{"gene":"JSRP1","run_date":"2026-06-10T01:55:23","timeline":{"discoveries":[{"year":2000,"finding":"JP-45 (JSRP1) is a 45 kDa integral membrane protein selectively localized in the junctional face membrane (JFM) of skeletal muscle sarcoplasmic reticulum, present in both neonatal and adult SR but absent from heart, liver, or kidney microsomes. The JP-45-containing complex can be phosphorylated in vitro by the catalytic subunit of protein kinase A.","method":"Subcellular fractionation, immunoprecipitation, in vitro PKA phosphorylation assay","journal":"The Biochemical journal","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — biochemical fractionation and immunoprecipitation with in vitro phosphorylation assay, single lab, multiple orthogonal methods","pmids":["11023841"],"is_preprint":false},{"year":2003,"finding":"JP-45 (JSRP1) is an integral protein of the skeletal muscle SR junctional face membrane with a cytoplasmic domain, single transmembrane segment, and positively charged intralumenal domain. It co-localizes with the ryanodine receptor (SR Ca2+ release channel) and co-immunoprecipitates with the alpha1.1 subunit of the voltage-gated calcium channel (Cav1.1) and calsequestrin, implicating it in excitation-contraction coupling.","method":"cDNA cloning, Northern blot, Western blot, double immunofluorescence, co-immunoprecipitation","journal":"The Journal of biological chemistry","confidence":"High","confidence_rationale":"Tier 2 / Strong — reciprocal co-immunoprecipitation with multiple partners, co-localization, multiple orthogonal methods, foundational characterization paper","pmids":["12871958"],"is_preprint":false},{"year":2006,"finding":"The cytoplasmic domain of JP-45 (residues 1–80) interacts with two distinct regions of Cav1.1: the I-II loop (via the alpha-interacting domain) and the C-terminal region. The beta1a subunit of Cav1 also interacts with the cytosolic domain of JP-45, and its presence drastically reduces JP-45 interaction with the I-II loop. Overexpression of JP-45 in C2C12 myotubes decreased peak charge movement and shifted VQ1/2 to more negative potential; JP-45 depletion decreased both Cav1.1 content and peak charge movement, demonstrating JP-45 is required for functional expression of voltage-dependent Ca2+ channels.","method":"Domain mapping by pulldown/interaction assays, overexpression and siRNA depletion in C2C12 myotubes, whole-cell voltage-clamp (charge movement recording)","journal":"Journal of cell science","confidence":"High","confidence_rationale":"Tier 1–2 / Strong — domain-level interaction mapping combined with functional electrophysiology (gain- and loss-of-function), multiple orthogonal methods in one study","pmids":["16638807"],"is_preprint":false},{"year":2006,"finding":"Overexpression of JP-45-DsRed2 in C2C12 myotubes did not significantly change voltage-activated Ca2+ current properties but decreased the amplitude of depolarization-induced Ca2+ transients. This decrease was attributed to a reduction in voltage-activated Ca2+ permeability per voltage-sensor charge, consistent with JP-45 modulating the coupling between the dihydropyridine receptor (DHPR) voltage sensor and SR Ca2+ release, rather than altering SR Ca2+ content or removal.","method":"Nuclear microinjection overexpression in C2C12 myotubes, whole-cell voltage-clamp, fura-2 Ca2+ imaging, Ca2+ flux modeling","journal":"The Journal of physiology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — functional electrophysiology and Ca2+ imaging with quantitative modeling, single lab, overexpression only (no loss-of-function)","pmids":["16423849"],"is_preprint":false},{"year":2012,"finding":"Two human JSRP1 variants (c.323C>T, p.P108L and c.449G>C, p.G150A) each decrease the sensitivity of the dihydropyridine receptor (DHPR) to activation during excitation-contraction coupling. These variants are not enriched in malignant hyperthermia susceptible individuals but may modulate EC coupling severity in patients carrying RYR1 mutations by counteracting DHPR hypersensitivity.","method":"Population genotyping, functional EC coupling assays in muscle cells expressing variant JP-45 proteins","journal":"Human mutation","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — functional