{"gene":"DZANK1","run_date":"2026-04-28T17:46:03","timeline":{"discoveries":[{"year":2015,"finding":"DZANK1 was identified as a novel interaction partner of Ninein-like protein (NINL) through proteomic approaches, and together they associate with complementary subunits of the cytoplasmic dynein 1 motor complex, supporting proper assembly and folding of the dynein 1 complex.","method":"Proteomic interaction screen (Co-IP/pulldown) identifying DZANK1-NINL interaction and their association with dynein 1 subunits","journal":"PLoS genetics","confidence":"High","confidence_rationale":"Tier 2 — reciprocal interaction data combined with in vivo genetic epistasis in zebrafish across multiple orthogonal methods","pmids":["26485514"],"is_preprint":false},{"year":2015,"finding":"Loss of Dzank1 in zebrafish leads to dysmorphic photoreceptor outer segments, accumulation of trans-Golgi-derived vesicles, and mislocalization of Rhodopsin and Ush2a, establishing DZANK1 as essential for photoreceptor outer segment formation and intracellular vesicle transport.","method":"Zebrafish loss-of-function (morpholino/genetic knockdown) with immunofluorescence and electron microscopy readouts","journal":"PLoS genetics","confidence":"High","confidence_rationale":"Tier 2 — clean loss-of-function in vivo with multiple defined cellular phenotypes and molecular markers","pmids":["26485514"],"is_preprint":false},{"year":2015,"finding":"Loss of Dzank1 in zebrafish severely impairs retrograde melanosome transport, placing DZANK1 in the cytoplasmic dynein 1-mediated minus-end directed transport pathway.","method":"Zebrafish loss-of-function with live imaging of retrograde melanosome transport","journal":"PLoS genetics","confidence":"High","confidence_rationale":"Tier 2 — direct functional readout of dynein-based transport in vivo","pmids":["26485514"],"is_preprint":false},{"year":2015,"finding":"Combined loss of both Ninl and Dzank1 in zebrafish leads to synergistic photoreceptor outer segment defects, demonstrating genetic epistasis and co-function of NINL and DZANK1 in the same pathway.","method":"Double morpholino knockdown in zebrafish with synergistic phenotype assessment (genetic epistasis)","journal":"PLoS genetics","confidence":"High","confidence_rationale":"Tier 2 — genetic epistasis via double knockdown with clear synergistic phenotype","pmids":["26485514"],"is_preprint":false}],"current_model":"DZANK1 interacts with Ninein-like protein (NINL) and together they associate with complementary subunits of the cytoplasmic dynein 1 motor complex, facilitating its proper assembly and enabling minus-end directed intracellular transport essential for photoreceptor outer segment formation and retrograde vesicle/melanosome transport."},"narrative":{"teleology":[{"year":2015,"claim":"The discovery that DZANK1 physically interacts with NINL and that both associate with complementary dynein 1 subunits established DZANK1 as a previously unrecognized component of the cytoplasmic dynein 1 assembly/folding machinery, resolving how NINL connects to the motor complex.","evidence":"Reciprocal co-immunoprecipitation and proteomic pulldown in mammalian cells","pmids":["26485514"],"confidence":"High","gaps":["Structural basis of the DZANK1-NINL interaction and which dynein 1 subunits each protein contacts directly are undefined","Whether DZANK1 functions as a true assembly chaperone or an adaptor remains unclear","Mammalian in vivo loss-of-function has not been reported"]},{"year":2015,"claim":"Zebrafish loss-of-function demonstrated that DZANK1 is required for photoreceptor outer segment biogenesis and dynein 1-dependent retrograde transport, linking the biochemical interaction to a specific cellular transport process.","evidence":"Morpholino knockdown in zebrafish with electron microscopy, immunofluorescence for Rhodopsin/Ush2a, and live imaging of melanosome transport","pmids":["26485514"],"confidence":"High","gaps":["Cargo specificity beyond rhodopsin, Ush2a, and melanosomes is not characterized","Whether DZANK1 loss phenocopies dynein heavy chain mutations in all tissues is untested","No mammalian knockout or patient mutation data exist"]},{"year":2015,"claim":"Synergistic defects from combined Ninl and Dzank1 loss confirmed genetic epistasis, proving the two proteins function in the same pathway rather than in parallel.","evidence":"Double morpholino knockdown in zebrafish with quantitative assessment of photoreceptor outer segment morphology","pmids":["26485514"],"confidence":"High","gaps":["Whether the synergy reflects co-dependent dynein subunit recruitment or a shared cargo-loading step is unresolved","Epistasis with other dynein adaptors (e.g., DYNC1H1 accessory chains) has not been tested"]},{"year":null,"claim":"The