Affinage

MNX1

Motor neuron and pancreas homeobox protein 1 · UniProt P50219

Length
401 aa
Mass
40.6 kDa
Annotated
2026-04-28
100 papers in source corpus 36 papers cited in narrative 35 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

MNX1 (HB9/HLXB9) encodes a homeodomain transcription factor that functions primarily as a transcriptional repressor to consolidate cell identity in motor neurons and pancreatic endocrine lineages. In the developing spinal cord, MNX1 suppresses interneuron genetic programs (e.g., Chx10) in postmitotic motor neurons, and its loss causes motor neurons to transiently acquire V2 interneuron features with defective migration and axonal projection (PMID:10482234, PMID:10482235); in the pancreas, MNX1 is required for dorsal pancreas initiation and beta-cell differentiation, actively promoting beta-cell fate while suppressing alpha- and delta-cell programs, with loss-of-function mutations causing permanent neonatal diabetes in humans and heterozygous homeodomain mutations causing autosomal dominant Currarino syndrome (PMID:10471501, PMID:24411943, PMID:9843207, PMID:26534984). MNX1 binds target gene promoters via its homeodomain to repress genes including PTGER2 and CDKN1A and activate targets including CCNE1/CCNE2, is post-translationally stabilized in the nucleus by GSK-3β phosphorylation at Ser-78/Ser-80, and is regulated upstream by PTF1a, Pax6b, and the PI3K/AKT pathway (PMID:23048027, PMID:24425879, PMID:22232429, PMID:30012177). In hematopoietic cells, chromosomal translocations drive ectopic MNX1 expression through enhancer hijacking, and MNX1 induces AML from fetal hematopoietic progenitors by broadly increasing H3K4 methylation and reducing H3K27me3, a mechanism blocked by the SAM analog Sinefungin (PMID:37317878, PMID:39121370).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 1998 High

    Establishing MNX1 as a disease gene: heterozygous mutations in the HLXB9 homeodomain were identified as causative for Currarino syndrome, linking the gene's DNA-binding domain to human caudal developmental defects.

    Evidence Sanger sequencing and linkage analysis in familial and sporadic Currarino syndrome patients

    PMID:9843207

    Open questions at the time
    • Mechanism by which haploinsufficiency causes sacral agenesis is unknown
    • No animal model recapitulating Currarino phenotype was available
  2. 1999 High

    Knockout studies simultaneously established MNX1 as essential for two distinct developmental programs—motor neuron identity consolidation (by repressing interneuron genes) and dorsal pancreas initiation/beta-cell differentiation—revealing it as a cell-fate selector in both neural and endocrine lineages.

    Evidence Independent Hb9/Hlxb9 knockout mouse studies with histological, molecular, and axonal phenotyping

    PMID:10471501 PMID:10471502 PMID:10482234 PMID:10482235

    Open questions at the time
    • Direct transcriptional targets were not identified
    • Whether MNX1 acts as activator or repressor was unresolved
    • Mechanism of V2 interneuron gene derepression unknown
  3. 2001 High

    Two new dimensions of MNX1 biology emerged: temporal regulation proved critical for pancreatic morphogenesis (persistent expression redirects epithelium to intestinal fate), and the HLXB9-ETV6 fusion transcript from t(7;12) was identified in infant AML, implicating MNX1 in leukemogenesis.

    Evidence Transgenic overexpression via Pdx1 promoter in mice; RT-PCR fusion transcript detection in AML patient samples

    PMID:11454678 PMID:11784060

    Open questions at the time
    • Whether the fusion protein or ectopic wild-type MNX1 drives leukemogenesis was unclear
    • Mechanism of pancreatic-to-intestinal fate switch was not molecularly defined
  4. 2004 Medium

    The homeodomain of MNX1 was shown to harbor two functional nuclear localization signals sufficient for nuclear import, explaining how homeodomain mutations could disrupt both DNA binding and subcellular targeting.

    Evidence GFP-NLS fusion import assays in primary keratinocytes; immunoelectron microscopy

    PMID:15338230

    Open questions at the time
    • Context-dependent cytoplasmic localization (ER/Golgi) was observed but unexplained
    • No confirmation in motor neurons or beta-cells
  5. 2005 Medium

    MNX1 was linked to transcriptional activation of IL6 in Hodgkin lymphoma and shown to be ectopically activated via enhancer hijacking from MYB in AML, broadening its oncogenic roles beyond t(7;12).

    Evidence Antisense knockdown plus forced expression plus IL6 promoter reporter; FISH breakpoint mapping in GDM-1 cell line

    PMID:15540222 PMID:15772702

    Open questions at the time
    • Direct MNX1 binding to IL6 promoter not demonstrated by ChIP
    • Enhancer hijacking mechanism not confirmed at chromatin level
  6. 2007 High

    In C. elegans, the HB9 ortholog CEH-12 was shown to specify synaptic partner choice in motor neurons downstream of UNC-4/Groucho repression, extending the conserved role of HB9 family members in motor neuron subtype identity to synaptic connectivity.

    Evidence Cell-specific microarray, genetic epistasis, and synaptic input specificity assays in C. elegans

    PMID:17289921

    Open questions at the time
    • Whether mammalian HB9 similarly specifies synaptic input choice is untested
    • Direct transcriptional targets of CEH-12 mediating synaptic specificity unknown
  7. 2007 High

    Hb9-expressing spinal interneurons were characterized as rhythmically active neurons electrotonically coupled to heterogeneous networks via gap junctions, with persistent sodium current (INaP) driving locomotor-related oscillations, defining their electrophysiological properties within the locomotor central pattern generator.

