-chromatin function lost in truncation mutants, broadening the functional consequences of pathogenic mutations beyond epigenetics.

    Evidence Phase separation assay, co-IP, knock-in mouse model, live imaging

    PMID:34433054

    Open questions at the time
    • How paraspeckle disruption contributes quantitatively to mutant ASXL1-driven disease
    • Whether phase separation also modulates ASXL1's chromatin functions
    • Confirmation in independent systems needed
  12. 2023 High

    The cryo-EM structure of BAP1–ASXL1 DEUBAD bound to an H2AK119Ub nucleosome provided atomic-level explanation for substrate specificity and mapped >50 cancer-associated mutations onto the structure, unifying biochemical and genetic observations.

    Evidence Cryo-EM at near-atomic resolution, mutagenesis, deubiquitinase assays, cellular complementation

    PMID:37556531

    Open questions at the time
    • Structure of full-length ASXL1 or truncated mutant in complex with BAP1 on nucleosomes not yet resolved
    • Dynamic conformational changes during catalysis remain uncharacterized
  13. 2024 High

    Genome-wide H2AK119Ub mapping in CRISPR-edited human HSPCs showed that truncated ASXL1 redistributes rather than simply depletes H2AK119Ub, activating myeloid/stem cell programs and establishing PRC1 inhibition as a mutation-specific therapeutic vulnerability.

    Evidence CUT&RUN, ATAC-seq, RNA-seq in primary human HSPCs, PRC1 inhibitor treatment

    PMID:38359087

    Open questions at the time
    • Whether H2AK119Ub redistribution pattern predicts clinical progression
    • Which PRC1 subcomplexes are responsible for the redistributed ubiquitination

Open questions

Synthesis pass · forward-looking unresolved questions
  • The full-length structure of ASXL1, the mechanistic basis for switching between its activating (PRC2, OGT) and repressive (HP1-LSD1) functions at specific loci, and the relative pathogenic contributions of its multiple neomorphic interactions (enhanced BAP1, BRD4, AKT deubiquitination, paraspeckle loss) remain unresolved.
  • No full-length ASXL1 structure
  • No quantitative model integrating chromatin and non-chromatin functions in disease
  • Therapeutic window for BAP1/PRC1 inhibition in ASXL1-mutant patients undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 5 GO:0060090 molecular adaptor activity 4 GO:0140110 transcription regulator activity 4 GO:0042393 histone binding 3
Localization
GO:0005634 nucleus 5 GO:0005694 chromosome 4
Pathway
R-HSA-4839726 Chromatin organization 9 R-HSA-1643685 Disease 5 R-HSA-74160 Gene expression (Transcription) 4 R-HSA-162582 Signal Transduction 3
Partners
BAP1BMI1BRD4FOXK1FOXK2HCFC1LSD1OGT
Complex memberships
ASXL1-HCFC1-OGTASXL1-HP1-LSD1PR-DUB (BAP1-ASXL1)

