{"gene":"RIMOC1","run_date":"2026-06-10T06:43:36","timeline":{"discoveries":[{"year":2021,"finding":"C5orf51 (RIMOC1) was identified as a specific interactor of GDP-locked (inactive) RAB7A using proximity-dependent biotinylation (miniTurbo), and also interacts with MON1 and CCZ1, the components of the RAB7A guanine nucleotide exchange factor complex, placing C5orf51 as a component of the MON1-CCZ1 complex.","method":"Proximity-dependent biotinylation (miniTurbo BioID), co-immunoprecipitation","journal":"Autophagy","confidence":"High","confidence_rationale":"Tier 2 / Moderate — proximity-dependent biotinylation plus co-IP with nucleotide-locked RAB7A mutant, single lab but multiple orthogonal methods","pmids":["34432599"],"is_preprint":false},{"year":2021,"finding":"In the absence of C5orf51 (RIMOC1), RAB7A fails to localize to depolarized mitochondria during mitophagy and is instead degraded by the proteasome, demonstrating that C5orf51 is required for RAB7A stability and correct subcellular translocation from late endosomes to the mitochondrial surface.","method":"C5orf51 knockout cells, fluorescence microscopy (RAB7A localization), proteasome inhibitor rescue (MG132)","journal":"Autophagy","confidence":"High","confidence_rationale":"Tier 2 / Moderate — genetic knockout with defined localization and stability phenotype, proteasome inhibitor rescue as orthogonal validation, single lab","pmids":["34432599"],"is_preprint":false},{"year":2021,"finding":"Depletion of C5orf51 (RIMOC1) inhibited ATG9A recruitment to depolarized mitochondria, establishing C5orf51 as an upstream positive regulator required for the mitophagy autophagy machinery to engage at the mitochondrial surface.","method":"C5orf51 knockout/depletion, fluorescence microscopy of ATG9A localization after mitochondrial depolarization (CCCP treatment)","journal":"Autophagy","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — clean genetic depletion with defined phenotypic readout, single lab, single method for this specific finding","pmids":["34432599"],"is_preprint":false}],"current_model":"RIMOC1 (C5orf51) is a component of the MON1-CCZ1 RAB7A guanine nucleotide exchange factor complex that binds GDP-locked RAB7A and is required for its stabilization and translocation from late endosomes to depolarized mitochondria during mitophagy, and also promotes ATG9A recruitment to mitochondria, functioning as a positive regulator of the RAB7A-dependent mitophagy pathway."},"narrative":{"mechanistic_narrative":"RIMOC1 (C5orf51) is a positive regulator of RAB7A-dependent mitophagy that functions as a component of the MON1-CCZ1 RAB7A guanine nucleotide exchange factor complex [PMID:34432599]. It associates specifically with GDP-locked (inactive) RAB7A and with the MON1 and CCZ1 subunits of the GEF complex [PMID:34432599], and is required for RAB7A stability and its translocation from late endosomes to the surface of depolarized mitochondria: in its absence RAB7A fails to localize to damaged mitochondria and is instead degraded by the proteasome [PMID:34432599]. Through this control of RAB7A, RIMOC1 acts upstream of the core autophagy machinery, being required for recruitment of ATG9A to depolarized mitochondria [PMID:34432599]. Beyond these roles in the RAB7A mitophagy pathway, no further mechanistic detail has been characterized in the available corpus.","teleology":[{"year":2021,"claim":"Establishing that the uncharacterized protein C5orf51/RIMOC1 physically associates with the RAB7A GEF machinery defined its molecular context as a component of the MON1-CCZ1 complex.","evidence":"Proximity-dependent biotinylation (miniTurbo BioID) and co-IP with nucleotide-locked RAB7A mutants, showing interaction with GDP-locked RAB7A, MON1 and CCZ1","pmids":["34432599"],"confidence":"High","gaps":["Stoichiometry and whether RIMOC1 is an obligate versus accessory subunit of MON1-CCZ1 not defined","Whether RIMOC1 directly contacts RAB7A or is bridged through MON1-CCZ1 not resolved","No structural model of the RIMOC1-containing