Affinage

ADNP

Activity-dependent neuroprotector homeobox protein · UniProt Q9H2P0

Length
1102 aa
Mass
123.6 kDa
Annotated
2026-06-09
100 papers in source corpus 28 papers cited in narrative 28 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

ADNP is a dual-compartment regulator of chromatin and the cytoskeleton that coordinates gene-expression programs underlying embryogenesis, neurogenesis, and immune cell differentiation (PMID:17222401, PMID:39808658, PMID:37285842). In the nucleus, ADNP is a core subunit of a chromatin-remodeling complex, binding BRG1 and other SWI/SNF core subunits through its C-terminus (PMID:25169753) and recruiting the CHD4 helicase together with BRG1 (the ChAHP complex) to specific loci, where it converts pioneer-factor binding into active histone modification and DNA accessibility (PMID:37285842, PMID:39808658). ADNP occupies defined promoters and chromatin regions—repressing endoderm genes while enhancing neurogenesis and organogenesis programs (PMID:17222401), binding the β-globin locus control region to drive erythroid maturation (PMID:23071114), and counteracting stable CTCF occupancy at SINE B2 elements to enforce H3K9me3 deposition and transcriptional silencing during preimplantation development (PMID:38479840). ADNP also stabilizes β-catenin by binding its armadillo domain and blocking assembly of the Axin/APC degradation complex, thereby sustaining Wnt/neuroectoderm signaling (PMID:32533114), and it acts as a Wnt repressor whose loss promotes colorectal cancer cell migration, invasion, and tumor growth (PMID:27903678). In the cytoplasm, ADNP is positioned by phosphorylation-dependent 14-3-3 binding (PMID:36631597) and engages microtubule end-binding proteins EB1 and EB3 through an SxIP motif in its NAP region, promoting EB3 homodimerization, EB-Tau recruitment to microtubules, and microtubule dynamics that support dendritic spine and PSD-95 maintenance (PMID:25178163, PMID:28115743). ADNP loss-of-function disrupts neurite formation, synaptic transmission, hippocampal neurogenesis, and synaptic plasticity through dysregulated CaMKIIα activity, with several phenotypes corrected by the ADNP-derived NAP peptide (PMID:36631597, PMID:37365244, PMID:39715923). Pathogenic ADNP truncating mutations, identified in autism spectrum disorder patients (PMID:25169753), disrupt nuclear localization and route the protein to cytoplasmic proteasomal degradation, producing mutation-specific neuronal phenotypes (PMID:29911927, PMID:36230962).

Mechanistic history

Synthesis pass · year-by-year structured walk · 28 steps
  1. 2006 Medium

    Establishing that ADNP physically engages chromatin at defined promoters addressed whether it acts as a direct, locus-specific transcriptional regulator rather than a diffuse factor.

    Evidence ChIP in P19 pluripotent cells plus knockout expression profiling in mouse embryos

    PMID:17222401

    Open questions at the time
    • Did not identify the remodeling complex mediating ADNP chromatin binding
    • Sequence specificity of ADNP-DNA recognition not defined
  2. 2006 Medium

    Identifying PACAP38 as an upstream inducer of ADNP transcription placed the gene within a defined neuropeptide signaling cascade.

    Evidence Pharmacological receptor/pathway dissection in mouse neuron-glia co-cultures with qRT-PCR

    PMID:16564114

    Open questions at the time
    • Transcription factors directly driving ADNP induction not identified
    • Link between induction and downstream ADNP function not established
  3. 2008 Medium

    Linking ADNP dosage to neuronal differentiation and showing compartment-specific localization framed ADNP as a developmental regulator acting in both nucleus and neurites.

    Evidence shRNA knockdown, immunohistochemistry, and subcellular fractionation in P19 cells and mouse brain

    PMID:18286385

    Open questions at the time
    • Molecular basis of differential localization not defined
    • Cytoplasmic function not yet mechanistically resolved
  4. 2012 Medium

    Demonstrating that the NAP region modulates the tubulin tyrosination cycle and microtubule dynamics provided the first cytoskeletal mechanism for ADNP-derived activity.

    Evidence Cellular microtubule and tau-tubulin interaction assays in PC12 cells and rat cortical cells

    PMID:23272107

    Open questions at the time
    • Direct molecular target of NAP on microtubules not identified at this stage
    • No mutagenesis or reconstitution
  5. 2012 High

    Showing ADNP binds the β-globin locus control region and is required for erythroid maturation extended its chromatin role beyond neural development and tied it to SWI/SNF in another lineage.

    Evidence ChIP in MEL cells, morpholino knockdown in zebrafish rescued by exogenous RNA

    PMID:23071114

    Open questions at the time
    • Mechanism of ADNP recruitment to the LCR not defined
    • Relationship to broader globin enhancer machinery unresolved
  6. 2014 High

    Mapping the SxIP motif that binds EB1/EB3 (but not EB2) gave ADNP a precise, isoform-selective molecular handle on microtubule plus-ends with a synaptic readout.

    Evidence Sequence analysis, isoform-specific EB siRNA with functional readout, Co-IP, dendritic spine imaging

    PMID:25178163

    Open questions at the time
    • How EB binding feeds into PSD-95 regulation mechanistically unresolved
    • In vivo relevance of the SxIP interaction not tested here
  7. 2014 Medium

    Direct C-terminal binding to BRG1 and SWI/SNF core subunits, alongside ASD patient mutations, defined ADNP as a chromatin-remodeling complex member relevant to disease.

    Evidence Binding assays/Co-IP plus genetic identification in ASD patients

    PMID:25169753

    Open questions at the time
    • Stoichiometry and architecture of the ADNP-SWI/SNF complex not resolved
    • Abstract-level method detail limits full assessment
  8. 2014 Low

    Co-IP linking ADNP to Brm and the splicing factor PSF raised the possibility that ADNP couples chromatin remodeling to tau transcript splicing.

    Evidence Co-immunoprecipitation from mouse brain lysates

    PMID:24489906

    Open questions at the time
    • Single Co-IP with no functional follow-up on the ADNP-PSF-Brm complex
    • Direct effect on tau splicing not demonstrated
  9. 2015 Medium

    Identifying eIF4E as a partner and showing sex- and age-dependent dysregulation positioned ADNP as a master regulator of ASD/AD risk genes.

