Affinage

PHF6

PHD finger protein 6 · UniProt Q8IWS0

Length
365 aa
Mass
41.3 kDa
Annotated
2026-04-28
100 papers in source corpus 25 papers cited in narrative 25 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

PHF6 is a chromatin-associated transcriptional regulator that controls gene expression programs governing hematopoietic lineage identity, neuronal development, and ribosomal RNA synthesis, functioning as both a tumor suppressor and a developmental regulator whose loss causes Börjeson-Forssman-Lehmann syndrome. PHF6 exerts transcriptional repression by recruiting the NuRD complex via direct binding of its disordered middle region to the RBBP4 β-propeller, by cooperating with SWI/SNF and ISWI remodeling complexes at promoters to maintain active chromatin, and by requiring PHIP as an obligate partner for chromatin occupancy (PMID:25601084, PMID:39181868, PMID:40721297). At rDNA loci, PHF6 suppresses rRNA transcription through its PHD1-mediated interaction with UBF and by recruiting the histone methyltransferases SUV39H1 and SUV4-20H2 to establish repressive H3K9me3 and H4K20me3 marks, with access gated by DNMT1-dependent DNA methylation (PMID:23229552, PMID:35847518, PMID:34520760). PHF6 also functions as an H2BK120 E3 ubiquitin ligase directed by ePHD2-mediated reading of H2BK12 acetylation, is recruited to DNA double-strand breaks in a PARP-dependent manner to promote NHEJ, and drives Ephrin receptor transcription in neural stem cells to control cortical neurogenesis (PMID:32735658, PMID:31782600, PMID:38429579).

Mechanistic history

Synthesis pass · year-by-year structured walk · 12 steps
  1. 2002 Medium

    Establishing PHF6 as a nuclear/nucleolar protein set the stage for understanding it as a chromatin-associated factor rather than a cytoplasmic signaling protein.

    Evidence GFP-tagged PHF6 transfection and fluorescence microscopy in cell lines

    PMID:12415272

    Open questions at the time
    • No functional consequence of nucleolar localization established
    • Single overexpression system without endogenous protein confirmation
  2. 2012 High

    Discovery that PHF6 physically associates with the NuRD complex (CHD4, HDAC1, RBBP4) in the nucleoplasm and separately binds UBF at rDNA to suppress rRNA transcription established PHF6 as a dual-compartment transcriptional repressor with distinct nucleoplasmic and nucleolar functions.

    Evidence Flag-tagged PHF6 Co-IP/MS from HEK293T cells with subcellular fractionation; ChIP at rDNA loci, Co-IP with UBF, siRNA knockdown with cell-cycle and γH2AX readouts

    PMID:22720776 PMID:23229552

    Open questions at the time
    • Mechanism by which PHF6 regulates UBF protein levels unknown
    • Genome-wide target repertoire of PHF6-NuRD not defined
  3. 2013 High

    Identification of the PHF6–PAF1 complex interaction and the in vivo neuronal migration phenotype upon PHF6 loss revealed PHF6 as a critical regulator of cortical development, linking chromatin regulation to brain lamination.

    Evidence Co-IP plus in utero electroporation knockdown in mouse cortex with live imaging and electrophysiology

    PMID:23791194

    Open questions at the time
    • How PHF6 toggles between PAF1 and NuRD complexes unclear
    • Direct transcriptional targets mediating migration beyond NGC/CSPG5 not mapped
  4. 2014 High

    Structural determination of the ePHD2 domain as a novel dsDNA-binding module, combined with crystallographic mapping of the RBBP4–PHF6 interface, provided the first atomic-level understanding of how PHF6 engages chromatin and recruits repressive machinery.

    Evidence X-ray crystallography of ePHD2 and RBBP4–PHF6 peptide complex, in vitro binding assays, GAL4 reporter repression assay, mutagenesis

    PMID:24554700 PMID:25601084

    Open questions at the time
    • No structure of full-length PHF6 or PHF6 on a nucleosome
    • How ePHD1 contributes to chromatin targeting structurally unresolved
  5. 2016 High

    Sub-nucleolar mapping of PHF6 to the fibrillar center/dense fibrillar component and demonstration that PHF6 gain-of-function elevates non-coding rDNA-derived RNAs refined its role as a repressor acting across the entire rDNA repeat.

    Evidence RNase/DNase/ActD treatment with immunocytochemistry, ChIP-qPCR across rDNA, rRNA quantification

    PMID:27165002

    Open questions at the time
    • Functional significance of pRNA and IGS RNA induction not tested directly
    • Whether PHF6 directly binds rDNA versus is tethered through UBF not resolved
  6. 2017 High

    Genome-wide chromatin accessibility analysis upon PHF6 loss in B-cell leukemia showed that PHF6 maintains hematopoietic lineage identity by preserving the chromatin landscape at lineage-specific transcription factor loci.

