{"gene":"SOX13","run_date":"2026-06-10T07:46:38","timeline":{"discoveries":[{"year":2000,"finding":"SOX13 protein binds to the SOX consensus DNA motif AACAAT, and homodimer formation inhibits DNA binding, suggesting activation requires heterodimer formation for nuclear import and DNA binding.","method":"Recombinant protein DNA-binding assay; deletion mapping of antibody epitopes; immunohistochemistry on pancreatic sections","journal":"Diabetes","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct in vitro DNA-binding assay with homodimer inhibition demonstrated, single lab with two orthogonal approaches (DNA binding + immunohistochemistry)","pmids":["10871192"],"is_preprint":false},{"year":1998,"finding":"Sox-13 protein contains an HMG box, a leucine zipper motif, and a glutamine-rich stretch; it binds the HMG box consensus motif AACAAAG but does not transactivate transcription through a concatamer of this motif.","method":"Cloning and sequence analysis; DNA-binding assay; transcriptional reporter assay","journal":"Nucleic acids research","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct DNA-binding assay and reporter assay performed, single lab with two orthogonal methods establishing both binding and lack of transactivation","pmids":["9421502"],"is_preprint":false},{"year":2007,"finding":"SOX13 promotes γδ T cell development while opposing αβ T cell differentiation; one mechanism is inhibition of Wnt/TCF signaling through interaction with TCF1. Loss of Sox13 impairs γδ T cell development but not αβ T cell development.","method":"Sox13 transgenic mice; Sox13-deficient mice; genetic epistasis with Wnt/TCF pathway reporter assays","journal":"Science","confidence":"High","confidence_rationale":"Tier 2 / Strong — reciprocal gain- and loss-of-function genetic models with defined cellular phenotypes, pathway placement via Wnt/TCF interaction, replicated across transgenic and knockout approaches","pmids":["17218525"],"is_preprint":false},{"year":2009,"finding":"SOX13 interacts directly with Hhex (hematopoietically expressed homeobox) protein; SOX13 represses Wnt/TCF signaling by interacting with TCF1, and Hhex blocks this SOX13-dependent repression by displacing SOX13 from the SOX13×TCF1 complex.","method":"Yeast two-hybrid screen; co-immunoprecipitation; domain mapping; Wnt/TCF luciferase reporter assay; mouse embryo electroporation","journal":"The Journal of biological chemistry","confidence":"High","confidence_rationale":"Tier 2 / Strong — yeast two-hybrid, co-IP domain mapping, and functional reporter assays combined with in vivo embryo electroporation, multiple orthogonal methods in single study","pmids":["20028982"],"is_preprint":false},{"year":2013,"finding":"A spontaneous loss-of-function mutation in Sox13 causes an intrinsic defect in development of Vγ4+ IL-17-committed γδ T cells (γδT17 cells) in the neonatal thymus, and Sox13-mutant mice are protected from psoriasis-like dermatitis.","method":"Natural mutant mouse substrain characterization; genetic mapping of Sox13 mutation; thymic developmental assays","journal":"Nature immunology","confidence":"High","confidence_rationale":"Tier 2 / Strong — natural loss-of-function mutation mapped to Sox13 with defined cellular phenotype in thymic development and inflammatory disease model, replicated functionally","pmids":["23624556"],"is_preprint":false},{"year":2018,"finding":"SOX13+ progenitors in the fetal thymus give rise to IL-17-producing γδ T cells (Tγδ17) independently of γδTCR signaling; generation of these lineage-committed progenitors and Tγδ17 cells is controlled by TCF1 and SOX13.","method":"SOX13 reporter knock-in mice; thymic organ culture developmental assays; single-cell transcriptome analysis of TCR-deficient mice","journal":"Immunity","confidence":"High","confidence_rationale":"Tier 2 / Strong — reporter mice, organ culture assays, and scRNA-seq in TCR-deficient mice using multiple orthogonal methods to establish TCR-independent SOX13/TCF1-dependent lineage programming","pmids":["30413363"],"is_preprint":false},{"year":2015,"finding":"Sox13 can bind to the same sites in myelin gene promoters as Sox5 and Sox6 in vitro, and reporter gene assays show Sox13 antagonizes Sox10-dependent transactivation of myelin gene promoters, similar to Sox5 and Sox6. Sox13 deletion alone does not impair oligodendrocyte development, but Sox6/Sox13 double-deficient mice show more prominent premature oligodendrocyte precursor differentiation than Sox6-deficient mice alone.","method":"In vitro DNA-binding assay; reporter gene assay; Sox13 knockout mice; Sox6/Sox13 double-knockout mice","journal":"Journal of neurochemistry","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — in vitro binding, reporter assays, and double-KO genetic epistasis in single study, single lab","pmids":["26525805"],"is_preprint":false},{"year":2020,"finding":"SOX13 promotes colorectal cancer metastasis by directly transactivating SNAI2 and MET (c-MET) promoters; SOX13 is itself a direct transcriptional target of HGF/STAT3 signaling, forming a HGF/STAT3/SOX13/c-MET axis.","method":"Serial deletion and site-directed mutagenesis luciferase reporter assays; ChIP assays; functional complementation analyses; migration/invasion assays with SOX13 overexpression and knockdown","journal":"Oncogene","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — ChIP, mutagenesis-based reporter assays, and functional complementation by single lab with multiple orthogonal methods","pmids":["32111984"],"is_preprint":false},{"year":2020,"finding":"Sox13 promotes hepatocellular carcinoma invasion and EMT by directly activating Twist1 transcription; Sox13 forms a heterodimer with Sox5, and this Sox13/Sox5 heterodimer cooperatively enhances transcriptional activity at the Twist1 promoter.","method":"Transcriptional reporter assays; co-immunoprecipitation (heterodimer detection); Transwell invasion assay; rescue experiments with Twist1 depletion","journal":"Laboratory investigation","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — reporter assays and co-IP for heterodimer, plus functional rescue, multiple orthogonal methods in single lab","pmids":["32461589"],"is_preprint":false},{"year":2021,"finding":"SOX13 activates TRIM11 transcription by binding to the TRIM11 promoter. TRIM11, an E3 ubiquitin ligase, then promotes mono-ubiquitination of YAP, prolonging YAP protein half-life and activating Hippo pathway target genes (CTGF, ANKRD1, CYR61), promoting anaplastic thyroid cancer proliferation, migration, and chemoresistance.","method":"TRIM11 promoter-luciferase reporter assay; co-immunoprecipitation; ubiquitin-based immunoprecipitation assays; domain mapping; CCK8/wound-healing/transwell assays","journal":"International journal of biological sciences","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — promoter reporter, ubiquitination IP, and domain mapping in single lab with multiple