    Evidence Co-IP, qRT-PCR, and behavioral testing in ADNP+/- mice

    PMID:25646590

    Open questions at the time
    • Functional consequence of ADNP-eIF4E binding not established
    • Single Co-IP without reciprocal validation
  10. 2016 Medium

    Demonstrating ADNP as a WNT repressor whose loss drives tumor progression generalized its signaling role beyond development into cancer.

    Evidence ADNP silencing in colon cancer cells, xenografts, and migration/invasion assays with omics

    PMID:27903678

    Open questions at the time
    • Molecular basis of WNT repression not yet defined at this stage
    • Single lab
  11. 2017 High

    Showing ADNP/NAP drives EB3 homodimers and EB-Tau microtubule recruitment, with Tau required for cytoprotection, established the mechanistic chain from ADNP to microtubule-associated protein function.

    Evidence Live imaging, Co-IP, and Tau transfection rescue under zinc intoxication

    PMID:28115743

    Open questions at the time
    • Structural basis of EB3 dimer preference not resolved
    • In vivo contribution to tauopathy not tested
  12. 2017 Medium

    Discovery that FMDV leader protease hijacks an ADNP-Lpro-BRG1 complex to repress interferon revealed an immune transcriptional repressive function for ADNP.

    Evidence Mass spectrometry, in vitro binding, Co-IP, RNAi, and ChIP at the IFN-α promoter

    PMID:28219017

    Open questions at the time
    • Endogenous (non-viral) role of ADNP in IFN regulation unresolved
    • Mechanistic follow-up limited
  13. 2018 Medium

    Mapping how patient mutations within the bipartite NLS stall ADNP in the cytoplasm and route truncations to proteasomal degradation connected genotype to subcellular mislocalization.

    Evidence GFP-tagged mutant transfection, immunocytochemistry, and MG132 rescue in HEK293T cells

    PMID:29911927

    Open questions at the time
    • Heterochromatin enrichment determinants not defined
    • Consequences in neurons not tested in this system
  14. 2020 High

    Showing ADNP stabilizes β-catenin by binding its armadillo domain and blocking the Axin/APC degradation complex provided the direct molecular mechanism for ADNP control of Wnt/neuroectoderm signaling.

    Evidence Reciprocal Co-IP, protein stability and proteasome-inhibitor assays, zebrafish knockout, neural differentiation

    PMID:32533114

    Open questions at the time
    • Whether nuclear ADNP also acts on β-catenin target transcription unresolved
    • Spatial coordination with the chromatin role not defined
  15. 2021 Medium

    Linking ADNP to SIRT1 at both the EB/Tau and chromatin levels, with WDR5-dependent histone modification, integrated its cytoskeletal and epigenetic activities into one regulatory axis.

    Evidence Co-IP, single-cell expression analysis, and in silico analysis

    PMID:33967268

    Open questions at the time
    • Functional necessity of the ADNP-SIRT1 complex not tested by perturbation
    • Direct DNA motif sharing with YY1/HDAC2 not validated
  16. 2022 Medium

    Identifying an SH3-ligand (NAPVSIP) motif and direct actin interaction, plus Shank3-Adnp-actin normalization by NAP, broadened ADNP's cytoskeletal repertoire beyond microtubules.

    Evidence ELM analysis, site-directed mutagenesis, live imaging, Co-IP from mouse brain, Shank3 mouse behavior

    PMID:35538192

    Open questions at the time
    • Direct actin-binding interface not biochemically reconstituted
    • In vivo significance of SH3 signaling unresolved
  17. 2022 Medium

    CRISPR-engineered ADNP truncations producing distinct neuronal phenotypes and aberrant nuclear-cytoplasmic boundaries, corrected by NAP, established mutation-specific pathomechanisms.

    Evidence CRISPR/Cas9 editing in N1E-115 cells, quantitative morphology, immunocytochemistry, live imaging

    PMID:36230962

    Open questions at the time
    • Molecular cause of nuclear-cytoplasmic boundary defects not defined
    • Single cell-line context
  18. 2023 High

    Defining ADNP as the bridge that recruits CHD4 and BRG1 after pioneer-factor binding to enable histone acetylation and accessibility established its central role in pioneer-to-remodeler transitions during Th2 differentiation.

    Evidence CRISPR-Cas9 TF screen plus ChIP/ATAC-seq in Th2 cells with ADNP loss

    PMID:37285842

    Open questions at the time
    • Generalizability of pioneer-to-ChAHP handoff to other lineages not tested here
    • Direct ADNP-GATA3/AP-1 contacts not mapped
  19. 2023 High

    Showing 14-3-3 phosphorylation-dependent binding controls ADNP cytoplasmic localization, with neuronal connectivity and calcium consequences upon knockdown, defined the switch governing where ADNP acts.

    Evidence Difopein inhibition, Co-IP, phosphoproteomics, in utero electroporation, calcium imaging, synaptic tracing

    PMID:36631597

    Open questions at the time
    • Kinase(s) phosphorylating ADNP for 14-3-3 binding not identified
    • How localization switching is developmentally timed unresolved
  20. 2023 Medium

    Linking Adnp haploinsufficiency to hyperphosphorylated CaMKIIα and excessive LTP, rescued by CaMKIIα inhibition, connected ADNP dosage to a defined synaptic plasticity mechanism.

    Evidence LTP electrophysiology, phospho-western blot, CaMKIIα inhibitor rescue in Adnp+/- mice

    PMID:37365244

    Open questions at the time
    • How ADNP loss elevates CaMKIIα phosphorylation mechanistically unresolved
    • Whether effect is chromatin- or cytoskeleton-mediated unclear
  21. 2023 Medium

    Region-specific Adnp knockdown causing neuroinflammation, microglial activation, and reduced glutamatergic transmission tied ADNP loss to circuit-level pathology overlapping POGZ deficiency.

    Evidence Viral knockdown in mouse PFC with RNA-seq, electrophysiology, IHC, and behavior

    PMID:35775424

    Open questions at the time
    • Cell-autonomous versus non-autonomous microglial effects not separated
    • Direct transcriptional targets driving inflammation not identified here
  22. 2023 Medium

    Showing NAP rapidly distributes to nucleus and cytoplasm and corrects microtubule-disruption-induced nuclear-cytoplasmic defects clarified NAP's mechanism and distinguished it from ketamine.

