Affinage

PAX1

Paired box protein Pax-1 · UniProt P15863

Length
534 aa
Mass
55.5 kDa
Annotated
2026-04-29
100 papers in source corpus 24 papers cited in narrative 24 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

PAX1 is a paired-box transcription factor that drives ventral axial skeleton formation, thymus/parathyroid organogenesis, and chondrocyte differentiation downstream of notochord-derived Sonic hedgehog signaling. In the sclerotome, PAX1 promotes cell proliferation and chondrogenesis by directly transactivating Bapx1/Nkx3.2 and positively regulating cartilage matrix genes, while competing with SOX9 at the Aggrecan upstream enhancer and physically interacting with SOX9, thereby modulating the balance between chondrocyte induction and maturation (PMID:12490554, PMID:30872687, PMID:24080012). PAX1 acts synergistically with PAX9 in vertebral body and intervertebral disc development—double-null embryos completely lack these structures due to failed sclerotome proliferation—and cooperates with Hoxa3 in thymic epithelial differentiation to support T-cell maturation (PMID:10556064, PMID:10820253). Biallelic loss-of-function PAX1 mutations cause severe combined immunodeficiency (SCID) through thymus aplasia, and a heterozygous paired-domain missense mutation (p.G166V) causes otofaciocervical syndrome via reduced transcriptional activity (PMID:32111619, PMID:23851939).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 1993 High

    Establishing that PAX1 lies downstream of notochord signaling resolved how dorsoventral vertebral patterning is transmitted from the axial midline to surrounding mesoderm.

    Evidence Genetic epistasis between Danforth's short-tail and undulated mutants with Pax1 expression analysis in mouse embryos

    PMID:8187635

    Open questions at the time
    • The notochord-derived signal molecule inducing Pax1 was not yet identified
    • Whether Pax1 is a direct target of notochord signals or responds indirectly was unresolved
  2. 1994 High

    Defining the Pax1-null skeletal phenotype revealed that Pax1 is specifically required for ventral sclerotome-derived structures (vertebral bodies, intervertebral discs) and acts at the proliferation stage before chondrogenesis.

    Evidence Analysis of three Pax1 allelic series (un, unex, Uns) in mouse with histology and immunohistochemistry

    PMID:8026324

    Open questions at the time
    • Molecular targets mediating Pax1-driven proliferation were unknown
    • Relationship to other sclerotome transcription factors (e.g., Pax9) was not addressed
  3. 1995 High

    Demonstrating that only paraxial mesoderm is competent to express Pax1 in response to notochord/floor plate established tissue-specific competence as a gating mechanism for sclerotome specification.

    Evidence In vitro co-culture and in vivo grafting of avian embryonic tissues with in situ hybridization

    PMID:7645756

    Open questions at the time
    • Molecular basis of competence in paraxial vs. lateral mesoderm was unknown
    • Whether Shh alone was sufficient to induce Pax1 had not been tested
  4. 1996 High

    Discovery that Pax1 is expressed in thymic epithelium and that its mutation impairs T-cell maturation expanded Pax1 function beyond skeleton to immune system organogenesis.

    Evidence Flow cytometry of thymocyte subsets and immunohistochemistry for Pax1 in undulated mutant mice

    PMID:8565834

    Open questions at the time
    • Whether the thymic defect is cell-autonomous to epithelium was not formally demonstrated
    • Downstream transcriptional targets of Pax1 in thymic epithelium were unknown
  5. 1998 High

    Identifying Pax1 as a transcriptional activator of PDGFRα and showing that undulated mutations abolish transactivation provided the first direct evidence that Pax1 functions as a sequence-specific transcription factor with cell-type-dependent activity.

    Evidence Luciferase reporter assay with PDGFRα promoter and EMSA in differentiated vs. undifferentiated human cell lines

    PMID:9826722

    Open questions at the time
    • Whether PDGFRα is a physiological target in sclerotome was not established
    • Cofactors determining cell-type-dependent activity were unknown
  6. 1999 High

    Compound Pax1/Pax9 and Pax1/Mfh1 double knockouts revealed synergistic and redundant functions of these factors downstream of Shh in sclerotome proliferation, explaining why single-gene mutations produce partial phenotypes.

    Evidence Double-mutant mouse analysis with BrdU proliferation, TUNEL apoptosis, and in situ hybridization for Sox9/ColII

    PMID:10364424 PMID:10556064

    Open questions at the time
    • Direct transcriptional targets shared or distinct between Pax1 and Pax9 were undefined
    • Whether Mfh1 and Pax1 regulate overlapping or parallel gene sets was unclear
  7. 2001 High

    Hoxa3/Pax1 compound mutant analysis placed these factors in a shared genetic pathway controlling thymic and parathyroid epithelial proliferation and differentiation, with the defect residing in radio-resistant stroma rather than hematopoietic cells.

