{"gene":"OMP","run_date":"2026-06-10T05:19:52","timeline":{"discoveries":[{"year":1996,"finding":"Deletion of the OMP gene in mice (OMP-null) causes a 20-40% reduction in maximal electroolfactogram (EOG) amplitude to multiple odorants, prolonged onset and recovery kinetics following isoamyl acetate stimulation, and impaired ability to respond to a second odor pulse, establishing OMP as a modulatory component of the odor detection/signal transduction cascade in olfactory sensory neurons.","method":"Gene targeting in embryonic stem cells; electroolfactogram recording; behavioral odorant stimulation paradigms","journal":"Proceedings of the National Academy of Sciences of the United States of America","confidence":"High","confidence_rationale":"Tier 2 / Strong — clean KO mouse with multiple orthogonal physiological and behavioral readouts, replicated across odorants","pmids":["8790421"],"is_preprint":false},{"year":1999,"finding":"OMP gene deletion results in a significant elevation in behavioral olfactory threshold sensitivity (OMP-null mice were ~300-fold less sensitive to propanol than controls), confirming OMP's role in modulating the odor detection/signal transduction process in vivo.","method":"Behavioral psychophysical threshold testing (air vs. odor discrimination) in OMP-null vs. wild-type mice","journal":"Neuroreport","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — clean KO with defined behavioral phenotype, single lab, single behavioral method","pmids":["10094125"],"is_preprint":false},{"year":2000,"finding":"Adenoviral vector-mediated reintroduction of OMP into olfactory receptor neurons of adult OMP-null mice rescues the kinetics of electrophysiological responses, restoring them to control phenotype; this demonstrates that OMP's role in olfactory transduction is direct and not a developmental artifact of gene deletion.","method":"Adenoviral gene delivery to olfactory epithelium; electroolfactogram recording before and after rescue","journal":"Nature neuroscience","confidence":"High","confidence_rationale":"Tier 2 / Strong — gain-of-function rescue in adult KO animals with electrophysiological readout, complementing KO phenotype","pmids":["11036268"],"is_preprint":false},{"year":2001,"finding":"OMP gene deletion alters odorant quality perception; OMP-null mice show a significantly different multidimensional odorant identification profile compared to controls in a 5-odorant confusion matrix task, indicating OMP is critically involved in odor quality processing.","method":"5-odorant identification confusion matrix behavioral task with multidimensional scaling analysis in OMP-null vs. wild-type mice","journal":"Behavioral neuroscience","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — clean KO with defined behavioral phenotype, single lab, single method","pmids":["11439451"],"is_preprint":false},{"year":2002,"finding":"NMR solution structure of OMP reveals a single globular domain with a beta-clam (beta-sandwich) fold comprising eight beta-strands forming two orthogonally oriented beta-sheets, with two long alpha-helices and three flexible loops. Peptide titration experiments identified the cleft between the two beta-sheets as the binding surface for a peptide derived from the Bex1 protein, implicating this surface in protein-protein interactions relevant to olfactory signal transduction.","method":"NMR structure determination; peptide titration NMR experiments mapping binding surface","journal":"Journal of molecular biology","confidence":"High","confidence_rationale":"Tier 1 / Moderate — NMR structure with functional binding mapping using peptide titration, single lab but multiple orthogonal NMR methods","pmids":["12054873"],"is_preprint":false},{"year":2003,"finding":"Members of the Bex gene family (Bex1, Bex2, Bex3) are binding partners of OMP in olfactory receptor neurons. Bex2 was identified by phage-display screening of an olfactory mucosal cDNA library, the OMP/Bex interaction was confirmed by chemical cross-linking of recombinant OMP with a Bex-derived peptide, and co-transfection in HEK293 cells revealed that OMP co-localizes with Bex in both cytoplasm and nucleus.","method":"Phage-display cDNA library screening; chemical cross-linking; in situ hybridization; co-transfection in HEK293 cells","journal":"Journal of neurochemistry","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — multiple orthogonal methods (phage display, cross-linking, co-transfection), single lab","pmids":["12911636"],"is_preprint":false},{"year":2003,"finding":"OMP gene deletion results in degraded and altered odorant-induced spatiotemporal mucosal activity patterns (recorded by voltage-sensitive dye optical imaging), providing a neurophysiological substrate for the previously observed changes in odorant quality perception in OMP-null mice.","method":"Voltage-sensitive dye optical imaging of olfactory epithelium in OMP-null vs. wild-type mice","journal":"Journal of neurophysiology","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — clean KO with specific imaging-based phenotypic readout, single lab, single method","pmids":["12917392"],"is_preprint":false},{"year":2004,"finding":"OMP forms a covalently cross-linked homodimer (38 kDa) in addition to the monomer (19 kDa) in vivo. The dimer is preferentially co-immunoprecipitated with Bex, has a much shorter half-life than the monomer, and is preferentially localized in a Triton X-100-insoluble cytoskeletal fraction, while the monomer is present in both nuclear and cytosolic compartments.","method":"Immunoprecipitation; in-gel tryptic digestion and mass spectrometry; 2D gel electrophoresis; subcellular fractionation; transfected cell stability assays","journal":"Journal of neurochemistry","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — multiple orthogonal methods (Co-IP, MS, fractionation), single lab","pmids":["15198671"],"is_preprint":false},{"year":2004,"finding":"Adenoviral vector-mediated rescue of OMP expression in OMP-null mice restores behavioral olfactory threshold sensitivity to control levels, confirming that OMP functions as an important component in olfactory signal amplification and/or transduction.","method":"Adenoviral gene delivery to olfactory epithelium; psychophysical behavioral threshold testing in OMP-null mice","journal":"Behavioral neuroscience","confidence":"High","confidence_rationale":"Tier 2 / Strong — gain-of-function rescue in adult KO with behavioral readout, complementing both KO and electrophysiological rescue studies","pmids":["15174942"],"is_preprint":false},{"year":2009,"finding":"OMP facilitates Na+/Ca2+-exchanger (NCX) activity in olfactory sensory neurons, enabling rapid Ca2+ extrusion from OSN dendritic knobs. OMP-null mice show impaired Ca2+ homeostasis with reduced NCX-mediated Ca2+ extrusion. Mechanistically, surface plasmon resonance demonstrated a direct interaction between the XIP regulatory peptide of NCX and calmodulin (CaM); since CaM also binds to Bex (an OMP interacting partner), OMP is proposed to influence