{"gene":"RCVRN","run_date":"2026-06-10T06:43:36","timeline":{"discoveries":[{"year":1993,"finding":"The mouse 23 kDa photoreceptor-specific protein (Rcvrn) was shown by deduced amino acid sequence comparison to be identical to the recoverin protein and the CAR (cancer-associated retinopathy) antigen, establishing these as the same gene product. Segregation analysis of restriction fragment length variants in recombinant inbred mouse strains mapped Rcvrn to Chromosome 11, between Sparc and Zfp-3, in close linkage with the tumor suppressor gene Trp53.","method":"DNA sequence analysis of mouse Rcvrn gene; restriction fragment length variant segregation analysis in recombinant inbred strains","journal":"Mammalian genome : official journal of the International Mammalian Genome Society","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — sequence identity established by deduced amino acid comparison with functional annotation; chromosomal mapping by segregation analysis; single lab, two orthogonal methods","pmids":["8422501"],"is_preprint":false},{"year":2002,"finding":"The canine RCV1 protein (202 amino acids) contains two canonical Ca2+-binding EF-hand motifs, as determined by sequence analysis of the cloned gene. Amino acid substitutions N3K and P202H identified in the canine ORF did not segregate with progressive retinal atrophy (PRA) in any of 22 dog breeds examined, providing negative evidence against RCV1 as the cause of PRA.","method":"Genomic library cloning, PCR-SSCP, DNA sequencing, breed-wide segregation analysis","journal":"Molecular vision","confidence":"Low","confidence_rationale":"Tier 3 / Weak — structural inference from sequence only (no functional validation of EF-hand activity); negative genetic result confirmed by single-lab segregation analysis","pmids":["12447165"],"is_preprint":false}],"current_model":"Based on the available abstracts, RCVRN (recoverin) is established as a photoreceptor-specific calcium-binding protein containing two EF-hand motifs and identical to the cancer-associated retinopathy (CAR) antigen; direct mechanistic experiments characterizing its enzymatic activity, binding partners, or calcium-dependent conformational mechanism are not represented in this corpus."},"narrative":{"mechanistic_narrative":"RCVRN encodes recoverin, a photoreceptor-specific protein that is identical to the cancer-associated retinopathy (CAR) antigen, establishing a single gene product underlying both the retinal protein and the autoimmune retinopathy target [PMID:8422501]. The protein contains two canonical Ca2+-binding EF-hand motifs as inferred from sequence analysis of the cloned gene [PMID:12447165]. Beyond this sequence-level characterization and chromosomal mapping near Trp53 [PMID:8422501], no direct mechanistic detail on its enzymatic activity, calcium-dependent conformational behavior, or binding partners has been characterized in the available corpus. Candidate-gene analysis of the canine ortholog found that coding substitutions did not segregate with progressive retinal atrophy, providing negative genetic evidence against this gene as the cause of that disorder [PMID:12447165].","teleology":[{"year":1993,"claim":"Resolved whether the photoreceptor 23 kDa protein, recoverin, and the CAR antigen represent the same molecule, unifying a retinal protein with an autoimmune retinopathy target.","evidence":"Deduced amino acid sequence comparison of the mouse Rcvrn gene plus restriction fragment length variant segregation mapping in recombinant inbred strains","pmids":["8422501"],"confidence":"Medium","gaps":["No functional or biochemical activity assigned to the protein","Calcium-binding behavior not experimentally tested","Mechanism linking the protein to the CAR autoimmune phenotype not addressed"]},{"year":2002,"claim":"Characterized the canine ortholog's structural features and tested it as a candidate disease gene, defining its EF-hand architecture and excluding it as a cause of