Affinage

IRX5

Iroquois-class homeodomain protein IRX-5 · UniProt P78411

Length
483 aa
Mass
50.4 kDa
Annotated
2026-06-10
38 papers in source corpus 26 papers cited in narrative 26 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/8 claims corpus-supported (88%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

IRX5 is a homeodomain transcription factor that controls cell-type identity, differentiation, and excitable-cell function across the heart, retina, brain, gonad, skeleton, and adipose tissue, acting context-dependently as a transcriptional repressor or activator (PMID:16239150, PMID:35245131, PMID:33859429). In the ventricular myocardium it establishes transmural electrical and contractile heterogeneity by repressing the Kv4.2 (Kcnd2) potassium-channel gene—through recruitment of the cardiac repressor mBop—to generate the inverse Ito,f gradient required for coordinated repolarization, with loss of Irx5 reducing endocardial cardiomyocyte contractility in a Kcnd2-dependent manner (PMID:16239150, PMID:35245131). It also forms a complex with GATA4 that potentiates SCN5A/Nav1.5 induction, and its loss in patient-derived cardiomyocytes slows depolarization through reduced sodium current (PMID:32898233); in conduction tissue Irx5 acts redundantly with Irx3, the pair repressing Bmp10 and Nav1.5 (PMID:22992950). In retinal development Irx5 specifies OFF cone bipolar cell differentiation independently of Vsx1 and, together with Vsx1, tunes OFF-circuit response properties (PMID:16182275, PMID:18322081). In the hypothalamus Irx3/Irx5 restrain neurogenesis from radial-glia-like neural stem cells, controlling the number of leptin-sensing arcuate neurons and thereby feeding and energy balance (PMID:33859429, PMID:34705510). In metabolic and skeletal tissues IRX5 acts downstream of WNT/β-catenin to direct chondrocyte-to-osteoblast and mesenchymal cell-fate decisions and to modulate thermogenesis via PGC-1α/UCP1 (PMID:32662900, PMID:32108023, PMID:36115924). IRX5 transcriptional output is shaped by direct protein partners GATA3, TRPS1, and GATA4, and its nuclear translocation requires HMGN4 (PMID:22581230, PMID:32898233, PMID:40208102). Human loss-of-function mutations in IRX5 cause Hamamy syndrome (PMID:32898233).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 2005 High

    Established the first molecular mechanism for IRX5 in cardiac physiology by showing it sets the ventricular repolarization gradient through repression of a specific ion-channel gene.

    Evidence Irx5 knockout mice with chromatin co-IP, electrophysiology, and gradient immunofluorescence

    PMID:16239150

    Open questions at the time
    • Did not define how Irx5 binds the Kcnd2 locus
    • mBop recruitment shown in heart only; generality to other Irx5 targets unknown
  2. 2005 High

    Defined a developmental role for Irx5 in retinal cell-type specification, distinct from the known Vsx1 bipolar-cell pathway.

    Evidence Irx5 knockout mice, cell-type marker IHC, Irx5/Vsx1 epistasis

    PMID:16182275

    Open questions at the time
    • Direct transcriptional targets in bipolar cells not identified
    • Cofactors mediating differentiation unknown
  3. 2008 High

    Extended the retinal role to circuit-level function, showing Irx5 with Vsx1 selectively tunes OFF visual pathway physiology rather than morphology.

    Evidence Vsx1/Irx5 double-KO mice, multi-electrode array recording, contrast adaptation modeling

    PMID:18322081

    Open questions at the time
    • Molecular targets underlying altered gain/threshold unknown
    • Functional separation of Irx5 vs Vsx1 contributions not resolved
  4. 2012 High

    Identified direct protein partners (GATA3, TRPS1) for IRX5 and linked it to progenitor migration via Sdf1 repression, while connecting IRX5 mutations to human disease.

    Evidence Xenopus loss-of-function, protein-protein interaction assays, human homozygosity mapping

    PMID:22581230

    Open questions at the time
    • Structural basis of GATA3/TRPS1 interaction not defined
    • Whether Sdf1 repression generalizes beyond branchial arches/gonads unknown
  5. 2012 High

    Resolved functional redundancy and antagonism between Irx3 and Irx5 in the endocardium and myocardium, refining the model of cardiac patterning and conduction.