    Evidence Fetal liver adoptive transfer, flow cytometry, Gcm2/Foxn1 in situ hybridization in compound mutant mice

    PMID:10820253 PMID:11476574

    Open questions at the time
    • Direct physical or transcriptional interaction between Hoxa3 and Pax1 was not demonstrated
    • Pax1 targets in thymic vs. parathyroid epithelium were not distinguished
  8. 2003 High

    Identification of Bapx1/Nkx3.2 as a direct transcriptional target of Pax1/Pax9 provided the first defined link between Pax1 DNA binding, transactivation, and initiation of chondrogenesis.

    Evidence Retroviral overexpression in chick PSM, Bapx1 promoter-luciferase reporter, ChIP, and Pax1/Pax9 double-mutant expression analysis

    PMID:12490554

    Open questions at the time
    • Genome-wide Pax1 binding targets beyond Bapx1 were not identified
    • Whether Bapx1 alone rescues Pax1 loss was not tested
  9. 2013 High

    A disease-associated PAX1 missense mutation (p.G166V) causing otofaciocervical syndrome was shown to reduce Nkx3.2 promoter transactivation, establishing a direct genotype-to-molecular-mechanism link for a human Mendelian skeletal disorder.

    Evidence Dual luciferase reporter assay with Nkx3.2 promoter in HEK293T cells overexpressing WT vs. G166V PAX1

    PMID:23851939

    Open questions at the time
    • DNA-binding affinity of the mutant was inferred but not quantitatively measured (e.g., by SPR or ITC)
    • Whether additional targets beyond Nkx3.2 are affected by G166V was not explored
  10. 2017 Medium

    Genome-wide ChIP-seq in Pax1/Pax9 mutant intervertebral disc cells identified a broad direct target network encompassing cartilage genes, Sox5/Sox6 feedback regulation, and BMP/TGF-β pathway components, defining PAX1 as a master regulator of chondrogenic gene programs.

    Evidence ChIP-sequencing and RNA-seq in Pax1/Pax9 single and double mutant mouse embryos

    PMID:28011632

    Open questions at the time
    • Functional validation of individual ChIP-seq targets was not performed
    • Relative contributions of Pax1 vs. Pax9 to individual binding events were not resolved
    • Motif analysis did not distinguish direct from indirect binding
  11. 2019 High

    Demonstration that PAX1 physically interacts with SOX9 and competes for overlapping Aggrecan enhancer binding sites revealed a molecular mechanism by which PAX1 fine-tunes cartilage matrix gene expression rather than simply activating it.

    Evidence Co-immunoprecipitation of PAX1 with SOX9, luciferase reporter with Aggrecan upstream enhancer, CRISPR deletion of enhancer, ChIP

    PMID:30872687

    Open questions at the time
    • Structural basis of the PAX1–SOX9 interaction is unknown
    • In vivo relevance in Pax1 mutant cartilage was not tested
  12. 2019 Medium

    Discovery that PAX1 interacts with the H3K4 methyltransferase SET1B and activates DUSP phosphatase genes revealed a chromatin-modifying mechanism by which PAX1 suppresses EGF/MAPK signaling, connecting its tumor-suppressive activity to epigenetic reprogramming.

    Evidence Co-immunoprecipitation of PAX1 with SET1B, kinase arrays, qRT-PCR for DUSPs, and histone/DNA methylation assays in cervical cancer cell lines

    PMID:31235851

    Open questions at the time
    • Co-IP was not validated by reciprocal pull-down or endogenous IP
    • Relevance to normal developmental contexts (sclerotome, thymus) was not tested
    • Whether SET1B recruitment is direct or via a complex was not resolved
  13. 2020 High

    Identifying biallelic PAX1 loss-of-function as a cause of human SCID via thymic aplasia, supported by iPSC-derived thymic epithelial progenitor defects, closed a decades-long question about whether PAX1 is essential for human thymus development.

    Evidence Whole-exome sequencing of SCID patients, iPSC differentiation to thymic epithelial progenitors, transcriptional activity assays, structural modeling of paired domain

    PMID:32111619

    Open questions at the time
    • Whether thymus transplant or gene correction rescues the immune defect in patients was not tested
    • Downstream gene network disrupted by PAX1 loss in human thymic epithelium was characterized only transcriptomically, not functionally
  14. 2022 Medium

    Demonstration of PAX1 promoter hypermethylation and reduced H3K9 acetylation in parathyroid adenomas, with pharmacological re-expression, implicated epigenetic silencing as a recurrent mechanism of PAX1 inactivation in endocrine tumors beyond cervical cancer.

