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organism_full: Homo sapiens (Human).
protein_family: Belongs to the PHF23 family. .
protein_domains: Znf_FYVE_PHD. (IPR011011); Znf_PHD. (IPR001965); Znf_PHD-finger.
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Question

Gene Research for Functional Annotation

⚠️ CRITICAL: Gene/Protein Identification Context

BEFORE YOU BEGIN RESEARCH: You MUST verify you are researching the CORRECT gene/protein. Gene symbols can be ambiguous, especially for less well-characterized genes from non-model organisms.

Target Gene/Protein Identity (from UniProt):

• UniProt Accession: Q9BUL5
• Protein Description: RecName: Full=PHD finger protein 23 {ECO:0000303|PubMed:25484098}; AltName: Full=PDH-containing protein JUNE-1 {ECO:0000250|UniProtKB:Q8BSN5};
• Gene Information: Name=PHF23 {ECO:0000303|PubMed:25484098};
• Organism (full): Homo sapiens (Human).
• Protein Family: Belongs to the PHF23 family. .
• Key Domains: Znf_FYVE_PHD. (IPR011011); Znf_PHD. (IPR001965); Znf_PHD-finger. (IPR019787); Znf_RING/FYVE/PHD. (IPR013083); PHD_2 (PF13831)

MANDATORY VERIFICATION STEPS:

1. Check if the gene symbol "PHF23" matches the protein description above
2. Verify the organism is correct: Homo sapiens (Human).
3. Check if protein family/domains align with what you find in literature
4. If you find literature for a DIFFERENT gene with the same or similar symbol, STOP

If Gene Symbol is Ambiguous or You Cannot Find Relevant Literature:

DO NOT PROCEED WITH RESEARCH ON A DIFFERENT GENE. Instead:
- State clearly: "The gene symbol 'PHF23' is ambiguous or literature is limited for this specific protein"
- Explain what you found (e.g., "Found extensive literature on a different gene with the same symbol in a different organism")
- Describe the protein based ONLY on the UniProt information provided above
- Suggest that the protein function can be inferred from domain/family information

Research Target:

Please provide a comprehensive research report on the gene PHF23 (gene ID: PHF23, UniProt: Q9BUL5) in human.

The research report should be a detailed narrative explaining the function, biological processes, and localization of the gene product. Citations should be given for all claims.

You should prioritize authoritative reviews and primary scientific literature when conducting research. You can supplement
this with annotations you find in gene/protein databases, but these can be outdated or inaccurate.

We are specifically interested in the primary function of the gene - for enzymes, what reaction is catalyzed, and what is the substrate specificity? For transporters, what is the substrate? For structural proteins or adapters, what is the broader structural role? For signaling molecules, what is the role in the pathway.

We are interested in where in or outside the cell the gene product carries out its function.

We are also interested in the signaling or biochemical pathways in which the gene functions. We are less interested in broad pleiotropic effects, except where these elucidate the precise role.

Include evidence where possible. We are interested in both experimental evidence as well as inference from structure, evolution, or bioinformatic analysis. Precise studies should be prioritized over high-throughput, where available.

Output

Question: You are an expert researcher providing comprehensive, well-cited information.

Provide detailed information focusing on:
1. Key concepts and definitions with current understanding
2. Recent developments and latest research (prioritize 2023-2024 sources)
3. Current applications and real-world implementations
4. Expert opinions and analysis from authoritative sources
5. Relevant statistics and data from recent studies

Format as a comprehensive research report with proper citations. Include URLs and publication dates where available.
Always prioritize recent, authoritative sources and provide specific citations for all major claims.

Gene Research for Functional Annotation

⚠️ CRITICAL: Gene/Protein Identification Context

BEFORE YOU BEGIN RESEARCH: You MUST verify you are researching the CORRECT gene/protein. Gene symbols can be ambiguous, especially for less well-characterized genes from non-model organisms.

Target Gene/Protein Identity (from UniProt):

• UniProt Accession: Q9BUL5
• Protein Description: RecName: Full=PHD finger protein 23 {ECO:0000303|PubMed:25484098}; AltName: Full=PDH-containing protein JUNE-1 {ECO:0000250|UniProtKB:Q8BSN5};
• Gene Information: Name=PHF23 {ECO:0000303|PubMed:25484098};
• Organism (full): Homo sapiens (Human).
• Protein Family: Belongs to the PHF23 family. .
• Key Domains: Znf_FYVE_PHD. (IPR011011); Znf_PHD. (IPR001965); Znf_PHD-finger. (IPR019787); Znf_RING/FYVE/PHD. (IPR013083); PHD_2 (PF13831)

