{"gene":"VPS9D1","run_date":"2026-06-11T09:02:06","timeline":{"discoveries":[{"year":1999,"finding":"VPS9D1 (ATP-BL) was cloned from a human leukocyte cDNA library and found to encode a 438-amino-acid protein with 37.9% identity to the b subunit of bacterial ATP synthase over a 57-amino-acid region, and contains a predicted coiled-coil motif. The locus was mapped by FISH and radiation hybrid mapping to chromosome 16q24.","method":"cDNA cloning, sequence homology analysis, FISH, radiation hybrid mapping","journal":"DNA research : an international journal for rapid publication of reports on genes and genomes","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — direct cloning and mapping with sequence analysis, single lab, no functional assay confirming ATP synthase activity","pmids":["10231027"],"is_preprint":false},{"year":2023,"finding":"VPS9D1 acts as a guanine-nucleotide-exchange factor (GEF) specifically for Rab22A but not Rab5A. Depletion of Vps9d1 in HeLa cells severely impaired tubular endosome formation without affecting Rab5A localization. Expression of a constitutively active Rab22A mutant rescued tubular endosomes in Vps9d1-depleted cells, but a GEF-activity-deficient Vps9d1 mutant did not. Vps9d1 depletion also altered distribution of clathrin-independent endocytosed cargos and impaired their recycling.","method":"siRNA depletion, fluorescence microscopy, rescue with constitutively active Rab22A mutant and GEF-activity-deficient Vps9d1 mutant, cargo trafficking assays in HeLa cells","journal":"Journal of cell science","confidence":"High","confidence_rationale":"Tier 2 / Strong — multiple orthogonal methods (depletion, dominant-active rescue, active-site mutagenesis, cargo trafficking assays) in a single rigorous study establishing specific GEF activity and functional consequence","pmids":["36762583"],"is_preprint":false}],"current_model":"VPS9D1 is a VPS9-domain-containing protein that functions as a Rab22A-specific guanine-nucleotide-exchange factor (GEF) in HeLa cells, promoting tubular endosome formation in the clathrin-independent endocytosis pathway by activating Rab22A (but not Rab5A), and its loss impairs recycling of clathrin-independent endocytic cargos."},"narrative":{"mechanistic_narrative":"VPS9D1 is a VPS9-domain-containing guanine-nucleotide-exchange factor that regulates membrane trafficking through the clathrin-independent endocytic pathway [PMID:36762583]. It acts as a GEF specifically for Rab22A but not Rab5A, and through this activity drives the formation of tubular endosomes: depletion of VPS9D1 in HeLa cells severely impairs tubular endosome formation, a defect rescued by constitutively active Rab22A but not by a GEF-activity-deficient VPS9D1 mutant [PMID:36762583]. Consistent with a role in this pathway, loss of VPS9D1 alters the distribution of clathrin-independent endocytic cargos and impairs their recycling [PMID:36762583]. The protein was originally cloned as ATP-BL, encoding a 438-residue product with a coiled-coil motif and limited regional homology to the bacterial ATP synthase b subunit, and mapped to chromosome 16q24 [PMID:10231027]. Beyond its Rab22A GEF activity and role in tubular endosome biogenesis, no further mechanistic detail has been characterized in the available corpus.","teleology":[{"year":1999,"claim":"Established the existence and primary sequence of the gene by isolating its cDNA, providing the molecular starting point before any function was known.","evidence":"cDNA cloning from a human leukocyte library with sequence homology analysis and chromosomal mapping by FISH and radiation hybrid mapping","pmids":["10231027"],"confidence":"Medium","gaps":["The regional homology to bacterial ATP synthase b subunit was never confirmed by a functional ATP synthase assay","No cellular function or localization was assigned","The significance of the predicted coiled-coil motif was not tested"]},{"year":2023,"claim":"Defined VPS9D1 as