progressive retinal atrophy.","evidence":"Genomic library cloning, PCR-SSCP, DNA sequencing, and breed-wide segregation analysis across 22 dog breeds","pmids":["12447165"],"confidence":"Low","gaps":["EF-hand calcium-binding activity inferred from sequence only, not functionally validated","Negative genetic result from single-lab segregation analysis","No mechanistic role established"]},{"year":null,"claim":"The calcium-dependent conformational mechanism, enzymatic or regulatory activity, binding partners, and downstream signaling role of recoverin remain uncharacterized in the available corpus.","evidence":"No direct mechanistic experiments represented","pmids":[],"confidence":"Low","gaps":["No direct measurement of calcium binding by the EF-hand motifs","No identified physical partners or substrates","No structural or functional characterization of the photoreceptor role"]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":[],"partners":[],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"P35243","full_name":"Recoverin","aliases":["Cancer-associated retinopathy protein","Protein CAR"],"length_aa":200,"mass_kda":23.1,"function":"Acts as a calcium sensor and regulates phototransduction of cone and rod photoreceptor cells (By similarity). Modulates light sensitivity of cone photoreceptor in dark and dim conditions (By similarity). In response to high Ca(2+) levels induced by low light levels, prolongs RHO/rhodopsin activation in rod photoreceptor cells by binding to and inhibiting GRK1-mediated phosphorylation of RHO/rhodopsin (By similarity). Plays a role in scotopic vision/enhances vision in dim light by enhancing signal transfer between rod photoreceptors and rod bipolar cells (By similarity). Improves rod photoreceptor sensitivity in dim light and mediates response of rod photoreceptors to facilitate detection of change and motion in bright light (By similarity)","subcellular_location":"Photoreceptor inner segment; Cell projection, cilium, photoreceptor outer segment; Photoreceptor outer segment membrane; Perikaryon","url":"https://www.uniprot.org/uniprotkb/P35243/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/RCVRN","classification":"Not Classified","n_dependent_lines":9,"n_total_lines":1208,"dependency_fraction":0.0074503311258278145},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[],"url":"https://opencell.sf.czbiohub.org/search/RCVRN","total_profiled":1310},"omim":[{"mim_id":"179618","title":"RECOVERIN; RCVRN","url":"https://www.omim.org/entry/179618"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Approved","locations":[{"location":"Mid piece","reliability":"Approved"},{"location":"Principal piece","reliability":"Approved"}],"tissue_specificity":"Tissue enriched","tissue_distribution":"Detected in some","driving_tissues":[{"tissue":"retina","ntpm":430.9}],"url":"https://www.proteinatlas.org/search/RCVRN"},"hgnc":{"alias_symbol":[],"prev_symbol":["RCV1"]},"alphafold":{"accession":"P35243","domains":[{"cath_id":"1.10.238.10","chopping":"14-96","consensus_level":"medium","plddt":84.8158,"start":14,"end":96},{"cath_id":"1.10.238.10","chopping":"98-187","consensus_level":"medium","plddt":91.0312,"start":98,"end":187}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/P35243","model_url":"https://alphafold.ebi.ac.uk/files/AF-P35243-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-P35243-F1-predicted_aligned_error_v6.png","plddt_mean":83.75},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=RCVRN","jax_strain_url":"https://www.jax.org/strain/search?query=RCVRN"},"sequence":{"accession":"P35243","fasta_url":"https://rest.uniprot.org/uniprotkb/P35243.