NCX activity through a Bex-CaM intermediary. NCX1 and OMP co-localize in cilia and knobs of OSNs by immunohistochemistry.","method":"Single-cell Ca2+ imaging in intact olfactory epithelium (WT vs. OMP-/- mice); surface plasmon resonance protein-peptide binding assays; immunohistochemistry co-localization","journal":"PloS one","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — multiple orthogonal methods (Ca2+ imaging, SPR, IHC), single lab, proposed pathway supported by direct binding data","pmids":["19165324"],"is_preprint":false},{"year":2018,"finding":"OMP is required for proper formation and refinement of the olfactory glomerular map. In OMP-/- mice, individual glomeruli are frequently co-innervated by olfactory sensory neurons expressing different odorant receptors, causing functionally heterogeneous glomeruli with distinct odor-response microdomains. OMP+/- mice show rare glomerular heterogeneity, indicating a dose-dependent role for OMP in axon targeting.","method":"Knock-in mice expressing synaptopHluorin in place of one or both OMP alleles; two-photon imaging of glomerular odor responses; genetic targeting of single odorant receptors to visualize innervation patterns","journal":"Nature communications","confidence":"High","confidence_rationale":"Tier 2 / Strong — multiple orthogonal methods (functional imaging, genetic single-OR targeting, anatomical analysis) in clean KO and heterozygous mice, single lab but rigorous and comprehensive","pmids":["30498219"],"is_preprint":false},{"year":1994,"finding":"The human OMP gene is intronless, lacks canonical TATA and CAAT motifs, and contains conserved Olf-1 binding sites and an upstream binding region (UBE) with similarity to NF-1 family transcription factor binding motifs; gel mobility shift assays confirm NF-1 family binding to the UBE site, providing insight into mechanisms of neuron-specific OMP transcriptional regulation.","method":"Gene cloning and sequencing; gel mobility shift assays (EMSA) for transcription factor binding","journal":"Genomics","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — EMSA binding assays for regulatory elements, cross-species conservation analysis, single lab","pmids":["8034318"],"is_preprint":false}],"current_model":"OMP (Olfactory Marker Protein) is a cytoplasmic protein with a beta-clam/beta-sandwich fold expressed exclusively in mature olfactory sensory neurons; it modulates olfactory signal transduction by facilitating Na+/Ca2+-exchanger (NCX) activity—likely through a protein interaction network involving Bex proteins and calmodulin—and is required for proper olfactory glomerular map formation and refinement, with its absence causing reduced electroolfactogram amplitudes, prolonged response kinetics, elevated odor detection thresholds, altered odor quality perception, and glomerular mistargeting of olfactory axons."},"narrative":{"mechanistic_narrative":"OMP (Olfactory Marker Protein) is a cytoplasmic protein of mature olfactory sensory neurons that functions as a modulator of the odor signal transduction cascade [PMID:8790421]. Genetic deletion in mice reduces electroolfactogram amplitudes, prolongs onset and recovery kinetics, and impairs responses to successive odor pulses [PMID:8790421], with parallel behavioral deficits including a ~300-fold elevation in detection threshold [PMID:10094125] and degraded odor quality discrimination [PMID:11439451]; adenoviral reintroduction of OMP into adult OMP-null olfactory epithelium restores both response kinetics [PMID:11036268] and threshold sensitivity [PMID:15174942], establishing a direct, non-developmental role in transduction. Structurally, OMP adopts a single globular beta-clam (beta-sandwich) fold whose inter-sheet cleft serves as a protein interaction surface that binds a Bex1-derived peptide [PMID:12054873], and Bex family members (Bex1/2/3) are physical partners of OMP in olfactory neurons [PMID:12911636]. Mechanistically, OMP facilitates Na+/Ca2+-exchanger (NCX) activity to enable rapid Ca2+ extrusion from sensory neuron dendritic knobs, with OMP-null neurons showing impaired NCX-mediated Ca2+ homeostasis; this is proposed to occur through a Bex–calmodulin intermediary, as the NCX XIP regulatory peptide binds calmodulin and calmodulin binds Bex, and NCX1 co-localizes with OMP in cilia and knobs [PMID:19165324]. Beyond signal transduction, OMP is required dose-dependently for formation and refinement of the olfactory glomerular map, with its loss producing glomeruli aberrantly co-innervated by neurons expressing different odorant receptors [PMID:30498219]. Neuron-specific expression is governed by an intronless, TATA/CAAT-less promoter containing Olf-1 sites and an NF-1-family binding element [PMID:8034318].","teleology":[{"year":1996,"claim":"Whether OMP played any functional role in olfaction was unknown; deleting it established OMP as a modulatory component of the odor detection/transduction cascade.","evidence":"Gene-targeted OMP-null mice assayed by electroolfactogram and behavioral odorant stimulation","pmids":["8790421"],"confidence":"High","gaps":["Does not identify the molecular target through which OMP shapes response kinetics","Cannot distinguish a transduction role from a developmental consequence of deletion"]},{"year":1999,"claim":"It was unclear whether the electrophysiological deficit translated to perceptual sensitivity; threshold testing showed OMP-null mice are ~300-fold less sensitive, confirming an in vivo role in odor detection.","evidence":"Behavioral psychophysical threshold testing in OMP-null vs. wild-type mice","pmids":["10094125"],"confidence":"Medium","gaps":["Single lab, single behavioral method","Does not connect the threshold shift to a defined molecular mechanism"]},{"year":2000,"claim":"It was uncertain whether the KO phenotype reflected a direct OMP function or a developmental artifact; adenoviral re-expression in adult null mice rescued response kinetics, proving a direct transduction role.","evidence":"Adenoviral OMP delivery to adult olfactory epithelium with before/after electroolfactogram recording","pmids":["11036268"],"confidence":"High","gaps":["Does not reveal the molecular partner or biochemical activity restored","Limited to kinetic readouts of the EOG"]},{"year":2001,"claim":"Beyond sensitivity, whether OMP affected odor identity was unknown; OMP-null mice showed altered multidimensional odor identification, implicating OMP in odor quality processing.","evidence":"5-odorant confusion-matrix identification task with multidimensional scaling in OMP-null mice","pmids":["11439451"],"confidence":"Medium","gaps":["Single behavioral assay, single lab","Does not localize the deficit to epithelium vs. central processing"]},{"year":2002,"claim":"The structural basis of OMP function was unknown; NMR revealed a beta-clam fold with an inter-sheet cleft that binds a Bex1-derived peptide, defining a protein-interaction surface.","evidence":"NMR solution structure determination with peptide-titration binding