Affinage

HNF4A

Hepatocyte nuclear factor 4-alpha · UniProt P41235

Length
474 aa
Mass
52.8 kDa
Annotated
2026-06-10
100 papers in source corpus 36 papers cited in narrative 36 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

HNF4A is a nuclear receptor transcription factor that sits at the apex of a tissue-restricted regulatory hierarchy, controlling differentiated cell identity and metabolic gene programs in liver, intestine, kidney, and pancreatic beta cells (PMID:8945471, PMID:9371825, PMID:30988513). It binds DR1 elements as a dimer and is positioned within a transcriptional cascade: GATA6 acts upstream to activate HNF4 in visceral endoderm, while HNF4A in turn drives HNF1A expression (PMID:9832509, PMID:8945471). Genome-wide, HNF4A occupies predominantly distal enhancers, co-occupying chromatin with the pioneer factor FOXA2, and it is required to establish enhancer–promoter chromatin loops and accessible chromatin at its target loci (PMID:19822575, PMID:33503426, PMID:30988513). Through this enhancer-organizing role it directly activates broad metabolic and differentiation programs — glucose-handling and glycolytic genes (GLUT2, aldolase B, GAPDH, pyruvate kinase) (PMID:9371825), hepatic lipoprotein and cholesterol genes including apoCIII, ACAT2, CYP7A1, and MTP (PMID:10551874, PMID:19478207, PMID:10627496, PMID:28128295), the beta-cell ATP-sensitive K+ channel subunit Kir6.2 driving insulin secretion (PMID:15761495), the hepatic glucagon receptor governing the liver–alpha-cell axis (PMID:36464036), and fatty acid oxidation genes that sustain intestinal stem cell renewal (PMID:31759926). HNF4A also acts as a lineage-determining factor that shapes glucocorticoid receptor binding in liver and as a transcriptional repressor of CLOCK:BMAL1 circadian activity and of hepatic acute-phase response genes (PMID:35443180, PMID:30530698, PMID:38755249). Its activity is reinforced by feedback and feed-forward loops with COUP-TFII (NR2F2) in beta cells and with SMAD4 in intestine, and is tuned by co-activators including DDX3, which enhances CBP/p300-mediated acetylation and displaces the SHP repressor to favor the active homodimer (PMID:18474611, PMID:30988513, PMID:28128295). Loss-of-function mutations in HNF4A cause MODY1 maturity-onset diabetes primarily through haploinsufficiency, with mutant proteins abolishing DNA binding and transactivation without exerting dominant-negative effects (PMID:8945471, PMID:9371825, PMID:10389854, PMID:31195238); a DNA-binding-domain mutation (R85W) additionally produces a Fanconi renotubular syndrome phenotype via serine-phosphorylation-driven nuclear export and cytosolic aggregation (PMID:31875549, PMID:30046000).

Mechanistic history

Synthesis pass · year-by-year structured walk · 35 steps
  1. 1996 High

    Established HNF4A's identity and its place in a transcriptional hierarchy, answering which gene underlies MODY1 and how it connects to beta-cell function.

    Evidence Positional cloning and genetic linkage in MODY1 pedigrees identifying HNF4A as an upstream regulator of HNF1A

    PMID:8945471

    Open questions at the time
    • Direct beta-cell target genes not yet defined
    • Mechanism of upstream HNF1A regulation not resolved at the binding-site level
  2. 1997 High

    Connected MODY1 loss-of-function to specific metabolic genes, showing HNF4A directly drives glucose transport and glycolytic gene expression.

    Evidence Functional assay of the Q268X mutant plus loss-of-function in ES-cell-derived visceral endoderm with gene expression profiling

    PMID:9371825

    Open questions at the time
    • Direct vs indirect regulation of individual targets not separated
    • Pancreatic relevance inferred from endoderm model
  3. 1998 High

    Resolved whether MODY1 acts by dominant-negative interference or loss of function, and identified an aberrant subcellular fate of mutant protein.

    Evidence EMSA, co-immunoprecipitation, transfection, and subcellular fractionation of Q268X mutant

    PMID:9604881

    Open questions at the time
    • Cause of cytoplasmic/insoluble localization not mechanistically defined
    • Single mutant studied
  4. 1998 High

    Placed HNF4A within a developmental cascade by identifying GATA6 as its upstream activator in visceral endoderm.

    Evidence GATA6 knockout ES cells/mice plus HNF4 promoter activation assay

    PMID:9832509

    Open questions at the time
    • Direct vs indirect promoter activation by GATA6 not fully resolved
    • Restricted to endoderm context
  5. 1999 High

    Mapped a critical LBD residue (E276) for DNA binding, transactivation, and stability, and distinguished true loss-of-function from neutral MODY variants.

    Evidence Transactivation, EMSA, co-IP, and Western analysis of E276Q, R127W, and V255M mutants in multiple cell types

    PMID:10389854

    Open questions at the time
    • Weak dominant-negative effect of truncated product not tested in beta cells in vivo
    • Structural basis of E276 role not directly determined
  6. 1999 Medium

    Demonstrated direct DR1-mediated regulation of a hepatic lipoprotein gene and a signaling input modulating HNF4A levels.

    Evidence Reporter assays, EMSA, promoter mapping, and MAP kinase inhibition in HepG2 for apoCIII

    PMID:10551874

    Open questions at the time
    • MAP kinase control of HNF4A expression is a secondary inference
    • Single cell line
  7. 2000 Medium

    Showed HNF4A synergizes with COUP-TFII at a lipid-metabolism promoter through protein–protein interaction rather than independent COUP-TFII DNA binding.

    Evidence EMSA, cotransfection, and promoter mutagenesis for CYP7A1 in HepG2

    PMID:10627496

    Open questions at the time
    • Direct physical interaction inferred from functional data, not co-IP
    • Single lab
  8. 2000 Medium

    Established that the in vivo MODY1 lipid phenotype arises from haploinsufficiency rather than secondary hyperglycemia.

    Evidence Serum protein measurement across genotyped MODY1 pedigree members

    PMID:10905494

    Open questions at the time
    • Single family pedigree
    • Direct transcriptional regulation of each serum protein not all demonstrated
  9. 2000 Medium

    Confirmed R127W as loss-of-function affecting DNA binding while preserving nuclear import and CBP synergy, refining genotype–mechanism mapping.