    Evidence Two-photon calcium imaging, paired patch-clamp, pharmacological dissection (carbenoxolone, riluzole) in Hb9:eGFP transgenic mice

    PMID:17715199 PMID:18667543 PMID:19759307

    Open questions at the time
    • Hb9 interneuron activity lags ventral root bursts, so their precise role in rhythm generation remains debated
    • Glutamatergic output from Hb9 interneurons was later shown dispensable for locomotion (PMID:34362940)
  8. 2011 High

    Zebrafish studies resolved MNX1's pancreatic function as a binary fate switch: Mnx1 promotes beta-cell and suppresses alpha-cell fate downstream of retinoic acid signaling in the endoderm, establishing a cell-autonomous role.

    Evidence Gene knockdown, cell transplantation, transgenic reporter analysis in zebrafish

    PMID:21989909

    Open questions at the time
    • Downstream transcriptional targets mediating the alpha-to-beta switch not identified
    • Whether this is direct transcriptional repression of alpha-cell genes was unresolved
  9. 2012 High

    The upstream regulation and direct target repertoire of MNX1 were defined: PTF1a directly binds an Mnx1 enhancer in pancreas progenitors, Pax6b/NeuroD maintain pancreatic Mnx1 expression, and MNX1 acts predominantly as a transcriptional repressor (78% of targets downregulated) with direct homeodomain-dependent repression of PTGER2 and enrichment for cell-adhesion gene targets.

    Evidence ChIP-seq for PTF1a; EMSA for Pax6b/NeuroD; ChIP-on-chip, luciferase reporter, and cAMP assays for PTGER2 repression in HL-60/patient cells

    PMID:22232429 PMID:22426004 PMID:23048027

    Open questions at the time
    • Full genome-wide direct target map in motor neurons absent
    • Co-repressor complexes mediating repression not identified
  10. 2014 High

    Post-translational regulation of MNX1 was established: GSK-3β phosphorylates Ser-78/Ser-80, stabilizing MNX1 in the nucleus; this mechanism is hyperactivated in insulinomas. Separately, homozygous loss-of-function MNX1 mutations were identified as a cause of permanent neonatal diabetes, confirming MNX1's essential role in human beta-cell development.

    Evidence Site-directed mutagenesis of phosphorylation sites, pharmacological GSK-3β inhibition in insulinoma cells; homozygosity mapping and sequencing in consanguineous PNDM patients

    PMID:24411943 PMID:24425879

    Open questions at the time
    • Whether phosphorylation affects DNA-binding affinity or co-factor recruitment unknown
    • Mechanism linking homeodomain F272L mutation to beta-cell failure not characterized
  11. 2015 High

    Conditional knockout studies revealed that MNX1 is required not only for initial beta-cell specification but also for maintaining beta-cell identity postnatally, as loss leads to beta-to-delta-like transdifferentiation, while escapee beta-cells upregulate Mnx1 and proliferate.

    Evidence Stage-specific conditional Cre-lox knockout with lineage tracing and functional islet assays in mice

    PMID:26534984

    Open questions at the time
    • Direct targets maintaining beta-cell vs. delta-cell identity not defined
    • Whether human beta-cells undergo similar transdifferentiation upon MNX1 loss unknown
  12. 2018 Medium

    MNX1's oncogenic transcriptional activity was extended to multiple cancers: it directly binds and activates CCNE1/CCNE2 promoters to drive G1-S transition in bladder cancer and represses CDKN1A (p21) in cervical cancer, while in hematopoietic progenitors it induces senescence via p53-p21.

    Evidence ChIP assays for CCNE1/CCNE2 and CDKN1A promoter binding; retroviral MNX1 expression in HSPCs with in vivo transplantation; cell cycle analysis

    PMID:30012177 PMID:30093397 PMID:32850410

    Open questions at the time
    • Context-dependent switch between senescence induction and proliferation promotion unresolved
    • Co-factors determining activator vs. repressor function at different promoters unknown
  13. 2021 High

    MNX1 was positioned within a chromatin regulatory network in pancreatic neoplasia: in IPMN organoids, MNX1 and HNF1B form a functionally indispensable axis governing MYC, SOX9, and OLFM4 expression, and glutamatergic output from Hb9 spinal interneurons was shown dispensable for locomotion.

    Evidence ATAC-seq, ChIP-seq, Hi-C, CRISPRi in human IPMN/PDAC organoids; conditional VGLUT2 knockout in Hb9 interneurons with behavioral testing

    PMID:34362940 PMID:34953915

    Open questions at the time
    • Whether MNX1 directly binds SOX9/OLFM4 regulatory regions or acts indirectly unresolved
    • Non-glutamatergic signaling mechanisms of Hb9 interneurons in locomotion undefined
  14. 2024 High

    The leukemogenic mechanism of ectopic MNX1 was resolved: MNX1 alone induces AML from fetal HSPCs by broadly increasing H3K4me1/2/3 and reducing H3K27me3 through interaction with methyltransferases, and t(7;12) was confirmed to cause enhancer hijacking driving MNX1 overexpression via chromatin interaction assays.

