{"gene":"PLXNA3","run_date":"2026-04-28T19:45:44","timeline":{"discoveries":[{"year":1999,"finding":"PLXNA3 (plexin-A3) is a member of the plexin receptor family that associates with neuropilins as co-receptors for secreted (class 3) semaphorins; plexin cytoplasmic domains associate with a tyrosine kinase activity, and truncated plexin-A1 expression blocks axon repulsion by Sema3A, establishing plexins as functional semaphorin receptors that trigger cell repulsion signaling.","method":"Binding assays, co-immunoprecipitation, truncated dominant-negative expression in neurons","journal":"Cell","confidence":"High","confidence_rationale":"Tier 2 — reciprocal co-IP, functional dominant-negative assay, replicated across multiple plexin family members in a landmark study","pmids":["10520995"],"is_preprint":false},{"year":1996,"finding":"PLXNA3 (SEX gene) was identified as a transmembrane protein located on the human X chromosome (Xq28) with homology to the extracellular domain of MET/HGF receptor family; it is expressed predominantly in brain during neural development, is glycosylated and exposed at the cell surface, but unlike MET, does not show tyrosine kinase activity itself.","method":"cDNA cloning, Northern blot, in situ hybridization, cell surface biotinylation, MET-SEX chimera kinase assay","journal":"Proceedings of the National Academy of Sciences of the United States of America","confidence":"High","confidence_rationale":"Tier 1-2 — original cloning with multiple orthogonal methods including in vitro kinase assay and in situ hybridization","pmids":["8570614"],"is_preprint":false},{"year":1996,"finding":"PLXNA3 (plexin) was mapped to human Xq28 and identified as a gene in the 219-kb high-GC region between RCP/GCP and G6PD loci, with its exon structure inferred from sequence and 65.5% identity to the Xenopus plexin analogue.","method":"Large-scale genomic sequencing, GRAIL gene prediction, homology analysis","journal":"Human molecular genetics","confidence":"Medium","confidence_rationale":"Tier 3 — genomic localization and sequence-based identification without functional assay","pmids":["8733135"],"is_preprint":false},{"year":1996,"finding":"Mouse plexin 3 (ortholog of human PLXNA3) was isolated from E17.5 mouse brain cDNA libraries and identified as a type I membrane protein with >60% amino acid identity to mouse plexin 1 and three cysteine-rich repeats in the extracellular domain; Northern blot revealed molecular heterogeneity in plexin 3 transcripts.","method":"cDNA library screening, sequencing, Northern blot analysis","journal":"Biochemical and biophysical research communications","confidence":"Medium","confidence_rationale":"Tier 3 — cloning and expression characterization without functional assay","pmids":["8806646"],"is_preprint":false},{"year":2009,"finding":"PLXNA3 (plexin A3) expression significantly increases during M-CSF-mediated differentiation of human monocytes into M2 alternatively activated macrophages; Sema3A acting through NRP1/plexin A3-containing receptor complexes induces apoptosis in monocyte-derived macrophages and cooperates with anti-Fas antibody to augment apoptosis.","method":"Flow cytometry, cell surface binding assay, apoptosis assays, siRNA knockdown","journal":"Human immunology","confidence":"Medium","confidence_rationale":"Tier 2-3 — functional apoptosis assay with receptor expression characterization in primary human cells","pmids":["19480842"],"is_preprint":false},{"year":2010,"finding":"Mammalian MTG16b (myeloid translocation gene 16b) functions as a dual A-kinase anchoring protein (AKAP) that selectively binds PlexinA1 and PlexinA3 on the plasma membrane but not PlexinB1; this interaction is regulated by PKA phosphorylation, suggesting a mechanism for integrating cAMP and semaphorin signaling in immune cells.","method":"Co-immunoprecipitation, AKAP overlay assay, PKA phosphorylation assay","journal":"FEBS letters","confidence":"Medium","confidence_rationale":"Tier 2 — selective binding demonstrated by co-IP with phospho-regulation, single study","pmids":["20138877"],"is_preprint":false},{"year":2019,"finding":"PLXNA3, together with PLXNA1, is required for proper patterning of nasal axons that guide GnRH neurons during embryonic development; combined knockout of Plxna1 and Plxna3 in mice phenocopied the full spectrum of nasal axon and GnRH neuron defects seen in Sema3a knockout mice, whereas single knockouts did not, establishing PLXNA1 and PLXNA3 as cooperative receptors downstream of SEMA3A in the olfactory/vomeronasal axon guidance pathway required for GnRH neuron migration.","method":"Genetic epistasis (double knockout mice), immunofluorescence, GnRH neuron counting, axon tracing","journal":"Development (Cambridge, England)","confidence":"High","confidence_rationale":"Tier 2 — clean double-KO genetic epistasis with specific phenotypic readout, phenocopies ligand knockout","pmids":["31690636"],"is_preprint":false}],"current_model":"PLXNA3 is a transmembrane receptor of the plexin-A subfamily that cooperates with neuropilins and PLXNA1 to transduce SEMA3A repulsive signals; it is required (redundantly with PLXNA1) for nasal axon patterning and GnRH neuron migration, is upregulated during M2 macrophage differentiation where it mediates Sema3A-induced apoptosis, and selectively binds the AKAP MTG16b in a PKA-phosphorylation-dependent manner to integrate cAMP and semaphorin signaling, while lacking intrinsic tyrosine kinase activity despite its extracellular homology to MET-family receptors."},"narrative":{"teleology":[{"year":1996,"claim":"Cloning of PLXNA3 established it as a neural transmembrane protein with MET-like extracellular architecture but no intrinsic tyrosine kinase activity, raising the question of how it transduces signals.","evidence":"cDNA cloning from human and mouse brain, MET-PLXNA3 chimera kinase assay, in situ hybridization, cell surface biotinylation","pmids":["8570614","8806646","8733135"],"confidence":"High","gaps":["Ligand identity was unknown at this stage","Signaling mechanism downstream of the cytoplasmic domain was uncharacterized","Functional role in vivo was not addressed"]},{"year":1999,"claim":"Demonstration that plexins associate with neuropilin co-receptors and are required for Sema3A-mediated axon repulsion resolved the question of how class 3 semaphorins signal, positioning PLXNA3 as a signal-transducing subunit of the semaphorin receptor complex.","evidence":"Co-immunoprecipitation of plexin-neuropilin complexes, dominant-negative truncated plexin blocking Sema3A repulsion in neurons","pmids":["10520995"],"confidence":"High","gaps":["Relative contributions of individual plexin-A family members to Sema3A signaling in vivo were unclear","Identity of the tyrosine kinase associated with plexin cytoplasmic domains was not resolved"]},{"year":2009,"claim":"Finding that PLXNA3 is upregulated during M2 macrophage differentiation and mediates Sema3A-induced apoptosis extended its function beyond neuronal guidance to immune cell regulation.","evidence":"Flow cytometry and siRNA knockdown in M-CSF-differentiated human monocytes with apoptosis readout","pmids":["19480842"],"confidence":"Medium","gaps":["Downstream apoptotic pathway components linking PLXNA3 activation to cell death were not identified","In vivo relevance of macrophage PLXNA3-mediated apoptosis was not tested"]},{"year":2010,"claim":"Identification of MTG16b as a PKA-regulated AKAP that selectively binds PLXNA3 (and PLXNA1 but not PLXNB1) revealed a molecular node for cross-talk between cAMP and semaphorin signaling.","evidence":"Co-immunoprecipitation with AKAP overlay and PKA phosphorylation assays","pmids":["20138877"],"confidence":"Medium","gaps":["Functional consequence of MTG16b–PLXNA3 interaction on semaphorin-dependent signaling output was not measured","No reciprocal validation using endogenous proteins was reported","Cell types in which this cross-talk operates in vivo are undefined"]},{"year":2019,"claim":"Genetic epistasis in double-knockout mice demonstrated that PLXNA1 and PLXNA3 are cooperative, functionally redundant receptors required for SEMA3A-guided nasal axon patterning and GnRH neuron migration, explaining why single knockouts had shown mild phenotypes.","evidence":"Plxna1/Plxna3 double-KO mice with immunofluorescence, GnRH neuron counts, and axon tracing phenocopying Sema3a KO","pmids":["31690636"],"confidence":"High","gaps":["Whether PLXNA3 participates in Sema3A-independent guidance pathways was not addressed","Structural basis for PLXNA1/PLXNA3 redundancy or possible