mechanism by which DZANK1 promotes dynein 1 complex assembly at the molecular level, its relevance in mammalian tissues, and whether DZANK1 mutations cause human disease remain open questions.","evidence":"","pmids":[],"confidence":"Low","gaps":["No mammalian genetic model or human disease association has been reported","No structural or reconstitution data defining how DZANK1 contacts dynein subunits","Tissue-specific versus ubiquitous requirement for DZANK1 is unknown"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0008092","term_label":"cytoskeletal protein binding","supporting_discovery_ids":[0]}],"localization":[{"term_id":"GO:0005829","term_label":"cytosol","supporting_discovery_ids":[0,2]}],"pathway":[{"term_id":"GO:0005794","term_label":"Golgi apparatus","supporting_discovery_ids":[1]},{"term_id":"R-HSA-9609507","term_label":"Protein localization","supporting_discovery_ids":[1,2]},{"term_id":"R-HSA-1852241","term_label":"Organelle biogenesis and maintenance","supporting_discovery_ids":[0,1]}],"complexes":["cytoplasmic dynein 1 complex"],"partners":["NINL"],"other_free_text":[]},"mechanistic_narrative":"DZANK1 is a direct interaction partner of Ninein-like protein (NINL) that associates with complementary subunits of the cytoplasmic dynein 1 motor complex, supporting its proper assembly and folding [PMID:26485514]. Loss of DZANK1 in zebrafish causes dysmorphic photoreceptor outer segments, accumulation of trans-Golgi-derived vesicles, mislocalization of Rhodopsin and Ush2a, and severely impaired retrograde melanosome transport, establishing DZANK1 as essential for dynein 1-mediated minus-end directed intracellular transport [PMID:26485514]. Genetic epistasis between DZANK1 and NINL, demonstrated by synergistic photoreceptor defects upon combined loss, confirms their co-function in this transport pathway [PMID:26485514]."},"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":23,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":2986,"output_tokens":865,"usd":0.010967},"stage2":{"model":"claude-opus-4-6","input_tokens":4064,"output_tokens":1240,"usd":0.07698},"total_usd":0.087947,"stage1_batch_id":"msgbatch_0118RScg3WGaGkaZRtWZbtce","stage2_batch_id":"msgbatch_01Cpfzvtbj42aqp5oYZ5Te2s","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2015,\n      \"finding\": \"DZANK1 was identified as a novel interaction partner of Ninein-like protein (NINL) through proteomic approaches, and together they associate with complementary subunits of the cytoplasmic dynein 1 motor complex, supporting proper assembly and folding of the dynein 1 complex.\",\n      \"method\": \"Proteomic interaction screen (Co-IP/pulldown) identifying DZANK1-NINL interaction and their association with dynein 1 subunits\",\n      \"journal\": \"PLoS genetics\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — reciprocal interaction data combined with in vivo genetic epistasis in zebrafish across multiple orthogonal methods\",\n      \"pmids\": [\"26485514\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2015,\n      \"finding\": \"Loss of Dzank1 in zebrafish leads to dysmorphic photoreceptor outer segments, accumulation of trans-Golgi-derived vesicles, and mislocalization of Rhodopsin and Ush2a, establishing DZANK1 as essential for photoreceptor outer segment formation and intracellular vesicle transport.\",\n      \"method\": \"Zebrafish loss-of-function (morpholino/genetic knockdown) with immunofluorescence and electron microscopy readouts\",\n      \"journal\": \"PLoS genetics\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — clean loss-of-function in vivo with multiple defined cellular phenotypes and molecular markers\",\n      \"pmids\": [\"26485514\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2015,\n      \"finding\": \"Loss of Dzank1 in zebrafish severely impairs retrograde melanosome transport, placing DZANK1 in the cytoplasmic dynein 1-mediated minus-end directed transport pathway.\",\n      \"method\": \"Zebrafish loss-of-function with live imaging of retrograde melanosome transport\",\n      \"journal\": \"PLoS genetics\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — direct functional readout of dynein-based transport in vivo\",\n      \"pmids\": [\"26485514\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2015,\n      \"finding\": \"Combined loss of both Ninl and Dzank1 in zebrafish leads to synergistic photoreceptor outer segment defects, demonstrating genetic epistasis and co-function of NINL and DZANK1 in the same pathway.