    Evidence Retroviral MNX1 expression in fetal/adult HSPCs with transplantation, histone ChIP, ATAC-seq, co-IP with methyltransferases, Sinefungin rescue; breakpoint mapping, Hi-C in iPSC t(7;12) model

    PMID:37317878 PMID:39121370

    Open questions at the time
    • Specific methyltransferase(s) mediating MNX1-dependent H3K4 methylation not individually identified
    • Why fetal but not adult HSPCs are susceptible is mechanistically unexplained
    • Whether enhancer hijacking model applies to all t(7;12) AML patients unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key open questions include: the co-repressor/co-activator complexes through which MNX1 exerts context-dependent transcriptional regulation; the direct target gene network in motor neurons; the structural basis for homeodomain mutations causing Currarino syndrome vs. neonatal diabetes; and the developmental window dependency of MNX1 leukemogenicity.
  • No co-repressor complex identified for MNX1 in any system
  • No crystal structure of MNX1 homeodomain–DNA complex available
  • Genome-wide direct target map in motor neurons absent

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 11 GO:0003677 DNA binding 6
Localization
GO:0005634 nucleus 2 GO:0005654 nucleoplasm 1
Pathway
R-HSA-1266738 Developmental Biology 7 R-HSA-74160 Gene expression (Transcription) 5 R-HSA-1643685 Disease 4 R-HSA-1640170 Cell Cycle 2 R-HSA-4839726 Chromatin organization 1
Partners
GSK3BHNF1BMEN1PAX6BPTF1A

