{"gene":"ARMH1","run_date":"2026-06-09T22:02:44","timeline":{"discoveries":[{"year":2024,"finding":"ARMH1 knockdown in leukemia cell lines significantly reduced cell proliferation and migration, and knockdown led to downregulation of key cell cycle regulators CDCA7 and EZH2, placing ARMH1 upstream of these regulators in the cell cycle pathway.","method":"ARMH1 knockdown and overexpression in leukemia cell lines with functional proliferation and migration assays, and bulk RNA-seq pathway analysis","journal":"Frontiers in oncology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — loss-of-function with defined cellular phenotype and RNA-seq pathway placement, single lab, multiple orthogonal methods","pmids":["39703843"],"is_preprint":false},{"year":2024,"finding":"ARMH1 physically interacts with EZH2, as established by co-immunoprecipitation in leukemia cell lines.","method":"Co-immunoprecipitation","journal":"Frontiers in oncology","confidence":"Medium","confidence_rationale":"Tier 3 / Weak — single Co-IP experiment, single lab, no reciprocal validation described in abstract","pmids":["39703843"],"is_preprint":false},{"year":2024,"finding":"ARMH1 knockdown led to significant reduction in CPT1A expression, ATP production, and Oxygen Consumption Rate, linking ARMH1 to mitochondrial fatty acid synthesis regulation; conversely, pharmacological inhibition of CPT1A (a key enzyme in fatty acid synthesis regulation) resulted in ARMH1 downregulation, indicating a reciprocal regulatory relationship.","method":"ARMH1 knockdown in leukemia cell lines, Seahorse mitochondrial function assay, pharmacological CPT1A inhibition","journal":"Frontiers in oncology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — functional assay (Seahorse) combined with pharmacological perturbation, single lab, multiple orthogonal methods","pmids":["39703843"],"is_preprint":false}],"current_model":"ARMH1 is a protein that physically interacts with the epigenetic regulator EZH2 and functionally connects to mitochondrial fatty acid synthesis (via CPT1A) and cell cycle regulation (CDCA7, EZH2), such that its loss reduces proliferation, migration, and mitochondrial oxidative metabolism in leukemia cells."},"narrative":{"mechanistic_narrative":"ARMH1 is a regulator of leukemia cell proliferation and migration that links cell cycle control to mitochondrial oxidative metabolism [PMID:39703843]. ARMH1 acts upstream of the cell cycle regulators CDCA7 and EZH2, with its knockdown downregulating both, and it physically associates with the epigenetic regulator EZH2 [PMID:39703843]. ARMH1 loss also reduces CPT1A expression, ATP production, and oxygen consumption, and CPT1A inhibition reciprocally lowers ARMH1, defining a feedback relationship between ARMH1 and mitochondrial fatty acid metabolism [PMID:39703843]. Beyond these findings in leukemia cell lines, no further mechanistic detail — including the molecular activity, domain function, or mechanism by which ARMH1 controls these targets — has been characterized in the available corpus.","teleology":[{"year":2024,"claim":"Whether ARMH1 has any role in cancer cell behavior was unknown; loss- and gain-of-function established it as a positive regulator of proliferation and migration acting upstream of cell cycle regulators.","evidence":"ARMH1 knockdown/overexpression with proliferation and migration assays plus bulk RNA-seq in leukemia cell lines","pmids":["39703843"],"confidence":"Medium","gaps":["Mechanism by which ARMH1 controls CDCA7 and EZH2 expression is not defined","Single lab, single cancer context (leukemia)","No in vivo validation of the proliferation/migration phenotype"]},{"year":2024,"claim":"To address how ARMH1 connects to epigenetic cell cycle control, a physical interaction with EZH2 was tested, establishing ARMH1 as an EZH2-associated protein.","evidence":"Co-immunoprecipitation in leukemia cell lines","pmids":["39703843"],"confidence":"Medium","gaps":["Single Co-IP without reciprocal validation","Interaction interface and whether it is direct are unknown","Functional consequence of the ARMH1–EZH2 interaction not dissected"]},{"year":2024,"claim":"Whether ARMH1 influences cellular metabolism was unaddressed; perturbation experiments linked it to mitochondrial oxidative function and CPT1A in a reciprocal regulatory loop.","evidence":"ARMH1 knockdown with Seahorse mitochondrial assay and pharmacological CPT1A inhibition in leukemia cell lines","pmids":["39703843"],"confidence":"Medium","gaps":["Molecular mechanism of the ARMH1–CPT1A reciprocal regulation is unknown","Whether the metabolic effect is direct or secondary to the proliferation phenotype is unresolved"]},{"year":null,"claim":"The biochemical activity of ARMH1 and how it mechanistically connects EZH2-dependent cell cycle control to mitochondrial fatty acid metabolism remain unknown.