{"gene":"PDCD7","run_date":"2026-04-29T11:37:58","timeline":{"discoveries":[{"year":1999,"finding":"Mouse ES18 (PDCD7) overexpression in T-cell lymphoma increased apoptotic cell death, and its transcript was selectively regulated during dexamethasone- and staurosporine-induced apoptosis, suggesting a role in specific apoptotic processes in T-cells.","method":"Transient overexpression in mouse T-cell lymphoma with apoptosis readout; transcript regulation by apoptotic stimuli","journal":"Nucleic acids research","confidence":"Low","confidence_rationale":"Tier 3 — single lab, overexpression phenotype without pathway placement or molecular mechanism","pmids":["10037816"],"is_preprint":false},{"year":2018,"finding":"PDCD7 is a direct target of miR-134; PDCD7 transcriptionally activates E-cadherin expression via a GC-box in its promoter, and PDCD7 knockout increases in vitro oncogenicity and neck nodal metastasis in mice while reducing E-cadherin levels.","method":"Luciferase reporter assays with wild-type and mutant constructs; CRISPR knockout; in vivo mouse metastasis model; promoter GC-box functional analysis","journal":"International journal of cancer","confidence":"Medium","confidence_rationale":"Tier 2-3 — multiple orthogonal methods (reporter assay, gene editing, in vivo) from single lab","pmids":["29971778"],"is_preprint":false}],"current_model":"PDCD7 functions as a transcriptional activator of E-cadherin (via a GC-box in its promoter) that suppresses tumor cell oncogenicity and metastasis, and is itself regulated by miR-134; it also plays a role in T-cell apoptosis, though the molecular mechanism of the latter remains unclear."},"narrative":{"teleology":[{"year":1999,"claim":"Initial cloning revealed that PDCD7 overexpression could promote apoptosis in T-cell lymphoma and that its transcript was selectively regulated by apoptotic stimuli, establishing a first link between PDCD7 and programmed cell death without placing it in a defined pathway.","evidence":"Transient overexpression in mouse T-cell lymphoma with apoptosis readout; transcript regulation during dexamethasone- and staurosporine-induced apoptosis","pmids":["10037816"],"confidence":"Low","gaps":["Overexpression-only phenotype without loss-of-function validation or pathway placement","No molecular mechanism linking PDCD7 to apoptotic signaling identified","Single lab observation not independently confirmed"]},{"year":2018,"claim":"PDCD7 was shown to act as a transcriptional activator of E-cadherin through a GC-box in its promoter and to suppress metastasis in vivo, while being itself regulated by miR-134, establishing a miR-134–PDCD7–E-cadherin axis in cancer progression.","evidence":"Luciferase reporter assays with wild-type/mutant constructs, CRISPR knockout, in vivo mouse nodal metastasis model, promoter GC-box functional analysis","pmids":["29971778"],"confidence":"Medium","gaps":["Findings originate from a single laboratory; independent replication is lacking","Mechanism by which PDCD7 binds or activates the GC-box (direct DNA binding vs. cofactor recruitment) not resolved","Relationship between the E-cadherin–activating function and the earlier apoptotic role remains unexplored"]},{"year":null,"claim":"It remains unknown whether PDCD7 directly binds DNA, what structural domains mediate its transcriptional activity, and whether its pro-apoptotic and tumor-suppressive functions reflect the same or distinct molecular mechanisms.","evidence":"","pmids":[],"confidence":"Low","gaps":["No structural or biochemical characterization of PDCD7 protein","No identified protein domains mediating transcriptional activation","No interactome or proteomics data placing PDCD7 in a defined complex"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0140110","term_label":"transcription regulator activity","supporting_discovery_ids":[1]}],"localization":[],"pathway":[{"term_id":"R-HSA-5357801","term_label":"Programmed Cell Death","supporting_discovery_ids":[0,1]}],"complexes":[],"partners":[],"other_free_text":[]},"mechanistic_narrative":"PDCD7 transcriptionally activates E-cadherin expression by binding a GC-box element in the E-cadherin promoter; CRISPR knockout of PDCD7 increases in vitro oncogenicity and neck nodal metastasis in mice while reducing E-cadherin levels, and PDCD7 is itself a direct target of miR-134 [PMID:29971778]. Overexpression of the mouse ortholog (ES18) in T-cell lymphoma promotes apoptotic cell death, though the molecular pathway linking PDCD7 to apoptosis has not been defined [PMID:10037816]."