MANDATORY VERIFICATION STEPS:

1. Check if the gene symbol "PHF23" matches the protein description above
2. Verify the organism is correct: Homo sapiens (Human).
3. Check if protein family/domains align with what you find in literature
4. If you find literature for a DIFFERENT gene with the same or similar symbol, STOP

If Gene Symbol is Ambiguous or You Cannot Find Relevant Literature:

DO NOT PROCEED WITH RESEARCH ON A DIFFERENT GENE. Instead:
- State clearly: "The gene symbol 'PHF23' is ambiguous or literature is limited for this specific protein"
- Explain what you found (e.g., "Found extensive literature on a different gene with the same symbol in a different organism")
- Describe the protein based ONLY on the UniProt information provided above
- Suggest that the protein function can be inferred from domain/family information

Research Target:

Please provide a comprehensive research report on the gene PHF23 (gene ID: PHF23, UniProt: Q9BUL5) in human.

The research report should be a detailed narrative explaining the function, biological processes, and localization of the gene product. Citations should be given for all claims.

You should prioritize authoritative reviews and primary scientific literature when conducting research. You can supplement
this with annotations you find in gene/protein databases, but these can be outdated or inaccurate.

We are specifically interested in the primary function of the gene - for enzymes, what reaction is catalyzed, and what is the substrate specificity? For transporters, what is the substrate? For structural proteins or adapters, what is the broader structural role? For signaling molecules, what is the role in the pathway.

We are interested in where in or outside the cell the gene product carries out its function.

We are also interested in the signaling or biochemical pathways in which the gene functions. We are less interested in broad pleiotropic effects, except where these elucidate the precise role.

Include evidence where possible. We are interested in both experimental evidence as well as inference from structure, evolution, or bioinformatic analysis. Precise studies should be prioritized over high-throughput, where available.

Plan and verification
- Objective 1 (identity/domains): Verified the target is human PHF23 (UniProt Q9BUL5), a ~403 aa PHD-finger–containing protein encoded at 17p13.1, with a C-terminal Zn-binding PHD domain and a nuclear localization signal (NLS) consistent with nuclear/chromatin functions (Frontiers in Cell & Developmental Biology, 2025; https://doi.org/10.3389/fcell.2025.1691318) (liu2025structurefunctionand pages 1-2, liu2025structurefunctionand pages 2-3).
- Objective 2–4 (evidence gathering): Focused on recent primary and mechanistic studies (2023–2025) for molecular function, localization, pathways, and disease links; prioritized peer-reviewed sources and supplemented with reviews. Key mechanistic literature includes: 2023 NSCLC study defining PHF23→ACTN4→ERK signaling (Cell Death & Disease, 2023; https://doi.org/10.1038/s41419-023-06069-4), JCI 2025 mechanistic study of NUP98–PHF23 leukemia biology (https://doi.org/10.1172/jci184743), and Blood 2020 defining CDK6 as a conserved NUP98-fusion target (https://doi.org/10.1182/blood.2019003267) (cheng2023phf23promotesnsclc pages 1-2, cheng2023phf23promotesnsclc pages 4-6, cheng2023phf23promotesnsclc pages 11-11, cheng2023phf23promotesnsclc pages 6-11, hamamoto2025hoxblinclncrnareprograms pages 1-2, schmoellerl2020cdk6isan pages 13-14, schmoellerl2020cdk6isan pages 1-1).
- Objective 5 (artifact): A structured table summarizing the most policy-relevant facts is embedded below.
- Objective 6: Final comprehensive report with citations, URLs, and dates.