    Evidence Bisulfite sequencing, ChIP for H3K9ac, 5-aza-dC treatment in rat parathyroid cells and human parathyroid adenoma tissues

    PMID:34453169

    Open questions at the time
    • Functional consequence of PAX1 re-expression on parathyroid cell growth was not assessed
    • Whether PAX1 silencing is a driver or passenger event in parathyroid tumorigenesis is unresolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • The structural basis of PAX1 interactions with its protein partners (SOX9, SET1B, Mox1), the genome-wide hierarchy of direct targets in thymic epithelium vs. sclerotome, and whether PAX1-based gene therapy can rescue SCID remain unresolved.
  • No crystal or cryo-EM structure of PAX1 in complex with SOX9, SET1B, or DNA
  • Tissue-specific PAX1 cistrome comparing sclerotome, IVD, and thymic epithelium has not been generated
  • Functional rescue of PAX1-null SCID by thymus organoid transplant or gene correction is untested

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 7 GO:0003677 DNA binding 4
Localization
GO:0005634 nucleus 5
Pathway
R-HSA-1266738 Developmental Biology 5 R-HSA-74160 Gene expression (Transcription) 5 R-HSA-168256 Immune System 3 R-HSA-4839726 Chromatin organization 1
Partners
HOXA3MEOX1MEOX2PAX9SET1BSOX9