mapping","pmids":["12054873"],"confidence":"High","gaps":["Peptide titration does not establish full-length Bex binding affinity in vivo","No structure of an OMP-partner complex"]},{"year":2003,"claim":"The identity of OMP partners was open; phage display and cross-linking identified the Bex family (Bex1/2/3) as binding partners that co-localize with OMP in cytoplasm and nucleus.","evidence":"Phage-display cDNA screening, chemical cross-linking, in situ hybridization, and HEK293 co-transfection","pmids":["12911636"],"confidence":"Medium","gaps":["Co-localization in HEK293 may not reflect olfactory neuron compartmentalization","Functional consequence of the OMP-Bex interaction not yet defined"]},{"year":2003,"claim":"A neurophysiological substrate for altered odor quality perception was lacking; voltage-sensitive dye imaging showed degraded spatiotemporal mucosal activity patterns in OMP-null mice.","evidence":"Voltage-sensitive dye optical imaging of olfactory epithelium in OMP-null vs. wild-type mice","pmids":["12917392"],"confidence":"Medium","gaps":["Imaging does not pinpoint the molecular defect causing pattern degradation","Single method, single lab"]},{"year":2004,"claim":"The oligomeric and subcellular state of OMP was unknown; OMP was found to form a covalent homodimer that preferentially associates with Bex and partitions to a cytoskeletal fraction, distinct from the monomer in nucleus and cytosol.","evidence":"Immunoprecipitation, mass spectrometry, 2D gels, subcellular fractionation, and stability assays","pmids":["15198671"],"confidence":"Medium","gaps":["Functional role of the dimer vs. monomer not established","Single lab, no in vivo manipulation of dimerization"]},{"year":2004,"claim":"Whether OMP re-expression could restore the perceptual deficit was untested; adenoviral rescue restored behavioral threshold sensitivity to control levels, confirming a role in olfactory amplification/transduction.","evidence":"Adenoviral OMP delivery to olfactory epithelium with psychophysical threshold testing in OMP-null mice","pmids":["15174942"],"confidence":"High","gaps":["Does not define the biochemical step amplified","Behavioral rescue does not resolve the molecular mechanism"]},{"year":2009,"claim":"The biochemical mechanism linking OMP to transduction was unresolved; OMP was shown to facilitate NCX-mediated Ca2+ extrusion, proposed to act via a Bex-calmodulin intermediary, providing a molecular model for its modulatory effect.","evidence":"Single-cell Ca2+ imaging in WT vs. OMP-/- epithelium, surface plasmon resonance peptide-binding assays, and immunohistochemistry co-localization","pmids":["19165324"],"confidence":"Medium","gaps":["The Bex-CaM-NCX linkage is inferred from separate binding pairs, not a reconstituted complex","Direct OMP-NCX or OMP-CaM interaction not demonstrated"]},{"year":2018,"claim":"Whether OMP shaped circuit wiring as well as transduction was unknown; functional and genetic imaging showed OMP is required dose-dependently for glomerular map refinement, preventing co-innervation by neurons of different odorant receptors.","evidence":"synaptopHluorin knock-in mice, two-photon glomerular imaging, and single-odorant-receptor genetic targeting in OMP-/- and OMP+/- mice","pmids":["30498219"],"confidence":"High","gaps":["Molecular mechanism by which OMP guides axon targeting is undefined","Does not connect the wiring role to the NCX/Ca2+ transduction function"]},{"year":null,"claim":"It remains unknown how OMP's biochemical activity (NCX facilitation, Bex/calmodulin binding, dimerization) mechanistically connects to its role in glomerular axon targeting, and whether a direct OMP-NCX-CaM complex exists.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No reconstituted OMP-Bex-CaM-NCX complex","No structure of OMP bound to a full-length partner","Mechanism coupling Ca2+ handling to axon guidance unresolved"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0098772","term_label":"molecular function regulator activity","supporting_discovery_ids":[9]},{"term_id":"GO:0060089","term_label":"molecular transducer activity","supporting_discovery_ids":[0,2]}],"localization":[{"term_id":"GO:0005829","term_label":"cytosol","supporting_discovery_ids":[5,7]},{"term_id":"GO:0005634","term_label":"nucleus","supporting_discovery_ids":[5,7]},{"term_id":"GO:0005856","term_label":"cytoskeleton","supporting_discovery_ids":[7]},{"term_id":"GO:0005929","term_label":"cilium","supporting_discovery_ids":[9]}],"pathway":[{"term_id":"R-HSA-9709957","term_label":"Sensory Perception","supporting_discovery_ids":[0,2,9]},{"term_id":"R-HSA-112316","term_label":"Neuronal System","supporting_discovery_ids":[0,9]}],"complexes":[],"partners":["BEX1","BEX2","BEX3","CALM1","NCX1"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"P47874","full_name":"Olfactory marker protein","aliases":["Olfactory neuronal-specific protein"],"length_aa":163,"mass_kda":18.9,"function":"May act as a modulator of the olfactory signal-transduction cascade","subcellular_location":"Cytoplasm","url":"https://www.uniprot.org/uniprotkb/P47874/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/OMP","classification":"Not Classified","n_dependent_lines":4,"n_total_lines":1208,"dependency_fraction":0.0033112582781456954},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[],"url":"https://opencell.sf.czbiohub.org/search/OMP","total_profiled":1310},"omim":[{"mim_id":"613891","title":"URIDINE MONOPHOSPHATE SYNTHETASE; UMPS","url":"https://www.omim.org/entry/613891"},{"mim_id":"609472","title":"CYCLIC NUCLEOTIDE-GATED CHANNEL, ALPHA-4; CNGA4","url":"https://www.omim.org/entry/609472"},{"mim_id":"604865","title":"KLF TRANSCRIPTION FACTOR 7; KLF7","url":"https://www.omim.org/entry/604865"},{"mim_id":"601138","title":"GUANYLATE CYCLASE 2E, PSEUDOGENE; GUCY2EP","url":"https://www.omim.org/entry/601138"},{"mim_id":"600060","title":"DEAFNESS, AUTOSOMAL RECESSIVE 2; DFNB2","url":"https://www.omim.org/entry/600060"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"","locations":[],"tissue_specificity":"Tissue enhanced","tissue_distribution":"Detected in some","driving_tissues":[{"tissue":"intestine","ntpm":2.5},{"tissue":"liver","ntpm":1.3}],"url":"https://www.proteinatlas.org/search/OMP"},"hgnc":{"alias_symbol":[],"prev_symbol":[]},"alphafold":{"accession":"P47874","domains":[{"cath_id":"2.60.120.390","chopping":"11-163","consensus_level":"high","plddt":96.818,"start":11,"end":163}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/P47874","model_url":"https://alphafold.ebi.ac.uk/files/AF-P47874-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-P47874-F1-predicted_aligned_error_v6.png","plddt_mean":94.81},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=OMP","jax_strain_url":"https://www.jax.org/strain/search?query=OMP"},"sequence":{"accession":"P47874","fasta_url":"https://rest.uniprot.org/uniprotkb/P47874.