complex"]},{"year":2021,"claim":"Loss-of-function showed that RIMOC1 is functionally required for RAB7A stability and its delivery to depolarized mitochondria, explaining why it matters for the pathway rather than merely being an interactor.","evidence":"C5orf51 knockout cells with RAB7A localization microscopy and MG132 proteasome-inhibitor rescue of RAB7A levels","pmids":["34432599"],"confidence":"High","gaps":["Mechanism by which RIMOC1 protects RAB7A from proteasomal turnover unknown","Whether the stabilization defect is direct or a consequence of failed translocation not separated"]},{"year":2021,"claim":"Placing RIMOC1 upstream of ATG9A recruitment connected its RAB7A function to engagement of the core autophagy machinery during mitophagy.","evidence":"C5orf51 depletion with ATG9A localization microscopy after CCCP-induced mitochondrial depolarization","pmids":["34432599"],"confidence":"Medium","gaps":["Single method and single lab for this specific readout","Whether ATG9A recruitment defect is solely downstream of lost RAB7A or an independent RIMOC1 role not distinguished","Impact on mitophagic flux and clearance endpoints not quantified"]},{"year":null,"claim":"It remains unknown whether RIMOC1 functions outside the RAB7A mitophagy pathway and what its enzymatic or structural contribution to the MON1-CCZ1 complex is.","evidence":"","pmids":[],"confidence":"Low","gaps":["No biochemical assay of any RIMOC1 catalytic activity","No characterization in conventional (non-mitochondrial) endolysosomal trafficking","Findings derive from a single study and single lab"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0098772","term_label":"molecular function regulator activity","supporting_discovery_ids":[0,1,2]}],"localization":[{"term_id":"GO:0005739","term_label":"mitochondrion","supporting_discovery_ids":[1,2]},{"term_id":"GO:0005768","term_label":"endosome","supporting_discovery_ids":[1]}],"pathway":[{"term_id":"R-HSA-9612973","term_label":"Autophagy","supporting_discovery_ids":[1,2]}],"complexes":["MON1-CCZ1 complex"],"partners":["RAB7A","MON1","CCZ1"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"A6NDU8","full_name":"RAB7A-interacting MON1-CCZ1 complex subunit 1","aliases":["UPF0600 protein C5orf51"],"length_aa":294,"mass_kda":33.6,"function":"Plays an important role in the removal of damaged mitochondria via mitophagy by controlling the stability and localization of RAB7A. Required for the recruitment of RAB7A and ATG9A vesicles to damaged mitochondria and promotes the stability of RAB7A by inhibiting its proteasomal degradation during mitophagy","subcellular_location":"Cytoplasm, cytosol","url":"https://www.uniprot.org/uniprotkb/A6NDU8/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/RIMOC1","classification":"Not Classified","n_dependent_lines":2,"n_total_lines":1208,"dependency_fraction":0.0016556291390728477},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[],"url":"https://opencell.sf.czbiohub.org/search/RIMOC1","total_profiled":1310},"omim":[{"mim_id":"620266","title":"RAB7A-INTERACTING MON1-CCZ1 COMPLEX SUBUNIT 1; RIMOC1","url":"https://www.omim.org/entry/620266"},{"mim_id":"602298","title":"RAS-ASSOCIATED PROTEIN RAB7A; RAB7A","url":"https://www.omim.org/entry/602298"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Enhanced","locations":[{"location":"Nucleoplasm","reliability":"Enhanced"},{"location":"Cytosol","reliability":"Additional"}],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in all","driving_tissues":[],"url":"https://www.proteinatlas.org/search/RIMOC1"},"hgnc":{"alias_symbol":["LOC285636"],"prev_symbol":["C5orf51"]},"alphafold":{"accession":"A6NDU8","domains":[{"cath_id":"1.20.1440","chopping":"1-121","consensus_level":"medium","plddt":86.8978,"start":1,"end":121},{"cath_id":"1.20.1050","chopping":"150-181_190-225_248-294","consensus_level":"medium","plddt":92.0388,"start":150,"end":294}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/A6NDU8","model_url":"https://alphafold.ebi.ac.uk/files/AF-A6NDU8-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-A6NDU8-F1-predicted_aligned_error_v6.png","plddt_mean":85.62},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=RIMOC1","jax_strain_url":"https://www.jax.org/strain/search?query=RIMOC1"},"sequence":{"accession":"A6NDU8","fasta_url":"https://rest.uniprot.org/uniprotkb/A6NDU8.