{"gene":"PRRC1","run_date":"2026-06-10T06:43:36","timeline":{"discoveries":[{"year":2021,"finding":"PRRC1 is recruited to endoplasmic reticulum (ER) exit sites, interacts with the inner COPII coat, and its absence increases membrane association of COPII, indicating PRRC1 regulates anterograde ER-to-Golgi trafficking.","method":"In vitro vesicle formation assay, quantitative mass spectrometry, co-immunoprecipitation/interaction assay, siRNA knockdown with COPII membrane association readout","journal":"Proceedings of the National Academy of Sciences of the United States of America","confidence":"High","confidence_rationale":"Tier 1–2 / Moderate — in vitro reconstitution assay plus MS identification, binding interaction with COPII coat, and functional KD phenotype (increased COPII membrane association), multiple orthogonal methods in one study","pmids":["34433667"],"is_preprint":false},{"year":2025,"finding":"PRRC1 acts as a cytosolic regulator essential for AP-4-mediated trans-Golgi network (TGN) export, functioning as an accessory factor for AP-4 vesicle biogenesis independently of clathrin.","method":"In vitro vesicle formation assay using AP4ε-deficient HeLa cells, label-free quantitative mass spectrometry, functional validation of PRRC1 requirement for AP-4-dependent trafficking","journal":"Proceedings of the National Academy of Sciences of the United States of America","confidence":"High","confidence_rationale":"Tier 1–2 / Moderate — in vitro reconstitution vesicle assay combined with quantitative MS and genetic (AP4ε KO) epistasis, multiple orthogonal methods in one rigorous study","pmids":["41032520"],"is_preprint":false},{"year":2014,"finding":"PRRC1 can serve as a fusion partner for MLL (KMT2A) in secondary acute lymphoblastic leukemia, producing an in-frame 5'MLL–3'PRRC1 fusion transcript resulting from a t(5;11)(q23-31;q23) chromosomal translocation.","method":"Banding cytogenetics, FISH, long-distance inverse PCR (LDI-PCR) to identify the fusion breakpoint","journal":"Leukemia research","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — molecularly characterized fusion gene in a single patient case using LDI-PCR; establishes the translocation but no functional mechanism of the fusion protein was tested","pmids":["25205603"],"is_preprint":false},{"year":2026,"finding":"shRNA-mediated knockdown of PRRC1 in GBM cells reduces proliferation, clonogenic survival, anchorage-independent growth, and 3D spheroid formation; under genotoxic stress, PRRC1-deficient cells show enhanced γ-H2AX accumulation, indicating PRRC1 supports DNA damage response and stress-adaptive programs in glioblastoma cells.","method":"shRNA knockdown in U87 and patient-derived GBM cells, clonogenic survival assay, γ-H2AX immunofluorescence under genotoxic stress, 3D spheroid assay","journal":"DNA repair","confidence":"Medium","confidence_rationale":"Tier 2–3 / Weak — clean KD with multiple defined cellular phenotypes (proliferation, DNA damage signaling) in two cell models, but single lab and no direct biochemical mechanism elucidated for PRRC1 in DDR","pmids":["41932066"],"is_preprint":false},{"year":2025,"finding":"MUC5AC interacts and colocalizes with PRRC1 in the Golgi, suggesting a role for PRRC1 in MUC5AC glycosylation.","method":"Co-localization/interaction assay (biochemical/proteomic analysis) in LUAD cells","journal":"The Journal of clinical investigation","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single co-localization/interaction observation in a study focused on ST6GalNAc-I; PRRC1's role in MUC5AC glycosylation is proposed but not functionally validated","pmids":["40371640"],"is_preprint":false}],"current_model":"PRRC1 is a proline-rich cytosolic protein that functions at multiple steps of vesicular trafficking: it is recruited to ER exit sites where it interacts with the inner COPII coat and negatively regulates COPII membrane association, and it also acts as an accessory factor required for AP-4-mediated export from the trans-Golgi network; additionally, PRRC1 supports DNA damage response and proliferative fitness in glioblastoma cells, and its locus is subject to MLL translocation in secondary leukemia."},"narrative":{"mechanistic_narrative":"PRRC1 is a cytosolic accessory factor that operates at multiple steps of the secretory pathway. At ER exit sites it is recruited to the inner COPII coat and limits COPII membrane association, thereby tuning anterograde ER-to-Golgi transport [PMID:34433667]. At the trans-Golgi network it acts as an essential cytosolic regulator of AP-4-mediated vesicle biogenesis, functioning independently of clathrin to support AP-4-dependent export [PMID:41032520]. Beyond trafficking, loss of PRRC1 in glioblastoma cells impairs proliferation, clonogenic survival, and anchorage-independent growth and elevates γ-H2AX under genotoxic stress, linking PRRC1 to proliferative fitness and the DNA damage response in these cells [PMID:41932066]. A t(5;11) chromosomal translocation can fuse PRRC1 in-frame to MLL (KMT2A) in secondary acute lymphoblastic leukemia [PMID:25205603]. The molecular basis connecting PRRC1's trafficking functions to its DNA-damage and oncogenic roles has not been characterized in the available corpus.","teleology":[{"year":2014,"claim":"Before any biochemical function was known, characterizing a leukemia breakpoint established that the PRRC1 locus can be rearranged, identifying it as an MLL fusion partner.","evidence":"Banding cytogenetics, FISH, and LDI-PCR breakpoint mapping in a secondary ALL patient case","pmids":["25205603"],"confidence":"Medium","gaps":["Single patient case; recurrence not established","No functional test of the 5'MLL-3'PRRC1 fusion protein","Does not address normal PRRC1 cellular function"]},{"year":2021,"claim":"The first mechanistic assignment placed PRRC1 at ER exit sites as a regulator of COPII, answering what cellular process it participates in.","evidence":"In vitro vesicle formation assay, quantitative MS, co-IP, and siRNA knockdown reading out COPII membrane association","pmids":["34433667"],"confidence":"High","gaps":["Precise binding interface within the inner COPII coat not defined","Structural basis for negative regulation of COPII membrane association unresolved"]},{"year":2025,"claim":"Extending its trafficking role, PRRC1 was shown to be required at a distinct compartment, the TGN, as an accessory factor for AP-4 vesicle biogenesis.","evidence":"In vitro vesicle formation assay in AP4ε-deficient HeLa cells with label-free quantitative MS and genetic epistasis","pmids":["41032520"],"confidence":"High","gaps":["Direct physical contact between PRRC1 and AP-4 not structurally defined","Whether the COPII and AP-4 roles share a common biochemical activity is unknown"]},{"year":2025,"claim":"A Golgi colocalization observation tentatively extended PRRC1 into cargo glycosylation, raising whether it influences MUC5AC processing.","evidence":"Co-localization/interaction assay in LUAD cells within a study focused on ST6GalNAc-I","pmids":["40371640"],"confidence":"Low","gaps":["Single co-localization observation without functional validation","No reciprocal or biochemical confirmation of the interaction","Role in MUC5AC glycosylation is inferred, not demonstrated"]},{"year":2026,"claim":"Loss-of-function studies connected PRRC1 to cancer cell fitness and stress adaptation, beyond its trafficking roles.","evidence":"shRNA knockdown in U87 and patient-derived GBM cells with clonogenic, anchorage-independent growth, spheroid, and γ-H2AX assays under genotoxic stress","pmids":["41932066"],"confidence":"Medium","gaps":["No direct biochemical mechanism linking PRRC1 to the DNA damage response","Single-lab finding without orthogonal genetic validation","Whether the DDR phenotype is secondary to trafficking defects is unknown"]},{"year":null,"claim":"It remains unknown what unifying molecular activity allows PRRC1 to act at both COPII and AP-4 vesicle steps and whether this relates to its proliferative and DNA-damage roles in cancer.","evidence":"","pmids":[],"confidence":"Low","gaps":["No defined catalytic or adaptor activity established","No structural model of PRRC1 or its interaction interfaces","Mechanistic link between trafficking function and DDR/oncogenic phenotypes absent"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0098772","term_label":"molecular function regulator activity","supporting_discovery_ids":[0,1]}],"localization":[{"term_id":"GO:0005829","term_label":"cytosol","supporting_discovery_ids":[0,1]},{"term_id":"GO:0005783","term_label":"endoplasmic reticulum","supporting_discovery_ids":[0]},{"term_id":"GO:0005794","term_label":"Golgi apparatus","supporting_discovery_ids":[1]}],"pathway":[{"term_id":"R-HSA-5653656","term_label":"Vesicle-mediated transport","supporting_discovery_ids":[0,1]}],"complexes":[],"partners":["AP4E1","MUC5AC"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q96M27","full_name":"Protein PRRC1","aliases":["Proline-rich and coiled-coil-containing protein 1"],"length_aa":445,"mass_kda":46.7,"function":"May act as a regulator of the protein kinase A (PKA) activity during embryonic development","subcellular_location":"Golgi apparatus; Cytoplasm","url":"https://www.uniprot.org/uniprotkb/Q96M27/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/PRRC1","classification":"Not Classified","n_dependent_lines":4,"n_total_lines":1208,"dependency_fraction":0.0033112582781456954},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[{"gene":"SEC23A","stoichiometry":10.0}],"url":"https://opencell.sf.czbiohub.org/search/PRRC1","total_profiled":1310},"omim":[{"mim_id":"621301","title":"PROLINE-RICH COILED-COIL PROTEIN 1; PRRC1","url":"https://www.omim.org/entry/621301"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Approved","locations":[{"location":"Vesicles","reliability":"Approved"}],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in all","driving_tissues":[],"url":"https://www.proteinatlas.org/search/PRRC1"},"hgnc":{"alias_symbol":["FLJ32875"],"prev_symbol":[]},"alphafold":{"accession":"Q96M27","domains":[{"cath_id":"-","chopping":"228-255","consensus_level":"medium","plddt":60.0121,"start":228,"end":255},{"cath_id":"3.90.950.10","chopping":"260-440","consensus_level":"high","plddt":96.4499,"start":260,"end":440}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q96M27","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q96M27-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q96M27-F1-predicted_aligned_error_v6.png","plddt_mean":67.75},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=PRRC1","jax_strain_url":"https://www.jax.org/strain/search?query=PRRC1"},"sequence":{"accession":"Q96M27","fasta_url":"https://rest.uniprot.org/uniprotkb/Q96M27.