{"gene":"HAUS4","run_date":"2026-06-10T01:55:21","timeline":{"discoveries":[{"year":2017,"finding":"HAUS4 is a component of the Augmin/HAUS complex that facilitates microtubule nucleation along the mitotic spindle; combined knockdown of HAUS5 with HAUS4 (or HAUS2) caused centrosome fragmentation and lethality in neural progenitor cells, demonstrating that HAUS4 functions redundantly within the Augmin/HAUS complex to maintain centrosome integrity during mitosis.","method":"siRNA knockdown (double knockdown of HAUS5 + HAUS4), phenotypic readout of centrosome fragmentation and cell viability in neural progenitor cells","journal":"Oncotarget","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — clean genetic knockdown with defined cellular phenotype (centrosome fragmentation, lethality), but single lab and HAUS4 role inferred from double-knockdown epistasis rather than direct mechanistic study of HAUS4 alone","pmids":["28596487"],"is_preprint":false},{"year":2020,"finding":"siRNA-mediated knockdown of HAUS4 decreased cell number, activated p16/p21, and produced morphological changes consistent with cellular senescence, placing HAUS4 among genes required to prevent senescence entry.","method":"siRNA knockdown with readouts of cell number, p16/p21 activation, and morphological assessment of senescence","journal":"Genome biology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct loss-of-function with multiple senescence markers measured, but part of a large screen and no molecular mechanism downstream of HAUS4 was defined","pmids":["32264951"],"is_preprint":false}],"current_model":"HAUS4 is a component of the Augmin/HAUS complex required for microtubule nucleation on the mitotic spindle and centrosome integrity; its loss triggers mitotic arrest, centrosome fragmentation, and cellular senescence markers including p16/p21 activation and reduced proliferation."},"narrative":{"mechanistic_narrative":"HAUS4 is a subunit of the Augmin/HAUS complex that promotes microtubule nucleation along the mitotic spindle and maintains centrosome integrity during mitosis [PMID:28596487]. Combined depletion of HAUS4 with HAUS5 causes centrosome fragmentation and lethality in neural progenitor cells, indicating that HAUS4 acts redundantly within the complex to support spindle and centrosome organization [PMID:28596487]. Loss of HAUS4 also reduces proliferation and activates the senescence markers p16 and p21, placing it among genes required to prevent senescence entry [PMID:32264951]. Beyond these complex- and phenotype-level observations, no direct biochemical mechanism for HAUS4 itself has been characterized in the available corpus.","teleology":[{"year":2017,"claim":"Established HAUS4 as a functional, partially redundant member of the Augmin/HAUS complex needed for spindle microtubule nucleation and centrosome integrity, addressing whether HAUS4 contributes to mitotic spindle assembly.","evidence":"siRNA double knockdown of HAUS5 with HAUS4 in neural progenitor cells, scoring centrosome fragmentation and viability","pmids":["28596487"],"confidence":"Medium","gaps":["HAUS4 role inferred from double-knockdown epistasis rather than direct mechanistic study of HAUS4 alone","No biochemical assay of HAUS4's contribution to microtubule nucleation","Single-lab, single cell-type observation"]},{"year":2020,"claim":"Linked HAUS4 loss-of-function to senescence entry, addressing the cellular consequence of HAUS4 depletion beyond mitotic defects.","evidence":"siRNA knockdown with readouts of cell number, p16/p21 activation, and senescence morphology","pmids":["32264951"],"confidence":"Medium","gaps":["Part of a large screen with no molecular mechanism defined downstream of HAUS4","Causal link between mitotic/centrosome defects and senescence not directly established"]},{"year":null,"claim":"The direct molecular activity of HAUS4 within the Augmin/HAUS complex and how its loss mechanistically triggers senescence remain undefined.