Artifact summary
| Category | Evidence-based details | Key sources (with year) |
|---|---|---|
| Identity | PHF23 (human); UniProt Q9BUL5; gene encodes ~403 aa PHD-family protein | Liu 2025 (liu2025structurefunctionand pages 1-2), Liu 2025 (liu2025structurefunctionand pages 2-3) |
| Domains | C-terminal PHD finger (Zn2+-binding Cys/His motif); predicted nuclear localization signal (NLS) | Liu 2025 (liu2025structurefunctionand pages 2-3), Liu 2025 (liu2025structurefunctionand pages 1-2) |
| Primary molecular function | PHD-containing epigenetic reader. Direct H3K4me3 recognition is well-supported for the NUP98–PHF23 fusion (chromatin targeting); direct biochemical proof for native PHF23 H3K4me3 binding is inferred but less definitive | Hamamoto 2025 (hamamoto2025hoxblinclncrnareprograms pages 1-2), Liu 2025 (liu2025structurefunctionand pages 2-3), Liu 2025 (liu2025structurefunctionand pages 8-9) |
| Cellular localization | Predominantly nuclear and chromatin-associated (consistent with PHD reader role) | Liu 2025 (liu2025structurefunctionand pages 2-3), Liu 2025 (liu2025structurefunctionand pages 3-5) |
| Interactors / complexes | Reported interactions: ACTN4 (stabilization), association with HDAC2 / SIN3 components, and functional linkage to NUP98 in fusion; NUP98 fusions recruit MLL1/SET1A-COMPASS activity to promoters | Liu 2025 (liu2025structurefunctionand pages 2-3), Liu 2025 (liu2025structurefunctionand pages 8-9), Schmoellerl 2020 (schmoellerl2020cdk6isan pages 13-14) |
| Pathways / Processes | Chromatin regulation and transcriptional control; NUP98–PHF23 drives HOX/MEIS (homeotic) gene activation via H3K4me3-targeting; PHF23 reported to negatively regulate autophagy in cartilage and influence differentiation programs | Hamamoto 2025 (hamamoto2025hoxblinclncrnareprograms pages 1-2), Liu 2025 (liu2025structurefunctionand pages 3-5), Liu 2025 (liu2025structurefunctionand pages 2-3) |
| Disease relevance | Oncogenic when fused to NUP98 in AML/AMKL (NUP98–PHF23); PHF23 overexpression/alteration linked to NSCLC progression and chemoresistance; implicated in osteoarthritis via autophagy repression | Hamamoto 2025 (hamamoto2025hoxblinclncrnareprograms pages 1-2), Liu 2025 (liu2025structurefunctionand pages 3-5), Liu 2025 (liu2025structurefunctionand pages 8-9) |
| 2023–2025 developments | 2023: cancer role studies cited (e.g., NSCLC association reported in recent literature); 2020–2025: mechanistic insights—CDK6 identified as essential target of diverse NUP98 fusions (Schmoellerl 2020); 2025 JCI work (HoxBlinc) details H3K4me3-directed chromatin/TAD reprogramming by NUP98–PHF23 | Cheng 2023 reported in reviews (liu2025structurefunctionand pages 3-5), Schmoellerl 2020 (schmoellerl2020cdk6isan pages 13-14), Hamamoto 2025 (hamamoto2025hoxblinclncrnareprograms pages 1-2) |
| Therapeutic angles | Preclinical sensitivity of NUP98-fusion AML to CDK4/6 inhibition (CDK6 dependency demonstrated in models); inhibition of PHD reader function proposed to reverse fusion-driven transcriptional programs | Schmoellerl 2020 (schmoellerl2020cdk6isan pages 13-14), Liu 2025 (liu2025structurefunctionand pages 8-9) |
| Key statistics / data points | CDK6 identified as a conserved direct target of NUP98 fusions; genetic loss or pharmacologic inhibition of CDK6 attenuates NUP98-fusion leukemogenesis in mouse models and in vitro (Schmoellerl 2020). NUP98–PHF23 described as recurrent but rare; precise population frequencies not well quantified in current literature | Schmoellerl 2020 (schmoellerl2020cdk6isan pages 13-14), Liu 2025 (liu2025structurefunctionand pages 8-9) |

Table: Concise, evidence-linked summary of PHF23 (UniProt Q9BUL5) covering identity, domains, functions, localization, interactions, pathways, disease links, recent developments, therapeutic angles, and key data points with source citations for rapid reference.

Comprehensive research report on PHF23 (Q9BUL5)
1) Key concepts and definitions
- Gene/protein identity and domains: PHF23 (Plant Homeodomain Finger Protein 23) encodes a 403–amino-acid protein with a C-terminal PHD finger (Cys/His Zn2+-binding motif) and a nuclear localization signal (NLS), consistent with roles as a chromatin-associated reader protein in human cells. The gene maps to 17p13.1. These structural features place PHF23 within the PHD-finger family of epigenetic effectors (Frontiers in Cell & Developmental Biology, 2025; published 2025-11; https://doi.org/10.3389/fcell.2025.1691318) (liu2025structurefunctionand pages 1-2, liu2025structurefunctionand pages 2-3).
- Epigenetic reader function: PHD fingers often recognize methyl-lysine marks on histone H3, especially H3K4me3. In the context of the NUP98–PHF23 fusion oncoprotein, the PHF23 PHD finger directly recognizes H3K4me3 at HOX/MEIS loci, anchoring the fusion to chromatin and driving leukemogenic transcription (The Journal of Clinical Investigation, 2025; published 2025-01; https://doi.org/10.1172/jci184743) (hamamoto2025hoxblinclncrnareprograms pages 1-2).

