{"gene":"PHF10","run_date":"2026-06-10T06:43:35","timeline":{"discoveries":[{"year":2014,"finding":"The PHF10 gene encodes two types of evolutionarily conserved isoforms that are incorporated into the PBAF complex in a mutually exclusive manner. One isoform contains C-terminal tandem PHD fingers (DPF domain); the other isoform has these replaced by a consensus sequence for phosphorylation-dependent SUMO 1 conjugation (PDSM). PBAF complexes containing different PHF10 isoforms can bind to the same gene promoters but produce different effects on Pol II recruitment and gene transcription levels, and only the PHD-containing isoform activates proliferation.","method":"Molecular cloning, co-immunoprecipitation, promoter binding assays, Pol II recruitment assays, proliferation assays","journal":"Cell cycle (Georgetown, Tex.)","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — reciprocal Co-IP and functional assays in a single lab with multiple orthogonal methods","pmids":["24763304"],"is_preprint":false},{"year":2017,"finding":"PHF10 protein stability is regulated by the E3 ubiquitin ligase β-TrCP, which degrades PHF10 via two non-canonical β-TrCP degrons in a phospho-dependent manner. Unusually, phosphorylation of PHF10-S isoform degrons by CK-1 prevents their degradation (molecular docking showed phosphorylated PHF10 binds β-TrCP with lower affinity). β-TrCP knockdown stabilizes PHF10 as well as other PBAF core subunits (BRG1, BAF155, BAF200, BAF180, BRD7).","method":"siRNA knockdown, half-life assays, phosphorylation analysis, targeted molecular docking","journal":"Scientific reports","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — functional knockdown combined with molecular docking, single lab, multiple methods","pmids":["28717195"],"is_preprint":false},{"year":2016,"finding":"All four PHF10 isoforms are extensively phosphorylated in human cells, and their phosphorylation occurs while they are incorporated as subunits of the PBAF complex. The phosphorylation level is cell-type dependent.","method":"Immunoprecipitation of PBAF complex, phosphorylation analysis across multiple human cell types","journal":"Molekuliarnaia biologiia","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single lab, single method described in abstract without full methodological detail","pmids":["27239853"],"is_preprint":false},{"year":2020,"finding":"PHF10 isoforms lacking C-terminal PHD domains contain an X-cluster of phosphorylated serine residues consisting of two independently phosphorylated subclusters; phosphorylation of the second subcluster depends on phosphorylation of a primary serine 327. A predicted nuclear localization sequence (NLS3) between the subclusters does not affect PHF10 localization but is essential for X-cluster phosphorylation and increased stability of PHD-lacking isoforms; conversely, NLS3 reduces stability of PHD-containing isoforms. Sequential phosphorylation thus regulates isoform cell-level and rate of incorporation into PBAF.","method":"Phospho-site mapping, mutagenesis of serine residues and NLS3, stability assays","journal":"Biology open","confidence":"Medium","confidence_rationale":"Tier 1-2 / Moderate — mutagenesis combined with functional stability assays, single lab","pmids":["31911482"],"is_preprint":false},{"year":2021,"finding":"PHF10 interacts with the MYC oncoprotein and facilitates recruitment of the PBAF complex to MYC target gene promoters, augmenting MYC-dependent transcriptional activation of cell cycle genes. Depletion of PHF10 induces G1 accumulation and a senescence-like phenotype in melanoma cells.","method":"Co-immunoprecipitation, ChIP, siRNA knockdown, cell cycle analysis","journal":"Oncogene","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — reciprocal Co-IP and ChIP with functional KD phenotype, single lab","pmids":["34465901"],"is_preprint":false},{"year":2019,"finding":"The c-MYC oncogene transcriptionally activates PHF10 expression in cancer cell lines.","method":"Reporter assays and expression analysis in cell lines with c-MYC manipulation","journal":"Doklady. Biochemistry and biophysics","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single lab, limited methodological detail in abstract","pmids":["31012017"],"is_preprint":false},{"year":2022,"finding":"ZC3H13-mediated m6A methylation of PHF10 mRNA promotes PHF10 translation in a YTHDF1-dependent manner. Fisetin suppresses HR repair of DNA double-strand breaks by reducing m6A modification of PHF10. PHF10 loss-of-function results in elevated recruitment of γH2AX, RAD51, and 53BP1 to DSB sites and decreased homologous recombination repair efficiency in pancreatic cancer cells.","method":"m6A methylation assays, siRNA knockdown, γH2AX/RAD51/53BP1 foci analysis, HR repair assays","journal":"Cancer letters","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — multiple functional assays (m6A, foci, HR efficiency) in single lab","pmids":["35033590"],"is_preprint":false},{"year":2016,"finding":"Deletion of BAF45a/PHF10 in the adult mouse hematopoietic system causes a dose-dependent decrease in the frequency of long-term repopulating hematopoietic stem cells and committed myeloid progenitors without affecting proliferation rate. BAF45a-deficient HSCs are selectively lost from mixed bone marrow chimeras, indicating impaired cell-intrinsic function.","method":"Conditional knockout mouse, mixed bone marrow chimeras, flow cytometry","journal":"Experimental hematology","confidence":"High","confidence_rationale":"Tier 2 / Strong — conditional KO with chimera rescue experiment in mouse model, rigorous cell-intrinsic functional test","pmids":["27931852"],"is_preprint":false},{"year":2010,"finding":"PHF10 is required for cell proliferation: both overexpression of truncated PHF10 (dominant negative effect) and RNAi-mediated knockdown of PHF10 result in reduced cell proliferation in normal human diploid fibroblasts and multiple cell lines.","method":"Overexpression of truncated cDNA constructs, RNAi knockdown, proliferation assays","journal":"Cytogenetic and genome research","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — two complementary loss-of-function approaches (truncation OE and RNAi) both showing proliferation defect","pmids":["20068294"],"is_preprint":false},{"year":2021,"finding":"PHF10 changes its subcellular localization in response to LTP induction in neuronal culture: PHF10 is normally nuclear but translocates to the cytoplasm 1 hour after LTP induction (KCl stimulation), then returns to the nucleus together with c-FOS. PHF10 physically interacts with the c-FOS transcriptional activator. This behavior is specific to neuronal cultures.","method":"Immunofluorescence, co-immunoprecipitation, KCl-induced LTP in neuronal cultures","journal":"Molekuliarnaia biologiia","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single lab, localization and pulldown without full functional validation of the interaction's downstream effect","pmids":["34837706"],"is_preprint":false},{"year":2024,"finding":"PHF10 forms a positive feedback loop with E2F1 (E2F1 drives PHF10 expression; PHF10 in turn activates E2F1 expression via PBAF complex assembly). PHF10 mediates transcriptional repression of DUSP5 through SWI/SNF complex assembly, leading to elevated pERK1/2. The E2F1-PHF10-DUSP5-pERK1/2 axis regulates differentiation inhibition and stemness