Evidence

Reading pass · 24 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1993 Pax1 expression in sclerotome cells is induced by and depends on an intact notochord; loss of notochord integrity in Danforth's short-tail (Sd) mice reduces Pax1 expression and produces vertebral defects similar to Pax1 null mutants, placing Pax1 downstream of notochord signaling in dorsoventral vertebral specification. Genetic epistasis (Sd × undulated double mutants), in situ hybridization for Pax1 expression, whole-mount T-antibody staining of notochord Development High 8187635
1994 Pax1 protein is required for the development of vertebral bodies and intervertebral discs (ventral sclerotome derivatives) but not neural arches; complete loss of Pax1 results in failure of sclerotome cells to undergo chondrogenesis, beginning with reduced cell proliferation from day 10.5 pc. Analysis of three Pax1 mouse mutant alleles (un, unex, Uns/null) including immunohistochemistry for Pax1 protein and skeletal phenotype characterization Development High 8026324
1995 Notochord and floor plate induce Pax1 expression in competent paraxial mesoderm (sclerotome) cells in avian embryos; limb bud mesoderm and paraxial head mesoderm lack competence to respond to notochordal signals. In vitro co-culture and in vivo grafting experiments established that Pax1 induction depends on proximity to notochord/floor plate. In vitro co-culture assays, in vivo grafting experiments, in situ hybridization in quail embryos Anatomy and Embryology High 7645756
1995 Antisense knockdown of Pax1 in chick embryos causes somite loss, somite fusion, and shortened body axis, demonstrating a functional role for Pax1 in somitogenesis and sclerotome boundary formation. Antisense phosphorothioate oligodeoxynucleotide injection/topical application in chick embryos, histology, whole-mount in situ hybridization Teratology Medium 8711620
1996 Pax1 protein is expressed in thymic epithelial cells throughout development; Pax1 mutations reduce thymus size and impair T-cell maturation, specifically reducing CD4+8+ and CD4+ mature thymocyte subsets and elevating Thy-1 expression, demonstrating Pax1 is required in thymic epithelium to establish the microenvironment for T-cell maturation. Immunohistochemistry for Pax1 protein in thymus, flow cytometry of thymocyte subsets in undulated mutant mice Development High 8565834
1996 Endodermal expression of Pax1 and Pax9 in pharyngeal pouches is an intrinsic property of the endoderm not requiring midline structures, whereas sclerotomal Pax1 expression requires notochord induction; lateral tissues (lateral plate, intermediate mesoderm) counteract notochord signaling and inhibit Shh and Pax1/Pax9 expression. Grafting experiments of avian pharyngeal endoderm, in vitro sclerotome explant assays, in situ hybridization Developmental Biology High 8812138
1998 Pax1 acts as a transcriptional activator of the PDGFRα gene promoter in differentiated cells; the undulated point mutation (and a spina bifida-associated Gln→His mutation at position 42) reduces or abolishes this transactivation. In undifferentiated cells, mutant Pax1 unexpectedly enhances PDGFRα promoter activity (gain-of-function), correlating with altered protein-DNA interaction in band-shift assays. Luciferase reporter assay with human PDGFRα promoter in Tera-2 and U-2 OS cells, electrophoretic mobility shift assay (EMSA/band-shift) PNAS High 9826722
1998 Targeted Pax1 null allele in mice confirms that Pax1 is haploinsufficient for development of some skeletal elements (vertebral column, sternum, scapula); phenotype differs from the Uns deletion mutant, implicating additional gene(s) deleted in Uns. Gene targeting/homologous recombination in mouse ES cells, skeletal phenotype analysis of heterozygotes and homozygotes PNAS High 9671740
1999 Pax1 and Pax9 act synergistically and redundantly during vertebral column development; Pax1/Pax9 double mutants completely lack vertebral bodies, intervertebral discs, and proximal ribs. The primary cellular defect is reduced proliferation in ventromedial sclerotome before mesenchymal condensation, followed by increased apoptosis, preventing chondrogenesis despite normal sclerotome induction and Sox9/ColII initiation. Generation and analysis of Pax1/Pax9 double mutant mice, BrdU proliferation assays, TUNEL apoptosis assays, in situ hybridization for Sox9 and ColII Development High 10556064
1999 MFH1 (Foxf2) expression, like Pax1, depends on Sonic hedgehog signals from the notochord; Mfh1 and Pax1 act synergistically downstream of Shh to maintain sclerotome cell proliferation, with Mfh1/Pax1 double mutants showing extreme spina bifida, missing vertebral bodies/IVD, and reduced mitotic rate in sclerotome cells. Analysis of Mfh1/Pax1 double mutant mice, BrdU labeling, in situ hybridization, Shh signaling pathway assessment Developmental Biology High 10364424
2000 Hoxa3 and Pax1 act synergistically in a transcriptional regulatory pathway required for thymic epithelial cell development; Hoxa3+/−Pax1−/− compound mutants have fewer MHC class II+ epithelial cells, reduced MHC expression, and reduced ability to promote thymocyte maturation, causing a block at the CD4−8− to CD4+8+ transition with increased apoptosis. The defect resides in radio-resistant stromal cells, not hematopoietic cells. Fetal liver adoptive transfer, flow cytometry, immunohistochemistry for MHC class II, genetic compound mutant analysis Journal of Immunology High 10820253
2001 Hoxa3 and Pax1 cooperate in a genetic pathway controlling epithelial cell proliferation and differentiation during thymus and parathyroid organogenesis; Pax1−/− single mutants show reduced Gcm2 expression (parathyroid-specific marker) and smaller parathyroids, revealing a previously unrecognized role for Pax1 in parathyroid development. Hoxa3+/−Pax1−/− compound mutants have increased apoptosis and hypoplasia of the shared thymus/parathyroid primordium. Analysis of Hoxa3;Pax1 compound mutant mice, in situ hybridization for Gcm2/Foxn1, TUNEL assay, BrdU proliferation assay Developmental Biology High 11476574
