{"gene":"PHF14","run_date":"2026-06-10T06:43:35","timeline":{"discoveries":[{"year":2021,"finding":"PHF14 reads unmodified histone H3(1-34) through an integrated PHD1-ZnK-PHD2 cassette (PZP domain), utilizing two distinct surfaces for bipartite recognition of H3-Nter (residues 1-15) and H3-middle (residues 14-34) segments. A PHF14-unique insertion loop in PHD1 dominates H3K4 readout rather than the core β-strands. Binding is sensitive to modifications at H3 R2, T3, K4, R8, and K23 but not K9 or K27, indicating active marks negatively regulate PHF14 engagement.","method":"X-ray crystallography, HDX-MS, binding assays, structural analysis of PHF14PZP-H3 complex","journal":"Nucleic acids research","confidence":"High","confidence_rationale":"Tier 1 / Strong — crystal structure with functional binding assays and HDX-MS, multiple orthogonal methods in a single rigorous study","pmids":["34365506"],"is_preprint":false},{"year":2012,"finding":"Phf14 acts as a transcription factor that directly represses PDGFRα expression in mesenchymal cells. Phf14-null mice show elevated PDGFRα expression and increased mesenchymal cell proliferation, leading to interstitial hyperplasia and neonatal lethality from respiratory failure. Anti-PDGFRα antibody treatment rescued mouse lung fibrosis in this model.","method":"Gene-targeting knockout (Phf14-null mice), histological analysis, gene expression assays, antibody rescue experiment","journal":"The Journal of biological chemistry","confidence":"High","confidence_rationale":"Tier 2 / Strong — genetic knockout with defined molecular phenotype (PDGFRα upregulation), replicated in renal fibrosis study (PMID:28045076) and neurocytoma study (PMID:36359362)","pmids":["22730381"],"is_preprint":false},{"year":2013,"finding":"PHF14α (the major isoform) localizes to the nucleus and binds chromatin during cell division. Co-immunoprecipitation showed PHF14α binds histones via its PHD fingers.","method":"Molecular cloning, co-immunoprecipitation, nuclear localization assay, chromatin-binding assay during cell division","journal":"Acta biochimica et biophysica Sinica","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — single Co-IP for histone binding, replicated conceptually by structural study (PMID:34365506), single lab","pmids":["23688586"],"is_preprint":false},{"year":2017,"finding":"In renal fibrosis, phospho-SMAD3 acts as a transcription factor that enhances PHF14 expression (ChIP assay). PHF14 in turn represses PDGFRα transcription to limit PDGF signaling overactivation, forming a TGF-β/SMAD3/PHF14 self-limiting feedback pathway in the renal pro-fibrotic process.","method":"Chromatin immunoprecipitation (ChIP), in vitro TGF-β stimulation of rat renal fibroblasts, PHF14-null mouse model with folic acid-induced injury","journal":"Scientific reports","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — ChIP assay with genetic KO model, single lab, two orthogonal methods","pmids":["28045076"],"is_preprint":false},{"year":2023,"finding":"PHF14 binds DNMT3B and serves as a DNA CpG motif reader, recruiting DNMT3B to the SMAD7 gene locus, resulting in DNA hypermethylation and transcriptional suppression of SMAD7. This suppresses TGF-β pathway antagonism and promotes lung adenocarcinoma metastasis.","method":"Co-immunoprecipitation (PHF14-DNMT3B interaction), ChIP assay, in vitro and in vivo metastasis experiments, DNA methylation analysis","journal":"Cell discovery","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — reciprocal Co-IP for complex formation plus ChIP and functional in vivo data, single lab","pmids":["37072414"],"is_preprint":false},{"year":2023,"finding":"PHF14 is a physical component of a PHF5A-PHF14-HMG20A-RAI1 protein subcomplex associated with histone methyltransferase KMT2A (MLL1) via RNA polymerase-associated interactions in pancreatic cancer stem cells. Targeting KMT2A-WDR5 interaction attenuates cancer stem cell self-renewal.","method":"Proteomic analysis, co-immunoprecipitation, KMT2A-WDR5 inhibitor treatment in pancreatic cancer stem cells, in vivo tumorigenicity assay","journal":"Nature communications","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — proteomic identification plus functional inhibitor data, single lab, multiple orthogonal methods","pmids":["37709746"],"is_preprint":false},{"year":2022,"finding":"PHF14 forms a stable complex with HMG20A via a two-stranded alpha-helical coiled-coil structure. The PHF14-HMG20A complex directly interacts with TEAD1 transcription factor to modulate the Hippo pathway. siRNA knockdown of either PHF14 or HMG20A causes similar defects in cell migration, invasion, and homotypic cell-cell adhesion, and impairs TGF-β-triggered epithelial-to-mesenchymal transition.","method":"Proteomic study, deletion analysis, AlphaFold2 structural modeling, siRNA knockdown, transcriptomic analysis, TEAD1 interaction assay","journal":"Nucleic acids research","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — proteomic plus structural modeling plus functional knockdown with transcriptomic validation, single lab","pmids":["36124662"],"is_preprint":false},{"year":2022,"finding":"PHF14 knockdown in colorectal cancer cells induces DNA damage and activates the ATR-CHK1-H2A.X pathway, leading to apoptosis. PHF14 interacts with KIF4A and contributes to formation of BRCA2/RAD51 foci, suggesting PHF14 participates in DNA damage response complex recruitment.","method":"siRNA knockdown, co-immunoprecipitation (PHF14-KIF4A), immunofluorescence for BRCA2/RAD51 foci, western blot for ATR-CHK1-γH2A.X, in vivo xenograft","journal":"Cancer letters","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — single Co-IP for KIF4A interaction, supported by foci assay and