promotion in gastric cancer cells.","method":"ChIP, co-immunoprecipitation, siRNA knockdown, rescue experiments, Western blot for pERK1/2","journal":"Cancer gene therapy","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — ChIP, Co-IP, and rescue experiments in single lab establishing pathway epistasis","pmids":["39127832"],"is_preprint":false},{"year":2025,"finding":"Keap1 binds PHF10 and promotes its polyubiquitination and proteasomal degradation. Cancer-associated Keap1 mutations are incapable of degrading PHF10, leading to PHF10 protein accumulation. PHF10 interacts with NRF2 and activates NRF2 downstream antioxidant targets by recruiting SMARCA2 to increase chromatin accessibility at NRF2-binding transcriptional regions, conferring ferroptosis resistance in Keap1-deficient NSCLC.","method":"Tandem affinity purification/mass spectrometry, Co-IP, ubiquitination assays, ATAC-seq, xenograft models","journal":"Cancer research and treatment","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — Co-IP and ubiquitination assays with ATAC-seq and in vivo model, single lab multiple orthogonal methods","pmids":["41197527"],"is_preprint":false},{"year":2025,"finding":"EZH2 mediates H3K27me3 enrichment on the PHF10 promoter region, suppressing PHF10 expression. PHF10 loss in cholangiocarcinoma activates NF-κB signaling by de-repressing HMGB1; PHF10 coordinates with Setdb1 to mediate H3K9me3 modifications on the HMGB1 promoter to suppress its expression.","method":"ChIP, transcriptome analysis, siRNA/CRISPR KO, in vitro and in vivo functional assays","journal":"Journal of cellular and molecular medicine","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — ChIP for histone marks, transcriptome, and in vivo validation in single lab","pmids":["39904827"],"is_preprint":false},{"year":2022,"finding":"BAF45A (PHF10) associates specifically with the PBAF complex (not cBAF). BAF45A overexpression in osteoblasts activates genes essential for osteoblast maturation and mineralization. Baf45a knockout reduces chromatin accessibility at osteoblast/odontoblast-specific gene loci (shown by ATAC-seq), and craniofacial mesenchyme-specific loss of Baf45a reduces tooth and mandibular bone mineralization. RUNX2 binds to Baf45a promoter, and PBAF-RUNX2 crosstalk mediates transcriptional activation for early differentiation.","method":"ChIP-seq (H3K9ac, H3K27ac), ATAC-seq, shRNA knockdown, overexpression, conditional KO mouse","journal":"Frontiers in endocrinology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — ChIP-seq, ATAC-seq, and conditional KO in single lab with multiple orthogonal approaches","pmids":["35046892"],"is_preprint":false},{"year":2024,"finding":"During neuronal and muscle differentiation of human and mouse cells, PHF10 isoform expression shifts: the DPF-lacking isoform replaces the DPF-containing isoform in the PBAF complex, potentially altering selectivity in gene regulation during differentiation.","method":"RT-PCR and Western blot analysis of isoform expression during in vitro differentiation","journal":"Doklady. Biochemistry and biophysics","confidence":"Low","confidence_rationale":"Tier 3 / Weak — expression-level observation during differentiation, single lab, no direct functional mechanistic test","pmids":["38189889"],"is_preprint":false}],"current_model":"PHF10 (BAF45a) is a signature subunit of the PBAF SWI/SNF chromatin remodeling complex that is expressed as four isoforms incorporating either a DPF (double PHD finger) domain or a PDSM phosphorylation site in a mutually exclusive fashion; these isoforms are differentially regulated by CK-1-dependent phosphorylation of an X-cluster and by β-TrCP- and Keap1-mediated ubiquitination/degradation, which together control isoform levels and PBAF complex composition. PHF10 physically interacts with transcriptional activators MYC and c-FOS (and NRF2 in the context of Keap1 loss), recruits PBAF to target gene promoters to regulate proliferation, differentiation, DNA damage repair (HR), and oxidative stress responses, and in the hematopoietic system is essential for long-term repopulating stem cell maintenance."},"narrative":{"mechanistic_narrative":"PHF10 (BAF45a) is a signature subunit of the PBAF SWI/SNF chromatin-remodeling complex that couples PBAF recruitment to transcriptional programs controlling proliferation, differentiation, and stress responses [PMID:24763304, PMID:35046892]. It is expressed as evolutionarily conserved isoforms that are incorporated into PBAF in a mutually exclusive manner: one bears C-terminal tandem PHD fingers (DPF domain) and activates proliferation, the other replaces these with a phosphorylation-dependent SUMO-conjugation motif, and PBAF complexes carrying different isoforms bind shared promoters yet differ in their effects on Pol II recruitment and transcription [PMID:24763304]. Isoform levels are set post-translationally by phosphorylation and regulated proteolysis: CK-1-dependent phosphorylation of an X-cluster of serines (organized as sequentially phosphorylated subclusters dependent on a primary Ser327 and the NLS3 element) stabilizes PHD-lacking isoforms, and the E3 ligase β-TrCP degrades PHF10 through non-canonical degrons whose phosphorylation paradoxically blocks degradation [PMID:28717195, PMID:31911482]. PHF10 directs PBAF to target promoters via direct interaction with sequence-specific activators, augmenting MYC-dependent activation of cell-cycle genes, engaging E2F1 in a positive feedback loop that represses DUSP5 to elevate pERK1/2, and recruiting SMARCA2 to NRF2-binding regions to drive antioxidant transcription and ferroptosis resistance when Keap1 (which normally ubiquitinates and degrades PHF10) is lost [PMID:34465901, PMID:39127832, PMID:41197527]. It also supports homologous-recombination repair of DNA double-strand breaks, its loss elevating γH2AX, RAD51, and 53BP1 foci and reducing repair efficiency [PMID:35033590]. Physiologically, PHF10 is required cell-intrinsically for maintenance of long-term repopulating hematopoietic stem cells and for osteoblast/odontoblast differentiation and mineralization downstream of RUNX2 [PMID:27931852, PMID:35046892]. PHF10 expression is itself constrained by repressive chromatin via EZH2-mediated H3K27me3, and PHF10 in turn cooperates with Setdb1 to deposit H3K9me3 and silence HMGB1, restraining NF-κB signaling [PMID:39904827].","teleology":[{"year":2010,"claim":"Established that PHF10 is functionally required for cell proliferation rather than being a passive complex subunit, by showing that both dominant-negative truncation and RNAi knockdown impair growth.","evidence":"Truncated cDNA overexpression and RNAi in human fibroblasts and cell lines with proliferation assays","pmids":["20068294"],"confidence":"Medium","gaps":["Did not define the molecular target genes or PBAF-dependent mechanism","No isoform-resolved analysis"]},{"year":2014,"claim":"Defined PHF10 as a PBAF-incorporated subunit existing as mutually exclusive DPF- versus PDSM-containing isoforms that confer distinct transcriptional outputs, explaining how a single gene tunes PBAF function.","evidence":"Molecular cloning, reciprocal Co-IP, promoter binding and Pol II recruitment assays, proliferation assays","pmids":["24763304"],"confidence":"Medium","gaps":["Mechanism by which isoforms differentially affect Pol II not resolved","Endogenous