    Evidence Transactivation, EMSA, co-IP with CBP, and immunofluorescence for HNF1A and PKL targets

    PMID:10819248

    Open questions at the time
    • Single lab
    • In vivo beta-cell consequence not measured
  10. 2005 High

    Linked HNF4A directly to the insulin secretion machinery by identifying Kir6.2 as a target underlying the beta-cell secretory phenotype.

    Evidence Beta-cell conditional knockout with perifusion/calcium imaging plus cotransfection target validation

    PMID:15761495

    Open questions at the time
    • Full set of beta-cell targets explaining hyperinsulinemia not enumerated
    • Direct binding by ChIP not shown in this study
  11. 2008 High

    Defined a positive feedback circuit between HNF4A and COUP-TFII in beta cells, explaining transcriptional network stabilization.

    Evidence ChIP, reporter mutagenesis, siRNA, and adenoviral overexpression in INS-1 cells and islets

    PMID:18474611

    Open questions at the time
    • Mechanism of COUP-TFII-mediated HNF4A upregulation not resolved
    • Tissue-specificity of loop not tested
  12. 2009 Medium

    Provided the first genome-wide view showing HNF4A acts predominantly at distal enhancers and co-occupies sites with FOXA2 and GABP.

    Evidence ChIP-seq in hepatic cells plus co-immunoprecipitation

    PMID:19822575

    Open questions at the time
    • Functional consequence of GABP interaction not dissected
    • Single lab
  13. 2009 High

    Established HNF4A as a direct hepatic regulator of cholesterol esterification via ACAT2, with human clinical correlation.

    Evidence ChIP in human liver, promoter mutagenesis, cotransfection, and MODY1 lipoprotein profiling

    PMID:19478207

    Open questions at the time
    • Relative contribution of direct vs HNF1A-mediated regulation unresolved
  14. 2014 Medium

    Showed HNF4A enhancer selection is developmentally dynamic and integrates Hippo (TEAD2/YAP1) signaling during hepatocyte differentiation.

    Evidence Developmental-stage ChIP-seq with chromatin and expression profiling in mouse liver

    PMID:25263553

    Open questions at the time
    • Functional Hippo–HNF4A link is indirect
    • Mechanism directing temporal enhancer choice unresolved
  15. 2016 High

    Demonstrated through the Drosophila ortholog that HNF4 drives a developmental metabolic switch toward oxidative phosphorylation and glucose-stimulated insulin secretion.

    Evidence Drosophila genetic loss-of-function with metabolic, glucose tolerance, and insulin secretion assays

    PMID:27185732

    Open questions at the time
    • Conservation of specific target genes in mammals not all established here
  16. 2016 Medium

    Identified cooperation with TCF7L2 to control an epithelial barrier gene during colonic differentiation.

    Evidence ChIP, expression profiling, cotransfection, and Hnf4a conditional knockout for Cldn23

    PMID:27583195

    Open questions at the time
    • Limited to a single target gene
    • Direct HNF4A–TCF7L2 interaction not shown
  17. 2017 Medium

    Revealed post-translational control of HNF4A: DDX3 promotes CBP/p300-mediated acetylation and shifts the equilibrium from the inactive SHP heterodimer to the active homodimer.

    Evidence Co-IP, ChIP, ATPase assay, and reporter/siRNA experiments on MTP regulation

    PMID:28128295

    Open questions at the time
    • Acetylation site mapping not defined
    • Single lab
  18. 2017 Medium

    Defined epigenetic control of HNF4A promoter choice, showing FOXA2-dependent TET activity deposits 5hmC at the P1 promoter to enable P1 isoform expression.

    Evidence 5hmC/5mC mapping, TET inhibition, and FOXA2 knockdown in a hepatocyte differentiation model

    PMID:28648900

    Open questions at the time
    • Functional difference between P1 and P2 isoforms not tested here
    • Single differentiation system
  19. 2018 High

    Identified HNF4A as a transrepressor of CLOCK:BMAL1, integrating it into the hepatic circadian clock with rhythmic genomic binding.

    Evidence Transrepression reporter, ChIP-seq, and cell-autonomous oscillation assays in liver and colon cells

    PMID:30530698

    Open questions at the time
    • Mechanism of transrepression at the molecular level not resolved
    • In vivo circadian phenotype of HNF4A loss not measured here
  20. 2018 High

    Established a non-diabetic, kidney-specific requirement for HNF4A in proximal tubule differentiation, modeling Fanconi renotubular syndrome.

    Evidence Kidney-specific conditional knockout with histology, expression, and physiological phenotyping

    PMID:30046000

    Open questions at the time
    • Direct proximal-tubule target genes not all defined here
    • Distinction from presumptive tubule formation mechanism unresolved
  21. 2019 High

    Defined a reinforcing HNF4A–SMAD4 feed-forward loop and showed HNF4A/HNF4G redundancy is essential for enterocyte differentiation and enhancer activation.

    Evidence Double conditional knockout with ChIP-seq, ATAC-seq, and RNA-seq

    PMID:30988513

    Open questions at the time
    • Direct HNF4A–SMAD4 physical interaction not shown
    • Paralog-specific contributions not separated
  22. 2019 High

    Linked HNF4 to intestinal stem cell renewal through direct activation of fatty acid oxidation genes feeding the TCA cycle.

    Evidence Double conditional knockout with ChIP-seq, metabolic tracing, and organoid acetyl-CoA rescue

    PMID:31759926

    Open questions at the time
    • Mechanism connecting acetyl-CoA to stem cell maintenance not fully resolved
  23. 2019 Medium

    Showed an additional MODY1 frameshift mutant acts by impaired transactivation without dominant negativity and perturbs foregut/hindgut identity.

    Evidence Patient-derived iPSC hepatopancreatic differentiation with expression profiling and localization

    PMID:31195238

    Open questions at the time
    • Mechanistic interpretation partly inferential
    • Single lab
  24. 2019 High

    Explained the FRTS R85W phenotype as a non-genomic mechanism: serine-phosphorylation-driven nuclear export causing cytosolic aggregation and cell stress.

    Evidence Drosophila nephrocyte expression with confocal/EM imaging, phosphosite mutagenesis, and genetic rescue

    PMID:31875549

    Open questions at the time
    • Identity of the responsible kinase not determined
    • Conservation in human kidney cells not tested here
  25. 2020 Medium

    Placed HNF4A upstream of ULK1-mediated autophagy in fatty liver via direct transcriptional activation, with miR-214-3p as an opposing regulator.