    Evidence Live imaging of Cy5-NAP in CRISPR-edited cells, microtubule disruption, in silico docking

    PMID:37759476

    Open questions at the time
    • Direct molecular target of NAP correction not biochemically defined
    • Docking predictions not experimentally validated
  23. 2024 High

    Demonstrating ADNP counteracts stable CTCF binding at SINE B2 elements to enforce H3K9me3 and silencing revealed a transposable-element-control mechanism essential for preimplantation cell-fate fidelity.

    Evidence CUT&RUN for CTCF, zygotic Adnp knockout, H3K9me3 ChIP, RNA-seq in mouse embryos

    PMID:38479840

    Open questions at the time
    • How ADNP physically antagonizes CTCF occupancy not resolved
    • Effector depositing H3K9me3 downstream of ADNP not identified
  24. 2024 Medium

    Establishing sex-dependent ADNP control of hippocampal neurogenesis with distinct UPR/mitochondrial signatures, and mitochondrial accessibility blocked by a truncating mutation, broadened ADNP's compartments and revealed sex-specific mechanisms.

    Evidence BrdU assay, hippocampal RNA-seq, mitochondrial fractionation, NAP rescue in Adnp+/- and mutant mice

    PMID:39715923

    Open questions at the time
    • Direct mitochondrial function of ADNP not defined
    • Mechanism underlying sex specificity unresolved
  25. 2025 High

    Conditional knockout showing ADNP-ChAHP recruits CHD4 to proliferation genes and co-regulates NDD risk genes established its in vivo requirement for neocortical neurogenesis and upper-layer neuron production.

    Evidence Conditional Adnp knockout, single-cell transcriptomics, and CUT&RUN-seq in mouse

    PMID:39808658

    Open questions at the time
    • Stage-specific switch between progenitor and postmitotic ADNP programs not fully mapped
    • Direct DNA-binding determinants in cortex not defined
  26. 2025 Medium

    Showing ADNP is a POU3F2 transcriptional target mediating Wnt signaling and NPC proliferation placed ADNP within an upstream developmental transcriptional hierarchy.

    Evidence POU3F2 disruption in human NPCs, unbiased target identification, Wnt and proliferation assays

    PMID:40498903

    Open questions at the time
    • Direct POU3F2 binding at the ADNP locus not demonstrated
    • Whether ADNP fully accounts for POU3F2's Wnt effects unresolved
  27. 2025 Medium

    Demonstrating LSD1-inhibitor rescue of Adnp-mutant synaptic transmission via altered histone marks linked ADNP chromatin regulation directly to synaptic gene expression and offered a therapeutic axis.

    Evidence Electrophysiology with LSD1 inhibitor, histone-mark western blots, and RNA-seq in Adnp mutant mice

    PMID:40536108

    Open questions at the time
    • Direct ADNP-LSD1 complex composition not biochemically resolved
    • Sex-specific responsiveness mechanism unclear
  28. 2025 Medium

    Identifying ADNP as a modifier of microglial endocytic trafficking and synaptic pruning extended its function to non-neuronal brain cells.

    Evidence CRISPRi knockdown in iPSC-derived microglia-neuron coculture with pruning flow cytometry and proteomics

    PMID:40188316

    Open questions at the time
    • Molecular pathway connecting ADNP to endocytic trafficking not defined
    • Whether pruning effect requires chromatin or cytoplasmic ADNP unresolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • How ADNP's nuclear chromatin-remodeling activity and its cytoplasmic microtubule/actin functions are coordinated within a single cell, and which compartment drives specific disease phenotypes, remains unresolved.
  • No structural model of ADNP defining DNA-binding versus cytoskeletal interfaces
  • Compartment-specific contribution to ASD phenotypes not dissected
  • Sequence specificity of ADNP-DNA recognition not defined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 4 GO:0003677 DNA binding 3 GO:0008092 cytoskeletal protein binding 3 GO:0060089 molecular transducer activity 1 GO:0140313 molecular sequestering activity 1
Localization
GO:0005634 nucleus 3 GO:0005829 cytosol 3 GO:0005856 cytoskeleton 3 GO:0000228 nuclear chromosome 2
Pathway
R-HSA-112316 Neuronal System 3 R-HSA-1266738 Developmental Biology 3 R-HSA-162582 Signal Transduction 3 R-HSA-4839726 Chromatin organization 3 R-HSA-74160 Gene expression (Transcription) 3 R-HSA-168256 Immune System 2
Partners
14-3-3BRG1CHD4CTNNB1EB1EB3EIF4ESIRT1
Complex memberships
ChAHP complex (ADNP-CHD4-BRG1)SWI/SNF (BAF) complex