promoter targets not genome-wide mapped"]},{"year":2016,"claim":"Showed that PHF10 isoforms are extensively phosphorylated while assembled in PBAF, in a cell-type-dependent manner, indicating signaling input onto the complex.","evidence":"Immunoprecipitation of PBAF and phosphorylation analysis across human cell types","pmids":["27239853"],"confidence":"Low","gaps":["Single method described without full detail in abstract","Kinases and functional consequences of phosphorylation not defined here"]},{"year":2016,"claim":"Demonstrated a cell-intrinsic physiological requirement for PHF10 in maintaining long-term repopulating hematopoietic stem cells, distinguishing this role from a general proliferation effect.","evidence":"Conditional knockout mouse with mixed bone marrow chimeras and flow cytometry","pmids":["27931852"],"confidence":"High","gaps":["Target genes mediating HSC maintenance not identified","Isoform contribution to HSC phenotype unaddressed"]},{"year":2017,"claim":"Identified β-TrCP as the E3 ligase controlling PHF10 stability through non-canonical phospho-degrons, with the unusual feature that degron phosphorylation prevents degradation and stabilizes PHF10 and other PBAF core subunits.","evidence":"siRNA knockdown, half-life assays, phosphorylation analysis, molecular docking","pmids":["28717195"],"confidence":"Medium","gaps":["Kinase generating the protective phosphorylation not pinned down here","Docking-based affinity claim not validated by direct binding measurement"]},{"year":2019,"claim":"Placed PHF10 downstream of MYC transcriptionally, showing c-MYC activates PHF10 expression and hinting at a regulatory circuit.","evidence":"Reporter assays and expression analysis with c-MYC manipulation in cell lines","pmids":["31012017"],"confidence":"Low","gaps":["Limited methodological detail in abstract","Direct promoter occupancy not shown"]},{"year":2020,"claim":"Resolved the phospho-code controlling PHF10 isoform levels, defining an X-cluster of serines with sequential, Ser327-dependent subcluster phosphorylation and an NLS3 element that oppositely modulates stability of PHD-lacking versus PHD-containing isoforms.","evidence":"Phospho-site mapping, serine and NLS3 mutagenesis, stability assays","pmids":["31911482"],"confidence":"Medium","gaps":["Responsible kinase(s) for each subcluster not all identified","Link between stability code and specific gene programs untested"]},{"year":2021,"claim":"Showed PHF10 physically binds MYC and recruits PBAF to MYC target promoters to amplify cell-cycle gene activation, with depletion causing G1 arrest and senescence-like phenotype, mechanistically connecting PHF10 to oncogenic transcription.","evidence":"Co-IP, ChIP, siRNA knockdown, cell cycle analysis in melanoma cells","pmids":["34465901"],"confidence":"Medium","gaps":["Isoform specificity of the MYC interaction not resolved","Single cancer-cell context"]},{"year":2021,"claim":"Revealed activity-dependent regulation of PHF10 in neurons, with nuclear-cytoplasmic shuttling upon LTP induction and physical interaction with c-FOS, extending PHF10 function to neuronal stimulus responses.","evidence":"Immunofluorescence, Co-IP, KCl-induced LTP in neuronal cultures","pmids":["34837706"],"confidence":"Low","gaps":["Downstream transcriptional consequence of the c-FOS interaction not demonstrated","Localization shuttling not mechanistically explained"]},{"year":2022,"claim":"Connected PHF10 to genome stability and its translational control, showing ZC3H13/YTHDF1 m6A-dependent translation of PHF10 mRNA and that PHF10 is required for efficient homologous-recombination repair of DSBs.","evidence":"m6A assays, siRNA knockdown, γH2AX/RAD51/53BP1 foci and HR repair assays in pancreatic cancer cells","pmids":["35033590"],"confidence":"Medium","gaps":["Whether PHF10 acts at break sites via PBAF chromatin remodeling not directly shown","Isoform dependence of the HR role unknown"]},{"year":2022,"claim":"Established PHF10 as a PBAF-specific subunit driving differentiation, demonstrating that BAF45A activates osteoblast/odontoblast maturation genes downstream of RUNX2 and that its loss reduces chromatin accessibility and mineralization in vivo.","evidence":"ChIP-seq, ATAC-seq, shRNA, overexpression, craniofacial conditional KO mouse","pmids":["35046892"],"confidence":"Medium","gaps":["Isoform usage during osteogenesis not dissected","Direct PBAF-RUNX2 physical contact at target loci not fully mapped"]},{"year":2024,"claim":"Defined an E2F1-PHF10-DUSP5-pERK1/2 feedback axis whereby PHF10 represses DUSP5 via SWI/SNF assembly to sustain ERK signaling, promoting stemness and inhibiting differentiation in gastric cancer.","evidence":"ChIP, Co-IP, siRNA knockdown and rescue, pERK1/2 Western blot","pmids":["39127832"],"confidence":"Medium","gaps":["Mechanism of PHF10-mediated repression at DUSP5 not detailed","Generality beyond gastric cancer unknown"]},{"year":2024,"claim":"Linked PHF10 isoform switching to lineage commitment, showing the DPF-lacking isoform replaces the DPF-containing isoform in PBAF during neuronal and muscle differentiation.","evidence":"RT-PCR and Western blot of isoform expression during in vitro differentiation","pmids":["38189889"],"confidence":"Low","gaps":["Observation is correlative without functional perturbation","Target-gene consequences of the switch untested"]},{"year":2025,"claim":"Identified Keap1 as a degrader of PHF10 and placed PHF10 in NRF2-driven antioxidant transcription, showing Keap1-mutant accumulation of PHF10 recruits SMARCA2 to NRF2 regions and confers ferroptosis resistance.","evidence":"TAP-MS, Co-IP, ubiquitination assays, ATAC-seq, xenograft models in NSCLC","pmids":["41197527"],"confidence":"Medium","gaps":["Isoform involved in NRF2 cooperation not defined","Relationship between Keap1- and β-TrCP-mediated degradation not reconciled"]},{"year":2025,"claim":"Showed PHF10 expression is epigenetically restrained by EZH2/H3K27me3 and that PHF10 in turn enforces H3K9me3 with Setdb1 at HMGB1 to suppress NF-κB signaling, embedding PHF10 in a repressive chromatin network in cholangiocarcinoma.","evidence":"ChIP for histone marks, transcriptome, siRNA/CRISPR KO, in vitro and in vivo assays","pmids":["39904827"],"confidence":"Medium","gaps":["How a PBAF subunit directs H3K9me3 deposition mechanistically is unclear","Direct PHF10-Setdb1 contact not structurally defined"]},{"year":null,"claim":"How the distinct phospho-states, isoform identities, and competing degradation pathways (β-TrCP versus Keap1) are integrated to select specific PBAF target programs across tissues remains unresolved.