orthogonal methods","pmids":["33613102"],"is_preprint":false},{"year":2022,"finding":"SOX13 is a flow-sensitive transcription factor preferentially expressed in endothelial cells under stable (unidirectional laminar) flow; siRNA-mediated knockdown of SOX13 increases endothelial inflammatory responses under laminar shear stress, and SOX13 represses pro-inflammatory chemokines CXCL10 and CCL5. SOX13 overexpression prevents endothelial inflammation.","method":"siRNA knockdown; SOX13 overexpression; RNAseq in human aortic ECs under shear conditions; ELISA validation; scRNAseq/scATACseq of mouse carotid ligation model","journal":"Frontiers in cardiovascular medicine","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — reciprocal KD/OE experiments with defined chemokine phenotype, RNAseq, and in vivo genomics, single lab","pmids":["36247423"],"is_preprint":false},{"year":2024,"finding":"SOX13 directly transactivates SCAF1, which promotes assembly of mitochondrial electron transport chain supercomplexes, increasing mitochondrial respiration and energetics, thereby conferring ferroptosis resistance in gastric cancer. The drug zanamivir targets SOX13 directly and promotes TRIM25-mediated ubiquitination and degradation of SOX13 to reverse ferroptosis resistance.","method":"ChIP/transactivation assays; SOX13/SCAF1 manipulation in cell lines; supercomplex assembly and mitochondrial respiration assays; molecular docking; ubiquitination assays; xenograft models","journal":"Nature communications","confidence":"High","confidence_rationale":"Tier 2 / Strong — multiple orthogonal methods (ChIP, functional assays, ubiquitination assays, in vivo models, molecular docking) in single rigorous study establishing mechanistic axis","pmids":["38769295"],"is_preprint":false},{"year":2019,"finding":"SOX13 transcriptionally activates SPON2 by binding directly to the SPON2 promoter; SOX13 also activates the FUS promoter, forming a FUS/circ_002136/miR-138-5p/SOX13 feedback loop regulating angiogenesis in glioma endothelial cells.","method":"ChIP assay; dual-luciferase reporter assay; RNA pulldown; RNA-IP; siRNA knockdown functional assays (migration, tube formation)","journal":"Journal of experimental & clinical cancer research","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — ChIP and reporter assays establishing direct promoter binding, plus functional assays, single lab","pmids":["30736838"],"is_preprint":false},{"year":2019,"finding":"SOX13 mediates PAX8 expression in gastric cancer cell lines and transcriptionally activates Aurora B and Cyclin B1 through PAX8; SOX13 expression can rescue arrested proliferation caused by PAX8 silencing.","method":"siRNA knockdown; overexpression rescue assays; flow cytometry; EdU incorporation; CCK8 and colony formation assays","journal":"Artificial cells, nanomedicine, and biotechnology","confidence":"Low","confidence_rationale":"Tier 3 / Weak — functional assays show epistatic relationship between SOX13 and PAX8 but promoter/ChIP evidence not described in abstract; single lab, single approach","pmids":["31353958"],"is_preprint":false},{"year":2024,"finding":"SOX13 binds the LRP11 promoter and directly activates LRP11 transcription in breast cancer cells; LRP11 upregulation activates β-catenin-mediated transcriptional activation of PD-L1, reducing CD8+ T cell immune activity.","method":"Promoter-binding assay (SOX13 binding to LRP11 promoter); gain-of-function assays; co-culture system with CD8+ T cells; mouse allograft tumor models","journal":"Cellular signalling","confidence":"Low","confidence_rationale":"Tier 3 / Weak — promoter binding stated but ChIP/mutagenesis details not described in abstract; single lab","pmids":["39243917"],"is_preprint":false},{"year":2009,"finding":"Sox5, Sox6, and Sox13 (SoxD group) share a coiled-coil domain that mediates homodimerization and heterodimerization, leading to preferential binding to pairs of DNA recognition sites. SoxD proteins can enhance or antagonize Sox9/SoxE protein transactivation depending on cellular context.","method":"Review/synthesis of existing biochemical data on SoxD dimerization and DNA binding; reporter assays cited from multiple studies","journal":"The international journal of biochemistry & cell biology","confidence":"Low","confidence_rationale":"Tier 3 / Weak — review article synthesizing prior data; no new primary experiment described for SOX13 specifically","pmids":["19647094"],"is_preprint":false},{"year":2025,"finding":"SOX13 is a transcriptional target of POU3F2 in human neural progenitor cells; POU3F2-driven SOX13 expression mediates canonical Wnt signalling to regulate NPC proliferation and prevent premature radial glia specification.","method":"POU3F2 disruption in human NPCs; unbiased transcriptional target analysis; Wnt signaling reporter assays; proliferation and differentiation assays","journal":"Brain","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — genetic disruption with pathway reporter assays and unbiased analysis identifying SOX13 as a downstream mediator, single study","pmids":["40498903"],"is_preprint":false}],"current_model":"SOX13 is a SoxD-family HMG-box transcription factor that binds DNA as a homodimer (with homodimerization inhibiting DNA binding) or heterodimer (e.g., with Sox5), directly transactivates or represses target gene promoters (including SNAI2, MET, Twist1, SPON2, FUS, SCAF1, LRP11, TRIM11, PAX8), represses Wnt/TCF signaling by interacting with TCF1 (an interaction competed by Hhex), acts as a lineage-specifying transcription factor for IL-17-committed γδ T cells in the thymus (opposing αβ T cell fate), functions as a flow-sensitive anti-inflammatory transcription factor in endothelial cells by repressing chemokines CXCL10 and CCL5, and promotes mitochondrial supercomplex assembly via SCAF1 transactivation to confer ferroptosis resistance in cancer cells."},"narrative":{"mechanistic_narrative":"SOX13 is a SoxD-family HMG-box transcription factor that binds the SOX consensus motif and controls cell-fate and inflammatory programs across immune, neural, vascular, and cancer contexts [PMID:10871192, PMID:17218525]. Its DNA-binding behavior is gated by dimerization: a coiled-coil/leucine-zipper domain mediates homodimerization, which inhibits DNA binding, so productive activity favors heterodimer formation (e.g., with Sox5) [PMID:10871192, PMID:32461589]. A central, well-established role is as a lineage-specifying factor for IL-17-committed γδ T cells (γδT17) in the thymus: SOX13 promotes γδ T cell development while opposing αβ fate, acts together with TCF1 to program TCR-independent γδT17 progenitors, and a loss-of-function mutation selectively ablates Vγ4+ γδT17 cells and protects from psoriasis-like dermatitis [PMID:17218525, PMID:23624556, PMID:30413363]. SOX13 represses Wnt/TCF signaling by interacting with TCF1, an interaction antagonized by Hhex, which displaces SOX13 from