    Evidence ChIP, luciferase 3'UTR assay, LNA miRNA silencing, and autophagy flux assays in mouse liver

    PMID:33078654

    Open questions at the time
    • Single lab
    • Direct binding site on Ulk1 promoter not mapped
  26. 2021 High

    Demonstrated therapeutic anti-fibrotic potential of restoring HNF4A and identified PON1 as a direct mediator.

    Evidence LNP HNF4A mRNA delivery in four fibrosis models, ChIP, and single-cell mechanistic dissection

    PMID:34453962

    Open questions at the time
    • Full anti-fibrotic target set beyond PON1 not defined
  27. 2021 High

    Established HNF4 as an organizer of enhancer–promoter chromatin looping required for target gene expression in the intestine.

    Evidence H3K4me3 HiChIP-seq, ATAC-seq, ChIP-seq with conditional HNF4 knockout

    PMID:33503426

    Open questions at the time
    • Whether HNF4 directly mediates loop formation or acts via cofactors unresolved
  28. 2021 High

    Generalized HNF4's role to a conserved brush-border gene program across intestine, kidney, and yolk sac with loop reorganization.

    Evidence Multi-organ conditional knockout with ChIP-seq, HiChIP, RNA-seq, and transport assays

    PMID:34001900

    Open questions at the time
    • Mechanism of gained looping at stress fiber loci not resolved
  29. 2022 High

    Defined HNF4A as a lineage-determining factor that shapes the liver glucocorticoid receptor cistrome.

    Evidence GR and HNF4A ChIP-seq plus ATAC-seq in Hnf4a-null liver

    PMID:35443180

    Open questions at the time
    • Direct HNF4A–GR physical interaction not demonstrated
  30. 2022 High

    Revealed HNF4A control of the liver–alpha-cell axis via direct regulation of the glucagon receptor.

    Evidence Liver-specific conditional knockout with ChIP, glucagon challenge, and metabolic phenotyping

    PMID:36464036

    Open questions at the time
    • Contribution to systemic glucose homeostasis vs local effects not fully separated
  31. 2022 High

    Extended HNF4A function to immune crosstalk, directly regulating butyrophilin and MHC-like genes controlling intraepithelial lymphocyte populations.

    Evidence IEC-specific conditional knockout, ChIP, and flow cytometry of IEL populations, with human conservation

    PMID:35792863

    Open questions at the time
    • Mechanism by which BTNL signals shape IEL selection not addressed here
  32. 2023 High

    Mapped tissue-dependent HNF4A target repertoires and distinguished the functional consequences of a T2D-associated variant from MODY1 loss-of-function alleles.

    Evidence ChIP-seq in pancreatic and hepatic cells with functional validation and variant comparison

    PMID:38909044

    Open questions at the time
    • Mechanism by which rs1800961 alters DNA-binding affinity not directly measured
  33. 2023 High

    Validated HNF4A as the dominant paralog for proximal tubule brush border identity in human kidney organoids.

    Evidence HNF4A/HNF4G knockout iPSC kidney organoids, CUT&RUN, CRISPRa, RNA-seq, and EM

    PMID:37488681

    Open questions at the time
    • Why HNF4A but not HNF4G is required in this context not resolved
  34. 2023 High

    Showed HNF4 paralogs activate mimetic-cell enhancers in thymic epithelium to recapitulate peripheral tissue gene programs for tolerance.

    Evidence Conditional Hnf4a/g knockout in TECs with scRNA-seq, ATAC-seq, ChIP, and CTCF analysis

    PMID:37399024

    Open questions at the time
    • Mechanism linking HNF4-driven enhancers to CTCF redistribution unresolved
  35. 2024 Medium

    Established HNF4A as a basal repressor of acute-phase genes whose loss permits inflammatory derepression, defining a chromatin-gating role.

    Evidence Liver organoid HNF4A overexpression with chromatin accessibility and transcriptome profiling

    PMID:38755249

    Open questions at the time
    • Single lab organoid model
    • Mechanism of chromatin retention at acute-phase loci not resolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • How HNF4A switches between activator and repressor states at distinct loci, and how post-translational modifications and cofactor competition mechanistically direct enhancer looping, remain unresolved.
  • No unified model linking acetylation/phosphorylation status to genomic outcome
  • Direct mediators of HNF4A-dependent chromatin looping not identified
  • Structural basis of activator vs repressor switching unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 8 GO:0003677 DNA binding 5
Localization
GO:0005634 nucleus 3 GO:0005829 cytosol 2
Pathway
R-HSA-1430728 Metabolism 5 R-HSA-1266738 Developmental Biology 4 R-HSA-4839726 Chromatin organization 4 R-HSA-74160 Gene expression (Transcription) 4 R-HSA-9612973 Autophagy 1 R-HSA-9909396 Circadian clock 1
Partners
CREBBPDDX3XFOXA2GABPNR0B2NR2F2SMAD4TCF7L2