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/P35243/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/P35243"}},"corpus_meta":[{"pmid":"27826002","id":"PMC_27826002","title":"3D culture of human pluripotent stem cells in RGD-alginate hydrogel improves retinal tissue development.","date":"2016","source":"Acta biomaterialia","url":"https://pubmed.ncbi.nlm.nih.gov/27826002","citation_count":120,"is_preprint":false},{"pmid":"21491544","id":"PMC_21491544","title":"Differentiation of induced pluripotent stem cells of swine into rod photoreceptors and their integration into the retina.","date":"2011","source":"Stem cells (Dayton, Ohio)","url":"https://pubmed.ncbi.nlm.nih.gov/21491544","citation_count":96,"is_preprint":false},{"pmid":"8586428","id":"PMC_8586428","title":"A gene for autosomal dominant progressive cone dystrophy (CORD5) maps to chromosome 17p12-p13.","date":"1995","source":"Genomics","url":"https://pubmed.ncbi.nlm.nih.gov/8586428","citation_count":71,"is_preprint":false},{"pmid":"29196060","id":"PMC_29196060","title":"miR-365 promotes diabetic retinopathy through inhibiting Timp3 and increasing oxidative stress.","date":"2017","source":"Experimental eye research","url":"https://pubmed.ncbi.nlm.nih.gov/29196060","citation_count":47,"is_preprint":false},{"pmid":"26283078","id":"PMC_26283078","title":"Characterization of Three-Dimensional Retinal Tissue Derived from Human Embryonic Stem Cells in Adherent Monolayer Cultures.","date":"2015","source":"Stem cells and development","url":"https://pubmed.ncbi.nlm.nih.gov/26283078","citation_count":47,"is_preprint":false},{"pmid":"8733141","id":"PMC_8733141","title":"Localisation of a gene for central areolar choroidal dystrophy to chromosome 17p.","date":"1996","source":"Human molecular genetics","url":"https://pubmed.ncbi.nlm.nih.gov/8733141","citation_count":45,"is_preprint":false},{"pmid":"30533172","id":"PMC_30533172","title":"Intravitreal Injection of Hydrogen Peroxide Induces Acute Retinal Degeneration, Apoptosis, and Oxidative Stress in Mice.","date":"2018","source":"Oxidative medicine and cellular longevity","url":"https://pubmed.ncbi.nlm.nih.gov/30533172","citation_count":30,"is_preprint":false},{"pmid":"8422501","id":"PMC_8422501","title":"Chromosomal assignment of the recoverin gene and cancer-associated retinopathy.","date":"1993","source":"Mammalian genome : official journal of the International Mammalian Genome Society","url":"https://pubmed.ncbi.nlm.nih.gov/8422501","citation_count":22,"is_preprint":false},{"pmid":"7607661","id":"PMC_7607661","title":"Evidence against involvement of recoverin in autosomal recessive retinitis pigmentosa in 42 Spanish families.","date":"1995","source":"Human genetics","url":"https://pubmed.ncbi.nlm.nih.gov/7607661","citation_count":20,"is_preprint":false},{"pmid":"38816767","id":"PMC_38816767","title":"Retinal organoids with X-linked retinoschisis RS1 (E72K) mutation exhibit a photoreceptor developmental delay and are rescued by gene augmentation therapy.","date":"2024","source":"Stem cell research & therapy","url":"https://pubmed.ncbi.nlm.nih.gov/38816767","citation_count":18,"is_preprint":false},{"pmid":"24327609","id":"PMC_24327609","title":"Swine cone and rod precursors arise sequentially and display sequential and transient integration and differentiation potential following transplantation.","date":"2014","source":"Investigative ophthalmology & visual science","url":"https://pubmed.ncbi.nlm.nih.gov/24327609","citation_count":18,"is_preprint":false},{"pmid":"36129723","id":"PMC_36129723","title":"Timed Notch Inhibition Drives Photoreceptor Fate Specification in Human Retinal Organoids.","date":"2022","source":"Investigative ophthalmology & visual science","url":"https://pubmed.ncbi.nlm.nih.gov/36129723","citation_count":17,"is_preprint":false},{"pmid":"32714647","id":"PMC_32714647","title":"Generation of a Retina Reporter hiPSC Line to Label Progenitor, Ganglion, and Photoreceptor Cell Types.","date":"2020","source":"Translational vision science & technology","url":"https://pubmed.ncbi.nlm.nih.gov/32714647","citation_count":16,"is_preprint":false},{"pmid":"35573687","id":"PMC_35573687","title":"Generation of an RCVRN-eGFP Reporter hiPSC Line by CRISPR/Cas9 to Monitor Photoreceptor Cell Development and Facilitate the Cell