{"gene":"DEPDC7","run_date":"2026-04-28T17:46:02","timeline":{"discoveries":[{"year":2014,"finding":"DEPDC7 physically binds to CARMA2 and CARMA3 proteins (components of the CBM complex), displays cytosolic distribution, and its expression induces NF-κB activation; shRNA-mediated knockdown of DEPDC7 impairs NF-κB activation downstream of G protein-coupled receptor stimulation in a CARMA2/CARMA3-dependent (but not CARMA1-dependent) manner.","method":"Co-immunoprecipitation (binding), shRNA knockdown with NF-κB reporter assay, subcellular localization imaging","journal":"PloS one","confidence":"Medium","confidence_rationale":"Tier 2-3 — reciprocal Co-IP plus functional KD with defined pathway readout, single lab","pmids":["25541973"],"is_preprint":false},{"year":2017,"finding":"Overexpression of DEPDC7 in hepatoma cell lines inhibits cell proliferation, cell cycle entry, and cell motility/invasion, while shRNA-mediated knockdown promotes these phenotypes, establishing DEPDC7 as a negative regulator of hepatoma cell growth and migration.","method":"Overexpression and shRNA knockdown in SK-Hep-1 and Huh-7/HepG2 hepatoma cell lines; proliferation, cell cycle, migration and invasion assays","journal":"Oncology letters","confidence":"Medium","confidence_rationale":"Tier 2 — bidirectional loss- and gain-of-function with multiple phenotypic readouts, single lab","pmids":["29344171"],"is_preprint":false},{"year":2016,"finding":"shRNA-mediated knockdown of DEPDC7 in HepG2 hepatocellular carcinoma cells significantly increases cell migration and invasion, confirming a role for DEPDC7 in suppressing cell motility.","method":"Lentiviral shRNA knockdown; Matrigel migration and invasion assay; RT-PCR and western blot for knockdown confirmation","journal":"Interdisciplinary sciences, computational life sciences","confidence":"Medium","confidence_rationale":"Tier 2 — clean KD with defined cellular phenotype, single lab, consistent with parallel studies","pmids":["27016254"],"is_preprint":false},{"year":2026,"finding":"DEPDC7 localizes to both cytoplasm and nucleus in HCC cells; its overexpression suppresses the JAK1/STAT3 signaling pathway (downregulating JAK1 and STAT3), inhibits EMT (increasing E-cadherin, decreasing N-cadherin and vimentin), and promotes cell cycle arrest and apoptosis. Co-immunoprecipitation and molecular docking confirmed direct physical interaction between DEPDC7 and the JAK1 kinase domain.","method":"RNA-seq, Co-immunoprecipitation, molecular docking, overexpression in Huh-7 cells, western blot, scanning electron microscopy, subcellular localization","journal":"Frontiers in oncology","confidence":"Medium","confidence_rationale":"Tier 2-3 — Co-IP plus RNA-seq plus functional overexpression with multiple readouts, single lab","pmids":["41930189"],"is_preprint":false}],"current_model":"DEPDC7 is a cytoplasmic (and nuclear) DEP/RhoGAP domain-containing protein that acts as a tumor suppressor in hepatocellular carcinoma by binding to CARMA2/CARMA3 to modulate NF-κB activation downstream of GPCRs, directly interacting with the JAK1 kinase domain to suppress JAK1/STAT3 signaling, attenuating epithelial-mesenchymal transition, and restraining hepatoma cell proliferation, cell cycle progression, and invasion."},"narrative":{"teleology":[{"year":2014,"claim":"The molecular partners and signaling output of DEPDC7 were unknown; co-immunoprecipitation revealed that DEPDC7 physically binds CARMA2 and CARMA3 and is required for NF-κB activation downstream of GPCRs, establishing it as a component of CBM-dependent innate signaling.","evidence":"Co-immunoprecipitation, shRNA knockdown with NF-κB reporter assay, subcellular localization imaging in HEK293T and related cell lines","pmids":["25541973"],"confidence":"Medium","gaps":["No reciprocal validation in an independent lab","Whether DEPDC7 acts catalytically (e.g., via its RhoGAP-like domain) or as a scaffold for CBM assembly is unresolved","Physiological GPCR ligands and tissue contexts for this NF-κB role are not defined"]},{"year":2016,"claim":"Whether DEPDC7 influences cancer cell behavior was untested; knockdown in hepatoma cells increased migration and invasion, providing the first evidence