{"gene":"DZANK1","run_date":"2026-06-09T23:54:42","timeline":{"discoveries":[{"year":2015,"finding":"DZANK1 physically interacts with NINL (Ninein-like protein), identified as a novel binding partner, and together they associate with complementary subunits of the cytoplasmic dynein 1 motor complex.","method":"Proteomic interaction screen and co-immunoprecipitation/pulldown","journal":"PLoS genetics","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — proteomic identification of interaction plus in vivo zebrafish functional validation with multiple orthogonal readouts (vesicle accumulation, rhodopsin mislocalization, melanosome transport), single lab","pmids":["26485514"],"is_preprint":false},{"year":2015,"finding":"Loss of Dzank1 in zebrafish causes dysmorphic photoreceptor outer segments, accumulation of trans-Golgi-derived vesicles, and mislocalization of Rhodopsin and Ush2a, establishing a role for DZANK1 in intracellular dynein-based (minus-end directed) vesicle transport essential for photoreceptor development.","method":"Zebrafish loss-of-function (morpholino/genetic knockdown) with confocal imaging, organelle marker localization, and electron microscopy","journal":"PLoS genetics","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — clean loss-of-function in vivo with multiple specific cellular phenotype readouts (vesicle accumulation, cargo mislocalization, retrograde transport defect), single lab","pmids":["26485514"],"is_preprint":false},{"year":2015,"finding":"Retrograde melanosome transport is severely impaired in zebrafish lacking Dzank1, demonstrating a direct role for DZANK1 in dynein-based retrograde intracellular transport.","method":"Zebrafish loss-of-function with live imaging of melanosome transport","journal":"PLoS genetics","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — functional transport assay in vivo, single lab, clear directional transport phenotype","pmids":["26485514"],"is_preprint":false},{"year":2015,"finding":"Double loss-of-function of both Ninl and Dzank1 in zebrafish leads to synergistic worsening of photoreceptor outer segment defects, supporting a co-functional relationship (genetic epistasis) between NINL and DZANK1 in the same dynein complex assembly pathway.","method":"Zebrafish double morpholino knockdown with epistasis analysis","journal":"PLoS genetics","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — genetic epistasis via double knockdown with quantified synergistic phenotype, single lab","pmids":["26485514"],"is_preprint":false}],"current_model":"DZANK1 physically interacts with NINL and together they associate with complementary subunits of the cytoplasmic dynein 1 motor complex, promoting its proper assembly and folding; loss of DZANK1 disrupts dynein-based minus-end directed vesicle transport, causing accumulation of trans-Golgi-derived vesicles, mislocalization of photoreceptor cargo (Rhodopsin, Ush2a), impaired retrograde melanosome transport, and dysmorphic photoreceptor outer segments in zebrafish."},"narrative":{"mechanistic_narrative":"DZANK1 functions as an assembly factor for the cytoplasmic dynein 1 motor that drives minus-end-directed, retrograde intracellular vesicle transport [PMID:26485514]. It physically interacts with NINL (Ninein-like protein), and the two proteins together associate with complementary subunits of the cytoplasmic dynein 1 complex, promoting its proper assembly [PMID:26485514]; double loss-of-function of NINL and DZANK1 produces synergistic photoreceptor defects, placing the two in a shared dynein-assembly pathway [PMID:26485514]. Loss of Dzank1 in zebrafish disrupts dynein-based transport, causing accumulation of trans-Golgi-derived vesicles, mislocalization of the photoreceptor cargoes Rhodopsin and Ush2a, dysmorphic photoreceptor outer segments [PMID:26485514], and severely impaired retrograde melanosome transport [PMID:26485514]. Beyond this dynein-assembly and retrograde transport role, no further mechanistic detail has been characterized in the available corpus.","teleology":[{"year":2015,"claim":"Established DZANK1's molecular context by identifying its physical partner and linking the pair to the dynein motor, answering what protein machinery DZANK1 acts within.","evidence":"Proteomic interaction screen with co-immunoprecipitation/pulldown identifying NINL binding and association with cytoplasmic