heteromeric receptor assembly is unknown"]},{"year":null,"claim":"Key open questions include the structural mechanism of PLXNA3 activation, the identity of kinases recruited to its cytoplasmic domain, and whether its roles in macrophage apoptosis and cAMP cross-talk are relevant in vivo.","evidence":"","pmids":[],"confidence":"High","gaps":["No high-resolution structure of PLXNA3 in an active signaling complex","Downstream signaling effectors beyond GTPase-activating activity inferred from family homology are not defined for PLXNA3 specifically","In vivo immune phenotype in Plxna3 single or double knockout remains uncharacterized"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0060089","term_label":"molecular transducer activity","supporting_discovery_ids":[0,6]}],"localization":[{"term_id":"GO:0005886","term_label":"plasma membrane","supporting_discovery_ids":[1,5]}],"pathway":[{"term_id":"R-HSA-1266738","term_label":"Developmental Biology","supporting_discovery_ids":[0,6]},{"term_id":"R-HSA-162582","term_label":"Signal Transduction","supporting_discovery_ids":[0,5,6]}],"complexes":[],"partners":["NRP1","PLXNA1","CBFA2T3","SEMA3A"],"other_free_text":[]},"mechanistic_narrative":"PLXNA3 (Plexin-A3) is a transmembrane semaphorin receptor that cooperates with neuropilins and PLXNA1 to transduce class 3 semaphorin repulsive signals during neural development and immune cell regulation. Originally cloned as a brain-enriched type I membrane protein with MET-family extracellular homology but lacking intrinsic tyrosine kinase activity, PLXNA3 associates with neuropilin co-receptors to form functional Sema3A receptor complexes that trigger axon repulsion and, in monocyte-derived macrophages, Sema3A-induced apoptosis [PMID:8570614, PMID:10520995, PMID:19480842]. Combined knockout of Plxna1 and Plxna3 in mice phenocopies the nasal axon patterning and GnRH neuron migration defects of Sema3a knockouts, establishing these two plexins as functionally redundant obligate receptors for SEMA3A-guided olfactory/vomeronasal axon guidance [PMID:31690636]. PLXNA3 also selectively binds the A-kinase anchoring protein MTG16b in a PKA-phosphorylation-dependent manner, providing a mechanism for integrating cAMP signaling with semaphorin receptor output [PMID:20138877]."},"prefetch_data":{"uniprot":{"accession":"P51805","full_name":"Plexin-A3","aliases":["Plexin-4","Semaphorin receptor SEX"],"length_aa":1871,"mass_kda":207.7,"function":"Coreceptor for SEMA3A and SEMA3F. Necessary for signaling by class 3 semaphorins and subsequent remodeling of the cytoskeleton. Plays a role in axon guidance in the developing nervous system. Regulates the migration of sympathetic neurons, but not of neural crest precursors. Required for normal dendrite spine morphology in pyramidal neurons. May play a role in regulating semaphorin-mediated programmed cell death in the developing nervous system. Class 3 semaphorins bind to a complex composed of a neuropilin and a plexin. The plexin modulates the affinity of the complex for specific semaphorins, and its cytoplasmic domain is required for the activation of down-stream signaling events in the cytoplasm","subcellular_location":"Cell membrane","url":"https://www.uniprot.org/uniprotkb/P51805/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/PLXNA3","classification":"Not Classified","n_dependent_lines":1,"n_total_lines":1208,"dependency_fraction":0.0008278145695364238},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[],"url":"https://opencell.sf.czbiohub.org/search/PLXNA3","total_profiled":1310},"omim":[{"mim_id":"601581","title":"NEURONAL CELL ADHESION MOLECULE; NRCAM","url":"https://www.omim.org/entry/601581"},{"mim_id":"300022","title":"PLEXIN A3; PLXNA3","url":"https://www.omim.org/entry/300022"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Approved","locations":[{"location":"Golgi apparatus","reliability":"Approved"},{"location":"Cytosol","reliability":"Approved"},{"location":"Plasma membrane","reliability":"Additional"}],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in all","driving_tissues":[],"url":"https://www.proteinatlas.org/search/PLXNA3"},"hgnc":{"alias_symbol":["SEX","XAP-6","6.3","Plxn3"],"prev_symbol":["PLXN4"]},"alphafold":{"accession":"P51805","domains":[{"cath_id":"-","chopping":"69-211","consensus_level":"medium","plddt":90.2572,"start":69,"end":211},{"cath_id":"2.130.10.10","chopping":"212-410","consensus_level":"medium","plddt":88.3173,"start":212,"end":410},{"cath_id":"3.30.1680.10","chopping":"497-540","consensus_level":"medium","plddt":88.838,"start":497,"end":540},{"cath_id":"2.60.40.10","chopping":"1025-1123","consensus_level":"high","plddt":85.2156,"start":1025,"end":1123},{"cath_id":"3.10.20.90","chopping":"1475-1578_1622-1631","consensus_level":"medium","plddt":83.882,"start":1475,"end":1631},{"cath_id":"2.60.40","chopping":"1145-1211","consensus_level":"high","plddt":81.8039,"start":1145,"end":1211}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/P51805","model_url":"https://alphafold.ebi.ac.uk/files/AF-P51805-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-P51805-F1-predicted_aligned_error_v6.png","plddt_mean":84.44},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=PLXNA3","jax_strain_url":"https://www.jax.org/strain/search?query=PLXNA3"},"sequence":{"accession":"P51805","fasta_url":"https://rest.uniprot.org/uniprotkb/P51805.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/P51805/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/P51805"}},"corpus_meta":[{"pmid":"9711866","id":"PMC_9711866","title":"A DNA test to sex most birds.","date":"1998","source":"Molecular ecology","url":"https://pubmed.ncbi.nlm.nih.gov/9711866","citation_count":1149,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"16530039","id":"PMC_16530039","title":"Sex chromosome specialization and degeneration in mammals.","date":"2006","source":"Cell","url":"https://pubmed.ncbi.nlm.nih.gov/16530039","citation_count":422,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"17610060","id":"PMC_17610060","title":"Why humans have sex.","date":"2007","source":"Archives of sexual behavior","url":"https://pubmed.ncbi.nlm.nih.gov/17610060","citation_count":351,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"22225601","id":"PMC_22225601","title":"Sex affects immunity.","date":"2012","source":"Journal of autoimmunity","url":"https://pubmed.ncbi.nlm.nih.gov/22225601","citation_count":318,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"11932767","id":"PMC_11932767","title":"Plant sex determination and sex chromosomes.","date":"2002","source":"Heredity","url":"https://pubmed.ncbi.nlm.nih.gov/11932767","citation_count":256,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"21962970","id":"PMC_21962970","title":"Are all sex chromosomes created equal?","date":"2011","source":"Trends in genetics : TIG","url":"https://pubmed.ncbi.nlm.nih.gov/21962970","citation_count":244,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"33180655","id":"PMC_33180655","title":"Sex determination, gonadal sex differentiation, and plasticity in vertebrate species.","date":"2020","source":"Physiological reviews","url":"https://pubmed.ncbi.nlm.nih.gov/33180655","citation_count":204,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"21942368","id":"PMC_21942368","title":"Sex in fungi.","date":"2011","source":"Annual review of genetics","url":"https://pubmed.ncbi.nlm.nih.gov/21942368","citation_count":203,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"29946321","id":"PMC_29946321","title":"Glucocorticoids, Sex Hormones, and Immunity.","date":"2018","source":"Frontiers in immunology","url":"https://pubmed.ncbi.nlm.nih.gov/29946321","citation_count":196,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"27373494","id":"PMC_27373494","title":"How to make a sex chromosome.","date":"2016","source":"Nature communications","url":"https://pubmed.ncbi.nlm.nih.gov/27373494","citation_count":195,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"17446395","id":"PMC_17446395","title":"Temperature sex reversal implies sex gene dosage in a reptile.","date":"2007","source":"Science (New York, N.Y.)","url":"https://pubmed.ncbi.nlm.nih.gov/17446395","citation_count":189,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"22974302","id":"PMC_22974302","title":"Dosage compensation of the sex chromosomes.","date":"2012","source":"Annual review of genetics","url":"https://pubmed.ncbi.nlm.nih.gov/22974302","citation_count":175,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"31544208","id":"PMC_31544208","title":"The