    Evidence ATAC-seq, RNA-seq, CRISPR knockout, in vivo transplantation in mouse B-cell leukemia

    PMID:28607179

    Open questions at the time
    • Direct versus indirect effects on chromatin accessibility not deconvolved
    • Whether PHF6 loss is sufficient for lineage switching in normal hematopoiesis unknown
  7. 2019 High

    Three parallel discoveries — PARP-dependent recruitment to DNA breaks promoting NHEJ, repression of immediate-early genes in AgRP neurons, and restraint of HSC self-renewal via TNFα signaling — expanded PHF6's functional repertoire beyond transcription to DNA repair and metabolic/immune signaling.

    Evidence Live-cell laser microirradiation with PARP inhibitor, NHEJ reporter; cell-type-specific ChIP in AgRP neurons with conditional KO and behavioral assays; conditional Phf6 KO mouse with competitive repopulation and serial transplantation

    PMID:30917958 PMID:31782600 PMID:32187544

    Open questions at the time
    • Biochemical mechanism of PHF6 in NHEJ (what step it facilitates) undefined
    • Whether TNFα pathway regulation is transcriptionally direct or indirect unknown
    • How hunger-state signals regulate PHF6 chromatin occupancy not established
  8. 2020 High

    Demonstration that PHF6 possesses intrinsic E3 ubiquitin ligase activity for H2BK120ub, directed by ePHD2 reading of H2BK12 acetylation, established a direct enzymatic function beyond chromatin adaptor roles.

    Evidence In vitro ubiquitination assay with recombinant domains, domain deletion/mutagenesis, ChIP, RNA-seq

    PMID:32735658

    Open questions at the time
    • E3 ligase activity not independently replicated by other groups
    • Whether PHF6 ubiquitin ligase activity is relevant outside trophectoderm differentiation context unknown
    • E2 partner not identified
  9. 2021 High

    Identification of PHF6-mediated recruitment of SUV39H1 and SUV4-20H2 to rDNA, gated by DNMT1-dependent DNA methylation, provided a mechanistic chain linking DNA methylation → PHF6 occupancy → repressive histone marks → rDNA silencing.

    Evidence Co-IP, ChIP, MeDIP-seq, bisulfite sequencing, DNMT1 knockdown/deficiency models, clinical PHF6 mutant analysis

    PMID:34520760 PMID:35847518

    Open questions at the time
    • How PHF6 senses hypomethylated versus methylated DNA at the structural level unknown
    • Relative contributions of SUV39H1 versus SUV4-20H2 to rDNA silencing not dissected
  10. 2022 High

    Proteomic and native ChIP-seq approaches revealed PHF6 engages NuRD, SWI/SNF, and ISWI remodelers and preferentially occupies heterochromatic satellite DNA enriched in H3K9me3, broadening its role to heterochromatin maintenance and satellite repeat integrity.

    Evidence IP-MS, native ChIP-seq, single-molecule locus-specific analysis, DNA damage assays

    PMID:35338774

    Open questions at the time
    • Whether PHF6 has distinct functions at satellite DNA versus promoters not tested
    • Functional consequence of satellite DNA occupancy for genome stability not directly shown
  11. 2024 High

    Convergent studies established that PHF6 co-localizes with SWI/SNF at promoters to maintain active chromatin (with Pol II progression dependent on PHF6 in SMARCB1-deficient contexts), drives Ephrin receptor transcription for neural stem cell self-renewal, interacts with RUNX1 at active enhancers in myeloid cells, and regulates cortical neurogenesis programs.

    Evidence CRISPR genome-scale screens, ChIP-seq, ATAC-seq, Co-IP, BFLS knockin mice, conditional KO, eNSC rescue, electrophysiology, proteomics

    PMID:38418452 PMID:38429579 PMID:39181868 PMID:39405291

    Open questions at the time
    • Whether PHF6–SWI/SNF cooperation is relevant beyond SMARCB1-deficient tumors not tested
    • How PHF6 switches between repressive (NuRD) and activating (SWI/SNF) functions mechanistically unresolved
    • Direct versus indirect transcriptional effects in cortical development not fully deconvolved
  12. 2025 High

    Discovery that PHIP is an obligate partner required for PHF6 chromatin occupancy unified the model: PHF6 depends on PHIP to access chromatin and execute its transcriptional repression program, and PHIP loss phenocopies PHF6 loss in AML leukemia-initiating cell expansion.