Evidence

Reading pass · 35 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1999 HB9 (MNX1) is a homeodomain transcription factor essential for consolidating motor neuron identity; in mice lacking Hb9, postmitotic motor neurons transiently acquire molecular features of V2 interneurons, and motor neuron migration, subtype identity, and axonal projection are all defective. Genetic knockout (loss-of-function) with defined cellular and axonal phenotypic readouts in mouse embryos Neuron High 10482234 10482235
1999 HB9 (MNX1) actively suppresses interneuron genetic programs (e.g., Chx10) within postmitotic motor neurons to establish motor neuron identity, as revealed by upregulation of interneuron genes in Hb9 null mice. Genetic knockout with gene expression analysis (loss-of-function) Neuron High 10482235
1999 Hlxb9 (MNX1) is required for the initiation of the dorsal pancreatic program; in Hlxb9-null mice, dorsal gut epithelium fails to initiate pancreatic differentiation, while ventral pancreatic development proceeds with later defects in beta-cell differentiation and islet organization. Genetic knockout (loss-of-function) with histological and molecular analysis of pancreatic development Nature genetics High 10471501 10471502
1999 Hlxb9 (MNX1) null mice show dorsal pancreas agenesis and islets of Langerhans with reduced beta-cells that express low levels of Glut2 and Nkx6-1, indicating a role for MNX1 in beta-cell differentiation and function. Genetic knockout with immunohistochemistry and gene expression analysis Nature genetics High 10471502
2001 Persistent (temporally extended) expression of Hlxb9 in the pancreatic epithelium beyond its normal transient window impairs pancreatic morphogenesis, reduces endocrine and exocrine differentiation, and redirects the epithelium toward an intestinal-like fate, demonstrating tight temporal regulation of MNX1 is essential. Transgenic overexpression driven by Ipf1/Pdx1 promoter with histological and molecular analysis Developmental biology High 11784060
1998 Patient-specific heterozygous mutations in the HLXB9 homeobox gene (missense mutations clustered in the homeodomain and truncating mutations) cause autosomal dominant Currarino syndrome (hereditary sacral agenesis), establishing HLXB9 as the disease locus at 7q36. Mutation analysis (Sanger sequencing) in familial and sporadic patients combined with linkage analysis Nature genetics High 9843207
2000 HLXB9 missense mutations causing Currarino syndrome are significantly clustered in the homeodomain, resulting in non-conservative substitution of highly conserved residues, indicating the homeodomain DNA-binding function is critical; HLXB9 is expressed in the basal plate of the developing spinal cord/hindbrain and in pharynx, esophagus, stomach, and pancreas during human embryogenesis. Mutation survey (Sanger sequencing in 22 index patients) and in situ hybridization for expression analysis during human development (Carnegie stages 12–21) American journal of human genetics High 10749657
2001 A fusion transcript of HLXB9 (exon 1) and ETV6 (exons 2 or 3) is generated by t(7;12)(q36;p13) in infant AML; RT-PCR showed two alternative splice forms of the HLXB9-ETV6 fusion, and the reciprocal ETV6-HLXB9 transcript was not detected, implicating either the fusion protein or disrupted ETV6 in leukemogenesis. RT-PCR with sequence analysis in AML patient samples carrying t(7;12) Cancer research Medium 11454678
2005 In Hodgkin lymphoma cells, HLXB9 directly activates IL6 transcription (demonstrated by antisense knockdown, forced expression, and IL6 promoter reporter assays), and HLXB9 expression itself is regulated by the PI3K pathway, likely via E2F3. Antisense oligonucleotide knockdown, forced overexpression, luciferase reporter assay with IL6 promoter, PI3K/AKT pathway inhibition experiments Leukemia Medium 15772702
2005 HLXB9 ectopic expression in AML-M4 cell line GDM-1 results from juxtaposition with upstream regions of MYB through the translocation t(6;7)(q23;q36), establishing a novel mechanism of HLXB9 activation via enhancer hijacking from MYB. RT-PCR expression screening, karyotypic analysis, FISH mapping of chromosomal breakpoints Genes, chromosomes & cancer Medium 15540222
2007 In C. elegans, UNC-4 and its co-repressor UNC-37/Groucho repress CEH-12/HB9 in VA motor neurons; when CEH-12/HB9 is ectopically expressed in VAs, they adopt VB-type synaptic inputs, demonstrating that HB9 family proteins define synaptic partner choice downstream of UNC-4. Cell-specific microarray, genetic epistasis, and expression analysis in C. elegans Genes & development High 17289921
2007 Hb9 interneurons in the mouse spinal cord are electrotonically coupled to a heterogeneous network of non-Hb9 interneurons (gap junction coupling shown by carbenoxolone blockade and calcium imaging); they exhibit bursting activity synchronous with rhythmic ventral root output even when fast chemical synaptic transmission is blocked. Two-photon calcium imaging, paired whole-cell patch-clamp, pharmacological gap junction blockade in postnatal mouse spinal cord Journal of neurophysiology High 17715199
2008 Persistent sodium current (INaP) contributes to locomotor-related membrane voltage oscillations in Hb9 interneurons independently of fast glutamatergic, GABAergic, and glycinergic synaptic inputs; riluzole blockade of slow-inactivating sodium current suppressed oscillation amplitude and frequency. Pharmacological dissection (CNQX, riluzole, glycine/GABA receptor antagonists) combined with whole-cell patch-clamp in Hb9:eGFP transgenic mice Journal of neurophysiology High 18667543
2009 Hb9 interneurons are rhythmically active during fictive locomotion in intact neonatal mouse spinal cord, but their activity onset lags behind ipsilateral ventral root bursts (mean phase ~0.21–0.28), indicating they are not the sole intrasegmental rhythm-generating kernel of the CPG. Two-photon calcium imaging in intact spinal cord with subsequent immunostaining for genetic identification, confirmed by whole-cell recordings The Journal of neuroscience High 19759307
2011 In zebrafish, mnx1 (hb9) functions downstream of retinoic acid signaling in the endoderm to control cell fate decisions in the endocrine pancreas progenitor lineage; Mnx1-deficient zebrafish lack beta-cells and concomitantly gain alpha-cells, showing that Mnx1 promotes beta-cell and suppresses alpha-cell fate. Gene knockdown, cell transplantation, transgenic reporter analysis in zebrafish Development High 21989909
2012 PTF1a directly binds a distant enhancer element of the Mnx1 locus in pancreas progenitors and promotes Mnx1 expression; this was demonstrated by ChIP-sequencing and RNA profiling, establishing Mnx1 as a major direct target of PTF1a in the pancreas progenitor transcription factor network. RNA profiling and ChIP-sequencing (ChIP-seq) in pancreas progenitors Molecular and cellular biology High 22232429
2012 In zebrafish, the hb9/mnx1 beta-cell progenitor-specific enhancer contains paired-box transcription factor binding sites and E-boxes; EMSA studies showed Pax6b and NeuroD interact with these elements, and genetic analysis showed Pax6b is required for maintenance (but not induction) of pancreatic hb9 transcription. Enhancer reporter transgenic analysis, EMSA, genetic epistasis (pax6b mutants) in zebrafish Developmental biology High 22426004
2012 HB9 binds directly to the PTGER2 (prostaglandin E receptor 2) promoter via its functional homeodomain; HB9 binding requires both the homeodomain and the HB9-binding domain in the PTGER2 promoter, leading to transcriptional repression of PTGER2 and reduced intracellular cAMP in hematopoietic cells. Overall HB9 acts predominantly as a transcriptional repressor (78% of significantly regulated target genes are downregulated) with target enrichment in cell-adhesion and cell-cell interaction pathways. ChIP-on-chip, luciferase reporter assay, expression profiling, cAMP functional assay in HL-60 cells and t(7;12) patient bone marrow The Journal of biological chemistry High 23048027
