{"gene":"SMIM30","run_date":"2026-06-10T07:46:36","timeline":{"discoveries":[{"year":2020,"finding":"SMIM30, a short peptide encoded by the smORF within lncRNA LINC00998, promotes HCC tumorigenesis by driving membrane anchoring of non-receptor tyrosine kinases SRC and YES1, leading to their phosphorylation and activation of the downstream MAPK signaling pathway. The RNA itself (LINC00998) was not responsible for this effect.","method":"Special vectors confirming coding potential; functional assays (cell proliferation, migration); mechanistic studies showing SRC/YES1 membrane anchoring and MAPK activation; c-Myc shown to transcribe SMIM30","journal":"Journal of hepatology","confidence":"High","confidence_rationale":"Tier 2 / Moderate — multiple orthogonal methods in a single rigorous study (coding vector confirmation, functional KD/OE, pathway activation readouts), RNA vs peptide distinction established","pmids":["32461121"],"is_preprint":false},{"year":2022,"finding":"SMIM30 peptide localizes to membranes of the endoplasmic reticulum (ER) and mitochondria, and promotes the G1/S cell cycle transition by enhancing SERCA (sarco/endoplasmic reticulum calcium ATPase) pump activity, thereby reducing cytosolic calcium levels and increasing CDK4, cyclin E2, phosphorylated-Rb, and E2F1. A premature stop codon introduced into the sORF abolished the growth-promoting effect, confirming it is peptide- not RNA-dependent.","method":"Subcellular fractionation/localization; gain- and loss-of-function studies; single-base deletion mutagenesis of sORF; calcium chelator and SERCA agonist rescue experiments; flow cytometry cell cycle analysis; Western blot for CDK4, cyclin E2, p-Rb, E2F1","journal":"Molecular oncology","confidence":"High","confidence_rationale":"Tier 1–2 / Moderate — mutagenesis (stop-codon insertion) confirming peptide requirement, multiple orthogonal rescue experiments (chelator, SERCA agonist), localization tied to functional consequence, single lab","pmids":["36495128"],"is_preprint":false},{"year":2023,"finding":"SMIM30 (alias MAVI1) is an endoplasmic reticulum-localized membrane microprotein that interacts with mitochondria-localized MAVS protein, inhibits MAVS aggregation, and suppresses type I interferon signaling activation during viral infection. Mavi1-knockout mice showed attenuated viral infection and increased survival. A peptide inhibitor targeting the MAVI1–MAVS interaction activated type I interferon signaling.","method":"Co-immunoprecipitation (interaction with MAVS); MAVS aggregation assay; type I interferon signaling reporter assays; Mavi1-knockout mouse model (viral infection survival); peptide inhibitor functional assay; ER localization confirmed","journal":"Science advances","confidence":"High","confidence_rationale":"Tier 2 / Strong — reciprocal interaction shown, KO mouse with defined phenotype, peptide inhibitor validation, multiple orthogonal methods across in vitro and in vivo systems","pmids":["37656786"],"is_preprint":false},{"year":2025,"finding":"Smim30 is expressed in adipose tissue macrophages and maintains adipose tissue insulin sensitivity by modulating inflammatory responses and macrophage-adipocyte communication, thereby safeguarding systemic metabolic homeostasis.","method":"Macrophage-specific expression studies; in vivo metabolic phenotyping (insulin sensitivity assays); macrophage-adipocyte communication assays","journal":"Diabetes","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — defined cellular phenotype and tissue context, but abstract provides limited mechanistic detail; single study","pmids":["40549483"],"is_preprint":false}],"current_model":"SMIM30 is a small integral membrane peptide encoded by a smORF within LINC00998 that (1) promotes HCC by anchoring SRC/YES1 kinases to the plasma membrane and activating MAPK signaling (transcriptionally driven by c-Myc); (2) promotes G1/S cell cycle progression from ER/mitochondrial membranes by enhancing SERCA pump activity to lower cytosolic calcium and upregulate CDK4/cyclin E2/p-Rb/E2F1; and (3) under its alias MAVI1, localizes to the ER membrane, binds mitochondrial MAVS, inhibits MAVS aggregation, and suppresses antiviral type I interferon signaling; additionally, it is expressed in adipose tissue macrophages where it modulates inflammatory responses and maintains insulin sensitivity."