pathway activation data, single lab","pmids":["35074497"],"is_preprint":false},{"year":2020,"finding":"PHF14 suppresses the expression of cell cycle inhibitor Cdkn1a (p21) by regulating H3K4me3 levels at the Cdkn1a locus, thereby controlling proliferation of germinal center B cells. PHF14 conditional knockout in germinal center B cells reduces GC response without affecting GC B cell survival.","method":"GC B cell-specific PHF14 knockout mice, SRBC/LCMV challenge, H3K4me3 ChIP, flow cytometry, qRT-PCR","journal":"Cellular immunology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — conditional knockout with ChIP-based mechanistic link, single lab, two orthogonal methods","pmids":["33035772"],"is_preprint":false},{"year":2022,"finding":"Loss of PHF14 (shRNA knockdown or CRISPR/Cas9 knockout) upregulates PDGFRα mRNA and protein in neuroblastoma SHSY-5Y cells, increases sensitivity to the PDGFR inhibitor Sunitinib, and enhances proliferation and colony formation. Overexpression of wild-type PHF14 reversed proliferation in neurocytoma primary cultures with PHF14 splicing mutations.","method":"shRNA knockdown, CRISPR/Cas9 knockout, PDGFR inhibitor (Sunitinib) treatment, nude mouse xenograft, primary culture rescue with WT PHF14","journal":"Biomedicines","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — multiple genetic tools (shRNA + CRISPR) with in vivo validation and rescue experiment, single lab","pmids":["36359362"],"is_preprint":false},{"year":2019,"finding":"Hypoxia-mediated inhibition of PHF14 is associated with increased cell cycle inhibitors p14ARF, p15INK4b, and p16INK4a (responsible for G1-S transition arrest) and decreased AKT-mTOR-4E-BP1/pS6K signaling, establishing PHF14 as a regulator of cell cycle progression and protein synthesis under hypoxic conditions.","method":"Pulsed-SILAC proteomics, biochemical assays, PHF14 KD xenograft model","journal":"Oncotarget","confidence":"Low","confidence_rationale":"Tier 3 / Weak — proteomic discovery with biochemical validation, single lab, limited mechanistic depth on direct targets","pmids":["31040906"],"is_preprint":false},{"year":2024,"finding":"SP4 transcription factor binds to the PHF14 promoter region and activates PHF14 transcription, placing SP4 as a direct upstream transcriptional regulator of PHF14 in esophageal squamous cell carcinoma.","method":"ChIP assay (SP4 binding to PHF14 promoter), luciferase reporter assay, knockdown/overexpression experiments, Wnt/β-catenin pathway analysis","journal":"Molecular cancer research : MCR","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — ChIP plus reporter assay demonstrating direct promoter binding, single lab, two orthogonal methods","pmids":["37768180"],"is_preprint":false}],"current_model":"PHF14 is a nuclear multi-PHD finger chromatin reader that recognizes unmodified histone H3(1-34) through a bipartite PZP (PHD1-ZnK-PHD2) domain; it functions as a transcriptional repressor of PDGFRα (regulated by upstream TGF-β/SMAD3 signaling), recruits DNMT3B to methylate and silence SMAD7, forms a complex with HMG20A to modulate Hippo/TEAD1 and TGF-β-driven EMT pathways, participates in a KMT2A-associated PHF5A-PHF14-HMG20A-RAI1 subcomplex in cancer stem cells, and supports DNA damage response via interaction with KIF4A and BRCA2/RAD51 foci formation, collectively linking PHF14 to mesenchymal homeostasis, organ development, and tumor progression."},"narrative":{"mechanistic_narrative":"PHF14 is a nuclear multi-PHD-finger chromatin reader that couples recognition of unmodified histone H3 to transcriptional control of mesenchymal proliferation, fibrosis, and tumor progression [PMID:34365506, PMID:22730381]. Structurally, it engages histone H3(1-34) through an integrated PHD1-ZnK-PHD2 (PZP) cassette that uses two surfaces for bipartite readout of the H3 N-terminus and middle region, with a PHF14-unique PHD1 insertion loop dominating H3K4 sensing; active marks at H3R2, T3, K4, R8, and K23 negatively regulate engagement, so PHF14 preferentially reads chromatin lacking these modifications [PMID:34365506]. A central transcriptional output is direct repression of PDGFRα: Phf14-null mice over-express PDGFRα and develop mesenchymal hyperplasia and lethal lung fibrosis rescuable by anti-PDGFRα antibody, and loss of PHF14 elevates PDGFRα across renal and neural tumor contexts [PMID:22730381, PMID:36359362]. This activity is embedded in TGF-β signaling, where phospho-SMAD3 induces PHF14 to form a self-limiting feedback loop restraining PDGF signaling [PMID:28045076], while in lung adenocarcinoma PHF14 recruits the DNA methyltransferase DNMT3B to silence the TGF-β antagonist SMAD7 by CpG hypermethylation [PMID:37072414]. PHF14 further acts through stable assembly with HMG20A via a coiled-coil interface, and this complex contacts TEAD1 to modulate Hippo signaling and TGF-β-driven epithelial-to-mesenchymal transition [PMID:36124662], and it is a component of a KMT2A-associated PHF5A-PHF14-HMG20A-RAI1 subcomplex in cancer stem cells [PMID:37709746]. Beyond transcription, PHF14 contributes to cell-cycle control by modulating H3K4me3 and repressing the cyclin-dependent kinase inhibitor Cdkn1a/p21 in germinal-center B cells [PMID:33035772], and supports the DNA damage response through interaction with KIF4A and BRCA2/RAD51 foci formation [PMID:35074497].","teleology":[{"year":2012,"claim":"Established PHF14's first in vivo function by showing it is a transcriptional repressor of PDGFRα required to restrain mesenchymal proliferation, answering whether PHF14 has a defined physiological role.","evidence":"Phf14-null mice with histology, expression assays, and anti-PDGFRα antibody rescue of lung fibrosis","pmids":["22730381"],"confidence":"High","gaps":["Did