Evidence

Reading pass · 36 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1996 HNF4A (TCF14) was identified as the MODY1 gene; it is a member of the steroid/thyroid hormone receptor superfamily and functions as an upstream transcriptional regulator of HNF-1alpha expression, establishing its position in a transcriptional hierarchy governing pancreatic beta-cell function. Genetic linkage analysis, gene identification, positional cloning Nature High 8945471
1997 The MODY1 nonsense mutation Q268X causes loss of HNF4A transcriptional transactivation activity and abolishes dimerization and DNA binding. Loss of HNF4A function in embryonic stem cells-derived visceral endoderm reduces expression of glucose transporter 2, aldolase B, glyceraldehyde-3-phosphate dehydrogenase, liver pyruvate kinase, and fatty acid binding proteins, demonstrating HNF4A directly regulates glucose transport and glycolysis genes. Functional assays in mutant protein; embryonic stem cell visceral endoderm differentiation system; gene expression analysis Proceedings of the National Academy of Sciences of the United States of America High 9371825
1998 The MODY1 Q268X mutant protein cannot bind DNA alone or as a dimer with wild-type HNF4A in EMSA, yet retains the ability to dimerize with wild-type HNF4A in solution (co-immunoprecipitation). Despite dimerization, it does not exert dominant-negative transcriptional effects in vivo; instead it shows striking cytoplasmic/insoluble localization (extractable only with SDS), suggesting MODY1 phenotype results from loss of functional nuclear HNF4A, particularly pronounced in pancreas where HNF4A levels are low. EMSA, co-immunoprecipitation, transient transfection, subcellular fractionation/immunofluorescence Diabetes High 9604881
1998 GATA6 lies upstream of HNF4A in a transcriptional cascade required for visceral endoderm differentiation: GATA6-deficient embryos lack HNF4 gene expression, and forced GATA6 expression activates the HNF4 promoter in non-endodermal cells. Gene targeting (GATA6 knockout ES cells and mice), promoter activation assay, in situ hybridization Genes & development High 9832509
1999 The MODY1 missense mutation HNF4(E276Q) is a loss-of-function mutation: it cannot bind HNF-4 consensus DNA sites or activate transcription. A truncated 40-kDa C-terminal product of E276Q can co-immunoprecipitate with wild-type HNF4A and exerts weak dominant-negative activity in non-beta-cell types. Glutamic acid 276 in helix 8 of the LBD is identified as critical for DNA binding, transactivation, and protein stability. HNF4(R127W) and HNF4(V255M) show transactivation indistinguishable from wild-type. Transcriptional activation assay, EMSA, co-immunoprecipitation, Western blot, cell-type-specific transfection Diabetes High 10389854
1999 HNF4 regulates apolipoprotein CIII (apoCIII) gene transcription through a DR1 binding site at position -746 in the apoCIII promoter. MAP kinase signaling modulates apoCIII expression partly via changes in HNF4 mRNA and protein levels; repression of MAP kinase increases HNF4 expression and apoCIII transcription. Transient transfection/reporter assay in HepG2, EMSA, promoter deletion mapping, pharmacological MAP kinase inhibition The Journal of biological chemistry Medium 10551874
2000 HNF4 and COUP-TFII synergistically activate transcription of the CYP7A1 (cholesterol 7alpha-hydroxylase) promoter. HNF4 binds a DR1 element at nt -146 to -134 of the CYP7A1 promoter, and synergy with COUP-TFII involves protein-protein interactions facilitated by juxtaposed binding elements rather than requiring independent COUP-TFII DNA binding. EMSA with rat liver nuclear extracts, cotransfection assays in HepG2, site-directed mutagenesis of promoter elements Journal of lipid research Medium 10627496
2000 HNF4A haploinsufficiency (not hyperglycemia) is the primary cause of reduced serum levels of apolipoprotein AII, apoCIII, lipoprotein(a), and triglycerides in MODY1 mutation carriers, demonstrating HNF4A is a required transcriptional regulator of these hepatic secretory proteins in vivo. Serum protein measurement in genotyped MODY1 pedigree members (diabetic HNF4+/-, nondiabetic HNF4+/-, normal HNF4+/+); genetic haploinsufficiency analysis Diabetes Medium 10905494
2000 The R127W-HNF4A mutation reduces DNA binding ability and transcriptional activation of HNF-1alpha and L-type pyruvate kinase (PKL) genes; nuclear import and functional synergy with coactivator CBP are normal, confirming R127W is a loss-of-function mutation. Transcriptional activation assay, EMSA, co-immunoprecipitation with CBP, immunofluorescence for nuclear localization Diabetologia Medium 10819248
2004 HNF4 stimulates expression of the precore RNA and core RNA from the hepatitis B virus (HBV) core promoter by binding to a nuclear receptor binding site; this effect is more prominent on the wild-type than on the A1762T/G1764A double-mutant core promoter. The X protein does not affect HNF4 activity on the core promoter. Reporter assay in Huh7 hepatoma cells, cotransfection, HBV genomic constructs with/without X protein Journal of virology Medium 15194767
2005 HNF4A is required in pancreatic beta cells for regulation of the ATP-dependent potassium channel pathway of insulin secretion; conditional beta-cell knockout mice show hyperinsulinemia but impaired glucose tolerance, with ~60% reduction in Kir6.2 (KCNJ11) expression. Cotransfection assays demonstrate Kir6.2 is a direct transcriptional target of HNF4A. Cre-loxP conditional knockout, islet perifusion, calcium imaging, cotransfection assay, quantitative gene expression The Journal of clinical investigation High 15761495
2008 HNF4A directly activates the COUP-TFII (NR2F2) promoter via a DR-1 binding site in pancreatic beta cells (demonstrated by ChIP and reporter/mutagenesis), and COUP-TFII in turn positively regulates HNF4A mRNA levels, forming a positive feedback loop. COUP-TFII also autorepreses its own promoter via the same DR-1 site. ChIP, promoter reporter assay, site-directed mutagenesis, dominant-negative suppression, siRNA knockdown, adenoviral overexpression in 832/13 INS-1 cells and mouse islets Molecular and cellular biology High 18474611