for a tumor-suppressive role.","evidence":"Lentiviral shRNA knockdown in HepG2 cells; Matrigel migration and invasion assays","pmids":["27016254"],"confidence":"Medium","gaps":["Single cell line and single lab; awaits independent confirmation","Downstream effectors mediating the anti-migratory effect are not identified"]},{"year":2017,"claim":"Bidirectional gain- and loss-of-function experiments extended the tumor-suppressive phenotype to proliferation and cell cycle control, consolidating DEPDC7 as a negative regulator of hepatoma cell growth and motility.","evidence":"Overexpression and shRNA knockdown in SK-Hep-1, Huh-7, and HepG2 hepatoma lines; proliferation, cell cycle, migration, and invasion assays","pmids":["29344171"],"confidence":"Medium","gaps":["No in vivo tumor model","Mechanism connecting DEPDC7 to cell cycle arrest not molecularly defined"]},{"year":2026,"claim":"The signaling pathway through which DEPDC7 suppresses hepatoma growth was identified: DEPDC7 directly binds the JAK1 kinase domain to suppress JAK1/STAT3 signaling and EMT, linking its tumor-suppressive activity to a defined kinase target.","evidence":"Co-immunoprecipitation, molecular docking, RNA-seq, overexpression in Huh-7 cells with western blot for JAK1/STAT3 and EMT markers","pmids":["41930189"],"confidence":"Medium","gaps":["JAK1 interaction demonstrated by Co-IP and docking but not by orthogonal methods (e.g., in vitro pulldown with purified proteins)","Whether DEPDC7 inhibits JAK1 catalytic activity directly or promotes its degradation is unresolved","Relationship between the CARMA/NF-κB axis and the JAK1/STAT3 axis of DEPDC7 function is not integrated"]},{"year":null,"claim":"It remains unknown whether DEPDC7's DEP or RhoGAP-like domains possess intrinsic enzymatic activity, how the NF-κB–promoting and JAK1/STAT3–suppressing functions are coordinated, and whether DEPDC7 acts as a tumor suppressor in vivo.","evidence":"","pmids":[],"confidence":"Low","gaps":["No in vivo genetic model (knockout mouse or xenograft rescue)","No biochemical characterization of DEP or RhoGAP domain catalytic activity","No structural data for DEPDC7 or its complexes"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0098772","term_label":"molecular function regulator activity","supporting_discovery_ids":[0,3]}],"localization":[{"term_id":"GO:0005829","term_label":"cytosol","supporting_discovery_ids":[0,3]},{"term_id":"GO:0005634","term_label":"nucleus","supporting_discovery_ids":[3]}],"pathway":[{"term_id":"R-HSA-162582","term_label":"Signal Transduction","supporting_discovery_ids":[0,3]}],"complexes":[],"partners":["CARD14","CARD10","JAK1"],"other_free_text":[]},"mechanistic_narrative":"DEPDC7 is a DEP-domain-containing cytoplasmic and nuclear protein that functions as a tumor suppressor in hepatocellular carcinoma by restraining cell proliferation, cell cycle progression, migration, invasion, and epithelial–mesenchymal transition [PMID:29344171, PMID:27016254, PMID:41930189]. It physically interacts with CARMA2 and CARMA3, components of the CBM signaling complex, and its expression is required for NF-κB activation downstream of G protein-coupled receptor stimulation [PMID:25541973]. DEPDC7 also directly binds the JAK1 kinase domain, and its overexpression suppresses JAK1/STAT3 signaling, promotes apoptosis, and reverses EMT marker expression in hepatoma cells [PMID:41930189]."},"prefetch_data":{"uniprot":{"accession":"Q96QD5","full_name":"DEP domain-containing protein 7","aliases":["Protein TR2/D15"],"length_aa":511,"mass_kda":58.3,"function":"","subcellular_location":"","url":"https://www.uniprot.org/uniprotkb/Q96QD5/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/DEPDC7","classification":"Not Classified","n_dependent_lines":3,"n_total_lines":1208,"dependency_fraction":0.0024834437086092716},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[],"url":"https://opencell.sf.czbiohub.org/search/DEPDC7","total_profiled":1310},"omim":[{"mim_id":"612294","title":"DEP DOMAIN-CONTAINING PROTEIN 7; DEPDC7","url":"https://www.omim.org/entry/612294"},{"mim_id":"609641","title":"EUKARYOTIC TRANSLATION INITIATION FACTOR 3, SUBUNIT M; EIF3M","url":"https://www.omim.org/entry/609641"},{"mim_id":"600367","title":"CLEAVAGE