    Evidence Irx3/Irx5 double and conditional KO mice, RT-PCR, electrophysiology, epistasis

    PMID:22992950

    Open questions at the time
    • Mechanism by which Irx5 represses Irx3 activity unknown
    • Direct vs indirect repression of Bmp10/Nav1.5 not fully separated
  6. 2021 High

    Defined a positive, GATA4-dependent arm of IRX5 cardiac function on SCN5A, complementing its repressive role and explaining the depolarization defect in patient cells.

    Evidence Hamamy-syndrome hiPSC-cardiomyocytes, patch clamp, Co-IP, transcriptomics

    PMID:32898233

    Open questions at the time
    • Structure/stoichiometry of the IRX5-GATA4 complex unknown
    • Whether the same complex acts at other cardiac genes untested
  7. 2021 High

    Established Irx3/Irx5 as dosage-sensitive regulators of postnatal hypothalamic neurogenesis controlling feeding and leptin response.

    Evidence Irx3/Irx5 double-heterozygous mice, lineage tracing, scRNA-seq, leptin/food-intake assays

    PMID:33859429

    Open questions at the time
    • Direct transcriptional targets in radial-glia-like NSCs not identified
    • Relative contribution of Irx3 vs Irx5 not separated
  8. 2021 Medium

    Showed that ectopic Irx3/Irx5 expression is the mechanism disrupting PVH development in Sim1 haploinsufficiency, linking IRX dosage to a genetic obesity syndrome.

    Evidence scRNA-seq, Irx dosage reduction in Sim1+/- mice, PVH-specific Irx3 deletion, food intake

    PMID:34705510

    Open questions at the time
    • How Sim1 normally restrains Irx3/Irx5 not defined
    • Irx5-specific contribution within the rescue not isolated
  9. 2022 High

    Linked the Irx5-Ito,f axis to mechanical function, showing Irx5 controls transmural contractility, not just electrical repolarization.

    Evidence Irx5-KO, KV4.2-KO, double-KO mice, cardiomyocyte contractility/Ca2+ measurement, echocardiography

    PMID:35245131

    Open questions at the time
    • Mechanistic coupling of Ito,f gradient to contractility incompletely defined
    • Role of Kcnip2 regulation by Irx5 not fully separated from Kcnd2
  10. 2020 Medium

    Placed Irx3/Irx5 downstream of WNT/β-catenin in gonad and skeletal cell-fate decisions, identifying TCF/LEF enhancers and sex-specific epigenetic control of the IrxB locus.

    Evidence ATAC/ChIP-seq analysis, gonad explant reporter assays, β-catenin gain/loss, lineage tracing, micro-CT (two studies)

    PMID:32108023 PMID:32662900

    Open questions at the time
    • Downstream osteoblast/chondrocyte targets of Irx5 not enumerated
    • Irx5-specific versus Irx3 roles not separated
  11. 2018 Medium

    Documented context-dependent roles of IRX5 in adipose metabolism and multiple cancers, mapping target promoters and signaling outputs.

    Evidence Irx5-KO mice, adipocyte knockdown, promoter-luciferase, Seahorse; gain/loss in TSCC, CRC cells with promoter assays and xenografts

    PMID:29463648 PMID:29761910 PMID:30538277

    Open questions at the time
    • Apparent opposing effects on PGC-1α/UCP1 across tissues unresolved
    • Direct vs indirect regulation of cancer-associated targets not always established
  12. 2024 Medium

    Identified HMGN4 as the factor driving IRX5 nuclear translocation, providing a mechanism for regulated IRX5 activity, and extended IRX5 function to hepatic lipid synthesis.

    Evidence GST pull-down, Co-IP, immunofluorescence co-localization in HCC cells

    PMID:40208102

    Open questions at the time
    • Whether HMGN4-dependent import operates in non-cancer tissues unknown
    • Interaction not reciprocally validated across systems
  13. 2024 Medium

    Defined IRX5 as a suppressor of osteogenesis through inhibition of mTOR-dependent translation and oxidative phosphorylation in human BMSCs.