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/P47874/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/P47874"}},"corpus_meta":[{"pmid":"12679035","id":"PMC_12679035","title":"OMP 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olfactory sensory neurons in vivo and in vitro.","date":"2011","source":"Journal of neuroscience methods","url":"https://pubmed.ncbi.nlm.nih.gov/21236301","citation_count":30,"is_preprint":false},{"pmid":"12917392","id":"PMC_12917392","title":"OMP gene deletion results in an alteration in odorant-induced mucosal activity patterns.","date":"2003","source":"Journal of neurophysiology","url":"https://pubmed.ncbi.nlm.nih.gov/12917392","citation_count":30,"is_preprint":false},{"pmid":"15668182","id":"PMC_15668182","title":"The effective molarity of the substrate phosphoryl group in the transition state for yeast OMP decarboxylase.","date":"2005","source":"Bioorganic chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/15668182","citation_count":30,"is_preprint":false},{"pmid":"18839943","id":"PMC_18839943","title":"Mechanism of OMP decarboxylation in orotidine 5'-monophosphate decarboxylase.","date":"2008","source":"Journal of the American Chemical 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Comparison to the OMP decarboxylase gene family.","date":"1992","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/1730672","citation_count":24,"is_preprint":false},{"pmid":"15174942","id":"PMC_15174942","title":"Adenoviral vector-mediated rescue of the OMP-null behavioral phenotype: enhancement of odorant threshold sensitivity.","date":"2004","source":"Behavioral neuroscience","url":"https://pubmed.ncbi.nlm.nih.gov/15174942","citation_count":24,"is_preprint":false},{"pmid":"17174032","id":"PMC_17174032","title":"First detection of olfactory marker protein (OMP) immunoreactivity in the olfactory epithelium of a cartilaginous fish.","date":"2006","source":"Neuroscience letters","url":"https://pubmed.ncbi.nlm.nih.gov/17174032","citation_count":23,"is_preprint":false},{"pmid":"9010731","id":"PMC_9010731","title":"Essential role of thyroid hormones in maturation of olfactory receptor neurons: an immunocytochemical study of number and cytoarchitecture of OMP-positive cells in developing rats.","date":"1996","source":"International journal of developmental neuroscience : the official journal of the International Society for Developmental Neuroscience","url":"https://pubmed.ncbi.nlm.nih.gov/9010731","citation_count":21,"is_preprint":false},{"pmid":"10839753","id":"PMC_10839753","title":"Comparison of outer membrane protein genes omp and pmp in the whole genome sequences of Chlamydia pneumoniae isolates from Japan and the United States.","date":"2000","source":"The Journal of infectious diseases","url":"https://pubmed.ncbi.nlm.nih.gov/10839753","citation_count":21,"is_preprint":false},{"pmid":"28193458","id":"PMC_28193458","title":"Inactivation of the olfactory marker protein (OMP) gene in river dolphins and other odontocete cetaceans.","date":"2017","source":"Molecular phylogenetics and evolution","url":"https://pubmed.ncbi.nlm.nih.gov/28193458","citation_count":20,"is_preprint":false},{"pmid":"19678695","id":"PMC_19678695","title":"Orotic acid decarboxylation in water and nonpolar solvents: a potential role for desolvation in the action of OMP decarboxylase.","date":"2009","source":"Biochemistry","url":"https://pubmed.ncbi.nlm.nih.gov/19678695","citation_count":20,"is_preprint":false},{"pmid":"12297406","id":"PMC_12297406","title":"Detection and characterization of pediatric serum antibody to the OMP P5-homologous adhesin of nontypeable Haemophilus influenzae during acute otitis media.","date":"2002","source":"Vaccine","url":"https://pubmed.ncbi.nlm.nih.gov/12297406","citation_count":20,"is_preprint":false},{"pmid":"17889251","id":"PMC_17889251","title":"OMP decarboxylase--An enigma persists.","date":"2007","source":"Bioorganic 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children.","date":"2015","source":"Vaccine","url":"https://pubmed.ncbi.nlm.nih.gov/26392013","citation_count":18,"is_preprint":false},{"pmid":"25275007","id":"PMC_25275007","title":"Investigating the role of a backbone to substrate hydrogen bond in OMP decarboxylase using a site-specific amide to ester substitution.","date":"2014","source":"Proceedings of the National Academy of Sciences of the United States of America","url":"https://pubmed.ncbi.nlm.nih.gov/25275007","citation_count":17,"is_preprint":false},{"pmid":"24189800","id":"PMC_24189800","title":"Measure of asymmetrical transcription of the yeast OMP decarboxylase gene expressed in yeast or in E. coli.","date":"1980","source":"Current genetics","url":"https://pubmed.ncbi.nlm.nih.gov/24189800","citation_count":17,"is_preprint":false},{"pmid":"9010727","id":"PMC_9010727","title":"LacZ and OMP are co-expressed during ontogeny and regeneration in olfactory receptor neurons of OMP promoter-lacZ transgenic mice.","date":"1996","source":"International journal of developmental neuroscience : the official journal of the International Society for Developmental Neuroscience","url":"https://pubmed.ncbi.nlm.nih.gov/9010727","citation_count":16,"is_preprint":false},{"pmid":"22531064","id":"PMC_22531064","title":"Structure of Salmonella typhimurium OMP synthase in a complete substrate complex.","date":"2012","source":"Biochemistry","url":"https://pubmed.ncbi.nlm.nih.gov/22531064","citation_count":15,"is_preprint":false},{"pmid":"7605954","id":"PMC_7605954","title":"Human olfactory receptor neurons contain OMP mRNA in their dendritic and axonal processes.","date":"1995","source":"Neuroreport","url":"https://pubmed.ncbi.nlm.nih.gov/7605954","citation_count":14,"is_preprint":false},{"pmid":"36706155","id":"PMC_36706155","title":"Conformational rearrangements in the sensory RcsF/OMP complex mediate signal transduction across the bacterial cell envelope.","date":"2023","source":"PLoS genetics","url":"https://pubmed.ncbi.nlm.nih.gov/36706155","citation_count":14,"is_preprint":false},{"pmid":"6323918","id":"PMC_6323918","title":"Sequence of the regulatory region of omp T, the gene specifying major outer membrane protein a (3b) of Escherichia coli K-12: implications for regulation and processing.","date":"1984","source":"Molecular & general genetics : MGG","url":"https://pubmed.ncbi.nlm.nih.gov/6323918","citation_count":14,"is_preprint":false},{"pmid":"31743968","id":"PMC_31743968","title":"Reversal of Olfactory Disturbance in Allergic Rhinitis Related to OMP Suppression by Intranasal Budesonide Treatment.","date":"2020","source":"Allergy, asthma & immunology research","url":"https://pubmed.ncbi.nlm.nih.gov/31743968","citation_count":13,"is_preprint":false},{"pmid":"27175202","id":"PMC_27175202","title":"Development of OMP based indirect ELISA to gauge the antibody titers in bovines against Pasteurella multocida.","date":"2015","source":"Iranian journal of veterinary research","url":"https://pubmed.ncbi.nlm.nih.gov/27175202","citation_count":13,"is_preprint":false},{"pmid":"15535676","id":"PMC_15535676","title":"OMP decarboxylase: an experimental test of electrostatic destabilization of the enzyme-substrate complex.","date":"2004","source":"Journal