the SOX13×TCF1 complex [PMID:17218525, PMID:20028982]. In endothelial cells, SOX13 is a flow-sensitive anti-inflammatory factor that represses the chemokines CXCL10 and CCL5 under laminar shear stress [PMID:36247423]. In cancer, SOX13 functions as a promoter-binding transactivator of effector genes—driving SNAI2/MET, Twist1, TRIM11, SPON2/FUS, LRP11, and SCAF1—to promote metastasis, EMT, angiogenesis, immune evasion, and, via SCAF1-dependent mitochondrial supercomplex assembly, ferroptosis resistance [PMID:32111984, PMID:32461589, PMID:33613102, PMID:38769295, PMID:30736838].","teleology":[{"year":1998,"claim":"Establishing SOX13's domain architecture and DNA-binding capacity defined it as an HMG-box factor with dimerization potential but no intrinsic transactivation on a simple motif concatamer.","evidence":"Cloning/sequence analysis with DNA-binding and reporter assays","pmids":["9421502"],"confidence":"Medium","gaps":["No physiological target promoter tested","Cofactor requirements for transactivation not identified"]},{"year":2000,"claim":"Demonstrating that homodimerization inhibits DNA binding revealed that SOX13 activity is gated by dimer state, implying heterodimer formation is needed for nuclear function.","evidence":"Recombinant protein DNA-binding assays with epitope/deletion mapping and immunohistochemistry","pmids":["10871192"],"confidence":"Medium","gaps":["Heterodimer partners not identified in this study","Structural basis of dimer-mediated inhibition unresolved"]},{"year":2007,"claim":"Reciprocal mouse genetics placed SOX13 as a γδ T cell lineage determinant acting through repression of Wnt/TCF signaling via TCF1, defining its first in vivo developmental pathway.","evidence":"Sox13 transgenic and knockout mice with Wnt/TCF reporter epistasis","pmids":["17218525"],"confidence":"High","gaps":["Direct transcriptional targets in γδ T cells not enumerated","Mechanism of TCF1 inhibition at chromatin not resolved"]},{"year":2009,"claim":"Identifying Hhex as a direct SOX13 partner that displaces SOX13 from TCF1 explained how SOX13-mediated Wnt repression is reversed, adding a regulatory layer to the pathway.","evidence":"Yeast two-hybrid, co-IP domain mapping, Wnt/TCF reporter assays, and embryo electroporation","pmids":["20028982"],"confidence":"High","gaps":["Physiological contexts where Hhex competition operates not fully mapped","Stoichiometry of SOX13/TCF1/Hhex complex unknown"]},{"year":2013,"claim":"A natural loss-of-function mutation showed the γδT17 defect is intrinsic and disease-relevant, linking SOX13 to inflammatory dermatitis.","evidence":"Natural mutant substrain mapping and thymic developmental assays plus psoriasis-like disease model","pmids":["23624556"],"confidence":"High","gaps":["Downstream effector genes of SOX13 in γδT17 cells not defined","Human relevance of the murine mutation not established"]},{"year":2018,"claim":"Reporter knock-in and scRNA-seq established that SOX13/TCF1 program γδT17 progenitors independently of TCR signaling, clarifying the timing and logic of lineage commitment.","evidence":"SOX13 reporter mice, thymic organ culture, and scRNA-seq of TCR-deficient mice","pmids":["30413363"],"confidence":"High","gaps":["Direct chromatin targets of the SOX13/TCF1 program not identified","How SOX13 cooperates mechanistically with TCF1 at target loci unresolved"]},{"year":2015,"claim":"Comparing SOX13 to Sox5/Sox6 in oligodendrocytes showed functional redundancy: it antagonizes Sox10-dependent myelin gene activation but is dispensable alone, revealing context-dependent SoxD redundancy.","evidence":"In vitro DNA binding, reporter assays, and Sox6/Sox13 double-knockout mice","pmids":["26525805"],"confidence":"Medium","gaps":["Direct SOX13 myelin targets in vivo not confirmed","Extent of SOX13/Sox6 redundancy across other lineages unknown"]},{"year":2019,"claim":"Multiple cancer studies began defining SOX13 as a direct promoter-binding transactivator of effector genes (SPON2, FUS, PAX8), extending its role beyond development into proliferation and angiogenesis.","evidence":"ChIP, dual-luciferase, RNA pulldown/RNA-IP, and knockdown/rescue functional assays in glioma and gastric cancer cells","pmids":["30736838","31353958"],"confidence":"Medium","gaps":["PAX8 axis lacks direct promoter/ChIP confirmation (Low confidence)","In vivo relevance of these axes limited"]},{"year":2020,"claim":"Mechanistic cancer studies defined direct SOX13 transcriptional targets driving metastasis/EMT and embedded SOX13 in upstream signaling, including HGF/STAT3 and Sox5 heterodimerization.","evidence":"ChIP, mutagenesis reporter assays, co-IP heterodimer detection, and invasion/rescue assays in colorectal and hepatocellular carcinoma","pmids":["32111984","32461589"],"confidence":"Medium","gaps":["Whether SNAI2/MET/Twist1 are conserved targets across tissues unknown","Relative contribution of homo- vs heterodimer to each target unresolved"]},{"year":2021,"claim":"Linking SOX13 to TRIM11 transactivation connected it to YAP/Hippo signaling via ubiquitin-mediated YAP stabilization, broadening its oncogenic output.","evidence":"Promoter-luciferase, co-IP, ubiquitination IP, and functional assays in anaplastic thyroid cancer","pmids":["33613102"],"confidence":"Medium","gaps":["Direct SOX13 binding site on TRIM11 promoter not finely mapped","Generality of the SOX13→TRIM11→YAP axis beyond thyroid cancer unknown"]},{"year":2022,"claim":"Identifying SOX13 as a flow-sensitive anti-inflammatory endothelial factor that represses CXCL10/CCL5 added a vascular homeostatic role distinct from its developmental functions.","evidence":"Reciprocal siRNA/overexpression, RNA-seq under shear, ELISA, and scRNA/scATAC of carotid ligation model","pmids":["36247423"],"confidence":"Medium","gaps":["Direct binding to CXCL10/CCL5 regulatory regions not demonstrated","Upstream flow-sensing mechanism controlling SOX13 expression unknown"]},{"year":2024,"claim":"Defining the SOX13→SCAF1→mitochondrial supercomplex axis established a metabolic mechanism for ferroptosis resistance and a druggable degradation strategy via zanamivir/TRIM25.","evidence":"ChIP/transactivation, supercomplex and respiration assays, molecular docking, ubiquitination assays, and xenografts in gastric cancer","pmids":["38769295"],"confidence":"High","gaps":["Whether SCAF1 is the dominant ferroptosis-relevant target unresolved","Selectivity of zanamivir for SOX13 in vivo not fully characterized"]},{"year":2024,"claim":"Placing SOX13 upstream of LRP11/β-catenin/PD-L1 implicated it in tumor immune evasion via CD8+ T cell suppression.","evidence":"Promoter-binding and gain-of-function assays, CD8+ T cell co-culture, and allograft models in breast cancer","pmids":["39243917"],"confidence":"Low","gaps":["ChIP/mutagenesis details for LRP11 promoter not described","Direct vs indirect activation of LRP11 not distinguished"]},{"year":2025,"claim":"Identifying SOX13 as a POU3F2 target mediating canonical Wnt signaling in human neural progenitors extended its developmental role to NPC proliferation and radial glia timing.","evidence":"POU3F2 disruption in human NPCs with unbiased target analysis and Wnt reporter/proliferation assays","pmids":["40498903"],"confidence":"Medium","gaps":["Direct SOX13 targets in NPCs not defined","Whether SOX13 activates or represses Wnt here vs its repressive role in T cells unresolved"]},{"year":null,"claim":"How dimer-state gating, partner choice (Sox5, TCF1, Hhex), and context determine whether SOX13 activates or represses a given target across its diverse developmental, vascular, and oncogenic roles remains unresolved.