{"gene":"GPATCH2","run_date":"2026-06-10T01:55:21","timeline":{"discoveries":[{"year":2009,"finding":"Human GPATCH2 protein interacts with hPrp43 (human DHX15), an RNA-dependent ATPase, and this interaction significantly enhances the ATPase activity of hPrp43, promoting cell growth.","method":"Co-immunoprecipitation and ATPase activity assay in breast cancer cell lines; siRNA knockdown causing growth suppression","journal":"Cancer science","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — reciprocal interaction demonstrated with ATPase assay readout, single lab, two orthogonal methods (co-IP + enzymatic assay)","pmids":["19432882"],"is_preprint":false},{"year":2014,"finding":"GPATCH2 (GPATC2) localizes predominantly to the nucleus of 293T cells, inhibits NF-κB transcriptional activity, and overexpression inhibits cell proliferation by decreasing the fraction of cells in S phase; conversely, siRNA knockdown of GPATCH2 promotes proliferation, indicating a role in G1-S phase transition.","method":"Transient transfection with EGFP-fusion constructs and DAPI nuclear staining for localization; NF-κB reporter assay; CCK-8, colony-forming efficiency, and flow cytometry for proliferation","journal":"Molecular medicine reports","confidence":"Medium","confidence_rationale":"Tier 2–3 / Moderate — multiple orthogonal functional assays in a single lab, nuclear localization confirmed by imaging, loss- and gain-of-function both tested","pmids":["25376275"],"is_preprint":false},{"year":2023,"finding":"Deletion of Gpatch2 in mice does not alter basal or LPS/SMAC-mimetic-induced Tnf expression in vivo; GPATCH2 protein is detected in mouse testis and at lower levels in other tissues, and Gpatch2-/- mice are viable with no overt phenotype, arguing against a role for GPATCH2 as a post-transcriptional repressor of Tnf through the 3' UTR.","method":"CRISPR-generated Gpatch2 knockout mice, LPS and SMAC-mimetic inflammation models, measurement of TNF expression in vivo","journal":"Cell death & disease","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — in vivo KO with defined readout; this is a rigorous negative result from a clean genetic model, single lab","pmids":["36973252"],"is_preprint":false},{"year":2025,"finding":"GPATCH2 expression in hepatocellular carcinoma is transcriptionally activated by the transcription factor YY1; silencing GPATCH2 suppresses HCC cell proliferation, migration, invasion, and xenograft tumor growth, and reduces SNAI2 expression while increasing CDH1, placing GPATCH2 upstream of SNAI2 in an EMT-related oncogenic pathway.","method":"Loss-of-function (siRNA/shRNA) in HCC cell lines and subcutaneous xenograft mouse model; rescue experiments restoring SNAI2; assessment of EMT markers; bioinformatics to identify YY1 as transcriptional activator","journal":"IUBMB life","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single lab, mechanistic pathway inferred from KD phenotype and rescue, YY1 regulation not directly confirmed by ChIP or mutagenesis in abstract","pmids":["41236130"],"is_preprint":false}],"current_model":"GPATCH2 is a nuclear G-patch domain-containing protein that physically interacts with and stimulates the ATPase activity of the DEAH-box RNA helicase hPrp43/DHX15, inhibits NF-κB transcriptional activity, and restrains G1-S cell cycle progression; in vivo knockout in mice causes no detectable change in TNF expression or gross phenotype, while in cancer contexts its expression is driven by the transcription factor YY1 and it promotes tumor cell growth partly through upregulation of SNAI2."},"narrative":{"mechanistic_narrative":"GPATCH2 is a predominantly nuclear G-patch domain protein that acts as a cofactor for the DEAH-box RNA-dependent ATPase hPrp43/DHX15, physically binding the helicase and stimulating its ATPase activity to promote cell growth [PMID:19432882]. Beyond this catalytic regulation, GPATCH2 inhibits NF-κB transcriptional activity and restrains G1-S cell cycle progression, with overexpression reducing the S-phase fraction and knockdown enhancing proliferation [PMID:25376275]. Its physiological role is constrained by a clean genetic test: deletion in mice yields viable animals with no overt phenotype and no change in basal or induced Tnf expression, arguing against a role as a post-transcriptional repressor of Tnf [PMID:36973252]. In hepatocellular carcinoma, GPATCH2 is transcriptionally activated by YY1 and supports proliferation, migration, invasion, and xenograft growth, acting upstream of SNAI2 in an EMT-related program [PMID:41236130].","teleology":[{"year":2009,"claim":"Established the first molecular function of GPATCH2 by identifying a direct binding partner and an enzymatic consequence of