    Evidence Gain/loss-of-function in hBMSCs, RNA-seq, SUnSET translation assay, Seahorse, mTOR-activator rescue

    PMID:38666481

    Open questions at the time
    • Direct transcriptional targets linking IRX5 to mTOR not identified
    • Reconciliation with PLAGL1-KLF4-IRX5 pro-osteogenic axis unresolved
  14. 2023 Medium

    Revealed a chromatin/repair role for IRX5 in hair follicle stem cell activation, with BRCA1 as a downstream target and Fgf18 suppression contributing to anagen onset.

    Evidence Irx5-/- mice, ATAC-seq of HFSCs, ChIP/reporter for BRCA1, FGF-kinase-inhibitor rescue

    PMID:37084727

    Open questions at the time
    • Direct binding of IRX5 to BRCA1/Fgf18 loci versus indirect effects not fully resolved
    • Generality of DNA-repair role beyond HFSCs unknown
  15. 2026 Medium

    Positioned IRX5 within a PLAGL1-KLF4-IRX5 transcriptional axis driving osteoblast differentiation during bone regeneration.

    Evidence PLAGL1-KO mice, CRISPR-dCas9-Tet1 epigenetic activation, reporter assays, mandible regeneration model

    PMID:42168182

    Open questions at the time
    • Direct osteogenic targets induced by IRX5 not enumerated
    • Apparent contradiction with IRX5 suppression of osteogenesis in hBMSCs unresolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • The molecular logic dictating whether IRX5 represses or activates a given target—and how its cofactor repertoire (mBop, GATA4, GATA3, TRPS1, HMGN4) selects context-specific programs—remains unresolved.
  • No structural model of IRX5 DNA binding or cofactor complexes
  • Tissue-specific direct target catalogs largely undefined
  • Opposing metabolic/osteogenic phenotypes across tissues not mechanistically reconciled

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 7 GO:0003677 DNA binding 5
Localization
GO:0005634 nucleus 1
Pathway
R-HSA-1266738 Developmental Biology 6 R-HSA-162582 Signal Transduction 3 R-HSA-74160 Gene expression (Transcription) 3
Partners
BHLHB9GATA3GATA4HMGN4TRPS1