2) Recent developments and latest research (emphasis 2023–2024)
- Oncogenic signaling in NSCLC (2023): PHF23 is overexpressed in non–small cell lung cancer (NSCLC) tissues and cell lines; higher PHF23 correlates with worse survival and poorer chemotherapy response. Mechanistically, PHF23 binds alpha-actinin-4 (ACTN4) via its PHD domain, stabilizes ACTN4 by reducing its ubiquitination, and activates ERK signaling, promoting proliferation, migration, DNA damage response changes, and chemoresistance. PHF23 localization in NSCLC is principally nuclear with cytoplasmic interactions with ACTN4; ERK inhibition blunts PHF23-driven phenotypes (Cell Death & Disease, 2023-08; https://doi.org/10.1038/s41419-023-06069-4) (cheng2023phf23promotesnsclc pages 1-2, cheng2023phf23promotesnsclc pages 4-6, cheng2023phf23promotesnsclc pages 6-11, cheng2023phf23promotesnsclc pages 11-11).
- Chromatin/TAD reprogramming in NUP98–PHF23 leukemia (2025): New work shows that in NUP98–PHF23 leukemias, the HoxBlinc lncRNA is aberrantly activated, recruits MLL1, and helps form CTCF-independent TADs that enhance chromatin accessibility and activate homeotic/hematopoietic oncogenes. NUP98–PHF23 occupancy correlates with H3K4me3, consistent with PHD-mediated chromatin recognition. HoxBlinc depletion disrupts this network and impairs leukemogenesis in models (JCI, 2025-01; https://doi.org/10.1172/jci184743) (hamamoto2025hoxblinclncrnareprograms pages 1-2).
- Core downstream dependency of NUP98 fusions (2020→ongoing relevance): CDK6 was identified as a conserved direct transcriptional target across diverse NUP98 fusions; genetic ablation or pharmacologic CDK6 inhibition impairs leukemogenesis in vitro and in vivo, nominating CDK4/6 inhibitors as a rational therapeutic strategy for NUP98-fusion AML. While this study did not test NUP98–PHF23 directly, it establishes a shared dependency framework among NUP98 fusions (Blood, 2020-07; https://doi.org/10.1182/blood.2019003267) (schmoellerl2020cdk6isan pages 13-14, schmoellerl2020cdk6isan pages 1-1).

3) Current applications and real-world implementations
- Preclinical therapeutic approach: CDK4/6 inhibition for NUP98-fusion AML. The definition of CDK6 as a direct target and essential effector suggests patients with NUP98 fusions (including NUP98–PHF23) may benefit from CDK4/6 inhibitors; supportive data come from murine and cellular models showing sensitivity upon CDK6 blockade. Translation to clinical practice will require prospective trials in molecularly characterized cohorts (Blood, 2020-07; https://doi.org/10.1182/blood.2019003267) (schmoellerl2020cdk6isan pages 13-14, schmoellerl2020cdk6isan pages 1-1).
- Mechanism-based target engagement: In NUP98–PHF23 leukemia, leukemogenic chromatin binding depends on the PHD-reader function that recognizes H3K4me3 at HOX/MEIS loci. These data motivate development of small molecules that disrupt PHD finger–H3K4me3 interactions or interfere with the NUP98 FG-repeat/condensate-driven transcriptional machinery (JCI, 2025-01; https://doi.org/10.1172/jci184743) (hamamoto2025hoxblinclncrnareprograms pages 1-2).
- Biomarker/use case in solid tumors: In NSCLC, PHF23/ACTN4/ERK axis activity may serve as a biomarker of poor prognosis and chemoresistance and a potential target for combinations with ERK pathway inhibitors, based on functional reversal of PHF23-driven phenotypes by ERK inhibition in preclinical systems (Cell Death & Disease, 2023-08; https://doi.org/10.1038/s41419-023-06069-4) (cheng2023phf23promotesnsclc pages 4-6, cheng2023phf23promotesnsclc pages 6-11, cheng2023phf23promotesnsclc pages 1-2).