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No genome-wide direct target map across cell types","No structural model of SOX13 dimer/heterodimer on DNA","Rules governing activation vs repression switching unknown"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0140110","term_label":"transcription regulator activity","supporting_discovery_ids":[2,7,8,9,11,12]},{"term_id":"GO:0003677","term_label":"DNA binding","supporting_discovery_ids":[0,1,6]}],"localization":[{"term_id":"GO:0005634","term_label":"nucleus","supporting_discovery_ids":[0]}],"pathway":[{"term_id":"R-HSA-162582","term_label":"Signal Transduction","supporting_discovery_ids":[2,3,9,16]},{"term_id":"R-HSA-168256","term_label":"Immune System","supporting_discovery_ids":[2,4,5,10]},{"term_id":"R-HSA-1266738","term_label":"Developmental Biology","supporting_discovery_ids":[2,5,6,16]},{"term_id":"R-HSA-74160","term_label":"Gene expression (Transcription)","supporting_discovery_ids":[7,8,11,12]}],"complexes":[],"partners":["TCF1","HHEX","SOX5"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q9UN79","full_name":"Transcription factor SOX-13","aliases":["Islet cell antigen 12","SRY (Sex determining region Y)-box 13","Type 1 diabetes autoantigen ICA12"],"length_aa":622,"mass_kda":69.2,"function":"Transcription factor that binds to DNA at the consensus sequence 5'-AACAAT-3' (PubMed:10871192). Binds to the proximal promoter region of the myelin protein MPZ gene, and may thereby be involved in the differentiation of oligodendroglia in the developing spinal tube (By similarity). Binds to the gene promoter of MBP and acts as a transcriptional repressor (By similarity). Binds to and modifies the activity of TCF7/TCF1, thereby inhibiting transcription and modulates normal gamma-delta T-cell development and differentiation of IL17A expressing gamma-delta T-cells (By similarity). Regulates expression of BLK in the differentiation of IL17A expressing gamma-delta T-cells (By similarity). Promotes brown adipocyte differentiation (By similarity). Inhibitor of WNT signaling (PubMed:20028982)","subcellular_location":"Nucleus; Cytoplasm","url":"https://www.uniprot.org/uniprotkb/Q9UN79/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/SOX13","classification":"Not Classified","n_dependent_lines":0,"n_total_lines":1208,"dependency_fraction":0.0},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[],"url":"https://opencell.sf.czbiohub.org/search/SOX13","total_profiled":1310},"omim":[{"mim_id":"604748","title":"SRY-BOX 13; SOX13","url":"https://www.omim.org/entry/604748"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Enhanced","locations":[{"location":"Nucleoplasm","reliability":"Enhanced"}],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in many","driving_tissues":[],"url":"https://www.proteinatlas.org/search/SOX13"},"hgnc":{"alias_symbol":["Sox-13","ICA12","MGC117216"],"prev_symbol":[]},"alphafold":{"accession":"Q9UN79","domains":[{"cath_id":"1.10.30.10","chopping":"428-489","consensus_level":"medium","plddt":97.3129,"start":428,"end":489},{"cath_id":"-","chopping":"499-526","consensus_level":"medium","plddt":85.8768,"start":499,"end":526},{"cath_id":"1.20.5","chopping":"145-222","consensus_level":"medium","plddt":94.2621,"start":145,"end":222}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q9UN79","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q9UN79-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q9UN79-F1-predicted_aligned_error_v6.png","plddt_mean":59.78},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=SOX13","jax_strain_url":"https://www.jax.org/strain/search?query=SOX13"},"sequence":{"accession":"Q9UN79","fasta_url":"https://rest.uniprot.org/uniprotkb/Q9UN79.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q9UN79/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q9UN79"}},"corpus_meta":[{"pmid":"14517545","id":"PMC_14517545","title":"Vertebrate neurogenesis is counteracted by Sox1-3 activity.","date":"2003","source":"Nature neuroscience","url":"https://pubmed.ncbi.nlm.nih.gov/14517545","citation_count":668,"is_preprint":false},{"pmid":"23624556","id":"PMC_23624556","title":"Deficiency in IL-17-committed Vγ4(+) γδ T cells in a spontaneous Sox13-mutant CD45.1(+) congenic mouse substrain provides protection from dermatitis.","date":"2013","source":"Nature immunology","url":"https://pubmed.ncbi.nlm.nih.gov/23624556","citation_count":176,"is_preprint":false},{"pmid":"30736838","id":"PMC_30736838","title":"FUS/circ_002136/miR-138-5p/SOX13 feedback loop regulates angiogenesis in Glioma.","date":"2019","source":"Journal of experimental & clinical cancer research : CR","url":"https://pubmed.ncbi.nlm.nih.gov/30736838","citation_count":156,"is_preprint":false},{"pmid":"17218525","id":"PMC_17218525","title":"Regulation of gammadelta versus alphabeta T lymphocyte differentiation by the transcription factor SOX13.","date":"2007","source":"Science (New York, N.Y.)","url":"https://pubmed.ncbi.nlm.nih.gov/17218525","citation_count":150,"is_preprint":false},{"pmid":"19647094","id":"PMC_19647094","title":"The SoxD transcription factors--Sox5, Sox6, and Sox13--are key cell fate modulators.","date":"2009","source":"The international journal of biochemistry & cell biology","url":"https://pubmed.ncbi.nlm.nih.gov/19647094","citation_count":135,"is_preprint":false},{"pmid":"30413363","id":"PMC_30413363","title":"Interleukin-17-Producing γδ T Cells Originate from SOX13+ Progenitors that Are Independent of γδTCR Signaling.","date":"2018","source":"Immunity","url":"https://pubmed.ncbi.nlm.nih.gov/30413363","citation_count":84,"is_preprint":false},{"pmid":"38769295","id":"PMC_38769295","title":"Targeting SOX13 inhibits assembly of respiratory chain supercomplexes to overcome ferroptosis resistance in gastric cancer.","date":"2024","source":"Nature communications","url":"https://pubmed.ncbi.nlm.nih.gov/38769295","citation_count":72,"is_preprint":false},{"pmid":"31953613","id":"PMC_31953613","title":"Long non-coding RNA MALAT1 facilitates the tumorigenesis, invasion and glycolysis of multiple myeloma via miR-1271-5p/SOX13 axis.","date":"2020","source":"Journal of cancer research and clinical