of the American Chemical Society","url":"https://pubmed.ncbi.nlm.nih.gov/15535676","citation_count":13,"is_preprint":false},{"pmid":"36342170","id":"PMC_36342170","title":"Efficacy and Immune Correlates of OMP-1B and VirB2-4 Vaccines for Protection of Dogs from Tick Transmission of Ehrlichia chaffeensis.","date":"2022","source":"mBio","url":"https://pubmed.ncbi.nlm.nih.gov/36342170","citation_count":12,"is_preprint":false},{"pmid":"34147613","id":"PMC_34147613","title":"Oral delivery of pVAX-OMP and pVAX-hly DNA vaccine using chitosan-tripolyphosphate (Cs-TPP) nanoparticles in Rohu, (Labeo rohita) for protection against Aeromonas hydrophila infection.","date":"2021","source":"Fish & shellfish immunology","url":"https://pubmed.ncbi.nlm.nih.gov/34147613","citation_count":12,"is_preprint":false},{"pmid":"34428402","id":"PMC_34428402","title":"Hybrid recombinant Omp 22, 25, and 31 immunodominant epitopes can be used for serodiagnosis of brucellosis.","date":"2021","source":"Journal of immunological methods","url":"https://pubmed.ncbi.nlm.nih.gov/34428402","citation_count":12,"is_preprint":false},{"pmid":"17479342","id":"PMC_17479342","title":"Positively selected codons in immune-exposed loops of the vaccine candidate OMP-P1 of Haemophilus influenzae.","date":"2007","source":"Journal of molecular evolution","url":"https://pubmed.ncbi.nlm.nih.gov/17479342","citation_count":12,"is_preprint":false},{"pmid":"19454021","id":"PMC_19454021","title":"Promoter analysis of macrophage- and tick cell-specific differentially expressed Ehrlichia chaffeensis p28-Omp genes.","date":"2009","source":"BMC microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/19454021","citation_count":11,"is_preprint":false},{"pmid":"16291671","id":"PMC_16291671","title":"Identification and characterization of a novel outer membrane protein (OMP J) of Moraxella catarrhalis that exists in two major forms.","date":"2005","source":"Journal of bacteriology","url":"https://pubmed.ncbi.nlm.nih.gov/16291671","citation_count":11,"is_preprint":false},{"pmid":"28246460","id":"PMC_28246460","title":"Proteomic characterization of oyster shell organic matrix proteins (OMP).","date":"2016","source":"Bioinformation","url":"https://pubmed.ncbi.nlm.nih.gov/28246460","citation_count":11,"is_preprint":false},{"pmid":"31417035","id":"PMC_31417035","title":"Distribution of Chlamydia trachomatis omp A genotypes in patients attending a sexually transmitted disease outpatient clinic in New Delhi, India.","date":"2019","source":"The Indian journal of medical research","url":"https://pubmed.ncbi.nlm.nih.gov/31417035","citation_count":11,"is_preprint":false},{"pmid":"32990553","id":"PMC_32990553","title":"Designing an Outer Membrane Protein (Omp-W) Based Vaccine for Immunization against Vibrio and Salmonella: An in silico Approach.","date":"2020","source":"Recent patents on biotechnology","url":"https://pubmed.ncbi.nlm.nih.gov/32990553","citation_count":10,"is_preprint":false},{"pmid":"27769003","id":"PMC_27769003","title":"In silico identification of outer membrane protein (Omp) and subunit vaccine design against pathogenic Vibrio cholerae.","date":"2016","source":"Computational biology and chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/27769003","citation_count":10,"is_preprint":false},{"pmid":"38253083","id":"PMC_38253083","title":"Anti-NOTCH1 therapy with OMP-52 M51 inhibits salivary adenoid cystic carcinoma by depressing epithelial-mesenchymal transition (EMT) process and inducing ferroptosis.","date":"2024","source":"Toxicology and applied pharmacology","url":"https://pubmed.ncbi.nlm.nih.gov/38253083","citation_count":10,"is_preprint":false},{"pmid":"11966914","id":"PMC_11966914","title":"Antimicrobial susceptibility changes and T-OMP shifts in pyrithione-passaged planktonic cultures of Pseudomonas aeruginosa PAO1.","date":"2002","source":"Journal of applied microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/11966914","citation_count":10,"is_preprint":false},{"pmid":"20170768","id":"PMC_20170768","title":"Detoxified endotoxin vaccine (J5dLPS/OMP) protects mice against lethal respiratory challenge with Francisella tularensis SchuS4.","date":"2010","source":"Vaccine","url":"https://pubmed.ncbi.nlm.nih.gov/20170768","citation_count":10,"is_preprint":false},{"pmid":"33590504","id":"PMC_33590504","title":"Evaluation of the diagnostic potential of recombinant leptospiral OMP A-like protein (Loa22) and transmembrane (OmpL37) protein in latex agglutination test for serodiagnosis of leptospirosis in animals.","date":"2021","source":"Letters in applied microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/33590504","citation_count":9,"is_preprint":false},{"pmid":"18721226","id":"PMC_18721226","title":"Induction of a protective immune response against swine Chlamydophila abortus infection in mice following co-vaccination of omp-1 DNA with recombinant MOMP.","date":"2008","source":"Zoonoses and public health","url":"https://pubmed.ncbi.nlm.nih.gov/18721226","citation_count":9,"is_preprint":false},{"pmid":"8216558","id":"PMC_8216558","title":"Detection of antibodies against Salmonella typhi outer membrane protein (OMP) preparation in typhoid fever patients.","date":"1993","source":"Asian Pacific journal of allergy and immunology","url":"https://pubmed.ncbi.nlm.nih.gov/8216558","citation_count":9,"is_preprint":false},{"pmid":"35810483","id":"PMC_35810483","title":"Efficacy of recombinant subunit OMP and hly vaccines against Aeromonas hydrophila in Rohu (Labeo rohita).","date":"2022","source":"Journal of fish diseases","url":"https://pubmed.ncbi.nlm.nih.gov/35810483","citation_count":8,"is_preprint":false},{"pmid":"38806617","id":"PMC_38806617","title":"Development of label-free electrochemical OMP-DNA probe biosensor as a highly sensitive system to detect of citrus huanglongbing.","date":"2024","source":"Scientific reports","url":"https://pubmed.ncbi.nlm.nih.gov/38806617","citation_count":8,"is_preprint":false},{"pmid":"35121302","id":"PMC_35121302","title":"Interaction of 43K OMP of Fusobacterium necrophorum with fibronectin mediates adhesion to bovine epithelial cells.","date":"2022","source":"Veterinary microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/35121302","citation_count":8,"is_preprint":false},{"pmid":"12918115","id":"PMC_12918115","title":"Construction and characterization of bivalent vaccine candidate expressing HspA and M(r)18,000 OMP from Helicobacter pylori.","date":"2003","source":"World journal of gastroenterology","url":"https://pubmed.ncbi.nlm.nih.gov/12918115","citation_count":8,"is_preprint":false},{"pmid":"24262852","id":"PMC_24262852","title":"Catalytic site interactions in yeast OMP synthase.","date":"2013","source":"Archives of biochemistry and biophysics","url":"https://pubmed.ncbi.nlm.nih.gov/24262852","citation_count":8,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":48403,"output_tokens":3118,"usd":0.09599,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":10426,"output_tokens":3748,"usd":0.072915,"stage2_stop_reason":"end_turn"},"total_usd":0.168905,"stage1_batch_id":"msgbatch_013a8chtv3AWyTqv4z4sEF4C","stage2_batch_id":"msgbatch_01AHsuW63vinsvuTgzmQ3n62","note":"batch pricing = 50% of standard"},"stage1_raw":"Looking at the corpus, I need to identify which papers are about the canonical human/mammalian OMP gene (Olfactory Marker Protein). Many papers use \"OMP\" as a generic abbreviation for \"outer membrane protein\" in bacteria, or refer to OMP decarboxylase (an enzyme), or other unrelated proteins. I'll focus on papers about the olfactory marker protein (OMP) gene/protein expressed in olfactory sensory neurons.