4) Expert opinions and analysis from authoritative sources
- Leukemia epigenetics: Authoritative mechanistic work converges on the view that NUP98 fusions hijack active chromatin by engaging H3K4me3-marked promoters and recruiting MLL1/COMPASS activities, sustaining HOX/MEIS transcription and hematopoietic precursor self-renewal. The JCI 2025 study advances this by placing HoxBlinc-driven, CTCF-independent TADs downstream of NUP98–PHF23, reinforcing the centrality of PHD-mediated chromatin reading in oncogenesis (JCI, 2025-01; https://doi.org/10.1172/jci184743) (hamamoto2025hoxblinclncrnareprograms pages 1-2).
- Shared vulnerabilities among NUP98 fusions: The Blood 2020 study’s identification of CDK6 as a conserved direct target across multiple NUP98 fusions provides a unifying therapeutic rationale, suggesting that fusions like NUP98–PHF23 may be susceptible to CDK4/6 inhibitors even if not individually tested in that work (Blood, 2020-07; https://doi.org/10.1182/blood.2019003267) (schmoellerl2020cdk6isan pages 13-14, schmoellerl2020cdk6isan pages 1-1).
- Solid tumor signaling: The 2023 NSCLC study provides mechanistic clarity—PHF23’s PHD-mediated binding to ACTN4 stabilizes ACTN4 and activates ERK—to explain associations with poor outcomes and chemoresistance, pointing to pathway-centric interventions (Cell Death & Disease, 2023-08; https://doi.org/10.1038/s41419-023-06069-4) (cheng2023phf23promotesnsclc pages 1-2, cheng2023phf23promotesnsclc pages 4-6, cheng2023phf23promotesnsclc pages 6-11).

5) Relevant statistics and data from recent studies
- NSCLC (Cell Death & Disease, 2023): PHF23 is significantly overexpressed in NSCLC versus normal tissues by TCGA/GEO and immunohistochemistry; high expression associates with shorter overall survival and poorer chemotherapy response. Mechanistically, PHF23 overexpression increased phospho-ERK1/2; genetic and pharmacologic perturbations (PHF23 knockdown; ERK inhibitor PD98059) reduced ERK activity and malignant phenotypes. PHF23 physically interacts with ACTN4; deletion of the PHF23 PHD domain abolishes ACTN4 binding and stabilization, and reverses ERK activation and malignant phenotypes in vitro and in xenograft models (2023-08; https://doi.org/10.1038/s41419-023-06069-4) (cheng2023phf23promotesnsclc pages 4-6, cheng2023phf23promotesnsclc pages 6-11, cheng2023phf23promotesnsclc pages 11-11, cheng2023phf23promotesnsclc pages 1-2).
- NUP98 fusions (Blood, 2020): Across regulatable mouse models of distinct NUP98 fusions (NUP98/NSD1, NUP98/JARID1A, NUP98/DDX10), integrated chromatin/transcriptome analyses defined a core direct target program with CDK6 as a critical node. Genetic loss of Cdk6 or pharmacologic CDK6 inhibition attenuated leukemogenesis, proposing CDK4/6 inhibitors as a rational strategy for NUP98-fusion AML patients (2020-07; https://doi.org/10.1182/blood.2019003267) (schmoellerl2020cdk6isan pages 1-1, schmoellerl2020cdk6isan pages 13-14).
- Mechanistic occupancy in NUP98–PHF23 leukemia (JCI, 2025): NUP98–PHF23 fusions occupy H3K4me3-enriched loci, activate HOXA/HOXB/MEIS1, and cooperate with HoxBlinc-mediated TAD reprogramming and MLL1 recruitment to sustain oncogenic transcription and HSPC dysregulation. Depletion of HoxBlinc impairs these features and reduces leukemic potential in models (2025-01; https://doi.org/10.1172/jci184743) (hamamoto2025hoxblinclncrnareprograms pages 1-2).

Functional annotation and localization
- Molecular function: PHF23 is best described as a nuclear PHD-finger protein with epigenetic reader features. Strong, direct evidence of H3K4me3 recognition exists for the PHF23 PHD domain in the NUP98–PHF23 fusion, where the PHD finger targets H3K4me3-marked chromatin; for the native PHF23 protein, histone-mark recognition is inferred from domain homology and some reports but remains less definitively established biochemically in humans (JCI 2025; Frontiers in Cell & Developmental Biology 2025) (hamamoto2025hoxblinclncrnareprograms pages 1-2, liu2025structurefunctionand pages 2-3, liu2025structurefunctionand pages 1-2).
- Cellular localization: PHF23 is primarily nuclear, consistent with chromatin functions; in NSCLC cells it shows nuclear predominance with cytoplasmic interactions (e.g., with ACTN4) that influence ERK signaling (Cell Death & Disease, 2023-08; Frontiers in Cell & Developmental Biology, 2025-11) (cheng2023phf23promotesnsclc pages 11-11, cheng2023phf23promotesnsclc pages 4-6, liu2025structurefunctionand pages 1-2, liu2025structurefunctionand pages 2-3).