},"narrative":{"mechanistic_narrative":"SMIM30 is a small integral membrane microprotein encoded by a smORF within the lncRNA LINC00998 whose translated peptide, rather than the RNA, drives its biological activity across cell growth, signaling, and antiviral defense [PMID:32461121, PMID:36495128]. In hepatocellular carcinoma, SMIM30 promotes tumorigenesis by anchoring the non-receptor tyrosine kinases SRC and YES1 to the membrane, driving their phosphorylation and activation of downstream MAPK signaling, and its expression is transcriptionally driven by c-Myc [PMID:32461121]. Localizing to ER and mitochondrial membranes, the peptide also accelerates the G1/S cell cycle transition by enhancing SERCA pump activity to lower cytosolic calcium, thereby upregulating CDK4, cyclin E2, phosphorylated Rb, and E2F1 [PMID:36495128]. Under the alias MAVI1, the same ER-localized microprotein binds mitochondrial MAVS, inhibits MAVS aggregation, and suppresses type I interferon signaling during viral infection, such that its loss in knockout mice attenuates infection and improves survival [PMID:37656786]. SMIM30 additionally functions in adipose tissue macrophages, where it modulates inflammatory responses and macrophage-adipocyte communication to maintain insulin sensitivity and systemic metabolic homeostasis [PMID:40549483].","teleology":[{"year":2020,"claim":"Established that the LINC00998 locus encodes a functional peptide rather than acting as a non-coding RNA, and that this peptide drives HCC by tethering SRC/YES1 to the membrane to activate MAPK signaling.","evidence":"Coding-potential vectors, KD/OE functional assays, and mechanistic studies of kinase membrane anchoring and MAPK activation in HCC cells","pmids":["32461121"],"confidence":"High","gaps":["Direct structural basis for SRC/YES1 membrane anchoring not defined","Whether SMIM30 binds SRC/YES1 directly or via an intermediate not resolved","In vivo tumor relevance limited to the assays in this study"]},{"year":2022,"claim":"Linked SMIM30 to ER/mitochondrial membrane localization and cell cycle control, showing it drives G1/S progression through SERCA-dependent calcium lowering rather than RNA function.","evidence":"Subcellular fractionation, stop-codon insertion mutagenesis, calcium chelator and SERCA agonist rescue, flow cytometry, and Western blot for CDK4/cyclin E2/p-Rb/E2F1","pmids":["36495128"],"confidence":"High","gaps":["Direct physical interaction between SMIM30 and SERCA not established","Relationship between the SERCA/calcium axis and the SRC/MAPK mechanism unclear","Single-lab finding"]},{"year":2023,"claim":"Identified SMIM30 (MAVI1) as a negative regulator of antiviral innate immunity that binds MAVS and blocks its aggregation, revealing a role distinct from its proliferative functions.","evidence":"Co-IP with MAVS, MAVS aggregation assay, interferon reporter assays, Mavi1-knockout mice in viral infection, and a peptide inhibitor of the MAVI1-MAVS interaction","pmids":["37656786"],"confidence":"High","gaps":["How an ER-localized peptide engages mitochondrial MAVS structurally not defined","Connection between antiviral and oncogenic/cell-cycle roles not integrated","Therapeutic window of the peptide inhibitor not characterized"]},{"year":2025,"claim":"Extended SMIM30 function to metabolic homeostasis, showing it acts in adipose tissue macrophages to modulate inflammation and preserve insulin sensitivity.","evidence":"Macrophage-specific expression studies, in vivo metabolic phenotyping, and macrophage-adipocyte communication assays","pmids":["40549483"],"confidence":"Medium","gaps":["Limited mechanistic detail on how SMIM30 modulates inflammatory signaling in macrophages","Whether the MAVS/interferon axis underlies the metabolic phenotype not tested","Single study"]},{"year":null,"claim":"How SMIM30's distinct membrane-localized activities — MAPK kinase anchoring, SERCA-dependent calcium control, MAVS regulation, and macrophage inflammatory modulation — are mechanistically unified or selectively deployed across tissues remains unresolved.