2001 Mox1 and Mox2 homeodomain proteins physically interact with Pax1 (and Pax3) through the homeodomain of Mox; Mox1 preferentially associates with Pax1, and Mox2 preferentially associates with Pax3, as shown by yeast two-hybrid and in vitro biochemical assays. Yeast two-hybrid assay, in vitro biochemical binding assay (pulldown) FEBS Letters Medium 11423130
2003 Pax1 and Pax9 directly activate Bapx1 (Nkx3.2) expression in the sclerotome; Pax1/Pax9 double mutants lose Bapx1 expression in a gene-dose-dependent manner, retroviral overexpression of Pax1 in chick PSM induces Bapx1 and initiates chondrogenesis substituting for Shh, and Pax1/Pax9 transactivate the Bapx1 promoter and physically interact with Bapx1 regulatory sequences, identifying Bapx1 as a direct downstream target. Retroviral overexpression in chick PSM explants, Bapx1 promoter-luciferase reporter assay, ChIP/promoter binding assay, Pax1/Pax9 double mutant analysis Development High 12490554
2003 The Pax1(Un-s) deletion causes ectopic activation of Nkx2-2 in Pax1-expressing tissues (sclerotome, limb buds) by disrupting an insulator between Pax1 enhancers and the Nkx2-2 promoter; this ectopic Nkx2-2 interferes with the Pax1–Bapx1 pathway, explaining why the Uns phenotype is more severe than the defined Pax1 null. Deletion interval mapping, in situ hybridization for Nkx2-2 and Bapx1 in Pax1(Un-s) and Pax1-null embryos, comparative genomic analysis Genetics Medium 14504237
2013 A PAX1 missense mutation (p.G166V in the paired-box domain) in otofaciocervical syndrome patients causes significantly reduced transactivation of an Nkx3-2 (Bapx1) promoter reporter, demonstrating reduced DNA-binding affinity of the mutant protein and establishing PAX1 as causative for OFCS via loss of transcriptional activator function. Dual luciferase reporter assay with Nkx3-2 promoter in HEK293T cells overexpressing WT vs. mutant Pax1, whole-exome sequencing Human Genetics High 23851939
2013 Forced Pax1 expression in chick forelimb causes shortened skeletal elements, reduced proteoglycan accumulation, and lack of ossification/vascularization; Pax1-misexpressing chondrocytes downregulate Sox9, Nkx3.2, Ihh, Col2a1, Chm1, and Aggrecan, demonstrating that Pax1 acts as a negative regulator of chondrocyte maturation, antagonizing Sox9-driven differentiation. Retroviral overexpression of Pax1 in chick forelimb, histology, in situ hybridization, cultured chondrocyte assay Experimental Cell Research Medium 24080012
2019 PAX1 inhibits phosphorylation of multiple kinases (EGF/MAPK pathway) and activates phosphatases (DUSP1, 5, 6) in cervical cancer cells upon oncogenic growth factor challenge. PAX1 physically interacts with SET1B, leading to increased histone H3K4 methylation and DNA demethylation of phosphatase-encoding genes. Co-immunoprecipitation of PAX1 with SET1B, kinase phosphorylation arrays, qRT-PCR for DUSPs, chromatin/methylation assays in cervical cancer cell lines with PAX1 overexpression Scientific Reports Medium 31235851
2019 PAX1 and PAX9 differentially regulate the upstream Aggrecan enhancer (UE) depending on the presence of SOX9; in the presence of SOX9, PAX1/9 competes with SOX9 for overlapping binding sites in the UE, reducing transactivation. Physical interaction between Pax1 and SOX9 was demonstrated by co-immunoprecipitation. Luciferase reporter assay (UE-driven), CRISPR/Cas9 deletion of UE, co-immunoprecipitation of Pax1 with SOX9, ChIP for PAX1/9 and SOX9 binding Scientific Reports High 30872687
2020 Biallelic loss-of-function PAX1 mutations cause SCID due to thymus aplasia/hypoplasia; patient-derived iPSC-differentiated thymic epithelial progenitor cells show an altered transcriptional profile for genes involved in thymus and pharyngeal pouch development. Mutant PAX1 proteins have altered conformation and flexibility of the paired box domain and reduced transcriptional activity. iPSC differentiation into thymic epithelial progenitors, transcriptional activity assays of mutant PAX1, structural modeling of paired box domain conformational changes, whole-exome sequencing Science Immunology High 32111619
2015 PAX1 reactivation by curcumin and resveratrol in cervical cancer cell lines is independent of promoter demethylation and is instead mediated by downregulation of UHRF1; UHRF1 silencing alone is sufficient to reactivate PAX1 expression, suggesting that non-methylation epigenetic mechanisms (histone deacetylation) regulate PAX1. qRT-PCR for PAX1 expression, bisulfite sequencing of PAX1 promoter, transient siRNA knockdown of UHRF1, treatment with 5-aza-dC and sodium butyrate in HeLa/SiHa/CaSki cells Clinical and Experimental Medicine Medium 26081871
2022 PAX1 expression is epigenetically silenced in parathyroid adenomas by promoter hypermethylation (35% of cases) and reduced H3K9 acetylation; pharmacological inhibition of DNA methylation with 5'-aza-2'-deoxycytidine re-expresses PAX1 in rat parathyroid cells, establishing epigenetic deregulation as a mechanism of PAX1 silencing in parathyroid tumorigenesis. Bisulfite-specific PCR sequencing of PAX1 promoter in adenoma tissues, ChIP for H3K9ac at PAX1 promoter, 5-aza-dC treatment of rat parathyroid cells Journal of Clinical Endocrinology and Metabolism Medium 34453169
2008 Pbx1/Pbx2 control Pax1/Pax9 expression in the sclerotome as part of their governance of axial skeletal patterning; in Pbx1/Pbx2 loss-of-function mice, Pax1/Pax9 expression in the sclerotome is reduced, placing Pbx1/Pbx2 upstream of Pax1/Pax9 in the sclerotome regulatory hierarchy. Pbx1/Pbx2 compound mutant mouse analysis, in situ hybridization for Pax1/Pax9 expression, skeletal phenotype analysis Developmental Biology Medium 18691704
2017 ChIP-sequencing combined with transcriptomics in Pax1/Pax9 mutant IVD cells identified Pax1/Pax9 direct targets involved in cell proliferation, cartilage development, and collagen fibrillogenesis. Pax1/Pax9 positively regulate Sox5/Sox6/Sox9 target cartilage genes and are connected to Sox5/Sox6 by a negative feedback loop; they also interact with BMP and TGF-β pathways and initiate chondrogenic gene expression during early IVD differentiation. ChIP-sequencing, RNA-seq in Pax1/Pax9 single and double mutant embryos, comparative transcriptomics Biology Open Medium 28011632