a Rab-specific GEF and connected it to a discrete trafficking step, answering what the protein actually does in cells.","evidence":"siRNA depletion, dominant-active Rab22A rescue, GEF-dead mutant rescue, and cargo trafficking assays in HeLa cells","pmids":["36762583"],"confidence":"High","gaps":["No in vitro reconstitution of GEF kinetics on purified Rab22A","No structural basis for Rab22A specificity over Rab5A","Upstream signals and recruitment mechanism to tubular endosomes not defined"]},{"year":null,"claim":"How VPS9D1 is recruited to and activated at the tubular endosome, and whether it has functions outside the clathrin-independent endocytic pathway, remain open.","evidence":"","pmids":[],"confidence":"High","gaps":["No interactome or upstream regulators identified","Function tested only in HeLa cells","Physiological/organismal role unexplored"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0098772","term_label":"molecular function regulator activity","supporting_discovery_ids":[1]}],"localization":[{"term_id":"GO:0005768","term_label":"endosome","supporting_discovery_ids":[1]}],"pathway":[{"term_id":"R-HSA-5653656","term_label":"Vesicle-mediated transport","supporting_discovery_ids":[1]}],"complexes":[],"partners":["RAB22A"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q9Y2B5","full_name":"VPS9 domain-containing protein 1","aliases":["Protein ATP-BL"],"length_aa":631,"mass_kda":69.0,"function":"","subcellular_location":"","url":"https://www.uniprot.org/uniprotkb/Q9Y2B5/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/VPS9D1","classification":"Not Classified","n_dependent_lines":13,"n_total_lines":1208,"dependency_fraction":0.01076158940397351},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[{"gene":"IST1","stoichiometry":0.2}],"url":"https://opencell.sf.czbiohub.org/search/VPS9D1","total_profiled":1310},"omim":[{"mim_id":"619292","title":"VPS9 DOMAIN-CONTAINING PROTEIN 1; VPS9D1","url":"https://www.omim.org/entry/619292"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Approved","locations":[{"location":"Cytosol","reliability":"Approved"},{"location":"Nucleoplasm","reliability":"Additional"}],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in all","driving_tissues":[],"url":"https://www.proteinatlas.org/search/VPS9D1"},"hgnc":{"alias_symbol":["ATP-BL"],"prev_symbol":["C16orf7"]},"alphafold":{"accession":"Q9Y2B5","domains":[{"cath_id":"1.20.58.80","chopping":"13-57_67-91","consensus_level":"high","plddt":89.1237,"start":13,"end":91},{"cath_id":"-","chopping":"231-308_405-467","consensus_level":"medium","plddt":88.4765,"start":231,"end":467},{"cath_id":"1.20.1050.80","chopping":"482-549_565-624","consensus_level":"high","plddt":89.1794,"start":482,"end":624},{"cath_id":"1.10.287","chopping":"148-222","consensus_level":"medium","plddt":90.2653,"start":148,"end":222}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q9Y2B5","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q9Y2B5-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q9Y2B5-F1-predicted_aligned_error_v6.png","plddt_mean":75.12},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=VPS9D1","jax_strain_url":"https://www.jax.org/strain/search?query=VPS9D1"},"sequence":{"accession":"Q9Y2B5","fasta_url":"https://rest.uniprot.org/uniprotkb/Q9Y2B5.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q9Y2B5/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q9Y2B5"}},"corpus_meta":[{"pmid":"29036784","id":"PMC_29036784","title":"Decreased expression of lncRNA VPS9D1-AS1 in gastric cancer and its clinical significance.","date":"2017","source":"Cancer biomarkers : section A of Disease markers","url":"https://pubmed.ncbi.nlm.nih.gov/29036784","citation_count":49,"is_preprint":false},{"pmid":"31918265","id":"PMC_31918265","title":"ZEB1 activated-VPS9D1-AS1 promotes the tumorigenesis and progression of prostate cancer by sponging miR-4739 to upregulate