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No structural or biochemical characterization of HAUS4's role in microtubule nucleation","No mapped interaction interfaces within the HAUS complex","Mechanism connecting centrosome fragmentation to p16/p21 activation unresolved"]}],"mechanism_profile":{"molecular_activity":[],"localization":[{"term_id":"GO:0005815","term_label":"microtubule organizing center","supporting_discovery_ids":[0]}],"pathway":[{"term_id":"R-HSA-1640170","term_label":"Cell Cycle","supporting_discovery_ids":[0]}],"complexes":["Augmin/HAUS complex"],"partners":["HAUS5","HAUS2"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q9H6D7","full_name":"HAUS augmin-like complex subunit 4","aliases":[],"length_aa":363,"mass_kda":42.4,"function":"Contributes to mitotic spindle assembly, maintenance of centrosome integrity and completion of cytokinesis as part of the HAUS augmin-like complex","subcellular_location":"Cytoplasm, cytoskeleton, microtubule organizing center, centrosome; Cytoplasm, cytoskeleton, spindle","url":"https://www.uniprot.org/uniprotkb/Q9H6D7/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":true,"resolved_as":"","url":"https://depmap.org/portal/gene/HAUS4","classification":"Common Essential","n_dependent_lines":1190,"n_total_lines":1208,"dependency_fraction":0.9850993377483444},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[{"gene":"TUBB4B","stoichiometry":0.2}],"url":"https://opencell.sf.czbiohub.org/search/HAUS4","total_profiled":1310},"omim":[{"mim_id":"613431","title":"HAUS AUGMIN-LIKE COMPLEX, SUBUNIT 4; HAUS4","url":"https://www.omim.org/entry/613431"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"","locations":[],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in all","driving_tissues":[],"url":"https://www.proteinatlas.org/search/HAUS4"},"hgnc":{"alias_symbol":["FLJ20424"],"prev_symbol":["C14orf94"]},"alphafold":{"accession":"Q9H6D7","domains":[{"cath_id":"-","chopping":"11-56","consensus_level":"medium","plddt":64.5385,"start":11,"end":56},{"cath_id":"-","chopping":"60-130_145-190","consensus_level":"medium","plddt":81.6721,"start":60,"end":190},{"cath_id":"1.20.5","chopping":"203-293","consensus_level":"medium","plddt":94.0985,"start":203,"end":293}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q9H6D7","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q9H6D7-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q9H6D7-F1-predicted_aligned_error_v6.png","plddt_mean":81.75},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=HAUS4","jax_strain_url":"https://www.jax.org/strain/search?query=HAUS4"},"sequence":{"accession":"Q9H6D7","fasta_url":"https://rest.uniprot.org/uniprotkb/Q9H6D7.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q9H6D7/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q9H6D7"}},"corpus_meta":[{"pmid":"32264951","id":"PMC_32264951","title":"A multidimensional systems biology analysis of cellular senescence in aging and disease.","date":"2020","source":"Genome biology","url":"https://pubmed.ncbi.nlm.nih.gov/32264951","citation_count":313,"is_preprint":false},{"pmid":"32285988","id":"PMC_32285988","title":"Saliva proteomics from children with caries at different severity stages.","date":"2020","source":"Oral diseases","url":"https://pubmed.ncbi.nlm.nih.gov/32285988","citation_count":16,"is_preprint":false},{"pmid":"28596487","id":"PMC_28596487","title":"ZNF131 suppresses centrosome fragmentation in glioblastoma stem-like cells through regulation of HAUS5.","date":"2017","source":"Oncotarget","url":"https://pubmed.ncbi.nlm.nih.gov/28596487","citation_count":15,"is_preprint":false},{"pmid":"41466703","id":"PMC_41466703","title":"Identification of upregulated genes in pulmonary hypertension using RNA sequencing profiling.","date":"2025","source":"Bioinformation","url":"https://pubmed.ncbi.nlm.nih.gov/41466703","citation_count":0,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":4049,"output_tokens":574,"usd":0.010379,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":6911,"output_tokens":1163,"usd":0.031815,"stage2_stop_reason":"end_turn"},"total_usd":0.042194,"stage1_batch_id":"msgbatch_01DUPACZi7AAWwuZiUjseQF4","stage2_batch_id":"msgbatch_018yt7chE3f48PEFtDwtj6AE","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2017,\n      \"finding\": \"HAUS4 is a component of the Augmin/HAUS complex that facilitates microtubule nucleation along the mitotic spindle; combined knockdown of HAUS5 with HAUS4 (or HAUS2) caused centrosome fragmentation and lethality in neural progenitor cells, demonstrating that HAUS4 functions redundantly within the Augmin/HAUS complex to maintain centrosome integrity during mitosis.