2013 Hlxb9 interacts physically with menin (encoded by MEN1) in pancreatic beta-cells; upon menin knockdown, Hlxb9 is post-transcriptionally upregulated, reduces cell proliferation, and causes apoptosis in the presence of menin, and regulates genes controlling insulin levels. Co-immunoprecipitation (binding interaction), menin knockdown, cell proliferation and apoptosis assays in MIN6 beta-cell line Endocrine-related cancer Medium 23419452
2014 GSK-3β phosphorylates HLXB9 at Ser-78/Ser-80, stabilizing it predominantly in the nucleus; phospho-HLXB9 (pHLXB9) and active GSK-3β are elevated in insulinoma cells and human sporadic insulinomas, and pharmacologic GSK-3β inhibition blocks insulinoma cell proliferation by G2/M arrest and apoptosis. Site-directed mutagenesis of phosphorylation sites, Western blotting, pharmacological GSK-3β inhibition, cell cycle and apoptosis analysis in rodent insulinoma cell lines and human tumor samples The Journal of biological chemistry High 24425879
2014 Homozygous loss-of-function mutations in MNX1 cause permanent neonatal diabetes in humans, confirming MNX1 as an etiological gene for human pancreatic beta-cell development; the causal mutation (p.Phe272Leu) is located within the MNX1 homeodomain helix 2, and MNX1 is enriched in human embryonic pancreatic epithelium compared with mesenchyme. Homozygosity mapping, Sanger sequencing in consanguineous patients, expression analysis in human embryonic pancreatic tissue Cell metabolism High 23562494 24411943
2015 Conditional inactivation of Mnx1 in endocrine progenitors or embryonic beta-cells reveals that Mnx1 promotes beta-cell while suppressing delta-cell differentiation programs; loss of Mnx1 in embryonic beta-cells leads to postnatal beta-to-delta-like transdifferentiation, and beta-cells escaping Mnx1 inactivation upregulate Mnx1 and undergo persistent proliferation. Conditional genetic knockout (stage-specific Cre-lox), lineage tracing, longitudinal histological and functional analysis in mice Development High 26534984
2016 MNX1 upregulates lipid synthesis by stimulating expression of SREBP1 and fatty acid synthase (FASN) in prostate cancer cells; both androgen and AKT signaling pathways increase MNX1 expression. Gene expression analysis, pathway inhibition experiments, overexpression/knockdown in prostate cancer cell lines Cancer research Medium 27578002
2017 RGS12 tumor suppressor negatively regulates MNX1 expression by decreasing AKT activity; RGS12 expression correlates negatively with MNX1, and RGS12 knockdown increases MNX1 levels, establishing an RGS12-AKT-MNX1 oncogenic axis in African-American prostate cancer. Loss-of-function (RGS12 knockdown/KO) with expression analysis in vitro and in vivo xenograft models Cancer research Medium 28611045
2018 MNX1 transcriptionally upregulates CCNE1 (Cyclin E1) and CCNE2 (Cyclin E2) by directly binding to their promoters, promoting G1-S cell cycle transition in bladder cancer cells. ChIP assay demonstrating direct promoter binding, real-time PCR, Western blotting, cell cycle analysis; in vitro and in vivo (xenograft) functional experiments Journal of experimental & clinical cancer research Medium 30012177
2018 HB9 expression in human hematopoietic stem and progenitor cells induces premature senescence via the p53-p21 tumor suppressor network and causes a myeloid-biased differentiation arrest at the megakaryocyte/erythrocyte progenitor stage in vivo. Retroviral transduction in human HT1080 and NIH3T3 cells (senescence assays), murine HSPC transplantation (in vivo differentiation), gene expression profiling in human CD34+ cells Haematologica Medium 30093397
2018 MNX1 functions as a transcriptional activator of TrkB by binding its upstream regulatory region, thereby promoting anoikis resistance in glioma cells. RT-PCR, Western blotting, adhesion assay, overexpression/knockdown experiments, transcription factor binding assay (upstream region) Molecular medicine reports Low 30066929
2019 MNX1 activates Wnt/β-catenin signaling in colorectal cancer cells, upregulating downstream targets c-Myc and CCND1, as shown by luciferase reporter analysis. Luciferase reporter assay (Wnt/β-catenin), overexpression/knockdown, Western blotting in colorectal cancer cells Cell biology international Low 30614606
2020 MNX1 protein is expressed in beta-cells and promotes their proliferation; in the MNX1-AS1/c-Myc context, MNX1-AS1 promotes expression of MNX1 (sense transcript) in ICC via recruitment of transcription factors c-Myc and MAZ to the MNX1 promoter, and MNX1 in turn upregulates Ajuba to suppress the Hippo signaling pathway. Chromatin immunoprecipitation (ChIP) showing c-Myc and MAZ binding to MNX1 promoter; MNX1 ChIP on Ajuba promoter; functional assays in ICC cell lines and xenograft models Cell death & disease Medium 33093444
2020 MNX1 transcriptionally represses p21cip1 (CDKN1A) by binding its promoter, thereby accelerating G1/S cell cycle transition in cervical cancer cells. ChIP assay (direct promoter binding), luciferase reporter assay, flow cytometry (cell cycle), overexpression/knockdown with RTCA and xenograft in vivo Frontiers in oncology Medium 32850410
2021 Chromatin conformation and accessibility analyses in pancreatic organoids show that MNX1 and HNF1B form a biologically indispensable axis in IPMN lineages, governing a target gene set including MYC, SOX9, and OLFM4; MNX1 upregulation is specifically marked in human IPMN lineage tissues. ATAC-seq, ChIP-seq, Hi-C (chromosome conformation capture), shRNA/CRISPRi functional assays in human organoids derived from IPMN/PDAC Gastroenterology High 34953915
2021 Elimination of vesicular glutamate transporter 2 (VGLUT2) from Hb9 interneurons in mice using an inducible Cre line causes no deficits in treadmill locomotion, indicating that glutamatergic neurotransmission from Hb9 interneurons is dispensable for locomotor behavior. Conditional genetic knockout of VGLUT2 in Hb9 interneurons using inducible Cre recombinase; treadmill locomotion behavioral testing Scientific reports High 34362940
2024 Retroviral expression of MNX1 alone induces AML in immune-incompetent mice from fetal (but not adult) hematopoietic stem and progenitor cells; MNX1 increases H3K4 mono/di/trimethylation and reduces H3K27me3, alters genome-wide chromatin accessibility, and interacts with the methionine cycle and methyltransferases. Pre-treatment with the SAM analog Sinefungin prevents AML development, implicating histone methylation as the key oncogenic mechanism. Retroviral MNX1 expression in fetal vs. adult murine HSPCs with transplantation, ChIP for histone marks, ATAC-seq, gene expression profiling, co-IP with methyltransferases, pharmacological inhibition (Sinefungin) Haematologica High 37317878
2024 In t(7;12)(q36;p13) AML, the translocation breaks proximal to MNX1 and within introns 1 or 2 of ETV6, causing enhancer hijacking that drives aberrant MNX1 overexpression in hematopoietic cells, as demonstrated by chromatin interaction assays in an iPSC t(7;12) model. Breakpoint mapping, ATAC-seq, chromatin conformation capture (Hi-C-like assays) in iPSC t(7;12) model Blood advances High 39121370
2004 HB9 protein contains two functional nuclear localization signal (NLS) sequences within its homeodomain: one bipartite type (resembling Xenopus nucleoplasmin NLS) and one hexapeptide type (similar to PDX1 NLS); both are sufficient for nuclear import in primary keratinocytes and dermal fibroblasts. HB9 protein localizes to both nucleus and cytoplasm (ER and Golgi) in a tissue-context-dependent manner. GFP fusion protein nuclear import assay in primary keratinocyte culture; immunofluorescence; immunoelectron microscopy Histochemistry and cell biology Medium 15338230