Evidence

Reading pass · 26 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2005 Irx5 represses Kv4.2 (Kcnd2) potassium-channel gene expression in endocardial myocardium by recruiting mBop (a cardiac transcriptional repressor), establishing an inverse Ito,f gradient that ensures coordinated cardiac ventricular repolarization and prevents arrhythmias. Irx5 knockout mice, chromatin co-IP (recruitment of mBop), electrophysiology (Ito,f measurement), immunofluorescence gradient analysis Cell High 16239150
2005 Irx5 is expressed in a subset of cone bipolar cells in the mature mouse retina (Type 2 and Type 3 OFF cone bipolar cells) starting at postnatal day 5, and is required for their differentiation independently of the Vsx1 pathway, as Irx5-deficient mice lack certain bipolar cell markers while Vsx1 expression is unaffected. Irx5 knockout mice, immunohistochemistry with cell-type specific markers, genetic epistasis (Irx5/Vsx1 double mutant analysis) Developmental biology High 16182275
2008 Vsx1 and Irx5 together control response threshold, gain, range, and contrast adaptation specifically in OFF (not ON) retinal ganglion cell circuits, demonstrated by loss-of-function in Vsx1−/−Irx5−/− double-mutant mice; bipolar cell morphology was normal but OFF circuit function was selectively impaired. Vsx1/Irx5 double knockout mice, multi-electrode array retinal ganglion cell recording, linear-nonlinear model of contrast adaptation The Journal of neuroscience High 18322081
2012 Irx5 modulates migration of progenitor cell populations in branchial arches and gonads by repressing Sdf1 expression; transcriptional control by Irx5 is modulated by direct protein-protein interaction with GATA3 and TRPS1 zinc-finger proteins. In vivo modeling in Xenopus laevis embryos (loss-of-function), protein-protein interaction assays, homozygosity mapping in human patients with IRX5 mutations Nature genetics High 22581230
2012 Irx3 and Irx5 have redundant function in the endocardium to regulate atrioventricular canal morphogenesis and outflow tract formation via direct transcriptional repression of Bmp10; combined postnatal loss of Irx3 and Irx5 in the myocardium activates Nav1.5 expression and prolongs atrioventricular conduction; postnatal Irx5 can repress Irx3 activity, as combined loss restores the repolarization gradient lost in Irx5-single mutants. Irx3/Irx5 double knockout and conditional knockout mice, RT-PCR, electrophysiology, genetic epistasis Development (Cambridge, England) High 22992950
2021 IRX5 forms a transcription factor complex with GATA4 in cardiac cells, in which IRX5 potentiates GATA4-induction of SCN5A (Nav1.5) expression; loss-of-function mutations in IRX5 in human hiPSC-derived cardiomyocytes reduce Nav1.5 and Cx40 expression and slow ventricular action potential depolarization due to reduced sodium current. hiPSC-derived cardiomyocytes from Hamamy syndrome patients with IRX5 loss-of-function mutations, electrophysiology (patch clamp), Co-IP (IRX5-GATA4 complex identification), transcriptomic analysis Cardiovascular research High 32898233
2003 Irx5 is a direct, positively regulated downstream transcriptional target of Hoxb4. Chick embryo gain-of-function experiments, reporter assays demonstrating direct transcriptional regulation Developmental dynamics Medium 12701098
2018 IRX5 promotes proliferation, migration, and invasion of tongue squamous cell carcinoma cells by directly targeting the osteopontin (OPN) promoter and activating the NF-κB pathway. Gain- and loss-of-function in CAL27 cells, promoter binding assays, xenograft tumor model, Western blot Journal of cellular and molecular medicine Medium 29761910
2018 IRX5 regulates adipocyte amyloid precursor protein (APP) expression by increasing APP promoter activity; both IRX5 and APP inhibit transactivation of PGC-1α and UCP1; knockdown of Irx5 or App increases mitochondrial respiration in adipocytes; Irx5 knockout mice are protected from diet-induced fat accumulation with upregulated Pgc-1α and Ucp1. Irx5 knockout mice (HF diet model), stable Irx5 knockdown in adipocytes, transcriptome analysis, transcriptional activation assays (APP promoter-luciferase), Seahorse metabolic assay International journal of obesity Medium 30538277