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No unified model linking isoform/phospho state to genome-wide target selection","Structural basis of PHF10 isoform incorporation into PBAF not determined","Reconciliation of opposing stabilizing/destabilizing inputs lacking"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0140110","term_label":"transcription regulator activity","supporting_discovery_ids":[0,4,10,11,12]},{"term_id":"GO:0003677","term_label":"DNA binding","supporting_discovery_ids":[4,10,13]},{"term_id":"GO:0042393","term_label":"histone binding","supporting_discovery_ids":[0]}],"localization":[{"term_id":"GO:0005634","term_label":"nucleus","supporting_discovery_ids":[9]},{"term_id":"GO:0005829","term_label":"cytosol","supporting_discovery_ids":[9]}],"pathway":[{"term_id":"R-HSA-74160","term_label":"Gene expression (Transcription)","supporting_discovery_ids":[0,4,10,11]},{"term_id":"R-HSA-4839726","term_label":"Chromatin organization","supporting_discovery_ids":[12,13]},{"term_id":"R-HSA-1640170","term_label":"Cell Cycle","supporting_discovery_ids":[4,8]},{"term_id":"R-HSA-73894","term_label":"DNA Repair","supporting_discovery_ids":[6]},{"term_id":"R-HSA-1266738","term_label":"Developmental Biology","supporting_discovery_ids":[7,13]}],"complexes":["PBAF (SWI/SNF) complex"],"partners":["MYC","C-FOS","E2F1","NRF2","KEAP1","BTRC","SMARCA2","SETDB1"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q8WUB8","full_name":"PHD finger protein 10","aliases":["BRG1-associated factor 45a","BAF45a","XAP135"],"length_aa":498,"mass_kda":56.1,"function":"Involved in transcription activity regulation by chromatin remodeling. Belongs to the neural progenitors-specific chromatin remodeling complex (npBAF complex) and is required for the proliferation of neural progenitors. During neural development a switch from a stem/progenitor to a post-mitotic chromatin remodeling mechanism occurs as neurons exit the cell cycle and become committed to their adult state. The transition from proliferating neural stem/progenitor cells to post-mitotic neurons requires a switch in subunit composition of the npBAF and nBAF complexes. As neural progenitors exit mitosis and differentiate into neurons, npBAF complexes which contain ACTL6A/BAF53A and PHF10/BAF45A, are exchanged for homologous alternative ACTL6B/BAF53B and DPF1/BAF45B or DPF3/BAF45C subunits in neuron-specific complexes (nBAF). The npBAF complex is essential for the self-renewal/proliferative capacity of the multipotent neural stem cells. The nBAF complex along with CREST plays a role regulating the activity of genes essential for dendrite growth (By similarity)","subcellular_location":"Nucleus","url":"https://www.uniprot.org/uniprotkb/Q8WUB8/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/PHF10","classification":"Not Classified","n_dependent_lines":21,"n_total_lines":1208,"dependency_fraction":0.0173841059602649},"opencell":{"profiled":true,"resolved_as":"","ensg_id":"ENSG00000130024","cell_line_id":"CID000798","localizations":[{"compartment":"nucleoplasm","grade":3},{"compartment":"chromatin","grade":2}],"interactors":[{"gene":"NVL","stoichiometry":10.0},{"gene":"SMARCA4","stoichiometry":10.0},{"gene":"SMARCE1","stoichiometry":10.0},{"gene":"SMARCC1","stoichiometry":10.0},{"gene":"BRD7","stoichiometry":10.0},{"gene":"SMARCB1","stoichiometry":10.0},{"gene":"STK32C","stoichiometry":10.0},{"gene":"PBRM1","stoichiometry":10.0},{"gene":"ACTL6A","stoichiometry":4.0},{"gene":"SMARCC2","stoichiometry":4.0}],"url":"https://opencell.sf.czbiohub.org/target/CID000798","total_profiled":1310},"omim":[{"mim_id":"615544","title":"PERIVENTRICULAR NODULAR HETEROTOPIA 6; PVNH6","url":"https://www.omim.org/entry/615544"},{"mim_id":"615532","title":"ENDOPLASMIC RETICULUM MEMBRANE-ASSOCIATED RNA DEGRADATION PROTEIN; ERMARD","url":"https://www.omim.org/entry/615532"},{"mim_id":"613069","title":"PHD FINGER PROTEIN 10; PHF10","url":"https://www.omim.org/entry/613069"},{"mim_id":"611186","title":"MICRO RNA 9-1; MIR9-1","url":"https://www.omim.org/entry/611186"},{"mim_id":"609327","title":"MICRO RNA 124-1; MIR124-1","url":"https://www.omim.org/entry/609327"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Supported","locations":[{"location":"Nucleoplasm","reliability":"Supported"}],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in all","driving_tissues":[],"url":"https://www.proteinatlas.org/search/PHF10"},"hgnc":{"alias_symbol":["FLJ10975","XAP135","BAF45a","SMARCG4"],"prev_symbol":[]},"alphafold":{"accession":"Q8WUB8","domains":[{"cath_id":"-","chopping":"70-182","consensus_level":"high","plddt":92.2919,"start":70,"end":182},{"cath_id":"3.30.40.10","chopping":"375-432","consensus_level":"medium","plddt":93.4591,"start":375,"end":432},{"cath_id":"3.30.40.10","chopping":"434-481","consensus_level":"medium","plddt":91.1848,"start":434,"end":481}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q8WUB8","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q8WUB8-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q8WUB8-F1-predicted_aligned_error_v6.png","plddt_mean":70.06},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=PHF10","jax_strain_url":"https://www.jax.org/strain/search?query=PHF10"},"sequence":{"accession":"Q8WUB8","fasta_url":"https://rest.uniprot.org/uniprotkb/Q8WUB8.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q8WUB8/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q8WUB8"}},"corpus_meta":[{"pmid":"22388101","id":"PMC_22388101","title":"MicroRNA-409-3p regulates cell proliferation and apoptosis by targeting PHF10 in gastric cancer.","date":"2012","source":"Cancer letters","url":"https://pubmed.ncbi.nlm.nih.gov/22388101","citation_count":76,"is_preprint":false},{"pmid":"27931852","id":"PMC_27931852","title":"The BAF45a/PHF10 subunit of SWI/SNF-like chromatin remodeling complexes is essential for hematopoietic stem cell maintenance.","date":"2016","source":"Experimental hematology","url":"https://pubmed.ncbi.nlm.nih.gov/27931852","citation_count":55,"is_preprint":false},{"pmid":"35033590","id":"PMC_35033590","title":"ZC3H13-mediated N6-methyladenosine modification of PHF10 is impaired by fisetin which inhibits the DNA damage response in pancreatic cancer.","date":"2022","source":"Cancer letters","url":"https://pubmed.ncbi.nlm.nih.gov/35033590","citation_count":45,"is_preprint":false},{"pmid":"24763304","id":"PMC_24763304","title":"Mammalian cells contain two functionally distinct PBAF complexes incorporating different isoforms of PHF10 signature subunit.","date":"2014","source":"Cell cycle (Georgetown, Tex.)","url":"https://pubmed.ncbi.nlm.nih.gov/24763304","citation_count":28,"is_preprint":false},{"pmid":"34465901","id":"PMC_34465901","title":"PHF10 subunit of PBAF complex mediates transcriptional activation by MYC.","date":"2021","source":"Oncogene","url":"https://pubmed.ncbi.nlm.nih.gov/34465901","citation_count":24,"is_preprint":false},{"pmid":"31227497","id":"PMC_31227497","title":"Integrative Copy Number Analysis of Uveal Melanoma Reveals Novel Candidate Genes Involved in Tumorigenesis Including a Tumor Suppressor Role for PHF10/BAF45a.","date":"2019","source":"Clinical cancer research : an official journal of the American Association for Cancer Research","url":"https://pubmed.ncbi.nlm.nih.gov/31227497","citation_count":23,"is_preprint":false},{"pmid":"28717195","id":"PMC_28717195","title":"Stability of the PHF10 subunit of PBAF signature module is regulated by phosphorylation: role of β-TrCP.","date":"2017","source":"Scientific reports","url":"https://pubmed.ncbi.nlm.nih.gov/28717195","citation_count":19,"is_preprint":false},{"pmid":"20068294","id":"PMC_20068294","title":"PHF10 is required for cell proliferation in normal and SV40-immortalized human fibroblast cells.","date":"2010","source":"Cytogenetic and genome research","url":"https://pubmed.ncbi.nlm.nih.gov/20068294","citation_count":17,"is_preprint":false},{"pmid":"34681795","id":"PMC_34681795","title":"Conserved Structure and Evolution of DPF Domain of PHF10-The Specific Subunit of PBAF Chromatin Remodeling Complex.","date":"2021","source":"International