STIMULATION FACTOR, 3-PRIME PRE-RNA, SUBUNIT 3, 77-KD; CSTF3","url":"https://www.omim.org/entry/600367"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Approved","locations":[{"location":"Nucleoli","reliability":"Approved"},{"location":"Nucleoplasm","reliability":"Additional"},{"location":"Cytosol","reliability":"Additional"}],"tissue_specificity":"Group enriched","tissue_distribution":"Detected in many","driving_tissues":[{"tissue":"intestine","ntpm":27.3},{"tissue":"kidney","ntpm":18.2},{"tissue":"liver","ntpm":69.2},{"tissue":"testis","ntpm":26.4}],"url":"https://www.proteinatlas.org/search/DEPDC7"},"hgnc":{"alias_symbol":[],"prev_symbol":[]},"alphafold":{"accession":"Q96QD5","domains":[{"cath_id":"1.10.10.10","chopping":"27-138_171-192","consensus_level":"medium","plddt":76.0216,"start":27,"end":192},{"cath_id":"-","chopping":"196-227_425-452","consensus_level":"medium","plddt":75.35,"start":196,"end":452},{"cath_id":"1.10.555.10","chopping":"262-421","consensus_level":"high","plddt":85.6081,"start":262,"end":421},{"cath_id":"-","chopping":"458-510","consensus_level":"high","plddt":82.9298,"start":458,"end":510}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q96QD5","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q96QD5-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q96QD5-F1-predicted_aligned_error_v6.png","plddt_mean":73.62},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=DEPDC7","jax_strain_url":"https://www.jax.org/strain/search?query=DEPDC7"},"sequence":{"accession":"Q96QD5","fasta_url":"https://rest.uniprot.org/uniprotkb/Q96QD5.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q96QD5/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q96QD5"}},"corpus_meta":[{"pmid":"32636717","id":"PMC_32636717","title":"The plasma peptides of sepsis.","date":"2020","source":"Clinical proteomics","url":"https://pubmed.ncbi.nlm.nih.gov/32636717","citation_count":26,"is_preprint":false},{"pmid":"25541973","id":"PMC_25541973","title":"The Dishevelled, EGL-10 and pleckstrin (DEP) domain-containing protein DEPDC7 binds to CARMA2 and CARMA3 proteins, and regulates NF-κB activation.","date":"2014","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/25541973","citation_count":21,"is_preprint":false},{"pmid":"24912414","id":"PMC_24912414","title":"A novel Alu-mediated microdeletion at 11p13 removes WT1 in a patient with cryptorchidism and azoospermia.","date":"2014","source":"Reproductive biomedicine online","url":"https://pubmed.ncbi.nlm.nih.gov/24912414","citation_count":17,"is_preprint":false},{"pmid":"29344171","id":"PMC_29344171","title":"DEPDC7 inhibits cell proliferation, migration and invasion in hepatoma cells.","date":"2017","source":"Oncology letters","url":"https://pubmed.ncbi.nlm.nih.gov/29344171","citation_count":10,"is_preprint":false},{"pmid":"25952135","id":"PMC_25952135","title":"Further evidence of DEPDC7 DNA hypomethylation in depression: A study in adult twins.","date":"2015","source":"European psychiatry : the journal of the Association of European Psychiatrists","url":"https://pubmed.ncbi.nlm.nih.gov/25952135","citation_count":10,"is_preprint":false},{"pmid":"27016254","id":"PMC_27016254","title":"Construction and Identification of the RNAi Recombinant Lentiviral Vector Targeting Human DEPDC7 Gene.","date":"2016","source":"Interdisciplinary sciences, computational life sciences","url":"https://pubmed.ncbi.nlm.nih.gov/27016254","citation_count":9,"is_preprint":false},{"pmid":"41930189","id":"PMC_41930189","title":"DEPDC7 as a potential tumor suppressor in hepatocellular carcinoma: preliminary evidence for targeting the JAK1/STAT3 axis.","date":"2026","source":"Frontiers in oncology","url":"https://pubmed.ncbi.nlm.nih.gov/41930189","citation_count":0,"is_preprint":false},{"pmid":"37672513","id":"PMC_37672513","title":"Identification of candidate genes for developmental colour agnosia in a single unique family.","date":"2023","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/37672513","citation_count":0,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":5540,"output_tokens":1052,"usd":0.0162},"stage2":{"model":"claude-opus-4-6","input_tokens":4263,"output_tokens":1462,"usd":0.086797},"total_usd":0.102997,"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\": 2014,\n      \"finding\": \"DEPDC7 physically binds to CARMA2 and CARMA3 proteins (components of the CBM complex), displays cytosolic distribution, and its expression induces NF-κB activation; shRNA-mediated knockdown of DEPDC7 impairs NF-κB activation downstream of G protein-coupled receptor stimulation in a CARMA2/CARMA3-dependent (but not CARMA1-dependent) manner.