},"prefetch_data":{"uniprot":{"accession":"Q8N8D1","full_name":"Programmed cell death protein 7","aliases":["ES18","hES18"],"length_aa":485,"mass_kda":54.7,"function":"Promotes apoptosis when overexpressed","subcellular_location":"Nucleus","url":"https://www.uniprot.org/uniprotkb/Q8N8D1/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":true,"resolved_as":"","url":"https://depmap.org/portal/gene/PDCD7","classification":"Common Essential","n_dependent_lines":1022,"n_total_lines":1208,"dependency_fraction":0.8460264900662252},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[],"url":"https://opencell.sf.czbiohub.org/search/PDCD7","total_profiled":1310},"omim":[{"mim_id":"608138","title":"PROGRAMMED CELL DEATH 7; PDCD7","url":"https://www.omim.org/entry/608138"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Approved","locations":[{"location":"Plasma membrane","reliability":"Approved"},{"location":"Nucleoli","reliability":"Additional"}],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in all","driving_tissues":[],"url":"https://www.proteinatlas.org/search/PDCD7"},"hgnc":{"alias_symbol":["HES18","ES18","59K"],"prev_symbol":[]},"alphafold":{"accession":"Q8N8D1","domains":[{"cath_id":"-","chopping":"423-481","consensus_level":"medium","plddt":77.4549,"start":423,"end":481},{"cath_id":"1.10.287","chopping":"170-267","consensus_level":"medium","plddt":93.2843,"start":170,"end":267},{"cath_id":"1.10.287","chopping":"268-411","consensus_level":"medium","plddt":92.0772,"start":268,"end":411}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q8N8D1","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q8N8D1-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q8N8D1-F1-predicted_aligned_error_v6.png","plddt_mean":76.44},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=PDCD7","jax_strain_url":"https://www.jax.org/strain/search?query=PDCD7"},"sequence":{"accession":"Q8N8D1","fasta_url":"https://rest.uniprot.org/uniprotkb/Q8N8D1.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q8N8D1/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q8N8D1"}},"corpus_meta":[{"pmid":"15659686","id":"PMC_15659686","title":"The generalized transducing Salmonella bacteriophage ES18: complete genome sequence and DNA packaging strategy.","date":"2005","source":"Journal of bacteriology","url":"https://pubmed.ncbi.nlm.nih.gov/15659686","citation_count":170,"is_preprint":false},{"pmid":"29971778","id":"PMC_29971778","title":"miR-134 targets PDCD7 to reduce E-cadherin expression and enhance oral cancer progression.","date":"2018","source":"International journal of cancer","url":"https://pubmed.ncbi.nlm.nih.gov/29971778","citation_count":53,"is_preprint":false},{"pmid":"16096647","id":"PMC_16096647","title":"The U11/U12 snRNP 65K protein acts as a molecular bridge, binding the U12 snRNA and U11-59K protein.","date":"2005","source":"The EMBO journal","url":"https://pubmed.ncbi.nlm.nih.gov/16096647","citation_count":52,"is_preprint":false},{"pmid":"16559160","id":"PMC_16559160","title":"Mapping of rfa Genes in Salmonella typhimurium by ES18 and P22 Transduction and by Conjugation.","date":"1972","source":"Journal of bacteriology","url":"https://pubmed.ncbi.nlm.nih.gov/16559160","citation_count":44,"is_preprint":false},{"pmid":"18347052","id":"PMC_18347052","title":"The U11-48K protein contacts the 5' splice site of U12-type introns and the U11-59K protein.","date":"2008","source":"Molecular and cellular biology","url":"https://pubmed.ncbi.nlm.nih.gov/18347052","citation_count":41,"is_preprint":false},{"pmid":"324978","id":"PMC_324978","title":"Genetics of sensitivity of Salmonella species to colicin M and bacteriophages T5, T1, and ES18.","date":"1977","source":"Journal of bacteriology","url":"https://pubmed.ncbi.nlm.nih.gov/324978","citation_count":39,"is_preprint":false},{"pmid":"783114","id":"PMC_783114","title":"Iron transport in Salmonella typhimurium LT-2: prevention, by ferrichrome, of adsorption of bacteriophages ES18 and ES18.h1 to a common cell envelope receptor.","date":"1976","source":"Journal of bacteriology","url":"https://pubmed.ncbi.nlm.nih.gov/783114","citation_count":20,"is_preprint":false},{"pmid":"9300826","id":"PMC_9300826","title":"Sequence comparison of the genes for immunity, DNA replication, and cell lysis of the P22-related Salmonella phages ES18 and L.","date":"1997","source":"Gene","url":"https://pubmed.ncbi.nlm.nih.gov/9300826","citation_count":19,"is_preprint":false},{"pmid":"10037816","id":"PMC_10037816","title":"Characterization of a novel mouse cDNA, ES18, involved in apoptotic cell death of T-cells.","date":"1999","source":"Nucleic acids research","url":"https://pubmed.ncbi.nlm.nih.gov/10037816","citation_count":16,"is_preprint":false},{"pmid":"3242498","id":"PMC_3242498","title":"Esterase-18 (ES-18) of the house mouse (Mus musculus): biochemical characterization and genetics of an allozyme system linked to chromosome 19.","date":"1988","source":"Biochemical genetics","url":"https://pubmed.ncbi.nlm.nih.gov/3242498","citation_count":7,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":5469,"output_tokens":517,"usd":0.012081},"stage2":{"model":"claude-opus-4-6","input_tokens":3680,"output_tokens":909,"usd":0.061687},"total_usd":0.073768,"stage1_batch_id":"msgbatch_012ZiiCUBfB62NCTQd4Bk1Jo","stage2_batch_id":"msgbatch_01Xuqq9aUHoQouS7UVGZNStZ","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 1999,\n      \"finding\": \"Mouse ES18 (PDCD7) overexpression in T-cell lymphoma increased apoptotic cell death, and its transcript was selectively regulated during dexamethasone- and staurosporine-induced apoptosis, suggesting a role in specific apoptotic processes in T-cells.