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No molecular activity or enzymatic function established","No structural model or domain-level mechanism","Subcellular localization not determined in the corpus"]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":[],"partners":["EZH2"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q6PIY5","full_name":"Armadillo-like helical domain containing protein 1","aliases":["p40"],"length_aa":440,"mass_kda":48.9,"function":"","subcellular_location":"","url":"https://www.uniprot.org/uniprotkb/Q6PIY5/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/ARMH1","classification":"Not Classified","n_dependent_lines":75,"n_total_lines":1208,"dependency_fraction":0.062086092715231786},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[],"url":"https://opencell.sf.czbiohub.org/search/ARMH1","total_profiled":1310},"omim":[],"hpa":{"profiled":true,"resolved_as":"","reliability":"Enhanced","locations":[{"location":"Plasma membrane","reliability":"Enhanced"},{"location":"Cytosol","reliability":"Enhanced"}],"tissue_specificity":"Tissue enhanced","tissue_distribution":"Detected in many","driving_tissues":[{"tissue":"fallopian tube","ntpm":7.7},{"tissue":"testis","ntpm":10.9}],"url":"https://www.proteinatlas.org/search/ARMH1"},"hgnc":{"alias_symbol":["MGC33556","p40"],"prev_symbol":["NCRNA00082","C1orf228"]},"alphafold":{"accession":"Q6PIY5","domains":[{"cath_id":"-","chopping":"222-278_291-411","consensus_level":"medium","plddt":90.1134,"start":222,"end":411}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q6PIY5","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q6PIY5-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q6PIY5-F1-predicted_aligned_error_v6.png","plddt_mean":87.94},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=ARMH1","jax_strain_url":"https://www.jax.org/strain/search?query=ARMH1"},"sequence":{"accession":"Q6PIY5","fasta_url":"https://rest.uniprot.org/uniprotkb/Q6PIY5.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q6PIY5/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q6PIY5"}},"corpus_meta":[{"pmid":"37798266","id":"PMC_37798266","title":"Single-cell analysis reveals altered tumor microenvironments of relapse- and remission-associated pediatric acute myeloid leukemia.","date":"2023","source":"Nature communications","url":"https://pubmed.ncbi.nlm.nih.gov/37798266","citation_count":56,"is_preprint":false},{"pmid":"26655762","id":"PMC_26655762","title":"A Fivefold Parallelized Biosynthetic Process Secures Chlorination of Armillaria mellea (Honey Mushroom) Toxins.","date":"2015","source":"Applied and environmental microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/26655762","citation_count":28,"is_preprint":false},{"pmid":"37532715","id":"PMC_37532715","title":"Pediatric T-cell acute lymphoblastic leukemia blast signature and MRD associated immune environment changes defined by single cell transcriptomics analysis.","date":"2023","source":"Scientific reports","url":"https://pubmed.ncbi.nlm.nih.gov/37532715","citation_count":16,"is_preprint":false},{"pmid":"39703843","id":"PMC_39703843","title":"ARMH1 is a novel marker associated with poor pediatric AML outcomes that affect the fatty acid synthesis and cell cycle pathways.","date":"2024","source":"Frontiers in oncology","url":"https://pubmed.ncbi.nlm.nih.gov/39703843","citation_count":1,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":4267,"output_tokens":688,"usd":0.01156,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":7119,"output_tokens":1376,"usd":0.034998,"stage2_stop_reason":"end_turn"},"total_usd":0.046558,"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\": 2024,\n      \"finding\": \"ARMH1 knockdown in leukemia cell lines significantly reduced cell proliferation and migration, and knockdown led to downregulation of key cell cycle regulators CDCA7 and EZH2, placing ARMH1 upstream of these regulators in the cell cycle pathway.\",\n      \"method\": \"ARMH1 knockdown and overexpression in leukemia cell lines with functional proliferation and migration assays, and bulk RNA-seq pathway analysis\",\n      \"journal\": \"Frontiers in oncology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — loss-of-function with defined cellular phenotype and RNA-seq pathway placement, single lab, multiple orthogonal methods\",\n      \"pmids\": [\"39703843\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"ARMH1 physically interacts with EZH2, as established by co-immunoprecipitation in leukemia cell lines.