oncology","url":"https://pubmed.ncbi.nlm.nih.gov/31953613","citation_count":64,"is_preprint":false},{"pmid":"10871192","id":"PMC_10871192","title":"Sex-determining region Y-related protein SOX13 is a diabetes autoantigen expressed in pancreatic islets.","date":"2000","source":"Diabetes","url":"https://pubmed.ncbi.nlm.nih.gov/10871192","citation_count":57,"is_preprint":false},{"pmid":"32111984","id":"PMC_32111984","title":"SOX13 promotes colorectal cancer metastasis by transactivating SNAI2 and c-MET.","date":"2020","source":"Oncogene","url":"https://pubmed.ncbi.nlm.nih.gov/32111984","citation_count":46,"is_preprint":false},{"pmid":"9421502","id":"PMC_9421502","title":"High expression of the HMG box factor sox-13 in arterial walls during embryonic development.","date":"1998","source":"Nucleic acids research","url":"https://pubmed.ncbi.nlm.nih.gov/9421502","citation_count":43,"is_preprint":false},{"pmid":"33613102","id":"PMC_33613102","title":"SOX13/TRIM11/YAP axis promotes the proliferation, migration and chemoresistance of anaplastic thyroid cancer.","date":"2021","source":"International journal of biological sciences","url":"https://pubmed.ncbi.nlm.nih.gov/33613102","citation_count":40,"is_preprint":false},{"pmid":"26045173","id":"PMC_26045173","title":"Expressions of Sox9, Sox5, and Sox13 transcription factors in mice testis during postnatal development.","date":"2015","source":"Molecular and cellular 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downregulation in peripheral blood mononuclear cells of patients with Klinefelter syndrome.","date":"2021","source":"Asian journal of andrology","url":"https://pubmed.ncbi.nlm.nih.gov/33109779","citation_count":1,"is_preprint":false},{"pmid":"12021128","id":"PMC_12021128","title":"Antibodies to new beta cell antigen ICA12 in Latvian diabetes patients.","date":"2002","source":"Annals of the New York Academy of Sciences","url":"https://pubmed.ncbi.nlm.nih.gov/12021128","citation_count":1,"is_preprint":false},{"pmid":"38270621","id":"PMC_38270621","title":"THAP9-AS1 promotes nasopharyngeal carcinoma progression through targeted regulation of the miR-185-5p/SOX13 axis.","date":"2024","source":"Physiology international","url":"https://pubmed.ncbi.nlm.nih.gov/38270621","citation_count":0,"is_preprint":false},{"pmid":"14679071","id":"PMC_14679071","title":"SOX13 autoantibodies are likely to be a supplementary marker for type 1 diabetes in Korea.","date":"2003","source":"Annals of the New York Academy of Sciences","url":"https://pubmed.ncbi.nlm.nih.gov/14679071","citation_count":0,"is_preprint":false},{"pmid":null,"id":"bio_10.1101_2025.11.25.687998","title":"A conserved transcriptional backbone and rewiring of gene-regulatory networks in activated human CD4⁺ T cells","date":"2025-11-27","source":"bioRxiv","url":"https://doi.org/10.1101/2025.11.25.687998","citation_count":0,"is_preprint":true}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":22996,"output_tokens":4115,"usd":0.065356,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":12157,"output_tokens":4506,"usd":0.086718,"stage2_stop_reason":"end_turn"},"total_usd":0.152074,"stage1_batch_id":"msgbatch_013LWZZT6MWaqB9qyTSeQBmU","stage2_batch_id":"msgbatch_0194ZzQaTGNpruoNJBbEMbt3","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2000,\n      \"finding\": \"SOX13 protein binds to the SOX consensus DNA motif AACAAT, and homodimer formation inhibits DNA binding, suggesting activation requires heterodimer formation for nuclear import and DNA binding.\",\n      \"method\": \"Recombinant protein DNA-binding assay; deletion mapping of antibody epitopes; immunohistochemistry on pancreatic sections\",\n      \"journal\": \"Diabetes\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct in vitro DNA-binding assay with homodimer inhibition demonstrated, single lab with two orthogonal approaches (DNA binding + immunohistochemistry)\",\n      \"pmids\": [\"10871192\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 1998,\n      \"finding\": \"Sox-13 protein contains an HMG box, a leucine zipper motif, and a glutamine-rich stretch; it binds the HMG box consensus motif AACAAAG but does not transactivate transcription through a concatamer of this motif.\",\n      \"method\": \"Cloning and sequence analysis; DNA-binding assay; transcriptional reporter assay\",\n      \"journal\": \"Nucleic acids research\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct DNA-binding assay and reporter assay performed, single lab with two orthogonal methods establishing both binding and lack of transactivation\",\n      \"pmids\": [\"9421502\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2007,\n      \"finding\": \"SOX13 promotes γδ T cell development while opposing αβ T cell differentiation; one mechanism is inhibition of Wnt/TCF signaling through interaction with TCF1. Loss of Sox13 impairs γδ T cell development but not αβ T cell development.\",\n      \"method\": \"Sox13 transgenic mice; Sox13-deficient mice; genetic epistasis with Wnt/TCF pathway reporter assays\",\n      \"journal\": \"Science\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — reciprocal gain- and loss-of-function genetic models with defined cellular phenotypes, pathway placement via Wnt/TCF interaction, replicated across transgenic and knockout approaches\",\n      \"pmids\": [\"17218525\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2009,\n      \"finding\": \"SOX13 interacts directly with Hhex (hematopoietically expressed homeobox) protein; SOX13 represses Wnt/TCF signaling by interacting with TCF1, and Hhex blocks this SOX13-dependent repression by displacing SOX13 from the SOX13×TCF1 complex.\",\n      \"method\": \"Yeast two-hybrid screen; co-immunoprecipitation; domain mapping; Wnt/TCF luciferase reporter assay; mouse embryo electroporation\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — yeast two-hybrid, co-IP domain mapping, and functional reporter assays combined with in vivo embryo electroporation, multiple orthogonal methods in single study\",\n      \"pmids\": [\"20028982\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2013,\n      \"finding\": \"A spontaneous loss-of-function mutation in Sox13 causes an intrinsic defect in development of Vγ4+ IL-17-committed γδ T cells (γδT17 cells) in the neonatal thymus, and Sox13-mutant mice are protected from psoriasis-like dermatitis.\",\n      \"method\": \"Natural mutant mouse substrain characterization; genetic mapping of Sox13 mutation; thymic developmental assays\",\n      \"journal\": \"Nature immunology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — natural loss-of-function mutation mapped to Sox13 with defined cellular phenotype in thymic development and inflammatory disease model, replicated functionally\",\n      \"pmids\": [\"23624556\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"SOX13+ progenitors in the fetal thymus give rise to IL-17-producing γδ T cells (Tγδ17) independently of γδTCR signaling; generation of these lineage-committed progenitors and Tγδ17 cells is controlled by TCF1 and SOX13.