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No single structural or binding model accounts for the multiple partners","Tissue- and context-specific partner selection not defined","Direct binding interfaces with SRC/YES1 and SERCA not mapped"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0098772","term_label":"molecular function regulator activity","supporting_discovery_ids":[0,1,2]},{"term_id":"GO:0060089","term_label":"molecular transducer activity","supporting_discovery_ids":[0]}],"localization":[{"term_id":"GO:0005783","term_label":"endoplasmic reticulum","supporting_discovery_ids":[1,2]},{"term_id":"GO:0005739","term_label":"mitochondrion","supporting_discovery_ids":[1]},{"term_id":"GO:0005886","term_label":"plasma membrane","supporting_discovery_ids":[0]}],"pathway":[{"term_id":"R-HSA-162582","term_label":"Signal Transduction","supporting_discovery_ids":[0]},{"term_id":"R-HSA-1640170","term_label":"Cell Cycle","supporting_discovery_ids":[1]},{"term_id":"R-HSA-168256","term_label":"Immune System","supporting_discovery_ids":[2,3]}],"complexes":[],"partners":["SRC","YES1","MAVS"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"A4D0T7","full_name":"Small integral membrane protein 30","aliases":["Microprotein in antiviral immunity 1"],"length_aa":59,"mass_kda":6.1,"function":"Negatively regulates antiviral innate immune responses (PubMed:37656786). Disrupts the interaction of antiviral protein MAVS with innate immune receptor RIGI and inhibits MAVS aggregation, resulting in the repression of type I interferon signaling and innate immune responses (PubMed:37656786)","subcellular_location":"Endoplasmic reticulum membrane; Mitochondrion membrane","url":"https://www.uniprot.org/uniprotkb/A4D0T7/entry"},"depmap":{"release":"DepMap","has_data":false,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/SMIM30"},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[],"url":"https://opencell.sf.czbiohub.org/search/SMIM30","total_profiled":1310},"omim":[],"hpa":{"profiled":true,"resolved_as":"","reliability":"","locations":[],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in all","driving_tissues":[],"url":"https://www.proteinatlas.org/search/SMIM30"},"hgnc":{"alias_symbol":["MAVI1"],"prev_symbol":["LINC00998"]},"alphafold":{"accession":"A4D0T7","domains":[{"cath_id":"1.10.287","chopping":"27-59","consensus_level":"medium","plddt":90.39,"start":27,"end":59}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/A4D0T7","model_url":"https://alphafold.ebi.ac.uk/files/AF-A4D0T7-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-A4D0T7-F1-predicted_aligned_error_v6.png","plddt_mean":85.25},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=SMIM30","jax_strain_url":"https://www.jax.org/strain/search?query=SMIM30"},"sequence":{"accession":"A4D0T7","fasta_url":"https://rest.uniprot.org/uniprotkb/A4D0T7.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/A4D0T7/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/A4D0T7"}},"corpus_meta":[{"pmid":"32461121","id":"PMC_32461121","title":"Peptide SMIM30 promotes HCC development by inducing SRC/YES1 membrane anchoring and MAPK pathway activation.","date":"2020","source":"Journal of hepatology","url":"https://pubmed.ncbi.nlm.nih.gov/32461121","citation_count":185,"is_preprint":false},{"pmid":"33268783","id":"PMC_33268783","title":"LncRNA LINC00998 inhibits the malignant glioma phenotype via the CBX3-mediated c-Met/Akt/mTOR axis.","date":"2020","source":"Cell death & disease","url":"https://pubmed.ncbi.nlm.nih.gov/33268783","citation_count":50,"is_preprint":false},{"pmid":"27940106","id":"PMC_27940106","title":"Intergenic variants may predispose to major depression disorder through regulation of long non-coding RNA expression.","date":"2016","source":"Gene","url":"https://pubmed.ncbi.nlm.nih.gov/27940106","citation_count":31,"is_preprint":false},{"pmid":"36495128","id":"PMC_36495128","title":"LINC00998-encoded micropeptide SMIM30 promotes the G1/S transition of cell cycle by regulating cytosolic calcium level.","date":"2022","source":"Molecular