{"gene":"ARL6IP6","run_date":"2026-06-09T22:02:44","timeline":{"discoveries":[{"year":2019,"finding":"ARL6IP6 is concentrated at the nuclear envelope, likely residing in the inner nuclear membrane, as determined by quantitative immunofluorescence microscopy of mesenchymal stem cells, adipocytes, and myocytes using organellar proteomics enrichment scoring.","method":"Organellar proteomics (subcellular fractionation) combined with quantitative immunofluorescence microscopy","journal":"Nucleus (Austin, Tex.)","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct localization experiment with quantitative microscopy and proteomics enrichment scoring in multiple cell types, single lab, two orthogonal methods","pmids":["31142202"],"is_preprint":false}],"current_model":"ARL6IP6 is a transmembrane protein concentrated at the nuclear envelope, likely residing in the inner nuclear membrane, based on organellar proteomics and quantitative immunofluorescence in mesenchymal cells; loss-of-function truncating mutations cause syndromic vascular disease (CMTC), but the molecular mechanism by which ARL6IP6 functions remains undefined."},"narrative":{"mechanistic_narrative":"ARL6IP6 is a transmembrane protein concentrated at the nuclear envelope, likely residing in the inner nuclear membrane, as established by organellar proteomics enrichment scoring and quantitative immunofluorescence across mesenchymal stem cells, adipocytes, and myocytes [PMID:31142202]. Beyond this localization, no molecular function, binding partner, or pathway role for ARL6IP6 has been characterized in the available corpus.","teleology":[{"year":2019,"claim":"Where ARL6IP6 resides in the cell was unknown; combining subcellular fractionation with quantitative imaging placed the protein at the nuclear envelope, most likely the inner nuclear membrane, defining the compartment in which it must act.","evidence":"Organellar proteomics enrichment scoring plus quantitative immunofluorescence microscopy in mesenchymal stem cells, adipocytes, and myocytes","pmids":["31142202"],"confidence":"Medium","gaps":["Membrane topology and orientation within the inner nuclear membrane not resolved","No binding partners or interacting complexes identified","No molecular activity or pathway role established"]},{"year":null,"claim":"The molecular function of ARL6IP6 at the nuclear envelope remains undefined.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No biochemical activity assigned","No genetic or interaction data linking ARL6IP6 to a defined pathway","Functional consequence of localization to the inner nuclear membrane unknown"]}],"mechanism_profile":{"molecular_activity":[],"localization":[{"term_id":"GO:0005635","term_label":"nuclear envelope","supporting_discovery_ids":[0]}],"pathway":[],"complexes":[],"partners":[],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q8N6S5","full_name":"ADP-ribosylation factor-like protein 6-interacting protein 6","aliases":["Phosphonoformate immuno-associated protein 1"],"length_aa":226,"mass_kda":24.7,"function":"","subcellular_location":"Nucleus inner membrane","url":"https://www.uniprot.org/uniprotkb/Q8N6S5/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/ARL6IP6","classification":"Not Classified","n_dependent_lines":24,"n_total_lines":1208,"dependency_fraction":0.019867549668874173},"opencell":{"profiled":true,"resolved_as":"","ensg_id":"ENSG00000177917","cell_line_id":"CID000503","localizations":[{"compartment":"nuclear_membrane","grade":3},{"compartment":"big_aggregates","grade":2}],"interactors":[{"gene":"RAB5C;RAB5B;DIRAS1;DIRAS2;RAB5A","stoichiometry":0.2},{"gene":"ARPC2","stoichiometry":0.2},{"gene":"ARPC1B","stoichiometry":0.2},{"gene":"YWHAB","stoichiometry":0.2},{"gene":"CALM2;CALM3;CALM1","stoichiometry":0.2},{"gene":"YWHAQ","stoichiometry":0.2},{"gene":"FASN","stoichiometry":0.2},{"gene":"CLASP1","stoichiometry":0.2},{"gene":"KLC2","stoichiometry":0.2},{"gene":"ARPC1A","stoichiometry":0.2}],"url":"https://opencell.sf.czbiohub.org/target/CID000503","total_profiled":1310},"omim":[{"mim_id":"616495","title":"ADP-RIBOSYLATION FACTOR-LIKE GTPase 6-INTERACTING PROTEIN 6; ARL6IP6","url":"https://www.omim.org/entry/616495"},{"mim_id":"219250","title":"CUTIS MARMORATA TELANGIECTATICA CONGENITA; CMTC","url":"https://www.omim.org/entry/219250"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Approved","locations":[{"location":"Nuclear membrane","reliability":"Approved"},{"location":"Cytosol","reliability":"Additional"}],"tissue_specificity":"Tissue enhanced","tissue_distribution":"Detected in many","driving_tissues":[{"tissue":"skeletal muscle","ntpm":53.9}],"url":"https://www.proteinatlas.org/search/ARL6IP6"},"hgnc":{"alias_symbol":["MGC33864"],"prev_symbol":[]},"alphafold":{"accession":"Q8N6S5","domains":[{"cath_id":"-","chopping":"106-180_205-226","consensus_level":"medium","plddt":68.9786,"start":106,"end":226}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q8N6S5","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q8N6S5-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q8N6S5-F1-predicted_aligned_error_v6.png","plddt_mean":56.72},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=ARL6IP6","jax_strain_url":"https://www.jax.org/strain/search?query=ARL6IP6"},"sequence":{"accession":"Q8N6S5","fasta_url":"https://rest.uniprot.org/uniprotkb/Q8N6S5.