EC coupling assays with defined variants, single lab, mechanistic follow-up of prior interaction data","pmids":["22927026"],"is_preprint":false}],"current_model":"JSRP1/JP-45 is an integral protein of the skeletal muscle sarcoplasmic reticulum junctional face membrane whose cytoplasmic domain (residues 1–80) directly interacts with Cav1.1 (at its I-II loop and C-terminal region) and with calsequestrin; the beta1a subunit competes for the I-II loop interaction site. JP-45 is required for normal functional expression and voltage-sensing of Cav1.1, modulating charge movement and SR Ca2+ release during excitation-contraction coupling, and human missense variants (P108L, G150A) reduce DHPR sensitivity to activation."},"narrative":{"mechanistic_narrative":"JSRP1 (JP-45) is an integral membrane protein of the skeletal muscle sarcoplasmic reticulum junctional face membrane that functions as a regulator of excitation-contraction coupling [PMID:12871958, PMID:16638807]. Tissue-selective and localized to the SR junctional face membrane, it co-localizes with the ryanodine receptor and forms a complex with the Cav1.1 (DHPR) alpha1.1 subunit and calsequestrin [PMID:11023841, PMID:12871958]. Its cytoplasmic domain (residues 1–80) binds two distinct Cav1.1 regions—the I-II loop and the C-terminus—and also engages the Cav1 beta1a subunit, which competes for the I-II loop interaction site [PMID:16638807]. Through these interactions JP-45 is required for functional expression and voltage sensing of Cav1.1, modulating charge movement and the coupling between the DHPR voltage sensor and SR Ca2+ release rather than altering SR Ca2+ content [PMID:16638807, PMID:16423849]. Two human missense variants (P108L, G150A) reduce DHPR sensitivity to activation during EC coupling [PMID:22927026].","teleology":[{"year":2000,"claim":"Establishing that a previously uncharacterized 45 kDa protein is a tissue-selective resident of the SR junctional face membrane defined where it could act in muscle.","evidence":"Subcellular fractionation, immunoprecipitation and in vitro PKA phosphorylation of microsomes from multiple tissues","pmids":["11023841"],"confidence":"Medium","gaps":["Binding partners not yet identified","Functional role in EC coupling not established","Physiological relevance of PKA phosphorylation untested"]},{"year":2003,"claim":"Identifying JP-45's molecular partners answered whether it is positioned to participate in the DHPR-RyR coupling machinery.","evidence":"cDNA cloning, double immunofluorescence and reciprocal co-immunoprecipitation in skeletal muscle SR","pmids":["12871958"],"confidence":"High","gaps":["Interaction interfaces not mapped","Functional consequence of the interactions untested","Direct vs indirect association within the complex unresolved"]},{"year":2006,"claim":"Mapping the cytoplasmic domain interactions and combining with gain/loss-of-function established that JP-45 is required for functional expression and voltage sensing of Cav1.1.","evidence":"Domain pulldown mapping plus overexpression and siRNA depletion in C2C12 myotubes with whole-cell charge-movement recording","pmids":["16638807"],"confidence":"High","gaps":["Stoichiometry of the JP-45/Cav1.1/beta1a complex unresolved","Mechanism by which beta1a competition is regulated in vivo unclear"]},{"year":2006,"claim":"Quantitative Ca2+ flux analysis distinguished whether JP-45 acts on SR Ca2+ load versus the voltage-sensor-to-release coupling step.","evidence":"Nuclear microinjection overexpression in C2C12 myotubes with voltage-clamp, fura-2 imaging and Ca2+ flux modeling","pmids":["16423849"],"confidence":"Medium","gaps":["Overexpression only, no loss-of-function confirmation","Molecular step in DHPR-RyR coupling affected not pinpointed"]},{"year":2012,"claim":"Testing human JSRP1 variants asked whether sequence variation in JP-45 alters EC coupling and disease modulation.","evidence":"Population genotyping and functional EC coupling assays in muscle cells expressing P108L and G150A variants","pmids":["22927026"],"confidence":"Medium","gaps":["Variants not enriched in malignant hyperthermia cohorts","Structural basis of reduced DHPR sensitivity not defined","Interaction with RYR1 mutations inferred, not directly demonstrated"]},{"year":null,"claim":"The structural basis of JP-45's regulation of Cav1.1 voltage sensing and how beta1a competition is dynamically controlled during EC coupling remain unresolved.