that interaction, framing it as a helicase cofactor that drives cell growth.","evidence":"Co-immunoprecipitation and ATPase activity assay with hPrp43/DHX15 plus siRNA knockdown in breast cancer cells","pmids":["19432882"],"confidence":"Medium","gaps":["No structural basis for the GPATCH2–hPrp43 interaction or the G-patch domain's role in ATPase stimulation","RNA substrate or splicing/processing context of the helicase activity not defined","Single lab"]},{"year":2014,"claim":"Connected GPATCH2 to transcriptional and cell-cycle control, showing it localizes to the nucleus, suppresses NF-κB activity, and restrains the G1-S transition.","evidence":"EGFP-fusion imaging, NF-κB reporter assay, and CCK-8/colony/flow-cytometry proliferation assays with gain- and loss-of-function in 293T cells","pmids":["25376275"],"confidence":"Medium","gaps":["Mechanism linking GPATCH2 to NF-κB inhibition not defined","Relationship between the helicase cofactor activity and cell-cycle/NF-κB effects unresolved","Direct cell-cycle targets unidentified"]},{"year":2023,"claim":"Tested GPATCH2's physiological necessity in vivo and excluded a proposed role as a 3'UTR-mediated post-transcriptional repressor of Tnf.","evidence":"CRISPR Gpatch2 knockout mice with LPS and SMAC-mimetic inflammation models and TNF expression readouts","pmids":["36973252"],"confidence":"Medium","gaps":["Viability with no overt phenotype leaves the essential in vivo function undefined","Testis-enriched expression hints at an unexplored tissue-specific role","Possible functional redundancy not addressed"]},{"year":2025,"claim":"Placed GPATCH2 in an oncogenic transcriptional circuit, identifying YY1 as an upstream activator and SNAI2/EMT as a downstream effector in hepatocellular carcinoma.","evidence":"siRNA/shRNA loss-of-function in HCC cell lines and xenografts with SNAI2 rescue, EMT marker analysis, and bioinformatic identification of YY1","pmids":["41236130"],"confidence":"Low","gaps":["YY1 regulation not confirmed by ChIP or promoter mutagenesis","How GPATCH2 mechanistically controls SNAI2 expression is unknown","Reconciliation with the earlier anti-proliferative role in 293T cells is unaddressed"]},{"year":null,"claim":"The RNA substrates and biological process served by the GPATCH2–DHX15 helicase complex, and how this connects to its transcriptional and cell-cycle effects, remain undefined.","evidence":"","pmids":[],"confidence":"Low","gaps":["No RNA target or processing pathway identified for the GPATCH2/DHX15 module","No structural model of the complex","Unifying mechanism linking helicase cofactor, NF-κB inhibition, and cancer growth not established"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0098772","term_label":"molecular function regulator activity","supporting_discovery_ids":[0]},{"term_id":"GO:0140110","term_label":"transcription regulator activity","supporting_discovery_ids":[1]}],"localization":[{"term_id":"GO:0005634","term_label":"nucleus","supporting_discovery_ids":[1]}],"pathway":[],"complexes":[],"partners":["DHX15"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q9NW75","full_name":"G patch domain-containing protein 2","aliases":[],"length_aa":528,"mass_kda":58.9,"function":"Enhances the ATPase activity of DHX15 in vitro","subcellular_location":"Nucleus speckle; Nucleus, nucleolus","url":"https://www.uniprot.org/uniprotkb/Q9NW75/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/GPATCH2","classification":"Not Classified","n_dependent_lines":7,"n_total_lines":1208,"dependency_fraction":0.005794701986754967},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[{"gene":"COMMD4","stoichiometry":0.2},{"gene":"COPA","stoichiometry":0.2},{"gene":"COPE","stoichiometry":0.2},{"gene":"CSNK2B","stoichiometry":0.2}],"url":"https://opencell.sf.czbiohub.org/search/GPATCH2","total_profiled":1310},"omim":[{"mim_id":"616836","title":"G-PATCH DOMAIN-CONTAINING PROTEIN 2; GPATCH2","url":"https://www.omim.org/entry/616836"},{"mim_id":"603403","title":"DEAH-BOX HELICASE 15; DHX15","url":"https://www.omim.org/entry/603403"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Supported","locations":[{"location":"Nuclear speckles","reliability":"Supported"}],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in all","driving_tissues":[],"url":"https://www.proteinatlas.org/search/GPATCH2"},"hgnc":{"alias_symbol":["FLJ10252","CT110","PPP1R30","Pfa1"],"prev_symbol":["GPATC2"]},"alphafold":{"accession":"Q9NW75","domains":[],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q9NW75","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q9NW75-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q9NW75-F1-predicted_aligned_error_v6.png","plddt_mean":55.69},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=GPATCH2","jax_strain_url":"https://www.jax.org/strain/search?query=GPATCH2"},"sequence":{"accession":"Q9NW75","fasta_url":"https://rest.uniprot.org/uniprotkb/Q9NW75.