{"gene":"DNAI7","run_date":"2026-06-09T23:54:42","timeline":{"discoveries":[{"year":2014,"finding":"CASC1 (PPP1R54/DNAI7 alias) is essential for microtubule polymerization and satisfaction of the spindle assembly checkpoint in NSCLC cells; RNAi-mediated attenuation of CASC1 sensitized paclitaxel-resistant cells to spindle poisons and inhibited tumor growth in vivo.","method":"Genome-wide RNAi screen combined with live-cell imaging to measure mitotic fate; in vivo xenograft growth assay after RNAi knockdown","journal":"Cancer research","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — clean RNAi knockdown with defined cellular phenotype (spindle checkpoint, microtubule polymerization) and in vivo validation, single lab, two orthogonal readouts","pmids":["24860162"],"is_preprint":false},{"year":2006,"finding":"Casc1 knockout mice showed increased susceptibility to chemical induction of lung tumors, establishing a tumor-suppressive role for CASC1 in vivo. Additionally, in vitro colony formation assays showed that the A/J allele of Casc1 produced ~5-6-fold fewer transfectants in human lung cancer cell lines compared to the C57BL/6J allele, indicating allele-specific modulation of cancer cell growth not mediated by apoptosis.","method":"Casc1 knockout mouse tumor bioassay; in vitro colony formation assay with allelic variant transfection in human lung cancer cell lines (A549, NCI-H520)","journal":"Nature genetics / Cancer letters","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — two independent experimental approaches (KO mouse bioassay and in vitro colony assay) from two papers, consistent direction of effect","pmids":["16862160","16458428"],"is_preprint":false},{"year":2024,"finding":"IC97 (the Chlamydomonas ortholog of DNAI7/CFAP94), an intermediate chain of the flagellar dynein IDA f/I1, is required for normal flagellar beat frequency and coordination between the two flagella; loss of IC97 in a Chlamydomonas mutant resulted in slow swimming, low beat frequency, and miscoordination of cis- and trans-flagella, without abolishing phototaxis.","method":"Isolation of Chlamydomonas ic97 null mutant; phenotypic analysis of flagellar motility (beat frequency, swimming path, phototaxis); biochemical analysis of IDA f/I1 complex assembly","journal":"mSphere","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — clean null mutant with defined flagellar phenotypes and biochemical complex assembly analysis; single lab but multiple orthogonal readouts (motility, beat frequency, coordination)","pmids":["39601552"],"is_preprint":false}],"current_model":"DNAI7 (also known as CASC1/CFAP94/PPP1R54) encodes an intermediate chain of the inner dynein arm IDA f/I1 complex required for flagellar beat frequency and inter-flagellar coordination (established in Chlamydomonas IC97 ortholog); in mammalian cells, CASC1 supports microtubule polymerization and spindle assembly checkpoint satisfaction, and functions as a tumor suppressor whose loss increases lung tumor susceptibility in mice."},"narrative":{"mechanistic_narrative":"DNAI7 (CASC1/CFAP94/PPP1R54) is an intermediate chain of the flagellar inner dynein arm IDA f/I1 complex and, in mammalian cells, a regulator of mitotic microtubule dynamics with tumor-suppressive activity. In Chlamydomonas, its ortholog IC97 is required for normal flagellar beat frequency and for coordination between the two flagella, and its loss produces slow swimming and beat miscoordination without abolishing phototaxis, defining a role in ciliary/flagellar motility [PMID:39601552]. In mammalian cells, CASC1 is required for microtubule polymerization and satisfaction of the spindle assembly checkpoint, and its depletion sensitizes paclitaxel-resistant lung cancer cells to spindle poisons and inhibits tumor growth in vivo [PMID:24860162]. Casc1 also acts as a tumor suppressor in vivo, where its loss increases susceptibility to chemically induced lung tumors and an allelic variant modulates cancer cell growth [PMID:16862160, PMID:16458428]. Beyond these motility and mitotic roles, no further mechanistic detail has been characterized in the available corpus.","teleology":[{"year":2006,"claim":"Established that CASC1 functions as a lung tumor suppressor in vivo, defining its physiological relevance to cancer susceptibility.","evidence":"Casc1 knockout mouse chemical-induction tumor bioassay plus allele-specific in vitro colony formation in human lung cancer cell lines","pmids":["16862160","16458428"],"confidence":"Medium","gaps":["Molecular mechanism linking CASC1 loss to tumorigenesis not defined","Allele-specific growth effect not mechanistically explained beyond exclusion of apoptosis"]},{"year":2014,"claim":"Connected CASC1 to mitotic spindle function, showing