not define how PHF14 binds the PDGFRα locus or whether repression is direct at the chromatin level","No structural basis for transcription factor activity"]},{"year":2013,"claim":"Localized PHF14 to the nucleus and linked its histone engagement to PHD fingers, framing it as a chromatin-associated reader during cell division.","evidence":"Molecular cloning, co-IP histone binding, nuclear and chromatin-binding assays of PHF14α isoform","pmids":["23688586"],"confidence":"Medium","gaps":["Single Co-IP without modification-state resolution","Histone target specificity undefined"]},{"year":2017,"claim":"Placed PHF14 within an upstream signaling circuit by showing phospho-SMAD3 induces PHF14, which then represses PDGFRα, defining a TGF-β/SMAD3/PHF14 self-limiting feedback loop in fibrosis.","evidence":"ChIP, TGF-β stimulation of renal fibroblasts, and PHF14-null injury model","pmids":["28045076"],"confidence":"Medium","gaps":["Single lab","Did not resolve direct PHF14 binding at the PDGFRα promoter versus indirect regulation"]},{"year":2019,"claim":"Connected PHF14 to cell-cycle and growth signaling under stress by linking its hypoxic inhibition to elevated CDK inhibitors and reduced AKT-mTOR signaling.","evidence":"Pulsed-SILAC proteomics and biochemical assays in a PHF14-knockdown xenograft","pmids":["31040906"],"confidence":"Low","gaps":["Limited mechanistic depth, no direct target identified","Correlative association between hypoxia and PHF14 activity"]},{"year":2020,"claim":"Defined a chromatin-modification mechanism for proliferation control by showing PHF14 modulates H3K4me3 at Cdkn1a to repress p21 in germinal-center B cells.","evidence":"GC B cell-specific knockout mice with H3K4me3 ChIP, flow cytometry, and qRT-PCR","pmids":["33035772"],"confidence":"Medium","gaps":["Mechanism connecting PHF14 to H3K4me3 deposition/removal unresolved","Single lab"]},{"year":2021,"claim":"Provided the structural basis for PHF14 as a reader of unmodified H3, showing bipartite recognition via a PZP cassette and negative regulation by active histone marks.","evidence":"X-ray crystallography, HDX-MS, and binding assays of the PHF14 PZP-H3 complex","pmids":["34365506"],"confidence":"High","gaps":["Did not connect the structural readout to specific gene-regulatory outcomes in cells","In vivo chromatin targets of the PZP domain not mapped"]},{"year":2022,"claim":"Showed PHF14 assembles with HMG20A through a coiled-coil and engages TEAD1, integrating PHF14 into Hippo signaling and EMT control.","evidence":"Proteomics, deletion analysis, AlphaFold2 modeling, siRNA knockdown, transcriptomics, and TEAD1 interaction assay","pmids":["36124662"],"confidence":"Medium","gaps":["Structural model from AlphaFold2 not experimentally solved","Direct versus indirect TEAD1 contact not fully resolved"]},{"year":2022,"claim":"Extended PHF14 function beyond transcription by linking it to the DNA damage response via KIF4A interaction and BRCA2/RAD51 foci formation, with loss activating ATR-CHK1-γH2A.X-driven apoptosis.","evidence":"siRNA knockdown, PHF14-KIF4A Co-IP, BRCA2/RAD51 immunofluorescence, pathway western blots, and xenograft in colorectal cancer","pmids":["35074497"],"confidence":"Medium","gaps":["Single Co-IP for KIF4A interaction","Mechanism of PHF14 recruitment to damage foci undefined"]},{"year":2022,"claim":"Generalized the PHF14-PDGFRα repressive axis to neural tumors and demonstrated rescue, reinforcing PDGFRα as a conserved PHF14 target.","evidence":"shRNA, CRISPR/Cas9 knockout, Sunitinib treatment, xenograft, and WT PHF14 rescue in neurocytoma primary cultures","pmids":["36359362"],"confidence":"Medium","gaps":["Direct chromatin binding at PDGFRα not shown in this system","Single lab"]},{"year":2023,"claim":"Revealed a DNA-methylation-based repressive mechanism by showing PHF14 recruits DNMT3B to hypermethylate and silence SMAD7, promoting TGF-β-driven metastasis.","evidence":"Reciprocal Co-IP, ChIP, DNA methylation analysis, and in vitro/in vivo metastasis assays in lung adenocarcinoma","pmids":["37072414"],"confidence":"Medium","gaps":["How PHF14 reads CpG motifs structurally not resolved","Single lab"]},{"year":2023,"claim":"Identified PHF14 as a stable subunit of a KMT2A-associated PHF5A-PHF14-HMG20A-RAI1 subcomplex supporting cancer stem cell self-renewal.","evidence":"Proteomics, Co-IP, KMT2A-WDR5 inhibitor treatment, and in vivo tumorigenicity in pancreatic cancer stem cells","pmids":["37709746"],"confidence":"Medium","gaps":["Functional contribution of PHF14 within the subcomplex not isolated","Stoichiometry and assembly order undefined"]},{"year":2024,"claim":"Defined an upstream transcriptional activator of PHF14 by showing SP4 binds and activates the PHF14 promoter in esophageal squamous cell carcinoma.","evidence":"ChIP, luciferase reporter assays, and knockdown/overexpression with Wnt/β-catenin analysis","pmids":["37768180"],"confidence":"Medium","gaps":["How SP4-driven PHF14 levels feed into chromatin or PDGFRα programs unresolved","Single lab"]},{"year":null,"claim":"It remains unresolved how the structurally defined unmodified-H3 reader activity is mechanistically connected to PHF14's diverse gene-regulatory and DNA-repair outputs in vivo.","evidence":"No timeline study links the PZP readout to genome-wide chromatin targeting and the downstream PDGFRα, SMAD7, Hippo, and DDR programs","pmids":[],"confidence":"Low","gaps":["No genome-wide map tying PZP histone recognition to regulated loci","Whether PHF14 acts as activator or repressor is context-dependent without a unifying mechanism","Interplay between transcriptional and DNA-repair roles uncharacterized"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0042393","term_label":"histone