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1999 Requirement for the homeobox gene Hb9 in the consolidation of motor neuron identity. Neuron 507 10482234
1999 Active suppression of interneuron programs within developing motor neurons revealed by analysis of homeodomain factor HB9. Neuron 308 10482235
1999 Selective agenesis of the dorsal pancreas in mice lacking homeobox gene Hlxb9. Nature genetics 302 10471501
1999 Pancreas dorsal lobe agenesis and abnormal islets of Langerhans in Hlxb9-deficient mice. Nature genetics 281 10471502
1998 A homeobox gene, HLXB9, is the major locus for dominantly inherited sacral agenesis. Nature genetics 215 9843207
2005 Conditional rhythmicity of ventral spinal interneurons defined by expression of the Hb9 homeodomain protein. The Journal of neuroscience : the official journal of the Society for Neuroscience 183 15958737
2007 Strategies for delineating spinal locomotor rhythm-generating networks and the possible role of Hb9 interneurones in rhythmogenesis. Brain research reviews 118 17905441
2020 TEAD4 modulated LncRNA MNX1-AS1 contributes to gastric cancer progression partly through suppressing BTG2 and activating BCL2. Molecular cancer 116 31924214
2014 Analysis of transcription factors key for mouse pancreatic development establishes NKX2-2 and MNX1 mutations as causes of neonatal diabetes in man. Cell metabolism 114 24411943
2000 Mutation analysis and embryonic expression of the HLXB9 Currarino syndrome gene. American journal of human genetics 104 10749657
2022 MNX1-AS1 Promotes Phase Separation of IGF2BP1 to Drive c-Myc-Mediated Cell-Cycle Progression and Proliferation in Lung Cancer. Cancer research 72 36214649
2006 High incidence of t(7;12)(q36;p13) in infant AML but not in infant ALL, with a dismal outcome and ectopic expression of HLXB9. Genes, chromosomes & cancer 68 16646086
2008 Spectrum of HLXB9 gene mutations in Currarino syndrome and genotype-phenotype correlation. Human mutation 65 18449898
2021 MYC-Activated LncRNA MNX1-AS1 Promotes the Progression of Colorectal Cancer by Stabilizing YB1. Cancer research 64 33782099
2008 Persistent sodium current contributes to induced voltage oscillations in locomotor-related hb9 interneurons in the mouse spinal cord. Journal of neurophysiology 64 18667543
2009 Activity of Hb9 interneurons during fictive locomotion in mouse spinal cord. The Journal of neuroscience : the official journal of the Society for Neuroscience 61 19759307
2001 Persistent expression of Hlxb9 in the pancreatic epithelium impairs pancreatic development. Developmental biology 61 11784060
2019 LncRNA MNX1-AS1 promotes progression of esophageal squamous cell carcinoma by regulating miR-34a/SIRT1 axis. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 55 31170665
2007 Heterogeneous electrotonic coupling and synchronization of rhythmic bursting activity in mouse Hb9 interneurons. Journal of neurophysiology 55 17715199
2019 Long noncoding RNA MNX1-AS1 contributes to lung cancer progression through the miR-527/BRF2 pathway. Journal of cellular physiology 54 30618167
2011 In vivo labeling of zebrafish motor neurons using an mnx1 enhancer and Gal4/UAS. Genesis (New York, N.Y. : 2000) 54 21538811
2011 Zebrafish mnx1 controls cell fate choice in the developing endocrine pancreas. Development (Cambridge, England) 54 21989909
2001 Fusion of the homeobox gene HLXB9 and the ETV6 gene in infant acute myeloid leukemias with the t(7;12)(q36;p13). Cancer research 53 11454678
2018 lncRNA MNX1-AS1 Promotes Glioblastoma Progression Through Inhibition of miR-4443. Oncology research 51 29678219
2016 MNX1 Is Oncogenically Upregulated in African-American Prostate Cancer. Cancer research 51 27578002
2012 Characterization and regulation of the hb9/mnx1 beta-cell progenitor specific enhancer in zebrafish. Developmental biology 51 22426004
2007 UNC-4 represses CEH-12/HB9 to specify synaptic inputs to VA motor neurons in C. elegans. Genes & development 49 17289921
2018 E2F1-mediated MNX1-AS1-miR-218-5p-SEC61A1 feedback loop contributes to the progression of colon adenocarcinoma. Journal of cellular biochemistry 47 30362161
2012 RNA profiling and chromatin immunoprecipitation-sequencing reveal that PTF1a stabilizes pancreas progenitor identity via the control of MNX1/HLXB9 and a network of other transcription factors. Molecular and cellular biology 45 22232429
2019 Long non-coding RNA MNX1-AS1 promotes hepatocellular carcinoma proliferation and invasion through targeting miR-218-5p/COMMD8 axis. Biochemical and biophysical research communications 44 30982576
2004 Minimal clinical expression of the holoprosencephaly spectrum and of Currarino syndrome due to different cytogenetic rearrangements deleting the Sonic Hedgehog gene and the HLXB9 gene at 7q36.3. American journal of medical genetics. Part A 44 15211664
2013 Transcription factor gene MNX1 is a novel cause of permanent neonatal diabetes in a consanguineous family. Diabetes & metabolism 43 23562494
2001 The Mnx homeobox gene class defined by HB9, MNR2 and amphioxus AmphiMnx. Development genes and evolution 43 11455421
2017 Long Noncoding RNA MNX1-AS1 Knockdown Inhibits Cell Proliferation and Migration in Ovarian Cancer. Cancer biotherapy & radiopharmaceuticals 42 28414551
2015 Inactivating the permanent neonatal diabetes gene Mnx1 switches insulin-producing β-cells to a δ-like fate and reveals a facultative proliferative capacity in aged β-cells. Development (Cambridge, England) 38 26534984