dynein 1 subunits","pmids":["26485514"],"confidence":"Medium","gaps":["Interaction characterized in a single lab without reciprocal structural validation","Stoichiometry and direct contact residues between DZANK1, NINL, and dynein subunits not defined","Whether DZANK1 acts catalytically or as a scaffold in assembly is unresolved"]},{"year":2015,"claim":"Defined the cellular consequence of DZANK1 loss, answering whether the protein is required for retrograde dynein-based transport and photoreceptor cargo trafficking.","evidence":"Zebrafish loss-of-function with confocal imaging, organelle marker localization, electron microscopy, and live melanosome transport assays","pmids":["26485514"],"confidence":"Medium","gaps":["Phenotypes from morpholino knockdown not confirmed with stable genetic alleles","Mechanism connecting DZANK1 loss to vesicle accumulation versus cargo mislocalization not separated","No mammalian or human cellular validation in the corpus"]},{"year":2015,"claim":"Tested the functional relationship between NINL and DZANK1, answering whether they act in a common pathway.","evidence":"Zebrafish double morpholino knockdown with quantified synergistic photoreceptor outer segment defects (epistasis analysis)","pmids":["26485514"],"confidence":"Medium","gaps":["Synergy inferred from double knockdown without biochemical reconstitution of the assembly pathway","Order of action between NINL and DZANK1 in dynein assembly not resolved"]},{"year":null,"claim":"Whether DZANK1 has any enzymatic activity, a defined structural role in dynein folding, or disease relevance in humans remains unaddressed.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No human disease linkage established in the corpus","No structural model of DZANK1 or its dynein-assembly interface","No biochemical definition of how DZANK1 promotes dynein assembly or folding"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0060090","term_label":"molecular adaptor activity","supporting_discovery_ids":[0]}],"localization":[{"term_id":"GO:0005794","term_label":"Golgi apparatus","supporting_discovery_ids":[1]},{"term_id":"GO:0031410","term_label":"cytoplasmic vesicle","supporting_discovery_ids":[1,2]}],"pathway":[{"term_id":"R-HSA-5653656","term_label":"Vesicle-mediated transport","supporting_discovery_ids":[1,2]}],"complexes":[],"partners":["NINL"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q9NVP4","full_name":"Double zinc ribbon and ankyrin repeat-containing protein 1","aliases":[],"length_aa":752,"mass_kda":82.2,"function":"Involved in vesicle transport in photoreceptor cells","subcellular_location":"Cytoplasm, cytoskeleton, microtubule organizing center, centrosome; Cytoplasm, cytoskeleton, cilium basal body","url":"https://www.uniprot.org/uniprotkb/Q9NVP4/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/DZANK1","classification":"Not Classified","n_dependent_lines":0,"n_total_lines":1208,"dependency_fraction":0.0},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[],"url":"https://opencell.sf.czbiohub.org/search/DZANK1","total_profiled":1310},"omim":[{"mim_id":"620905","title":"DOUBLE ZINC RIBBON AND ANKYRIN REPEAT DOMAINS 1; DZANK1","url":"https://www.omim.org/entry/620905"},{"mim_id":"609580","title":"NINEIN-LIKE PROTEIN; NINL","url":"https://www.omim.org/entry/609580"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"","locations":[],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in many","driving_tissues":[],"url":"https://www.proteinatlas.org/search/DZANK1"},"hgnc":{"alias_symbol":["FLJ10600","dJ568F9.2","FLJ30892","bA189K21.8","ANKRD64"],"prev_symbol":["C20orf84","C20orf12"]},"alphafold":{"accession":"Q9NVP4","domains":[{"cath_id":"2.60.40","chopping":"11-104","consensus_level":"high","plddt":84.2616,"start":11,"end":104},{"cath_id":"-","chopping":"215-242_287-313_363-392","consensus_level":"medium","plddt":69.5342,"start":215,"end":392},{"cath_id":"1.25.40.20","chopping":"605-747","consensus_level":"high","plddt":87.522,"start":605,"end":747}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q9NVP4","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q9NVP4-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q9NVP4-F1-predicted_aligned_error_v6.png","plddt_mean":64.88},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=DZANK1","jax_strain_url":"https://www.jax.org/strain/search?query=DZANK1"},"sequence":{"accession":"Q9NVP4","fasta_url":"https://rest.uniprot.org/uniprotkb/Q9NVP4.