binding","supporting_discovery_ids":[0,2]},{"term_id":"GO:0140110","term_label":"transcription regulator activity","supporting_discovery_ids":[1,3]},{"term_id":"GO:0003677","term_label":"DNA binding","supporting_discovery_ids":[4]}],"localization":[{"term_id":"GO:0005634","term_label":"nucleus","supporting_discovery_ids":[2]},{"term_id":"GO:0005694","term_label":"chromosome","supporting_discovery_ids":[0,2]}],"pathway":[{"term_id":"R-HSA-74160","term_label":"Gene expression (Transcription)","supporting_discovery_ids":[1,4]},{"term_id":"R-HSA-162582","term_label":"Signal Transduction","supporting_discovery_ids":[3,6]},{"term_id":"R-HSA-4839726","term_label":"Chromatin organization","supporting_discovery_ids":[0,8]}],"complexes":["PHF14-HMG20A complex","PHF5A-PHF14-HMG20A-RAI1 (KMT2A-associated) subcomplex"],"partners":["HMG20A","TEAD1","DNMT3B","KIF4A","PHF5A","RAI1","KMT2A","SMAD3"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"O94880","full_name":"PHD finger protein 14","aliases":[],"length_aa":948,"mass_kda":107.0,"function":"Histone-binding protein (PubMed:23688586). Binds preferentially to unmodified histone H3 but can also bind to a lesser extent to histone H3 trimethylated at 'Lys-9' (H3K9me3) as well as to histone H3 monomethylated at 'Lys-27' (H3K27ac) and trimethylated at 'Lys-27' (H3K27me3) (By similarity). Represses PDGFRA expression, thus playing a role in regulation of mesenchymal cell proliferation (By similarity). Suppresses the expression of CDKN1A/p21 by reducing the level of trimethylation of histone H3 'Lys-4', leading to enhanced proliferation of germinal center B cells (By similarity)","subcellular_location":"Cytoplasm","url":"https://www.uniprot.org/uniprotkb/O94880/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/PHF14","classification":"Not Classified","n_dependent_lines":1,"n_total_lines":1208,"dependency_fraction":0.0008278145695364238},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[{"gene":"CBX1","stoichiometry":0.2},{"gene":"DRG1","stoichiometry":0.2},{"gene":"H2AFZ","stoichiometry":0.2},{"gene":"HDAC1","stoichiometry":0.2},{"gene":"HDAC2","stoichiometry":0.2},{"gene":"HIST2H2BE","stoichiometry":0.2},{"gene":"HMGA1","stoichiometry":0.2},{"gene":"HMGN5","stoichiometry":0.2},{"gene":"HNRNPH1","stoichiometry":0.2},{"gene":"MIF","stoichiometry":0.2}],"url":"https://opencell.sf.czbiohub.org/search/PHF14","total_profiled":1310},"omim":[{"mim_id":"619907","title":"PHD FINGER PROTEIN 14; PHF14","url":"https://www.omim.org/entry/619907"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Approved","locations":[{"location":"Vesicles","reliability":"Approved"},{"location":"Nucleoplasm","reliability":"Additional"},{"location":"Cytosol","reliability":"Additional"}],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in all","driving_tissues":[],"url":"https://www.proteinatlas.org/search/PHF14"},"hgnc":{"alias_symbol":["KIAA0783"],"prev_symbol":[]},"alphafold":{"accession":"O94880","domains":[{"cath_id":"3.30.40.10","chopping":"335-355_369-575","consensus_level":"medium","plddt":85.3247,"start":335,"end":575},{"cath_id":"3.30.40.10","chopping":"726-764","consensus_level":"medium","plddt":84.1313,"start":726,"end":764},{"cath_id":"1.20.5","chopping":"613-695","consensus_level":"medium","plddt":86.3129,"start":613,"end":695}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/O94880","model_url":"https://alphafold.ebi.ac.uk/files/AF-O94880-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-O94880-F1-predicted_aligned_error_v6.png","plddt_mean":62.66},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=PHF14","jax_strain_url":"https://www.jax.org/strain/search?query=PHF14"},"sequence":{"accession":"O94880","fasta_url":"https://rest.uniprot.org/uniprotkb/O94880.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/O94880/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/O94880"}},"corpus_meta":[{"pmid":"30940184","id":"PMC_30940184","title":"LINC00612 enhances the proliferation and invasion ability of bladder cancer cells as ceRNA by sponging miR-590 to elevate expression of PHF14.","date":"2019","source":"Journal of experimental & clinical cancer research : CR","url":"https://pubmed.ncbi.nlm.nih.gov/30940184","citation_count":50,"is_preprint":false},{"pmid":"22730381","id":"PMC_22730381","title":"Phf14, a novel regulator of mesenchyme growth via platelet-derived growth factor (PDGF) receptor-α.","date":"2012","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/22730381","citation_count":30,"is_preprint":false},{"pmid":"37072414","id":"PMC_37072414","title":"PHF14 enhances DNA methylation of SMAD7 gene to promote TGF-β-driven lung adenocarcinoma metastasis.","date":"2023","source":"Cell discovery","url":"https://pubmed.ncbi.nlm.nih.gov/37072414","citation_count":27,"is_preprint":false},{"pmid":"35074497","id":"PMC_35074497","title":"PHF14 knockdown causes apoptosis by inducing DNA damage and impairing the activity of the damage response complex in colorectal cancer.","date":"2022","source":"Cancer letters","url":"https://pubmed.ncbi.nlm.nih.gov/35074497","citation_count":24,"is_preprint":false},{"pmid":"23688586","id":"PMC_23688586","title":"Depletion of PHF14, a novel histone-binding protein gene, causes neonatal lethality in mice due to respiratory failure.","date":"2013","source":"Acta biochimica et biophysica Sinica","url":"https://pubmed.ncbi.nlm.nih.gov/23688586","citation_count":24,"is_preprint":false},{"pmid":"34365506","id":"PMC_34365506","title":"Molecular basis for bipartite recognition of histone H3 by the PZP domain of PHF14.","date":"2021","source":"Nucleic acids research","url":"https://pubmed.ncbi.nlm.nih.gov/34365506","citation_count":21,"is_preprint":false},{"pmid":"31040906","id":"PMC_31040906","title":"Pulsed