Evidence

Reading pass · 28 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2014 ADNP is a member of the SWI/SNF chromatin remodeling complex; its C-terminus directly and experimentally binds three core components of the BAF/SWI/SNF complex (BRG1 and two other core subunits), linking it to transcriptional regulation. Experimental binding assays / Co-IP demonstrating direct C-terminus interaction with SWI/SNF core components; genetic identification in ASD patients American journal of medical genetics. Part C, Seminars in medical genetics Medium 25169753
2006 ADNP directly interacts with chromatin at specific gene promoters (including apolipoproteins, cathepsins, neurogenesis markers such as Ngfr/neurogenin1/neurod1, and heart development markers like Myl2), acting to repress potential endoderm genes while enhancing organogenesis/neurogenesis genes; interaction with chromatin is increased in neuro-differentiated versus non-differentiated P19 cells. Chromatin immunoprecipitation (ChIP) in P19 pluripotent cells; Affymetrix microarray gene expression profiling of ADNP knockout vs. control mouse embryos Developmental biology Medium 17222401
2008 ADNP localizes differentially to the nucleus versus cytoplasm/neurites in neuronal-differentiated P19 cells compared to cardiovascular or non-differentiated cells; ADNP knockdown (~80% reduction) substantially reduces embryoid body formation and neurite numbers (~50%), placing ADNP in direct association with neuronal differentiation and maturation. shRNA knockdown in P19 cells; immunohistochemistry; subcellular fractionation/localization analysis in P19 cells and mouse brain cortex/olfactory bulb Journal of molecular neuroscience : MN Medium 18286385
2014 The NAP motif of ADNP contains an SxIP (SIP) microtubule end-binding protein (EB) interaction motif that binds EB1 and EB3 (but not EB2); NAP/ADNP-EB3 interaction increases PSD-95 expression in dendritic spines; EB1 or EB3 (but not EB2) silencing abolishes NAP-mediated cell protection; ADNP shows similar EB interactions enhanced by NAP treatment. Sequence analysis, EB protein silencing (siRNA), immunofluorescence, co-immunoprecipitation, dendritic spine imaging Molecular psychiatry High 25178163
2017 ADNP/NAP dramatically increases EB3 homodimer formation while decreasing EB1-EB3 heterodimer content; drives EB1- and EB3-Tau interactions (20-fold increases); recruits EB1/EB3 and Tau to microtubules under zinc intoxication. NAP protection against zinc intoxication requires Tau (or other MAPs), as NAP did not protect NIH3T3 fibroblasts unless transfected with Tau. Live cell imaging of fluorescent EB1, co-immunoprecipitation, cell transfection, zinc intoxication assays, Tau transfection rescue experiments Molecular psychiatry High 28115743
2012 NAP (ADNP-derived peptide) significantly affects the alpha-tubulin tyrosination/detyrosination cycle in neuronal differentiation models (PC12 cells and rat cortical astrocytes), increases microtubule network area, increases tubulin beta3 (marker for neurite outgrowth), doubles dynamic microtubule invasion area in neuronal growth cones, and reverses zinc-decreased tau-tubulin-MT interaction. In vitro assay in PC12 cells and rat cortical neurons/astrocytes; immunofluorescence; microtubule network area quantification; tau-tubulin interaction assays PloS one Medium 23272107
2012 ADNP directly associates with (binds to) the mouse β-globin locus control region (by ChIP), and is required for erythroid maturation; knockdown of ADNP in zebrafish embryos or mouse erythroleukemia (MEL) cells inhibits erythroid maturation and hemoglobin production. ADNP also interacts with Brg1 (SWI/SNF component) in the context of erythropoiesis. Chromatin immunoprecipitation (ChIP) in MEL cells; morpholino knockdown in zebrafish; siRNA in MEL cells; rescue by exogenous ADNP RNA The Journal of biological chemistry High 23071114
2015 ADNP haploinsufficiency in mice exhibits co-immunoprecipitation with eIF4E (eukaryotic translation initiation factor 4E), with hippocampal eIF4E expression specifically increased in young ADNP+/- male mice; ADNP expression is a master regulator of key ASD and AD risk genes in a sex- and age-dependent manner. Co-immunoprecipitation; qRT-PCR; behavioral testing in ADNP+/- mice Translational psychiatry Medium 25646590
2014 ADNP interacts with Brahma (Brm), a SWI/SNF chromatin remodeling component that regulates alternative splicing, and with polypyrimidine tract-binding protein-associated splicing factor (PSF), a direct regulator of tau transcript splicing; immunoprecipitations in mouse brain tissue showed Brm-ADNP interaction coupled to ADNP-PSF binding. Co-immunoprecipitation from mouse brain lysates PloS one Low 24489906
2020 ADNP stabilizes β-catenin by binding to its armadillo domain, preventing association of β-catenin with key components of the degradation complex (Axin and APC); loss of ADNP promotes formation of the degradation complex and β-catenin degradation via the ubiquitin-proteasome pathway, resulting in downregulation of key neuroectoderm developmental genes. Co-immunoprecipitation, protein stability assays, proteasome inhibitor rescue, zebrafish adnp knockout, neural differentiation assays Nature communications High 32533114
2017 FMDV leader protease (Lpro) interacts with ADNP (identified by mass spectrometry and confirmed in vitro and in cell culture); ADNP RNAi leads to reduced FMDV replication and increased IFN/ISG expression; FMDV infection recruits ADNP to IFN-α promoter sites; ADNP, Lpro, and Brg-1 (SWI/SNF) form a protein complex, and ADNP has a transcription repressive function on IFN expression. Mass spectrometry, in vitro binding assay, co-immunoprecipitation, RNAi, ChIP (promoter recruitment assay) Virology Medium 28219017
2018 ADNP mutations affect subcellular localization: mutations within the bipartite nuclear localization signal (NLS) stall the mutant protein in the cytoplasm; wild-type ADNP co-localizes with heterochromatin; certain mutant proteins show partially lost enrichment at pericentromeric heterochromatin; N-terminal truncated ADNP mutants are routed towards cytosolic proteasomal degradation (rescued by MG132). Transfection of GFP-tagged mutant transcripts in HEK293T cells; immunocytochemistry; proteasome inhibitor (MG132) rescue experiment Cell cycle (Georgetown, Tex.) Medium 29911927
2021 ADNP interacts with SIRT1 at two sites: (1) at the microtubule end-binding protein (EB1/EB3)-Tau level, with EB1/EB3 amplifying microtubule dynamics; and (2) on the DNA/chromatin site, sharing a DNA binding motif with YY1 and HDAC2, and regulating SIRT1, ADNP, and EB1 (MAPRE1). This ADNP-SIRT1 complex is associated with sex- and age-dependent altered histone modification via WD repeat-containing protein 5 (WDR5). Co-immunoprecipitation, single-cell RNA/protein expression analysis, gene expression correlations, in silico analysis Molecular psychiatry Medium 33967268
2016 ADNP acts as a repressor of WNT signaling in colorectal cancer; silencing ADNP expression increases migration, invasion, and proliferation of colon cancer cells and accelerates tumor growth in xenografts in vivo. ADNP silencing in colon cancer cells; in vivo xenograft tumor growth; migration/invasion assays; transcriptomic and proteomic analysis Clinical cancer research Medium 27903678