\",\n      \"method\": \"Co-immunoprecipitation\",\n      \"journal\": \"Frontiers in oncology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single Co-IP experiment, single lab, no reciprocal validation described in abstract\",\n      \"pmids\": [\"39703843\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"ARMH1 knockdown led to significant reduction in CPT1A expression, ATP production, and Oxygen Consumption Rate, linking ARMH1 to mitochondrial fatty acid synthesis regulation; conversely, pharmacological inhibition of CPT1A (a key enzyme in fatty acid synthesis regulation) resulted in ARMH1 downregulation, indicating a reciprocal regulatory relationship.\",\n      \"method\": \"ARMH1 knockdown in leukemia cell lines, Seahorse mitochondrial function assay, pharmacological CPT1A inhibition\",\n      \"journal\": \"Frontiers in oncology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — functional assay (Seahorse) combined with pharmacological perturbation, single lab, multiple orthogonal methods\",\n      \"pmids\": [\"39703843\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"ARMH1 is a protein that physically interacts with the epigenetic regulator EZH2 and functionally connects to mitochondrial fatty acid synthesis (via CPT1A) and cell cycle regulation (CDCA7, EZH2), such that its loss reduces proliferation, migration, and mitochondrial oxidative metabolism in leukemia cells.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"ARMH1 is a regulator of leukemia cell proliferation and migration that links cell cycle control to mitochondrial oxidative metabolism [#0, #2]. ARMH1 acts upstream of the cell cycle regulators CDCA7 and EZH2, with its knockdown downregulating both, and it physically associates with the epigenetic regulator EZH2 [#0, #1]. ARMH1 loss also reduces CPT1A expression, ATP production, and oxygen consumption, and CPT1A inhibition reciprocally lowers ARMH1, defining a feedback relationship between ARMH1 and mitochondrial fatty acid metabolism [#2]. Beyond these findings in leukemia cell lines, no further mechanistic detail — including the molecular activity, domain function, or mechanism by which ARMH1 controls these targets — has been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2024,\n      \"claim\": \"Whether ARMH1 has any role in cancer cell behavior was unknown; loss- and gain-of-function established it as a positive regulator of proliferation and migration acting upstream of cell cycle regulators.\",\n      \"evidence\": \"ARMH1 knockdown/overexpression with proliferation and migration assays plus bulk RNA-seq in leukemia cell lines\",\n      \"pmids\": [\"39703843\"],\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\n        \"Mechanism by which ARMH1 controls CDCA7 and EZH2 expression is not defined\",\n        \"Single lab, single cancer context (leukemia)\",\n        \"No in vivo validation of the proliferation/migration phenotype\"\n      ]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"To address how ARMH1 connects to epigenetic cell cycle control, a physical interaction with EZH2 was tested, establishing ARMH1 as an EZH2-associated protein.\",\n      \"evidence\": \"Co-immunoprecipitation in leukemia cell lines\",\n      \"pmids\": [\"39703843\"],\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\n        \"Single Co-IP without reciprocal validation\",\n        \"Interaction interface and whether it is direct are unknown\",\n        \"Functional consequence of the ARMH1–EZH2 interaction not dissected\"\n      ]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Whether ARMH1 influences cellular metabolism was unaddressed; perturbation experiments linked it to mitochondrial oxidative function and CPT1A in a reciprocal regulatory loop.\",\n      \"evidence\": \"ARMH1 knockdown with Seahorse mitochondrial assay and pharmacological CPT1A inhibition in leukemia cell lines\",\n      \"pmids\": [\"39703843\"],\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\n        \"Molecular mechanism of the ARMH1–CPT1A reciprocal regulation is unknown\",\n        \"Whether the metabolic effect is direct or secondary to the proliferation phenotype is unresolved\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The biochemical activity of ARMH1 and how it mechanistically connects EZH2-dependent cell cycle control to mitochondrial fatty acid metabolism remain unknown.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\n        \"No molecular activity or enzymatic function established\",\n        \"No structural model or domain-level mechanism\",\n        \"Subcellular localization not determined in the corpus\"\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [],\n    \"localization\": [],\n    \"pathway\": [],\n    \"complexes\": [],\n    \"partners\": [\"EZH2\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"faith_supported":3,"faith_total":3,"faith_pct":100.0}}