Evidence

Reading pass · 30 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2006 ASXL1 functions as a ligand-dependent coactivator for retinoic acid receptor (RAR), interacting through its C-terminal nuclear receptor box (LVMQLL) with the AF-2 AD core of RAR, and cooperates with SRC-1 to increase acetylated histone H3 on RA-responsive promoters, enhancing RAR-mediated transcription. GST pulldown, co-immunoprecipitation, chromatin IP, luciferase reporter assay, confocal microscopy The Journal of biological chemistry High 16606617
2006 Murine Asxl1 protein contains two regions conserved with Drosophila Asx: an N-terminal ASX homology domain (ASXH) with nuclear receptor co-regulator binding motifs, and a C-terminal PHD domain; it is expressed ubiquitously in adult tissues and embryos. Sequence analysis, Northern blot, whole-mount RNA in situ hybridization Gene Medium 16412590
2009 ASXL1 represses RAR-mediated transcription through its N-terminal region by directly interacting with HP1 (via an HP1 box, PXVXL motif) and histone demethylase LSD1, forming a ternary ASXL1-HP1-LSD1 complex that removes H3K4 methylation at RA-responsive promoters. In vitro GST pulldown, in vivo co-immunoprecipitation, chromatin IP, transcription assays, siRNA knockdown The Journal of biological chemistry High 19880879
2012 ASXL1 associates with the PRC2 complex and loss of ASXL1 results in reduced H3K27 tri-methylation genome-wide, leading to derepression of posterior HOXA cluster genes and collaborating with NRASG12D to promote myeloid leukemogenesis. Co-immunoprecipitation, ChIP-Seq, microarray, in vivo mouse model Cancer cell High 22897849
2013 Constitutive or hematopoietic-specific deletion of Asxl1 in mice results in global reduction of H3K27 trimethylation and H3K4me3, dysregulated expression of hematopoietic regulators, progressive cytopenias and dysplasia recapitulating MDS; compound Asxl1/Tet2 deletion accelerates myeloid disease. Conditional knockout mouse model, RNA-Seq, ChIP-Seq, serial transplantation The Journal of experimental medicine High 24218140
2013 C-terminal truncating ASXL1 mutations inhibit PRC2-mediated H3K27 methylation, leading to derepression of Hoxa9 and miR-125a, which reduces Clec5a expression and blocks myeloid differentiation, inducing MDS-like disease in mice. Mouse bone marrow transplantation model, ChIP, qRT-PCR, miRNA target validation The Journal of clinical investigation High 24216483
2015 ASXL1 truncation mutations confer gain-of-function on the ASXL1-BAP1 deubiquitinase complex, resulting in enhanced BAP1 activity, global erasure of H2AK119Ub, striking depletion of H3K27me3, and upregulation of bivalently marked genes, driving mast cell differentiation; effects require BAP1 catalytic activity. Stable cell line expression, genome-wide histone ChIP, functional differentiation assays, in vivo bone marrow reconstitution Nature communications High 26095772
2015 ASXL1 is required for BAP1-mediated deubiquitylation of H2AK119ub1 at the INK4B locus; ASXL1 and BAP1 co-occupy the INK4B promoter, and ASXL1 loss prevents H2AK119 deubiquitylation and induction of p15(INK4B) in response to oncogenic signaling or anti-proliferative signals. ChIP, siRNA knockdown, luciferase reporter, primary bone marrow cell functional assays Cell research High 26470845
2016 BAP1's C-terminal extension auto-recruits BAP1 to nucleosomes in an unproductive complex; ASXL1 (or ASXL2/3) DEUBAD domains activate BAP1 by increasing its affinity for ubiquitin on H2A K119, driving deubiquitination specifically for Polycomb H2A modifications but not DNA damage-associated H2A K13/15 ubiquitination. Biochemical reconstitution, in vitro deubiquitinase assay, mutagenesis, nucleosome binding assays Nature communications High 26739236
2015 Truncated ASXL1 mutant proteins (C-terminal truncations) are detectable at the protein level in cell lines harboring homozygous ASXL1 mutations, demonstrating that ASXL1 truncation mutations produce stable expressed proteins rather than undergoing nonsense-mediated decay. Mass spectrometry, Western blot, cell lines with homozygous ASXL1 mutations Experimental hematology High 26700326