    Evidence Reciprocal Co-IP, ChIP-seq of PHF6 ± PHIP, CRISPR KO of both genes, mouse AML models, transcriptomics

    PMID:40721297

    Open questions at the time
    • Whether PHIP is required for all PHF6 functions (e.g., rDNA silencing, DNA repair) or only leukemic contexts unknown
    • Structural basis of the PHF6–PHIP complex not determined

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include how PHF6 switches between repressive (NuRD) and activating (SWI/SNF) modes at different loci, whether its E3 ubiquitin ligase activity operates broadly or is context-restricted, the structural basis of the full-length PHF6–PHIP–chromatin complex, and how PHF6 integrates DNA damage repair with its transcriptional functions.
  • No full-length PHF6 structure or cryo-EM of PHF6 on nucleosomes
  • Context-dependent switching between activation and repression not mechanistically explained
  • E3 ligase activity awaits independent replication and E2 identification
  • Interplay between DNA repair and transcriptional roles not connected

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 8 GO:0003677 DNA binding 3 GO:0042393 histone binding 2 GO:0016874 ligase activity 1 GO:0140096 catalytic activity, acting on a protein 1
Localization
GO:0005634 nucleus 5 GO:0005730 nucleolus 5 GO:0005654 nucleoplasm 4 GO:0005694 chromosome 2
Pathway
R-HSA-74160 Gene expression (Transcription) 8 R-HSA-4839726 Chromatin organization 6 R-HSA-1266738 Developmental Biology 4 R-HSA-1643685 Disease 4 R-HSA-8953854 Metabolism of RNA 3 R-HSA-73894 DNA Repair 2
Partners
BPTFCHD4HIF1APHIPRBBP4RUNX1SUV39H1UBF
Complex memberships
NuRDPAF1 complexPHF6-PHIP complexSWI/SNF