\n\nRelevant papers: 6, 9, 14, 18, 23, 25, 33, 42, 46, 48, 53, 59, 63, 74\n\n```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 1996,\n      \"finding\": \"Deletion of the OMP gene in mice (OMP-null) causes a 20-40% reduction in maximal electroolfactogram (EOG) amplitude to multiple odorants, prolonged onset and recovery kinetics following isoamyl acetate stimulation, and impaired ability to respond to a second odor pulse, establishing OMP as a modulatory component of the odor detection/signal transduction cascade in olfactory sensory neurons.\",\n      \"method\": \"Gene targeting in embryonic stem cells; electroolfactogram recording; behavioral odorant stimulation paradigms\",\n      \"journal\": \"Proceedings of the National Academy of Sciences of the United States of America\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — clean KO mouse with multiple orthogonal physiological and behavioral readouts, replicated across odorants\",\n      \"pmids\": [\"8790421\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 1999,\n      \"finding\": \"OMP gene deletion results in a significant elevation in behavioral olfactory threshold sensitivity (OMP-null mice were ~300-fold less sensitive to propanol than controls), confirming OMP's role in modulating the odor detection/signal transduction process in vivo.\",\n      \"method\": \"Behavioral psychophysical threshold testing (air vs. odor discrimination) in OMP-null vs. wild-type mice\",\n      \"journal\": \"Neuroreport\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — clean KO with defined behavioral phenotype, single lab, single behavioral method\",\n      \"pmids\": [\"10094125\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2000,\n      \"finding\": \"Adenoviral vector-mediated reintroduction of OMP into olfactory receptor neurons of adult OMP-null mice rescues the kinetics of electrophysiological responses, restoring them to control phenotype; this demonstrates that OMP's role in olfactory transduction is direct and not a developmental artifact of gene deletion.\",\n      \"method\": \"Adenoviral gene delivery to olfactory epithelium; electroolfactogram recording before and after rescue\",\n      \"journal\": \"Nature neuroscience\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — gain-of-function rescue in adult KO animals with electrophysiological readout, complementing KO phenotype\",\n      \"pmids\": [\"11036268\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2001,\n      \"finding\": \"OMP gene deletion alters odorant quality perception; OMP-null mice show a significantly different multidimensional odorant identification profile compared to controls in a 5-odorant confusion matrix task, indicating OMP is critically involved in odor quality processing.\",\n      \"method\": \"5-odorant identification confusion matrix behavioral task with multidimensional scaling analysis in OMP-null vs. wild-type mice\",\n      \"journal\": \"Behavioral neuroscience\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — clean KO with defined behavioral phenotype, single lab, single method\",\n      \"pmids\": [\"11439451\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2002,\n      \"finding\": \"NMR solution structure of OMP reveals a single globular domain with a beta-clam (beta-sandwich) fold comprising eight beta-strands forming two orthogonally oriented beta-sheets, with two long alpha-helices and three flexible loops. Peptide titration experiments identified the cleft between the two beta-sheets as the binding surface for a peptide derived from the Bex1 protein, implicating this surface in protein-protein interactions relevant to olfactory signal transduction.\",\n      \"method\": \"NMR structure determination; peptide titration NMR experiments mapping binding surface\",\n      \"journal\": \"Journal of molecular biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Moderate — NMR structure with functional binding mapping using peptide titration, single lab but multiple orthogonal NMR methods\",\n      \"pmids\": [\"12054873\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2003,\n      \"finding\": \"Members of the Bex gene family (Bex1, Bex2, Bex3) are binding partners of OMP in olfactory receptor neurons. Bex2 was identified by phage-display screening of an olfactory mucosal cDNA library, the OMP/Bex interaction was confirmed by chemical cross-linking of recombinant OMP with a Bex-derived peptide, and co-transfection in HEK293 cells revealed that OMP co-localizes with Bex in both cytoplasm and nucleus.\",\n      \"method\": \"Phage-display cDNA library screening; chemical cross-linking; in situ hybridization; co-transfection in HEK293 cells\",\n      \"journal\": \"Journal of neurochemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — multiple orthogonal methods (phage display, cross-linking, co-transfection), single lab\",\n      \"pmids\": [\"12911636\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2003,\n      \"finding\": \"OMP gene deletion results in degraded and altered odorant-induced spatiotemporal mucosal activity patterns (recorded by voltage-sensitive dye optical imaging), providing a neurophysiological substrate for the previously observed changes in odorant quality perception in OMP-null mice.\",\n      \"method\": \"Voltage-sensitive dye optical imaging of olfactory epithelium in OMP-null vs. wild-type mice\",\n      \"journal\": \"Journal of neurophysiology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — clean KO with specific imaging-based phenotypic readout, single lab, single method\",\n      \"pmids\": [\"12917392\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2004,\n      \"finding\": \"OMP forms a covalently cross-linked homodimer (38 kDa) in addition to the monomer (19 kDa) in vivo. The dimer is preferentially co-immunoprecipitated with Bex, has a much shorter half-life than the monomer, and is preferentially localized in a Triton X-100-insoluble cytoskeletal fraction, while the monomer is present in both nuclear and cytosolic compartments.\",\n      \"method\": \"Immunoprecipitation; in-gel tryptic digestion and mass spectrometry; 2D gel electrophoresis; subcellular fractionation; transfected cell stability assays\",\n      \"journal\": \"Journal of neurochemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — multiple orthogonal methods (Co-IP, MS, fractionation), single lab\",\n      \"pmids\": [\"15198671\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2004,\n      \"finding\": \"Adenoviral vector-mediated rescue of OMP expression in OMP-null mice restores behavioral olfactory threshold sensitivity to control levels, confirming that OMP functions as an important component in olfactory signal amplification and/or transduction.