journal of molecular sciences","url":"https://pubmed.ncbi.nlm.nih.gov/34681795","citation_count":14,"is_preprint":false},{"pmid":"35046892","id":"PMC_35046892","title":"Baf45a Mediated Chromatin Remodeling Promotes Transcriptional Activation for Osteogenesis and Odontogenesis.","date":"2022","source":"Frontiers in endocrinology","url":"https://pubmed.ncbi.nlm.nih.gov/35046892","citation_count":9,"is_preprint":false},{"pmid":"32547084","id":"PMC_32547084","title":"Circ_0001023 Promotes Proliferation and Metastasis of Gastric Cancer Cells Through miR-409-3p/PHF10 Axis.","date":"2020","source":"OncoTargets and therapy","url":"https://pubmed.ncbi.nlm.nih.gov/32547084","citation_count":9,"is_preprint":false},{"pmid":"39127832","id":"PMC_39127832","title":"PHF10 inhibits gastric epithelium differentiation and induces gastric cancer carcinogenesis.","date":"2024","source":"Cancer gene therapy","url":"https://pubmed.ncbi.nlm.nih.gov/39127832","citation_count":4,"is_preprint":false},{"pmid":"31911482","id":"PMC_31911482","title":"The sequential phosphorylation of PHF10 subunit of the PBAF chromatin-remodeling complex determines different properties of the PHF10 isoforms.","date":"2020","source":"Biology open","url":"https://pubmed.ncbi.nlm.nih.gov/31911482","citation_count":4,"is_preprint":false},{"pmid":"27239853","id":"PMC_27239853","title":"[PHF10 isoforms are phosphorylated in the PBAF mammalian chromatin remodeling complex].","date":"2016","source":"Molekuliarnaia biologiia","url":"https://pubmed.ncbi.nlm.nih.gov/27239853","citation_count":4,"is_preprint":false},{"pmid":"39904827","id":"PMC_39904827","title":"EZH2-Mediated PHF10 Suppression Amplifies HMGB1/NF-κB Axis That Confers Chemotherapy Resistance in Cholangiocarcinoma.","date":"2025","source":"Journal of cellular and molecular medicine","url":"https://pubmed.ncbi.nlm.nih.gov/39904827","citation_count":4,"is_preprint":false},{"pmid":"38189889","id":"PMC_38189889","title":"Neuronal and Muscle Differentiation of Mammalian Cells Is Accompanied by a Change in PHF10 Isoform Expression.","date":"2024","source":"Doklady. Biochemistry and biophysics","url":"https://pubmed.ncbi.nlm.nih.gov/38189889","citation_count":3,"is_preprint":false},{"pmid":"31012017","id":"PMC_31012017","title":"Oncogene c-MYC Controls the Expression of PHF10 Subunit of PBAF Chromatin Remodeling Complex in SW620 Cell Line.","date":"2019","source":"Doklady. Biochemistry and biophysics","url":"https://pubmed.ncbi.nlm.nih.gov/31012017","citation_count":3,"is_preprint":false},{"pmid":"20815984","id":"PMC_20815984","title":"[Preparation of PHF10 antibody and analysis of PHF10 expression gastric cancer tissues].","date":"2010","source":"Xi bao yu fen zi mian yi xue za zhi = Chinese journal of cellular and molecular immunology","url":"https://pubmed.ncbi.nlm.nih.gov/20815984","citation_count":2,"is_preprint":false},{"pmid":"27193724","id":"PMC_27193724","title":"The level of the Phf10 protein, a PBAF chromatin-remodeling complex subunit, correlates with the Mts1/S100A4 expression in human cancer cell lines.","date":"2016","source":"Doklady. Biochemistry and biophysics","url":"https://pubmed.ncbi.nlm.nih.gov/27193724","citation_count":2,"is_preprint":false},{"pmid":"34837706","id":"PMC_34837706","title":"[PHF10, a Subunit of the PBAF Chromatin Remodeling Complex, Changes Its Localization and Interacts with c-FOS during the Initiation of Long-Term Potentiation in Neuronal Culture].","date":"2021","source":"Molekuliarnaia biologiia","url":"https://pubmed.ncbi.nlm.nih.gov/34837706","citation_count":2,"is_preprint":false},{"pmid":"27668607","id":"PMC_27668607","title":"[Ratio of transcription factor PHF10 splice variants in lymphocytes as a molecular marker of Parkinson's disease].","date":"2016","source":"Molekuliarnaia biologiia","url":"https://pubmed.ncbi.nlm.nih.gov/27668607","citation_count":1,"is_preprint":false},{"pmid":"35622521","id":"PMC_35622521","title":"New alleles of the SWI/SNF chromatin remodeling complex gene phf-10.","date":"2022","source":"microPublication biology","url":"https://pubmed.ncbi.nlm.nih.gov/35622521","citation_count":1,"is_preprint":false},{"pmid":"41197527","id":"PMC_41197527","title":"PHF10 is a Novel Substrate of Keap1 to Protect Non-Small-Cell Lung Cancer (NSCLC) Cells Against Oxidative Stress and Confer Ferroptosis Resistance.","date":"2025","source":"Cancer research and treatment","url":"https://pubmed.ncbi.nlm.nih.gov/41197527","citation_count":0,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":12138,"output_tokens":3765,"usd":0.046444,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":11479,"output_tokens":4990,"usd":0.091073,"stage2_stop_reason":"end_turn"},"total_usd":0.137517,"stage1_batch_id":"msgbatch_01CNoDbkChHEkgrJnL7BwtGJ","stage2_batch_id":"msgbatch_016Y4x9E9Wg5VQDANj9quSQD","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2014,\n      \"finding\": \"The PHF10 gene encodes two types of evolutionarily conserved isoforms that are incorporated into the PBAF complex in a mutually exclusive manner. One isoform contains C-terminal tandem PHD fingers (DPF domain); the other isoform has these replaced by a consensus sequence for phosphorylation-dependent SUMO 1 conjugation (PDSM). PBAF complexes containing different PHF10 isoforms can bind to the same gene promoters but produce different effects on Pol II recruitment and gene transcription levels, and only the PHD-containing isoform activates proliferation.\",\n      \"method\": \"Molecular cloning, co-immunoprecipitation, promoter binding assays, Pol II recruitment assays, proliferation assays\",\n      \"journal\": \"Cell cycle (Georgetown, Tex.)\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reciprocal Co-IP and functional assays in a single lab with multiple orthogonal methods\",\n      \"pmids\": [\"24763304\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"PHF10 protein stability is regulated by the E3 ubiquitin ligase β-TrCP, which degrades PHF10 via two non-canonical β-TrCP degrons in a phospho-dependent manner. Unusually, phosphorylation of PHF10-S isoform degrons by CK-1 prevents their degradation (molecular docking showed phosphorylated PHF10 binds β-TrCP with lower affinity). β-TrCP knockdown stabilizes PHF10 as well as other PBAF core subunits (BRG1, BAF155, BAF200, BAF180, BRD7).\",\n      \"method\": \"siRNA knockdown, half-life assays, phosphorylation analysis, targeted molecular docking\",\n      \"journal\": \"Scientific reports\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — functional knockdown combined with molecular docking, single lab, multiple methods\",\n      \"pmids\": [\"28717195\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2016,\n      \"finding\": \"All four PHF10 isoforms are extensively phosphorylated in human cells, and their phosphorylation occurs while they are incorporated as subunits of the PBAF complex. The phosphorylation level is cell-type dependent.