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No structural model of the JP-45/Cav1.1 interface","In vivo regulatory role of PKA phosphorylation unknown","Whole-animal phenotype of JSRP1 loss not characterized in the corpus"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0098772","term_label":"molecular function regulator activity","supporting_discovery_ids":[2,3]}],"localization":[{"term_id":"GO:0005783","term_label":"endoplasmic reticulum","supporting_discovery_ids":[0,1]}],"pathway":[{"term_id":"R-HSA-397014","term_label":"Muscle contraction","supporting_discovery_ids":[2,3]}],"complexes":[],"partners":["CACNA1S","CASQ1","RYR1","CACNB1"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q96MG2","full_name":"Junctional sarcoplasmic reticulum protein 1","aliases":["Junctional-face membrane protein of 45 kDa homolog","JP-45"],"length_aa":331,"mass_kda":36.3,"function":"Involved in skeletal muscle excitation/contraction coupling (EC), probably acting as a regulator of the voltage-sensitive calcium channel CACNA1S. EC is a physiological process whereby an electrical signal (depolarization of the plasma membrane) is converted into a chemical signal, a calcium gradient, by the opening of ryanodine receptor calcium release channels. May regulate CACNA1S membrane targeting and activity","subcellular_location":"Sarcoplasmic reticulum membrane; Endoplasmic reticulum membrane","url":"https://www.uniprot.org/uniprotkb/Q96MG2/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/JSRP1","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/JSRP1","total_profiled":1310},"omim":[{"mim_id":"608743","title":"JUNCTIONAL SARCOPLASMIC RETICULUM PROTEIN 1; JSRP1","url":"https://www.omim.org/entry/608743"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Approved","locations":[{"location":"Endoplasmic reticulum","reliability":"Approved"}],"tissue_specificity":"Tissue enriched","tissue_distribution":"Detected in some","driving_tissues":[{"tissue":"skeletal muscle","ntpm":325.7}],"url":"https://www.proteinatlas.org/search/JSRP1"},"hgnc":{"alias_symbol":["JP-45","FLJ32416"],"prev_symbol":[]},"alphafold":{"accession":"Q96MG2","domains":[],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q96MG2","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q96MG2-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q96MG2-F1-predicted_aligned_error_v6.png","plddt_mean":52.75},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=JSRP1","jax_strain_url":"https://www.jax.org/strain/search?query=JSRP1"},"sequence":{"accession":"Q96MG2","fasta_url":"https://rest.uniprot.org/uniprotkb/Q96MG2.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q96MG2/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q96MG2"}},"corpus_meta":[{"pmid":"21529320","id":"PMC_21529320","title":"Expression and regulation of excitation-contraction coupling proteins in aging skeletal muscle.","date":"2011","source":"Current aging science","url":"https://pubmed.ncbi.nlm.nih.gov/21529320","citation_count":69,"is_preprint":false},{"pmid":"34101221","id":"PMC_34101221","title":"Differential DNA methylation and mRNA transcription in gingival tissues in periodontal health and disease.","date":"2021","source":"Journal of clinical periodontology","url":"https://pubmed.ncbi.nlm.nih.gov/34101221","citation_count":41,"is_preprint":false},{"pmid":"12871958","id":"PMC_12871958","title":"The novel skeletal muscle sarcoplasmic reticulum JP-45 protein. Molecular cloning, tissue distribution, developmental expression, and interaction with alpha 1.1 subunit of the voltage-gated calcium channel.","date":"2003","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/12871958","citation_count":35,"is_preprint":false},{"pmid":"34139469","id":"PMC_34139469","title":"Epigenetic landscape in blood leukocytes following ketosis and weight loss induced by a very low calorie ketogenic diet (VLCKD) in patients with obesity.","date":"2021","source":"Clinical nutrition (Edinburgh, Scotland)","url":"https://pubmed.ncbi.nlm.nih.gov/34139469","citation_count":34,"is_preprint":false},{"pmid":"16638807","id":"PMC_16638807","title":"The junctional SR protein JP-45 affects the functional expression of the voltage-dependent Ca2+ channel Cav1.1.","date":"2006","source":"Journal of cell science","url":"https://pubmed.ncbi.nlm.nih.gov/16638807","citation_count":31,"is_preprint":false},{"pmid":"11023841","id":"PMC_11023841","title":"Identification of a novel 45 kDa protein (JP-45) from rabbit sarcoplasmic-reticulum junctional-face membrane.","date":"2000","source":"The Biochemical journal","url":"https://pubmed.ncbi.nlm.nih.gov/11023841","citation_count":29,"is_preprint":false},{"pmid":"16423849","id":"PMC_16423849","title":"A possible role of the junctional face protein JP-45 in modulating Ca2+ release in skeletal muscle.","date":"2006","source":"The Journal of physiology","url":"https://pubmed.ncbi.nlm.nih.gov/16423849","citation_count":20,"is_preprint":false},{"pmid":"22927026","id":"PMC_22927026","title":"JP-45/JSRP1 variants affect skeletal muscle excitation-contraction coupling by decreasing the sensitivity of the dihydropyridine receptor.","date":"2012","source":"Human mutation","url":"https://pubmed.ncbi.nlm.nih.gov/22927026","citation_count":13,"is_preprint":false},{"pmid":"20442750","id":"PMC_20442750","title":"Follow-up of potential novel Graves' disease susceptibility loci, identified in the UK WTCCC genome-wide nonsynonymous SNP study.","date":"2010","source":"European journal of human genetics : EJHG","url":"https://pubmed.ncbi.nlm.nih.gov/20442750","citation_count":13,"is_preprint":false},{"pmid":"33763463","id":"PMC_33763463","title":"Characterization of Anti-Müllerian Hormone (AMH) Gene in Buffaloes and Goats.","date":"2021","source":"Frontiers in veterinary science","url":"https://pubmed.ncbi.nlm.nih.gov/33763463","citation_count":6,"is_preprint":false},{"pmid":"36267987","id":"PMC_36267987","title":"Case report: Novel junctional sarcoplasmic reticulum protein 1 intergenic region-anaplastic lymphoma kinase fusion in a patient with lung adenocarcinoma responds to alectinib.","date":"2022","source":"Frontiers in oncology","url":"https://pubmed.ncbi.nlm.nih.gov/36267987","citation_count":1,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":7443,"output_tokens":1538,"usd":0.0227,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":8283,"output_tokens":1903,"usd":0.044495,"stage2_stop_reason":"end_turn"},"total_usd":0.067195,"stage1_batch_id":"msgbatch_01DUPACZi7AAWwuZiUjseQF4","stage2_batch_id":"msgbatch_018yt7chE3f48PEFtDwtj6AE","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2000,\n      \"finding\": \"JP-45 (JSRP1) is a 45 kDa integral membrane protein selectively localized in the junctional face membrane (JFM) of skeletal muscle sarcoplasmic reticulum, present in both neonatal and adult SR but absent from heart, liver, or kidney microsomes. The JP-45-containing complex can be phosphorylated in vitro by the catalytic subunit of protein kinase A.\",\n      \"method\": \"Subcellular fractionation, immunoprecipitation, in vitro PKA phosphorylation assay\",\n      \"journal\": \"The Biochemical journal\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — biochemical fractionation and immunoprecipitation with in vitro phosphorylation assay, single lab, multiple orthogonal methods\",\n      \"pmids\": [\"11023841\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2003,\n      \"finding\": \"JP-45 (JSRP1) is an integral protein of the skeletal muscle SR junctional face membrane with a cytoplasmic domain, single transmembrane segment, and positively charged intralumenal domain. It co-localizes with the ryanodine receptor (SR Ca2+ release channel) and co-immunoprecipitates with the alpha1.1 subunit of the voltage-gated calcium channel (Cav1.1) and calsequestrin, implicating it in excitation-contraction coupling.