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1994 The role of Pax-1 in axial skeleton development. Development (Cambridge, England) 312 8026324
1995 Characterization and developmental expression of Pax9, a paired-box-containing gene related to Pax1. Developmental biology 232 7649395
1999 Pax1 and Pax9 synergistically regulate vertebral column development. Development (Cambridge, England) 204 10556064
1996 Pax1 is expressed during development of the thymus epithelium and is required for normal T-cell maturation. Development (Cambridge, England) 200 8565834
1993 A role for Pax-1 as a mediator of notochordal signals during the dorsoventral specification of vertebrae. Development (Cambridge, England) 167 8187635
1998 Targeted disruption of Pax1 defines its null phenotype and proves haploinsufficiency. Proceedings of the National Academy of Sciences of the United States of America 125 9671740
2001 Hoxa3 and pax1 regulate epithelial cell death and proliferation during thymus and parathyroid organogenesis. Developmental biology 113 11476574
2015 A PAX1 enhancer locus is associated with susceptibility to idiopathic scoliosis in females. Nature communications 112 25784220
2003 Pax1 and Pax9 activate Bapx1 to induce chondrogenic differentiation in the sclerotome. Development (Cambridge, England) 108 12490554
1995 Pax-1, a regulator of sclerotome development is induced by notochord and floor plate signals in avian embryos. Anatomy and embryology 102 7645756
1999 Developmental expression of Pax1/9 genes in urochordate and hemichordate gills: insight into function and evolution of the pharyngeal epithelium. Development (Cambridge, England) 99 10226012
1995 undulated phenotypes suggest a role of Pax-1 for the development of vertebral and extravertebral structures. Developmental biology 98 7875377
1996 Expression of avian Pax1 and Pax9 is intrinsically regulated in the pharyngeal endoderm, but depends on environmental influences in the paraxial mesoderm. Developmental biology 93 8812138
1999 Notochord-dependent expression of MFH1 and PAX1 cooperates to maintain the proliferation of sclerotome cells during the vertebral column development. Developmental biology 79 10364424
2003 Mutations in PAX1 may be associated with Klippel-Feil syndrome. European journal of human genetics : EJHG 78 12774041
2020 PAX1 is essential for development and function of the human thymus. Science immunology 75 32111619
2014 PAX1 methylation as a potential biomarker for cervical cancer screening. International journal of gynecological cancer : official journal of the International Gynecological Cancer Society 66 24844223
2000 Hoxa3 and pax1 transcription factors regulate the ability of fetal thymic epithelial cells to promote thymocyte development. Journal of immunology (Baltimore, Md. : 1950) 61 10820253
2000 Pax1/Pax9-Related genes in an agnathan vertebrate, Lampetra japonica: expression pattern of LjPax9 implies sequential evolutionary events toward the gnathostome body plan. Developmental biology 55 10882524
1998 Retinoic acid-induced thymic abnormalities in the mouse are associated with altered pharyngeal morphology, thymocyte maturation defects, and altered expression of Hoxa3 and Pax1. Teratology 54 9894676
2014 High methylation rate of LMX1A, NKX6-1, PAX1, PTPRR, SOX1, and ZNF582 genes in cervical adenocarcinoma. International journal of gynecological cancer : official journal of the International Gynecological Cancer Society 52 24407576
1996 PAX genes and human neural tube defects: an amino acid substitution in PAX1 in a patient with spina bifida. Journal of medical genetics 52 8863157
2017 A developmental transcriptomic analysis of Pax1 and Pax9 in embryonic intervertebral disc development. Biology open 51 28011632
2010 Quantitative analysis of methylation status of the PAX1 gene for detection of cervical cancer. International journal of gynecological cancer : official journal of the International Gynecological Cancer Society 51 20442585
1995 Differential expression of the chicken Pax-1 and Pax-9 gene: in situ hybridization and immunohistochemical analysis. Developmental dynamics : an official publication of the American Association of Anatomists 51 7647370
2013 A hypofunctional PAX1 mutation causes autosomal recessively inherited otofaciocervical syndrome. Human genetics 48 23851939
2005 An analysis of PAX1 in the development of vertebral malformations. Clinical genetics 48 16207213
2017 A novel PAX1 null homozygous mutation in autosomal recessive otofaciocervical syndrome associated with severe combined immunodeficiency. Clinical genetics 45 28657137
2016 Hypermethylated ZNF582 and PAX1 are effective biomarkers for detection of oral dysplasia and oral cancer. Oral oncology 45 27865370
2019 Paired Box-1 (PAX1) Activates Multiple Phosphatases and Inhibits Kinase Cascades in Cervical Cancer. Scientific reports 44 31235851
2014 PAX1/SOX1 DNA methylation and cervical neoplasia detection: a Taiwanese Gynecologic Oncology Group (TGOG) study. Cancer medicine 44 24799352
2017 Hypermethylated ZNF582 and PAX1 genes in mouth rinse samples as biomarkers for oral dysplasia and oral cancer detection. Head & neck 43 28960639
2010 Cervical dysplasia: assessing methylation status (Methylight) of CCNA1, DAPK1, HS3ST2, PAX1 and TFPI2 to improve diagnostic accuracy. Gynecologic oncology 39 20708786
2019 Aberrant DNA methylation of PAX1, SOX1 and ZNF582 genes as potential biomarkers for esophageal squamous cell carcinoma. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 38 31629253