2019 IRX5 promotes colorectal cancer cell migration and invasion by inhibiting the core components of the RHOA/ROCK1/LIMK1 signaling pathway; overexpression of LIMK1 reverses the enhanced cellular motility caused by IRX5 overexpression. IRX5 overexpression/knockdown in CRC cells, migration/invasion assays, rescue with LIMK1 overexpression, in vivo nude mouse metastasis model Molecular carcinogenesis Medium 31432570
2016 IRX5 promotes G1/S-phase transition in vascular smooth muscle cells (VSMCs) via CDK2-dependent activation; Irx5 gain- and loss-of-function modulates DNA synthesis and regulates expression of p27(kip1), E2F1, and PCNA; IRX5 overexpression also induces apoptosis via caspase-3 activation; Irx5 expression is elevated in vivo in balloon-injured rat carotid arteries. Thymidine/BrdU incorporation assays in primary rat aortic VSMCs, RT-PCR, immunohistochemistry of injured arteries, caspase-3 activation assay American journal of physiology. Cell physiology Medium 27170637
2018 During follicle development, Irx3 and Irx5 are colocalized in pre-granulosa cells; Irx5 transitions to granulosa cell-specific expression during primordial follicle formation. Loss of both Irx3 and Irx5 causes defects in granulosa cell basement membrane deposition, mis-localization of gap junction proteins, and fewer cell projections, compromising granulosa cell-oocyte communication. Multiple Irx3/Irx5 mutant mouse models, reporter mice for lineage tracing, immunofluorescence, histology PLoS genetics Medium 30071018
2020 Canonical Wnt/β-catenin signaling directly stimulates Irx3 and Irx5 transcription in the developing ovary through TCF/LEF-binding sequences in two distal enhancers of the IrxB locus; in the developing testis, these same sites carry H3K27me3 marks that suppress Irx3 and Irx5 transcription. ATAC-seq and ChIP-seq database analysis, mouse gonad explant transfection/reporter assays, β-catenin gain/loss-of-function in gonads Development (Cambridge, England) Medium 32108023
2020 IRX3 and IRX5 inhibit adipogenic differentiation of hypertrophic chondrocytes and promote their transition to osteoblasts; this function is downstream of WNT/β-catenin signaling, as β-catenin gain- and loss-of-function in hypertrophic chondrocytes affects Irx3 and Irx5 expression. Irx3/Irx5 single and compound null mutant mice, lineage tracing, bone histomorphometry, micro-CT, β-catenin conditional KO and gain-of-function in hypertrophic chondrocytes Journal of bone and mineral research Medium 32662900
2021 Irx3 and Irx5 regulate postnatal hypothalamic neurogenesis from a radial glia-like neural stem cell (RGL-NSC) population; reduced Irx3/Irx5 dosage promotes neurogenesis leading to elevated numbers of leptin-sensing arcuate neurons, resulting in enhanced leptin response and lower food intake. Irx3/Irx5 double heterozygous mice, Ins2-Cre lineage tracing, single-cell RNA sequencing, leptin response assays, food intake measurement Nature metabolism High 33859429
2021 Irx3 and Irx5 are ectopically expressed in Sim1+ PVH neurons of Sim1+/− mice; reducing Irx3/Irx5 dosage or PVH-specific deletion of Irx3 rescues PVH neuron defects and hyperphagia in Sim1+/− mice, demonstrating that misexpression of Irx3 and Irx5 is a central mechanism disrupting PVH development and feeding regulation in Sim1 haploinsufficiency. Single-cell RNA sequencing, Irx3/Irx5 dosage reduction in Sim1+/− mice, PVH-specific conditional Irx3 deletion, food intake measurement Science advances Medium 34705510
2022 Irx5 is a vital transcription factor that establishes transmural heterogeneity of ventricular myocyte contractility by regulating Ito,f gradients (via Kcnd2 and Kcnip2 expression specifically in endocardium); Irx5-KO mice show decreased global LV contractility and reduced cell shortening/Ca2+ transients in endocardial but not epicardial cardiomyocytes; double KO of Irx5 and Kcnd2 restores contractility to KV4.2-KO levels, demonstrating dominant role of Irx5-dependent Ito,f. Irx5-KO, KV4.2-KO, and Irx5/KV4.2 double-KO mice, isolated cardiomyocyte contractility/Ca2+ measurements, transcriptional profiling, echocardiography American journal of physiology. Heart and circulatory physiology High 35245131