\",\n      \"method\": \"siRNA knockdown (double knockdown of HAUS5 + HAUS4), phenotypic readout of centrosome fragmentation and cell viability in neural progenitor cells\",\n      \"journal\": \"Oncotarget\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — clean genetic knockdown with defined cellular phenotype (centrosome fragmentation, lethality), but single lab and HAUS4 role inferred from double-knockdown epistasis rather than direct mechanistic study of HAUS4 alone\",\n      \"pmids\": [\"28596487\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"siRNA-mediated knockdown of HAUS4 decreased cell number, activated p16/p21, and produced morphological changes consistent with cellular senescence, placing HAUS4 among genes required to prevent senescence entry.\",\n      \"method\": \"siRNA knockdown with readouts of cell number, p16/p21 activation, and morphological assessment of senescence\",\n      \"journal\": \"Genome biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct loss-of-function with multiple senescence markers measured, but part of a large screen and no molecular mechanism downstream of HAUS4 was defined\",\n      \"pmids\": [\"32264951\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"HAUS4 is a component of the Augmin/HAUS complex required for microtubule nucleation on the mitotic spindle and centrosome integrity; its loss triggers mitotic arrest, centrosome fragmentation, and cellular senescence markers including p16/p21 activation and reduced proliferation.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"HAUS4 is a subunit of the Augmin/HAUS complex that promotes microtubule nucleation along the mitotic spindle and maintains centrosome integrity during mitosis [#0]. Combined depletion of HAUS4 with HAUS5 causes centrosome fragmentation and lethality in neural progenitor cells, indicating that HAUS4 acts redundantly within the complex to support spindle and centrosome organization [#0]. Loss of HAUS4 also reduces proliferation and activates the senescence markers p16 and p21, placing it among genes required to prevent senescence entry [#1]. Beyond these complex- and phenotype-level observations, no direct biochemical mechanism for HAUS4 itself has been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2017,\n      \"claim\": \"Established HAUS4 as a functional, partially redundant member of the Augmin/HAUS complex needed for spindle microtubule nucleation and centrosome integrity, addressing whether HAUS4 contributes to mitotic spindle assembly.\",\n      \"evidence\": \"siRNA double knockdown of HAUS5 with HAUS4 in neural progenitor cells, scoring centrosome fragmentation and viability\",\n      \"pmids\": [\"28596487\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"HAUS4 role inferred from double-knockdown epistasis rather than direct mechanistic study of HAUS4 alone\",\n        \"No biochemical assay of HAUS4's contribution to microtubule nucleation\",\n        \"Single-lab, single cell-type observation\"\n      ]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"Linked HAUS4 loss-of-function to senescence entry, addressing the cellular consequence of HAUS4 depletion beyond mitotic defects.\",\n      \"evidence\": \"siRNA knockdown with readouts of cell number, p16/p21 activation, and senescence morphology\",\n      \"pmids\": [\"32264951\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Part of a large screen with no molecular mechanism defined downstream of HAUS4\",\n        \"Causal link between mitotic/centrosome defects and senescence not directly established\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The direct molecular activity of HAUS4 within the Augmin/HAUS complex and how its loss mechanistically triggers senescence remain undefined.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No structural or biochemical characterization of HAUS4's role in microtubule nucleation\",\n        \"No mapped interaction interfaces within the HAUS complex\",\n        \"Mechanism connecting centrosome fragmentation to p16/p21 activation unresolved\"\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [],\n    \"localization\": [\n      {\"term_id\": \"GO:0005815\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-1640170\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"complexes\": [\"Augmin/HAUS complex\"],\n    \"partners\": [\"HAUS5\", \"HAUS2\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":3,"faith_total":3,"faith_pct":100.0}}