2009 HNF4A binds to and regulates the hepatocyte-specific expression of the ACAT2 (cholesterol esterification enzyme) promoter, as confirmed by ChIP assay in human liver and site-directed mutagenesis of an HNF4 binding site; HNF4A can act directly or indirectly via HNF1alpha. MODY1 patients have lower VLDL and LDL esterified cholesterol consistent with reduced ACAT2 activity. ChIP assay in human liver, mutagenesis, cotransfection in HuH7 cells, lipoprotein profiling in MODY1 patients Arteriosclerosis, thrombosis, and vascular biology High 19478207
2009 Genome-wide ChIP-seq reveals HNF4A binds ~18,783 peaks in hepatic cells, predominantly at non-promoter positions (90% distal elements). HNF4A co-occupies sites with FOXA2, and an HNF4A–GABP interaction at transcription start sites was identified and verified by co-immunoprecipitation. ChIP-seq, co-immunoprecipitation Nucleic acids research Medium 19822575
2014 In mouse liver development, HNF4A binding to enhancers is differentiation-dependent, with embryonic enhancers responsive to TEAD2/YAP1 (Hippo signaling). Hippo pathway activity influences which temporal enhancers HNF4A and FOXA2 occupy during hepatocyte differentiation. ChIP-seq in vivo across developmental stages, chromatin remodeling analysis, gene expression profiling Cell reports Medium 25263553
2016 Drosophila HNF4 (dHNF4) is required in the fat body and insulin-producing cells for a developmental switch toward oxidative phosphorylation and glucose-stimulated insulin secretion at the adult transition. Loss of dHNF4 causes adult-onset hyperglycemia, glucose intolerance, and impaired GSIS, linked to reduced mitochondrial function and decreased expression of Hex-C (glucokinase homolog). Drosophila genetic loss-of-function, metabolic assays, glucose tolerance test, insulin secretion assay, gene expression eLife High 27185732
2017 DDX3 RNA helicase interacts with HNF4A and co-activates HNF4A-mediated transactivation of the MTP (microsomal triglyceride transfer protein) promoter. DDX3 enhances HNF4A acetylation via CBP/p300 interaction, increases HNF4A promoter binding affinity, and competes with the repressor SHP for HNF4A binding, disrupting the inactive HNF4A/SHP heterodimer and promoting active HNF4A homodimer formation. Co-immunoprecipitation, luciferase reporter assay, ChIP, ATPase activity assay, siRNA knockdown Scientific reports Medium 28128295
2017 TET-catalyzed 5-hydroxymethylation (5hmC) at the HNF4A P1 promoter precedes expression of P1 promoter-derived HNF4A isoforms during hepatocyte differentiation. TET dioxygenases and the pioneer factor FOXA2 are required for 5hmC at P1 and subsequent P1-driven HNF4A expression; FOXA2 is necessary for TET1 binding to the P1 locus. 5hmC/5mC mapping, TET inhibition, FOXA2 knockdown, in vitro hepatocyte differentiation model Stem cell reports Medium 28648900
2018 HNF4A strongly transrepresses CLOCK:BMAL1 heterodimer transcriptional activity, defining a negative feedback loop in the hepatic circadian clock. Genome-wide ChIP-seq shows HNF4A binding at CLOCK:BMAL1 co-occupied metabolic gene loci is rhythmic in mouse liver. HNF4A maintains cell-autonomous circadian oscillations in a tissue-specific manner in liver and colon cells. Transcriptional reporter assay (transrepression), ChIP-seq, circadian oscillation assay (luciferase reporter), cell-autonomous oscillation measurement Proceedings of the National Academy of Sciences of the United States of America High 30530698
2018 Kidney-specific deletion of Hnf4a in mice causes Fanconi renotubular syndrome-like phenotype (polyuria, polydipsia, glycosuria, phosphaturia) with failure of proximal tubule differentiation and loss of proximal tubule-specific gene expression; Hnf4a is required for differentiated but not presumptive proximal tubule formation. Conditional kidney-specific Hnf4a knockout mice, histology, gene expression, physiological phenotyping JCI insight High 30046000
2019 HNF4A and SMAD4 form a reinforcing feed-forward loop in the intestine: they activate each other's expression and co-bind regulatory elements of differentiation genes. Double knockout of HNF4A and its paralog HNF4G abolishes enterocyte differentiation; HNF4 activates enhancer chromatin and upregulates the majority of transcripts enriched in differentiated intestinal epithelium. Double conditional knockout (HNF4A/HNF4G), ChIP-seq, ATAC-seq, RNA-seq, gene expression profiling Nature genetics High 30988513
2019 HNF4A and HNF4G are required for intestinal stem cell renewal via direct transcriptional activation of fatty acid oxidation (FAO) genes including Acsl5, Acsf2, Slc27a2, Fabp2, and Hadh. Loss of both paralogs reduces FAO activity, TCA cycle metabolites, and Lgr5+ stem cell markers; restoration of acetyl-CoA via acetate or dichloroacetate rescues stem cells. Double conditional knockout (Hnf4a/Hnf4g), ChIP-seq, metabolic assays (FAO activity, TCA metabolites), isotope tracing, organoid rescue experiments Gastroenterology High 31759926
2019 The HNF4A p.Ile271fs MODY1 mutant does not undergo complete nonsense-mediated decay and does not exert dominant negativity; loss of function is due to impaired transcriptional activation of target genes. MODY1-iPSC-derived hepatopancreatic progenitors with reduced HNF4A show downregulation of foregut genes and upregulation of hindgut HOX genes. Patient-derived iPSC differentiation, gene expression profiling, HNF4A localization by immunofluorescence iScience Medium 31195238
2019 The FRTS-associated HNF4A R85W mutation (in the DNA-binding domain) causes nuclear depletion and cytosolic aggregation of wild-type dHNF4 protein in Drosophila nephrocytes. Nuclear depletion leads to mitochondrial defects and lipid droplet accumulation; cytosolic aggregates trigger ER expansion, autophagy, and cell death. Blocking serine phosphorylation in the DBD prevents nuclear export and rescues the cytosolic aggregation phenotype. Drosophila nephrocyte expression system, confocal microscopy, electron microscopy, phosphorylation site mutagenesis, genetic rescue Cell reports High 31875549