\",\n      \"method\": \"Co-immunoprecipitation (binding), shRNA knockdown with NF-κB reporter assay, subcellular localization imaging\",\n      \"journal\": \"PloS one\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2-3 — reciprocal Co-IP plus functional KD with defined pathway readout, single lab\",\n      \"pmids\": [\"25541973\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"Overexpression of DEPDC7 in hepatoma cell lines inhibits cell proliferation, cell cycle entry, and cell motility/invasion, while shRNA-mediated knockdown promotes these phenotypes, establishing DEPDC7 as a negative regulator of hepatoma cell growth and migration.\",\n      \"method\": \"Overexpression and shRNA knockdown in SK-Hep-1 and Huh-7/HepG2 hepatoma cell lines; proliferation, cell cycle, migration and invasion assays\",\n      \"journal\": \"Oncology letters\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — bidirectional loss- and gain-of-function with multiple phenotypic readouts, single lab\",\n      \"pmids\": [\"29344171\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2016,\n      \"finding\": \"shRNA-mediated knockdown of DEPDC7 in HepG2 hepatocellular carcinoma cells significantly increases cell migration and invasion, confirming a role for DEPDC7 in suppressing cell motility.\",\n      \"method\": \"Lentiviral shRNA knockdown; Matrigel migration and invasion assay; RT-PCR and western blot for knockdown confirmation\",\n      \"journal\": \"Interdisciplinary sciences, computational life sciences\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — clean KD with defined cellular phenotype, single lab, consistent with parallel studies\",\n      \"pmids\": [\"27016254\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2026,\n      \"finding\": \"DEPDC7 localizes to both cytoplasm and nucleus in HCC cells; its overexpression suppresses the JAK1/STAT3 signaling pathway (downregulating JAK1 and STAT3), inhibits EMT (increasing E-cadherin, decreasing N-cadherin and vimentin), and promotes cell cycle arrest and apoptosis. Co-immunoprecipitation and molecular docking confirmed direct physical interaction between DEPDC7 and the JAK1 kinase domain.\",\n      \"method\": \"RNA-seq, Co-immunoprecipitation, molecular docking, overexpression in Huh-7 cells, western blot, scanning electron microscopy, subcellular localization\",\n      \"journal\": \"Frontiers in oncology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2-3 — Co-IP plus RNA-seq plus functional overexpression with multiple readouts, single lab\",\n      \"pmids\": [\"41930189\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"DEPDC7 is a cytoplasmic (and nuclear) DEP/RhoGAP domain-containing protein that acts as a tumor suppressor in hepatocellular carcinoma by binding to CARMA2/CARMA3 to modulate NF-κB activation downstream of GPCRs, directly interacting with the JAK1 kinase domain to suppress JAK1/STAT3 signaling, attenuating epithelial-mesenchymal transition, and restraining hepatoma cell proliferation, cell cycle progression, and invasion.\"\n}\n```","stage2_raw":"```json\n{\n  \"mechanistic_narrative\": \"DEPDC7 is a DEP-domain-containing cytoplasmic and nuclear protein that functions as a tumor suppressor in hepatocellular carcinoma by restraining cell proliferation, cell cycle progression, migration, invasion, and epithelial–mesenchymal transition [PMID:29344171, PMID:27016254, PMID:41930189]. It physically interacts with CARMA2 and CARMA3, components of the CBM signaling complex, and its expression is required for NF-κB activation downstream of G protein-coupled receptor stimulation [PMID:25541973]. DEPDC7 also directly binds the JAK1 kinase domain, and its overexpression suppresses JAK1/STAT3 signaling, promotes apoptosis, and reverses EMT marker expression in hepatoma cells [PMID:41930189].