Enrichment for Transplantation.","date":"2022","source":"Frontiers in cell and developmental biology","url":"https://pubmed.ncbi.nlm.nih.gov/35573687","citation_count":14,"is_preprint":false},{"pmid":"34093110","id":"PMC_34093110","title":"Knock-Out of Tenascin-C Ameliorates Ischemia-Induced Rod-Photoreceptor Degeneration and Retinal Dysfunction.","date":"2021","source":"Frontiers in neuroscience","url":"https://pubmed.ncbi.nlm.nih.gov/34093110","citation_count":14,"is_preprint":false},{"pmid":"27122963","id":"PMC_27122963","title":"Molecular studies of phenotype variation in canine RPGR-XLPRA1.","date":"2016","source":"Molecular vision","url":"https://pubmed.ncbi.nlm.nih.gov/27122963","citation_count":12,"is_preprint":false},{"pmid":"30483479","id":"PMC_30483479","title":"A Wor1-Like Transcription Factor Is Essential for Virulence of Cryptococcus neoformans.","date":"2018","source":"Frontiers in cellular and infection microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/30483479","citation_count":10,"is_preprint":false},{"pmid":"12447165","id":"PMC_12447165","title":"The canine Recoverin (RCV1) gene: a candidate gene for generalized progressive retinal atrophy.","date":"2002","source":"Molecular vision","url":"https://pubmed.ncbi.nlm.nih.gov/12447165","citation_count":8,"is_preprint":false},{"pmid":"35266580","id":"PMC_35266580","title":"RNA-Seq analysis reveals sex-dependent transcriptomic profiles of human subacromial bursa stratified by tear etiology.","date":"2022","source":"Journal of orthopaedic research : official publication of the Orthopaedic Research Society","url":"https://pubmed.ncbi.nlm.nih.gov/35266580","citation_count":8,"is_preprint":false},{"pmid":"36041510","id":"PMC_36041510","title":"Legumain affects the PI3K/AKT tumor progression pathway in retinoblastoma.","date":"2022","source":"Experimental eye research","url":"https://pubmed.ncbi.nlm.nih.gov/36041510","citation_count":8,"is_preprint":false},{"pmid":"10894563","id":"PMC_10894563","title":"Measurement of plasma volume using 99Tc(m)-labelled DMP-HSA.","date":"2000","source":"Nuclear medicine communications","url":"https://pubmed.ncbi.nlm.nih.gov/10894563","citation_count":8,"is_preprint":false},{"pmid":"34192607","id":"PMC_34192607","title":"Downregulation of CRX, a Group 3-specific oncogenic transcription factor, inhibits TGF-β/activin signaling in medulloblastoma cells.","date":"2021","source":"Biochemical and biophysical research communications","url":"https://pubmed.ncbi.nlm.nih.gov/34192607","citation_count":6,"is_preprint":false},{"pmid":"29161152","id":"PMC_29161152","title":"Proliferative Cells Isolated from the Adult Human Peripheral Retina only Transiently Upregulate Key Retinal Markers upon Induced Differentiation.","date":"2017","source":"Current eye research","url":"https://pubmed.ncbi.nlm.nih.gov/29161152","citation_count":6,"is_preprint":false},{"pmid":"38884674","id":"PMC_38884674","title":"NR2E3 inhibits the inflammation and apoptosis in diabetic retinopathy by regulating the AHR/IL-17A signaling pathway.","date":"2024","source":"Naunyn-Schmiedeberg's archives of pharmacology","url":"https://pubmed.ncbi.nlm.nih.gov/38884674","citation_count":4,"is_preprint":false},{"pmid":"23557786","id":"PMC_23557786","title":"Irx7, a Smarca4-regulated gene for retinal differentiation, regulates other genes controlled by Smarca4 in zebrafish retinas.","date":"2013","source":"Gene expression patterns : GEP","url":"https://pubmed.ncbi.nlm.nih.gov/23557786","citation_count":4,"is_preprint":false},{"pmid":"37329550","id":"PMC_37329550","title":"The probiotic-induced disregulation of immune-related genes in colon cells and relation with colorectal cancer.","date":"2023","source":"Cellular and molecular biology (Noisy-le-Grand, France)","url":"https://pubmed.ncbi.nlm.nih.gov/37329550","citation_count":1,"is_preprint":false},{"pmid":"41327005","id":"PMC_41327005","title":"A comparative transcriptomic analysis provides new insights into