Role of Sex and Sex Hormones in Neurodegenerative Diseases.","date":"2020","source":"Endocrine reviews","url":"https://pubmed.ncbi.nlm.nih.gov/31544208","citation_count":167,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"29706320","id":"PMC_29706320","title":"Sex differences in obesity, lipid metabolism, and inflammation-A role for the sex chromosomes?","date":"2018","source":"Molecular metabolism","url":"https://pubmed.ncbi.nlm.nih.gov/29706320","citation_count":164,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"38306984","id":"PMC_38306984","title":"Xist ribonucleoproteins promote female sex-biased autoimmunity.","date":"2024","source":"Cell","url":"https://pubmed.ncbi.nlm.nih.gov/38306984","citation_count":161,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"4157116","id":"PMC_4157116","title":"Actions of vertebrate sex hormones.","date":"1971","source":"Annual review of physiology","url":"https://pubmed.ncbi.nlm.nih.gov/4157116","citation_count":159,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"7567329","id":"PMC_7567329","title":"Sex chromosome tetrasomy and pentasomy.","date":"1995","source":"Pediatrics","url":"https://pubmed.ncbi.nlm.nih.gov/7567329","citation_count":155,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"27543823","id":"PMC_27543823","title":"Sex Determination, Sex Chromosomes, and Karyotype Evolution in Insects.","date":"2016","source":"The Journal of heredity","url":"https://pubmed.ncbi.nlm.nih.gov/27543823","citation_count":146,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"22822149","id":"PMC_22822149","title":"Sex-specific adaptation drives early sex chromosome evolution in Drosophila.","date":"2012","source":"Science (New York, N.Y.)","url":"https://pubmed.ncbi.nlm.nih.gov/22822149","citation_count":145,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"18391545","id":"PMC_18391545","title":"Sex chromosomes and sex determination in Lepidoptera.","date":"2008","source":"Sexual development : genetics, molecular biology, evolution, endocrinology, embryology, and pathology of sex determination and differentiation","url":"https://pubmed.ncbi.nlm.nih.gov/18391545","citation_count":144,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"38383754","id":"PMC_38383754","title":"The conneXion between sex and immune responses.","date":"2024","source":"Nature reviews. Immunology","url":"https://pubmed.ncbi.nlm.nih.gov/38383754","citation_count":136,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"30127341","id":"PMC_30127341","title":"Sex differences in psychiatric disorders: what we can learn from sex chromosome aneuploidies.","date":"2018","source":"Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology","url":"https://pubmed.ncbi.nlm.nih.gov/30127341","citation_count":125,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"18050479","id":"PMC_18050479","title":"Somatic sex determination.","date":"2006","source":"WormBook : the online review of C. elegans biology","url":"https://pubmed.ncbi.nlm.nih.gov/18050479","citation_count":108,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"20623803","id":"PMC_20623803","title":"The mechanism of sex determination in vertebrates-are sex steroids the key-factor?","date":"2010","source":"Journal of experimental zoology. Part A, Ecological genetics and physiology","url":"https://pubmed.ncbi.nlm.nih.gov/20623803","citation_count":107,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"11932771","id":"PMC_11932771","title":"Origins of the machinery of recombination and sex.","date":"2002","source":"Heredity","url":"https://pubmed.ncbi.nlm.nih.gov/11932771","citation_count":104,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"29451715","id":"PMC_29451715","title":"Transitions in sex determination and sex chromosomes across vertebrate species.","date":"2018","source":"Molecular ecology","url":"https://pubmed.ncbi.nlm.nih.gov/29451715","citation_count":104,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"29716744","id":"PMC_29716744","title":"Why Do Sex Chromosomes Stop Recombining?","date":"2018","source":"Trends in genetics : TIG","url":"https://pubmed.ncbi.nlm.nih.gov/29716744","citation_count":103,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"12350340","id":"PMC_12350340","title":"Sex comes in from the cold: the integration of sex and pattern.","date":"2002","source":"Trends in genetics : TIG","url":"https://pubmed.ncbi.nlm.nih.gov/12350340","citation_count":101,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"9558474","id":"PMC_9558474","title":"Sex in the 90s: SRY and the switch to the male pathway.","date":"1998","source":"Annual review of physiology","url":"https://pubmed.ncbi.nlm.nih.gov/9558474","citation_count":101,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"21047257","id":"PMC_21047257","title":"Evolution of sex chromosomes in insects.","date":"2010","source":"Annual review of genetics","url":"https://pubmed.ncbi.nlm.nih.gov/21047257","citation_count":100,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"31171460","id":"PMC_31171460","title":"Do Microglial Sex Differences Contribute to Sex Differences in Neurodegenerative Diseases?","date":"2019","source":"Trends in molecular medicine","url":"https://pubmed.ncbi.nlm.nih.gov/31171460","citation_count":96,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"30394940","id":"PMC_30394940","title":"Sex bias in autoimmunity.","date":"2019","source":"Current opinion in rheumatology","url":"https://pubmed.ncbi.nlm.nih.gov/30394940","citation_count":95,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"28597825","id":"PMC_28597825","title":"Fungal Sex: The Basidiomycota.","date":"2017","source":"Microbiology spectrum","url":"https://pubmed.ncbi.nlm.nih.gov/28597825","citation_count":93,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"15930959","id":"PMC_15930959","title":"Insulin resistance: sex matters.","date":"2005","source":"Current opinion in clinical nutrition and metabolic care","url":"https://pubmed.ncbi.nlm.nih.gov/15930959","citation_count":90,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"31309157","id":"PMC_31309157","title":"Stress, novel sex genes, and epigenetic reprogramming orchestrate socially controlled sex change.","date":"2019","source":"Science advances","url":"https://pubmed.ncbi.nlm.nih.gov/31309157","citation_count":89,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"23390004","id":"PMC_23390004","title":"Just how conserved is vertebrate sex determination?","date":"2013","source":"Developmental dynamics : an official publication of the American Association of Anatomists","url":"https://pubmed.ncbi.nlm.nih.gov/23390004","citation_count":86,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"7826621","id":"PMC_7826621","title":"The biochemical role of SRY in sex determination.","date":"1994","source":"Molecular reproduction and development","url":"https://pubmed.ncbi.nlm.nih.gov/7826621","citation_count":80,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"24157234","id":"PMC_24157234","title":"Sex- and estrogen-dependent regulation of a miRNA network in the healthy and hypertrophied heart.","date":"2013","source":"International journal of cardiology","url":"https://pubmed.ncbi.nlm.nih.gov/24157234","citation_count":79,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"35583710","id":"PMC_35583710","title":"Sex determination mechanisms and sex control approaches in aquaculture animals.","date":"2022","source":"Science China. Life sciences","url":"https://pubmed.ncbi.nlm.nih.gov/35583710","citation_count":75,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"27029841","id":"PMC_27029841","title":"Why we should consider sex (and study sex differences) in addiction research.","date":"2016","source":"Addiction biology","url":"https://pubmed.ncbi.nlm.nih.gov/27029841","citation_count":75,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"1765003","id":"PMC_1765003","title":"Sex chimaerism, fertility and sex determination in the mouse.","date":"1991","source":"Development (Cambridge, England)","url":"https://pubmed.ncbi.nlm.nih.gov/1765003","citation_count":73,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"20035442","id":"PMC_20035442","title":"Molecular mechanisms of sex determination and gonadal sex differentiation in fish.","date":"2005","source":"Fish physiology and biochemistry","url":"https://pubmed.ncbi.nlm.nih.gov/20035442","citation_count":73,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"28890443","id":"PMC_28890443","title":"Stress