2022 ADNP contains SH3 domain-ligand association sites (NAPVSIP motif) responsible for controlling cytoskeletal signaling; ADNP mutations differentially affect microtubule dynamics and Tau interactions; ADNP interacts with actin (co-immunoprecipitation from mouse brain), and NAP treatment normalizes Shank3-Adnp-actin interactions; NAP also contains an actin-binding site identified by ELM analysis. ELM resource analysis, site-directed mutagenesis, live-cell fluorescence microscopy, co-immunoprecipitation from mouse brain extracts, behavioral testing in Shank3 mutant mice Molecular psychiatry Medium 35538192
2023 ADNP forms a critical bridge in the transition from pioneer transcription factors to chromatin remodeling during Th2 cell differentiation: ADNP recruits CHD4 helicase and BRG1 ATPase (the ChAHP complex) following GATA3 and AP-1 binding; without ADNP, these pioneer TFs bind the type 2 cytokine locus but cannot initiate histone acetylation or DNA accessibility, resulting in impaired type 2 cytokine expression. CRISPR-Cas9 screen targeting 1,131 TFs; mechanistic studies in Th2 cells with ADNP loss; ChIP/ATAC-seq for histone acetylation and DNA accessibility Immunity High 37285842
2023 ADNP is localized to the cytoplasm during neurite formation through interaction with 14-3-3 proteins (phosphorylation-dependent binding); inhibition of 14-3-3 with difopein blocks Adnp cytoplasmic localization; Adnp knockdown in cortical layer 2/3 pyramidal neurons via in utero electroporation alters neurite formation (increased basal dendrite number, increased axon length) and causes greater spontaneous calcium influx (especially in females) and increased interhemispheric connectivity. 14-3-3 inhibitor (difopein) treatment; co-immunoprecipitation; proteomic analysis of phosphorylation sites; in utero electroporation knockdown; ex vivo calcium imaging; GRAPHIC synaptic tracing Molecular psychiatry High 36631597
2024 ADNP counteracts stable association of CTCF at SINE B2-derived CTCF-binding sites during preimplantation development; Adnp knockout leads to impaired CTCF binding signal recovery, failed deposition of H3K9me3, and transcriptional derepression of SINE B2 elements during morula-to-blastocyst transition, resulting in unfaithful cell differentiation around implantation. CUT&RUN for CTCF occupancy in mouse preimplantation embryos; Adnp zygote knockout; H3K9me3 ChIP; RNA-seq Genes & development High 38479840
2025 ADNP, as a core subunit of the ChAHP complex, recruits CHD4 to genes associated with progenitor proliferation during neocortical neurogenesis; in postmitotic neurons, ADNP and CHD4 co-regulate a network of neurodevelopmental disorder risk genes; conditional Adnp knockout during neocortical development impairs production of late-born upper-layer neurons. Conditional Adnp knockout in mouse; single-cell transcriptomics; CUT&RUN-seq; histological analysis Proceedings of the National Academy of Sciences of the United States of America High 39808658
2022 Different ADNP mutations (p.Pro403*/p.Ser404* and p.Tyr718*/p.Tyr719*) produce distinct neuronal phenotypes: p.Pro403* increases neurite numbers and lengths upon differentiation; p.Tyr718* decreases cell numbers; both mutations increase mutant protein in the cytoplasm and reduce nuclear/cytoplasmic boundary integrity (aberrant nuclear-cytoplasmic crosstalk), which is corrected by the NAP fragment. CRISPR/Cas9 genome editing in N1E-115 neuroblastoma cells; quantitative morphology; immunocytochemistry; live cell imaging Cells Medium 36230962
2025 In microglia, ADNP loss (CRISPRi knockdown) leads to altered endocytic trafficking, remodeled proteomes, and increased motility; ADNP functions as a modifier of microglial synaptic pruning. CRISPRi knockdown; iPSC-derived microglia-neuron coculture; high-throughput flow cytometry for synaptic pruning; proteomic analysis Molecular psychiatry Medium 40188316
2023 NAP (ADNP-derived peptide) rapidly distributes in both cytoplasm and nucleus; disrupting microtubules by zinc or nocodazole intoxication mimics ADNP mutation phenotypes (aberrant nuclear-cytoplasmic boundaries) and NAP rapidly corrects this; NAP and ketamine both exhibit direct interactions with ADNP by in silico docking, but ketamine is ineffective at correcting mutant ADNP phenotypes while NAP is effective. Live imaging of Cy5-conjugated NAP in CRISPR-edited cell lines; microtubule disruption (zinc/nocodazole); quantitative morphology; in silico docking Cells Medium 37759476
2023 ADNP knockdown in mouse prefrontal cortex (via viral-based gene transfer) causes cognitive impairment, prominent upregulation of neuroinflammation genes (overlapping with POGZ deficiency), pro-phagocytic microglial activation, and significant decrease in glutamatergic transmission and postsynaptic protein expression. Viral-based gene transfer for Adnp knockdown in mouse PFC; RNA-sequencing; electrophysiology; immunohistochemistry; behavioral testing Brain : a journal of neurology Medium 35775424
2023 Adnp haploinsufficiency in mice leads to hyperphosphorylated CaMKIIα and its substrates (including SynGAP1) in the adult hippocampus, and to excessive long-term potentiation (LTP); CaMKIIα inhibition normalizes the excessive LTP, linking ADNP to regulation of synaptic plasticity through CaMKIIα activity. Electrophysiology (LTP measurements), western blot for phospho-CaMKIIα and substrates, CaMKIIα inhibitor treatment, behavioral testing in Adnp heterozygous mice Molecular psychiatry Medium 37365244
2025 ADNP is a transcriptional target of POU3F2 in human neural progenitor cells, and mediates POU3F2's effects on canonical Wnt signaling; POU3F2 disruption reduces baseline Wnt signaling and decreases NPC proliferation, with ADNP identified as a downstream effector through unbiased analyses. POU3F2 disruption in human NPCs; transcriptional target identification via unbiased analysis; Wnt signaling assays; proliferation assays Brain : a journal of neurology Medium 40498903
2006 PACAP38 stimulates ADNP mRNA expression in mouse neuron-glia co-cultures via multiple receptor subtypes (PAC1-R at both sub-picomolar and nanomolar concentrations; VPAC1-R at nanomolar concentrations only); signaling is mediated through IP3/PLC pathway at both concentrations, and PKA pathway at nanomolar concentration only; MAPK inhibition has no effect. Mouse neuron-glia co-cultures; PACAP38 treatment with selective receptor antagonists; intracellular signaling pathway inhibitors; quantitative RT-PCR Peptides Medium 16564114
2024 ADNP is essential for sex-dependent hippocampal neurogenesis: male Adnp+/- mice show dramatic reductions in BrdU incorporation in hippocampal sub-ventricular zone; mechanistically, male-specific downregulation of endoplasmic reticulum unfolded protein response genes and female-specific downregulation of mitochondrial ATP6 are observed; mitochondrial accessibility of ADNP is inhibited by the p.Tyr718* mutation. BrdU incorporation assay; hippocampal RNA-seq in Adnp+/- and CRISPR p.Tyr718* mutant mice; subcellular fractionation (mitochondrial accessibility); NAP treatment rescue Molecular psychiatry Medium 39715923
2025 Adnp heterozygous mutation (C-terminus) in mice causes significantly reduced glutamatergic and GABAergic synaptic transmission in PFC pyramidal neurons; treatment with an LSD1 inhibitor rescues synaptic transmission (particularly in females), associated with increased H3K4me2 and decreased H3K9me2/3 and elevated expression of synaptic genes; this links ADNP chromatin regulation (via LSD1/ADNP complex association) to synaptic gene expression. Electrophysiology (EPSC/IPSC measurements) in Adnp mutant mice; LSD1 inhibitor treatment; western blot for histone marks; RNA-seq for synaptic gene expression Autism research Medium 40536108