\",\n      \"method\": \"SOX13 reporter knock-in mice; thymic organ culture developmental assays; single-cell transcriptome analysis of TCR-deficient mice\",\n      \"journal\": \"Immunity\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — reporter mice, organ culture assays, and scRNA-seq in TCR-deficient mice using multiple orthogonal methods to establish TCR-independent SOX13/TCF1-dependent lineage programming\",\n      \"pmids\": [\"30413363\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2015,\n      \"finding\": \"Sox13 can bind to the same sites in myelin gene promoters as Sox5 and Sox6 in vitro, and reporter gene assays show Sox13 antagonizes Sox10-dependent transactivation of myelin gene promoters, similar to Sox5 and Sox6. Sox13 deletion alone does not impair oligodendrocyte development, but Sox6/Sox13 double-deficient mice show more prominent premature oligodendrocyte precursor differentiation than Sox6-deficient mice alone.\",\n      \"method\": \"In vitro DNA-binding assay; reporter gene assay; Sox13 knockout mice; Sox6/Sox13 double-knockout mice\",\n      \"journal\": \"Journal of neurochemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — in vitro binding, reporter assays, and double-KO genetic epistasis in single study, single lab\",\n      \"pmids\": [\"26525805\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"SOX13 promotes colorectal cancer metastasis by directly transactivating SNAI2 and MET (c-MET) promoters; SOX13 is itself a direct transcriptional target of HGF/STAT3 signaling, forming a HGF/STAT3/SOX13/c-MET axis.\",\n      \"method\": \"Serial deletion and site-directed mutagenesis luciferase reporter assays; ChIP assays; functional complementation analyses; migration/invasion assays with SOX13 overexpression and knockdown\",\n      \"journal\": \"Oncogene\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — ChIP, mutagenesis-based reporter assays, and functional complementation by single lab with multiple orthogonal methods\",\n      \"pmids\": [\"32111984\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"Sox13 promotes hepatocellular carcinoma invasion and EMT by directly activating Twist1 transcription; Sox13 forms a heterodimer with Sox5, and this Sox13/Sox5 heterodimer cooperatively enhances transcriptional activity at the Twist1 promoter.\",\n      \"method\": \"Transcriptional reporter assays; co-immunoprecipitation (heterodimer detection); Transwell invasion assay; rescue experiments with Twist1 depletion\",\n      \"journal\": \"Laboratory investigation\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reporter assays and co-IP for heterodimer, plus functional rescue, multiple orthogonal methods in single lab\",\n      \"pmids\": [\"32461589\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"SOX13 activates TRIM11 transcription by binding to the TRIM11 promoter. TRIM11, an E3 ubiquitin ligase, then promotes mono-ubiquitination of YAP, prolonging YAP protein half-life and activating Hippo pathway target genes (CTGF, ANKRD1, CYR61), promoting anaplastic thyroid cancer proliferation, migration, and chemoresistance.\",\n      \"method\": \"TRIM11 promoter-luciferase reporter assay; co-immunoprecipitation; ubiquitin-based immunoprecipitation assays; domain mapping; CCK8/wound-healing/transwell assays\",\n      \"journal\": \"International journal of biological sciences\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — promoter reporter, ubiquitination IP, and domain mapping in single lab with multiple orthogonal methods\",\n      \"pmids\": [\"33613102\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"SOX13 is a flow-sensitive transcription factor preferentially expressed in endothelial cells under stable (unidirectional laminar) flow; siRNA-mediated knockdown of SOX13 increases endothelial inflammatory responses under laminar shear stress, and SOX13 represses pro-inflammatory chemokines CXCL10 and CCL5. SOX13 overexpression prevents endothelial inflammation.\",\n      \"method\": \"siRNA knockdown; SOX13 overexpression; RNAseq in human aortic ECs under shear conditions; ELISA validation; scRNAseq/scATACseq of mouse carotid ligation model\",\n      \"journal\": \"Frontiers in cardiovascular medicine\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reciprocal KD/OE experiments with defined chemokine phenotype, RNAseq, and in vivo genomics, single lab\",\n      \"pmids\": [\"36247423\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"SOX13 directly transactivates SCAF1, which promotes assembly of mitochondrial electron transport chain supercomplexes, increasing mitochondrial respiration and energetics, thereby conferring ferroptosis resistance in gastric cancer. The drug zanamivir targets SOX13 directly and promotes TRIM25-mediated ubiquitination and degradation of SOX13 to reverse ferroptosis resistance.\",\n      \"method\": \"ChIP/transactivation assays; SOX13/SCAF1 manipulation in cell lines; supercomplex assembly and mitochondrial respiration assays; molecular docking; ubiquitination assays; xenograft models\",\n      \"journal\": \"Nature communications\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — multiple orthogonal methods (ChIP, functional assays, ubiquitination assays, in vivo models, molecular docking) in single rigorous study establishing mechanistic axis\",\n      \"pmids\": [\"38769295\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"SOX13 transcriptionally activates SPON2 by binding directly to the SPON2 promoter; SOX13 also activates the FUS promoter, forming a FUS/circ_002136/miR-138-5p/SOX13 feedback loop regulating angiogenesis in glioma endothelial cells.\",\n      \"method\": \"ChIP assay; dual-luciferase reporter assay; RNA pulldown; RNA-IP; siRNA knockdown functional assays (migration, tube formation)\",\n      \"journal\": \"Journal of experimental & clinical cancer research\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — ChIP and reporter assays establishing direct promoter binding, plus functional assays, single lab\",\n      \"pmids\": [\"30736838\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"SOX13 mediates PAX8 expression in gastric cancer cell lines and transcriptionally activates Aurora B and Cyclin B1 through PAX8; SOX13 expression can rescue arrested proliferation caused by PAX8 silencing.\",\n      \"method\": \"siRNA knockdown; overexpression rescue assays; flow cytometry; EdU incorporation; CCK8 and colony formation assays\",\n      \"journal\": \"Artificial cells, nanomedicine, and biotechnology\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — functional assays show epistatic relationship between SOX13 and PAX8 but promoter/ChIP evidence not described in abstract; single lab, single approach\",\n      \"pmids\": [\"31353958\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"SOX13 binds the LRP11 promoter and directly activates LRP11 transcription in breast cancer cells; LRP11 upregulation activates β-catenin-mediated transcriptional activation of PD-L1, reducing CD8+ T cell immune activity.