oncology","url":"https://pubmed.ncbi.nlm.nih.gov/36495128","citation_count":28,"is_preprint":false},{"pmid":"37656786","id":"PMC_37656786","title":"MAVI1, an endoplasmic reticulum-localized microprotein, suppresses antiviral innate immune response by targeting MAVS on mitochondrion.","date":"2023","source":"Science advances","url":"https://pubmed.ncbi.nlm.nih.gov/37656786","citation_count":23,"is_preprint":false},{"pmid":"34699314","id":"PMC_34699314","title":"LINC00998 functions as a novel tumor suppressor in acute myeloid leukemia via regulating the ZFP36 ring finger protein/mammalian target of rapamycin complex 2 axis.","date":"2021","source":"Bioengineered","url":"https://pubmed.ncbi.nlm.nih.gov/34699314","citation_count":10,"is_preprint":false},{"pmid":"38638161","id":"PMC_38638161","title":"LINC00998 Modulating M2 Macrophage Activation in Allergic Rhinitis by Stabilizing BOB.1 mRNA.","date":"2024","source":"Journal of inflammation research","url":"https://pubmed.ncbi.nlm.nih.gov/38638161","citation_count":2,"is_preprint":false},{"pmid":"40549483","id":"PMC_40549483","title":"Macrophage-Expressed Micropeptide Smim30 Maintains Adipose Tissue Insulin Sensitivity and Safeguards Systemic Metabolic Homeostasis.","date":"2025","source":"Diabetes","url":"https://pubmed.ncbi.nlm.nih.gov/40549483","citation_count":1,"is_preprint":false},{"pmid":"41961104","id":"PMC_41961104","title":"The hidden players: LncRNA-Encoded micropeptides in cancer hallmarks.","date":"2026","source":"Cellular and molecular life sciences : CMLS","url":"https://pubmed.ncbi.nlm.nih.gov/41961104","citation_count":0,"is_preprint":false},{"pmid":"42140456","id":"PMC_42140456","title":"Micropeptides in Cancer and Immunity: Diagnostic, Therapeutic, and Synthetic Biology Frontiers.","date":"2026","source":"Gene","url":"https://pubmed.ncbi.nlm.nih.gov/42140456","citation_count":0,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":6986,"output_tokens":1283,"usd":0.020102,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":7990,"output_tokens":2218,"usd":0.0477,"stage2_stop_reason":"end_turn"},"total_usd":0.067802,"stage1_batch_id":"msgbatch_013LWZZT6MWaqB9qyTSeQBmU","stage2_batch_id":"msgbatch_0194ZzQaTGNpruoNJBbEMbt3","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2020,\n      \"finding\": \"SMIM30, a short peptide encoded by the smORF within lncRNA LINC00998, promotes HCC tumorigenesis by driving membrane anchoring of non-receptor tyrosine kinases SRC and YES1, leading to their phosphorylation and activation of the downstream MAPK signaling pathway. The RNA itself (LINC00998) was not responsible for this effect.\",\n      \"method\": \"Special vectors confirming coding potential; functional assays (cell proliferation, migration); mechanistic studies showing SRC/YES1 membrane anchoring and MAPK activation; c-Myc shown to transcribe SMIM30\",\n      \"journal\": \"Journal of hepatology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — multiple orthogonal methods in a single rigorous study (coding vector confirmation, functional KD/OE, pathway activation readouts), RNA vs peptide distinction established\",\n      \"pmids\": [\"32461121\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"SMIM30 peptide localizes to membranes of the endoplasmic reticulum (ER) and mitochondria, and promotes the G1/S cell cycle transition by enhancing SERCA (sarco/endoplasmic reticulum calcium ATPase) pump activity, thereby reducing cytosolic calcium levels and increasing CDK4, cyclin E2, phosphorylated-Rb, and E2F1. A premature stop codon introduced into the sORF abolished the growth-promoting effect, confirming it is peptide- not RNA-dependent.