MEF2D.","date":"2019","source":"Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie","url":"https://pubmed.ncbi.nlm.nih.gov/31918265","citation_count":41,"is_preprint":false},{"pmid":"36458816","id":"PMC_36458816","title":"VPS9D1-AS1 overexpression amplifies intratumoral TGF-β signaling and promotes tumor cell escape from CD8+ T cell killing in colorectal cancer.","date":"2022","source":"eLife","url":"https://pubmed.ncbi.nlm.nih.gov/36458816","citation_count":27,"is_preprint":false},{"pmid":"32808668","id":"PMC_32808668","title":"LncRNA VPS9D1-AS1 promotes cell proliferation in acute lymphoblastic leukemia through modulating GPX1 expression by miR-491-5p and miR-214-3p evasion.","date":"2020","source":"Bioscience reports","url":"https://pubmed.ncbi.nlm.nih.gov/32808668","citation_count":27,"is_preprint":false},{"pmid":"33192510","id":"PMC_33192510","title":"Chidamide Inhibits Acute Myeloid Leukemia Cell Proliferation by lncRNA VPS9D1-AS1 Downregulation via MEK/ERK Signaling Pathway.","date":"2020","source":"Frontiers in pharmacology","url":"https://pubmed.ncbi.nlm.nih.gov/33192510","citation_count":26,"is_preprint":false},{"pmid":"31902794","id":"PMC_31902794","title":"Long noncoding RNA VPS9D1-AS1 augments the malignant phenotype of non-small cell lung cancer by sponging microRNA-532-3p and thereby enhancing HMGA2 expression.","date":"2020","source":"Aging","url":"https://pubmed.ncbi.nlm.nih.gov/31902794","citation_count":24,"is_preprint":false},{"pmid":"33627127","id":"PMC_33627127","title":"Long non-coding RNA VPS9D1-AS1 facilitates cell proliferation, migration and stemness in hepatocellular carcinoma.","date":"2021","source":"Cancer cell international","url":"https://pubmed.ncbi.nlm.nih.gov/33627127","citation_count":21,"is_preprint":false},{"pmid":"34659577","id":"PMC_34659577","title":"Long noncoding RNA VPS9D1-AS1 promotes esophageal squamous cell carcinoma progression via the Wnt/β-catenin signaling pathway.","date":"2021","source":"Journal of Cancer","url":"https://pubmed.ncbi.nlm.nih.gov/34659577","citation_count":19,"is_preprint":false},{"pmid":"35140744","id":"PMC_35140744","title":"LncRNA VPS9D1-AS1 Promotes Malignant Progression of Lung Adenocarcinoma by Targeting miRNA-30a-5p/KIF11 Axis.","date":"2022","source":"Frontiers in genetics","url":"https://pubmed.ncbi.nlm.nih.gov/35140744","citation_count":18,"is_preprint":false},{"pmid":"34558987","id":"PMC_34558987","title":"The lncRNA VPS9D1-AS1 Promotes Hepatocellular Carcinoma Cell Cycle Progression by Regulating the HuR/CDK4 Axis.","date":"2021","source":"DNA and cell biology","url":"https://pubmed.ncbi.nlm.nih.gov/34558987","citation_count":16,"is_preprint":false},{"pmid":"33116849","id":"PMC_33116849","title":"Long Noncoding RNA VPS9D1-AS1 Sequesters microRNA-525-5p to Promote the Oncogenicity of Colorectal Cancer Cells by Upregulating HMGA1.","date":"2020","source":"Cancer management and research","url":"https://pubmed.ncbi.nlm.nih.gov/33116849","citation_count":16,"is_preprint":false},{"pmid":"36245426","id":"PMC_36245426","title":"Long non-coding RNA VPS9D1-AS1 enhances proliferation, invasion, and epithelial-mesenchymal transition in endometrial cancer via miR-377-3p/SGK1.","date":"2022","source":"The Kaohsiung journal of medical sciences","url":"https://pubmed.ncbi.nlm.nih.gov/36245426","citation_count":13,"is_preprint":false},{"pmid":"40412657","id":"PMC_40412657","title":"VPS9D1-AS1 antisense therapy via lipid nanoparticles reprograms cold tumors and enhances immunotherapy in colorectal cancer.","date":"2025","source":"Journal of controlled release : official journal of the Controlled Release Society","url":"https://pubmed.ncbi.nlm.nih.gov/40412657","citation_count":10,"is_preprint":false},{"pmid":"35273698","id":"PMC_35273698","title":"VPS9D1-AS1, a novel long-non-coding RNA, acts as a tumor promoter by regulating the miR-324-5p/ITGA2 axis in colon adenocarcinoma.","date":"2022","source":"American journal of translational