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q9NVP4/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q9NVP4"}},"corpus_meta":[{"pmid":"24523945","id":"PMC_24523945","title":"Functionally enigmatic genes: a case study of the brain ignorome.","date":"2014","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/24523945","citation_count":78,"is_preprint":false},{"pmid":"26485514","id":"PMC_26485514","title":"NINL and DZANK1 Co-function in Vesicle Transport and Are Essential for Photoreceptor Development in Zebrafish.","date":"2015","source":"PLoS genetics","url":"https://pubmed.ncbi.nlm.nih.gov/26485514","citation_count":25,"is_preprint":false},{"pmid":"29541990","id":"PMC_29541990","title":"A genome-wide association study on growth traits in orange-spotted grouper (Epinephelus coioides) with RAD-seq genotyping.","date":"2018","source":"Science China. Life sciences","url":"https://pubmed.ncbi.nlm.nih.gov/29541990","citation_count":24,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":3784,"output_tokens":950,"usd":0.012801,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":7454,"output_tokens":1600,"usd":0.038635,"stage2_stop_reason":"end_turn"},"total_usd":0.051436,"stage1_batch_id":"msgbatch_01AsR7g8dGTEiEw9U83bJeWn","stage2_batch_id":"msgbatch_01YV5ZyxtFNUZEjxRcpd9jzb","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2015,\n      \"finding\": \"DZANK1 physically interacts with NINL (Ninein-like protein), identified as a novel binding partner, and together they associate with complementary subunits of the cytoplasmic dynein 1 motor complex.\",\n      \"method\": \"Proteomic interaction screen and co-immunoprecipitation/pulldown\",\n      \"journal\": \"PLoS genetics\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — proteomic identification of interaction plus in vivo zebrafish functional validation with multiple orthogonal readouts (vesicle accumulation, rhodopsin mislocalization, melanosome transport), single lab\",\n      \"pmids\": [\"26485514\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2015,\n      \"finding\": \"Loss of Dzank1 in zebrafish causes dysmorphic photoreceptor outer segments, accumulation of trans-Golgi-derived vesicles, and mislocalization of Rhodopsin and Ush2a, establishing a role for DZANK1 in intracellular dynein-based (minus-end directed) vesicle transport essential for photoreceptor development.\",\n      \"method\": \"Zebrafish loss-of-function (morpholino/genetic knockdown) with confocal imaging, organelle marker localization, and electron microscopy\",\n      \"journal\": \"PLoS genetics\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — clean loss-of-function in vivo with multiple specific cellular phenotype readouts (vesicle accumulation, cargo mislocalization, retrograde transport defect), single lab\",\n      \"pmids\": [\"26485514\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2015,\n      \"finding\": \"Retrograde melanosome transport is severely impaired in zebrafish lacking Dzank1, demonstrating a direct role for DZANK1 in dynein-based retrograde intracellular transport.\",\n      \"method\": \"Zebrafish loss-of-function with live imaging of melanosome transport\",\n      \"journal\": \"PLoS genetics\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — functional transport assay in vivo, single lab, clear directional transport phenotype\",\n      \"pmids\": [\"26485514\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2015,\n      \"finding\": \"Double loss-of-function of both Ninl and Dzank1 in zebrafish leads to synergistic worsening of photoreceptor outer segment defects, supporting a co-functional relationship (genetic epistasis) between NINL and DZANK1 in the same dynein complex assembly pathway.\",\n      \"method\": \"Zebrafish double morpholino knockdown with epistasis analysis\",\n      \"journal\": \"PLoS genetics\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — genetic epistasis via double knockdown with quantified synergistic phenotype, single lab\",\n      \"pmids\": [\"26485514\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"DZANK1 physically interacts with NINL and together they associate with complementary subunits of the cytoplasmic dynein 1 motor complex, promoting its proper assembly and folding; loss of DZANK1 disrupts dynein-based minus-end directed vesicle transport, causing accumulation of trans-Golgi-derived vesicles, mislocalization of photoreceptor cargo (Rhodopsin, Ush2a), impaired retrograde melanosome transport, and dysmorphic photoreceptor outer segments in zebrafish.