\",\n      \"method\": \"Subcellular fractionation/localization; gain- and loss-of-function studies; single-base deletion mutagenesis of sORF; calcium chelator and SERCA agonist rescue experiments; flow cytometry cell cycle analysis; Western blot for CDK4, cyclin E2, p-Rb, E2F1\",\n      \"journal\": \"Molecular oncology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1–2 / Moderate — mutagenesis (stop-codon insertion) confirming peptide requirement, multiple orthogonal rescue experiments (chelator, SERCA agonist), localization tied to functional consequence, single lab\",\n      \"pmids\": [\"36495128\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"SMIM30 (alias MAVI1) is an endoplasmic reticulum-localized membrane microprotein that interacts with mitochondria-localized MAVS protein, inhibits MAVS aggregation, and suppresses type I interferon signaling activation during viral infection. Mavi1-knockout mice showed attenuated viral infection and increased survival. A peptide inhibitor targeting the MAVI1–MAVS interaction activated type I interferon signaling.\",\n      \"method\": \"Co-immunoprecipitation (interaction with MAVS); MAVS aggregation assay; type I interferon signaling reporter assays; Mavi1-knockout mouse model (viral infection survival); peptide inhibitor functional assay; ER localization confirmed\",\n      \"journal\": \"Science advances\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — reciprocal interaction shown, KO mouse with defined phenotype, peptide inhibitor validation, multiple orthogonal methods across in vitro and in vivo systems\",\n      \"pmids\": [\"37656786\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"Smim30 is expressed in adipose tissue macrophages and maintains adipose tissue insulin sensitivity by modulating inflammatory responses and macrophage-adipocyte communication, thereby safeguarding systemic metabolic homeostasis.\",\n      \"method\": \"Macrophage-specific expression studies; in vivo metabolic phenotyping (insulin sensitivity assays); macrophage-adipocyte communication assays\",\n      \"journal\": \"Diabetes\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — defined cellular phenotype and tissue context, but abstract provides limited mechanistic detail; single study\",\n      \"pmids\": [\"40549483\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"SMIM30 is a small integral membrane peptide encoded by a smORF within LINC00998 that (1) promotes HCC by anchoring SRC/YES1 kinases to the plasma membrane and activating MAPK signaling (transcriptionally driven by c-Myc); (2) promotes G1/S cell cycle progression from ER/mitochondrial membranes by enhancing SERCA pump activity to lower cytosolic calcium and upregulate CDK4/cyclin E2/p-Rb/E2F1; and (3) under its alias MAVI1, localizes to the ER membrane, binds mitochondrial MAVS, inhibits MAVS aggregation, and suppresses antiviral type I interferon signaling; additionally, it is expressed in adipose tissue macrophages where it modulates inflammatory responses and maintains insulin sensitivity.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"SMIM30 is a small integral membrane microprotein encoded by a smORF within the lncRNA LINC00998 whose translated peptide, rather than the RNA, drives its biological activity across cell growth, signaling, and antiviral defense [#0, #1]. In hepatocellular carcinoma, SMIM30 promotes tumorigenesis by anchoring the non-receptor tyrosine kinases SRC and YES1 to the membrane, driving their phosphorylation and activation of downstream MAPK signaling, and its expression is transcriptionally driven by c-Myc [#0]. Localizing to ER and mitochondrial membranes, the peptide also accelerates the G1/S cell cycle transition by enhancing SERCA pump activity to lower cytosolic calcium, thereby upregulating CDK4, cyclin E2, phosphorylated Rb, and E2F1 [#1]. Under the alias MAVI1, the same ER-localized microprotein binds mitochondrial MAVS, inhibits MAVS aggregation, and suppresses type I interferon signaling during viral infection, such that its loss in knockout mice attenuates infection and improves survival [#2]. SMIM30 additionally functions in adipose tissue macrophages, where it modulates inflammatory responses and macrophage-adipocyte communication to maintain insulin sensitivity and systemic metabolic homeostasis [#3].\",\n  \"teleology\": [\n    {\n      \"year\": 2020,\n      \"claim\": \"Established that the LINC00998 locus encodes a functional peptide rather than acting as a non-coding RNA, and that this peptide drives HCC by tethering SRC/YES1 to the membrane to activate MAPK signaling.