Evidence

Reading pass · 25 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2002 PHF6 localizes diffusely to the nucleus with prominent nucleolar accumulation, as shown by transient transfection of GFP-tagged PHF6, suggesting a role in transcription. Transient transfection with GFP-tagged PHF6, fluorescence microscopy Nature genetics Medium 12415272
2012 PHF6 physically associates with multiple components of the NuRD (nucleosome remodeling and deacetylation) complex, including CHD4, HDAC1, and RBBP4; this PHF6-NuRD interaction is restricted to the nucleoplasm and is not present in the nucleolus. Flag-tagged PHF6 co-immunoprecipitation from HEK 293T cells followed by mass spectrometry; subcellular fractionation Journal of proteome research High 22720776
2012 PHF6 localizes to the nucleolus and to ribosomal DNA (rDNA) promoter regions, directly interacts with upstream binding factor (UBF) through its PHD1 domain, and suppresses ribosomal RNA (rRNA) transcription by affecting UBF protein levels; PHF6 knockdown causes G2/M arrest and accumulation of DNA damage at the rDNA locus, reversible by knocking down UBF or overexpressing RNase I. ChIP, Co-IP, siRNA knockdown, cell cycle analysis, γH2AX measurement, RNase I rescue experiment The Journal of biological chemistry High 23229552
2013 PHF6 physically associates with the PAF1 transcription elongation complex, and knockdown of PHF6 profoundly impairs neuronal migration in the mouse cerebral cortex in vivo, forming white matter heterotopias with neuronal hyperexcitability; inhibition of PAF1 phenocopies this migration defect, and PHF6/PAF1 regulate the downstream target NGC/CSPG5. Co-IP, in utero electroporation knockdown in mouse cortex, live imaging, electrophysiology Neuron High 23791194
2014 Crystal structure of the PHF6 ePHD2 domain (comprising an N-terminal pre-PHD C2HC zinc finger, a linker, and an atypical PHD finger) reveals it as a novel integrated structural module; ePHD2 binds dsDNA but not histones; PHF6 directly interacts with RBBP4 (a NuRD component) and exerts transcriptional repression activity through this interaction. X-ray crystallography, in vitro binding assays, GAL4 reporter transcriptional repression assay, mutagenesis The Journal of biological chemistry High 24554700
2015 Crystal structure of the RBBP4–PHF6 peptide complex (residues 162–170) shows that PHF6 binds the top surface of the RBBP4 β-propeller via a pair of positively charged residues inserting into a negatively charged pocket; corresponding PHF6 mutants impair this interaction in vitro and in vivo; the PHF6 middle disordered region (residues 145–207) is sufficient for transcriptional repression mediated through RBBP4 recruitment, and RBBP4 knockdown diminishes PHF6-mediated repression. X-ray crystallography, mutagenesis, in vitro binding assay, GAL4 reporter assay, RBBP4 knockdown The Journal of biological chemistry High 25601084
2015 miR-128 directly targets PHF6 mRNA; restoring PHF6 expression counteracts the deleterious effect of miR-128 on neuronal migration, dendritic outgrowth, and intrinsic physiological properties in vivo, placing miR-128 upstream of PHF6 in cortical lamination and neuronal development. miRNA sponge experiments, rescue overexpression of PHF6, in utero electroporation, electrophysiology eLife High 25556700
2016 PHF6 localizes to the sub-nucleolar fibrillar center (FC) and dense fibrillar component (DFC) in an RNA-dependent manner; ChIP-qPCR shows PHF6 enrichment across the entire rDNA-coding sequence but not the intergenic spacer; PHF6 gain-of-function decreases overall rRNA transcription and increases repressive pRNA and non-coding IGS36RNA/IGS39RNA levels. RNase A/DNase I/ActD treatment followed by immunocytochemistry, ChIP-qPCR, rRNA quantification in gain-of-function model European journal of human genetics High 27165002
2017 Loss of PHF6 in B-cell leukemia causes systematic changes in chromatin accessibility at transcriptional start sites of B-cell- and T-cell-specific factors, down-regulation of B-cell identity genes, up-regulation of T-cell signaling genes, and gives rise to mixed-lineage lymphoma in vivo, indicating PHF6 maintains lineage identity through chromatin landscape maintenance. ATAC-seq, RNA-seq, CRISPR/Cas9 knockout, in vivo transplantation Genes & development High 28607179
2019 PHF6 is rapidly recruited to sites of DNA lesions in a PARP-dependent manner; loss of PHF6 dramatically compromises G2 checkpoint recovery and impairs DNA repair through classical non-homologous end joining (NHEJ). RNAi screen, live-cell imaging of PHF6 recruitment to laser-induced damage, PARP inhibitor treatment, NHEJ reporter assay, checkpoint recovery assay EMBO reports High 31782600
2019 PHF6 acts as a transcriptional repressor in AgRP neurons, binding promoters of immediate-early genes (IEGs); PHF6 chromatin binding is dynamically regulated by hunger state; loss of PHF6 shifts the transcriptional profile to a hunger-state-like pattern in satiated mice and impairs hunger-driven feeding behavior. Cell-type-specific ChIP, RNA-seq in AgRP neurons, conditional KO, behavioral assays Cell reports High 32187544
2019 Phf6 deficiency in hematopoietic stem cells (HSCs) represses expression of genes associated with TNFα signaling, conferring resistance to TNFα-mediated growth inhibition and enhancing HSC self-renewal and repopulating capacity. Conditional Phf6 knockout mouse, competitive repopulation assays, serial transplantation, gene expression analysis Blood High 30917958