and sex: does cortisol mediate sex change in fish?","date":"2017","source":"Reproduction (Cambridge, England)","url":"https://pubmed.ncbi.nlm.nih.gov/28890443","citation_count":72,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"21631471","id":"PMC_21631471","title":"Sex matters: evaluating sex and gender in migraine and headache research.","date":"2011","source":"Headache","url":"https://pubmed.ncbi.nlm.nih.gov/21631471","citation_count":71,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"15463609","id":"PMC_15463609","title":"Leishmania: sex, lies and karyotype.","date":"1992","source":"Parasitology today (Personal ed.)","url":"https://pubmed.ncbi.nlm.nih.gov/15463609","citation_count":70,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"16950097","id":"PMC_16950097","title":"Of what use is sex to bacteria?","date":"2006","source":"Current biology : CB","url":"https://pubmed.ncbi.nlm.nih.gov/16950097","citation_count":70,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"35860276","id":"PMC_35860276","title":"The Hepatoprotective and Hepatotoxic Roles of Sex and Sex-Related Hormones.","date":"2022","source":"Frontiers in immunology","url":"https://pubmed.ncbi.nlm.nih.gov/35860276","citation_count":66,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"8631274","id":"PMC_8631274","title":"Sex-specific control of Sex-lethal is a conserved mechanism for sex determination in the genus Drosophila.","date":"1996","source":"Development (Cambridge, England)","url":"https://pubmed.ncbi.nlm.nih.gov/8631274","citation_count":63,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"18062774","id":"PMC_18062774","title":"Endothelin, sex and hypertension.","date":"2008","source":"Clinical science (London, England : 1979)","url":"https://pubmed.ncbi.nlm.nih.gov/18062774","citation_count":62,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"11074290","id":"PMC_11074290","title":"Mammalian sex reversal and intersexuality: deciphering the sex-determination cascade.","date":"2000","source":"Trends in genetics : TIG","url":"https://pubmed.ncbi.nlm.nih.gov/11074290","citation_count":62,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"18005182","id":"PMC_18005182","title":"Sex-linked deafness.","date":"2007","source":"Clinical genetics","url":"https://pubmed.ncbi.nlm.nih.gov/18005182","citation_count":60,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"25524548","id":"PMC_25524548","title":"Sex chromosome drive.","date":"2014","source":"Cold Spring Harbor perspectives in biology","url":"https://pubmed.ncbi.nlm.nih.gov/25524548","citation_count":59,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"29325624","id":"PMC_29325624","title":"Sex chromosome aneuploidies.","date":"2018","source":"Handbook of clinical neurology","url":"https://pubmed.ncbi.nlm.nih.gov/29325624","citation_count":54,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"23044875","id":"PMC_23044875","title":"WNT4, RSPO1, and FOXL2 in sex development.","date":"2012","source":"Seminars in reproductive medicine","url":"https://pubmed.ncbi.nlm.nih.gov/23044875","citation_count":54,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"29616724","id":"PMC_29616724","title":"Sex determination and gonadal sex differentiation in the chicken model.","date":"2018","source":"The International journal of developmental biology","url":"https://pubmed.ncbi.nlm.nih.gov/29616724","citation_count":53,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"28267976","id":"PMC_28267976","title":"Plant Sex Determination.","date":"2017","source":"Current biology : CB","url":"https://pubmed.ncbi.nlm.nih.gov/28267976","citation_count":50,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"3896453","id":"PMC_3896453","title":"Schizophrenia: sex differences.","date":"1985","source":"Canadian journal of psychiatry. Revue canadienne de psychiatrie","url":"https://pubmed.ncbi.nlm.nih.gov/3896453","citation_count":50,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"23634199","id":"PMC_23634199","title":"Characterization of sex determination and sex differentiation genes in Latimeria.","date":"2013","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/23634199","citation_count":49,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"35447091","id":"PMC_35447091","title":"Multilayered omics reveal sex- and depot-dependent adipose progenitor cell heterogeneity.","date":"2022","source":"Cell metabolism","url":"https://pubmed.ncbi.nlm.nih.gov/35447091","citation_count":47,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"19684453","id":"PMC_19684453","title":"The sex determining loci and sex chromosomes in the family salmonidae.","date":"2009","source":"Sexual development : genetics, molecular biology, evolution, endocrinology, embryology, and pathology of sex determination and differentiation","url":"https://pubmed.ncbi.nlm.nih.gov/19684453","citation_count":45,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"6209512","id":"PMC_6209512","title":"Origin of sex.","date":"1984","source":"Journal of theoretical biology","url":"https://pubmed.ncbi.nlm.nih.gov/6209512","citation_count":45,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"17187356","id":"PMC_17187356","title":"Determination and stability of sex.","date":"2007","source":"BioEssays : news and reviews in molecular, cellular and developmental biology","url":"https://pubmed.ncbi.nlm.nih.gov/17187356","citation_count":43,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"33592115","id":"PMC_33592115","title":"When and how do sex-linked regions become sex chromosomes?","date":"2021","source":"Evolution; international journal of organic evolution","url":"https://pubmed.ncbi.nlm.nih.gov/33592115","citation_count":42,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"34403484","id":"PMC_34403484","title":"Autosomal sex-associated co-methylated regions predict biological sex from DNA methylation.","date":"2021","source":"Nucleic acids research","url":"https://pubmed.ncbi.nlm.nih.gov/34403484","citation_count":42,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"23044871","id":"PMC_23044871","title":"The molecular genetics of sex determination and sex reversal in mammals.","date":"2012","source":"Seminars in reproductive medicine","url":"https://pubmed.ncbi.nlm.nih.gov/23044871","citation_count":42,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"7849739","id":"PMC_7849739","title":"Sex determination.","date":"1994","source":"Human molecular genetics","url":"https://pubmed.ncbi.nlm.nih.gov/7849739","citation_count":42,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"31771477","id":"PMC_31771477","title":"Repeated sex chromosome evolution in vertebrates supported by expanded avian sex chromosomes.","date":"2019","source":"Proceedings. Biological sciences","url":"https://pubmed.ncbi.nlm.nih.gov/31771477","citation_count":42,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"17300986","id":"PMC_17300986","title":"Genomics of sex chromosomes.","date":"2007","source":"Current opinion in plant biology","url":"https://pubmed.ncbi.nlm.nih.gov/17300986","citation_count":41,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"34304592","id":"PMC_34304592","title":"Sex chromosome evolution among amniotes: is the origin of sex chromosomes non-random?","date":"2021","source":"Philosophical transactions of the Royal Society of London. Series B, Biological sciences","url":"https://pubmed.ncbi.nlm.nih.gov/34304592","citation_count":41,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"30256978","id":"PMC_30256978","title":"Sex difference of mutation clonality in diffuse glioma evolution.","date":"2019","source":"Neuro-oncology","url":"https://pubmed.ncbi.nlm.nih.gov/30256978","citation_count":41,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"17124606","id":"PMC_17124606","title":"The right dose for every sex.","date":"2006","source":"Chromosoma","url":"https://pubmed.ncbi.nlm.nih.gov/17124606","citation_count":40,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"24599719","id":"PMC_24599719","title":"Avian sex, sex chromosomes, and dosage compensation in the age of genomics.","date":"2014","source":"Chromosome research : an international journal on the molecular, supramolecular and evolutionary aspects of chromosome biology","url":"https://pubmed.ncbi.nlm.nih.gov/24599719","citation_count":40,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"27641730","id":"PMC_27641730","title":"Random sex determination: When developmental noise tips the sex balance.","date":"2016","source":"BioEssays : news and reviews in molecular, cellular and developmental biology","url":"https://pubmed.ncbi.nlm.nih.gov/27641730","citation_count":40,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"29436502","id":"PMC_29436502","title":"How oxygen gave rise to eukaryotic sex.","date":"2018","source":"Proceedings. Biological sciences","url":"https://pubmed.ncbi.nlm.nih.gov/29436502","citation_count":39,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"24929952","id":"PMC_24929952","title":"Yes! Sex matters: sex, the brain and blood pressure.","date":"2014","source":"Current hypertension reports","url":"https://pubmed.ncbi.nlm.nih.gov/24929952","citation_count":39,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"18987495","id":"PMC_18987495","title":"WNT4 and sex development.","date":"2008","source":"Sexual development : genetics, molecular biology, evolution, endocrinology, embryology, and pathology of sex determination and differentiation","url":"https://pubmed.ncbi.nlm.nih.gov/18987495","citation_count":39,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"14644845","id":"PMC_14644845","title":"CNS: sex steroids and SERMs.","date":"2003","source":"Annals of the New York Academy of Sciences","url":"https://pubmed.ncbi.nlm.nih.gov/14644845","citation_count":39,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"26526145","id":"PMC_26526145","title":"Human sex-determination and disorders of sex-development (DSD).","date":"2015","source":"Seminars in cell & developmental biology","url":"https://pubmed.ncbi.nlm.nih.gov/26526145","citation_count":38,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"12160637","id":"PMC_12160637","title":"Tying rings for sex.","date":"2002","source":"Trends in microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/12160637","citation_count":38,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"16214335","id":"PMC_16214335","title":"Sex chromosomes and sex determination in reptiles.","date":"2005","source":"Current opinion in genetics & development","url":"https://pubmed.ncbi.nlm.nih.gov/16214335","citation_count":38,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"11931222","id":"PMC_11931222","title":"Sex and the single chromosome.","date":"2002","source":"Advances in genetics","url":"https://pubmed.ncbi.nlm.nih.gov/11931222","citation_count":36,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"31951035","id":"PMC_31951035","title":"Climate change, sex reversal and lability of sex-determining systems.","date":"2020","source":"Journal of evolutionary biology","url":"https://pubmed.ncbi.nlm.nih.gov/31951035","citation_count":35,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"21753256","id":"PMC_21753256","title":"Sex differences in cardiomyocyte connexin43 expression.","date":"2011","source":"Journal of cardiovascular pharmacology","url":"https://pubmed.ncbi.nlm.nih.gov/21753256","citation_count":35,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"11750731","id":"PMC_11750731","title":"46,XX sex reversal.","date":"2001","source":"Archives of medical research","url":"https://pubmed.ncbi.nlm.nih.gov/11750731","citation_count":34,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"34247500","id":"PMC_34247500","title":"Sex determination without sex chromosomes.","date":"2021","source":"Philosophical transactions of the Royal Society of London. Series B, Biological sciences","url":"https://pubmed.ncbi.nlm.nih.gov/34247500","citation_count":34,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"33043626","id":"PMC_33043626","title":"Let's Talk About Sex-Biological Sex Is Underreported in Biomaterial Studies.","date":"2020","source":"Advanced healthcare materials","url":"https://pubmed.ncbi.nlm.nih.gov/33043626","citation_count":34,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"27529790","id":"PMC_27529790","title":"Sex Reversal in Birds.","date":"2016","source":"Sexual development : genetics, molecular biology, evolution, endocrinology, embryology, and pathology of sex determination and differentiation","url":"https://pubmed.ncbi.nlm.nih.gov/27529790","citation_count":34,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"30319350","id":"PMC_30319350","title":"Sex Hormones Regulate SHANK Expression.","date":"2018","source":"Frontiers in molecular neuroscience","url":"https://pubmed.ncbi.nlm.nih.gov/30319350","citation_count":32,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"34247502","id":"PMC_34247502","title":"Sex-chromosome evolution in frogs: what role for sex-antagonistic genes?","date":"2021","source":"Philosophical transactions of the Royal Society of London. Series B, Biological sciences","url":"https://pubmed.ncbi.nlm.nih.gov/34247502","citation_count":32,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"32160920","id":"PMC_32160920","title":"Obesity: sex and sympathetics.","date":"2020","source":"Biology of sex differences","url":"https://pubmed.ncbi.nlm.nih.gov/32160920","citation_count":31,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"18391538","id":"PMC_18391538","title":"Sex determination in birds: HINTs from the W sex chromosome?","date":"2007","source":"Sexual development : genetics, molecular biology, evolution, endocrinology, embryology, and pathology of sex determination and differentiation","url":"https://pubmed.ncbi.nlm.nih.gov/18391538","citation_count":31,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"39731171","id":"PMC_39731171","title":"Sex differences in disease: sex chromosome and immunity.","date":"2024","source":"Journal of translational medicine","url":"https://pubmed.ncbi.nlm.nih.gov/39731171","citation_count":31,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"35416774","id":"PMC_35416774","title":"Genetic variation of putative myokine signaling is dominated by biological sex and sex hormones.","date":"2022","source":"eLife","url":"https://pubmed.ncbi.nlm.nih.gov/35416774","citation_count":29,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"21810650","id":"PMC_21810650","title":"Sex chromosome complement contributes to sex differences in bradycardic baroreflex response.","date":"2011","source":"Hypertension (Dallas, Tex. : 1979)","url":"https://pubmed.ncbi.nlm.nih.gov/21810650","citation_count":29,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"38631602","id":"PMC_38631602","title":"Sex and sex steroids as determinants of cardiovascular risk.","date":"2024","source":"Steroids","url":"https://pubmed.ncbi.nlm.nih.gov/38631602","citation_count":28,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"32648258","id":"PMC_32648258","title":"Evolution of Sex Determination and Sex Chromosomes: A Novel Alternative Paradigm.","date":"2020","source":"BioEssays : news and reviews in molecular, cellular and developmental biology","url":"https://pubmed.ncbi.nlm.nih.gov/32648258","citation_count":26,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"15350606","id":"PMC_15350606","title":"ATRX and sex differentiation.","date":"2004","source":"Trends in endocrinology and metabolism: TEM","url":"https://pubmed.ncbi.nlm.nih.gov/15350606","citation_count":24,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"17875487","id":"PMC_17875487","title":"Age-specific changes in sex steroid biosynthesis and sex development.","date":"2007","source":"Best practice & research. Clinical endocrinology & metabolism","url":"https://pubmed.ncbi.nlm.nih.gov/17875487","citation_count":24,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"31690636","id":"PMC_31690636","title":"PLXNA1 and PLXNA3 cooperate to pattern the nasal axons that guide gonadotropin-releasing hormone neurons.","date":"2019","source":"Development (Cambridge, England)","url":"https://pubmed.ncbi.nlm.nih.gov/31690636","citation_count":22,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"36151581","id":"PMC_36151581","title":"Repeated turnovers keep sex chromosomes young in willows.","date":"2022","source":"Genome biology","url":"https://pubmed.ncbi.nlm.nih.gov/36151581","citation_count":22,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"26186194","id":"PMC_26186194","title":"The BioPlex Network: A Systematic Exploration of the Human Interactome.","date":"2015","source":"Cell","url":"https://pubmed.ncbi.nlm.nih.gov/26186194","citation_count":1118,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"28514442","id":"PMC_28514442","title":"Architecture of the human interactome defines protein communities and disease networks.","date":"2017","source":"Nature","url":"https://pubmed.ncbi.nlm.nih.gov/28514442","citation_count":1085,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"26496610","id":"PMC_26496610","title":"A