\",\n      \"method\": \"Promoter-binding assay (SOX13 binding to LRP11 promoter); gain-of-function assays; co-culture system with CD8+ T cells; mouse allograft tumor models\",\n      \"journal\": \"Cellular signalling\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — promoter binding stated but ChIP/mutagenesis details not described in abstract; single lab\",\n      \"pmids\": [\"39243917\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2009,\n      \"finding\": \"Sox5, Sox6, and Sox13 (SoxD group) share a coiled-coil domain that mediates homodimerization and heterodimerization, leading to preferential binding to pairs of DNA recognition sites. SoxD proteins can enhance or antagonize Sox9/SoxE protein transactivation depending on cellular context.\",\n      \"method\": \"Review/synthesis of existing biochemical data on SoxD dimerization and DNA binding; reporter assays cited from multiple studies\",\n      \"journal\": \"The international journal of biochemistry & cell biology\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — review article synthesizing prior data; no new primary experiment described for SOX13 specifically\",\n      \"pmids\": [\"19647094\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"SOX13 is a transcriptional target of POU3F2 in human neural progenitor cells; POU3F2-driven SOX13 expression mediates canonical Wnt signalling to regulate NPC proliferation and prevent premature radial glia specification.\",\n      \"method\": \"POU3F2 disruption in human NPCs; unbiased transcriptional target analysis; Wnt signaling reporter assays; proliferation and differentiation assays\",\n      \"journal\": \"Brain\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — genetic disruption with pathway reporter assays and unbiased analysis identifying SOX13 as a downstream mediator, single study\",\n      \"pmids\": [\"40498903\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"SOX13 is a SoxD-family HMG-box transcription factor that binds DNA as a homodimer (with homodimerization inhibiting DNA binding) or heterodimer (e.g., with Sox5), directly transactivates or represses target gene promoters (including SNAI2, MET, Twist1, SPON2, FUS, SCAF1, LRP11, TRIM11, PAX8), represses Wnt/TCF signaling by interacting with TCF1 (an interaction competed by Hhex), acts as a lineage-specifying transcription factor for IL-17-committed γδ T cells in the thymus (opposing αβ T cell fate), functions as a flow-sensitive anti-inflammatory transcription factor in endothelial cells by repressing chemokines CXCL10 and CCL5, and promotes mitochondrial supercomplex assembly via SCAF1 transactivation to confer ferroptosis resistance in cancer cells.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"SOX13 is a SoxD-family HMG-box transcription factor that binds the SOX consensus motif and controls cell-fate and inflammatory programs across immune, neural, vascular, and cancer contexts [#0, #2]. Its DNA-binding behavior is gated by dimerization: a coiled-coil/leucine-zipper domain mediates homodimerization, which inhibits DNA binding, so productive activity favors heterodimer formation (e.g., with Sox5) [#0, #8]. A central, well-established role is as a lineage-specifying factor for IL-17-committed \\u03b3\\u03b4 T cells (\\u03b3\\u03b4T17) in the thymus: SOX13 promotes \\u03b3\\u03b4 T cell development while opposing \\u03b1\\u03b2 fate, acts together with TCF1 to program TCR-independent \\u03b3\\u03b4T17 progenitors, and a loss-of-function mutation selectively ablates V\\u03b34+ \\u03b3\\u03b4T17 cells and protects from psoriasis-like dermatitis [#2, #4, #5]. SOX13 represses Wnt/TCF signaling by interacting with TCF1, an interaction antagonized by Hhex, which displaces SOX13 from the SOX13\\u00d7TCF1 complex [#2, #3]. In endothelial cells, SOX13 is a flow-sensitive anti-inflammatory factor that represses the chemokines CXCL10 and CCL5 under laminar shear stress [#10]. In cancer, SOX13 functions as a promoter-binding transactivator of effector genes\\u2014driving SNAI2/MET, Twist1, TRIM11, SPON2/FUS, LRP11, and SCAF1\\u2014to promote metastasis, EMT, angiogenesis, immune evasion, and, via SCAF1-dependent mitochondrial supercomplex assembly, ferroptosis resistance [#7, #8, #9, #11, #12].\",\n  \"teleology\": [\n    {\n      \"year\": 1998,\n      \"claim\": \"Establishing SOX13's domain architecture and DNA-binding capacity defined it as an HMG-box factor with dimerization potential but no intrinsic transactivation on a simple motif concatamer.\",\n      \"evidence\": \"Cloning/sequence analysis with DNA-binding and reporter assays\",\n      \"pmids\": [\"9421502\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No physiological target promoter tested\", \"Cofactor requirements for transactivation not identified\"]\n    },\n    {\n      \"year\": 2000,\n      \"claim\": \"Demonstrating that homodimerization inhibits DNA binding revealed that SOX13 activity is gated by dimer state, implying heterodimer formation is needed for nuclear function.\",\n      \"evidence\": \"Recombinant protein DNA-binding assays with epitope/deletion mapping and immunohistochemistry\",\n      \"pmids\": [\"10871192\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Heterodimer partners not identified in this study\", \"Structural basis of dimer-mediated inhibition unresolved\"]\n    },\n    {\n      \"year\": 2007,\n      \"claim\": \"Reciprocal mouse genetics placed SOX13 as a \\u03b3\\u03b4 T cell lineage determinant acting through repression of Wnt/TCF signaling via TCF1, defining its first in vivo developmental pathway.\",\n      \"evidence\": \"Sox13 transgenic and knockout mice with Wnt/TCF reporter epistasis\",\n      \"pmids\": [\"17218525\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Direct transcriptional targets in \\u03b3\\u03b4 T cells not enumerated\", \"Mechanism of TCF1 inhibition at chromatin not resolved\"]\n    },\n    {\n      \"year\": 2009,\n      \"claim\": \"Identifying Hhex as a direct SOX13 partner that displaces SOX13 from TCF1 explained how SOX13-mediated Wnt repression is reversed, adding a regulatory layer to the pathway.\",\n      \"evidence\": \"Yeast two-hybrid, co-IP domain mapping, Wnt/TCF reporter assays, and embryo electroporation\",\n      \"pmids\": [\"20028982\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Physiological contexts where Hhex competition operates not fully mapped\", \"Stoichiometry of SOX13/TCF1/Hhex complex unknown\"]\n    },\n    {\n      \"year\": 2013,\n      \"claim\": \"A natural loss-of-function mutation showed the \\u03b3\\u03b4T17 defect is intrinsic and disease-relevant, linking SOX13 to inflammatory dermatitis.