2020 PHF6 acts as an E3 ubiquitin ligase for ubiquitination of histone H2B at K120 (H2BK120ub) via its extended PHD1 domain; the extended PHD2 domain of PHF6 recognizes acetylation of H2BK12 (H2BK12Ac), and this recognition by ePHD2 is required for PHF6's E3 ubiquitin ligase activity for H2BK120ub, thereby activating trophectodermal genes. RNA-seq, ChIP assays, in vitro ubiquitination assay, domain deletion/mutagenesis Nucleic acids research High 32735658
2021 PHF6 binds H3K9me3 and H3K27me1 on nucleolar chromatin and recruits histone methyltransferase SUV39H1 to rDNA loci; PHF6 loss decreases SUV39H1 recruitment and H3K9me3 levels at rDNA, promoting rDNA transcription; clinical PHF6 mutants impair this interaction. Co-IP, ChIP, knockdown/overexpression of PHF6 and SUV39H1, xenograft models, patient sample analysis Acta pharmaceutica sinica. B High 35847518
2021 PHF6 represses p21 expression by directly binding to the p21 promoter region and recruiting RBBP4; loss of PHF6 derepresses p21, contributing to prednisolone resistance in T-ALL cells. ChIP, CRISPR-Cas9 correction of PHF6 point mutation, siRNA knockdown, MTT assay Biomedicine & pharmacotherapy Medium 30551478
2021 PHF6 deficiency promotes JAK3M511I-induced T-ALL progression in mice by inhibiting the Bai1-Mdm2-P53 signaling pathway, independent of JAK3/STAT5 signaling. Mouse leukemia models, genetic epistasis (PHF6 KO + JAK3M511I), pathway analysis, inhibitor combination in vivo Leukemia Medium 34465864
2021 DNMT1-mediated gene body methylation at rDNA prevents PHF6 binding to hypomethylated rDNA gene bodies; when gene body methylation is reduced, PHF6 occupancy increases and PHF6 recruits histone methyltransferase SUV4-20H2 to establish H4K20me3, thereby inhibiting rDNA transcription. MeDIP-seq, bisulfite sequencing, ChIP, immunofluorescence, DNMT1 knockdown/deficiency models The Journal of biological chemistry High 34520760
2022 PHF6 engages multiple nucleosome remodeling protein complexes including NuRD, SWI/SNF, and ISWI factors, as well as replication machinery and DNA repair proteins; native ChIP-seq shows PHF6 specifically associates with heterochromatin satellite DNA regions enriched in H3K9me3; PHF6 loss impairs resolution of single- and double-strand DNA breaks. Proteomics (immunoprecipitation-MS), native ChIP-seq, single-molecule locus-specific analysis, DNA damage assays Blood High 35338774
2023 PHF6 physically interacts with NF-κB subunit p50; PHF6 depletion disrupts the PHF6-p50 complex and partially inhibits nuclear translocation of p50, suppressing BCL2 expression and inhibiting AML cell proliferation/survival. Co-IP, siRNA knockdown, NF-κB inhibitor treatment, apoptosis and proliferation assays Leukemia Medium 37393343
2023 PHF6 physically interacts with HIF-1α and HIF-2α to potentiate HIF-driven transcriptional activity; PHF6 recruits BPTF to mediate epigenetic remodeling at HIF target gene loci; HIF double-knockout abolishes PHF6-mediated breast tumor growth. Co-IP, ChIP-qPCR, CRISPR HIF double-KO, xenograft models Journal of translational medicine Medium 36967443
2024 PHF6 co-localizes with SWI/SNF complexes at promoters and is essential for maintaining active chromatin state at those loci; in SMARCB1-deficient cells, PHF6 loss disrupts the recruitment and stability of residual SWI/SNF complex members, resulting in loss of active chromatin at promoters and stalling of RNA Polymerase II progression. CRISPR-Cas9 genome-scale screen, ChIP-seq, ATAC-seq, co-IP, RNA Pol II occupancy assays Nature communications High 39181868
2024 PHF6 directly interacts with RUNX1; both proteins co-localize at active enhancer regions that define lineage differentiation context in myeloid neoplasms. Proteomics, ChIP-seq co-localization, co-IP Nature communications Medium 38418452
2024 PHF6 genome-wide binding in the developing cortex is enriched near genes involved in CNS development and neurogenesis; PHF6 directly promotes transcription of Ephrin receptors (EphRs); PHF6 regulation of EphR is impaired in BFLS mice and conditional Phf6 KO mice; EphR-A knockdown phenocopies PHF6 loss in embryonic neural stem cells (eNSCs) and forced EphR expression rescues BFLS mouse-derived eNSC defects. Genome-wide ChIP-seq in developing cortex, BFLS knockin mice, conditional KO, in vitro eNSC assays, rescue experiments EMBO reports High 38429579
2024 PHF6 loss in the developing cortex causes upregulation of genes including Reln, Nr4a2, Slc12a5, Phip, and ZIC transcription factors; Phf6-deficient neural precursor cells show reduced self-renewal and increased neuronal differentiation; Phf6-deficient cortical neurons show premature spontaneous neuronal activity. Germline and nervous-system-specific Phf6 KO mice, transcriptomic analysis, neurosphere assays, electrophysiology PLoS genetics High 39405291
2025 PHF6 and PHIP form a functional chromatin complex; PHF6 requires PHIP to occupy chromatin and execute its downstream transcriptional repression program; PHF6 loss expands AML leukemia-initiating cells and upregulates a stemness gene network; PHIP loss phenocopies PHF6 loss. Co-IP, ChIP-seq, CRISPR/Cas9 KO of PHF6 and PHIP, mouse leukemia models, transcriptomics Genes & development High 40721297