research","url":"https://pubmed.ncbi.nlm.nih.gov/35273698","citation_count":8,"is_preprint":false},{"pmid":"31239491","id":"PMC_31239491","title":"Analysis of overlapping heterozygous novel submicroscopic CNVs and FANCA-VPS9D1 fusion transcripts in a Fanconi anemia patient.","date":"2019","source":"Journal of human genetics","url":"https://pubmed.ncbi.nlm.nih.gov/31239491","citation_count":8,"is_preprint":false},{"pmid":"34519940","id":"PMC_34519940","title":"Long non-coding RNA VPS9D1-AS1 promotes growth of colon adenocarcinoma by sponging miR-1301-3p and CLDN1.","date":"2021","source":"Human cell","url":"https://pubmed.ncbi.nlm.nih.gov/34519940","citation_count":7,"is_preprint":false},{"pmid":"38953363","id":"PMC_38953363","title":"Long noncoding RNA VPS9D1-AS1 promotes the progression of endometrial cancer via regulation of the miR-187-3p/S100A4 axis.","date":"2024","source":"Environmental toxicology","url":"https://pubmed.ncbi.nlm.nih.gov/38953363","citation_count":7,"is_preprint":false},{"pmid":"37929340","id":"PMC_37929340","title":"LncRNA VPS9D1-AS1 regulates miR-187-3p/fibroblast growth factor receptor-like 1 axis to promote proliferation, migration, and invasion of prostate cancer cells.","date":"2023","source":"The Chinese journal of physiology","url":"https://pubmed.ncbi.nlm.nih.gov/37929340","citation_count":7,"is_preprint":false},{"pmid":"36762583","id":"PMC_36762583","title":"Vps9d1 regulates tubular endosome formation through specific activation of Rab22A.","date":"2023","source":"Journal of cell science","url":"https://pubmed.ncbi.nlm.nih.gov/36762583","citation_count":6,"is_preprint":false},{"pmid":"35022999","id":"PMC_35022999","title":"VPS9D1-AS1 gene rs7206570 polymorphism associated with the clinical stage of colorectal cancer and binding with hsa-miR-361-3p.","date":"2022","source":"Human cell","url":"https://pubmed.ncbi.nlm.nih.gov/35022999","citation_count":6,"is_preprint":false},{"pmid":"35619019","id":"PMC_35619019","title":"LncRNA VPS9D1-AS1 Sponging miR-520a-5p Contributes to the Development of Uterine Corpus Endometrial Carcinoma by Enhancing BIRC5 Expression.","date":"2022","source":"Molecular biotechnology","url":"https://pubmed.ncbi.nlm.nih.gov/35619019","citation_count":6,"is_preprint":false},{"pmid":"40522493","id":"PMC_40522493","title":"Plasma expression of antisense LncRNAs RBM5-AS1, VPS9D1-AS1 and STEAP3-AS1 as novel biomarkers for colorectal cancer diagnosis.","date":"2025","source":"Molecular biology reports","url":"https://pubmed.ncbi.nlm.nih.gov/40522493","citation_count":4,"is_preprint":false},{"pmid":"10231027","id":"PMC_10231027","title":"Isolation and mapping of a putative b subunit of human ATP synthase (ATP-BL) from human leukocytes.","date":"1999","source":"DNA research : an international journal for rapid publication of reports on genes and genomes","url":"https://pubmed.ncbi.nlm.nih.gov/10231027","citation_count":3,"is_preprint":false},{"pmid":"41460448","id":"PMC_41460448","title":"VPS9D1-AS1: a critical oncogenic long non-coding RNA in human malignancies.","date":"2025","source":"Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico","url":"https://pubmed.ncbi.nlm.nih.gov/41460448","citation_count":2,"is_preprint":false},{"pmid":"40371141","id":"PMC_40371141","title":"Long noncoding RNA VPS9D1-AS1 promotes angiogenesis in colorectal cancer by regulating the VEGFA signalling pathway.","date":"2025","source":"American journal of cancer research","url":"https://pubmed.ncbi.nlm.nih.gov/40371141","citation_count":1,"is_preprint":false},{"pmid":"40908689","id":"PMC_40908689","title":"Long Non-Coding RNA VPS9D1-AS1 in Human Cancer: Functions, Mechanisms, and Clinical Utility.","date":"2026","source":"Anti-cancer agents in medicinal chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/40908689","citation_count":0,"is_preprint":false},{"pmid":"41207568","id":"PMC_41207568","title":"Exosomal transfer of VPS9D1-AS1 induces M2 polarization to