human interactome in three quantitative dimensions organized by stoichiometries and abundances.","date":"2015","source":"Cell","url":"https://pubmed.ncbi.nlm.nih.gov/26496610","citation_count":1015,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"10520995","id":"PMC_10520995","title":"Plexins are a large family of receptors for transmembrane, secreted, and GPI-anchored semaphorins in vertebrates.","date":"1999","source":"Cell","url":"https://pubmed.ncbi.nlm.nih.gov/10520995","citation_count":954,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"33961781","id":"PMC_33961781","title":"Dual proteome-scale networks reveal cell-specific remodeling of the human interactome.","date":"2021","source":"Cell","url":"https://pubmed.ncbi.nlm.nih.gov/33961781","citation_count":705,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"21873635","id":"PMC_21873635","title":"Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium.","date":"2011","source":"Briefings in bioinformatics","url":"https://pubmed.ncbi.nlm.nih.gov/21873635","citation_count":656,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"15146197","id":"PMC_15146197","title":"Transcriptome characterization elucidates signaling networks that control human ES cell growth and differentiation.","date":"2004","source":"Nature biotechnology","url":"https://pubmed.ncbi.nlm.nih.gov/15146197","citation_count":266,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"21900206","id":"PMC_21900206","title":"A directed protein interaction network for investigating intracellular signal transduction.","date":"2011","source":"Science signaling","url":"https://pubmed.ncbi.nlm.nih.gov/21900206","citation_count":258,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"8570614","id":"PMC_8570614","title":"A family of transmembrane proteins with homology to the MET-hepatocyte growth factor receptor.","date":"1996","source":"Proceedings of the National Academy of Sciences of the United States of America","url":"https://pubmed.ncbi.nlm.nih.gov/8570614","citation_count":149,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"10737800","id":"PMC_10737800","title":"Shotgun sequencing of the human transcriptome with ORF expressed sequence tags.","date":"2000","source":"Proceedings of the National Academy of Sciences of the United States of America","url":"https://pubmed.ncbi.nlm.nih.gov/10737800","citation_count":135,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"34857952","id":"PMC_34857952","title":"Paralog knockout profiling identifies DUSP4 and DUSP6 as a digenic dependence in MAPK pathway-driven cancers.","date":"2021","source":"Nature genetics","url":"https://pubmed.ncbi.nlm.nih.gov/34857952","citation_count":116,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"19480842","id":"PMC_19480842","title":"Expression and function of semaphorin 3A and its receptors in human monocyte-derived macrophages.","date":"2009","source":"Human immunology","url":"https://pubmed.ncbi.nlm.nih.gov/19480842","citation_count":90,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"34709727","id":"PMC_34709727","title":"SARS-CoV-2-host proteome interactions for antiviral drug discovery.","date":"2021","source":"Molecular systems biology","url":"https://pubmed.ncbi.nlm.nih.gov/34709727","citation_count":86,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"8733135","id":"PMC_8733135","title":"Long-range sequence analysis in Xq28: thirteen known and six candidate genes in 219.4 kb of high GC DNA between the RCP/GCP and G6PD loci.","date":"1996","source":"Human molecular genetics","url":"https://pubmed.ncbi.nlm.nih.gov/8733135","citation_count":73,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"8248200","id":"PMC_8248200","title":"Transcriptional organization of a 450-kb region of the human X chromosome in Xq28.","date":"1993","source":"Proceedings of the National Academy of Sciences of the United States of America","url":"https://pubmed.ncbi.nlm.nih.gov/8248200","citation_count":70,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"8281148","id":"PMC_8281148","title":"Construction of a transcription map of a 300 kb region around the human G6PD locus by direct cDNA selection.","date":"1993","source":"Human molecular genetics","url":"https://pubmed.ncbi.nlm.nih.gov/8281148","citation_count":54,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"22199357","id":"PMC_22199357","title":"Cytoplasmic Metadherin (MTDH) provides survival advantage under conditions of stress by acting as RNA-binding protein.","date":"2011","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/22199357","citation_count":53,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"36138187","id":"PMC_36138187","title":"NUDT21 limits CD19 levels through alternative mRNA polyadenylation in B cell acute lymphoblastic leukemia.","date":"2022","source":"Nature immunology","url":"https://pubmed.ncbi.nlm.nih.gov/36138187","citation_count":46,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"8806646","id":"PMC_8806646","title":"Identification of plexin family molecules in mice.","date":"1996","source":"Biochemical and biophysical research communications","url":"https://pubmed.ncbi.nlm.nih.gov/8806646","citation_count":40,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"30745168","id":"PMC_30745168","title":"POH1 contributes to hyperactivation of TGF-β signaling and facilitates hepatocellular carcinoma metastasis through deubiquitinating TGF-β receptors and caveolin-1.","date":"2019","source":"EBioMedicine","url":"https://pubmed.ncbi.nlm.nih.gov/30745168","citation_count":38,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"35575683","id":"PMC_35575683","title":"In-Depth In Vivo Crosslinking in Minutes by a Compact, Membrane-Permeable, and Alkynyl-Enrichable Crosslinker.","date":"2022","source":"Analytical chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/35575683","citation_count":38,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"11604131","id":"PMC_11604131","title":"Plexin signaling via off-track and rho family GTPases.","date":"2001","source":"Neuron","url":"https://pubmed.ncbi.nlm.nih.gov/11604131","citation_count":37,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"19909241","id":"PMC_19909241","title":"The role of neuropilins in cell signalling.","date":"2009","source":"Biochemical Society transactions","url":"https://pubmed.ncbi.nlm.nih.gov/19909241","citation_count":33,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"21925246","id":"PMC_21925246","title":"Semaphorin-plexin signalling genes associated with human breast tumourigenesis.","date":"2011","source":"Gene","url":"https://pubmed.ncbi.nlm.nih.gov/21925246","citation_count":27,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"31391242","id":"PMC_31391242","title":"DCAF8, a novel MuRF1 interaction partner, promotes muscle atrophy.","date":"2019","source":"Journal of cell science","url":"https://pubmed.ncbi.nlm.nih.gov/31391242","citation_count":25,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"35748872","id":"PMC_35748872","title":"A dual-activity topoisomerase complex regulates mRNA translation and turnover.","date":"2022","source":"Nucleic acids research","url":"https://pubmed.ncbi.nlm.nih.gov/35748872","citation_count":25,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"36215168","id":"PMC_36215168","title":"TRIM67 drives tumorigenesis in oligodendrogliomas through Rho GTPase-dependent membrane blebbing.","date":"2023","source":"Neuro-oncology","url":"https://pubmed.ncbi.nlm.nih.gov/36215168","citation_count":25,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"35696571","id":"PMC_35696571","title":"ESCPE-1 mediates retrograde endosomal sorting of the SARS-CoV-2 host factor Neuropilin-1.","date":"2022","source":"Proceedings of the National Academy of Sciences of the United States of America","url":"https://pubmed.ncbi.nlm.nih.gov/35696571","citation_count":22,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"25518740","id":"PMC_25518740","title":"PlexinA polymorphisms mediate the developmental trajectory of human corpus callosum microstructure.","date":"2014","source":"Journal of human genetics","url":"https://pubmed.ncbi.nlm.nih.gov/25518740","citation_count":15,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"20138877","id":"PMC_20138877","title":"Myeloid translocation gene 16b is a dual A-kinase anchoring protein that interacts selectively with plexins in a phospho-regulated manner.","date":"2010","source":"FEBS letters","url":"https://pubmed.ncbi.nlm.nih.gov/20138877","citation_count":12,"is_preprint":false,"source_track":"gene2pubmed"}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":35450,"output_tokens":403,"usd":0.056197},"stage2":{"model":"claude-opus-4-6","input_tokens":3549,"output_tokens":936,"usd":0.061718},"total_usd":0.312259,"stage1_batch_id":"msgbatch_01SUR8NDzVrNmyszWyJeCct7","stage2_batch_id":"msgbatch_01G7Yfutko3cDWzejrwH5AMx","note":"batch pricing = 50% of standard","round2_stage1":{"model":"claude-sonnet-4-6","input_tokens":48928,"output_tokens":1781,"usd":0.086749},"round2_rules_fired":"R3","round2_stage2":{"model":"claude-opus-4-6","input_tokens":5276,"output_tokens":1814,"usd":0.107595}},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2019,\n      \"finding\": \"PLXNA3 cooperates with PLXNA1 as a co-receptor for SEMA3A signaling to pattern nasal axons that guide gonadotropin-releasing hormone (GnRH) neurons during embryonic development. Combined loss of PLXNA1 and PLXNA3 phenocopied the full spectrum of nasal axon and GnRH neuron defects observed in SEMA3A knockout mice, whereas loss of either receptor alone did not recapitulate the complete phenotype.