\",\n      \"evidence\": \"Natural mutant substrain mapping and thymic developmental assays plus psoriasis-like disease model\",\n      \"pmids\": [\"23624556\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Downstream effector genes of SOX13 in \\u03b3\\u03b4T17 cells not defined\", \"Human relevance of the murine mutation not established\"]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"Reporter knock-in and scRNA-seq established that SOX13/TCF1 program \\u03b3\\u03b4T17 progenitors independently of TCR signaling, clarifying the timing and logic of lineage commitment.\",\n      \"evidence\": \"SOX13 reporter mice, thymic organ culture, and scRNA-seq of TCR-deficient mice\",\n      \"pmids\": [\"30413363\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Direct chromatin targets of the SOX13/TCF1 program not identified\", \"How SOX13 cooperates mechanistically with TCF1 at target loci unresolved\"]\n    },\n    {\n      \"year\": 2015,\n      \"claim\": \"Comparing SOX13 to Sox5/Sox6 in oligodendrocytes showed functional redundancy: it antagonizes Sox10-dependent myelin gene activation but is dispensable alone, revealing context-dependent SoxD redundancy.\",\n      \"evidence\": \"In vitro DNA binding, reporter assays, and Sox6/Sox13 double-knockout mice\",\n      \"pmids\": [\"26525805\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Direct SOX13 myelin targets in vivo not confirmed\", \"Extent of SOX13/Sox6 redundancy across other lineages unknown\"]\n    },\n    {\n      \"year\": 2019,\n      \"claim\": \"Multiple cancer studies began defining SOX13 as a direct promoter-binding transactivator of effector genes (SPON2, FUS, PAX8), extending its role beyond development into proliferation and angiogenesis.\",\n      \"evidence\": \"ChIP, dual-luciferase, RNA pulldown/RNA-IP, and knockdown/rescue functional assays in glioma and gastric cancer cells\",\n      \"pmids\": [\"30736838\", \"31353958\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"PAX8 axis lacks direct promoter/ChIP confirmation (Low confidence)\", \"In vivo relevance of these axes limited\"]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"Mechanistic cancer studies defined direct SOX13 transcriptional targets driving metastasis/EMT and embedded SOX13 in upstream signaling, including HGF/STAT3 and Sox5 heterodimerization.\",\n      \"evidence\": \"ChIP, mutagenesis reporter assays, co-IP heterodimer detection, and invasion/rescue assays in colorectal and hepatocellular carcinoma\",\n      \"pmids\": [\"32111984\", \"32461589\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Whether SNAI2/MET/Twist1 are conserved targets across tissues unknown\", \"Relative contribution of homo- vs heterodimer to each target unresolved\"]\n    },\n    {\n      \"year\": 2021,\n      \"claim\": \"Linking SOX13 to TRIM11 transactivation connected it to YAP/Hippo signaling via ubiquitin-mediated YAP stabilization, broadening its oncogenic output.\",\n      \"evidence\": \"Promoter-luciferase, co-IP, ubiquitination IP, and functional assays in anaplastic thyroid cancer\",\n      \"pmids\": [\"33613102\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Direct SOX13 binding site on TRIM11 promoter not finely mapped\", \"Generality of the SOX13\\u2192TRIM11\\u2192YAP axis beyond thyroid cancer unknown\"]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"Identifying SOX13 as a flow-sensitive anti-inflammatory endothelial factor that represses CXCL10/CCL5 added a vascular homeostatic role distinct from its developmental functions.\",\n      \"evidence\": \"Reciprocal siRNA/overexpression, RNA-seq under shear, ELISA, and scRNA/scATAC of carotid ligation model\",\n      \"pmids\": [\"36247423\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Direct binding to CXCL10/CCL5 regulatory regions not demonstrated\", \"Upstream flow-sensing mechanism controlling SOX13 expression unknown\"]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Defining the SOX13\\u2192SCAF1\\u2192mitochondrial supercomplex axis established a metabolic mechanism for ferroptosis resistance and a druggable degradation strategy via zanamivir/TRIM25.\",\n      \"evidence\": \"ChIP/transactivation, supercomplex and respiration assays, molecular docking, ubiquitination assays, and xenografts in gastric cancer\",\n      \"pmids\": [\"38769295\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Whether SCAF1 is the dominant ferroptosis-relevant target unresolved\", \"Selectivity of zanamivir for SOX13 in vivo not fully characterized\"]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Placing SOX13 upstream of LRP11/\\u03b2-catenin/PD-L1 implicated it in tumor immune evasion via CD8+ T cell suppression.\",\n      \"evidence\": \"Promoter-binding and gain-of-function assays, CD8+ T cell co-culture, and allograft models in breast cancer\",\n      \"pmids\": [\"39243917\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"ChIP/mutagenesis details for LRP11 promoter not described\", \"Direct vs indirect activation of LRP11 not distinguished\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Identifying SOX13 as a POU3F2 target mediating canonical Wnt signaling in human neural progenitors extended its developmental role to NPC proliferation and radial glia timing.\",\n      \"evidence\": \"POU3F2 disruption in human NPCs with unbiased target analysis and Wnt reporter/proliferation assays\",\n      \"pmids\": [\"40498903\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Direct SOX13 targets in NPCs not defined\", \"Whether SOX13 activates or represses Wnt here vs its repressive role in T cells unresolved\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How dimer-state gating, partner choice (Sox5, TCF1, Hhex), and context determine whether SOX13 activates or represses a given target across its diverse developmental, vascular, and oncogenic roles remains unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No genome-wide direct target map across cell types\", \"No structural model of SOX13 dimer/heterodimer on DNA\", \"Rules governing activation vs repression switching unknown\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0140110\", \"supporting_discovery_ids\": [2, 7, 8, 9, 11, 12]},\n      {\"term_id\": \"GO:0003677\", \"supporting_discovery_ids\": [0, 1, 6]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005634\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-162582\", \"supporting_discovery_ids\": [2, 3, 9, 16]},\n      {\"term_id\": \"R-HSA-168256\", \"supporting_discovery_ids\": [2, 4, 5, 10]},\n      {\"term_id\": \"R-HSA-1266738\", \"supporting_discovery_ids\": [2, 5, 6, 16]},\n      {\"term_id\": \"R-HSA-74160\", \"supporting_discovery_ids\": [7, 8, 11, 12]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\"TCF1\", \"Hhex\", \"Sox5\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":6,"faith_total":6,"faith_pct":100.0}}