\",\n      \"method\": \"cDNA cloning, Northern blot, Western blot, double immunofluorescence, co-immunoprecipitation\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — reciprocal co-immunoprecipitation with multiple partners, co-localization, multiple orthogonal methods, foundational characterization paper\",\n      \"pmids\": [\"12871958\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2006,\n      \"finding\": \"The cytoplasmic domain of JP-45 (residues 1–80) interacts with two distinct regions of Cav1.1: the I-II loop (via the alpha-interacting domain) and the C-terminal region. The beta1a subunit of Cav1 also interacts with the cytosolic domain of JP-45, and its presence drastically reduces JP-45 interaction with the I-II loop. Overexpression of JP-45 in C2C12 myotubes decreased peak charge movement and shifted VQ1/2 to more negative potential; JP-45 depletion decreased both Cav1.1 content and peak charge movement, demonstrating JP-45 is required for functional expression of voltage-dependent Ca2+ channels.\",\n      \"method\": \"Domain mapping by pulldown/interaction assays, overexpression and siRNA depletion in C2C12 myotubes, whole-cell voltage-clamp (charge movement recording)\",\n      \"journal\": \"Journal of cell science\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1–2 / Strong — domain-level interaction mapping combined with functional electrophysiology (gain- and loss-of-function), multiple orthogonal methods in one study\",\n      \"pmids\": [\"16638807\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2006,\n      \"finding\": \"Overexpression of JP-45-DsRed2 in C2C12 myotubes did not significantly change voltage-activated Ca2+ current properties but decreased the amplitude of depolarization-induced Ca2+ transients. This decrease was attributed to a reduction in voltage-activated Ca2+ permeability per voltage-sensor charge, consistent with JP-45 modulating the coupling between the dihydropyridine receptor (DHPR) voltage sensor and SR Ca2+ release, rather than altering SR Ca2+ content or removal.\",\n      \"method\": \"Nuclear microinjection overexpression in C2C12 myotubes, whole-cell voltage-clamp, fura-2 Ca2+ imaging, Ca2+ flux modeling\",\n      \"journal\": \"The Journal of physiology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — functional electrophysiology and Ca2+ imaging with quantitative modeling, single lab, overexpression only (no loss-of-function)\",\n      \"pmids\": [\"16423849\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2012,\n      \"finding\": \"Two human JSRP1 variants (c.323C>T, p.P108L and c.449G>C, p.G150A) each decrease the sensitivity of the dihydropyridine receptor (DHPR) to activation during excitation-contraction coupling. These variants are not enriched in malignant hyperthermia susceptible individuals but may modulate EC coupling severity in patients carrying RYR1 mutations by counteracting DHPR hypersensitivity.\",\n      \"method\": \"Population genotyping, functional EC coupling assays in muscle cells expressing variant JP-45 proteins\",\n      \"journal\": \"Human mutation\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — functional EC coupling assays with defined variants, single lab, mechanistic follow-up of prior interaction data\",\n      \"pmids\": [\"22927026\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"JSRP1/JP-45 is an integral protein of the skeletal muscle sarcoplasmic reticulum junctional face membrane whose cytoplasmic domain (residues 1–80) directly interacts with Cav1.1 (at its I-II loop and C-terminal region) and with calsequestrin; the beta1a subunit competes for the I-II loop interaction site. JP-45 is required for normal functional expression and voltage-sensing of Cav1.1, modulating charge movement and SR Ca2+ release during excitation-contraction coupling, and human missense variants (P108L, G150A) reduce DHPR sensitivity to activation.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"JSRP1 (JP-45) is an integral membrane protein of the skeletal muscle sarcoplasmic reticulum junctional face membrane that functions as a regulator of excitation-contraction coupling [#1, #2]. Tissue-selective and localized to the SR junctional face membrane, it co-localizes with the ryanodine receptor and forms a complex with the Cav1.1 (DHPR) alpha1.1 subunit and calsequestrin [#0, #1]. Its cytoplasmic domain (residues 1\\u201380) binds two distinct Cav1.1 regions\\u2014the I-II loop and the C-terminus\\u2014and also engages the Cav1 beta1a subunit, which competes for the I-II loop interaction site [#2]. Through these interactions JP-45 is required for functional expression and voltage sensing of Cav1.1, modulating charge movement and the coupling between the DHPR voltage sensor and SR Ca2+ release rather than altering SR Ca2+ content [#2, #3]. Two human missense variants (P108L, G150A) reduce DHPR sensitivity to activation during EC coupling [#4].