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q9NW75/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q9NW75"}},"corpus_meta":[{"pmid":"29909548","id":"PMC_29909548","title":"Molecular heterogeneity and CXorf67 alterations in posterior fossa group A (PFA) 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A Case-Control Study in the Indian Population","date":"2024-08-22","source":"bioRxiv","url":"https://doi.org/10.1101/2024.08.22.24311857","citation_count":0,"is_preprint":true}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":22400,"output_tokens":1124,"usd":0.04203,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":7737,"output_tokens":1878,"usd":0.042818,"stage2_stop_reason":"end_turn"},"total_usd":0.084848,"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\": 2009,\n      \"finding\": \"Human GPATCH2 protein interacts with hPrp43 (human DHX15), an RNA-dependent ATPase, and this interaction significantly enhances the ATPase activity of hPrp43, promoting cell growth.\",\n      \"method\": \"Co-immunoprecipitation and ATPase activity assay in breast cancer cell lines; siRNA knockdown causing growth suppression\",\n      \"journal\": \"Cancer science\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reciprocal interaction demonstrated with ATPase assay readout, single lab, two orthogonal methods (co-IP + enzymatic assay)\",\n      \"pmids\": [\"19432882\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"GPATCH2 (GPATC2) localizes predominantly to the nucleus of 293T cells, inhibits NF-κB transcriptional activity, and overexpression inhibits cell proliferation by decreasing the fraction of cells in S phase; conversely, siRNA knockdown of GPATCH2 promotes proliferation, indicating a role in G1-S phase transition.\",\n      \"method\": \"Transient transfection with EGFP-fusion constructs and DAPI nuclear staining for localization; NF-κB reporter assay; CCK-8, colony-forming efficiency, and flow cytometry for proliferation\",\n      \"journal\": \"Molecular medicine reports\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2–3 / Moderate — multiple orthogonal functional assays in a single lab, nuclear localization confirmed by imaging, loss- and gain-of-function both tested\",\n      \"pmids\": [\"25376275\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"Deletion of Gpatch2 in mice does not alter basal or LPS/SMAC-mimetic-induced Tnf expression in vivo; GPATCH2 protein is detected in mouse testis and at lower levels in other tissues, and Gpatch2-/- mice are viable with no overt phenotype, arguing against a role for GPATCH2 as a post-transcriptional repressor of Tnf through the 3' UTR.\",\n      \"method\": \"CRISPR-generated Gpatch2 knockout mice, LPS and SMAC-mimetic inflammation models, measurement of TNF expression in vivo\",\n      \"journal\": \"Cell death & disease\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — in vivo KO with defined readout; this is a rigorous negative result from a clean genetic model, single lab\",\n      \"pmids\": [\"36973252\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"GPATCH2 expression in hepatocellular carcinoma is transcriptionally activated by the transcription factor YY1; silencing GPATCH2 suppresses HCC cell proliferation, migration, invasion, and xenograft tumor growth, and reduces SNAI2 expression while increasing CDH1, placing GPATCH2 upstream of SNAI2 in an EMT-related oncogenic pathway.\",\n      \"method\": \"Loss-of-function (siRNA/shRNA) in HCC cell lines and subcutaneous xenograft mouse model; rescue experiments restoring SNAI2; assessment of EMT markers; bioinformatics to identify YY1 as transcriptional activator\",\n      \"journal\": \"IUBMB life\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single lab, mechanistic pathway inferred from KD phenotype and rescue, YY1 regulation not directly confirmed by ChIP or mutagenesis in abstract\",\n      \"pmids\": [\"41236130\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"GPATCH2 is a nuclear G-patch domain-containing protein that physically interacts with and stimulates the ATPase activity of the DEAH-box RNA helicase hPrp43/DHX15, inhibits NF-κB transcriptional activity, and restrains G1-S cell cycle progression; in vivo knockout in mice causes no detectable change in TNF expression or gross phenotype, while in cancer contexts its expression is driven by the transcription factor YY1 and it promotes tumor cell growth partly through upregulation of SNAI2.