\",\n      \"method\": \"Adenoviral gene delivery to olfactory epithelium; psychophysical behavioral threshold testing in OMP-null mice\",\n      \"journal\": \"Behavioral neuroscience\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — gain-of-function rescue in adult KO with behavioral readout, complementing both KO and electrophysiological rescue studies\",\n      \"pmids\": [\"15174942\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2009,\n      \"finding\": \"OMP facilitates Na+/Ca2+-exchanger (NCX) activity in olfactory sensory neurons, enabling rapid Ca2+ extrusion from OSN dendritic knobs. OMP-null mice show impaired Ca2+ homeostasis with reduced NCX-mediated Ca2+ extrusion. Mechanistically, surface plasmon resonance demonstrated a direct interaction between the XIP regulatory peptide of NCX and calmodulin (CaM); since CaM also binds to Bex (an OMP interacting partner), OMP is proposed to influence NCX activity through a Bex-CaM intermediary. NCX1 and OMP co-localize in cilia and knobs of OSNs by immunohistochemistry.\",\n      \"method\": \"Single-cell Ca2+ imaging in intact olfactory epithelium (WT vs. OMP-/- mice); surface plasmon resonance protein-peptide binding assays; immunohistochemistry co-localization\",\n      \"journal\": \"PloS one\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — multiple orthogonal methods (Ca2+ imaging, SPR, IHC), single lab, proposed pathway supported by direct binding data\",\n      \"pmids\": [\"19165324\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"OMP is required for proper formation and refinement of the olfactory glomerular map. In OMP-/- mice, individual glomeruli are frequently co-innervated by olfactory sensory neurons expressing different odorant receptors, causing functionally heterogeneous glomeruli with distinct odor-response microdomains. OMP+/- mice show rare glomerular heterogeneity, indicating a dose-dependent role for OMP in axon targeting.\",\n      \"method\": \"Knock-in mice expressing synaptopHluorin in place of one or both OMP alleles; two-photon imaging of glomerular odor responses; genetic targeting of single odorant receptors to visualize innervation patterns\",\n      \"journal\": \"Nature communications\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — multiple orthogonal methods (functional imaging, genetic single-OR targeting, anatomical analysis) in clean KO and heterozygous mice, single lab but rigorous and comprehensive\",\n      \"pmids\": [\"30498219\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 1994,\n      \"finding\": \"The human OMP gene is intronless, lacks canonical TATA and CAAT motifs, and contains conserved Olf-1 binding sites and an upstream binding region (UBE) with similarity to NF-1 family transcription factor binding motifs; gel mobility shift assays confirm NF-1 family binding to the UBE site, providing insight into mechanisms of neuron-specific OMP transcriptional regulation.\",\n      \"method\": \"Gene cloning and sequencing; gel mobility shift assays (EMSA) for transcription factor binding\",\n      \"journal\": \"Genomics\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — EMSA binding assays for regulatory elements, cross-species conservation analysis, single lab\",\n      \"pmids\": [\"8034318\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"OMP (Olfactory Marker Protein) is a cytoplasmic protein with a beta-clam/beta-sandwich fold expressed exclusively in mature olfactory sensory neurons; it modulates olfactory signal transduction by facilitating Na+/Ca2+-exchanger (NCX) activity—likely through a protein interaction network involving Bex proteins and calmodulin—and is required for proper olfactory glomerular map formation and refinement, with its absence causing reduced electroolfactogram amplitudes, prolonged response kinetics, elevated odor detection thresholds, altered odor quality perception, and glomerular mistargeting of olfactory axons.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"OMP (Olfactory Marker Protein) is a cytoplasmic protein of mature olfactory sensory neurons that functions as a modulator of the odor signal transduction cascade [#0]. Genetic deletion in mice reduces electroolfactogram amplitudes, prolongs onset and recovery kinetics, and impairs responses to successive odor pulses [#0], with parallel behavioral deficits including a ~300-fold elevation in detection threshold [#1] and degraded odor quality discrimination [#3]; adenoviral reintroduction of OMP into adult OMP-null olfactory epithelium restores both response kinetics [#2] and threshold sensitivity [#8], establishing a direct, non-developmental role in transduction. Structurally, OMP adopts a single globular beta-clam (beta-sandwich) fold whose inter-sheet cleft serves as a protein interaction surface that binds a Bex1-derived peptide [#4], and Bex family members (Bex1/2/3) are physical partners of OMP in olfactory neurons [#5]. Mechanistically, OMP facilitates Na+/Ca2+-exchanger (NCX) activity to enable rapid Ca2+ extrusion from sensory neuron dendritic knobs, with OMP-null neurons showing impaired NCX-mediated Ca2+ homeostasis; this is proposed to occur through a Bex–calmodulin intermediary, as the NCX XIP regulatory peptide binds calmodulin and calmodulin binds Bex, and NCX1 co-localizes with OMP in cilia and knobs [#9]. Beyond signal transduction, OMP is required dose-dependently for formation and refinement of the olfactory glomerular map, with its loss producing glomeruli aberrantly co-innervated by neurons expressing different odorant receptors [#10]. Neuron-specific expression is governed by an intronless, TATA/CAAT-less promoter containing Olf-1 sites and an NF-1-family binding element [#11].\",\n  \"teleology\": [\n    {\n      \"year\": 1996,\n      \"claim\": \"Whether OMP played any functional role in olfaction was unknown; deleting it established OMP as a modulatory component of the odor detection/transduction cascade.\",\n      \"evidence\": \"Gene-targeted OMP-null mice assayed by electroolfactogram and behavioral odorant stimulation\",\n      \"pmids\": [\"8790421\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Does not identify the molecular target through which OMP shapes response kinetics\", \"Cannot distinguish a transduction role from a developmental consequence of deletion\"]\n    },\n    {\n      \"year\": 1999,\n      \"claim\": \"It was unclear whether the electrophysiological deficit translated to perceptual sensitivity; threshold testing showed OMP-null mice are ~300-fold less sensitive, confirming an in vivo role in odor detection.