\",\n      \"method\": \"Genetic epistasis using double-knockout mice (Plxna1/Plxna3 combined loss-of-function) compared to single knockouts and Sema3a knockout, with analysis of nasal axon patterning and GnRH neuron migration as phenotypic readouts\",\n      \"journal\": \"Development (Cambridge, England)\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — clean double-KO genetic epistasis with specific cellular phenotype, replicated against Sema3a KO benchmark\",\n      \"pmids\": [\"31690636\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"PLXNA3 functions as a co-receptor alongside PLXNA1 for the secreted guidance cue SEMA3A, and their combined activity is required to pattern olfactory/vomeronasal nasal axons that serve as the migratory scaffold for GnRH neurons traveling from the nose to the hypothalamus during embryonic development.\"\n}\n```\n\n--- ROUND 2 (R2/R3, augmented corpus) ---\n\n```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 1999,\n      \"finding\": \"PLXNA3 (plexin-A3) is a member of the plexin receptor family that associates with neuropilins as co-receptors for secreted (class 3) semaphorins; plexin cytoplasmic domains associate with a tyrosine kinase activity, and truncated plexin-A1 expression blocks axon repulsion by Sema3A, establishing plexins as functional semaphorin receptors that trigger cell repulsion signaling.\",\n      \"method\": \"Binding assays, co-immunoprecipitation, truncated dominant-negative expression in neurons\",\n      \"journal\": \"Cell\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — reciprocal co-IP, functional dominant-negative assay, replicated across multiple plexin family members in a landmark study\",\n      \"pmids\": [\"10520995\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 1996,\n      \"finding\": \"PLXNA3 (SEX gene) was identified as a transmembrane protein located on the human X chromosome (Xq28) with homology to the extracellular domain of MET/HGF receptor family; it is expressed predominantly in brain during neural development, is glycosylated and exposed at the cell surface, but unlike MET, does not show tyrosine kinase activity itself.\",\n      \"method\": \"cDNA cloning, Northern blot, in situ hybridization, cell surface biotinylation, MET-SEX chimera kinase assay\",\n      \"journal\": \"Proceedings of the National Academy of Sciences of the United States of America\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1-2 — original cloning with multiple orthogonal methods including in vitro kinase assay and in situ hybridization\",\n      \"pmids\": [\"8570614\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 1996,\n      \"finding\": \"PLXNA3 (plexin) was mapped to human Xq28 and identified as a gene in the 219-kb high-GC region between RCP/GCP and G6PD loci, with its exon structure inferred from sequence and 65.5% identity to the Xenopus plexin analogue.\",\n      \"method\": \"Large-scale genomic sequencing, GRAIL gene prediction, homology analysis\",\n      \"journal\": \"Human molecular genetics\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 — genomic localization and sequence-based identification without functional assay\",\n      \"pmids\": [\"8733135\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 1996,\n      \"finding\": \"Mouse plexin 3 (ortholog of human PLXNA3) was isolated from E17.5 mouse brain cDNA libraries and identified as a type I membrane protein with >60% amino acid identity to mouse plexin 1 and three cysteine-rich repeats in the extracellular domain; Northern blot revealed molecular heterogeneity in plexin 3 transcripts.\",\n      \"method\": \"cDNA library screening, sequencing, Northern blot analysis\",\n      \"journal\": \"Biochemical and biophysical research communications\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 — cloning and expression characterization without functional assay\",\n      \"pmids\": [\"8806646\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2009,\n      \"finding\": \"PLXNA3 (plexin A3) expression significantly increases during M-CSF-mediated differentiation of human monocytes into M2 alternatively activated macrophages; Sema3A acting through NRP1/plexin A3-containing receptor complexes induces apoptosis in monocyte-derived macrophages and cooperates with anti-Fas antibody to augment apoptosis.\",\n      \"method\": \"Flow cytometry, cell surface binding assay, apoptosis assays, siRNA knockdown\",\n      \"journal\": \"Human immunology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2-3 — functional apoptosis assay with receptor expression characterization in primary human cells\",\n      \"pmids\": [\"19480842\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2010,\n      \"finding\": \"Mammalian MTG16b (myeloid translocation gene 16b) functions as a dual A-kinase anchoring protein (AKAP) that selectively binds PlexinA1 and PlexinA3 on the plasma membrane but not PlexinB1; this interaction is regulated by PKA phosphorylation, suggesting a mechanism for integrating cAMP and semaphorin signaling in immune cells.\",\n      \"method\": \"Co-immunoprecipitation, AKAP overlay assay, PKA phosphorylation assay\",\n      \"journal\": \"FEBS letters\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — selective binding demonstrated by co-IP with phospho-regulation, single study\",\n      \"pmids\": [\"20138877\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"PLXNA3, together with PLXNA1, is required for proper patterning of nasal axons that guide GnRH neurons during embryonic development; combined knockout of Plxna1 and Plxna3 in mice phenocopied the full spectrum of nasal axon and GnRH neuron defects seen in Sema3a knockout mice, whereas single knockouts did not, establishing PLXNA1 and PLXNA3 as cooperative receptors downstream of SEMA3A in the olfactory/vomeronasal axon guidance pathway required for GnRH neuron migration.\",\n      \"method\": \"Genetic epistasis (double knockout mice), immunofluorescence, GnRH neuron counting, axon tracing\",\n      \"journal\": \"Development (Cambridge, England)\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — clean double-KO genetic epistasis with specific phenotypic readout, phenocopies ligand knockout\",\n      \"pmids\": [\"31690636\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"PLXNA3 is a transmembrane receptor of the plexin-A subfamily that cooperates with neuropilins and PLXNA1 to transduce SEMA3A repulsive signals; it is required (redundantly with PLXNA1) for nasal axon patterning and GnRH neuron migration, is upregulated during M2 macrophage differentiation where it mediates Sema3A-induced apoptosis, and selectively binds the AKAP MTG16b in a PKA-phosphorylation-dependent manner to integrate cAMP and semaphorin signaling, while lacking intrinsic tyrosine kinase activity despite its extracellular homology to MET-family receptors.\"\n}\n```","stage2_raw":"```json\n{\n  \"mechanistic_narrative\": \"PLXNA3 functions as a co-receptor with PLXNA1 for the secreted semaphorin SEMA3A, and their combined activity is required for patterning nasal axons that serve as the migratory scaffold for gonadotropin-releasing hormone (GnRH) neurons during embryonic development [PMID:31690636]. Combined loss of PLXNA1 and PLXNA3 in mice phenocopies the full spectrum of nasal axon and GnRH neuron migration defects seen in SEMA3A knockouts, whereas loss of either receptor alone produces only partial defects, establishing functional redundancy between the two plexin-A family members in this signaling axis [PMID:31690636].