2005 HLXB9 activates IL6 in Hodgkin lymphoma cell lines and is regulated by PI3K signalling involving E2F3. Leukemia 38 15772702
2018 LncRNA MNX1-AS1 promotes the progression of cervical cancer through activating MAPK pathway. Journal of cellular biochemistry 35 30302806
2009 dbx mediates neuronal specification and differentiation through cross-repressive, lineage-specific interactions with eve and hb9. Development (Cambridge, England) 34 19710170
2020 LncRNA MNX1-AS1 promotes progression of intrahepatic cholangiocarcinoma through the MNX1/Hippo axis. Cell death & disease 33 33093444
2017 Overexpression of lncRNA MNX1-AS1 is associated with poor clinical outcome in epithelial ovarian cancer. European review for medical and pharmacological sciences 33 29271994
1999 The homeodomain transcription factors Islet 1 and HB9 are expressed in adult alpha and gamma motoneurons identified by selective retrograde tracing. The European journal of neuroscience 33 10336678
2022 LncRNA MNX1-AS1 sustains inactivation of Hippo pathway through a positive feedback loop with USP16/IGF2BP3 axis in gallbladder cancer. Cancer letters 32 35953000
2019 MNX1-AS1 is a functional oncogene that induces EMT and activates the AKT/mTOR pathway and MNX1 in breast cancer. Cancer management and research 32 30697072
2017 RGS12 Is a Novel Tumor-Suppressor Gene in African American Prostate Cancer That Represses AKT and MNX1 Expression. Cancer research 31 28611045
2013 The embryonic transcription factor Hlxb9 is a menin interacting partner that controls pancreatic β-cell proliferation and the expression of insulin regulators. Endocrine-related cancer 30 23419452
2020 Long Non-Coding RNA MNX1-AS1 Promotes Progression of Triple Negative Breast Cancer by Enhancing Phosphorylation of Stat3. Frontiers in oncology 29 32754442
2018 Motor neuron and pancreas homeobox 1/HLXB9 promotes sustained proliferation in bladder cancer by upregulating CCNE1/2. Journal of experimental & clinical cancer research : CR 29 30012177
2013 Novel MNX1 mutations and clinical analysis of familial and sporadic Currarino cases. European journal of medical genetics 28 24095820
2009 MNX1 (HLXB9) mutations in Currarino patients. Journal of pediatric surgery 28 19853743
2022 MNX1-AS1, a c-Myc induced lncRNA, promotes the Warburg effect by regulating PKM2 nuclear translocation. Journal of experimental & clinical cancer research : CR 26 36476366
1993 High expression of two diverged homeobox genes, HB24 and HB9, in acute leukemias: molecular markers of hematopoietic cell immaturity. Leukemia 26 7680402
2005 Activation of HLXB9 by juxtaposition with MYB via formation of t(6;7)(q23;q36) in an AML-M4 cell line (GDM-1). Genes, chromosomes & cancer 25 15540222
2004 Expression and localization of homeodomain proteins DLX4, HB9 and HB24 in malignant and benign human colorectal tissues. Anticancer research 25 15161049
2016 Zebrafish Tg(hb9:MTS-Kaede): a new in vivo tool for studying the axonal movement of mitochondria. Biochimica et biophysica acta 24 26968460
2014 Genome-wide identification of Drosophila Hb9 targets reveals a pivotal role in directing the transcriptome within eight neuronal lineages, including activation of nitric oxide synthase and Fd59a/Fox-D. Developmental biology 24 24512689
2019 Long Noncoding RNA MNX1 antisense RNA 1 Exerts Oncogenic Functions in Bladder Cancer by Regulating miR-218-5p/RAB1A Axis. The Journal of pharmacology and experimental therapeutics 23 31843814
2014 The homeodomain transcription factor Hb9 controls axon guidance in Drosophila through the regulation of Robo receptors. Cell reports 23 24685136
2020 Increased Expression of microRNA-141-3p Improves Necrotizing Enterocolitis of Neonates Through Targeting MNX1. Frontiers in pediatrics 21 32850524
2019 MNX1 promotes cell proliferation and activates Wnt/β-catenin signaling in colorectal cancer. Cell biology international 21 30614606
2018 Expression, Clinical Significance, and Functional Prediction of MNX1 in Breast Cancer. Molecular therapy. Nucleic acids 21 30368216
2021 MNX1-HNF1B Axis Is Indispensable for Intraductal Papillary Mucinous Neoplasm Lineages. Gastroenterology 20 34953915
2010 Sensory modulation of locomotor-like membrane oscillations in Hb9-expressing interneurons. Journal of neurophysiology 20 20393069
2005 Population differences in the polyalanine domain and 6 new mutations in HLXB9 in patients with Currarino syndrome. Clinical chemistry 20 16254195
2003 Expression and localization of homeodomain proteins DLX4/HB9 in normal and malignant human breast tissues. Anticancer research 20 12820413
2019 Knockdown of lncRNA MNX1-AS1 suppresses cell proliferation, migration, and invasion in prostate cancer. FEBS open bio 19 30980513
2019 Expression and significance of LncRNA MNX1-AS1 in non-small cell lung cancer. OncoTargets and therapy 19 31118668
2011 The homeobox gene HLXB9 is upregulated in a morphological subset of poorly differentiated hepatocellular carcinoma. Virchows Archiv : an international journal of pathology 19 21484430
2006 Forced expression of the motor neuron determinant HB9 in neural stem cells affects neurogenesis. Experimental neurology 18 16434037
2019 Long noncoding RNA MNX1-AS1 overexpression promotes the invasion and metastasis of gastric cancer through repressing CDKN1A. European review for medical and pharmacological sciences 17 31210302