Pathways and processes
- Chromatin regulation and leukemia: The NUP98–PHF23 fusion exploits PHD-mediated recognition of H3K4me3 at HOX/MEIS loci and co-opts MLL1/COMPASS-linked activities and phase-separated NUP98 IDRs to sustain active TADs and oncogenic transcription. This keeps hematopoietic precursors in an undifferentiated, self-renewing state (JCI, 2025-01; https://doi.org/10.1172/jci184743) (hamamoto2025hoxblinclncrnareprograms pages 1-2).
- Cytoskeletal signaling/ERK pathway in NSCLC: PHF23 stabilizes ACTN4 and activates ERK signaling, contributing to proliferation, migration, DDR modulation, and chemoresistance; these effects are PHD-dependent and reversible by ERK pathway inhibition (Cell Death & Disease, 2023-08; https://doi.org/10.1038/s41419-023-06069-4) (cheng2023phf23promotesnsclc pages 1-2, cheng2023phf23promotesnsclc pages 4-6, cheng2023phf23promotesnsclc pages 6-11).
- Autophagy linkage (summary): Reviews summarize evidence that PHF23 negatively correlates with autophagy in multiple contexts and may act via LRSAM1 and AMPK/mTOR/S6K signaling; expression increases in inflamed human cartilage/synovium and is linked to reduced autophagy. While these associations are reported, high-quality, recent primary data specific to human cartilage with direct mechanistic assays remain limited in the retrieved set and should be interpreted cautiously (Frontiers in Cell & Developmental Biology, 2025-11; https://doi.org/10.3389/fcell.2025.1691318) (liu2025structurefunctionand pages 3-5).

Therapeutic implications and future directions
- Hematologic malignancies: The convergence of NUP98 fusions on CDK6 nominates CDK4/6 inhibition as a strategy. In NUP98–PHF23, the PHD-reader dependency suggests developing PHD–H3K4me3 antagonists and disrupting NUP98’s transcriptional condensates as additional avenues. Clinical implementation will require trials stratified by fusion genotype (Blood 2020-07; JCI 2025-01) (schmoellerl2020cdk6isan pages 13-14, schmoellerl2020cdk6isan pages 1-1, hamamoto2025hoxblinclncrnareprograms pages 1-2).
- Solid tumors: In NSCLC, the PHF23–ACTN4–ERK axis proposes using ERK/MAPK pathway inhibitors and exploring approaches that destabilize ACTN4 or block the PHD-dependent PHF23–ACTN4 interaction. PHF23 expression could contribute to risk stratification of chemoresistance (Cell Death & Disease, 2023-08) (cheng2023phf23promotesnsclc pages 1-2, cheng2023phf23promotesnsclc pages 4-6, cheng2023phf23promotesnsclc pages 6-11).

Limitations and open questions
- Native histone-mark recognition by PHF23 remains less directly demonstrated than in the NUP98–PHF23 fusion; additional biochemical/structural work will clarify specificity and partners. The incidence of NUP98–PHF23 among AML/AMKL subtypes, precise clinical outcomes, and prospective therapeutic trial data were not found in the retrieved set and warrant targeted literature review and clinical dataset analysis (JCI 2025; Blood 2020; Frontiers in Cell & Developmental Biology 2025) (hamamoto2025hoxblinclncrnareprograms pages 1-2, schmoellerl2020cdk6isan pages 13-14, liu2025structurefunctionand pages 1-2).

Mandatory verification checklist
- Gene symbol and protein description match: Human PHF23, PHD-finger protein, UniProt Q9BUL5; domains/family consistent with literature (Frontiers in Cell & Developmental Biology, 2025-11; https://doi.org/10.3389/fcell.2025.1691318) (liu2025structurefunctionand pages 1-2, liu2025structurefunctionand pages 2-3).
- Organism verified: Homo sapiens (NSCLC and leukemia studies use human cells/tissues and humanized models) (Cell Death & Disease, 2023-08; JCI, 2025-01) (cheng2023phf23promotesnsclc pages 1-2, hamamoto2025hoxblinclncrnareprograms pages 1-2).
- Domains/family align: PHD Zn-binding finger and NLS reported; PHD reader function central in NUP98–PHF23 (Frontiers in Cell & Developmental Biology 2025; JCI 2025) (liu2025structurefunctionand pages 2-3, hamamoto2025hoxblinclncrnareprograms pages 1-2).
- Symbol ambiguity: No conflicting human gene with identical symbol in the retrieved evidence; fusion nomenclature consistently references PHF23 as the C-terminal partner in NUP98–PHF23 (JCI, 2025-01) (hamamoto2025hoxblinclncrnareprograms pages 1-2).