2017 ASXL1 truncating protein (aa1-587) acquires an interaction with BRD4 (not present with full-length ASXL1), resulting in more open chromatin at critical hematopoietic genes; expression of truncated ASXL1 drives myeloid malignancies in transgenic mice and confers hypersensitivity to BET bromodomain inhibitors. LC-MS/MS, co-immunoprecipitation, ATAC-seq, RNA-seq, transgenic mouse model, epigenetic drug screening Blood High 29113963
2017 ASXL1 interacts directly with the kinase domain of AKT1 through amino acids 371-655; loss of Asxl1 prevents IGF-1-induced AKT1 phosphorylation, retains p27Kip1 in the nucleus, suppresses Rb phosphorylation and E2F target genes, and promotes cellular senescence; Asxl1 also cooperates with Ezh2 through direct interaction. Co-immunoprecipitation, domain mapping, AKT inhibitor treatment, microarray, SA-β-gal staining in Asxl1-null MEFs Scientific reports Medium 28701722
2018 Physiological expression of C-terminal truncated Asxl1 mutant in knock-in mice reduces H3K4me3 and H2AK119Ub without significant reduction in H3K27me3—distinct from Asxl1 loss—and wild-type versus mutant Asxl1 have opposing effects on H3K4me3 at specific loci, altering the HSC epigenome and increasing susceptibility to leukemic transformation. Conditional knock-in mouse model, ChIP-Seq, competitive transplantation, viral insertional mutagenesis The Journal of experimental medicine High 29643185
2018 ASXL1 forms a protein complex with HCFC1 and OGT; OGT directly stabilizes ASXL1 through O-GlcNAcylation; disruption of this ASXL1-OGT axis inhibits H3K4 methylation, H2B glycosylation, and myeloid differentiation, implicating MLL5 as the downstream H3K4 methyltransferase. Co-immunoprecipitation, mass spectrometry, O-GlcNAcylation assay, ChIP, in vivo leukemogenicity assay Leukemia High 29556021
2018 Asxl1G643fs mutant ASXL1 loses the ability to interact with BMI1 (PRC1 subunit), reducing H2AK119ub1 at the p16Ink4a promoter; derepression of p16Ink4a induces cellular senescence in HSCs, producing low-risk MDS-like phenotypes; heterozygous p16Ink4a deletion restores HSC pool. Co-immunoprecipitation, ChIP at p16Ink4a locus, knock-in mouse model, genetic rescue with p16Ink4a heterozygosity Leukemia High 29967380
2018 Loss of ASXL1 in bone marrow stromal cells (BMSCs) impairs hematopoietic stem/progenitor cell maintenance; ASXL1 interacts with core subunits of RNA polymerase II complex in BMSCs and regulates RNAPII-dependent transcription of genes critical for HSC/HPC maintenance (e.g., Vcam1). Co-immunoprecipitation, ChIP-seq, RNA-seq, BMSC co-culture assays Cell discovery Medium 29423272
2018 ASXL1 and SETBP1 co-mutations repress TGFβ pathway genes through reduced histone H3 and H4 acetylation at their promoters; HDAC inhibitor vorinostat restores histone acetylation, derepresses TGFβ pathway genes, and selectively inhibits growth of ASXL1-mutant cells. ChIP for H3/H4 acetylation, HDAC inhibitor treatment, gene expression analysis, in vivo mouse model Scientific reports Medium 30367089
2020 PR-DUB complex (BAP1 with ASXL1/2/3, FOXK1/2, HCFC1, OGT) is recruited to chromatin through FOXK1/2 and ASXL proteins; BAP1 is dependent on ASXL proteins and FOXK1/2 for genome-wide H2AK119ub1 removal and activation of metabolic and homeostatic genes, with minimal functional overlap with PRC2 in ESCs. ChIP-seq, genome-wide H2AK119ub1 profiling, genetic knockouts, proteomics Genome research High 32747411
2020 Wild-type ASXL1 interacts with forkhead transcription factors FOXK1 and FOXK2 to regulate target genes; C-terminally truncated mutant ASXL1 loses FOXK1/K2 interaction and is expressed at higher levels than wild-type in heterozygous leukemia cells; specific deletion of mutant allele restores BAP1-ASXL1 association and FOXK1/K2 target gene expression. Co-immunoprecipitation, CRISPR allele-specific deletion, gene expression analysis Protein & cell Medium 32683582
2021 ASXL1-mutant (C-terminally truncated) cooperates with BAP1 to deubiquitinate and activate AKT; overactive Akt/mTOR signaling causes aberrant HSC proliferation, age-related DNA damage accumulation, and clonal expansion; mTOR inhibitor rapamycin ameliorates the phenotype in knock-in mice. Conditional knock-in mouse model, biochemical AKT deubiquitination assay, genetic mosaic model, rapamycin treatment Nature communications High 33758188