\",\n      \"method\": \"Immunoprecipitation of PBAF complex, phosphorylation analysis across multiple human cell types\",\n      \"journal\": \"Molekuliarnaia biologiia\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single lab, single method described in abstract without full methodological detail\",\n      \"pmids\": [\"27239853\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"PHF10 isoforms lacking C-terminal PHD domains contain an X-cluster of phosphorylated serine residues consisting of two independently phosphorylated subclusters; phosphorylation of the second subcluster depends on phosphorylation of a primary serine 327. A predicted nuclear localization sequence (NLS3) between the subclusters does not affect PHF10 localization but is essential for X-cluster phosphorylation and increased stability of PHD-lacking isoforms; conversely, NLS3 reduces stability of PHD-containing isoforms. Sequential phosphorylation thus regulates isoform cell-level and rate of incorporation into PBAF.\",\n      \"method\": \"Phospho-site mapping, mutagenesis of serine residues and NLS3, stability assays\",\n      \"journal\": \"Biology open\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1-2 / Moderate — mutagenesis combined with functional stability assays, single lab\",\n      \"pmids\": [\"31911482\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"PHF10 interacts with the MYC oncoprotein and facilitates recruitment of the PBAF complex to MYC target gene promoters, augmenting MYC-dependent transcriptional activation of cell cycle genes. Depletion of PHF10 induces G1 accumulation and a senescence-like phenotype in melanoma cells.\",\n      \"method\": \"Co-immunoprecipitation, ChIP, siRNA knockdown, cell cycle analysis\",\n      \"journal\": \"Oncogene\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reciprocal Co-IP and ChIP with functional KD phenotype, single lab\",\n      \"pmids\": [\"34465901\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"The c-MYC oncogene transcriptionally activates PHF10 expression in cancer cell lines.\",\n      \"method\": \"Reporter assays and expression analysis in cell lines with c-MYC manipulation\",\n      \"journal\": \"Doklady. Biochemistry and biophysics\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single lab, limited methodological detail in abstract\",\n      \"pmids\": [\"31012017\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"ZC3H13-mediated m6A methylation of PHF10 mRNA promotes PHF10 translation in a YTHDF1-dependent manner. Fisetin suppresses HR repair of DNA double-strand breaks by reducing m6A modification of PHF10. PHF10 loss-of-function results in elevated recruitment of γH2AX, RAD51, and 53BP1 to DSB sites and decreased homologous recombination repair efficiency in pancreatic cancer cells.\",\n      \"method\": \"m6A methylation assays, siRNA knockdown, γH2AX/RAD51/53BP1 foci analysis, HR repair assays\",\n      \"journal\": \"Cancer letters\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — multiple functional assays (m6A, foci, HR efficiency) in single lab\",\n      \"pmids\": [\"35033590\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2016,\n      \"finding\": \"Deletion of BAF45a/PHF10 in the adult mouse hematopoietic system causes a dose-dependent decrease in the frequency of long-term repopulating hematopoietic stem cells and committed myeloid progenitors without affecting proliferation rate. BAF45a-deficient HSCs are selectively lost from mixed bone marrow chimeras, indicating impaired cell-intrinsic function.\",\n      \"method\": \"Conditional knockout mouse, mixed bone marrow chimeras, flow cytometry\",\n      \"journal\": \"Experimental hematology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — conditional KO with chimera rescue experiment in mouse model, rigorous cell-intrinsic functional test\",\n      \"pmids\": [\"27931852\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2010,\n      \"finding\": \"PHF10 is required for cell proliferation: both overexpression of truncated PHF10 (dominant negative effect) and RNAi-mediated knockdown of PHF10 result in reduced cell proliferation in normal human diploid fibroblasts and multiple cell lines.\",\n      \"method\": \"Overexpression of truncated cDNA constructs, RNAi knockdown, proliferation assays\",\n      \"journal\": \"Cytogenetic and genome research\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — two complementary loss-of-function approaches (truncation OE and RNAi) both showing proliferation defect\",\n      \"pmids\": [\"20068294\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"PHF10 changes its subcellular localization in response to LTP induction in neuronal culture: PHF10 is normally nuclear but translocates to the cytoplasm 1 hour after LTP induction (KCl stimulation), then returns to the nucleus together with c-FOS. PHF10 physically interacts with the c-FOS transcriptional activator. This behavior is specific to neuronal cultures.\",\n      \"method\": \"Immunofluorescence, co-immunoprecipitation, KCl-induced LTP in neuronal cultures\",\n      \"journal\": \"Molekuliarnaia biologiia\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single lab, localization and pulldown without full functional validation of the interaction's downstream effect\",\n      \"pmids\": [\"34837706\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"PHF10 forms a positive feedback loop with E2F1 (E2F1 drives PHF10 expression; PHF10 in turn activates E2F1 expression via PBAF complex assembly). PHF10 mediates transcriptional repression of DUSP5 through SWI/SNF complex assembly, leading to elevated pERK1/2. The E2F1-PHF10-DUSP5-pERK1/2 axis regulates differentiation inhibition and stemness promotion in gastric cancer cells.\",\n      \"method\": \"ChIP, co-immunoprecipitation, siRNA knockdown, rescue experiments, Western blot for pERK1/2\",\n      \"journal\": \"Cancer gene therapy\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — ChIP, Co-IP, and rescue experiments in single lab establishing pathway epistasis\",\n      \"pmids\": [\"39127832\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"Keap1 binds PHF10 and promotes its polyubiquitination and proteasomal degradation. Cancer-associated Keap1 mutations are incapable of degrading PHF10, leading to PHF10 protein accumulation. PHF10 interacts with NRF2 and activates NRF2 downstream antioxidant targets by recruiting SMARCA2 to increase chromatin accessibility at NRF2-binding transcriptional regions, conferring ferroptosis resistance in Keap1-deficient NSCLC.\",\n      \"method\": \"Tandem affinity purification/mass spectrometry, Co-IP, ubiquitination assays, ATAC-seq, xenograft models\",\n      \"journal\": \"Cancer research and treatment\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — Co-IP and ubiquitination assays with ATAC-seq and in vivo model, single lab multiple orthogonal methods\",\n      \"pmids\": [\"41197527\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"EZH2 mediates H3K27me3 enrichment on the PHF10 promoter region, suppressing PHF10 expression. PHF10 loss in cholangiocarcinoma activates NF-κB signaling by de-repressing HMGB1; PHF10 coordinates with Setdb1 to mediate H3K9me3 modifications on the HMGB1 promoter to suppress its expression.\",\n      \"method\": \"ChIP, transcriptome analysis, siRNA/CRISPR KO, in vitro and in vivo functional assays\",\n      \"journal\": \"Journal of cellular and molecular medicine\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — ChIP for histone marks, transcriptome, and in vivo validation in single lab\",\n      \"pmids\": [\"39904827\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"BAF45A (PHF10) associates specifically with the PBAF complex (not cBAF). BAF45A overexpression in osteoblasts activates genes essential for osteoblast maturation and mineralization. Baf45a knockout reduces chromatin accessibility at osteoblast/odontoblast-specific gene loci (shown by ATAC-seq), and craniofacial mesenchyme-specific loss of Baf45a reduces tooth and mandibular bone mineralization. RUNX2 binds to Baf45a promoter, and PBAF-RUNX2 crosstalk mediates transcriptional activation for early differentiation.