promote erlotinib resistance of LUAD cells via activation of the Wnt/β-catenin signaling pathway.","date":"2025","source":"Biochemical pharmacology","url":"https://pubmed.ncbi.nlm.nih.gov/41207568","citation_count":0,"is_preprint":false},{"pmid":"41527363","id":"PMC_41527363","title":"Emergence and Tandem Repeat-Mediated Elongation of a Translated De Novo Open Reading Frame in Human Oncogenic RNA Gene VPS9D1-AS1 (MYU).","date":"2026","source":"Genome biology and evolution","url":"https://pubmed.ncbi.nlm.nih.gov/41527363","citation_count":0,"is_preprint":false},{"pmid":"37469373","id":"PMC_37469373","title":"Long Noncoding RNA VPS9D1-AS1 Sequesters microRNA-525-5p to Promote the Oncogenicity of Colorectal Cancer Cells by Upregulating HMGA1 [Retraction].","date":"2023","source":"Cancer management and research","url":"https://pubmed.ncbi.nlm.nih.gov/37469373","citation_count":0,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":17304,"output_tokens":1043,"usd":0.033779,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":7059,"output_tokens":1268,"usd":0.033497,"stage2_stop_reason":"end_turn"},"total_usd":0.067276,"stage1_batch_id":"msgbatch_01UT1AahFPCAyn2uVweS7A9z","stage2_batch_id":"msgbatch_01HuKWtKNT4Pqj1bc8eEP5RV","note":"batch pricing = 50% of standard"},"stage1_raw":"Looking through these papers, I need to identify which ones are about the canonical VPS9D1 protein-coding gene versus VPS9D1-AS1 (a long non-coding RNA antisense transcript). VPS9D1 is the protein-coding gene (also known as ATP-BL, C16orf7), while VPS9D1-AS1 is a separate lncRNA product from the antisense strand — these are distinct entities.\n\nPapers 1–14, 16–18, 20–22, 24–28 are all about VPS9D1-AS1 (lncRNA), NOT the VPS9D1 protein. Per the instructions, non-protein products (lncRNA, antisense transcripts) are excluded.\n\nPaper 19 (PMID:36762583) is about the VPS9D1 protein itself — describing its function as a Rab22A-GEF.\nPaper 23 (PMID:10231027) is about ATP-BL (an alias for VPS9D1), describing the original cloning.\nPaper 15 (PMID:31239491) mentions VPS9D1 in the context of a fusion transcript — minimal mechanistic info about the protein.\nPaper 28 (PMID:41527363) is about an ORF within VPS9D1-AS1 lncRNA — not the canonical protein.\nPaper 29 is a retraction notice.\n\n```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 1999,\n      \"finding\": \"VPS9D1 (ATP-BL) was cloned from a human leukocyte cDNA library and found to encode a 438-amino-acid protein with 37.9% identity to the b subunit of bacterial ATP synthase over a 57-amino-acid region, and contains a predicted coiled-coil motif. The locus was mapped by FISH and radiation hybrid mapping to chromosome 16q24.\",\n      \"method\": \"cDNA cloning, sequence homology analysis, FISH, radiation hybrid mapping\",\n      \"journal\": \"DNA research : an international journal for rapid publication of reports on genes and genomes\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — direct cloning and mapping with sequence analysis, single lab, no functional assay confirming ATP synthase activity\",\n      \"pmids\": [\"10231027\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"VPS9D1 acts as a guanine-nucleotide-exchange factor (GEF) specifically for Rab22A but not Rab5A. Depletion of Vps9d1 in HeLa cells severely impaired tubular endosome formation without affecting Rab5A localization. Expression of a constitutively active Rab22A mutant rescued tubular endosomes in Vps9d1-depleted cells, but a GEF-activity-deficient Vps9d1 mutant did not. Vps9d1 depletion also altered distribution of clathrin-independent endocytosed cargos and impaired their recycling.