2021 ASXL1 forms phase-separated droplets via its C-terminal intrinsically disordered region (IDR), upregulates NEAT1 expression, and increases NONO-NEAT1 interactions to support paraspeckle formation in hematopoietic cells; pathogenic truncated ASXL1 lacking the IDR fails to support paraspeckle components, causing abnormal cytoplasmic NONO localization and impaired HSPC repopulating potential. Co-immunoprecipitation, phase separation assay, knock-in mouse model, live imaging, NONO shRNA knockdown Cell reports Medium 34433054
2021 Cancer-associated ASXL1 frameshift mutations encode stable truncated gain-of-function proteins that increase BAP1 protein stability, enhance BAP1 chromatin recruitment, and drive expression of a pro-leukemic transcriptional signature; BAP1 catalytic inhibitors identified by biochemical screen suppress truncated-ASXL1-driven leukemic gene expression and impair tumor progression in vivo. Protein stability assays, ChIP, RNA-seq, biochemical inhibitor screen, in vivo tumor models Nature cancer High 35122023
2021 Oncogenic ASXL1 truncation mutations enhance binding to the ET domain of BRD4 via a specific motif near the truncation breakpoint; ASXL1Y591X truncation markedly increases BRD4 ET-domain binding relative to full-length ASXL1, providing a molecular mechanism for aberrant BRD4 recruitment to transcriptional complexes. Binding assays (ITC, SPR), domain mapping, recombinant protein analysis Journal of molecular biology High 34536441
2023 Cryo-EM structure of human BAP1-ASXL1 DEUBAD in complex with H2AK119Ub nucleosome reveals molecular interactions of BAP1 and ASXL1 with histones and DNA that restructure the nucleosome to establish specificity for H2AK119Ub; structure explains how >50 cancer-associated mutations in BAP1 and ASXL1 dysregulate deubiquitination. Cryo-EM structure determination, biochemical deubiquitinase assays, mutagenesis, cellular complementation Science advances High 37556531
2013 ASXL1 interacts with WTIP (Wilms tumor 1-interacting protein) via its PHD domain; loss of Asxl1 in mice causes kidney podocyte morphology defects and up-regulation of Wt1/Wtip target genes, placing ASXL1 in a WT1 regulatory pathway during kidney development. Co-immunoprecipitation, Asxl1-null mouse analysis, gene expression assays Biochemical and biophysical research communications Medium 26385183
2013 ASXL1 suppresses LXRα-mediated transcription and lipid accumulation, while ASXL2 activates LXRα, acting through direct interaction with LXRα; ChIP shows ligand-dependent recruitment of ASXL1 to ABCA1 promoters; ASXL1 expression increases under fasting and decreases in insulin-treated or high-fat-diet conditions. Co-immunoprecipitation, ChIP, siRNA knockdown, lipid accumulation assays Biochemical and biophysical research communications Medium 24321552
2020 Asxl1 is required for transcriptional activation of Pten by facilitating H2AK119 deubiquitylation at the Pten promoter; loss of Asxl1 reduces PTEN expression, sustains PI3K/AKT signaling, and confers sensitivity to AKT inhibitor MK2206. ChIP at Pten promoter, AKT activity assays, siRNA knockdown, inhibitor sensitivity assay Journal of molecular cell biology Medium 32236560
2024 Truncated ASXL1 leads to global redistribution (not simply loss) of H2AK119Ub, increased transposase-accessible chromatin, and activation of myeloid and stem cell gene-expression programs in human HSPCs; H2AK119Ub levels are tied to truncated ASXL1 expression levels, and PRC1 complex inhibition is an ASXL1-mutant-specific therapeutic vulnerability. CRISPR-edited human HSPCs, CUT&RUN for H2AK119Ub, ATAC-seq, RNA-seq, PRC1 inhibitor treatment Blood cancer discovery High 38359087
2017 BAP1 mutations in cancer act allosterically to inhibit ASXL2 ASXH-domain binding to BAP1's ULD domain; BAP1-UCH, BAP1-ULD, and ASXH form a cooperative ternary complex required for deubiquitination activity; four classes of BAP1 mutations outside the UCH domain all fail to productively recruit ASXH, abolishing enzyme activity. Computational modeling, in vitro reconstitution biochemistry, domain binding and enzymatic assays, mutagenesis Cancer research High 29284740
2020 Truncated ASXL1 mutant protein expression in T cells (but not myeloid cells) promotes solid tumor progression by inducing aberrant intrathymic T-cell development, decreased CD4/CD8 ratio, naïve-memory imbalance, and PD-1 upregulation on CD8+ T cells, creating a pro-tumor immune microenvironment. Conditional knock-in mouse syngeneic tumor models, MMTV-PyMT spontaneous tumor model, intratumor T-cell analysis Cancer science Medium 35133065