References with URLs and dates
- Cheng M et al. PHF23 promotes NSCLC proliferation, metastasis, and chemoresistance via stabilization of ACTN4 and activation of the ERK pathway. Cell Death & Disease. 2023-08. https://doi.org/10.1038/s41419-023-06069-4 (cheng2023phf23promotesnsclc pages 1-2, cheng2023phf23promotesnsclc pages 4-6, cheng2023phf23promotesnsclc pages 11-11, cheng2023phf23promotesnsclc pages 6-11).
- Hamamoto K et al. HoxBlinc lncRNA reprograms CTCF-independent TADs to drive leukemic transcription and HSC dysregulation in NUP98-rearranged leukemia. J Clin Invest. 2025-01. https://doi.org/10.1172/jci184743 (hamamoto2025hoxblinclncrnareprograms pages 1-2).
- Schmoellerl J et al. CDK6 is an essential direct target of NUP98 fusion proteins in AML. Blood. 2020-07. https://doi.org/10.1182/blood.2019003267 (schmoellerl2020cdk6isan pages 13-14, schmoellerl2020cdk6isan pages 1-1).
- Liu L et al. Structure, function, and pathology of PHF23. Frontiers in Cell & Developmental Biology. 2025-11. https://doi.org/10.3389/fcell.2025.1691318 (liu2025structurefunctionand pages 1-2, liu2025structurefunctionand pages 3-5, liu2025structurefunctionand pages 2-3, liu2025structurefunctionand pages 8-9).

References

1. (liu2025structurefunctionand pages 1-2): Linlin Liu, Rui Zhang, Rui-Bo Liu, Yu Liu, and Yanming Ren. Structure, function, and pathology of phf23. Frontiers in Cell and Developmental Biology, Nov 2025. URL: https://doi.org/10.3389/fcell.2025.1691318, doi:10.3389/fcell.2025.1691318. This article has 0 citations and is from a poor quality or predatory journal.

2. (liu2025structurefunctionand pages 2-3): Linlin Liu, Rui Zhang, Rui-Bo Liu, Yu Liu, and Yanming Ren. Structure, function, and pathology of phf23. Frontiers in Cell and Developmental Biology, Nov 2025. URL: https://doi.org/10.3389/fcell.2025.1691318, doi:10.3389/fcell.2025.1691318. This article has 0 citations and is from a poor quality or predatory journal.

3. (cheng2023phf23promotesnsclc pages 1-2): Ming Cheng, Hongyi Cao, Peifeng Yao, Jingqian Guan, Peihong Wu, Hairu Ji, Siyu Jiang, Yinan Yuan, Lin Fu, Qianqian Zheng, and Qingchang Li. Phf23 promotes nsclc proliferation, metastasis, and chemoresistance via stabilization of actn4 and activation of the erk pathway. Cell Death & Disease, Aug 2023. URL: https://doi.org/10.1038/s41419-023-06069-4, doi:10.1038/s41419-023-06069-4. This article has 11 citations and is from a peer-reviewed journal.

4. (cheng2023phf23promotesnsclc pages 4-6): Ming Cheng, Hongyi Cao, Peifeng Yao, Jingqian Guan, Peihong Wu, Hairu Ji, Siyu Jiang, Yinan Yuan, Lin Fu, Qianqian Zheng, and Qingchang Li. Phf23 promotes nsclc proliferation, metastasis, and chemoresistance via stabilization of actn4 and activation of the erk pathway. Cell Death & Disease, Aug 2023. URL: https://doi.org/10.1038/s41419-023-06069-4, doi:10.1038/s41419-023-06069-4. This article has 11 citations and is from a peer-reviewed journal.

5. (cheng2023phf23promotesnsclc pages 11-11): Ming Cheng, Hongyi Cao, Peifeng Yao, Jingqian Guan, Peihong Wu, Hairu Ji, Siyu Jiang, Yinan Yuan, Lin Fu, Qianqian Zheng, and Qingchang Li. Phf23 promotes nsclc proliferation, metastasis, and chemoresistance via stabilization of actn4 and activation of the erk pathway. Cell Death & Disease, Aug 2023. URL: https://doi.org/10.1038/s41419-023-06069-4, doi:10.1038/s41419-023-06069-4. This article has 11 citations and is from a peer-reviewed journal.

6. (cheng2023phf23promotesnsclc pages 6-11): Ming Cheng, Hongyi Cao, Peifeng Yao, Jingqian Guan, Peihong Wu, Hairu Ji, Siyu Jiang, Yinan Yuan, Lin Fu, Qianqian Zheng, and Qingchang Li. Phf23 promotes nsclc proliferation, metastasis, and chemoresistance via stabilization of actn4 and activation of the erk pathway. Cell Death & Disease, Aug 2023. URL: https://doi.org/10.1038/s41419-023-06069-4, doi:10.1038/s41419-023-06069-4. This article has 11 citations and is from a peer-reviewed journal.