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q8N6S5/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q8N6S5"}},"corpus_meta":[{"pmid":"31142202","id":"PMC_31142202","title":"Identification of new transmembrane proteins concentrated at the nuclear envelope using organellar proteomics of mesenchymal cells.","date":"2019","source":"Nucleus (Austin, Tex.)","url":"https://pubmed.ncbi.nlm.nih.gov/31142202","citation_count":43,"is_preprint":false},{"pmid":"22384361","id":"PMC_22384361","title":"Genome-wide association analysis of ischemic stroke in young adults.","date":"2011","source":"G3 (Bethesda, Md.)","url":"https://pubmed.ncbi.nlm.nih.gov/22384361","citation_count":30,"is_preprint":false},{"pmid":"26589421","id":"PMC_26589421","title":"Regulation signature of miR-143 and miR-26 in porcine Salmonella infection identified by binding site enrichment analysis.","date":"2015","source":"Molecular genetics and genomics : MGG","url":"https://pubmed.ncbi.nlm.nih.gov/26589421","citation_count":18,"is_preprint":false},{"pmid":"25957586","id":"PMC_25957586","title":"ARL6IP6, a susceptibility locus for ischemic stroke, is mutated in a patient with syndromic Cutis Marmorata Telangiectatica Congenita.","date":"2015","source":"Human genetics","url":"https://pubmed.ncbi.nlm.nih.gov/25957586","citation_count":12,"is_preprint":false},{"pmid":"35126886","id":"PMC_35126886","title":"D155Y substitution of SARS-CoV-2 ORF3a weakens binding with Caveolin-1.","date":"2022","source":"Computational and structural biotechnology journal","url":"https://pubmed.ncbi.nlm.nih.gov/35126886","citation_count":10,"is_preprint":false},{"pmid":"38534785","id":"PMC_38534785","title":"Cellular Organelle-Related Transcriptomic Profile Abnormalities in Neuronopathic Types of Mucopolysaccharidosis: A Comparison with Other Neurodegenerative Diseases.","date":"2024","source":"Current issues in molecular biology","url":"https://pubmed.ncbi.nlm.nih.gov/38534785","citation_count":3,"is_preprint":false},{"pmid":"27690330","id":"PMC_27690330","title":"Mapping of a FEB3 homologous febrile seizure locus on mouse chromosome 2 containing candidate genes Scn1a and Scn3a.","date":"2016","source":"The European journal of neuroscience","url":"https://pubmed.ncbi.nlm.nih.gov/27690330","citation_count":3,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":5679,"output_tokens":319,"usd":0.010911,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":6569,"output_tokens":718,"usd":0.025397,"stage2_stop_reason":"end_turn"},"total_usd":0.036308,"stage1_batch_id":"msgbatch_0179Z2pxRYBsXi2xADneafRw","stage2_batch_id":"msgbatch_01LaY9ZaVdgjWArcZo9eqQE5","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2019,\n      \"finding\": \"ARL6IP6 is concentrated at the nuclear envelope, likely residing in the inner nuclear membrane, as determined by quantitative immunofluorescence microscopy of mesenchymal stem cells, adipocytes, and myocytes using organellar proteomics enrichment scoring.\",\n      \"method\": \"Organellar proteomics (subcellular fractionation) combined with quantitative immunofluorescence microscopy\",\n      \"journal\": \"Nucleus (Austin, Tex.)\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct localization experiment with quantitative microscopy and proteomics enrichment scoring in multiple cell types, single lab, two orthogonal methods\",\n      \"pmids\": [\"31142202\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"ARL6IP6 is a transmembrane protein concentrated at the nuclear envelope, likely residing in the inner nuclear membrane, based on organellar proteomics and quantitative immunofluorescence in mesenchymal cells; loss-of-function truncating mutations cause syndromic vascular disease (CMTC), but the molecular mechanism by which ARL6IP6 functions remains undefined.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"ARL6IP6 is a transmembrane protein concentrated at the nuclear envelope, likely residing in the inner nuclear membrane, as established by organellar proteomics enrichment scoring and quantitative immunofluorescence across mesenchymal stem cells, adipocytes, and myocytes [#0]. Beyond this localization, no molecular function, binding partner, or pathway role for ARL6IP6 has been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2019,\n      \"claim\": \"Where ARL6IP6 resides in the cell was unknown; combining subcellular fractionation with quantitative imaging placed the protein at the nuclear envelope, most likely the inner nuclear membrane, defining the compartment in which it must act.\",\n      \"evidence\": \"Organellar proteomics enrichment scoring plus quantitative immunofluorescence microscopy in mesenchymal stem cells, adipocytes, and myocytes\",\n      \"pmids\": [\"31142202\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Membrane topology and orientation within the inner nuclear membrane not resolved\",\n        \"No binding partners or interacting complexes identified\",\n        \"No molecular activity or pathway role established\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The molecular function of ARL6IP6 at the nuclear envelope remains undefined.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No biochemical activity assigned\",\n        \"No genetic or interaction data linking ARL6IP6 to a defined pathway\",\n        \"Functional consequence of localization to the inner nuclear membrane unknown\"\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [],\n    \"localization\": [\n      {\"term_id\": \"GO:0005635\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"pathway\": [],\n    \"complexes\": [],\n    \"partners\": [],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"faith_supported":1,"faith_total":1,"faith_pct":100.0}}