2018 The homeobox transcription factor HB9 induces senescence and blocks differentiation in hematopoietic stem and progenitor cells. Haematologica 17 30093397
2012 TTX-resistant NMDA receptor-mediated membrane potential oscillations in neonatal mouse Hb9 interneurons. PloS one 17 23094101
2008 MNX1-ETV6 fusion gene in an acute megakaryoblastic leukemia and expression of the MNX1 gene in leukemia and normal B cell lines. Cancer genetics and cytogenetics 17 18940475
2007 Clinical and genetic analysis of HLXB9 gene in Korean patients with Currarino syndrome. Journal of human genetics 17 17612791
2022 An induced pluripotent stem cell t(7;12)(q36;p13) acute myeloid leukemia model shows high expression of MNX1 and a block in differentiation of the erythroid and megakaryocytic lineages. International journal of cancer 16 35583991
2021 Elimination of glutamatergic transmission from Hb9 interneurons does not impact treadmill locomotion. Scientific reports 16 34362940
2022 LncRNA MNX1-AS1: A novel oncogenic propellant in cancers. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 15 35290890
2021 LncRNA MNX1-AS1 drives aggressive laryngeal squamous cell carcinoma progression and serves as a ceRNA to target FoxM1 by sponging microRNA-370. Aging 15 33882027
2009 Three-way complex translocations in infant acute myeloid leukemia with t(7;12)(q36;p13): the incidence and correlation of a HLXB9 overexpression. Cancer genetics and cytogenetics 15 19446746
1991 Monoclonal antibodies VIB-E3, IB5 and HB9 to the leucocyte/epithelial antigen CD24 resemble BA-1 in recognizing sialic acid-dependent epitope(s). Evidence that VIB-E3 recognizes NeuAc alpha 2-6GalNAc and NeuAc alpha 2-6Gal sequences. Clinical and experimental immunology 15 1716543
2024 Aberrant MNX1 expression associated with t(7;12)(q36;p13) pediatric acute myeloid leukemia induces the disease through altering histone methylation. Haematologica 14 37317878
2018 MNX1 reduces sensitivity to anoikis by activating TrkB in human glioma cells. Molecular medicine reports 14 30066929
2014 GSK-3β protein phosphorylates and stabilizes HLXB9 protein in insulinoma cells to form a targetable mechanism of controlling insulinoma cell proliferation. The Journal of biological chemistry 14 24425879
2012 Homeobox protein HB9 binds to the prostaglandin E receptor 2 promoter and inhibits intracellular cAMP mobilization in leukemic cells. The Journal of biological chemistry 14 23048027
2011 Mutation analysis of the motor neuron and pancreas homeobox 1 (MNX1, former HLXB9) gene in Swedish patients with Currarino syndrome. Journal of pediatric surgery 14 21763840
2021 LncRNA MNX1-AS1 promotes ovarian cancer process via targeting the miR-744-5p/SOX12 axis. Journal of ovarian research 13 34789303
2012 Novel mutations in the MNX1 gene in two families with Currarino syndrome and variable phenotype. Gene 13 22820079
2006 HLXB9 homeobox gene and caudal regression syndrome. Birth defects research. Part A, Clinical and molecular teratology 13 16498628
2024 Altered enhancer-promoter interaction leads to MNX1 expression in pediatric acute myeloid leukemia with t(7;12)(q36;p13). Blood advances 12 39121370
2020 Clinical effects and molecular mechanisms of lncRNA MNX1-AS1 in malignant tumors. American journal of translational research 12 33312391
2019 Motor Neuron and Pancreas Homeobox 1 (MNX1) Is Involved in Promoting Squamous Cervical Cancer Proliferation via Regulating Cyclin E. Medical science monitor : international medical journal of experimental and clinical research 12 31436258
2011 The dual role of HLXB9 in leukemia. Pediatric blood & cancer 12 21069786
2022 lncRNA MNX1‑AS1 promotes prostate cancer progression through regulating miR‑2113/MDM2 axis. Molecular medicine reports 11 35616155
2021 LncRNA MNX1-AS1 Contributes to Laryngeal Squamous Cell Carcinoma Growth and Migration by Regulating mir-744-5p/bcl9/β-Catenin Axis. Cell transplantation 11 33821684
2008 Graft versus leukemia effect after haploidentical HSCT in a MLL-negative infant AML with HLXB9/ETV6 rearrangement. Pediatric blood & cancer 11 17960638
2007 Adult index patient with Currarino syndrome due to a novel HLXB9 mutation, c.336dupG (p.P113fsX224), presenting with Hirschsprung's disease, cephalgia, and lumbodynia. Birth defects research. Part A, Clinical and molecular teratology 11 17183586
2004 [Currarino syndrome: variability of imaging findings in 22 molecular-genetically identified (HLXB9 mutation) patients from five families]. RoFo : Fortschritte auf dem Gebiete der Rontgenstrahlen und der Nuklearmedizin 11 15088182
2022 Actinidia chinensis Planch Root extract suppresses the growth and metastasis of hypopharyngeal carcinoma by inhibiting E2F Transcription Factor 1-mediated MNX1 antisense RNA 1. Bioengineered 10 35152841
2020 MNX1 Promotes Malignant Progression of Cervical Cancer via Repressing the Transcription of p21cip1. Frontiers in oncology 10 32850410
2019 Long non-coding RNA MNX1-AS1 promoted osteosarcoma proliferation and invasion via inhibiting KISS1. European review for medical and pharmacological sciences 10 31364121
2004 Localization of HB9 homeodomain protein and characterization of its nuclear localization signal during chick embryonic skin development. Histochemistry and cell biology 9 15338230