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2014 A SWI/SNF-related autism syndrome caused by de novo mutations in ADNP. Nature genetics 281 24531329
2001 A peptide derived from activity-dependent neuroprotective protein (ADNP) ameliorates injury response in closed head injury in mice. The Journal of pharmacology and experimental therapeutics 193 11123362
2006 Activity-dependent neuroprotective protein (ADNP) differentially interacts with chromatin to regulate genes essential for embryogenesis. Developmental biology 149 17222401
2005 NAP: research and development of a peptide derived from activity-dependent neuroprotective protein (ADNP). CNS drug reviews 127 16614735
2018 Clinical Presentation of a Complex Neurodevelopmental Disorder Caused by Mutations in ADNP. Biological psychiatry 123 29724491
2014 The NAP motif of activity-dependent neuroprotective protein (ADNP) regulates dendritic spines through microtubule end binding proteins. Molecular psychiatry 111 25178163
2020 ADNP promotes neural differentiation by modulating Wnt/β-catenin signaling. Nature communications 92 32533114
2015 Activity-dependent neuroprotective protein (ADNP) exhibits striking sexual dichotomy impacting on autistic and Alzheimer's pathologies. Translational psychiatry 88 25646590
2003 From vasoactive intestinal peptide (VIP) through activity-dependent neuroprotective protein (ADNP) to NAP: a view of neuroprotection and cell division. Journal of molecular neuroscience : MN 80 14501014
2008 ADNP differential nucleus/cytoplasm localization in neurons suggests multiple roles in neuronal differentiation and maintenance. Journal of molecular neuroscience : MN 79 18286385
2019 Gene domain-specific DNA methylation episignatures highlight distinct molecular entities of ADNP syndrome. Clinical epigenetics 78 31029150
2012 The ADNP derived peptide, NAP modulates the tubulin pool: implication for neurotrophic and neuroprotective activities. PloS one 76 23272107
2019 Discovery of autism/intellectual disability somatic mutations in Alzheimer's brains: mutated ADNP cytoskeletal impairments and repair as a case study. Molecular psychiatry 75 31664177
2017 ADNP/NAP dramatically increase microtubule end-binding protein-Tau interaction: a novel avenue for protection against tauopathy. Molecular psychiatry 71 28115743
2014 The transcriptional regulator ADNP links the BAF (SWI/SNF) complexes with autism. American journal of medical genetics. Part C, Seminars in medical genetics 65 25169753
2017 Premature primary tooth eruption in cognitive/motor-delayed ADNP-mutated children. Translational psychiatry 62 28221363
2017 ADNP Plays a Key Role in Autophagy: From Autism to Schizophrenia and Alzheimer's Disease. BioEssays : news and reviews in molecular, cellular and developmental biology 49 28940660
2016 Blood-Borne Activity-Dependent Neuroprotective Protein (ADNP) is Correlated with Premorbid Intelligence, Clinical Stage, and Alzheimer's Disease Biomarkers. Journal of Alzheimer's disease : JAD 49 26639975
2014 Novel marker for the onset of frontotemporal dementia: early increase in activity-dependent neuroprotective protein (ADNP) in the face of Tau mutation. PloS one 49 24489906
2019 The autism/neuroprotection-linked ADNP/NAP regulate the excitatory glutamatergic synapse. Translational psychiatry 45 30664622
2018 The autism spectrum phenotype in ADNP syndrome. Autism research : official journal of the International Society for Autism Research 45 30107084
2021 Introducing ADNP and SIRT1 as new partners regulating microtubules and histone methylation. Molecular psychiatry 43 33967268
2005 The expression of activity-dependent neuroprotective protein (ADNP) is regulated by brain damage and treatment of mice with the ADNP derived peptide, NAP, reduces the severity of traumatic head injury. Current Alzheimer research 43 15974912
2012 Novel evolutionary-conserved role for the activity-dependent neuroprotective protein (ADNP) family that is important for erythropoiesis. The Journal of biological chemistry 42 23071114
2022 SH3- and actin-binding domains connect ADNP and SHANK3, revealing a fundamental shared mechanism underlying autism. Molecular psychiatry 38 35538192
2007 Silencing of the ADNP-family member, ADNP2, results in changes in cellular viability under oxidative stress. Journal of neurochemistry 37 18179478
2012 Involvement of PACAP/ADNP signaling in the resistance to cell death in malignant peripheral nerve sheath tumor (MPNST) cells. Journal of molecular neuroscience : MN 36 22454142
2006 Signaling involved in pituitary adenylate cyclase-activating polypeptide-stimulated ADNP expression. Peptides 36 16564114
2007 Pituitary adenylate cyclase-activating polypeptide (PACAP) type 1 receptor (PAC1R) co-localizes with activity-dependent neuroprotective protein (ADNP) in the mouse brains. Regulatory peptides 33 17942168
2020 The ADNP Syndrome and CP201 (NAP) Potential and Hope. Frontiers in neurology 32 33329371
2011 Activity-dependent neuroprotective protein (ADNP)-derived peptide (NAP) ameliorates hypobaric hypoxia induced oxidative stress in rat brain. Peptides 32 21453737
2019 The autism-mutated ADNP plays a key role in stress response. Translational psychiatry 31 31534115
2008 Regulation of activity-dependent neuroprotective protein (ADNP) by the NO-cGMP pathway in the hippocampus during kainic acid-induced seizure. Neurobiology of disease 31 18375135
2019 Cellular and animal models of skin alterations in the autism-related ADNP syndrome. Scientific reports 30 30679581