\",\n  \"teleology\": [\n    {\n      \"year\": 2019,\n      \"claim\": \"It was unknown whether PLXNA3 contributes to SEMA3A-dependent nasal axon guidance and GnRH neuron migration; double-knockout experiments demonstrated that PLXNA3 cooperates with PLXNA1 as a co-receptor for SEMA3A, with combined loss fully phenocopying the SEMA3A knockout, establishing functional redundancy in this developmental guidance pathway.\",\n      \"evidence\": \"Genetic epistasis using Plxna1/Plxna3 single- and double-knockout mice compared to Sema3a knockout, with nasal axon patterning and GnRH neuron migration as phenotypic readouts\",\n      \"pmids\": [\"31690636\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Whether PLXNA3 forms a direct physical complex with PLXNA1 and/or neuropilin co-receptors at the cell surface has not been determined\",\n        \"The downstream signaling effectors activated by the PLXNA1/PLXNA3 co-receptor pair upon SEMA3A binding are uncharacterized\",\n        \"Whether PLXNA3 contributes to SEMA3A signaling in tissues beyond the nasal axon/GnRH neuron system has not been tested\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The biochemical mechanism by which PLXNA3 and PLXNA1 jointly transduce SEMA3A signals — including receptor complex stoichiometry, GAP domain activation, and downstream Rho GTPase regulation — remains unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No structural or biochemical data on the PLXNA1–PLXNA3 receptor complex\",\n        \"No identification of intracellular signaling intermediates downstream of the co-receptor pair\",\n        \"Potential roles for PLXNA3 in responding to other class-3 semaphorins have not been systematically explored\"\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\n        \"term_id\": \"GO:0060089\",\n        \"supporting_discovery_ids\": [0]\n      }\n    ],\n    \"localization\": [\n      {\n        \"term_id\": \"GO:0005886\",\n        \"supporting_discovery_ids\": [0]\n      }\n    ],\n    \"pathway\": [\n      {\n        \"term_id\": \"R-HSA-1266738\",\n        \"supporting_discovery_ids\": [0]\n      },\n      {\n        \"term_id\": \"R-HSA-162582\",\n        \"supporting_discovery_ids\": [0]\n      }\n    ],\n    \"complexes\": [],\n    \"partners\": [\n      \"PLXNA1\",\n      \"SEMA3A\"\n    ],\n    \"other_free_text\": []\n  }\n}\n```\n\n--- ROUND 2 (R2/R3, augmented corpus) ---\n\n```json\n{\n  \"mechanistic_narrative\": \"PLXNA3 (Plexin-A3) is a transmembrane semaphorin receptor that cooperates with neuropilins and PLXNA1 to transduce class 3 semaphorin repulsive signals during neural development and immune cell regulation. Originally cloned as a brain-enriched type I membrane protein with MET-family extracellular homology but lacking intrinsic tyrosine kinase activity, PLXNA3 associates with neuropilin co-receptors to form functional Sema3A receptor complexes that trigger axon repulsion and, in monocyte-derived macrophages, Sema3A-induced apoptosis [PMID:8570614, PMID:10520995, PMID:19480842]. Combined knockout of Plxna1 and Plxna3 in mice phenocopies the nasal axon patterning and GnRH neuron migration defects of Sema3a knockouts, establishing these two plexins as functionally redundant obligate receptors for SEMA3A-guided olfactory/vomeronasal axon guidance [PMID:31690636]. PLXNA3 also selectively binds the A-kinase anchoring protein MTG16b in a PKA-phosphorylation-dependent manner, providing a mechanism for integrating cAMP signaling with semaphorin receptor output [PMID:20138877].\",\n  \"teleology\": [\n    {\n      \"year\": 1996,\n      \"claim\": \"Cloning of PLXNA3 established it as a neural transmembrane protein with MET-like extracellular architecture but no intrinsic tyrosine kinase activity, raising the question of how it transduces signals.\",\n      \"evidence\": \"cDNA cloning from human and mouse brain, MET-PLXNA3 chimera kinase assay, in situ hybridization, cell surface biotinylation\",\n      \"pmids\": [\"8570614\", \"8806646\", \"8733135\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Ligand identity was unknown at this stage\",\n        \"Signaling mechanism downstream of the cytoplasmic domain was uncharacterized\",\n        \"Functional role in vivo was not addressed\"\n      ]\n    },\n    {\n      \"year\": 1999,\n      \"claim\": \"Demonstration that plexins associate with neuropilin co-receptors and are required for Sema3A-mediated axon repulsion resolved the question of how class 3 semaphorins signal, positioning PLXNA3 as a signal-transducing subunit of the semaphorin receptor complex.\",\n      \"evidence\": \"Co-immunoprecipitation of plexin-neuropilin complexes, dominant-negative truncated plexin blocking Sema3A repulsion in neurons\",\n      \"pmids\": [\"10520995\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Relative contributions of individual plexin-A family members to Sema3A signaling in vivo were unclear\",\n        \"Identity of the tyrosine kinase associated with plexin cytoplasmic domains was not resolved\"\n      ]\n    },\n    {\n      \"year\": 2009,\n      \"claim\": \"Finding that PLXNA3 is upregulated during M2 macrophage differentiation and mediates Sema3A-induced apoptosis extended its function beyond neuronal guidance to immune cell regulation.\",\n      \"evidence\": \"Flow cytometry and siRNA knockdown in M-CSF-differentiated human monocytes with apoptosis readout\",\n      \"pmids\": [\"19480842\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Downstream apoptotic pathway components linking PLXNA3 activation to cell death were not identified\",\n        \"In vivo relevance of macrophage PLXNA3-mediated apoptosis was not tested\"\n      ]\n    },\n    {\n      \"year\": 2010,\n      \"claim\": \"Identification of MTG16b as a PKA-regulated AKAP that selectively binds PLXNA3 (and PLXNA1 but not PLXNB1) revealed a molecular node for cross-talk between cAMP and semaphorin signaling.\",\n      \"evidence\": \"Co-immunoprecipitation with AKAP overlay and PKA phosphorylation assays\",\n      \"pmids\": [\"20138877\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Functional consequence of MTG16b–PLXNA3 interaction on semaphorin-dependent signaling output was not measured\",\n        \"No reciprocal validation using endogenous proteins was reported\",\n        \"Cell types in which this cross-talk operates in vivo are undefined\"\n      ]\n    },\n    {\n      \"year\": 2019,\n      \"claim\": \"Genetic epistasis in double-knockout mice demonstrated that PLXNA1 and PLXNA3 are cooperative, functionally redundant receptors required for SEMA3A-guided nasal axon patterning and GnRH neuron migration, explaining why single knockouts had shown mild phenotypes.\",\n      \"evidence\": \"Plxna1/Plxna3 double-KO mice with immunofluorescence, GnRH neuron counts, and axon tracing phenocopying Sema3a KO\",\n      \"pmids\": [\"31690636\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Whether PLXNA3 participates in Sema3A-independent guidance pathways was not addressed\",\n        \"Structural basis for PLXNA1/PLXNA3 redundancy or possible heteromeric receptor assembly is unknown\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"Key open questions include the structural mechanism of PLXNA3 activation, the identity of kinases recruited to its cytoplasmic domain, and whether its roles in macrophage apoptosis and cAMP cross-talk are relevant in vivo.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"No high-resolution structure of PLXNA3 in an active signaling complex\",\n        \"Downstream signaling effectors beyond GTPase-activating activity inferred from family homology are not defined for PLXNA3 specifically\",\n        \"In vivo immune phenotype in Plxna3 single or double knockout remains uncharacterized\"\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0060089\", \"supporting_discovery_ids\": [0, 6]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005886\", \"supporting_discovery_ids\": [1, 5]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-1266738\", \"supporting_discovery_ids\": [0, 6]},\n      {\"term_id\": \"R-HSA-162582\", \"supporting_discovery_ids\": [0, 5, 6]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\n      \"NRP1\",\n      \"PLXNA1\",\n      \"CBFA2T3\",\n      \"SEMA3A\"\n    ],\n    \"other_free_text\": []\n  }\n}\n```"}