SILAC-based proteomic analysis unveils hypoxia- and serum starvation-induced de novo protein synthesis with PHD finger protein 14 (PHF14) as a hypoxia sensitive epigenetic regulator in cell cycle progression.","date":"2019","source":"Oncotarget","url":"https://pubmed.ncbi.nlm.nih.gov/31040906","citation_count":17,"is_preprint":false},{"pmid":"32596345","id":"PMC_32596345","title":"PHF14 Promotes Cell Proliferation and Migration through the AKT and ERK1/2 Pathways in Gastric Cancer Cells.","date":"2020","source":"BioMed research international","url":"https://pubmed.ncbi.nlm.nih.gov/32596345","citation_count":15,"is_preprint":false},{"pmid":"31798343","id":"PMC_31798343","title":"Silencing expression of PHF14 in glioblastoma promotes apoptosis, mitigates proliferation and invasiveness via Wnt signal pathway.","date":"2019","source":"Cancer cell international","url":"https://pubmed.ncbi.nlm.nih.gov/31798343","citation_count":14,"is_preprint":false},{"pmid":"23833654","id":"PMC_23833654","title":"Aberrant expression of the PHF14 gene in biliary tract cancer cells.","date":"2013","source":"Oncology letters","url":"https://pubmed.ncbi.nlm.nih.gov/23833654","citation_count":13,"is_preprint":false},{"pmid":"37709746","id":"PMC_37709746","title":"KMT2A associates with PHF5A-PHF14-HMG20A-RAI1 subcomplex in pancreatic cancer stem cells and epigenetically regulates their characteristics.","date":"2023","source":"Nature communications","url":"https://pubmed.ncbi.nlm.nih.gov/37709746","citation_count":12,"is_preprint":false},{"pmid":"36124662","id":"PMC_36124662","title":"The high mobility group protein HMG20A cooperates with the histone reader PHF14 to modulate TGFβ and Hippo pathways.","date":"2022","source":"Nucleic acids research","url":"https://pubmed.ncbi.nlm.nih.gov/36124662","citation_count":8,"is_preprint":false},{"pmid":"28045076","id":"PMC_28045076","title":"PHF14: an innate inhibitor against the progression of renal fibrosis following folic acid-induced kidney injury.","date":"2017","source":"Scientific 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analysis unveiling the oncogenic effect of plant homeodomain finger protein 14 (PHF14) in human tumors.","date":"2023","source":"Frontiers in genetics","url":"https://pubmed.ncbi.nlm.nih.gov/37007943","citation_count":3,"is_preprint":false},{"pmid":"28814329","id":"PMC_28814329","title":"Severe persistent pulmonary hypertension of the newborn and dysmorphic features in neonate with a deletion involving TWIST1 and PHF14: a case report.","date":"2017","source":"Journal of medical case reports","url":"https://pubmed.ncbi.nlm.nih.gov/28814329","citation_count":3,"is_preprint":false},{"pmid":"36359362","id":"PMC_36359362","title":"Whole Exome Sequencing Identifies PHF14 Mutations in Neurocytoma and Predicts Responsivity to the PDGFR Inhibitor Sunitinib.","date":"2022","source":"Biomedicines","url":"https://pubmed.ncbi.nlm.nih.gov/36359362","citation_count":2,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":11253,"output_tokens":3154,"usd":0.040535,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":10641,"output_tokens":4171,"usd":0.07874,"stage2_stop_reason":"end_turn"},"total_usd":0.119275,"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\": 2021,\n      \"finding\": \"PHF14 reads unmodified histone H3(1-34) through an integrated PHD1-ZnK-PHD2 cassette (PZP domain), utilizing two distinct surfaces for bipartite recognition of H3-Nter (residues 1-15) and H3-middle (residues 14-34) segments. A PHF14-unique insertion loop in PHD1 dominates H3K4 readout rather than the core β-strands. Binding is sensitive to modifications at H3 R2, T3, K4, R8, and K23 but not K9 or K27, indicating active marks negatively regulate PHF14 engagement.\",\n      \"method\": \"X-ray crystallography, HDX-MS, binding assays, structural analysis of PHF14PZP-H3 complex\",\n      \"journal\": \"Nucleic acids research\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — crystal structure with functional binding assays and HDX-MS, multiple orthogonal methods in a single rigorous study\",\n      \"pmids\": [\"34365506\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2012,\n      \"finding\": \"Phf14 acts as a transcription factor that directly represses PDGFRα expression in mesenchymal cells. Phf14-null mice show elevated PDGFRα expression and increased mesenchymal cell proliferation, leading to interstitial hyperplasia and neonatal lethality from respiratory failure. Anti-PDGFRα antibody treatment rescued mouse lung fibrosis in this model.\",\n      \"method\": \"Gene-targeting knockout (Phf14-null mice), histological analysis, gene expression assays, antibody rescue experiment\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — genetic knockout with defined molecular phenotype (PDGFRα upregulation), replicated in renal fibrosis study (PMID:28045076) and neurocytoma study (PMID:36359362)\",\n      \"pmids\": [\"22730381\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2013,\n      \"finding\": \"PHF14α (the major isoform) localizes to the nucleus and binds chromatin during cell division. Co-immunoprecipitation showed PHF14α binds histones via its PHD fingers.\",\n      \"method\": \"Molecular cloning, co-immunoprecipitation, nuclear localization assay, chromatin-binding assay during cell division\",\n      \"journal\": \"Acta biochimica et biophysica Sinica\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — single Co-IP for histone binding, replicated conceptually by structural study (PMID:34365506), single lab\",\n      \"pmids\": [\"23688586\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"In renal fibrosis, phospho-SMAD3 acts as a transcription factor that enhances PHF14 expression (ChIP assay). PHF14 in turn represses PDGFRα transcription to limit PDGF signaling overactivation, forming a TGF-β/SMAD3/PHF14 self-limiting feedback pathway in the renal pro-fibrotic process.