2009 Activity-dependent neuroprotective protein (ADNP) expression in the amyloid precursor protein/presenilin 1 mouse model of Alzheimer's disease. Journal of molecular neuroscience : MN 29 19844808
2023 Chromatin remodeler Activity-Dependent Neuroprotective Protein (ADNP) contributes to syndromic autism. Clinical epigenetics 28 36945042
2015 Activity-dependent neuroprotective protein (ADNP): a case study for highly conserved chordata-specific genes shaping the brain and mutated in cancer. Journal of Alzheimer's disease : JAD 28 25428252
2016 ADNP Is a Therapeutically Inducible Repressor of WNT Signaling in Colorectal Cancer. Clinical cancer research : an official journal of the American Association for Cancer Research 27 27903678
2022 A convergent mechanism of high risk factors ADNP and POGZ in neurodevelopmental disorders. Brain : a journal of neurology 26 35775424
2023 The cytoplasmic localization of ADNP through 14-3-3 promotes sex-dependent neuronal morphogenesis, cortical connectivity, and calcium signaling. Molecular psychiatry 25 36631597
2018 Mutations in ADNP affect expression and subcellular localization of the protein. Cell cycle (Georgetown, Tex.) 25 29911927
2008 Xenon induces transcription of ADNP in neonatal rat brain. Neuroscience letters 24 18571851
2007 Vasoactive intestinal peptide (VIP) regulates activity-dependent neuroprotective protein (ADNP) expression in vivo. Journal of molecular neuroscience : MN 23 17952637
2023 Neuroprotective protein ADNP-dependent histone remodeling complex promotes T helper 2 immune cell differentiation. Immunity 21 37285842
2022 Distinct Impairments Characterizing Different ADNP Mutants Reveal Aberrant Cytoplasmic-Nuclear Crosstalk. Cells 21 36230962
2017 Interaction between FMDV Lpro and transcription factor ADNP is required for optimal viral replication. Virology 21 28219017
2023 Adnp-mutant mice with cognitive inflexibility, CaMKIIα hyperactivity, and synaptic plasticity deficits. Molecular psychiatry 20 37365244
2021 Sensory Reactivity Symptoms Are a Core Feature of ADNP Syndrome Irrespective of Autism Diagnosis. Genes 19 33673501
2021 ADNP prompts the cisplatin-resistance of bladder cancer via TGF-β-mediated epithelial-mesenchymal transition (EMT) pathway. Journal of Cancer 19 34335928
2020 Activity-dependent neuroprotective protein (ADNP)-end-binding protein (EB) interactions regulate microtubule dynamics toward protection against tauopathy. Progress in molecular biology and translational science 19 33453943
2025 CRISPRi-based screen of autism spectrum disorder risk genes in microglia uncovers roles of ADNP in microglia endocytosis and synaptic pruning. Molecular psychiatry 18 40188316
2022 Activity-Dependent Neuroprotective Protein (ADNP)-Derived Peptide (NAP) Counteracts UV-B Radiation-Induced ROS Formation in Corneal Epithelium. Antioxidants (Basel, Switzerland) 18 35052632
2024 ADNP modulates SINE B2-derived CTCF-binding sites during blastocyst formation in mice. Genes & development 17 38479840
2023 A novel davunetide (NAPVSIPQQ to NAPVSIPQE) point mutation in activity-dependent neuroprotective protein (ADNP) causes a mild developmental syndrome. The European journal of neuroscience 17 36669790
2022 An open-label study evaluating the safety, behavioral, and electrophysiological outcomes of low-dose ketamine in children with ADNP syndrome. HGG advances 17 36119806
2018 Activity-dependent neuroprotective protein (ADNP) is an alcohol-responsive gene and negative regulator of alcohol consumption in female mice. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology 16 30008470
2016 The cytoskeleton as a drug target for neuroprotection: the case of the autism- mutated ADNP. Biological chemistry 16 25955282
2010 VIP, PACAP-38, BDNF and ADNP in NMDA-induced excitotoxicity in the rat retina. Acta ophthalmologica 16 20064115
2023 NAP (Davunetide): The Neuroprotective ADNP Drug Candidate Penetrates Cell Nuclei Explaining Pleiotropic Mechanisms. Cells 14 37759476
2020 Single Cell ADNP Predictive of Human Muscle Disorders: Mouse Knockdown Results in Muscle Wasting. Cells 14 33086621
2015 ADNP: in search for molecular mechanisms and innovative therapeutic strategies for frontotemporal degeneration. Frontiers in aging neuroscience 14 26578950
2022 Vineland Adaptive Behavior Scale in a Cohort of Four ADNP Syndrome Patients Implicates Age-Dependent Developmental Delays with Increased Impact of Activities of Daily Living. Journal of molecular neuroscience : MN 13 35920977
2020 Microbiota changes associated with ADNP deficiencies: rapid indicators for NAP (CP201) treatment of the ADNP syndrome and beyond. Journal of neural transmission (Vienna, Austria : 1996) 12 32072336
2020 ADNP Upregulation Promotes Bladder Cancer Cell Proliferation via the AKT Pathway. Frontiers in oncology 12 33240802
2019 ADNP differentially interact with genes/proteins in correlation with aging: a novel marker for muscle aging. GeroScience 12 31264075
2009 Nitric oxide regulates activity-dependent neuroprotective protein (ADNP) in the dentate gyrus of the rodent model of kainic acid-induced seizure. Journal of molecular neuroscience : MN 12 19130308
2007 Nitric oxide-NGF mediated PPTA/SP, ADNP, and VIP expression in the peripheral nervous system. Journal of molecular neuroscience : MN 12 17952636
2015 ADNP/ADNP2 expression in oligodendrocytes: implication for myelin-related neurodevelopment. Journal of molecular neuroscience : MN 11 26315608
2023 Loss of function of ADNP by an intragenic inversion. European journal of human genetics : EJHG 10 36828924