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2012 ASXL1 mutations promote myeloid transformation through loss of PRC2-mediated gene repression. Cancer cell 502 22897849
2009 Mutations of polycomb-associated gene ASXL1 in myelodysplastic syndromes and chronic myelomonocytic leukaemia. British journal of haematology 478 19388938
2013 Deletion of Asxl1 results in myelodysplasia and severe developmental defects in vivo. The Journal of experimental medicine 284 24218140
2010 Distinct clinical and biological features of de novo acute myeloid leukemia with additional sex comb-like 1 (ASXL1) mutations. Blood 180 20693432
2015 Cancer-associated ASXL1 mutations may act as gain-of-function mutations of the ASXL1-BAP1 complex. Nature communications 172 26095772
2016 BAP1/ASXL1 recruitment and activation for H2A deubiquitination. Nature communications 165 26739236
2013 Loss of Asxl1 leads to myelodysplastic syndrome-like disease in mice. Blood 155 24255920
2013 Myelodysplastic syndromes are induced by histone methylation–altering ASXL1 mutations. The Journal of clinical investigation 147 24216483
2020 Clonal myelopoiesis in the UK Biobank cohort: ASXL1 mutations are strongly associated with smoking. Leukemia 145 32518416
2017 Gain of function of ASXL1 truncating protein in the pathogenesis of myeloid malignancies. Blood 141 29113963
2010 Combined mutations of ASXL1, CBL, FLT3, IDH1, IDH2, JAK2, KRAS, NPM1, NRAS, RUNX1, TET2 and WT1 genes in myelodysplastic syndromes and acute myeloid leukemias. BMC cancer 134 20678218
2018 Expression of mutant Asxl1 perturbs hematopoiesis and promotes susceptibility to leukemic transformation. The Journal of experimental medicine 128 29643185
2011 CBL, CBLB, TET2, ASXL1, and IDH1/2 mutations and additional chromosomal aberrations constitute molecular events in chronic myelogenous leukemia. Blood 128 21346257
2006 Additional sex comb-like 1 (ASXL1), in cooperation with SRC-1, acts as a ligand-dependent coactivator for retinoic acid receptor. The Journal of biological chemistry 124 16606617
2012 Mutation analysis of ASXL1, CBL, DNMT3A, IDH1, IDH2, JAK2, MPL, NF1, SF3B1, SUZ12, and TET2 in myeloproliferative neoplasms. Genes, chromosomes & cancer 123 22489043
2013 Acquired ASXL1 mutations are common in patients with inherited GATA2 mutations and correlate with myeloid transformation. Haematologica 116 24077845
2014 Next-generation sequencing of acute myeloid leukemia identifies the significance of TP53, U2AF1, ASXL1, and TET2 mutations. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 113 25412851
2019 The role of ASXL1 in hematopoiesis and myeloid malignancies. Cellular and molecular life sciences : CMLS 104 30927018
2012 Single nucleotide polymorphism array lesions, TET2, DNMT3A, ASXL1 and CBL mutations are present in systemic mastocytosis. PloS one 98 22905207
2019 Impact of the variant allele frequency of ASXL1, DNMT3A, JAK2, TET2, TP53, and NPM1 on the outcomes of patients with newly diagnosed acute myeloid leukemia. Cancer 85 31742675
2014 Dynamics of ASXL1 mutation and other associated genetic alterations during disease progression in patients with primary myelodysplastic syndrome. Blood cancer journal 83 24442206
2021 Mutant ASXL1 induces age-related expansion of phenotypic hematopoietic stem cells through activation of Akt/mTOR pathway. Nature communications 82 33758188
2006 Characterization of Asxl1, a murine homolog of Additional sex combs, and analysis of the Asx-like gene family. Gene 78 16412590
2014 SETBP1 mutations drive leukemic transformation in ASXL1-mutated MDS. Leukemia 77 25306901
2009 ASXL1 represses retinoic acid receptor-mediated transcription through associating with HP1 and LSD1. The Journal of biological chemistry 77 19880879