2022 IRX5 promotes adipogenesis of human bone marrow-derived mesenchymal stem cells (hMSCs) by transcriptionally activating PGC-1α and inhibiting glycolysis; metformin and PGC-1α inhibitor reverse IRX5-induced adipogenesis. Lentiviral IRX5 gain/loss-of-function in hMSCs, RNA-seq, metabolomics, dual-luciferase reporter assay (PGC-1α promoter), adipogenesis assays Cell death discovery Medium 35428362
2022 Irx5 deficiency in mice protects against diet-induced obesity primarily through increased adipose thermogenesis (upregulation of PGC-1α and UCP1) and improved hypothalamic leptin response; scRNA-seq of the arcuate-median eminence region shows elevated neuron numbers in Irx5KO mice. Irx5 knockout mice on high-fat diet, body composition measurement, energy expenditure assays, scRNA-seq of hypothalamic ARC-ME region International journal of obesity Medium 36115924
2023 IRX5 promotes DNA damage repair and hair follicle stem cell (HFSC) activation; Irx5-/- mice show delayed anagen onset, increased DNA damage, diminished HFSC proliferation, and open chromatin near cell cycle and DNA damage repair genes; BRCA1 is an IRX5 downstream transcriptional target; Irx5-/- quiescence is partly due to failure to suppress Fgf18, as FGF kinase signaling inhibition partially rescues the anagen delay. Irx5-/- mice, ATAC-seq of HFSCs, ChIP/reporter assays for BRCA1 as downstream target, pharmacological rescue with FGF kinase inhibitor, proliferation/DNA damage assays Stem cell reports Medium 37084727
2018 IRX3 and IRX5 are essential for mammalian nephrogenesis; in Wilms tumour, IRX5 expression is activated in early proliferative blastema and IRX5-/- Wilms tumour cells activate Hippo and non-canonical WNT signaling, generating small tumours with abundant tubulogenesis. Irx3-/Irx5- double knockout mice (embryonic nephron formation), orthotopic xenograft mouse model with IRX3-/- and IRX5-/- Wilms tumour cells, pathway analysis The Journal of pathology Medium 30246301
2018 Id2 represses Irx5 in the midgut endoderm to establish intestinal identity; transgenic mice expressing Irx5 in midgut endoderm develop gastric metaplasia-like intestinal tumors, recapitulating the Id2-/- phenotype. Id2-/- mice, Irx5 transgenic mice with midgut-specific expression, gene expression analysis, histology Molecular and cellular biology Medium 29463648
2024 IRX5 interacts directly with HMGN4; HMGN4 drives IRX5 nuclear translocation and co-localizes with IRX5 in the nucleus; IRX5 promotes de novo fatty acid synthesis in hepatocellular carcinoma, accelerating cancer cell proliferation and progression. GST pull-down combined with GC/MS, co-immunoprecipitation, immunofluorescence co-localization, HMGN4 overexpression effects on IRX5 nuclear transport Journal of cellular and molecular medicine Medium 40208102
2024 IRX5 suppresses osteogenic differentiation of human BMSCs by inhibiting mTOR-mediated ribosomal translation and impairing mitochondrial oxidative phosphorylation; mTOR activator MHY1485 reverses the inhibitory impact of IRX5 on osteogenesis. IRX5 gain/loss-of-function in hBMSCs, RNA-seq, transmission electron microscopy, Seahorse mito-stress assay, Surface Sensing of Translation (SUnSET) assay, pharmacological rescue with mTOR activator Journal of cellular physiology Medium 38666481
2024 IRX5 transcriptionally regulates YWHAB (14-3-3β) expression by acting on its promoter sequence upstream of the transcription start site, as demonstrated by dual luciferase assay. Dual luciferase reporter assay, gain/loss-of-function in breast cancer cells Oncology letters Low 39119237
2026 PLAGL1 transcriptionally activates Irx5 synergistically with KLF4 in periosteal stem/progenitor cells (PSPCs), and IRX5 in turn induces downstream osteogenic genes; this PLAGL1-KLF4-IRX5 axis controls osteoblast differentiation of PSPCs during mandibular bone regeneration. PLAGL1 KO mice, CRISPR-dCas9-Tet1 epigenetic activation system, transcriptional reporter assays, mandible regeneration model Nature communications Medium 42168182