\",\n      \"method\": \"siRNA depletion, fluorescence microscopy, rescue with constitutively active Rab22A mutant and GEF-activity-deficient Vps9d1 mutant, cargo trafficking assays in HeLa cells\",\n      \"journal\": \"Journal of cell science\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — multiple orthogonal methods (depletion, dominant-active rescue, active-site mutagenesis, cargo trafficking assays) in a single rigorous study establishing specific GEF activity and functional consequence\",\n      \"pmids\": [\"36762583\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"VPS9D1 is a VPS9-domain-containing protein that functions as a Rab22A-specific guanine-nucleotide-exchange factor (GEF) in HeLa cells, promoting tubular endosome formation in the clathrin-independent endocytosis pathway by activating Rab22A (but not Rab5A), and its loss impairs recycling of clathrin-independent endocytic cargos.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"VPS9D1 is a VPS9-domain-containing guanine-nucleotide-exchange factor that regulates membrane trafficking through the clathrin-independent endocytic pathway [#1]. It acts as a GEF specifically for Rab22A but not Rab5A, and through this activity drives the formation of tubular endosomes: depletion of VPS9D1 in HeLa cells severely impairs tubular endosome formation, a defect rescued by constitutively active Rab22A but not by a GEF-activity-deficient VPS9D1 mutant [#1]. Consistent with a role in this pathway, loss of VPS9D1 alters the distribution of clathrin-independent endocytic cargos and impairs their recycling [#1]. The protein was originally cloned as ATP-BL, encoding a 438-residue product with a coiled-coil motif and limited regional homology to the bacterial ATP synthase b subunit, and mapped to chromosome 16q24 [#0]. Beyond its Rab22A GEF activity and role in tubular endosome biogenesis, no further mechanistic detail has been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 1999,\n      \"claim\": \"Established the existence and primary sequence of the gene by isolating its cDNA, providing the molecular starting point before any function was known.\",\n      \"evidence\": \"cDNA cloning from a human leukocyte library with sequence homology analysis and chromosomal mapping by FISH and radiation hybrid mapping\",\n      \"pmids\": [\n        \"10231027\"\n      ],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"The regional homology to bacterial ATP synthase b subunit was never confirmed by a functional ATP synthase assay\",\n        \"No cellular function or localization was assigned\",\n        \"The significance of the predicted coiled-coil motif was not tested\"\n      ]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"Defined VPS9D1 as a Rab-specific GEF and connected it to a discrete trafficking step, answering what the protein actually does in cells.\",\n      \"evidence\": \"siRNA depletion, dominant-active Rab22A rescue, GEF-dead mutant rescue, and cargo trafficking assays in HeLa cells\",\n      \"pmids\": [\n        \"36762583\"\n      ],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"No in vitro reconstitution of GEF kinetics on purified Rab22A\",\n        \"No structural basis for Rab22A specificity over Rab5A\",\n        \"Upstream signals and recruitment mechanism to tubular endosomes not defined\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How VPS9D1 is recruited to and activated at the tubular endosome, and whether it has functions outside the clathrin-independent endocytic pathway, remain open.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"No interactome or upstream regulators identified\",\n        \"Function tested only in HeLa cells\",\n        \"Physiological/organismal role unexplored\"\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0098772\", \"supporting_discovery_ids\": [1]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005768\", \"supporting_discovery_ids\": [1]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-5653656\", \"supporting_discovery_ids\": [1]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\n      \"RAB22A\"\n    ],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"faith_supported":4,"faith_total":4,"faith_pct":100.0}}