2023 PACAP-ADNP axis prevents outer retinal barrier breakdown and choroidal neovascularization by interfering with VEGF secreted from retinal pigmented epitelium cells. Peptides 10 37495040
2022 Modulatory activity of ADNP on the hypoxia‑induced angiogenic process in glioblastoma. International journal of oncology 10 36484392
2020 Early behavioral and developmental interventions in ADNP-syndrome: A case report of SWI/SNF-related neurodevelopmental syndrome. Molecular genetics & genomic medicine 10 32275126
2017 Further evidence that a blepharophimosis syndrome phenotype is associated with a specific class of mutation in the ADNP gene. American journal of medical genetics. Part A 10 28407407
2015 ADNP: A major autism mutated gene is differentially distributed (age and gender) in the songbird brain. Peptides 10 25895853
2025 The chromatin remodeler ADNP regulates neurodevelopmental disorder risk genes and neocortical neurogenesis. Proceedings of the National Academy of Sciences of the United States of America 9 39808658
2023 Regulation of UV-B-Induced Inflammatory Mediators by Activity-Dependent Neuroprotective Protein (ADNP)-Derived Peptide (NAP) in Corneal Epithelium. International journal of molecular sciences 9 37108060
2018 A heterozygous microdeletion of 20q13.13 encompassing ADNP gene in a child with Helsmoortel-van der Aa syndrome. European journal of human genetics : EJHG 9 29899371
2024 Clinical impact and in vitro characterization of ADNP variants in pediatric patients. Molecular autism 8 38254177
2024 Loss-of-function of activity-dependent neuroprotective protein (ADNP) by a splice-acceptor site mutation causes Helsmoortel-Van der Aa syndrome. European journal of human genetics : EJHG 8 38424297
2024 ADNP is essential for sex-dependent hippocampal neurogenesis, through male unfolded protein response and female mitochondrial gene regulation. Molecular psychiatry 8 39715923
2015 Assessment of plasma brain-derived neurotrophic factor (BDNF), activity-dependent neurotrophin protein (ADNP) and vasoactive intestinal peptide (VIP) concentrations in treatment-naïve humans with multiple sclerosis. Neuro endocrinology letters 8 26071584
2024 Integrated ribosome and proteome analyses reveal insights into sevoflurane-induced long-term social behavior and cognitive dysfunctions through ADNP inhibition in neonatal mice. Zoological research 7 38766748
2024 Tracing the invisible mutant ADNP protein in Helsmoortel-Van der Aa syndrome patients. Scientific reports 7 38926592
2023 Tau, ADNP, and sex. Cytoskeleton (Hoboken, N.J.) 7 37572043
2023 Abnormal fetal ultrasound leading to the diagnosis of ADNP syndrome. European journal of medical genetics 7 37758165
2020 Sex-and Region-Dependent Expression of the Autism-Linked ADNP Correlates with Social- and Speech-Related Genes in the Canary Brain. Journal of molecular neuroscience : MN 7 32926339
2024 Shared and divergent mental health characteristics of ADNP-, CHD8- and DYRK1A-related neurodevelopmental conditions. Journal of neurodevelopmental disorders 6 38622540
2022 Expanding the spectrum of ADNP-related disorder-Antenatally diagnosed congenital diaphragmatic hernia and a novel de novo mutation in ADNP gene. American journal of medical genetics. Part A 6 36321748
2020 VIP/PACAP-Based Drug Development: The ADNP/NAP-Derived Mirror Peptides SKIP and D-SKIP Exhibit Distinctive in vivo and in silico Effects. Frontiers in cellular neuroscience 6 31992971
2025 Synaptic Deficits in Adnp-Mutant Mice Are Ameliorated by Histone Demethylase LSD1 Inhibition. Autism research : official journal of the International Society for Autism Research 5 40536108
2024 Longitudinal Genotype-Phenotype (Vineland Questionnaire) Characterization of 15 ADNP Syndrome Cases Highlights Mutated Protein Length and Structural Characteristics Correlation with Communicative Abilities Accentuated in Males. Journal of molecular neuroscience : MN 5 38282129
2024 Moderate Physical Activity Increases the Expression of ADNP in Rat Brain. International journal of molecular sciences 5 38673966
2024 Genetic and Environmental Factors Co-Contributing to Behavioral Abnormalities in adnp/adnp2 Mutant Zebrafish. International journal of molecular sciences 5 39273418
2023 Helsmoortel-van der Aa syndrome in a Chinese pediatric patient due to ADNP nonsense mutation: A case report. Frontiers in pediatrics 5 37063667
2022 Activity-Dependent Neuroprotective Protein (ADNP): An Overview of Its Role in the Eye. International journal of molecular sciences 5 36362439
2019 GENYOi004-A: An induced pluripotent stem cells (iPSCs) line generated from a patient with autism-related ADNP syndrome carrying a pTyr719* mutation. Stem cell research 4 31035039
2025 POU3F2 regulates canonical Wnt signalling via SOX13 and ADNP to expand the neural progenitor population. Brain : a journal of neurology 3 40498903
2024 CRISPRi-based screen of Autism Spectrum Disorder risk genes in microglia uncovers roles of ADNP in microglia endocytosis and synaptic pruning. bioRxiv : the preprint server for biology 3 39605704
2022 [Analysis of clinical features and ADNP variant in a child with Helsmoortel-Van der Aa syndrome]. Zhonghua yi xue yi chuan xue za zhi = Zhonghua yixue yichuanxue zazhi = Chinese journal of medical genetics 3 36082574
2018 Correction to: The Compassionate Side of Neuroscience: Tony Sermone's Undiagnosed Genetic Journey-ADNP Mutation. Journal of molecular neuroscience : MN 3 29353437

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