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"GPATCH2 is a predominantly nuclear G-patch domain protein that acts as a cofactor for the DEAH-box RNA-dependent ATPase hPrp43/DHX15, physically binding the helicase and stimulating its ATPase activity to promote cell growth [#0]. Beyond this catalytic regulation, GPATCH2 inhibits NF-\\u03baB transcriptional activity and restrains G1-S cell cycle progression, with overexpression reducing the S-phase fraction and knockdown enhancing proliferation [#1]. Its physiological role is constrained by a clean genetic test: deletion in mice yields viable animals with no overt phenotype and no change in basal or induced Tnf expression, arguing against a role as a post-transcriptional repressor of Tnf [#2]. In hepatocellular carcinoma, GPATCH2 is transcriptionally activated by YY1 and supports proliferation, migration, invasion, and xenograft growth, acting upstream of SNAI2 in an EMT-related program [#3].\",\n  \"teleology\": [\n    {\n      \"year\": 2009,\n      \"claim\": \"Established the first molecular function of GPATCH2 by identifying a direct binding partner and an enzymatic consequence of that interaction, framing it as a helicase cofactor that drives cell growth.\",\n      \"evidence\": \"Co-immunoprecipitation and ATPase activity assay with hPrp43/DHX15 plus siRNA knockdown in breast cancer cells\",\n      \"pmids\": [\"19432882\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No structural basis for the GPATCH2\\u2013hPrp43 interaction or the G-patch domain's role in ATPase stimulation\",\n        \"RNA substrate or splicing/processing context of the helicase activity not defined\",\n        \"Single lab\"\n      ]\n    },\n    {\n      \"year\": 2014,\n      \"claim\": \"Connected GPATCH2 to transcriptional and cell-cycle control, showing it localizes to the nucleus, suppresses NF-\\u03baB activity, and restrains the G1-S transition.\",\n      \"evidence\": \"EGFP-fusion imaging, NF-\\u03baB reporter assay, and CCK-8/colony/flow-cytometry proliferation assays with gain- and loss-of-function in 293T cells\",\n      \"pmids\": [\"25376275\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Mechanism linking GPATCH2 to NF-\\u03baB inhibition not defined\",\n        \"Relationship between the helicase cofactor activity and cell-cycle/NF-\\u03baB effects unresolved\",\n        \"Direct cell-cycle targets unidentified\"\n      ]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"Tested GPATCH2's physiological necessity in vivo and excluded a proposed role as a 3'UTR-mediated post-transcriptional repressor of Tnf.\",\n      \"evidence\": \"CRISPR Gpatch2 knockout mice with LPS and SMAC-mimetic inflammation models and TNF expression readouts\",\n      \"pmids\": [\"36973252\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Viability with no overt phenotype leaves the essential in vivo function undefined\",\n        \"Testis-enriched expression hints at an unexplored tissue-specific role\",\n        \"Possible functional redundancy not addressed\"\n      ]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Placed GPATCH2 in an oncogenic transcriptional circuit, identifying YY1 as an upstream activator and SNAI2/EMT as a downstream effector in hepatocellular carcinoma.\",\n      \"evidence\": \"siRNA/shRNA loss-of-function in HCC cell lines and xenografts with SNAI2 rescue, EMT marker analysis, and bioinformatic identification of YY1\",\n      \"pmids\": [\"41236130\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"YY1 regulation not confirmed by ChIP or promoter mutagenesis\",\n        \"How GPATCH2 mechanistically controls SNAI2 expression is unknown\",\n        \"Reconciliation with the earlier anti-proliferative role in 293T cells is unaddressed\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The RNA substrates and biological process served by the GPATCH2\\u2013DHX15 helicase complex, and how this connects to its transcriptional and cell-cycle effects, remain undefined.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No RNA target or processing pathway identified for the GPATCH2/DHX15 module\",\n        \"No structural model of the complex\",\n        \"Unifying mechanism linking helicase cofactor, NF-\\u03baB inhibition, and cancer growth not established\"\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0098772\", \"supporting_discovery_ids\": [0]},\n      {\"term_id\": \"GO:0140110\", \"supporting_discovery_ids\": [1]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005634\", \"supporting_discovery_ids\": [1]}\n    ],\n    \"pathway\": [],\n    \"complexes\": [],\n    \"partners\": [\"DHX15\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"faith_supported":4,"faith_total":4,"faith_pct":100.0}}