\",\n      \"method\": \"Transient overexpression in mouse T-cell lymphoma with apoptosis readout; transcript regulation by apoptotic stimuli\",\n      \"journal\": \"Nucleic acids research\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 — single lab, overexpression phenotype without pathway placement or molecular mechanism\",\n      \"pmids\": [\"10037816\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"PDCD7 is a direct target of miR-134; PDCD7 transcriptionally activates E-cadherin expression via a GC-box in its promoter, and PDCD7 knockout increases in vitro oncogenicity and neck nodal metastasis in mice while reducing E-cadherin levels.\",\n      \"method\": \"Luciferase reporter assays with wild-type and mutant constructs; CRISPR knockout; in vivo mouse metastasis model; promoter GC-box functional analysis\",\n      \"journal\": \"International journal of cancer\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2-3 — multiple orthogonal methods (reporter assay, gene editing, in vivo) from single lab\",\n      \"pmids\": [\"29971778\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"PDCD7 functions as a transcriptional activator of E-cadherin (via a GC-box in its promoter) that suppresses tumor cell oncogenicity and metastasis, and is itself regulated by miR-134; it also plays a role in T-cell apoptosis, though the molecular mechanism of the latter remains unclear.\"\n}\n```","stage2_raw":"```json\n{\n  \"mechanistic_narrative\": \"PDCD7 transcriptionally activates E-cadherin expression by binding a GC-box element in the E-cadherin promoter; CRISPR knockout of PDCD7 increases in vitro oncogenicity and neck nodal metastasis in mice while reducing E-cadherin levels, and PDCD7 is itself a direct target of miR-134 [PMID:29971778]. Overexpression of the mouse ortholog (ES18) in T-cell lymphoma promotes apoptotic cell death, though the molecular pathway linking PDCD7 to apoptosis has not been defined [PMID:10037816].\",\n  \"teleology\": [\n    {\n      \"year\": 1999,\n      \"claim\": \"Initial cloning revealed that PDCD7 overexpression could promote apoptosis in T-cell lymphoma and that its transcript was selectively regulated by apoptotic stimuli, establishing a first link between PDCD7 and programmed cell death without placing it in a defined pathway.\",\n      \"evidence\": \"Transient overexpression in mouse T-cell lymphoma with apoptosis readout; transcript regulation during dexamethasone- and staurosporine-induced apoptosis\",\n      \"pmids\": [\"10037816\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"Overexpression-only phenotype without loss-of-function validation or pathway placement\",\n        \"No molecular mechanism linking PDCD7 to apoptotic signaling identified\",\n        \"Single lab observation not independently confirmed\"\n      ]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"PDCD7 was shown to act as a transcriptional activator of E-cadherin through a GC-box in its promoter and to suppress metastasis in vivo, while being itself regulated by miR-134, establishing a miR-134–PDCD7–E-cadherin axis in cancer progression.\",\n      \"evidence\": \"Luciferase reporter assays with wild-type/mutant constructs, CRISPR knockout, in vivo mouse nodal metastasis model, promoter GC-box functional analysis\",\n      \"pmids\": [\"29971778\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Findings originate from a single laboratory; independent replication is lacking\",\n        \"Mechanism by which PDCD7 binds or activates the GC-box (direct DNA binding vs. cofactor recruitment) not resolved\",\n        \"Relationship between the E-cadherin–activating function and the earlier apoptotic role remains unexplored\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"It remains unknown whether PDCD7 directly binds DNA, what structural domains mediate its transcriptional activity, and whether its pro-apoptotic and tumor-suppressive functions reflect the same or distinct molecular mechanisms.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No structural or biochemical characterization of PDCD7 protein\",\n        \"No identified protein domains mediating transcriptional activation\",\n        \"No interactome or proteomics data placing PDCD7 in a defined complex\"\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0140110\", \"supporting_discovery_ids\": [1]}\n    ],\n    \"localization\": [],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-5357801\", \"supporting_discovery_ids\": [0, 1]}\n    ],\n    \"complexes\": [],\n    \"partners\": [],\n    \"other_free_text\": []\n  }\n}\n```"}