\",\n      \"evidence\": \"Behavioral psychophysical threshold testing in OMP-null vs. wild-type mice\",\n      \"pmids\": [\"10094125\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Single lab, single behavioral method\", \"Does not connect the threshold shift to a defined molecular mechanism\"]\n    },\n    {\n      \"year\": 2000,\n      \"claim\": \"It was uncertain whether the KO phenotype reflected a direct OMP function or a developmental artifact; adenoviral re-expression in adult null mice rescued response kinetics, proving a direct transduction role.\",\n      \"evidence\": \"Adenoviral OMP delivery to adult olfactory epithelium with before/after electroolfactogram recording\",\n      \"pmids\": [\"11036268\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Does not reveal the molecular partner or biochemical activity restored\", \"Limited to kinetic readouts of the EOG\"]\n    },\n    {\n      \"year\": 2001,\n      \"claim\": \"Beyond sensitivity, whether OMP affected odor identity was unknown; OMP-null mice showed altered multidimensional odor identification, implicating OMP in odor quality processing.\",\n      \"evidence\": \"5-odorant confusion-matrix identification task with multidimensional scaling in OMP-null mice\",\n      \"pmids\": [\"11439451\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Single behavioral assay, single lab\", \"Does not localize the deficit to epithelium vs. central processing\"]\n    },\n    {\n      \"year\": 2002,\n      \"claim\": \"The structural basis of OMP function was unknown; NMR revealed a beta-clam fold with an inter-sheet cleft that binds a Bex1-derived peptide, defining a protein-interaction surface.\",\n      \"evidence\": \"NMR solution structure determination with peptide-titration binding mapping\",\n      \"pmids\": [\"12054873\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Peptide titration does not establish full-length Bex binding affinity in vivo\", \"No structure of an OMP-partner complex\"]\n    },\n    {\n      \"year\": 2003,\n      \"claim\": \"The identity of OMP partners was open; phage display and cross-linking identified the Bex family (Bex1/2/3) as binding partners that co-localize with OMP in cytoplasm and nucleus.\",\n      \"evidence\": \"Phage-display cDNA screening, chemical cross-linking, in situ hybridization, and HEK293 co-transfection\",\n      \"pmids\": [\"12911636\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Co-localization in HEK293 may not reflect olfactory neuron compartmentalization\", \"Functional consequence of the OMP-Bex interaction not yet defined\"]\n    },\n    {\n      \"year\": 2003,\n      \"claim\": \"A neurophysiological substrate for altered odor quality perception was lacking; voltage-sensitive dye imaging showed degraded spatiotemporal mucosal activity patterns in OMP-null mice.\",\n      \"evidence\": \"Voltage-sensitive dye optical imaging of olfactory epithelium in OMP-null vs. wild-type mice\",\n      \"pmids\": [\"12917392\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Imaging does not pinpoint the molecular defect causing pattern degradation\", \"Single method, single lab\"]\n    },\n    {\n      \"year\": 2004,\n      \"claim\": \"The oligomeric and subcellular state of OMP was unknown; OMP was found to form a covalent homodimer that preferentially associates with Bex and partitions to a cytoskeletal fraction, distinct from the monomer in nucleus and cytosol.\",\n      \"evidence\": \"Immunoprecipitation, mass spectrometry, 2D gels, subcellular fractionation, and stability assays\",\n      \"pmids\": [\"15198671\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Functional role of the dimer vs. monomer not established\", \"Single lab, no in vivo manipulation of dimerization\"]\n    },\n    {\n      \"year\": 2004,\n      \"claim\": \"Whether OMP re-expression could restore the perceptual deficit was untested; adenoviral rescue restored behavioral threshold sensitivity to control levels, confirming a role in olfactory amplification/transduction.\",\n      \"evidence\": \"Adenoviral OMP delivery to olfactory epithelium with psychophysical threshold testing in OMP-null mice\",\n      \"pmids\": [\"15174942\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Does not define the biochemical step amplified\", \"Behavioral rescue does not resolve the molecular mechanism\"]\n    },\n    {\n      \"year\": 2009,\n      \"claim\": \"The biochemical mechanism linking OMP to transduction was unresolved; OMP was shown to facilitate NCX-mediated Ca2+ extrusion, proposed to act via a Bex-calmodulin intermediary, providing a molecular model for its modulatory effect.\",\n      \"evidence\": \"Single-cell Ca2+ imaging in WT vs. OMP-/- epithelium, surface plasmon resonance peptide-binding assays, and immunohistochemistry co-localization\",\n      \"pmids\": [\"19165324\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"The Bex-CaM-NCX linkage is inferred from separate binding pairs, not a reconstituted complex\", \"Direct OMP-NCX or OMP-CaM interaction not demonstrated\"]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"Whether OMP shaped circuit wiring as well as transduction was unknown; functional and genetic imaging showed OMP is required dose-dependently for glomerular map refinement, preventing co-innervation by neurons of different odorant receptors.\",\n      \"evidence\": \"synaptopHluorin knock-in mice, two-photon glomerular imaging, and single-odorant-receptor genetic targeting in OMP-/- and OMP+/- mice\",\n      \"pmids\": [\"30498219\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Molecular mechanism by which OMP guides axon targeting is undefined\", \"Does not connect the wiring role to the NCX/Ca2+ transduction function\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"It remains unknown how OMP's biochemical activity (NCX facilitation, Bex/calmodulin binding, dimerization) mechanistically connects to its role in glomerular axon targeting, and whether a direct OMP-NCX-CaM complex exists.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No reconstituted OMP-Bex-CaM-NCX complex\", \"No structure of OMP bound to a full-length partner\", \"Mechanism coupling Ca2+ handling to axon guidance unresolved\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0098772\", \"supporting_discovery_ids\": [9]},\n      {\"term_id\": \"GO:0060089\", \"supporting_discovery_ids\": [0, 2]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005829\", \"supporting_discovery_ids\": [5, 7]},\n      {\"term_id\": \"GO:0005634\", \"supporting_discovery_ids\": [5, 7]},\n      {\"term_id\": \"GO:0005856\", \"supporting_discovery_ids\": [7]},\n      {\"term_id\": \"GO:0005929\", \"supporting_discovery_ids\": [9]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-9709957\", \"supporting_discovery_ids\": [0, 2, 9]},\n      {\"term_id\": \"R-HSA-112316\", \"supporting_discovery_ids\": [0, 9]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\"BEX1\", \"BEX2\", \"BEX3\", \"CALM1\", \"NCX1\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":6,"faith_total":6,"faith_pct":100.0}}