\",\n      \"method\": \"ChIP-seq (H3K9ac, H3K27ac), ATAC-seq, shRNA knockdown, overexpression, conditional KO mouse\",\n      \"journal\": \"Frontiers in endocrinology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — ChIP-seq, ATAC-seq, and conditional KO in single lab with multiple orthogonal approaches\",\n      \"pmids\": [\"35046892\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"During neuronal and muscle differentiation of human and mouse cells, PHF10 isoform expression shifts: the DPF-lacking isoform replaces the DPF-containing isoform in the PBAF complex, potentially altering selectivity in gene regulation during differentiation.\",\n      \"method\": \"RT-PCR and Western blot analysis of isoform expression during in vitro differentiation\",\n      \"journal\": \"Doklady. Biochemistry and biophysics\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — expression-level observation during differentiation, single lab, no direct functional mechanistic test\",\n      \"pmids\": [\"38189889\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"PHF10 (BAF45a) is a signature subunit of the PBAF SWI/SNF chromatin remodeling complex that is expressed as four isoforms incorporating either a DPF (double PHD finger) domain or a PDSM phosphorylation site in a mutually exclusive fashion; these isoforms are differentially regulated by CK-1-dependent phosphorylation of an X-cluster and by β-TrCP- and Keap1-mediated ubiquitination/degradation, which together control isoform levels and PBAF complex composition. PHF10 physically interacts with transcriptional activators MYC and c-FOS (and NRF2 in the context of Keap1 loss), recruits PBAF to target gene promoters to regulate proliferation, differentiation, DNA damage repair (HR), and oxidative stress responses, and in the hematopoietic system is essential for long-term repopulating stem cell maintenance.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"PHF10 (BAF45a) is a signature subunit of the PBAF SWI/SNF chromatin-remodeling complex that couples PBAF recruitment to transcriptional programs controlling proliferation, differentiation, and stress responses [#0, #13]. It is expressed as evolutionarily conserved isoforms that are incorporated into PBAF in a mutually exclusive manner: one bears C-terminal tandem PHD fingers (DPF domain) and activates proliferation, the other replaces these with a phosphorylation-dependent SUMO-conjugation motif, and PBAF complexes carrying different isoforms bind shared promoters yet differ in their effects on Pol II recruitment and transcription [#0]. Isoform levels are set post-translationally by phosphorylation and regulated proteolysis: CK-1-dependent phosphorylation of an X-cluster of serines (organized as sequentially phosphorylated subclusters dependent on a primary Ser327 and the NLS3 element) stabilizes PHD-lacking isoforms, and the E3 ligase \\u03b2-TrCP degrades PHF10 through non-canonical degrons whose phosphorylation paradoxically blocks degradation [#1, #3]. PHF10 directs PBAF to target promoters via direct interaction with sequence-specific activators, augmenting MYC-dependent activation of cell-cycle genes, engaging E2F1 in a positive feedback loop that represses DUSP5 to elevate pERK1/2, and recruiting SMARCA2 to NRF2-binding regions to drive antioxidant transcription and ferroptosis resistance when Keap1 (which normally ubiquitinates and degrades PHF10) is lost [#4, #10, #11]. It also supports homologous-recombination repair of DNA double-strand breaks, its loss elevating \\u03b3H2AX, RAD51, and 53BP1 foci and reducing repair efficiency [#6]. Physiologically, PHF10 is required cell-intrinsically for maintenance of long-term repopulating hematopoietic stem cells and for osteoblast/odontoblast differentiation and mineralization downstream of RUNX2 [#7, #13]. PHF10 expression is itself constrained by repressive chromatin via EZH2-mediated H3K27me3, and PHF10 in turn cooperates with Setdb1 to deposit H3K9me3 and silence HMGB1, restraining NF-\\u03baB signaling [#12].\",\n  \"teleology\": [\n    {\n      \"year\": 2010,\n      \"claim\": \"Established that PHF10 is functionally required for cell proliferation rather than being a passive complex subunit, by showing that both dominant-negative truncation and RNAi knockdown impair growth.\",\n      \"evidence\": \"Truncated cDNA overexpression and RNAi in human fibroblasts and cell lines with proliferation assays\",\n      \"pmids\": [\"20068294\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Did not define the molecular target genes or PBAF-dependent mechanism\", \"No isoform-resolved analysis\"]\n    },\n    {\n      \"year\": 2014,\n      \"claim\": \"Defined PHF10 as a PBAF-incorporated subunit existing as mutually exclusive DPF- versus PDSM-containing isoforms that confer distinct transcriptional outputs, explaining how a single gene tunes PBAF function.\",\n      \"evidence\": \"Molecular cloning, reciprocal Co-IP, promoter binding and Pol II recruitment assays, proliferation assays\",\n      \"pmids\": [\"24763304\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Mechanism by which isoforms differentially affect Pol II not resolved\", \"Endogenous promoter targets not genome-wide mapped\"]\n    },\n    {\n      \"year\": 2016,\n      \"claim\": \"Showed that PHF10 isoforms are extensively phosphorylated while assembled in PBAF, in a cell-type-dependent manner, indicating signaling input onto the complex.\",\n      \"evidence\": \"Immunoprecipitation of PBAF and phosphorylation analysis across human cell types\",\n      \"pmids\": [\"27239853\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"Single method described without full detail in abstract\", \"Kinases and functional consequences of phosphorylation not defined here\"]\n    },\n    {\n      \"year\": 2016,\n      \"claim\": \"Demonstrated a cell-intrinsic physiological requirement for PHF10 in maintaining long-term repopulating hematopoietic stem cells, distinguishing this role from a general proliferation effect.\",\n      \"evidence\": \"Conditional knockout mouse with mixed bone marrow chimeras and flow cytometry\",\n      \"pmids\": [\"27931852\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Target genes mediating HSC maintenance not identified\", \"Isoform contribution to HSC phenotype unaddressed\"]\n    },\n    {\n      \"year\": 2017,\n      \"claim\": \"Identified \\u03b2-TrCP as the E3 ligase controlling PHF10 stability through non-canonical phospho-degrons, with the unusual feature that degron phosphorylation prevents degradation and stabilizes PHF10 and other PBAF core subunits.\",\n      \"evidence\": \"siRNA knockdown, half-life assays, phosphorylation analysis, molecular docking\",\n      \"pmids\": [\"28717195\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Kinase generating the protective phosphorylation not pinned down here\", \"Docking-based affinity claim not validated by direct binding measurement\"]\n    },\n    {\n      \"year\": 2019,\n      \"claim\": \"Placed PHF10 downstream of MYC transcriptionally, showing c-MYC activates PHF10 expression and hinting at a regulatory circuit.