\",\n      \"evidence\": \"Coding-potential vectors, KD/OE functional assays, and mechanistic studies of kinase membrane anchoring and MAPK activation in HCC cells\",\n      \"pmids\": [\"32461121\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Direct structural basis for SRC/YES1 membrane anchoring not defined\",\n        \"Whether SMIM30 binds SRC/YES1 directly or via an intermediate not resolved\",\n        \"In vivo tumor relevance limited to the assays in this study\"\n      ]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"Linked SMIM30 to ER/mitochondrial membrane localization and cell cycle control, showing it drives G1/S progression through SERCA-dependent calcium lowering rather than RNA function.\",\n      \"evidence\": \"Subcellular fractionation, stop-codon insertion mutagenesis, calcium chelator and SERCA agonist rescue, flow cytometry, and Western blot for CDK4/cyclin E2/p-Rb/E2F1\",\n      \"pmids\": [\"36495128\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Direct physical interaction between SMIM30 and SERCA not established\",\n        \"Relationship between the SERCA/calcium axis and the SRC/MAPK mechanism unclear\",\n        \"Single-lab finding\"\n      ]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"Identified SMIM30 (MAVI1) as a negative regulator of antiviral innate immunity that binds MAVS and blocks its aggregation, revealing a role distinct from its proliferative functions.\",\n      \"evidence\": \"Co-IP with MAVS, MAVS aggregation assay, interferon reporter assays, Mavi1-knockout mice in viral infection, and a peptide inhibitor of the MAVI1-MAVS interaction\",\n      \"pmids\": [\"37656786\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"How an ER-localized peptide engages mitochondrial MAVS structurally not defined\",\n        \"Connection between antiviral and oncogenic/cell-cycle roles not integrated\",\n        \"Therapeutic window of the peptide inhibitor not characterized\"\n      ]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Extended SMIM30 function to metabolic homeostasis, showing it acts in adipose tissue macrophages to modulate inflammation and preserve insulin sensitivity.\",\n      \"evidence\": \"Macrophage-specific expression studies, in vivo metabolic phenotyping, and macrophage-adipocyte communication assays\",\n      \"pmids\": [\"40549483\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Limited mechanistic detail on how SMIM30 modulates inflammatory signaling in macrophages\",\n        \"Whether the MAVS/interferon axis underlies the metabolic phenotype not tested\",\n        \"Single study\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How SMIM30's distinct membrane-localized activities — MAPK kinase anchoring, SERCA-dependent calcium control, MAVS regulation, and macrophage inflammatory modulation — are mechanistically unified or selectively deployed across tissues remains unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No single structural or binding model accounts for the multiple partners\",\n        \"Tissue- and context-specific partner selection not defined\",\n        \"Direct binding interfaces with SRC/YES1 and SERCA not mapped\"\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0098772\", \"supporting_discovery_ids\": [0, 1, 2]},\n      {\"term_id\": \"GO:0060089\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005783\", \"supporting_discovery_ids\": [1, 2]},\n      {\"term_id\": \"GO:0005739\", \"supporting_discovery_ids\": [1]},\n      {\"term_id\": \"GO:0005886\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-162582\", \"supporting_discovery_ids\": [0]},\n      {\"term_id\": \"R-HSA-1640170\", \"supporting_discovery_ids\": [1]},\n      {\"term_id\": \"R-HSA-168256\", \"supporting_discovery_ids\": [2, 3]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\"SRC\", \"YES1\", \"MAVS\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":{"gene":"SMIM30","tier":"IDENTITY","verdict":"Identity concern","subtype":"alt_product","uniprot_band":"medium","rules_fired":"R4","issue":"R4: alt-product term(s) in opening sentences"},"evaluation":{"pairwise":"win","faith_supported":5,"faith_total":5,"faith_pct":100.0}}