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2010 PHF6 mutations in T-cell acute lymphoblastic leukemia. Nature genetics 248 20228800
2002 Mutations in PHF6 are associated with Börjeson-Forssman-Lehmann syndrome. Nature genetics 177 12415272
2015 Tau assembly: the dominant role of PHF6 (VQIVYK) in microtubule binding region repeat R3. The journal of physical chemistry. B 150 25775228
2010 PHF6 mutations in adult acute myeloid leukemia. Leukemia 141 21030981
2013 The X-linked intellectual disability protein PHF6 associates with the PAF1 complex and regulates neuronal migration in the mammalian brain. Neuron 87 23791194
2012 PHF6 interacts with the nucleosome remodeling and deacetylation (NuRD) complex. Journal of proteome research 86 22720776
2015 miR-128 regulates neuronal migration, outgrowth and intrinsic excitability via the intellectual disability gene Phf6. eLife 85 25556700
2012 PHF6 regulates cell cycle progression by suppressing ribosomal RNA synthesis. The Journal of biological chemistry 81 23229552
1999 Fibroblast growth factor homologous factor 2 (FHF2): gene structure, expression and mapping to the Börjeson-Forssman-Lehmann syndrome region in Xq26 delineated by a duplication breakpoint in a BFLS-like patient. Human genetics 74 10071193
2011 Mutations of PHF6 are associated with mutations of NOTCH1, JAK1 and rearrangement of SET-NUP214 in T-cell acute lymphoblastic leukemia. Haematologica 70 21880637
2018 Phf6 Loss Enhances HSC Self-Renewal Driving Tumor Initiation and Leukemia Stem Cell Activity in T-ALL. Cancer discovery 62 30567843
2014 Structural and functional insights into the human Börjeson-Forssman-Lehmann syndrome-associated protein PHF6. The Journal of biological chemistry 62 24554700
2004 The clinical picture of the Börjeson-Forssman-Lehmann syndrome in males and heterozygous females with PHF6 mutations. Clinical genetics 61 14756673
2015 A genome-scale in vivo loss-of-function screen identifies Phf6 as a lineage-specific regulator of leukemia cell growth. Genes & development 58 25737277
2018 PHF6 and DNMT3A mutations are enriched in distinct subgroups of mixed phenotype acute leukemia with T-lineage differentiation. Blood advances 56 30530780
2014 MicroRNA-128-3p is a novel oncomiR targeting PHF6 in T-cell acute lymphoblastic leukemia. Haematologica 51 24895337
2017 PHF6 regulates phenotypic plasticity through chromatin organization within lineage-specific genes. Genes & development 49 28607179
2018 Mechanistic insights into remodeled Tau-derived PHF6 peptide fibrils by Naphthoquinone-Tryptophan hybrids. Scientific reports 46 29311706
2013 A new face of Borjeson-Forssman-Lehmann syndrome? De novo mutations in PHF6 in seven females with a distinct phenotype. Journal of medical genetics 46 24092917
2005 Mutation screening in Borjeson-Forssman-Lehmann syndrome: identification of a novel de novo PHF6 mutation in a female patient. Journal of medical genetics 46 15994862
2006 The Börjeson-Forssman-Lehman syndrome (BFLS, MIM #301900). European journal of human genetics : EJHG 45 16912705
2019 PHF6 regulates hematopoietic stem and progenitor cells and its loss synergizes with expression of TLX3 to cause leukemia. Blood 44 30755422
2016 Primary Fibril Nucleation of Aggregation Prone Tau Fragments PHF6 and PHF6. The journal of physical chemistry. B 44 27776213
2010 T-cell acute lymphoblastic leukemia in association with Börjeson-Forssman-Lehmann syndrome due to a mutation in PHF6. Pediatric blood & cancer 43 20806366
2021 Aggregated Tau-PHF6 (VQIVYK) Potentiates NLRP3 Inflammasome Expression and Autophagy in Human Microglial Cells. Cells 42 34209408
2019 Membrane-mediated fibrillation and toxicity of the tau hexapeptide PHF6. The Journal of biological chemistry 42 31439664
2015 Structural basis of plant homeodomain finger 6 (PHF6) recognition by the retinoblastoma binding protein 4 (RBBP4) component of the nucleosome remodeling and deacetylase (NuRD) complex. The Journal of biological chemistry 39 25601084
2015 PHF6 Degrees of Separation: The Multifaceted Roles of a Chromatin Adaptor Protein. Genes 39 26103525
2016 Naphthoquinone-Tryptophan Hybrid Inhibits Aggregation of the Tau-Derived Peptide PHF6 and Reduces Neurotoxicity. Journal of Alzheimer's disease : JAD 37 26836184
2019 The chromatin-binding protein Phf6 restricts the self-renewal of hematopoietic stem cells. Blood 36 30917958
2021 PHF6 and JAK3 mutations cooperate to drive T-cell acute lymphoblastic leukemia progression. Leukemia 35 34465864
2019 Disclosing the Mechanism of Spontaneous Aggregation and Template-Induced Misfolding of the Key Hexapeptide (PHF6) of Tau Protein Based on Molecular Dynamics Simulation. ACS chemical neuroscience 35 31661961
2021 Effects of All-Atom Molecular Mechanics Force Fields on Amyloid Peptide Assembly: The Case of PHF6 Peptide of Tau Protein. Journal of chemical theory and computation 34 34491058
2021 PHF6 Mutations in Hematologic Malignancies. Frontiers in oncology 32 34381727
2011 PHF6 Deletions May Cause Borjeson-Forssman-Lehmann Syndrome in Females. Molecular syndromology 32 22190899