2013 IDH mutations are closely associated with mutations of DNMT3A, ASXL1 and SRSF2 in patients with myelodysplastic syndromes and are stable during disease evolution. American journal of hematology 74 24115220
2013 Cooperating gene mutations in childhood acute myeloid leukemia with special reference on mutations of ASXL1, TET2, IDH1, IDH2, and DNMT3A. Blood 69 23365461
2021 Epigenetic targeted therapy of stabilized BAP1 in ASXL1 gain-of-function mutated leukemia. Nature cancer 68 35122023
2019 Circ-ITGA7 sponges miR-3187-3p to upregulate ASXL1, suppressing colorectal cancer proliferation. Cancer management and research 63 31372051
2018 A novel ASXL1-OGT axis plays roles in H3K4 methylation and tumor suppression in myeloid malignancies. Leukemia 60 29556021
2015 Truncation mutants of ASXL1 observed in myeloid malignancies are expressed at detectable protein levels. Experimental hematology 60 26700326
2015 Clinical management of patients with ASXL1 mutations and Bohring-Opitz syndrome, emphasizing the need for Wilms tumor surveillance. American journal of medical genetics. Part A 56 25921057
2021 ASXL1 mutations are associated with distinct epigenomic alterations that lead to sensitivity to venetoclax and azacytidine. Blood cancer journal 54 34548471
2010 Genetic typing of CBL, ASXL1, RUNX1, TET2 and JAK2 in juvenile myelomonocytic leukaemia reveals a genetic profile distinct from chronic myelomonocytic leukaemia. British journal of haematology 54 20955399
2020 PR-DUB maintains the expression of critical genes through FOXK1/2- and ASXL1/2/3-dependent recruitment to chromatin and H2AK119ub1 deubiquitination. Genome research 53 32747411
2010 Spectrum of molecular defects in juvenile myelomonocytic leukaemia includes ASXL1 mutations. British journal of haematology 52 20408841
2020 ASXL1 mutation in clonal hematopoiesis. Experimental hematology 51 31945396
2015 Functional proteomics of the epigenetic regulators ASXL1, ASXL2 and ASXL3: a convergence of proteomics and epigenetics for translational medicine. Expert review of proteomics 51 25835095
2015 Genetic landscape of recurrent ASXL1, U2AF1, SF3B1, SRSF2, and EZH2 mutations in 304 Chinese patients with myelodysplastic syndromes. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 46 26508027
2022 Asxl1 loss cooperates with oncogenic Nras in mice to reprogram the immune microenvironment and drive leukemic transformation. Blood 43 34699595
2020 Thrombotic Risk Detection in Patients with Polycythemia Vera: The Predictive Role of DNMT3A/TET2/ASXL1 Mutations. Cancers 43 32290079
2017 The distinct biological implications of Asxl1 mutation and its roles in leukemogenesis revealed by a knock-in mouse model. Journal of hematology & oncology 43 28697759
2016 Myeloid neoplasms with isolated isochromosome 17q demonstrate a high frequency of mutations in SETBP1, SRSF2, ASXL1 and NRAS. Oncotarget 43 26883102
2022 ASXL1 and STAG2 are common mutations in GATA2 deficiency patients with bone marrow disease and myelodysplastic syndrome. Blood advances 42 34529785
2018 Modeling ASXL1 mutation revealed impaired hematopoiesis caused by derepression of p16Ink4a through aberrant PRC1-mediated histone modification. Leukemia 42 29967380
2023 Structural basis of histone H2A lysine 119 deubiquitination by Polycomb repressive deubiquitinase BAP1/ASXL1. Science advances 41 37556531
2015 Tumor suppressor ASXL1 is essential for the activation of INK4B expression in response to oncogene activity and anti-proliferative signals. Cell research 41 26470845
2011 TET2, ASXL1, IDH1, IDH2, and c-CBL genes in JAK2- and MPL-negative myeloproliferative neoplasms. Annals of hematology 41 21904853
2022 ASXL1/2 mutations and myeloid malignancies. Journal of hematology & oncology 39 36068610