\",\n      \"evidence\": \"Reporter assays and expression analysis with c-MYC manipulation in cell lines\",\n      \"pmids\": [\"31012017\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"Limited methodological detail in abstract\", \"Direct promoter occupancy not shown\"]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"Resolved the phospho-code controlling PHF10 isoform levels, defining an X-cluster of serines with sequential, Ser327-dependent subcluster phosphorylation and an NLS3 element that oppositely modulates stability of PHD-lacking versus PHD-containing isoforms.\",\n      \"evidence\": \"Phospho-site mapping, serine and NLS3 mutagenesis, stability assays\",\n      \"pmids\": [\"31911482\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Responsible kinase(s) for each subcluster not all identified\", \"Link between stability code and specific gene programs untested\"]\n    },\n    {\n      \"year\": 2021,\n      \"claim\": \"Showed PHF10 physically binds MYC and recruits PBAF to MYC target promoters to amplify cell-cycle gene activation, with depletion causing G1 arrest and senescence-like phenotype, mechanistically connecting PHF10 to oncogenic transcription.\",\n      \"evidence\": \"Co-IP, ChIP, siRNA knockdown, cell cycle analysis in melanoma cells\",\n      \"pmids\": [\"34465901\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Isoform specificity of the MYC interaction not resolved\", \"Single cancer-cell context\"]\n    },\n    {\n      \"year\": 2021,\n      \"claim\": \"Revealed activity-dependent regulation of PHF10 in neurons, with nuclear-cytoplasmic shuttling upon LTP induction and physical interaction with c-FOS, extending PHF10 function to neuronal stimulus responses.\",\n      \"evidence\": \"Immunofluorescence, Co-IP, KCl-induced LTP in neuronal cultures\",\n      \"pmids\": [\"34837706\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"Downstream transcriptional consequence of the c-FOS interaction not demonstrated\", \"Localization shuttling not mechanistically explained\"]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"Connected PHF10 to genome stability and its translational control, showing ZC3H13/YTHDF1 m6A-dependent translation of PHF10 mRNA and that PHF10 is required for efficient homologous-recombination repair of DSBs.\",\n      \"evidence\": \"m6A assays, siRNA knockdown, \\u03b3H2AX/RAD51/53BP1 foci and HR repair assays in pancreatic cancer cells\",\n      \"pmids\": [\"35033590\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Whether PHF10 acts at break sites via PBAF chromatin remodeling not directly shown\", \"Isoform dependence of the HR role unknown\"]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"Established PHF10 as a PBAF-specific subunit driving differentiation, demonstrating that BAF45A activates osteoblast/odontoblast maturation genes downstream of RUNX2 and that its loss reduces chromatin accessibility and mineralization in vivo.\",\n      \"evidence\": \"ChIP-seq, ATAC-seq, shRNA, overexpression, craniofacial conditional KO mouse\",\n      \"pmids\": [\"35046892\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Isoform usage during osteogenesis not dissected\", \"Direct PBAF-RUNX2 physical contact at target loci not fully mapped\"]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Defined an E2F1-PHF10-DUSP5-pERK1/2 feedback axis whereby PHF10 represses DUSP5 via SWI/SNF assembly to sustain ERK signaling, promoting stemness and inhibiting differentiation in gastric cancer.\",\n      \"evidence\": \"ChIP, Co-IP, siRNA knockdown and rescue, pERK1/2 Western blot\",\n      \"pmids\": [\"39127832\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Mechanism of PHF10-mediated repression at DUSP5 not detailed\", \"Generality beyond gastric cancer unknown\"]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Linked PHF10 isoform switching to lineage commitment, showing the DPF-lacking isoform replaces the DPF-containing isoform in PBAF during neuronal and muscle differentiation.\",\n      \"evidence\": \"RT-PCR and Western blot of isoform expression during in vitro differentiation\",\n      \"pmids\": [\"38189889\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"Observation is correlative without functional perturbation\", \"Target-gene consequences of the switch untested\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Identified Keap1 as a degrader of PHF10 and placed PHF10 in NRF2-driven antioxidant transcription, showing Keap1-mutant accumulation of PHF10 recruits SMARCA2 to NRF2 regions and confers ferroptosis resistance.\",\n      \"evidence\": \"TAP-MS, Co-IP, ubiquitination assays, ATAC-seq, xenograft models in NSCLC\",\n      \"pmids\": [\"41197527\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Isoform involved in NRF2 cooperation not defined\", \"Relationship between Keap1- and \\u03b2-TrCP-mediated degradation not reconciled\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Showed PHF10 expression is epigenetically restrained by EZH2/H3K27me3 and that PHF10 in turn enforces H3K9me3 with Setdb1 at HMGB1 to suppress NF-\\u03baB signaling, embedding PHF10 in a repressive chromatin network in cholangiocarcinoma.\",\n      \"evidence\": \"ChIP for histone marks, transcriptome, siRNA/CRISPR KO, in vitro and in vivo assays\",\n      \"pmids\": [\"39904827\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"How a PBAF subunit directs H3K9me3 deposition mechanistically is unclear\", \"Direct PHF10-Setdb1 contact not structurally defined\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How the distinct phospho-states, isoform identities, and competing degradation pathways (\\u03b2-TrCP versus Keap1) are integrated to select specific PBAF target programs across tissues remains unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No unified model linking isoform/phospho state to genome-wide target selection\", \"Structural basis of PHF10 isoform incorporation into PBAF not determined\", \"Reconciliation of opposing stabilizing/destabilizing inputs lacking\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0140110\", \"supporting_discovery_ids\": [0, 4, 10, 11, 12]},\n      {\"term_id\": \"GO:0003677\", \"supporting_discovery_ids\": [4, 10, 13]},\n      {\"term_id\": \"GO:0042393\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005634\", \"supporting_discovery_ids\": [9]},\n      {\"term_id\": \"GO:0005829\", \"supporting_discovery_ids\": [9]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-74160\", \"supporting_discovery_ids\": [0, 4, 10, 11]},\n      {\"term_id\": \"R-HSA-4839726\", \"supporting_discovery_ids\": [12, 13]},\n      {\"term_id\": \"R-HSA-1640170\", \"supporting_discovery_ids\": [4, 8]},\n      {\"term_id\": \"R-HSA-73894\", \"supporting_discovery_ids\": [6]},\n      {\"term_id\": \"R-HSA-1266738\", \"supporting_discovery_ids\": [7, 13]}\n    ],\n    \"complexes\": [\"PBAF (SWI/SNF) complex\"],\n    \"partners\": [\"MYC\", \"c-FOS\", \"E2F1\", \"NRF2\", \"Keap1\", \"BTRC\", \"SMARCA2\", \"SETDB1\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":7,"faith_total":7,"faith_pct":100.0}}