\",\n  \"teleology\": [\n    {\n      \"year\": 2000,\n      \"claim\": \"Establishing that a previously uncharacterized 45 kDa protein is a tissue-selective resident of the SR junctional face membrane defined where it could act in muscle.\",\n      \"evidence\": \"Subcellular fractionation, immunoprecipitation and in vitro PKA phosphorylation of microsomes from multiple tissues\",\n      \"pmids\": [\"11023841\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Binding partners not yet identified\", \"Functional role in EC coupling not established\", \"Physiological relevance of PKA phosphorylation untested\"]\n    },\n    {\n      \"year\": 2003,\n      \"claim\": \"Identifying JP-45's molecular partners answered whether it is positioned to participate in the DHPR-RyR coupling machinery.\",\n      \"evidence\": \"cDNA cloning, double immunofluorescence and reciprocal co-immunoprecipitation in skeletal muscle SR\",\n      \"pmids\": [\"12871958\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Interaction interfaces not mapped\", \"Functional consequence of the interactions untested\", \"Direct vs indirect association within the complex unresolved\"]\n    },\n    {\n      \"year\": 2006,\n      \"claim\": \"Mapping the cytoplasmic domain interactions and combining with gain/loss-of-function established that JP-45 is required for functional expression and voltage sensing of Cav1.1.\",\n      \"evidence\": \"Domain pulldown mapping plus overexpression and siRNA depletion in C2C12 myotubes with whole-cell charge-movement recording\",\n      \"pmids\": [\"16638807\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Stoichiometry of the JP-45/Cav1.1/beta1a complex unresolved\", \"Mechanism by which beta1a competition is regulated in vivo unclear\"]\n    },\n    {\n      \"year\": 2006,\n      \"claim\": \"Quantitative Ca2+ flux analysis distinguished whether JP-45 acts on SR Ca2+ load versus the voltage-sensor-to-release coupling step.\",\n      \"evidence\": \"Nuclear microinjection overexpression in C2C12 myotubes with voltage-clamp, fura-2 imaging and Ca2+ flux modeling\",\n      \"pmids\": [\"16423849\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Overexpression only, no loss-of-function confirmation\", \"Molecular step in DHPR-RyR coupling affected not pinpointed\"]\n    },\n    {\n      \"year\": 2012,\n      \"claim\": \"Testing human JSRP1 variants asked whether sequence variation in JP-45 alters EC coupling and disease modulation.\",\n      \"evidence\": \"Population genotyping and functional EC coupling assays in muscle cells expressing P108L and G150A variants\",\n      \"pmids\": [\"22927026\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Variants not enriched in malignant hyperthermia cohorts\", \"Structural basis of reduced DHPR sensitivity not defined\", \"Interaction with RYR1 mutations inferred, not directly demonstrated\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The structural basis of JP-45's regulation of Cav1.1 voltage sensing and how beta1a competition is dynamically controlled during EC coupling remain unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No structural model of the JP-45/Cav1.1 interface\", \"In vivo regulatory role of PKA phosphorylation unknown\", \"Whole-animal phenotype of JSRP1 loss not characterized in the corpus\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0098772\", \"supporting_discovery_ids\": [2, 3]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005783\", \"supporting_discovery_ids\": [0, 1]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-397014\", \"supporting_discovery_ids\": [2, 3]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\"CACNA1S\", \"CASQ1\", \"RYR1\", \"CACNB1\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":5,"faith_total":5,"faith_pct":100.0}}