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/A6NDU8/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/A6NDU8"}},"corpus_meta":[{"pmid":"34432599","id":"PMC_34432599","title":"C5orf51 is a component of the MON1-CCZ1 complex and controls RAB7A localization and stability during mitophagy.","date":"2021","source":"Autophagy","url":"https://pubmed.ncbi.nlm.nih.gov/34432599","citation_count":35,"is_preprint":false},{"pmid":"42072025","id":"PMC_42072025","title":"Transcriptional and Alternative Splicing Regulation of Autophagy and Vesicle Transport Pathways in Large Yellow Croaker Cells During Megalocytivirus Infection.","date":"2026","source":"Animals : an open access journal from MDPI","url":"https://pubmed.ncbi.nlm.nih.gov/42072025","citation_count":0,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":3571,"output_tokens":810,"usd":0.011432,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":7217,"output_tokens":1636,"usd":0.038492,"stage2_stop_reason":"end_turn"},"total_usd":0.049924,"stage1_batch_id":"msgbatch_01CNoDbkChHEkgrJnL7BwtGJ","stage2_batch_id":"msgbatch_016Y4x9E9Wg5VQDANj9quSQD","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2021,\n      \"finding\": \"C5orf51 (RIMOC1) was identified as a specific interactor of GDP-locked (inactive) RAB7A using proximity-dependent biotinylation (miniTurbo), and also interacts with MON1 and CCZ1, the components of the RAB7A guanine nucleotide exchange factor complex, placing C5orf51 as a component of the MON1-CCZ1 complex.\",\n      \"method\": \"Proximity-dependent biotinylation (miniTurbo BioID), co-immunoprecipitation\",\n      \"journal\": \"Autophagy\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — proximity-dependent biotinylation plus co-IP with nucleotide-locked RAB7A mutant, single lab but multiple orthogonal methods\",\n      \"pmids\": [\"34432599\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"In the absence of C5orf51 (RIMOC1), RAB7A fails to localize to depolarized mitochondria during mitophagy and is instead degraded by the proteasome, demonstrating that C5orf51 is required for RAB7A stability and correct subcellular translocation from late endosomes to the mitochondrial surface.\",\n      \"method\": \"C5orf51 knockout cells, fluorescence microscopy (RAB7A localization), proteasome inhibitor rescue (MG132)\",\n      \"journal\": \"Autophagy\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — genetic knockout with defined localization and stability phenotype, proteasome inhibitor rescue as orthogonal validation, single lab\",\n      \"pmids\": [\"34432599\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"Depletion of C5orf51 (RIMOC1) inhibited ATG9A recruitment to depolarized mitochondria, establishing C5orf51 as an upstream positive regulator required for the mitophagy autophagy machinery to engage at the mitochondrial surface.\",\n      \"method\": \"C5orf51 knockout/depletion, fluorescence microscopy of ATG9A localization after mitochondrial depolarization (CCCP treatment)\",\n      \"journal\": \"Autophagy\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — clean genetic depletion with defined phenotypic readout, single lab, single method for this specific finding\",\n      \"pmids\": [\"34432599\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"RIMOC1 (C5orf51) is a component of the MON1-CCZ1 RAB7A guanine nucleotide exchange factor complex that binds GDP-locked RAB7A and is required for its stabilization and translocation from late endosomes to depolarized mitochondria during mitophagy, and also promotes ATG9A recruitment to mitochondria, functioning as a positive regulator of the RAB7A-dependent mitophagy pathway.