\",\n      \"method\": \"Chromatin immunoprecipitation (ChIP), in vitro TGF-β stimulation of rat renal fibroblasts, PHF14-null mouse model with folic acid-induced injury\",\n      \"journal\": \"Scientific reports\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — ChIP assay with genetic KO model, single lab, two orthogonal methods\",\n      \"pmids\": [\"28045076\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"PHF14 binds DNMT3B and serves as a DNA CpG motif reader, recruiting DNMT3B to the SMAD7 gene locus, resulting in DNA hypermethylation and transcriptional suppression of SMAD7. This suppresses TGF-β pathway antagonism and promotes lung adenocarcinoma metastasis.\",\n      \"method\": \"Co-immunoprecipitation (PHF14-DNMT3B interaction), ChIP assay, in vitro and in vivo metastasis experiments, DNA methylation analysis\",\n      \"journal\": \"Cell discovery\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reciprocal Co-IP for complex formation plus ChIP and functional in vivo data, single lab\",\n      \"pmids\": [\"37072414\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"PHF14 is a physical component of a PHF5A-PHF14-HMG20A-RAI1 protein subcomplex associated with histone methyltransferase KMT2A (MLL1) via RNA polymerase-associated interactions in pancreatic cancer stem cells. Targeting KMT2A-WDR5 interaction attenuates cancer stem cell self-renewal.\",\n      \"method\": \"Proteomic analysis, co-immunoprecipitation, KMT2A-WDR5 inhibitor treatment in pancreatic cancer stem cells, in vivo tumorigenicity assay\",\n      \"journal\": \"Nature communications\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — proteomic identification plus functional inhibitor data, single lab, multiple orthogonal methods\",\n      \"pmids\": [\"37709746\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"PHF14 forms a stable complex with HMG20A via a two-stranded alpha-helical coiled-coil structure. The PHF14-HMG20A complex directly interacts with TEAD1 transcription factor to modulate the Hippo pathway. siRNA knockdown of either PHF14 or HMG20A causes similar defects in cell migration, invasion, and homotypic cell-cell adhesion, and impairs TGF-β-triggered epithelial-to-mesenchymal transition.\",\n      \"method\": \"Proteomic study, deletion analysis, AlphaFold2 structural modeling, siRNA knockdown, transcriptomic analysis, TEAD1 interaction assay\",\n      \"journal\": \"Nucleic acids research\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — proteomic plus structural modeling plus functional knockdown with transcriptomic validation, single lab\",\n      \"pmids\": [\"36124662\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"PHF14 knockdown in colorectal cancer cells induces DNA damage and activates the ATR-CHK1-H2A.X pathway, leading to apoptosis. PHF14 interacts with KIF4A and contributes to formation of BRCA2/RAD51 foci, suggesting PHF14 participates in DNA damage response complex recruitment.\",\n      \"method\": \"siRNA knockdown, co-immunoprecipitation (PHF14-KIF4A), immunofluorescence for BRCA2/RAD51 foci, western blot for ATR-CHK1-γH2A.X, in vivo xenograft\",\n      \"journal\": \"Cancer letters\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — single Co-IP for KIF4A interaction, supported by foci assay and pathway activation data, single lab\",\n      \"pmids\": [\"35074497\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"PHF14 suppresses the expression of cell cycle inhibitor Cdkn1a (p21) by regulating H3K4me3 levels at the Cdkn1a locus, thereby controlling proliferation of germinal center B cells. PHF14 conditional knockout in germinal center B cells reduces GC response without affecting GC B cell survival.\",\n      \"method\": \"GC B cell-specific PHF14 knockout mice, SRBC/LCMV challenge, H3K4me3 ChIP, flow cytometry, qRT-PCR\",\n      \"journal\": \"Cellular immunology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — conditional knockout with ChIP-based mechanistic link, single lab, two orthogonal methods\",\n      \"pmids\": [\"33035772\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"Loss of PHF14 (shRNA knockdown or CRISPR/Cas9 knockout) upregulates PDGFRα mRNA and protein in neuroblastoma SHSY-5Y cells, increases sensitivity to the PDGFR inhibitor Sunitinib, and enhances proliferation and colony formation. Overexpression of wild-type PHF14 reversed proliferation in neurocytoma primary cultures with PHF14 splicing mutations.\",\n      \"method\": \"shRNA knockdown, CRISPR/Cas9 knockout, PDGFR inhibitor (Sunitinib) treatment, nude mouse xenograft, primary culture rescue with WT PHF14\",\n      \"journal\": \"Biomedicines\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — multiple genetic tools (shRNA + CRISPR) with in vivo validation and rescue experiment, single lab\",\n      \"pmids\": [\"36359362\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"Hypoxia-mediated inhibition of PHF14 is associated with increased cell cycle inhibitors p14ARF, p15INK4b, and p16INK4a (responsible for G1-S transition arrest) and decreased AKT-mTOR-4E-BP1/pS6K signaling, establishing PHF14 as a regulator of cell cycle progression and protein synthesis under hypoxic conditions.