2020 Mir214-3p suppresses Ulk1 expression by direct binding to the 3' UTR of Ulk1, while HNF4A (Hnf4a) directly activates Ulk1 transcription (demonstrated by ChIP). In nonalcoholic fatty liver, increased Mir214-3p and decreased Hnf4a reduce autophagic activity; silencing Mir214-3p increases Ulk1 and autophagic flux, but not under Ulk1 suppression, placing HNF4A upstream of ULK1-mediated autophagy. ChIP (HNF4A binding to Ulk1 promoter), luciferase 3'UTR assay, LNA-mediated miRNA silencing, autophagy flux assays in mouse liver Autophagy Medium 33078654
2021 Therapeutic delivery of HNF4A mRNA via lipid nanoparticles to mouse liver attenuates fibrosis in four independent models. Paraoxonase 1 (PON1) was identified as a direct HNF4A transcriptional target by ChIP; PON1 contributes to HNF4A-mediated anti-fibrotic effect via modulation of liver macrophages and hepatic stellate cells. LNP-mediated mRNA delivery in vivo, ChIP, microarray/scRNA-seq, primary cell experiments, human liver bud model Journal of hepatology High 34453962
2021 HNF4 transcription factors are required for chromatin looping between enhancers and promoters at target genes in the intestinal epithelium. HNF4 depletion disrupts local enhancer-promoter chromatin interactions, histone modifications, and target gene expression; despite dynamic gene regulation during differentiation, enhancer-promoter loops are relatively stable. H3K4me3 HiChIP-seq, ATAC-seq, ChIP-seq, conditional HNF4 knockout Cell reports High 33503426
2021 HNF4 (HNF4A and HNF4G) drives a conserved brush border gene program in intestine, kidney, and yolk sac by directly binding and activating brush border genes. HNF4 loss results in impaired chromatin looping between enhancers and promoters at brush border gene loci and enhanced looping at stress fiber gene loci. Conditional knockout (intestine, kidney, yolk sac), ChIP-seq, H3K4me3 HiChIP-seq, RNA-seq, transport assays Nature communications High 34001900
2022 HNF4A defines liver-specific glucocorticoid receptor (GR) action by acting as a lineage-determining factor: the HNF4A motif lies adjacent to glucocorticoid response elements at GR binding sites in open chromatin. In Hnf4a-null liver, the GR cistrome is remodeled—loss of GR recruitment occurs at weak GRE sites with HNF4A-marked chromatin, while GR binding is gained at strong GRE motifs normally restricted to non-liver tissues. ChIP-seq (GR, HNF4A), ATAC-seq in Hnf4a-null liver, transcriptional response analysis Cell reports High 35443180
2022 HNF4A directly regulates the glucagon receptor (Gcgr) gene in mouse liver (confirmed by ChIP); liver-specific Hnf4a knockout mice show markedly reduced Gcgr expression, glucagon resistance, alpha-cell hyperplasia, and dramatically elevated glucagon levels, revealing a role for HNF4A in controlling the liver-alpha-cell axis and blood glucose homeostasis. Liver-specific conditional Hnf4a knockout (Alb-Cre), ChIP assay, glucagon challenge test, metabolic phenotyping, gene expression Metabolism: clinical and experimental High 36464036
2022 HNF4A in intestinal epithelial cells directly regulates expression of immune signaling molecules Btnl1, Btnl6, H2-T3, and Clec2e that control epithelial-intraepithelial lymphocyte (IEL) crosstalk, selectively expanding TCRγδ+ and TCRαβ+CD8αα+ natural IELs; in the small intestine HNF4A cooperates with HNF4G for this function. The HNF4A-BTNL regulatory axis is conserved in human IECs. IEC-specific conditional knockout, ChIP, gene expression, flow cytometry of IEL populations The Journal of experimental medicine High 35792863
2023 HNF4A binds and directly regulates known targets (ACY3, HAAO, HNF1A, MAP3K11) and previously unidentified loci (ABCD3, CDKN2AIP, USH1C, VIL1) in a tissue-dependent manner in pancreatic beta cells and hepatocytes. The T2D-associated HNF4A variant rs1800961 (unlike the loss-of-function MODY1 variant I271fs) activates AKAP1, GAD2, and HOPX expression, potentially through altered DNA-binding affinity. ChIP-seq in pancreatic and hepatic cells, functional validation of selected targets, comparison of MODY1 vs T2D variants Nature communications High 38909044
2023 HNF4A directly regulates its target genes in human proximal tubules (validated by CUT&RUN sequencing showing binding at promoters and enhancers of downregulated genes). HNF4A loss (not HNF4G) in human kidney organoids impairs expression of transport-related, endocytosis-related, and brush border genes and disorganizes apical brush border structure. CRISPRa-mediated induction of HNF4A or HNF4G drives increased expression of selected target genes. HNF4A/HNF4G knockout iPSC-derived kidney organoids, CUT&RUN sequencing, CRISPRa, RNA-seq, electron microscopy Journal of the American Society of Nephrology : JASN High 37488681
2024 HNF4A binds to and represses acute-phase response genes under basal hepatic conditions. During inflammation, loss of HNF4A function is required for derepression of acute-phase genes; overexpression of HNF4A in liver organoids retains chromatin at regulatory regions of acute-phase genes inaccessible to transcription, potently impairing the acute-phase response while maintaining hepatocyte functionality. Pre-clinical liver organoid model, HNF4A overexpression, chromatin accessibility assay, transcriptome profiling Communications biology Medium 38755249
2016 In the colonic epithelium, HNF4A cooperates with TCF7L2 in a cascade that upregulates Claudin-23 expression during differentiation, as confirmed by ChIP and Hnf4a conditional knockout mice (which fail to induce Cldn23). ChIP, microarray/gene expression, in vitro cotransfection, Hnf4a conditional knockout mice Tissue barriers Medium 27583195
2023 In medullary thymic epithelial cells (mTECs), HNF4α and HNF4γ activate mimetic-cell enhancers to recapitulate entero-hepato gene expression programs, with HNF4γ providing primary contribution. Loss of both Hnf4 paralogs ablates entero-hepato mTECs, impairs enhancer activation and CTCF redistribution, but does not affect Polycomb repression or promoter-proximal histone marks. Conditional Hnf4α/γ knockout in TECs, scRNA-seq, ATAC-seq, ChIP, CTCF binding analysis The Journal of experimental medicine High 37399024