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"RIMOC1 (C5orf51) is a positive regulator of RAB7A-dependent mitophagy that functions as a component of the MON1-CCZ1 RAB7A guanine nucleotide exchange factor complex [#0]. It associates specifically with GDP-locked (inactive) RAB7A and with the MON1 and CCZ1 subunits of the GEF complex [#0], and is required for RAB7A stability and its translocation from late endosomes to the surface of depolarized mitochondria: in its absence RAB7A fails to localize to damaged mitochondria and is instead degraded by the proteasome [#1]. Through this control of RAB7A, RIMOC1 acts upstream of the core autophagy machinery, being required for recruitment of ATG9A to depolarized mitochondria [#2]. Beyond these roles in the RAB7A mitophagy pathway, no further mechanistic detail has been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2021,\n      \"claim\": \"Establishing that the uncharacterized protein C5orf51/RIMOC1 physically associates with the RAB7A GEF machinery defined its molecular context as a component of the MON1-CCZ1 complex.\",\n      \"evidence\": \"Proximity-dependent biotinylation (miniTurbo BioID) and co-IP with nucleotide-locked RAB7A mutants, showing interaction with GDP-locked RAB7A, MON1 and CCZ1\",\n      \"pmids\": [\"34432599\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Stoichiometry and whether RIMOC1 is an obligate versus accessory subunit of MON1-CCZ1 not defined\",\n        \"Whether RIMOC1 directly contacts RAB7A or is bridged through MON1-CCZ1 not resolved\",\n        \"No structural model of the RIMOC1-containing complex\"\n      ]\n    },\n    {\n      \"year\": 2021,\n      \"claim\": \"Loss-of-function showed that RIMOC1 is functionally required for RAB7A stability and its delivery to depolarized mitochondria, explaining why it matters for the pathway rather than merely being an interactor.\",\n      \"evidence\": \"C5orf51 knockout cells with RAB7A localization microscopy and MG132 proteasome-inhibitor rescue of RAB7A levels\",\n      \"pmids\": [\"34432599\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Mechanism by which RIMOC1 protects RAB7A from proteasomal turnover unknown\",\n        \"Whether the stabilization defect is direct or a consequence of failed translocation not separated\"\n      ]\n    },\n    {\n      \"year\": 2021,\n      \"claim\": \"Placing RIMOC1 upstream of ATG9A recruitment connected its RAB7A function to engagement of the core autophagy machinery during mitophagy.\",\n      \"evidence\": \"C5orf51 depletion with ATG9A localization microscopy after CCCP-induced mitochondrial depolarization\",\n      \"pmids\": [\"34432599\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Single method and single lab for this specific readout\",\n        \"Whether ATG9A recruitment defect is solely downstream of lost RAB7A or an independent RIMOC1 role not distinguished\",\n        \"Impact on mitophagic flux and clearance endpoints not quantified\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"It remains unknown whether RIMOC1 functions outside the RAB7A mitophagy pathway and what its enzymatic or structural contribution to the MON1-CCZ1 complex is.\",\n      \"evidence\": null,\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No biochemical assay of any RIMOC1 catalytic activity\",\n        \"No characterization in conventional (non-mitochondrial) endolysosomal trafficking\",\n        \"Findings derive from a single study and single lab\"\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0098772\", \"supporting_discovery_ids\": [0, 1, 2]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005739\", \"supporting_discovery_ids\": [1, 2]},\n      {\"term_id\": \"GO:0005768\", \"supporting_discovery_ids\": [1]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-9612973\", \"supporting_discovery_ids\": [1, 2]}\n    ],\n    \"complexes\": [\"MON1-CCZ1 complex\"],\n    \"partners\": [\"RAB7A\", \"MON1\", \"CCZ1\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":3,"faith_total":3,"faith_pct":100.0}}