the ecological adaptations in Ichthyophis bannanicus.","date":"2025","source":"BMC genomics","url":"https://pubmed.ncbi.nlm.nih.gov/41327005","citation_count":0,"is_preprint":false},{"pmid":"41742262","id":"PMC_41742262","title":"Short-term exposure of sleep deprivation male model rats to dutasteride promotes the discovery of gene profiles related to fertility impairments.","date":"2026","source":"BMC medical genomics","url":"https://pubmed.ncbi.nlm.nih.gov/41742262","citation_count":0,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":18197,"output_tokens":1040,"usd":0.035096,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":7008,"output_tokens":1098,"usd":0.031245,"stage2_stop_reason":"end_turn"},"total_usd":0.066341,"stage1_batch_id":"msgbatch_01CNoDbkChHEkgrJnL7BwtGJ","stage2_batch_id":"msgbatch_016Y4x9E9Wg5VQDANj9quSQD","note":"batch pricing = 50% of standard"},"stage1_raw":"Looking through the abstracts, I need to identify papers about the canonical RCVRN/RCV1 protein (recoverin, a calcium-binding protein in photoreceptors) and extract mechanistic findings.\n\n**Paper-by-paper classification:**\n- Papers [1-16, 18, 23-27]: Most use RCVRN as a photoreceptor marker in stem cell/retinal studies — these are expression/marker studies, not mechanistic. \n- Paper [17]: About *Cryptococcus* \"Rcv1\" — this is a fungal transcription factor, completely incompatible with the mammalian photoreceptor protein. **Exclude** (symbol collision).\n- Paper [18]: Canine RCV1 gene cloning — describes EF-hand Ca2+-binding motifs and exclusion as PRA candidate. Contains some structural annotation from sequence.\n- Paper [8]: Mouse Rcvrn chromosomal assignment and CAR protein identity — establishes identity between recoverin, 23kD photoreceptor protein, and CAR antigen.\n- Paper [25]: Zebrafish rcv1 regulated by irx7/smarca4 — this is about gene regulation in retina, expression-level finding.\n- Papers [3], [6], [9]: Genetic linkage/exclusion studies — no direct mechanistic experiments on the protein.\n- Paper [21]: RCV1 = red cell volume measurement — symbol collision, exclude.\n\nNone of the abstracts contain direct mechanistic experiments (in vitro assays, co-IPs, structures, active-site mutagenesis) establishing HOW the RCVRN protein functions. The closest are gene identity (paper [8]) and sequence-based identification of EF-hand motifs (paper [18]), but these are not direct functional experiments from the abstracts.\n\n```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 1993,\n      \"finding\": \"The mouse 23 kDa photoreceptor-specific protein (Rcvrn) was shown by deduced amino acid sequence comparison to be identical to the recoverin protein and the CAR (cancer-associated retinopathy) antigen, establishing these as the same gene product. Segregation analysis of restriction fragment length variants in recombinant inbred mouse strains mapped Rcvrn to Chromosome 11, between Sparc and Zfp-3, in close linkage with the tumor suppressor gene Trp53.\",\n      \"method\": \"DNA sequence analysis of mouse Rcvrn gene; restriction fragment length variant segregation analysis in recombinant inbred strains\",\n      \"journal\": \"Mammalian genome : official journal of the International Mammalian Genome Society\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — sequence identity established by deduced amino acid comparison with functional annotation; chromosomal mapping by segregation analysis; single lab, two orthogonal methods\",\n      \"pmids\": [\"8422501\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2002,\n      \"finding\": \"The canine RCV1 protein (202 amino acids) contains two canonical Ca2+-binding EF-hand motifs, as determined by sequence analysis of the cloned gene. Amino acid substitutions N3K and P202H identified in the canine ORF did not segregate with progressive retinal atrophy (PRA) in any of 22 dog breeds examined, providing negative evidence against RCV1 as the cause of PRA.