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1996 Mutations in the hepatocyte nuclear factor-4alpha gene in maturity-onset diabetes of the young (MODY1). Nature 985 8945471
1998 GATA6 regulates HNF4 and is required for differentiation of visceral endoderm in the mouse embryo. Genes & development 534 9832509
1997 The maturity-onset diabetes of the young (MODY1) transcription factor HNF4alpha regulates expression of genes required for glucose transport and metabolism. Proceedings of the National Academy of Sciences of the United States of America 335 9371825
2005 The MODY1 gene HNF-4alpha regulates selected genes involved in insulin secretion. The Journal of clinical investigation 188 15761495
2019 HNF4 Regulates Fatty Acid Oxidation and Is Required for Renewal of Intestinal Stem Cells in Mice. Gastroenterology 180 31759926
1990 Scope and heterogeneous nature of MODY. Diabetes care 162 2404717
2019 Maturity-onset diabetes of the young (MODY): current perspectives on diagnosis and treatment. Diabetes, metabolic syndrome and obesity : targets and therapy 148 31360071
1994 Characterization of the mouse HNF-4 gene and its expression during mouse embryogenesis. Mechanisms of development 146 7873404
2021 Therapeutic HNF4A mRNA attenuates liver fibrosis in a preclinical model. Journal of hepatology 132 34453962
2020 The epidemiology, molecular pathogenesis, diagnosis, and treatment of maturity-onset diabetes of the young (MODY). Clinical diabetes and endocrinology 131 33292863
2019 A reinforcing HNF4-SMAD4 feed-forward module stabilizes enterocyte identity. Nature genetics 125 30988513
2015 Maturity-onset diabetes of the young (MODY): an update. Journal of pediatric endocrinology & metabolism : JPEM 124 25581748
2000 Genotype/phenotype relationships in HNF-4alpha/MODY1: haploinsufficiency is associated with reduced apolipoprotein (AII), apolipoprotein (CIII), lipoprotein(a), and triglyceride levels. Diabetes 120 10905494
1995 Altered insulin secretory responses to glucose in subjects with a mutation in the MODY1 gene on chromosome 20. Diabetes 119 7789636
2020 HNF4A and GATA6 Loss Reveals Therapeutically Actionable Subtypes in Pancreatic Cancer. Cell reports 113 32402285
2020 Treatment Options for MODY Patients: A Systematic Review of Literature. Diabetes therapy : research, treatment and education of diabetes and related disorders 113 32583173
2000 HNF4 and COUP-TFII interact to modulate transcription of the cholesterol 7alpha-hydroxylase gene (CYP7A1). Journal of lipid research 110 10627496
1998 Mutation screening in 18 Caucasian families suggest the existence of other MODY genes. Diabetologia 110 9754819
1997 Organization and partial sequence of the hepatocyte nuclear factor-4 alpha/MODY1 gene and identification of a missense mutation, R127W, in a Japanese family with MODY. Diabetes 105 9313765
1989 Maturity-onset diabetes of the young (MODY). Diabetes/metabolism reviews 100 2689121
2014 Hippo signaling influences HNF4A and FOXA2 enhancer switching during hepatocyte differentiation. Cell reports 94 25263553
2004 Regulation of hepatitis B virus core promoter by transcription factors HNF1 and HNF4 and the viral X protein. Journal of virology 91 15194767
2013 De novo mutations of GCK, HNF1A and HNF4A may be more frequent in MODY than previously assumed. Diabetologia 90 24323243
2016 The Drosophila HNF4 nuclear receptor promotes glucose-stimulated insulin secretion and mitochondrial function in adults. eLife 82 27185732
2022 Reduced penetrance of MODY-associated HNF1A/HNF4A variants but not GCK variants in clinically unselected cohorts. American journal of human genetics 76 36257325
2009 Species-specific differences in the expression of the HNF1A, HNF1B and HNF4A genes. PloS one 75 19924231
2013 Fertility and germline stem cell maintenance under different diets requires nhr-114/HNF4 in C. elegans. Current biology : CB 73 23499532
2018 Nuclear receptor HNF4A transrepresses CLOCK:BMAL1 and modulates tissue-specific circadian networks. Proceedings of the National Academy of Sciences of the United States of America 70 30530698
2013 MicroRNA-24/MODY gene regulatory pathway mediates pancreatic β-cell dysfunction. Diabetes 68 23761103
2008 The diabetic phenotype in HNF4A mutation carriers is moderated by the expression of HNF4A isoforms from the P1 promoter during fetal development. Diabetes 66 18356407
2020 Update on clinical screening of maturity-onset diabetes of the young (MODY). Diabetology & metabolic syndrome 65 32528556
1997 Hepatic function in a family with a nonsense mutation (R154X) in the hepatocyte nuclear factor-4alpha/MODY1 gene. The Journal of clinical investigation 64 9294105
2018 Hnf4a deletion in the mouse kidney phenocopies Fanconi renotubular syndrome. JCI insight 62 30046000
2019 Novel insights into genetics and clinics of the HNF1A-MODY. Endocrine regulations 61 31517624
2020 Clinical features, complications and treatment of rarer forms of maturity-onset diabetes of the young (MODY) - A review. Journal of diabetes and its complications 60 32763092
2009 Molecular interactions between HNF4a, FOXA2 and GABP identified at regulatory DNA elements through ChIP-sequencing. Nucleic acids research 58 19822575
2008 HNF4 alpha and the Ca-channel TRPC1 are novel disease candidate genes in diabetic nephropathy. Diabetes 58 18184923
2022 Precision diabetes: Lessons learned from maturity-onset diabetes of the young (MODY). Journal of diabetes investigation 55 35638342
2020 ABAT and ALDH6A1, regulated by transcription factor HNF4A, suppress tumorigenic capability in clear cell renal cell carcinoma. Journal of translational medicine 54 32093682
2020 HNF4A-AS1/hnRNPU/CTCF axis as a therapeutic target for aerobic glycolysis and neuroblastoma progression. Journal of hematology & oncology 54 32216806
2020 Control of Cell Identity by the Nuclear Receptor HNF4 in Organ Pathophysiology. Cells 53 32998360
2010 Deregulation of hepatocyte nuclear factor 4 (HNF4)as a marker of epithelial tumors progression. Experimental oncology 53 21403612
2002 Molecular etiologies of MODY and other early-onset forms of diabetes. Current diabetes reports 50 12643132
1999 Functional characterization of the MODY1 gene mutations HNF4(R127W), HNF4(V255M), and HNF4(E276Q). Diabetes 49 10389854
2023 HNF4A-BAP31-VDAC1 axis synchronously regulates cell proliferation and ferroptosis in gastric cancer. Cell death & disease 47 37296105
2019 HNF4A Haploinsufficiency in MODY1 Abrogates Liver and Pancreas Differentiation from Patient-Derived Induced Pluripotent Stem Cells. iScience 47 31195238
2020 Lineage-Specific Epigenomic and Genomic Activation of Oncogene HNF4A Promotes Gastrointestinal Adenocarcinomas. Cancer research 45 32332020
2020 Mir214-3p and Hnf4a/Hnf4α reciprocally regulate Ulk1 expression and autophagy in nonalcoholic hepatic steatosis. Autophagy 44 33078654
1999 Mitogen-activated protein kinase regulates transcription of the ApoCIII gene. Involvement of the orphan nuclear receptor HNF4. The Journal of biological chemistry 42 10551874
2022 HNF4A modulates glucocorticoid action in the liver. Cell reports 39 35443180
1998 MODY1 mutation Q268X in hepatocyte nuclear factor 4alpha allows for dimerization in solution but causes abnormal subcellular localization. Diabetes 39 9604881
2021 The nuclear receptor HNF4 drives a brush border gene program conserved across murine intestine, kidney, and embryonic yolk sac. Nature communications 38 34001900