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"DZANK1 functions as an assembly factor for the cytoplasmic dynein 1 motor that drives minus-end-directed, retrograde intracellular vesicle transport [#0, #1]. It physically interacts with NINL (Ninein-like protein), and the two proteins together associate with complementary subunits of the cytoplasmic dynein 1 complex, promoting its proper assembly [#0]; double loss-of-function of NINL and DZANK1 produces synergistic photoreceptor defects, placing the two in a shared dynein-assembly pathway [#3]. Loss of Dzank1 in zebrafish disrupts dynein-based transport, causing accumulation of trans-Golgi-derived vesicles, mislocalization of the photoreceptor cargoes Rhodopsin and Ush2a, dysmorphic photoreceptor outer segments [#1], and severely impaired retrograde melanosome transport [#2]. Beyond this dynein-assembly and retrograde transport role, no further mechanistic detail has been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2015,\n      \"claim\": \"Established DZANK1's molecular context by identifying its physical partner and linking the pair to the dynein motor, answering what protein machinery DZANK1 acts within.\",\n      \"evidence\": \"Proteomic interaction screen with co-immunoprecipitation/pulldown identifying NINL binding and association with cytoplasmic dynein 1 subunits\",\n      \"pmids\": [\"26485514\"],\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\n        \"Interaction characterized in a single lab without reciprocal structural validation\",\n        \"Stoichiometry and direct contact residues between DZANK1, NINL, and dynein subunits not defined\",\n        \"Whether DZANK1 acts catalytically or as a scaffold in assembly is unresolved\"\n      ]\n    },\n    {\n      \"year\": 2015,\n      \"claim\": \"Defined the cellular consequence of DZANK1 loss, answering whether the protein is required for retrograde dynein-based transport and photoreceptor cargo trafficking.\",\n      \"evidence\": \"Zebrafish loss-of-function with confocal imaging, organelle marker localization, electron microscopy, and live melanosome transport assays\",\n      \"pmids\": [\"26485514\"],\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\n        \"Phenotypes from morpholino knockdown not confirmed with stable genetic alleles\",\n        \"Mechanism connecting DZANK1 loss to vesicle accumulation versus cargo mislocalization not separated\",\n        \"No mammalian or human cellular validation in the corpus\"\n      ]\n    },\n    {\n      \"year\": 2015,\n      \"claim\": \"Tested the functional relationship between NINL and DZANK1, answering whether they act in a common pathway.\",\n      \"evidence\": \"Zebrafish double morpholino knockdown with quantified synergistic photoreceptor outer segment defects (epistasis analysis)\",\n      \"pmids\": [\"26485514\"],\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\n        \"Synergy inferred from double knockdown without biochemical reconstitution of the assembly pathway\",\n        \"Order of action between NINL and DZANK1 in dynein assembly not resolved\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"Whether DZANK1 has any enzymatic activity, a defined structural role in dynein folding, or disease relevance in humans remains unaddressed.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\n        \"No human disease linkage established in the corpus\",\n        \"No structural model of DZANK1 or its dynein-assembly interface\",\n        \"No biochemical definition of how DZANK1 promotes dynein assembly or folding\"\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0060090\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005794\", \"supporting_discovery_ids\": [1]},\n      {\"term_id\": \"GO:0031410\", \"supporting_discovery_ids\": [1, 2]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-5653656\", \"supporting_discovery_ids\": [1, 2]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\"NINL\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"faith_supported":3,"faith_total":3,"faith_pct":100.0}}