2013 DNA methylation of PAX1 as a biomarker for oral squamous cell carcinoma. Clinical oral investigations 38 23907469
2008 Pbx1/Pbx2 govern axial skeletal development by controlling Polycomb and Hox in mesoderm and Pax1/Pax9 in sclerotome. Developmental biology 38 18691704
1995 Pax-1 in the development of the cervico-occipital transitional zone. Anatomy and embryology 37 8651506
2017 DNA Methylation Status of PAX1 and ZNF582 in Esophageal Squamous Cell Carcinoma. International journal of environmental research and public health 35 28241446
2016 PAX1 and SOX1 methylation as an initial screening method for cervical cancer: a meta-analysis of individual studies in Asians. Annals of translational medicine 35 27826568
2011 Triage of cervical cytological diagnoses of atypical squamous cells by DNA methylation of paired boxed gene 1 (PAX1). Diagnostic cytopathology 34 21710649
2001 Homeodomain proteins Mox1 and Mox2 associate with Pax1 and Pax3 transcription factors. FEBS letters 34 11423130
2002 Cooperation of Hoxa5 and Pax1 genes during formation of the pectoral girdle. Developmental biology 33 11900462
1999 Expression of the paired-box genes Pax-1 and Pax-9 in limb skeleton development. Developmental dynamics : an official publication of the American Association of Anatomists 33 10030590
2015 Assessing methylation status of PAX1 in cervical scrapings, as a novel diagnostic and predictive biomarker, was closely related to screen cervical cancer. International journal of clinical and experimental pathology 32 25973053
2003 Aberrant Pax1 and Pax9 expression in Jarcho-Levin syndrome: report of two Caucasian siblings and literature review. American journal of medical genetics. Part A 32 12833407
1995 Functional involvement of Pax-1 in somite development: somite dysmorphogenesis in chick embryos treated with Pax-1 paired-box antisense oligodeoxynucleotide. Teratology 30 8711620
1992 Pax1, a member of the paired box-containing class of developmental control genes, is mapped to human chromosome 20p11.2 by in situ hybridization (ISH and FISH). Genomics 29 1358810
2019 The promising role of PAX1 (aliases: HUP48, OFC2) gene methylation in cancer screening. Molecular genetics & genomic medicine 28 30636379
2017 Human Papillomavirus Genotypes and Methylation of CADM1, PAX1, MAL and ADCYAP1 Genes in Epithelial Ovarian Cancer Patients. Asian Pacific journal of cancer prevention : APJCP 28 28240513
2015 Promoter methylation-independent reactivation of PAX1 by curcumin and resveratrol is mediated by UHRF1. Clinical and experimental medicine 27 26081871
1996 Chicken Pax-1 gene: structure and expression during embryonic somite development. Differentiation; research in biological diversity 27 8921581
2005 The scoliosis (sco) mouse: a new allele of Pax1. Cytogenetic and genome research 25 16093716
2013 Characterization of pax1, pax9, and uncx sclerotomal genes during Xenopus laevis embryogenesis. Developmental dynamics : an official publication of the American Association of Anatomists 24 23401059
2008 Function of Pax1 and Pax9 in the sclerotome of medaka fish. Genesis (New York, N.Y. : 2000) 24 18395830
2018 Autosomal recessive otofaciocervical syndrome type 2 with novel homozygous small insertion in PAX1 gene. American journal of medical genetics. Part A 23 29681087
2015 PAX1 methylation as an auxiliary biomarker for cervical cancer screening: a meta-analysis. Cancer epidemiology 23 26234429
1998 Inhibitory action of BMPs on Pax1 expression and on shoulder girdle formation during limb development. Developmental dynamics : an official publication of the American Association of Anatomists 23 9786420
2022 Aberrant Epigenetic Alteration of PAX1 Expression Contributes to Parathyroid Tumorigenesis. The Journal of clinical endocrinology and metabolism 21 34453169
2019 Differential transactivation of the upstream aggrecan enhancer regulated by PAX1/9 depends on SOX9-driven transactivation. Scientific reports 21 30872687
2013 Pax1 acts as a negative regulator of chondrocyte maturation. Experimental cell research 21 24080012
1998 Altered regulation of platelet-derived growth factor receptor-alpha gene-transcription in vitro by spina bifida-associated mutant Pax1 proteins. Proceedings of the National Academy of Sciences of the United States of America 21 9826722
2022 An overview of PAX1: Expression, function and regulation in development and diseases. Frontiers in cell and developmental biology 20 36393845
2006 Comparison of Pax1/9 locus reveals 500-Myr-old syntenic block and evolutionary conserved noncoding regions. Molecular biology and evolution 20 17182894
2016 Real-time colorimetric detection of DNA methylation of the PAX1 gene in cervical scrapings for cervical cancer screening with thiol-labeled PCR primers and gold nanoparticles. International journal of nanomedicine 19 27789946
2017 PAX1 Methylation as a Potential Biomarker to Predict the Progression of Cervical Intraepithelial Neoplasia: A Meta-analysis of Related Studies. International journal of gynecological cancer : official journal of the International Gynecological Cancer Society 18 28472814
2015 Value of PAX1 Methylation Analysis by MS-HRM in the Triage of Atypical Squamous Cells of Undetermined Significance. Asian Pacific journal of cancer prevention : APJCP 18 26320460
2003 Undulated short-tail deletion mutation in the mouse ablates Pax1 and leads to ectopic activation of neighboring Nkx2-2 in domains that normally express Pax1. Genetics 17 14504237