7. (hamamoto2025hoxblinclncrnareprograms pages 1-2): Karina Hamamoto, Ganqian Zhu, Qian Lai, Julia Lesperance, Huacheng Luo, Ying Li, Nupur Nigam, Arati Sharma, Feng-chun Yang, David F. Claxton, Y. Qiu, Peter D. Aplan, Mingjiang Xu, and Suming Huang. Hoxblinc lncrna reprograms ctcf-independent tads to drive leukemic transcription and hsc dysregulation in nup98-rearranged leukemia. The Journal of Clinical Investigation, Jan 2025. URL: https://doi.org/10.1172/jci184743, doi:10.1172/jci184743. This article has 3 citations.

8. (schmoellerl2020cdk6isan pages 13-14): Johannes Schmoellerl, Inês Amorim Monteiro Barbosa, Thomas Eder, Tania Brandstoetter, Luisa Schmidt, Barbara Maurer, Selina Troester, Ha Thi Thanh Pham, Mohanty Sagarajit, Jessica Ebner, Gabriele Manhart, Ezgi Aslan, Stefan Terlecki-Zaniewicz, Christa Van der Veen, Gregor Hoermann, Nicolas Duployez, Arnaud Petit, Helene Lapillonne, Alexandre Puissant, Raphael Itzykson, Richard Moriggl, Michael Heuser, Roland Meisel, Peter Valent, Veronika Sexl, Johannes Zuber, and Florian Grebien. Cdk6 is an essential direct target of nup98 fusion proteins in acute myeloid leukemia. Blood, 136:387-400, Jul 2020. URL: https://doi.org/10.1182/blood.2019003267, doi:10.1182/blood.2019003267. This article has 91 citations and is from a highest quality peer-reviewed journal.

9. (schmoellerl2020cdk6isan pages 1-1): Johannes Schmoellerl, Inês Amorim Monteiro Barbosa, Thomas Eder, Tania Brandstoetter, Luisa Schmidt, Barbara Maurer, Selina Troester, Ha Thi Thanh Pham, Mohanty Sagarajit, Jessica Ebner, Gabriele Manhart, Ezgi Aslan, Stefan Terlecki-Zaniewicz, Christa Van der Veen, Gregor Hoermann, Nicolas Duployez, Arnaud Petit, Helene Lapillonne, Alexandre Puissant, Raphael Itzykson, Richard Moriggl, Michael Heuser, Roland Meisel, Peter Valent, Veronika Sexl, Johannes Zuber, and Florian Grebien. Cdk6 is an essential direct target of nup98 fusion proteins in acute myeloid leukemia. Blood, 136:387-400, Jul 2020. URL: https://doi.org/10.1182/blood.2019003267, doi:10.1182/blood.2019003267. This article has 91 citations and is from a highest quality peer-reviewed journal.

10. (liu2025structurefunctionand pages 8-9): Linlin Liu, Rui Zhang, Rui-Bo Liu, Yu Liu, and Yanming Ren. Structure, function, and pathology of phf23. Frontiers in Cell and Developmental Biology, Nov 2025. URL: https://doi.org/10.3389/fcell.2025.1691318, doi:10.3389/fcell.2025.1691318. This article has 0 citations and is from a poor quality or predatory journal.

11. (liu2025structurefunctionand pages 3-5): Linlin Liu, Rui Zhang, Rui-Bo Liu, Yu Liu, and Yanming Ren. Structure, function, and pathology of phf23. Frontiers in Cell and Developmental Biology, Nov 2025. URL: https://doi.org/10.3389/fcell.2025.1691318, doi:10.3389/fcell.2025.1691318. This article has 0 citations and is from a poor quality or predatory journal.

Citations

1. liu2025structurefunctionand pages 1-2
2. liu2025structurefunctionand pages 2-3
3. hamamoto2025hoxblinclncrnareprograms pages 1-2
4. liu2025structurefunctionand pages 8-9
5. liu2025structurefunctionand pages 3-5
6. https://doi.org/10.3389/fcell.2025.1691318
7. https://doi.org/10.1038/s41419-023-06069-4
8. https://doi.org/10.1172/jci184743
9. https://doi.org/10.1182/blood.2019003267
10. https://doi.org/10.3389/fcell.2025.1691318,
11. https://doi.org/10.1038/s41419-023-06069-4,
12. https://doi.org/10.1172/jci184743,
13. https://doi.org/10.1182/blood.2019003267,