it is required for microtubule polymerization and spindle assembly checkpoint satisfaction and that its loss can resensitize drug-resistant tumor cells.","evidence":"Genome-wide RNAi screen with live-cell imaging of mitotic fate and in vivo xenograft growth assay in NSCLC cells","pmids":["24860162"],"confidence":"Medium","gaps":["Direct biochemical interaction of CASC1 with microtubules or checkpoint proteins not demonstrated","Single-lab RNAi without genetic rescue","Relationship between this mitotic role and the dynein/flagellar role unresolved"]},{"year":2024,"claim":"Identified the molecular identity of the DNAI7 ortholog as an IDA f/I1 inner dynein arm intermediate chain governing flagellar beat frequency and inter-flagellar coordination.","evidence":"Chlamydomonas ic97 null mutant with flagellar motility, beat frequency, and coordination phenotyping plus biochemical analysis of IDA f/I1 assembly","pmids":["39601552"],"confidence":"Medium","gaps":["Direct evidence for an analogous dynein role in human cells absent","How the same protein reconciles flagellar dynein and mitotic spindle functions unknown"]},{"year":null,"claim":"Whether the mammalian mitotic/tumor-suppressor role and the conserved flagellar dynein intermediate-chain role reflect a single unified molecular activity remains unresolved.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No structural model of human DNAI7 in either context","Direct binding partners in human cells not identified","Tissue-specific functions of motility vs mitotic roles not delineated"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0008092","term_label":"cytoskeletal protein binding","supporting_discovery_ids":[0,2]}],"localization":[{"term_id":"GO:0005929","term_label":"cilium","supporting_discovery_ids":[2]},{"term_id":"GO:0005856","term_label":"cytoskeleton","supporting_discovery_ids":[0]}],"pathway":[{"term_id":"R-HSA-1640170","term_label":"Cell Cycle","supporting_discovery_ids":[0]}],"complexes":["inner dynein arm IDA f/I1"],"partners":[],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q6TDU7","full_name":"Dynein axonemal intermediate chain 7","aliases":["Cancer susceptibility candidate gene 1 protein","Protein CASC1","Cilia and flagella associated protein 94","Lung adenoma susceptibility 1-like protein","Protein phosphatase 1 regulatory subunit 54"],"length_aa":716,"mass_kda":83.2,"function":"Via its association with the multisubunit axonemal dynein complex, is potentially involved in the regulation of cilia function. May also act as a cell cycle regulator","subcellular_location":"Cell projection, cilium; Cytoplasm","url":"https://www.uniprot.org/uniprotkb/Q6TDU7/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/DNAI7","classification":"Not Classified","n_dependent_lines":6,"n_total_lines":1208,"dependency_fraction":0.004966887417218543},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[],"url":"https://opencell.sf.czbiohub.org/search/DNAI7","total_profiled":1310},"omim":[],"hpa":{"profiled":true,"resolved_as":"","reliability":"Approved","locations":[{"location":"Cytosol","reliability":"Approved"},{"location":"Vesicles","reliability":"Additional"}],"tissue_specificity":"Tissue enhanced","tissue_distribution":"Detected in many","driving_tissues":[{"tissue":"choroid plexus","ntpm":13.5},{"tissue":"fallopian tube","ntpm":13.2},{"tissue":"testis","ntpm":21.4}],"url":"https://www.proteinatlas.org/search/DNAI7"},"hgnc":{"alias_symbol":["LAS1","FLJ10921","PPP1R54"],"prev_symbol":["CASC1","CFAP94"]},"alphafold":{"accession":"Q6TDU7","domains":[{"cath_id":"2.60.220,2.60.220","chopping":"195-262_371-424_433-496","consensus_level":"medium","plddt":92.3324,"start":195,"end":496},{"cath_id":"-","chopping":"505-711","consensus_level":"high","plddt":92.8311,"start":505,"end":711},{"cath_id":"1.20.1280","chopping":"104-193","consensus_level":"medium","plddt":91.3934,"start":104,"end":193}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q6TDU7","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q6TDU7-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q6TDU7-F1-predicted_aligned_error_v6.png","plddt_mean":84.75},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=DNAI7","jax_strain_url":"https://www.jax.org/strain/search?query=DNAI7"},"sequence":{"accession":"Q6TDU7","fasta_url":"https://rest.uniprot.org/uniprotkb/Q6TDU7.