\",\n      \"method\": \"Pulsed-SILAC proteomics, biochemical assays, PHF14 KD xenograft model\",\n      \"journal\": \"Oncotarget\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — proteomic discovery with biochemical validation, single lab, limited mechanistic depth on direct targets\",\n      \"pmids\": [\"31040906\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"SP4 transcription factor binds to the PHF14 promoter region and activates PHF14 transcription, placing SP4 as a direct upstream transcriptional regulator of PHF14 in esophageal squamous cell carcinoma.\",\n      \"method\": \"ChIP assay (SP4 binding to PHF14 promoter), luciferase reporter assay, knockdown/overexpression experiments, Wnt/β-catenin pathway analysis\",\n      \"journal\": \"Molecular cancer research : MCR\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — ChIP plus reporter assay demonstrating direct promoter binding, single lab, two orthogonal methods\",\n      \"pmids\": [\"37768180\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"PHF14 is a nuclear multi-PHD finger chromatin reader that recognizes unmodified histone H3(1-34) through a bipartite PZP (PHD1-ZnK-PHD2) domain; it functions as a transcriptional repressor of PDGFRα (regulated by upstream TGF-β/SMAD3 signaling), recruits DNMT3B to methylate and silence SMAD7, forms a complex with HMG20A to modulate Hippo/TEAD1 and TGF-β-driven EMT pathways, participates in a KMT2A-associated PHF5A-PHF14-HMG20A-RAI1 subcomplex in cancer stem cells, and supports DNA damage response via interaction with KIF4A and BRCA2/RAD51 foci formation, collectively linking PHF14 to mesenchymal homeostasis, organ development, and tumor progression.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"PHF14 is a nuclear multi-PHD-finger chromatin reader that couples recognition of unmodified histone H3 to transcriptional control of mesenchymal proliferation, fibrosis, and tumor progression [#0, #1]. Structurally, it engages histone H3(1-34) through an integrated PHD1-ZnK-PHD2 (PZP) cassette that uses two surfaces for bipartite readout of the H3 N-terminus and middle region, with a PHF14-unique PHD1 insertion loop dominating H3K4 sensing; active marks at H3R2, T3, K4, R8, and K23 negatively regulate engagement, so PHF14 preferentially reads chromatin lacking these modifications [#0]. A central transcriptional output is direct repression of PDGFRα: Phf14-null mice over-express PDGFRα and develop mesenchymal hyperplasia and lethal lung fibrosis rescuable by anti-PDGFRα antibody, and loss of PHF14 elevates PDGFRα across renal and neural tumor contexts [#1, #9]. This activity is embedded in TGF-β signaling, where phospho-SMAD3 induces PHF14 to form a self-limiting feedback loop restraining PDGF signaling [#3], while in lung adenocarcinoma PHF14 recruits the DNA methyltransferase DNMT3B to silence the TGF-β antagonist SMAD7 by CpG hypermethylation [#4]. PHF14 further acts through stable assembly with HMG20A via a coiled-coil interface, and this complex contacts TEAD1 to modulate Hippo signaling and TGF-β-driven epithelial-to-mesenchymal transition [#6], and it is a component of a KMT2A-associated PHF5A-PHF14-HMG20A-RAI1 subcomplex in cancer stem cells [#5]. Beyond transcription, PHF14 contributes to cell-cycle control by modulating H3K4me3 and repressing the cyclin-dependent kinase inhibitor Cdkn1a/p21 in germinal-center B cells [#8], and supports the DNA damage response through interaction with KIF4A and BRCA2/RAD51 foci formation [#7].\",\n  \"teleology\": [\n    {\n      \"year\": 2012,\n      \"claim\": \"Established PHF14's first in vivo function by showing it is a transcriptional repressor of PDGFRα required to restrain mesenchymal proliferation, answering whether PHF14 has a defined physiological role.\",\n      \"evidence\": \"Phf14-null mice with histology, expression assays, and anti-PDGFRα antibody rescue of lung fibrosis\",\n      \"pmids\": [\"22730381\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Did not define how PHF14 binds the PDGFRα locus or whether repression is direct at the chromatin level\", \"No structural basis for transcription factor activity\"]\n    },\n    {\n      \"year\": 2013,\n      \"claim\": \"Localized PHF14 to the nucleus and linked its histone engagement to PHD fingers, framing it as a chromatin-associated reader during cell division.\",\n      \"evidence\": \"Molecular cloning, co-IP histone binding, nuclear and chromatin-binding assays of PHF14α isoform\",\n      \"pmids\": [\"23688586\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Single Co-IP without modification-state resolution\", \"Histone target specificity undefined\"]\n    },\n    {\n      \"year\": 2017,\n      \"claim\": \"Placed PHF14 within an upstream signaling circuit by showing phospho-SMAD3 induces PHF14, which then represses PDGFRα, defining a TGF-β/SMAD3/PHF14 self-limiting feedback loop in fibrosis.\",\n      \"evidence\": \"ChIP, TGF-β stimulation of renal fibroblasts, and PHF14-null injury model\",\n      \"pmids\": [\"28045076\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Single lab\", \"Did not resolve direct PHF14 binding at the PDGFRα promoter versus indirect regulation\"]\n    },\n    {\n      \"year\": 2019,\n      \"claim\": \"Connected PHF14 to cell-cycle and growth signaling under stress by linking its hypoxic inhibition to elevated CDK inhibitors and reduced AKT-mTOR signaling.\",\n      \"evidence\": \"Pulsed-SILAC proteomics and biochemical assays in a PHF14-knockdown xenograft\",\n      \"pmids\": [\"31040906\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"Limited mechanistic depth, no direct target identified\", \"Correlative association between hypoxia and PHF14 activity\"]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"Defined a chromatin-modification mechanism for proliferation control by showing PHF14 modulates H3K4me3 at Cdkn1a to repress p21 in germinal-center B cells.