2012 TET2, ASXL1 and EZH2 mutations in Chinese with myelodysplastic syndromes. Leukemia research 38 23099237
2024 Atrial Fibrillation and Clonal Hematopoiesis in TET2 and ASXL1. JAMA cardiology 36 38598228
2022 CHIP-associated mutant ASXL1 in blood cells promotes solid tumor progression. Cancer science 33 35133065
2019 RUNX1 mutations promote leukemogenesis of myeloid malignancies in ASXL1-mutated leukemia. Journal of hematology & oncology 33 31640815
2017 Exome sequencing reveals DNMT3A and ASXL1 variants associate with progression of chronic myeloid leukemia after tyrosine kinase inhibitor therapy. Leukemia research 32 28667884
2015 Impact of TET2, SRSF2, ASXL1 and SETBP1 mutations on survival of patients with chronic myelomonocytic leukemia. Experimental hematology & oncology 32 26019984
2015 Bohring-Opitz syndrome (BOS) with a new ASXL1 pathogenic variant: Review of the most prevalent molecular and phenotypic features of the syndrome. American journal of medical genetics. Part A 32 26364555
2018 ASXL1 and SETBP1 mutations promote leukaemogenesis by repressing TGFβ pathway genes through histone deacetylation. Scientific reports 30 30367089
2021 A histone modifier, ASXL1, interacts with NONO and is involved in paraspeckle formation in hematopoietic cells. Cell reports 29 34433054
2020 Tumor-derived neomorphic mutations in ASXL1 impairs the BAP1-ASXL1-FOXK1/K2 transcription network. Protein & cell 29 32683582
2018 Loss of ASXL1 in the bone marrow niche dysregulates hematopoietic stem and progenitor cell fates. Cell discovery 28 29423272
2014 AML with gain of chromosome 8 as the sole chromosomal abnormality (+8sole) is associated with a specific molecular mutation pattern including ASXL1 mutations in 46.8% of the patients. Leukemia research 27 25592059
2012 Role of TET2 and ASXL1 mutations in the pathogenesis of myeloproliferative neoplasms. Hematology/oncology clinics of North America 27 23009937
2018 Chromatin regulator Asxl1 loss and Nf1 haploinsufficiency cooperate to accelerate myeloid malignancy. The Journal of clinical investigation 25 30226831
2018 ASXL1 mutations in AML are associated with specific clinical and cytogenetic characteristics. Leukemia & lymphoma 24 29411666
2017 ASXL1 mutations in myeloid neoplasms: pathogenetic considerations, impact on clinical outcomes and survival. Current medical research and opinion 24 28027687
2021 Asxl1 C-terminal mutation perturbs neutrophil differentiation in zebrafish. Leukemia 23 33483612
2018 Clinical molecular testing for ASXL1 c.1934dupG p.Gly646fs mutation in hematologic neoplasms in the NGS era. PloS one 23 30222780
2017 Familial and Somatic BAP1 Mutations Inactivate ASXL1/2-Mediated Allosteric Regulation of BAP1 Deubiquitinase by Targeting Multiple Independent Domains. Cancer research 22 29284740
2017 Asxl1 deficiency in embryonic fibroblasts leads to cellular senescence via impairment of the AKT-E2F pathway and Ezh2 inactivation. Scientific reports 21 28701722
2018 Bohring-Opitz syndrome caused by an ASXL1 mutation inherited from a germline mosaic mother. American journal of medical genetics. Part A 20 29681100
2013 Silencing of ASXL1 impairs the granulomonocytic lineage potential of human CD34⁺ progenitor cells. British journal of haematology 20 23294243
2024 Human ASXL1-Mutant Hematopoiesis Is Driven by a Truncated Protein Associated with Aberrant Deubiquitination of H2AK119. Blood cancer discovery 19 38359087
2022 Role of ASXL1 in hematopoiesis and myeloid diseases. Experimental hematology 19 36183966
2019 Co-occurrence of RUNX1 and ASXL1 mutations underlie poor response and outcome for MDS patients treated with HMAs. American journal of translational research 19 31312376