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q6TDU7/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q6TDU7"}},"corpus_meta":[{"pmid":"25118175","id":"PMC_25118175","title":"Crystal structure of the RNA-guided immune surveillance Cascade complex in Escherichia coli.","date":"2014","source":"Nature","url":"https://pubmed.ncbi.nlm.nih.gov/25118175","citation_count":151,"is_preprint":false},{"pmid":"16862160","id":"PMC_16862160","title":"Candidate lung tumor susceptibility genes identified through whole-genome association analyses in inbred mice.","date":"2006","source":"Nature genetics","url":"https://pubmed.ncbi.nlm.nih.gov/16862160","citation_count":69,"is_preprint":false},{"pmid":"30377236","id":"PMC_30377236","title":"HCN Regulates Cellular Processes through Posttranslational Modification of Proteins by S-cyanylation.","date":"2018","source":"Plant physiology","url":"https://pubmed.ncbi.nlm.nih.gov/30377236","citation_count":50,"is_preprint":false},{"pmid":"33860955","id":"PMC_33860955","title":"Hydrogen sulfide: An emerging signaling molecule regulating drought stress response in plants.","date":"2021","source":"Physiologia plantarum","url":"https://pubmed.ncbi.nlm.nih.gov/33860955","citation_count":35,"is_preprint":false},{"pmid":"24860162","id":"PMC_24860162","title":"Mechanisms promoting escape from mitotic stress-induced tumor cell death.","date":"2014","source":"Cancer research","url":"https://pubmed.ncbi.nlm.nih.gov/24860162","citation_count":32,"is_preprint":false},{"pmid":"29490083","id":"PMC_29490083","title":"ß-Cyanoalanine Synthase Action in Root Hair Elongation is Exerted at Early Steps of the Root Hair Elongation Pathway and is Independent of Direct Cyanide Inactivation of NADPH Oxidase.","date":"2018","source":"Plant & cell physiology","url":"https://pubmed.ncbi.nlm.nih.gov/29490083","citation_count":23,"is_preprint":false},{"pmid":"29459759","id":"PMC_29459759","title":"Genomics of a pediatric ovarian fibrosarcoma. 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in Bladder Cancer Is Regulated by Exosomal miRNA-150: A Comprehensive Pan-Cancer and Bioinformatics Study.","date":"2022","source":"Computational and mathematical methods in medicine","url":"https://pubmed.ncbi.nlm.nih.gov/35836922","citation_count":4,"is_preprint":false},{"pmid":"38068690","id":"PMC_38068690","title":"New Insights on the Role of ß-Cyanoalanine Synthase CAS-C1 in Root Hair Elongation through Single-Cell Proteomics.","date":"2023","source":"Plants (Basel, Switzerland)","url":"https://pubmed.ncbi.nlm.nih.gov/38068690","citation_count":2,"is_preprint":false},{"pmid":"24112636","id":"PMC_24112636","title":"Induced resistance to Botrytis cinerea in Capsicum annuum by a Fusarium crude elicitor fraction, free of proteins.","date":"2013","source":"Plant biology (Stuttgart, Germany)","url":"https://pubmed.ncbi.nlm.nih.gov/24112636","citation_count":2,"is_preprint":false},{"pmid":"38094437","id":"PMC_38094437","title":"Retracted: CASC1 Expression in Bladder Cancer Is Regulated 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in vivo xenograft growth assay after RNAi knockdown\",\n      \"journal\": \"Cancer research\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — clean RNAi knockdown with defined cellular phenotype (spindle checkpoint, microtubule polymerization) and in vivo validation, single lab, two orthogonal readouts\",\n      \"pmids\": [\"24860162\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2006,\n      \"finding\": \"Casc1 knockout mice showed increased susceptibility to chemical induction of lung tumors, establishing a tumor-suppressive role for CASC1 in vivo. Additionally, in vitro colony formation assays showed that the A/J allele of Casc1 produced ~5-6-fold fewer transfectants in human lung cancer cell lines compared to the C57BL/6J allele, indicating allele-specific modulation of cancer cell growth not mediated by apoptosis.\",\n      \"method\": \"Casc1 knockout mouse tumor bioassay; in vitro colony formation assay with allelic variant transfection in human lung cancer cell lines (A549, NCI-H520)\",\n      \"journal\": \"Nature genetics / Cancer letters\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — two independent experimental approaches (KO mouse bioassay and in vitro colony assay) from two papers, consistent direction of effect\",\n      \"pmids\": [\"16862160\", \"16458428\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"IC97 (the Chlamydomonas ortholog of DNAI7/CFAP94), an intermediate chain of the flagellar dynein IDA f/I1, is required for normal flagellar beat frequency and coordination between the two flagella; loss of IC97 in a Chlamydomonas mutant resulted in slow swimming, low beat frequency, and miscoordination of cis- and trans-flagella, without abolishing phototaxis.