2019 Phf6-null hematopoietic stem cells have enhanced self-renewal capacity and oncogenic potentials. Blood advances 31 31395598
2018 Effective suppression of the modified PHF6 peptide/1N4R Tau amyloid aggregation by intact curcumin, not its degradation products: Another evidence for the pigment as preventive/therapeutic "functional food". International journal of biological macromolecules 29 30172816
2016 Pathogenesis of Börjeson-Forssman-Lehmann syndrome: Insights from PHF6 function. Neurobiology of disease 28 27633282
2020 The chromatin-binding protein PHF6 functions as an E3 ubiquitin ligase of H2BK120 via H2BK12Ac recognition for activation of trophectodermal genes. Nucleic acids research 26 32735658
2019 PHF6 promotes non-homologous end joining and G2 checkpoint recovery. EMBO reports 26 31782600
2016 The sub-nucleolar localization of PHF6 defines its role in rDNA transcription and early processing events. European journal of human genetics : EJHG 26 27165002
2020 Selection of a d-Enantiomeric Peptide Specifically Binding to PHF6 for Inhibiting Tau Aggregation in Transgenic Mice. ACS chemical neuroscience 25 33284003
2011 Somatic mutation of PHF6 gene in T-cell acute lymphoblatic leukemia, acute myelogenous leukemia and hepatocellular carcinoma. Acta oncologica (Stockholm, Sweden) 25 21736506
2006 Conformational sampling with implicit solvent models: application to the PHF6 peptide in tau protein. Biophysical journal 24 17040986
2004 Clinical and behavioral features of patients with Borjeson-Forssman-Lehmann syndrome with mutations in PHF6. The Journal of pediatrics 24 15580208
2022 Epigenetic reversal of hematopoietic stem cell aging in Phf6-knockout mice. Nature aging 21 37118089
2021 Gene body methylation safeguards ribosomal DNA transcription by preventing PHF6-mediated enrichment of repressive histone mark H4K20me3. The Journal of biological chemistry 21 34520760
2018 The depletion of PHF6 decreases the drug sensitivity of T-cell acute lymphoblastic leukemia to prednisolone. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 18 30551478
2009 Börjeson-Forssman-Lehmann Syndrome due to a novel plant homeodomain zinc finger mutation in the PHF6 gene. Journal of child neurology 18 19264739
2022 Functional mapping of PHF6 complexes in chromatin remodeling, replication dynamics, and DNA repair. Blood 17 35338774
2013 Distinct phenotype of PHF6 deletions in females. European journal of medical genetics 17 24380767
2005 Radiation leukemia virus common integration at the Kis2 locus: simultaneous overexpression of a novel noncoding RNA and of the proximal Phf6 gene. Journal of virology 17 16103195
2019 MicroRNA-214 suppresses cell proliferation and migration and cell metabolism by targeting PDK2 and PHF6 in hepatocellular carcinoma. Cell biology international 16 31329335
2023 Mapping the configurational landscape and aggregation phase behavior of the tau protein fragment PHF6. Proceedings of the National Academy of Sciences of the United States of America 15 37983502
2021 LINC00958/miR-3174/PHF6 axis is responsible for triggering proliferation, migration and invasion of endometrial cancer. European review for medical and pharmacological sciences 15 34859848
2016 Co-existence of PHF6 and NOTCH1 mutations in adult T-cell acute lymphoblastic leukemia. Oncology letters 15 27347093
2023 PHF6 maintains acute myeloid leukemia via regulating NF-κB signaling pathway. Leukemia 14 37393343
2024 Molecular and clinical analyses of PHF6 mutant myeloid neoplasia provide their pathogenesis and therapeutic targeting. Nature communications 13 38418452
2023 PHF6 recruits BPTF to promote HIF-dependent pathway and progression in YAP-high breast cancer. Journal of translational medicine 12 36967443
2021 PHF6 functions as a tumor suppressor by recruiting methyltransferase SUV39H1 to nucleolar region and offers a novel therapeutic target for PHF6-muntant leukemia. Acta pharmaceutica Sinica. B 12 35847518
2019 A Novel Nonsense Mutation of PHF6 in a Female with Extended Phenotypes of Borjeson-Forssman-Lehmann Syndrome. Journal of clinical research in pediatric endocrinology 12 30630810
2024 Exploring the Aggregation Propensity of PHF6 Peptide Segments of the Tau Protein Using Ion Mobility Mass Spectrometry Techniques. Analytical chemistry 11 38517679
2024 PHF6 cooperates with SWI/SNF complexes to facilitate transcriptional progression. Nature communications 11 39181868
2023 Atomistic Insights into the Inhibitory Mechanism of Tyrosine Phosphorylation against the Aggregation of Human Tau Fragment PHF6. The journal of physical chemistry. B 11 36594671
2021 Transgenic mice with an R342X mutation in Phf6 display clinical features of Börjeson-Forssman-Lehmann Syndrome. Human molecular genetics 11 33772537
2023 Identification of Aggregation Mechanism of Acetylated PHF6* and PHF6 Tau Peptides Based on Molecular Dynamics Simulations and Markov State Modeling. ACS chemical neuroscience 10 37830541
2022 On the Tracks of the Aggregation Mechanism of the PHF6 Peptide from Tau Protein: Molecular Dynamics, Energy, and Interaction Network Investigations. ACS chemical neuroscience 10 36153969