2018 Genetic Variant of PAX1 Gene Is Functionally Associated With Adolescent Idiopathic Scoliosis in the Chinese Population. Spine 16 29095406
2007 Diaphanospondylodysostosis: six new cases and exclusion of the candidate genes, PAX1 and MEOX1. American journal of medical genetics. Part A 16 17764081
2021 The application of PAX1 methylation detection and HPV E6/E7 mRNA detection in cervical cancer screening. The journal of obstetrics and gynaecology research 15 34036681
2020 Hypermethylated PAX1 and ZNF582 genes in the tissue sample are associated with aggressive progression of oral squamous cell carcinoma. Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology 15 32428271
2023 Clinical utility of HPV typing and quantification combined with PAX1/ZNF582 methylation detection in accurate cervical cancer screening. CytoJournal 14 37681081
2020 Real time quantitative methylation detection of PAX1 gene in cervical cancer screening. International journal of gynecological cancer : official journal of the International Gynecological Cancer Society 14 32616628
2018 Genetic polymorphisms of PAX1 are functionally associated with different PUMC types of adolescent idiopathic scoliosis in a northern Chinese Han population. Gene 14 30572100
2016 Reiterative expression of pax1 directs pharyngeal pouch segmentation in medaka. Development (Cambridge, England) 14 27034424
2008 Association between the development of the body axis and the craniofacial skeleton studied by immunohistochemical analyses using collagen II, Pax9, Pax1, and Noggin antibodies. Spine 14 18594453
2022 Triage by PAX1 and ZNF582 Methylation in Women With Cervical Intraepithelial Neoplasia Grade 3: A Multicenter Case-Control Study. Open forum infectious diseases 13 35402629
2021 Methylation of PAX1 gene promoter in the prediction of concurrent chemo-radiotherapy efficacy in cervical cancer. Journal of Cancer 13 34335930
2014 PAX1 methylation analysis by MS-HRM is useful in triage of high-grade squamous intraepithelial lesions. Asian Pacific journal of cancer prevention : APJCP 13 24568514
2024 PAX1/SOX1 DNA Methylation Versus Cytology and HPV16/18 Genotyping for the Triage of High-Risk HPV-Positive Women in Cervical Cancer Screening: Retrospective Analysis of Archival Samples. BJOG : an international journal of obstetrics and gynaecology 12 39327707
2007 pax1-1 partially suppresses gain-of-function mutations in Arabidopsis AXR3/IAA17. BMC plant biology 12 17430601
2020 The application value of PAX1 and ZNF582 gene methylation in high grade intraepithelial lesion and cervical cancer. Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico 11 32514824
2013 Pax1(EGFP): new wildtype and mutant EGFP mouse lines for molecular and fate mapping studies. Genesis (New York, N.Y. : 2000) 11 23377878
2002 Stage-specific changes in fetal thymocyte proliferation during the CD4-8- to CD4+8+ transition in wild type, Rag1-/-, and Hoxa3,Pax1 mutant mice. BMC immunology 11 12241558
2024 Analysis of the diagnostic performance of PAX1/SOX1 gene methylation in cervical precancerous lesions and its role in triage diagnosis. Journal of medical virology 10 38727013
2024 Triage performance of PAX1m/JAM3m in opportunistic cervical cancer screening of non‒16/18 human papillomavirus-positive women: a multicenter prospective study in China. Clinical epigenetics 10 39152491
2016 Generation of Pax1/PAX1-Specific Monoclonal Antibodies. Monoclonal antibodies in immunodiagnosis and immunotherapy 10 27705080
2015 The role of the Pax1/9 gene in the early development of amphioxus pharyngeal gill slits. Journal of experimental zoology. Part B, Molecular and developmental evolution 10 25504927
2000 Evolutionary conservation of gene structures of the Pax1/9 gene family. Biochimica et biophysica acta 10 10899593
2023 PAX1 and SEPT9 methylation analyses in cervical exfoliated cells are highly efficient for detecting cervical (pre)cancer in hrHPV-positive women. Journal of obstetrics and gynaecology : the journal of the Institute of Obstetrics and Gynaecology 8 36799003
2023 Evaluation of PAX1/ST6GALNAC5 methylation as a triage test for cervical intraepithelial neoplasia and cervical cancer. Epigenomics 8 37020401
2021 The effects of Tbx15 and Pax1 on facial and other physical morphology in mice. FASEB bioAdvances 8 34938962
2024 Relationship between p16/ki67 immunoscores and PAX1/ZNF582 methylation status in precancerous and cancerous cervical lesions in high-risk HPV-positive women. BMC cancer 7 39304838
2024 Cervical cancer screening: efficacy of PAX1 and JAM3 methylation assay in the triage of atypical squamous cell of undetermined significance (ASC-US). BMC cancer 7 39528979
2024 Evaluating PAX1/JAM3 methylation for triage in HPV 16/18-infected women. Clinical epigenetics 7 39726021
2015 PAX1 Methylation Hallmarks Promising Accuracy for Cervical Cancer Screening in Asians: Results from a Meta-Analysis. Clinical laboratory 7 26642709
2023 Expanding the clinical and immunological phenotypes of PAX1-deficient SCID and CID patients. Clinical immunology (Orlando, Fla.) 6 37689091
2022 Dysmorphism and immunodeficiency - One of the differential diagnoses is PAX1 related otofaciocervical syndrome type 2. European journal of medical genetics 6 35595062
2019 Association between dense PAX1 promoter methylation and HPV16 infection in cervical squamous epithelial neoplasms of Xin Jiang Uyghur and Han women. Gene 6 31589957
1994 The undulated mouse and the development of the vertebral column. Is there a human PAX-1 homologue? Clinical dysmorphology 6 7981852