\",\n      \"evidence\": \"GC B cell-specific knockout mice with H3K4me3 ChIP, flow cytometry, and qRT-PCR\",\n      \"pmids\": [\"33035772\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Mechanism connecting PHF14 to H3K4me3 deposition/removal unresolved\", \"Single lab\"]\n    },\n    {\n      \"year\": 2021,\n      \"claim\": \"Provided the structural basis for PHF14 as a reader of unmodified H3, showing bipartite recognition via a PZP cassette and negative regulation by active histone marks.\",\n      \"evidence\": \"X-ray crystallography, HDX-MS, and binding assays of the PHF14 PZP-H3 complex\",\n      \"pmids\": [\"34365506\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Did not connect the structural readout to specific gene-regulatory outcomes in cells\", \"In vivo chromatin targets of the PZP domain not mapped\"]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"Showed PHF14 assembles with HMG20A through a coiled-coil and engages TEAD1, integrating PHF14 into Hippo signaling and EMT control.\",\n      \"evidence\": \"Proteomics, deletion analysis, AlphaFold2 modeling, siRNA knockdown, transcriptomics, and TEAD1 interaction assay\",\n      \"pmids\": [\"36124662\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Structural model from AlphaFold2 not experimentally solved\", \"Direct versus indirect TEAD1 contact not fully resolved\"]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"Extended PHF14 function beyond transcription by linking it to the DNA damage response via KIF4A interaction and BRCA2/RAD51 foci formation, with loss activating ATR-CHK1-γH2A.X-driven apoptosis.\",\n      \"evidence\": \"siRNA knockdown, PHF14-KIF4A Co-IP, BRCA2/RAD51 immunofluorescence, pathway western blots, and xenograft in colorectal cancer\",\n      \"pmids\": [\"35074497\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Single Co-IP for KIF4A interaction\", \"Mechanism of PHF14 recruitment to damage foci undefined\"]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"Generalized the PHF14-PDGFRα repressive axis to neural tumors and demonstrated rescue, reinforcing PDGFRα as a conserved PHF14 target.\",\n      \"evidence\": \"shRNA, CRISPR/Cas9 knockout, Sunitinib treatment, xenograft, and WT PHF14 rescue in neurocytoma primary cultures\",\n      \"pmids\": [\"36359362\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Direct chromatin binding at PDGFRα not shown in this system\", \"Single lab\"]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"Revealed a DNA-methylation-based repressive mechanism by showing PHF14 recruits DNMT3B to hypermethylate and silence SMAD7, promoting TGF-β-driven metastasis.\",\n      \"evidence\": \"Reciprocal Co-IP, ChIP, DNA methylation analysis, and in vitro/in vivo metastasis assays in lung adenocarcinoma\",\n      \"pmids\": [\"37072414\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"How PHF14 reads CpG motifs structurally not resolved\", \"Single lab\"]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"Identified PHF14 as a stable subunit of a KMT2A-associated PHF5A-PHF14-HMG20A-RAI1 subcomplex supporting cancer stem cell self-renewal.\",\n      \"evidence\": \"Proteomics, Co-IP, KMT2A-WDR5 inhibitor treatment, and in vivo tumorigenicity in pancreatic cancer stem cells\",\n      \"pmids\": [\"37709746\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Functional contribution of PHF14 within the subcomplex not isolated\", \"Stoichiometry and assembly order undefined\"]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Defined an upstream transcriptional activator of PHF14 by showing SP4 binds and activates the PHF14 promoter in esophageal squamous cell carcinoma.\",\n      \"evidence\": \"ChIP, luciferase reporter assays, and knockdown/overexpression with Wnt/β-catenin analysis\",\n      \"pmids\": [\"37768180\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"How SP4-driven PHF14 levels feed into chromatin or PDGFRα programs unresolved\", \"Single lab\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"It remains unresolved how the structurally defined unmodified-H3 reader activity is mechanistically connected to PHF14's diverse gene-regulatory and DNA-repair outputs in vivo.\",\n      \"evidence\": \"No timeline study links the PZP readout to genome-wide chromatin targeting and the downstream PDGFRα, SMAD7, Hippo, and DDR programs\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"No genome-wide map tying PZP histone recognition to regulated loci\", \"Whether PHF14 acts as activator or repressor is context-dependent without a unifying mechanism\", \"Interplay between transcriptional and DNA-repair roles uncharacterized\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0042393\", \"supporting_discovery_ids\": [0, 2]},\n      {\"term_id\": \"GO:0140110\", \"supporting_discovery_ids\": [1, 3]},\n      {\"term_id\": \"GO:0003677\", \"supporting_discovery_ids\": [4]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005634\", \"supporting_discovery_ids\": [2]},\n      {\"term_id\": \"GO:0005694\", \"supporting_discovery_ids\": [0, 2]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-74160\", \"supporting_discovery_ids\": [1, 4]},\n      {\"term_id\": \"R-HSA-162582\", \"supporting_discovery_ids\": [3, 6]},\n      {\"term_id\": \"R-HSA-4839726\", \"supporting_discovery_ids\": [0, 8]}\n    ],\n    \"complexes\": [\n      \"PHF14-HMG20A complex\",\n      \"PHF5A-PHF14-HMG20A-RAI1 (KMT2A-associated) subcomplex\"\n    ],\n    \"partners\": [\n      \"HMG20A\",\n      \"TEAD1\",\n      \"DNMT3B\",\n      \"KIF4A\",\n      \"PHF5A\",\n      \"RAI1\",\n      \"KMT2A\",\n      \"SMAD3\"\n    ],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":6,"faith_total":6,"faith_pct":100.0}}