\",\n      \"method\": \"Isolation of Chlamydomonas ic97 null mutant; phenotypic analysis of flagellar motility (beat frequency, swimming path, phototaxis); biochemical analysis of IDA f/I1 complex assembly\",\n      \"journal\": \"mSphere\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — clean null mutant with defined flagellar phenotypes and biochemical complex assembly analysis; single lab but multiple orthogonal readouts (motility, beat frequency, coordination)\",\n      \"pmids\": [\"39601552\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"DNAI7 (also known as CASC1/CFAP94/PPP1R54) encodes an intermediate chain of the inner dynein arm IDA f/I1 complex required for flagellar beat frequency and inter-flagellar coordination (established in Chlamydomonas IC97 ortholog); in mammalian cells, CASC1 supports microtubule polymerization and spindle assembly checkpoint satisfaction, and functions as a tumor suppressor whose loss increases lung tumor susceptibility in mice.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"DNAI7 (CASC1/CFAP94/PPP1R54) is an intermediate chain of the flagellar inner dynein arm IDA f/I1 complex and, in mammalian cells, a regulator of mitotic microtubule dynamics with tumor-suppressive activity. In Chlamydomonas, its ortholog IC97 is required for normal flagellar beat frequency and for coordination between the two flagella, and its loss produces slow swimming and beat miscoordination without abolishing phototaxis, defining a role in ciliary/flagellar motility [#2]. In mammalian cells, CASC1 is required for microtubule polymerization and satisfaction of the spindle assembly checkpoint, and its depletion sensitizes paclitaxel-resistant lung cancer cells to spindle poisons and inhibits tumor growth in vivo [#0]. Casc1 also acts as a tumor suppressor in vivo, where its loss increases susceptibility to chemically induced lung tumors and an allelic variant modulates cancer cell growth [#1]. Beyond these motility and mitotic roles, no further mechanistic detail has been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2006,\n      \"claim\": \"Established that CASC1 functions as a lung tumor suppressor in vivo, defining its physiological relevance to cancer susceptibility.\",\n      \"evidence\": \"Casc1 knockout mouse chemical-induction tumor bioassay plus allele-specific in vitro colony formation in human lung cancer cell lines\",\n      \"pmids\": [\"16862160\", \"16458428\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Molecular mechanism linking CASC1 loss to tumorigenesis not defined\",\n        \"Allele-specific growth effect not mechanistically explained beyond exclusion of apoptosis\"\n      ]\n    },\n    {\n      \"year\": 2014,\n      \"claim\": \"Connected CASC1 to mitotic spindle function, showing it is required for microtubule polymerization and spindle assembly checkpoint satisfaction and that its loss can resensitize drug-resistant tumor cells.\",\n      \"evidence\": \"Genome-wide RNAi screen with live-cell imaging of mitotic fate and in vivo xenograft growth assay in NSCLC cells\",\n      \"pmids\": [\"24860162\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Direct biochemical interaction of CASC1 with microtubules or checkpoint proteins not demonstrated\",\n        \"Single-lab RNAi without genetic rescue\",\n        \"Relationship between this mitotic role and the dynein/flagellar role unresolved\"\n      ]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Identified the molecular identity of the DNAI7 ortholog as an IDA f/I1 inner dynein arm intermediate chain governing flagellar beat frequency and inter-flagellar coordination.\",\n      \"evidence\": \"Chlamydomonas ic97 null mutant with flagellar motility, beat frequency, and coordination phenotyping plus biochemical analysis of IDA f/I1 assembly\",\n      \"pmids\": [\"39601552\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Direct evidence for an analogous dynein role in human cells absent\",\n        \"How the same protein reconciles flagellar dynein and mitotic spindle functions unknown\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"Whether the mammalian mitotic/tumor-suppressor role and the conserved flagellar dynein intermediate-chain role reflect a single unified molecular activity remains unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No structural model of human DNAI7 in either context\",\n        \"Direct binding partners in human cells not identified\",\n        \"Tissue-specific functions of motility vs mitotic roles not delineated\"\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0008092\", \"supporting_discovery_ids\": [0, 2]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005929\", \"supporting_discovery_ids\": [2]},\n      {\"term_id\": \"GO:0005856\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-1640170\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"complexes\": [\"inner dynein arm IDA f/I1\"],\n    \"partners\": [],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":3,"faith_total":3,"faith_pct":100.0}}