2021 LncRNA Bmp1 promotes the healing of intestinal mucosal lesions via the miR-128-3p/PHF6/PI3K/AKT pathway. Cell death & disease 10 34108447
2019 Downregulation of PHF6 Inhibits Cell Proliferation and Migration in Hepatocellular Carcinoma. Cancer biotherapy & radiopharmaceuticals 10 30888215
2014 Detection of an activated JAK3 variant and a Xq26.3 microdeletion causing loss of PHF6 and miR-424 expression in myelodysplastic syndromes by combined targeted next generation sequencing and SNP array analysis. Pathology, research and practice 10 24674452
2024 PHF6 suppresses self-renewal of leukemic stem cells in AML. Leukemia 9 39004675
2015 The potential role of PHF6 as an oncogene: a genotranscriptomic/proteomic meta-analysis. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 9 26561469
2022 Oncogenesis induced by combined Phf6 and Idh2 mutations through increased oncometabolites and impaired DNA repair. Oncogene 8 35091680
2022 Deciphering the Role of ATP on PHF6 Aggregation. The journal of physical chemistry. B 8 35759245
2022 The Role of PHF6 in Hematopoiesis and Hematologic Malignancies. Stem cell reviews and reports 8 36008597
2021 Notoginsenoside R1 induces DNA damage via PHF6 protein to inhibit cervical carcinoma cell proliferation. Molecular medicine reports 8 33537816
2024 PHF6-altered T-ALL Harbor Epigenetic Repressive Switch at Bivalent Promoters and Respond to 5-Azacitidine and Venetoclax. Clinical cancer research : an official journal of the American Association for Cancer Research 7 37889114
2024 Molecular Dynamics Simulation Study of the Self-Assembly of Tau-Derived PHF6 and Its Inhibition by Oleuropein Aglycone from Extra Virgin Olive Oil. The journal of physical chemistry. B 7 38814052
2023 PHF6 promotes the progression of endometrial carcinoma by increasing cancer cells growth and decreasing T-cell infiltration. Journal of cellular and molecular medicine 7 36756714
2021 Comparison of the force fields on monomeric and fibrillar PHF6 of tau protein. Biophysical chemistry 7 34116358
2020 Chromatin-Binding Protein PHF6 Regulates Activity-Dependent Transcriptional Networks to Promote Hunger Response. Cell reports 7 32187544
2020 A Novel Missense Variant in PHF6 Gene Causing Börjeson-Forssman-Lehman Syndrome. Journal of molecular neuroscience : MN 7 32399860
2020 Loss of PHF6 leads to aberrant development of human neuron-like cells. Scientific reports 7 33149206
2015 The PHF6 Mutation c.1A>G; pM1V Causes Börjeson-Forsman-Lehmann Syndrome in a Family with Four Affected Young Boys. Molecular syndromology 7 26648834
2022 Circ_0039569 contributes to the paclitaxel resistance of endometrial cancer via targeting miR-1271-5p/PHF6 pathway. Anti-cancer drugs 6 36136988
2022 PHF6 mutation is associated with poor outcome in acute myeloid leukaemia. Cancer medicine 6 36176187
2021 Molecular dynamics simulations reveal the disruption mechanism of a 2,4-thiazolidinedione derivative C30 against tau hexapeptide (PHF6) oligomer. Proteins 5 34331342
2024 Unraveling the Structure and Dynamics of Ac-PHF6-NH2 Tau Segment Oligomers. ACS chemical neuroscience 4 39215387
2023 Deciphering the Inhibitory Mechanism of Naphthoquinone-Dopamine on the Aggregation of Tau Core Fragments PHF6* and PHF6. ACS chemical neuroscience 4 37585669
2022 MiR-1306-5p promotes cell proliferation and inhibits cell apoptosis in acute myeloid leukemia by downregulating PHF6 expression. Leukemia research 4 35780573
2025 Substitution of tyrosine with electron-deficient aromatic amino acids improves Ac-PHF6 self-assembly and hydrogelation. RSC advances 3 40599564
2024 PHF6-mediated transcriptional control of NSC via Ephrin receptors is impaired in the intellectual disability syndrome BFLS. EMBO reports 3 38429579
2023 R274X-mutated Phf6 increased the self-renewal and skewed T cell differentiation of hematopoietic stem cells. iScience 3 37288345
2022 Effect of Trehalose and Ceftriaxone on the Stability of Aggregating-Prone Tau Peptide Containing PHF6* Sequence: An SRCD Study. International journal of molecular sciences 3 35328353
2025 Leukemia mutated proteins PHF6 and PHIP form a chromatin complex that represses acute myeloid leukemia stemness. Genes & development 2 40721297
2024 PHF6 loss reduces leukemia stem cell activity in an acute myeloid leukemia mouse model. Cancer cell international 2 38336746
2024 A selection and optimization strategy for single-domain antibodies targeting the PHF6 linear peptide within the tau intrinsically disordered protein. The Journal of biological chemistry 2 38484799
2024 Disruption of PHF6 Peptide Aggregation from Tau Protein: Mechanisms of Palmatine Chloride in Preventing Early PHF6 Aggregation. ACS chemical neuroscience 1 39404232
2024 Loss of PHF6 causes spontaneous seizures, enlarged brain ventricles and altered transcription in the cortex of a mouse model of the Börjeson-Forssman-Lehmann intellectual disability syndrome. PLoS genetics 1 39405291
2022 Concurrent Mutations in SF3B1 and PHF6 in Myeloid Neoplasms. Biology 1 36671709