2019 HNF4 factors control chromatin accessibility and are redundantly required for maturation of the fetal intestine. Development (Cambridge, England) 38 31345929
1996 A yeast artificial chromosome-based map of the region of chromosome 20 containing the diabetes-susceptibility gene, MODY1, and a myeloid leukemia related gene. Proceedings of the National Academy of Sciences of the United States of America 38 8632993
2019 Frequency and Characteristics of MODY 1 (HNF4A Mutation) and MODY 5 (HNF1B Mutation): Analysis From the DPV Database. The Journal of clinical endocrinology and metabolism 37 30535056
2000 Analysis of the HNF4 alpha gene in Caucasian type II diabetic nephropathic patients. Diabetologia 37 10768098
2024 HNF4A and HNF1A exhibit tissue specific target gene regulation in pancreatic beta cells and hepatocytes. Nature communications 35 38909044
2019 Genetic Dissection and Clinical Features of MODY6 (NEUROD1-MODY). Current diabetes reports 35 30793219
2016 Searching for Maturity-Onset Diabetes of the Young (MODY): When and What for? Canadian journal of diabetes 35 27103109
2011 Identification of HNF1A-MODY and HNF4A-MODY in Irish families: phenotypic characteristics and therapeutic implications. Diabetes & metabolism 35 21683639
2023 Multiple roles and regulatory mechanisms of the transcription factor HNF4 in the intestine. Frontiers in endocrinology 33 37635981
2007 HNF4A genetic variants: role in diabetes. Current opinion in clinical nutrition and metabolic care 33 17563455
2002 Maturity-onset diabetes of the young (MODY): genetic and clinical characteristics. Hormone research 33 11979019
2017 TET-Catalyzed 5-Hydroxymethylation Precedes HNF4A Promoter Choice during Differentiation of Bipotent Liver Progenitors. Stem cell reports 32 28648900
2007 Expression of HNF-4alpha (MODY1), HNF-1beta (MODY5), and HNF-1alpha (MODY3) proteins in the developing mouse pancreas. Gene expression patterns : GEP 32 17996499
2019 Molecular Basis for Autosomal-Dominant Renal Fanconi Syndrome Caused by HNF4A. Cell reports 30 31875549
2018 Identification of TAF1, HNF4A, and CALM2 as potential therapeutic target genes for liver fibrosis. Journal of cellular physiology 29 30317608
2022 AMPKα2/HNF4A/BORIS/GLUT4 pathway promotes hepatocellular carcinoma cell invasion and metastasis in low glucose microenviroment. Biochemical pharmacology 28 35940258
2005 The role of HNF4A variants in the risk of type 2 diabetes. Current diabetes reports 28 15794920
2020 Clinical implications of the glucokinase impaired function - GCK MODY today. Physiological research 27 33129248
2018 Role of conventional immunomarkers, HNF4-α and SATB2, in the differential diagnosis of pulmonary and colorectal adenocarcinomas. Histopathology 27 29243296
2014 HNF4A immunohistochemistry facilitates distinction between primary and metastatic breast and gastric carcinoma. Virchows Archiv : an international journal of pathology 27 24711169
2023 Elucidating the Proximal Tubule HNF4A Gene Regulatory Network in Human Kidney Organoids. Journal of the American Society of Nephrology : JASN 26 37488681
2021 Three-dimensional interactions between enhancers and promoters during intestinal differentiation depend upon HNF4. Cell reports 26 33503426
2018 Derivation and molecular characterization of pancreatic differentiated MODY1-iPSCs. Stem cell research 26 29990710
2017 RNA helicase DDX3 maintains lipid homeostasis through upregulation of the microsomal triglyceride transfer protein by interacting with HNF4 and SHP. Scientific reports 26 28128295
2009 Control of ACAT2 liver expression by HNF4{alpha}: lesson from MODY1 patients. Arteriosclerosis, thrombosis, and vascular biology 26 19478207
2000 R127W-HNF-4alpha is a loss of function mutation but not a rare polymorphism and causes Type II diabetes in a Japanese family with MODY1. Diabetologia 26 10819248
2023 TUBB2B facilitates progression of hepatocellular carcinoma by regulating cholesterol metabolism through targeting HNF4A/CYP27A1. Cell death & disease 25 36872411
2022 Epithelial HNF4A shapes the intraepithelial lymphocyte compartment via direct regulation of immune signaling molecules. The Journal of experimental medicine 25 35792863
2012 Regulation of neural stem cell differentiation by transcription factors HNF4-1 and MAZ-1. Molecular neurobiology 25 22944911
2024 Downregulation of HNF4A enables transcriptomic reprogramming during the hepatic acute-phase response. Communications biology 24 38755249
2022 Impaired hepatic glucose metabolism and liver-α-cell axis in mice with liver-specific ablation of the Hepatocyte Nuclear Factor 4α (Hnf4a) gene. Metabolism: clinical and experimental 24 36464036
2021 First Japanese Family With PDX1-MODY (MODY4): A Novel PDX1 Frameshift Mutation, Clinical Characteristics, and Implications. Journal of the Endocrine Society 23 34988346
2022 HNF4A Regulates the Proliferation and Tumor Formation of Cervical Cancer Cells through the Wnt/β-Catenin Pathway. Oxidative medicine and cellular longevity 22 35132353
2020 Genetics and Pathophysiology of Maturity-onset Diabetes of the Young (MODY): A Review of Current Trends. Oman medical journal 22 32489678
2018 COL4A3 Gene Variants and Diabetic Kidney Disease in MODY. Clinical journal of the American Society of Nephrology : CJASN 22 30012629
2014 Glucokinase gene mutations (MODY 2) in Asian Indians. Diabetes technology & therapeutics 22 24405491
1996 Maturity onset diabetes of the young (MODY). Diabetic medicine : a journal of the British Diabetic Association 22 8894490
2024 Maturity-onset diabetes of the young (MODY) - in search of ideal diagnostic criteria and precise treatment. Progress in cardiovascular diseases 21 38513726
2023 Structural insights into the HNF4 biology. Frontiers in endocrinology 21 37404310
2010 Double heterozygous mutations involving both HNF1A/MODY3 and HNF4A/MODY1 genes: a case report. Diabetes care 21 20705777
2008 The MODY1 gene for hepatocyte nuclear factor 4alpha and a feedback loop control COUP-TFII expression in pancreatic beta cells. Molecular and cellular biology 21 18474611
2025 Targeting FDFT1 Reduces Cholesterol and Bile Acid Production and Delays Hepatocellular Carcinoma Progression Through the HNF4A/ALDOB/AKT1 Axis. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 20 39899681
2024 Decreased lncRNA HNF4A-AS1 facilitates resistance to sorafenib-induced ferroptosis of hepatocellular carcinoma by reprogramming lipid metabolism. Theranostics 20 39629121
2023 Hnf4 activates mimetic-cell enhancers to recapitulate gut and liver development within the thymus. The Journal of experimental medicine 20 37399024
1997 Maturity-onset diabetes of the young (MODY), MODY genes and non-insulin-dependent diabetes mellitus. Diabetes & metabolism 20 9162575
2016 When is it MODY? Challenges in the Interpretation of Sequence Variants in MODY Genes. The review of diabetic studies : RDS 18 27111119
2016 Claudin-based barrier differentiation in the colonic epithelial crypt niche involves Hopx/Klf4 and Tcf7l2/Hnf4-α cascades. Tissue barriers 17 27583195
2000 Reduced pancreatic polypeptide response to hypoglycemia and amylin response to arginine in subjects with a mutation in the HNF-4alpha/MODY1 gene. Diabetes 17 10866048

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