Source papers

Stage 0 corpus · 38 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2005 The homeodomain transcription factor Irx5 establishes the mouse cardiac ventricular repolarization gradient. Cell 194 16239150
2021 Extensive pleiotropism and allelic heterogeneity mediate metabolic effects of IRX3 and IRX5. Science (New York, N.Y.) 93 34083488
2005 The Iroquois homeobox gene, Irx5, is required for retinal cone bipolar cell development. Developmental biology 87 16182275
2012 Cooperative and antagonistic roles for Irx3 and Irx5 in cardiac morphogenesis and postnatal physiology. Development (Cambridge, England) 74 22992950
2012 Mutations in IRX5 impair craniofacial development and germ cell migration via SDF1. Nature genetics 68 22581230
2000 Identification of a novel mouse Iroquois homeobox gene, Irx5, and chromosomal localisation of all members of the mouse Iroquois gene family. Developmental dynamics : an official publication of the American Association of Anatomists 59 10822268
2020 IRX3 and IRX5 Inhibit Adipogenic Differentiation of Hypertrophic Chondrocytes and Promote Osteogenesis. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 40 32662900
2021 Irx3 and Irx5 in Ins2-Cre+ cells regulate hypothalamic postnatal neurogenesis and leptin response. Nature metabolism 35 33859429
2008 Genetic control of circuit function: Vsx1 and Irx5 transcription factors regulate contrast adaptation in the mouse retina. The Journal of neuroscience : the official journal of the Society for Neuroscience 34 18322081
2021 Irx3 and Irx5 - Novel Regulatory Factors of Postnatal Hypothalamic Neurogenesis. Frontiers in neuroscience 32 34795556
2018 IRX5 regulates adipocyte amyloid precursor protein and mitochondrial respiration in obesity. International journal of obesity (2005) 30 30538277
2018 Long-Noncoding RNA Colorectal Neoplasia Differentially Expressed Gene as a Potential Target to Upregulate the Expression of IRX5 by miR-136-5P to Promote Oncogenic Properties in Hepatocellular Carcinoma. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 29 30423553
2018 The Iroquois homeobox proteins IRX3 and IRX5 have distinct roles in Wilms tumour development and human nephrogenesis. The Journal of pathology 27 30246301
2018 Dynamic expression patterns of Irx3 and Irx5 during germline nest breakdown and primordial follicle formation promote follicle survival in mouse ovaries. PLoS genetics 25 30071018
2001 Developmental expression of the Xenopus Iroquois-family homeobox genes, Irx4 and Irx5. Development genes and evolution 25 11455441
2019 IRX5 promotes colorectal cancer metastasis by negatively regulating the core components of the RHOA pathway. Molecular carcinogenesis 24 31432570
2018 IRX5 promotes NF-κB signalling to increase proliferation, migration and invasion via OPN in tongue squamous cell carcinoma. Journal of cellular and molecular medicine 24 29761910
2021 Human model of IRX5 mutations reveals key role for this transcription factor in ventricular conduction. Cardiovascular research 21 32898233
2003 TALE class homeodomain gene Irx5 is an immediate downstream target for Hoxb4 transcriptional regulation. Developmental dynamics : an official publication of the American Association of Anatomists 20 12701098
2022 The Hematopoietic TALE-Code Shows Normal Activity of IRX1 in Myeloid Progenitors and Reveals Ectopic Expression of IRX3 and IRX5 in Acute Myeloid Leukemia. International journal of molecular sciences 16 35328612
2015 Complete re-sequencing of a 2Mb topological domain encompassing the FTO/IRXB genes identifies a novel obesity-associated region upstream of IRX5. Genome medicine 16 26642925
2020 IRX3 and IRX5 collaborate during ovary development and follicle formation to establish responsive granulosa cells in the adult mouse†. Biology of reproduction 15 32507881
2022 Deficiency of Irx5 protects mice from obesity and associated metabolic abnormalities. International journal of obesity (2005) 10 36115924
2021 Ectopic expression of Irx3 and Irx5 in the paraventricular nucleus of the hypothalamus contributes to defects in Sim1 haploinsufficiency. Science advances 10 34705510
2016 Iroquois homeobox transcription factor (Irx5) promotes G1/S-phase transition in vascular smooth muscle cells by CDK2-dependent activation. American journal of physiology. Cell physiology 10 27170637
2022 IRX5 promotes adipogenesis of hMSCs by repressing glycolysis. Cell death discovery 9 35428362
2018 Id2 Determines Intestinal Identity through Repression of the Foregut Transcription Factor Irx5. Molecular and cellular biology 9 29463648
2020 Canonical Wnt/β-catenin activity and differential epigenetic marks direct sexually dimorphic regulation of Irx3 and Irx5 in developing mouse gonads. Development (Cambridge, England) 8 32108023
2020 IRX5 prompts genomic instability in colorectal cancer cells. Journal of cellular biochemistry 8 32162364
2024 IRX5's influence on macrophage polarization and outcome in papillary thyroid cancer. Frontiers in oncology 6 38868535
2024 YWHAB is regulated by IRX5 and inhibits the migration and invasion of breast cancer cells. Oncology letters 6 39119237
2023 IRX5 promotes DNA damage repair and activation of hair follicle stem cells. Stem cell reports 6 37084727
2025 IRX5 Promoted SREBP1-Mediated de Novo Fatty Acid Synthesis via HMGN4 in Hepatocellular Carcinoma. Journal of cellular and molecular medicine 3 40208102
2024 IRX5 suppresses osteogenic differentiation of hBMSCs by inhibiting protein synthesis. Journal of cellular physiology 3 38666481
2021 Generation of three human induced pluripotent stem cell lines with IRX5 knockout and knockin genetic editions using CRISPR-Cas9 system. Stem cell research 3 34929443
2022 Irx5 and transient outward K+ currents contribute to transmural contractile heterogeneities in the mouse ventricle. American journal of physiology. Heart and circulatory physiology 2 35245131
2024 A novel genetic mouse model of osteoporosis with double heterozygosity of Irx3 and Irx5 characterizes sex-dependent phenotypes in bone homeostasis. Bone 1 39401533
2026 The PLAGL1-KLF4-IRX5 axis promotes the osteogenesis of periosteal progenitors during mandible regeneration. Nature communications 0 42168182

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