\",\n      \"method\": \"Double morpholino knockdown in zebrafish with synergistic phenotype assessment (genetic epistasis)\",\n      \"journal\": \"PLoS genetics\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — genetic epistasis via double knockdown with clear synergistic phenotype\",\n      \"pmids\": [\"26485514\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"DZANK1 interacts with Ninein-like protein (NINL) and together they associate with complementary subunits of the cytoplasmic dynein 1 motor complex, facilitating its proper assembly and enabling minus-end directed intracellular transport essential for photoreceptor outer segment formation and retrograde vesicle/melanosome transport.\"\n}\n```","stage2_raw":"```json\n{\n  \"mechanistic_narrative\": \"DZANK1 is a direct interaction partner of Ninein-like protein (NINL) that associates with complementary subunits of the cytoplasmic dynein 1 motor complex, supporting its proper assembly and folding [PMID:26485514]. Loss of DZANK1 in zebrafish causes dysmorphic photoreceptor outer segments, accumulation of trans-Golgi-derived vesicles, mislocalization of Rhodopsin and Ush2a, and severely impaired retrograde melanosome transport, establishing DZANK1 as essential for dynein 1-mediated minus-end directed intracellular transport [PMID:26485514]. Genetic epistasis between DZANK1 and NINL, demonstrated by synergistic photoreceptor defects upon combined loss, confirms their co-function in this transport pathway [PMID:26485514].\",\n  \"teleology\": [\n    {\n      \"year\": 2015,\n      \"claim\": \"The discovery that DZANK1 physically interacts with NINL and that both associate with complementary dynein 1 subunits established DZANK1 as a previously unrecognized component of the cytoplasmic dynein 1 assembly/folding machinery, resolving how NINL connects to the motor complex.\",\n      \"evidence\": \"Reciprocal co-immunoprecipitation and proteomic pulldown in mammalian cells\",\n      \"pmids\": [\"26485514\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Structural basis of the DZANK1-NINL interaction and which dynein 1 subunits each protein contacts directly are undefined\",\n        \"Whether DZANK1 functions as a true assembly chaperone or an adaptor remains unclear\",\n        \"Mammalian in vivo loss-of-function has not been reported\"\n      ]\n    },\n    {\n      \"year\": 2015,\n      \"claim\": \"Zebrafish loss-of-function demonstrated that DZANK1 is required for photoreceptor outer segment biogenesis and dynein 1-dependent retrograde transport, linking the biochemical interaction to a specific cellular transport process.\",\n      \"evidence\": \"Morpholino knockdown in zebrafish with electron microscopy, immunofluorescence for Rhodopsin/Ush2a, and live imaging of melanosome transport\",\n      \"pmids\": [\"26485514\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Cargo specificity beyond rhodopsin, Ush2a, and melanosomes is not characterized\",\n        \"Whether DZANK1 loss phenocopies dynein heavy chain mutations in all tissues is untested\",\n        \"No mammalian knockout or patient mutation data exist\"\n      ]\n    },\n    {\n      \"year\": 2015,\n      \"claim\": \"Synergistic defects from combined Ninl and Dzank1 loss confirmed genetic epistasis, proving the two proteins function in the same pathway rather than in parallel.\",\n      \"evidence\": \"Double morpholino knockdown in zebrafish with quantitative assessment of photoreceptor outer segment morphology\",\n      \"pmids\": [\"26485514\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Whether the synergy reflects co-dependent dynein subunit recruitment or a shared cargo-loading step is unresolved\",\n        \"Epistasis with other dynein adaptors (e.g., DYNC1H1 accessory chains) has not been tested\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The mechanism by which DZANK1 promotes dynein 1 complex assembly at the molecular level, its relevance in mammalian tissues, and whether DZANK1 mutations cause human disease remain open questions.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No mammalian genetic model or human disease association has been reported\",\n        \"No structural or reconstitution data defining how DZANK1 contacts dynein subunits\",\n        \"Tissue-specific versus ubiquitous requirement for DZANK1 is unknown\"\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0008092\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005829\", \"supporting_discovery_ids\": [0, 2]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0005794\", \"supporting_discovery_ids\": [1]},\n      {\"term_id\": \"R-HSA-9609507\", \"supporting_discovery_ids\": [1, 2]},\n      {\"term_id\": \"R-HSA-1852241\", \"supporting_discovery_ids\": [0, 1]}\n    ],\n    \"complexes\": [\n      \"cytoplasmic dynein 1 complex\"\n    ],\n    \"partners\": [\n      \"NINL\"\n    ],\n    \"other_free_text\": []\n  }\n}\n```"}