\",\n      \"method\": \"Genomic library cloning, PCR-SSCP, DNA sequencing, breed-wide segregation analysis\",\n      \"journal\": \"Molecular vision\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — structural inference from sequence only (no functional validation of EF-hand activity); negative genetic result confirmed by single-lab segregation analysis\",\n      \"pmids\": [\"12447165\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"Based on the available abstracts, RCVRN (recoverin) is established as a photoreceptor-specific calcium-binding protein containing two EF-hand motifs and identical to the cancer-associated retinopathy (CAR) antigen; direct mechanistic experiments characterizing its enzymatic activity, binding partners, or calcium-dependent conformational mechanism are not represented in this corpus.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"RCVRN encodes recoverin, a photoreceptor-specific protein that is identical to the cancer-associated retinopathy (CAR) antigen, establishing a single gene product underlying both the retinal protein and the autoimmune retinopathy target [#0]. The protein contains two canonical Ca2+-binding EF-hand motifs as inferred from sequence analysis of the cloned gene [#1]. Beyond this sequence-level characterization and chromosomal mapping near Trp53 [#0], no direct mechanistic detail on its enzymatic activity, calcium-dependent conformational behavior, or binding partners has been characterized in the available corpus. Candidate-gene analysis of the canine ortholog found that coding substitutions did not segregate with progressive retinal atrophy, providing negative genetic evidence against this gene as the cause of that disorder [#1].\",\n  \"teleology\": [\n    {\n      \"year\": 1993,\n      \"claim\": \"Resolved whether the photoreceptor 23 kDa protein, recoverin, and the CAR antigen represent the same molecule, unifying a retinal protein with an autoimmune retinopathy target.\",\n      \"evidence\": \"Deduced amino acid sequence comparison of the mouse Rcvrn gene plus restriction fragment length variant segregation mapping in recombinant inbred strains\",\n      \"pmids\": [\"8422501\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No functional or biochemical activity assigned to the protein\",\n        \"Calcium-binding behavior not experimentally tested\",\n        \"Mechanism linking the protein to the CAR autoimmune phenotype not addressed\"\n      ]\n    },\n    {\n      \"year\": 2002,\n      \"claim\": \"Characterized the canine ortholog's structural features and tested it as a candidate disease gene, defining its EF-hand architecture and excluding it as a cause of progressive retinal atrophy.\",\n      \"evidence\": \"Genomic library cloning, PCR-SSCP, DNA sequencing, and breed-wide segregation analysis across 22 dog breeds\",\n      \"pmids\": [\"12447165\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"EF-hand calcium-binding activity inferred from sequence only, not functionally validated\",\n        \"Negative genetic result from single-lab segregation analysis\",\n        \"No mechanistic role established\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The calcium-dependent conformational mechanism, enzymatic or regulatory activity, binding partners, and downstream signaling role of recoverin remain uncharacterized in the available corpus.\",\n      \"evidence\": \"No direct mechanistic experiments represented\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No direct measurement of calcium binding by the EF-hand motifs\",\n        \"No identified physical partners or substrates\",\n        \"No structural or functional characterization of the photoreceptor role\"\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [],\n    \"localization\": [],\n    \"pathway\": [],\n    \"complexes\": [],\n    \"partners\": [],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"tie","faith_supported":3,"faith_total":4,"faith_pct":75.0}}