\",\n  \"teleology\": [\n    {\n      \"year\": 2014,\n      \"claim\": \"The molecular partners and signaling output of DEPDC7 were unknown; co-immunoprecipitation revealed that DEPDC7 physically binds CARMA2 and CARMA3 and is required for NF-κB activation downstream of GPCRs, establishing it as a component of CBM-dependent innate signaling.\",\n      \"evidence\": \"Co-immunoprecipitation, shRNA knockdown with NF-κB reporter assay, subcellular localization imaging in HEK293T and related cell lines\",\n      \"pmids\": [\"25541973\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No reciprocal validation in an independent lab\",\n        \"Whether DEPDC7 acts catalytically (e.g., via its RhoGAP-like domain) or as a scaffold for CBM assembly is unresolved\",\n        \"Physiological GPCR ligands and tissue contexts for this NF-κB role are not defined\"\n      ]\n    },\n    {\n      \"year\": 2016,\n      \"claim\": \"Whether DEPDC7 influences cancer cell behavior was untested; knockdown in hepatoma cells increased migration and invasion, providing the first evidence for a tumor-suppressive role.\",\n      \"evidence\": \"Lentiviral shRNA knockdown in HepG2 cells; Matrigel migration and invasion assays\",\n      \"pmids\": [\"27016254\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Single cell line and single lab; awaits independent confirmation\",\n        \"Downstream effectors mediating the anti-migratory effect are not identified\"\n      ]\n    },\n    {\n      \"year\": 2017,\n      \"claim\": \"Bidirectional gain- and loss-of-function experiments extended the tumor-suppressive phenotype to proliferation and cell cycle control, consolidating DEPDC7 as a negative regulator of hepatoma cell growth and motility.\",\n      \"evidence\": \"Overexpression and shRNA knockdown in SK-Hep-1, Huh-7, and HepG2 hepatoma lines; proliferation, cell cycle, migration, and invasion assays\",\n      \"pmids\": [\"29344171\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No in vivo tumor model\",\n        \"Mechanism connecting DEPDC7 to cell cycle arrest not molecularly defined\"\n      ]\n    },\n    {\n      \"year\": 2026,\n      \"claim\": \"The signaling pathway through which DEPDC7 suppresses hepatoma growth was identified: DEPDC7 directly binds the JAK1 kinase domain to suppress JAK1/STAT3 signaling and EMT, linking its tumor-suppressive activity to a defined kinase target.\",\n      \"evidence\": \"Co-immunoprecipitation, molecular docking, RNA-seq, overexpression in Huh-7 cells with western blot for JAK1/STAT3 and EMT markers\",\n      \"pmids\": [\"41930189\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"JAK1 interaction demonstrated by Co-IP and docking but not by orthogonal methods (e.g., in vitro pulldown with purified proteins)\",\n        \"Whether DEPDC7 inhibits JAK1 catalytic activity directly or promotes its degradation is unresolved\",\n        \"Relationship between the CARMA/NF-κB axis and the JAK1/STAT3 axis of DEPDC7 function is not integrated\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"It remains unknown whether DEPDC7's DEP or RhoGAP-like domains possess intrinsic enzymatic activity, how the NF-κB–promoting and JAK1/STAT3–suppressing functions are coordinated, and whether DEPDC7 acts as a tumor suppressor in vivo.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No in vivo genetic model (knockout mouse or xenograft rescue)\",\n        \"No biochemical characterization of DEP or RhoGAP domain catalytic activity\",\n        \"No structural data for DEPDC7 or its complexes\"\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0098772\", \"supporting_discovery_ids\": [0, 3]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005829\", \"supporting_discovery_ids\": [0, 3]},\n      {\"term_id\": \"GO:0005634\", \"supporting_discovery_ids\": [3]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-162582\", \"supporting_discovery_ids\": [0, 3]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\n      \"CARD14\",\n      \"CARD10\",\n      \"JAK1\"\n    ],\n    \"other_free_text\": []\n  }\n}\n```"}