2018 ASXL1/EZH2 mutations promote clonal expansion of neoplastic HSC and impair erythropoiesis in PMF. Leukemia 19 29907810
2020 ASXL1 mutation as a surrogate marker in acute myeloid leukemia with myelodysplasia-related changes and normal karyotype. Cancer medicine 17 32216059
2018 Aberrant histone modifications induced by mutant ASXL1 in myeloid neoplasms. International journal of hematology 17 30515738
2023 Epigenetic regulation by ASXL1 in myeloid malignancies. International journal of hematology 16 37062051
2020 HHEX promotes myeloid transformation in cooperation with mutant ASXL1. Blood 16 32492700
2019 Pathological ASXL1 Mutations and Protein Variants Impair Neural Crest Development. Stem cell reports 16 31006630
2019 Disruption of asxl1 results in myeloproliferative neoplasms in zebrafish. Disease models & mechanisms 16 31064769
2017 Epigenetic changes in myelofibrosis: Distinct methylation changes in the myeloid compartments and in cases with ASXL1 mutations. Scientific reports 15 28754985
2016 Dynamic ASXL1 Exon Skipping and Alternative Circular Splicing in Single Human Cells. PloS one 15 27736885
2013 Delineation of a new chromosome 20q11.2 duplication syndrome including the ASXL1 gene. American journal of medical genetics. Part A 15 23704076
2013 Reciprocal regulation of LXRα activity by ASXL1 and ASXL2 in lipogenesis. Biochemical and biophysical research communications 15 24321552
2020 Deregulation of tumor suppressive ASXL1-PTEN/AKT axis in myeloid malignancies. Journal of molecular cell biology 14 32236560
2015 Familial hematological malignancies: ASXL1 gene investigation. Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico 13 26286068
2014 ASXL1 and DNMT3A mutation in a cytogenetically normal B3 thymoma. Oncogenesis 13 25000259
2013 ASXL1 mutations are infrequent in young patients with primary acute myeloid leukemia and their detection has a limited role in therapeutic risk stratification. Leukemia & lymphoma 13 23952244
2020 ASXL1 mutations, previous vascular complications and age at diagnosis predict survival in 85 WHO-defined polycythaemia vera patients. British journal of haematology 12 32066200
2016 Loss of ASXL1 triggers an apoptotic response in human hematopoietic stem and progenitor cells. Experimental hematology 12 27616637
2013 Leukemic transformation driven by an ASXL1 mutation after a JAK2V617F-positive primary myelofibrosis: clonal evolution and hierarchy revealed by next-generation sequencing. Journal of hematology & oncology 12 24011025
2023 Multiomics of Bohring-Opitz syndrome truncating ASXL1 mutations identify canonical and noncanonical Wnt signaling dysregulation. JCI insight 11 37053013
2020 Loss of ASXL1 expression is associated with lymph node metastasis in colorectal cancer. Indian journal of pathology & microbiology 11 32317519
2015 Role of Asxl1 in kidney podocyte development via its interaction with Wtip. Biochemical and biophysical research communications 11 26385183
2015 Screening of CD96 and ASXL1 in 11 patients with Opitz C or Bohring-Opitz syndromes. American journal of medical genetics. Part A 11 26768331
2012 Rapid screening of ASXL1, IDH1, IDH2, and c-CBL mutations in de novo acute myeloid leukemia by high-resolution melting. The Journal of molecular diagnostics : JMD 11 22929312
2022 LINC00586 Represses ASXL1 Expression Thus Inducing Epithelial-To-Mesenchymal Transition of Colorectal Cancer Cells Through LSD1-Mediated H3K4me2 Demethylation. Frontiers in pharmacology 10 35586041
2021 Oncogenic Truncations of ASXL1 Enhance a Motif for BRD4 ET-Domain Binding. Journal of molecular biology 10 34536441
2018 Acute myeloid leukemia in a father and son with a germline mutation of ASXL1. Biomarker research 10 29456859