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q96M27/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q96M27"}},"corpus_meta":[{"pmid":"34433667","id":"PMC_34433667","title":"An in vitro vesicle formation assay reveals cargo clients and factors that mediate vesicular trafficking.","date":"2021","source":"Proceedings of the National Academy of Sciences of the United States of America","url":"https://pubmed.ncbi.nlm.nih.gov/34433667","citation_count":40,"is_preprint":false},{"pmid":"40371640","id":"PMC_40371640","title":"ST6GalNAc-I regulates tumor cell sialylation via NECTIN2/MUC5AC-mediated immunosuppression and angiogenesis in non-small cell lung cancer.","date":"2025","source":"The Journal of clinical investigation","url":"https://pubmed.ncbi.nlm.nih.gov/40371640","citation_count":11,"is_preprint":false},{"pmid":"25205603","id":"PMC_25205603","title":"MLL partner genes in secondary acute lymphoblastic leukemia: report of a new partner PRRC1 and review of the literature.","date":"2014","source":"Leukemia research","url":"https://pubmed.ncbi.nlm.nih.gov/25205603","citation_count":6,"is_preprint":false},{"pmid":"24349040","id":"PMC_24349040","title":"Complex variation in measures of general intelligence and cognitive change.","date":"2013","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/24349040","citation_count":6,"is_preprint":false},{"pmid":"41932066","id":"PMC_41932066","title":"Single-cell transcriptomics reveal PRRC1 as a malignant cell enriched driver of DNA repair and therapy resistance in glioblastoma.","date":"2026","source":"DNA repair","url":"https://pubmed.ncbi.nlm.nih.gov/41932066","citation_count":1,"is_preprint":false},{"pmid":"41032520","id":"PMC_41032520","title":"Uncovering cargo clients and accessory factors of AP-1 and AP-4 through vesicle proteomics.","date":"2025","source":"Proceedings of the National Academy of Sciences of the United States of America","url":"https://pubmed.ncbi.nlm.nih.gov/41032520","citation_count":1,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":5398,"output_tokens":1333,"usd":0.018094,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":7997,"output_tokens":2050,"usd":0.045617,"stage2_stop_reason":"end_turn"},"total_usd":0.063711,"stage1_batch_id":"msgbatch_01CNoDbkChHEkgrJnL7BwtGJ","stage2_batch_id":"msgbatch_016Y4x9E9Wg5VQDANj9quSQD","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2021,\n      \"finding\": \"PRRC1 is recruited to endoplasmic reticulum (ER) exit sites, interacts with the inner COPII coat, and its absence increases membrane association of COPII, indicating PRRC1 regulates anterograde ER-to-Golgi trafficking.\",\n      \"method\": \"In vitro vesicle formation assay, quantitative mass spectrometry, co-immunoprecipitation/interaction assay, siRNA knockdown with COPII membrane association readout\",\n      \"journal\": \"Proceedings of the National Academy of Sciences of the United States of America\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1–2 / Moderate — in vitro reconstitution assay plus MS identification, binding interaction with COPII coat, and functional KD phenotype (increased COPII membrane association), multiple orthogonal methods in one study\",\n      \"pmids\": [\"34433667\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"PRRC1 acts as a cytosolic regulator essential for AP-4-mediated trans-Golgi network (TGN) export, functioning as an accessory factor for AP-4 vesicle biogenesis independently of clathrin.\",\n      \"method\": \"In vitro vesicle formation assay using AP4ε-deficient HeLa cells, label-free quantitative mass spectrometry, functional validation of PRRC1 requirement for AP-4-dependent trafficking\",\n      \"journal\": \"Proceedings of the National Academy of Sciences of the United States of America\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1–2 / Moderate — in vitro reconstitution vesicle assay combined with quantitative MS and genetic (AP4ε KO) epistasis, multiple orthogonal methods in one rigorous study\",\n      \"pmids\": [\"41032520\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"PRRC1 can serve as a fusion partner for MLL (KMT2A) in secondary acute lymphoblastic leukemia, producing an in-frame 5'MLL–3'PRRC1 fusion transcript resulting from a t(5;11)(q23-31;q23) chromosomal translocation.\",\n      \"method\": \"Banding cytogenetics, FISH, long-distance inverse PCR (LDI-PCR) to identify the fusion breakpoint\",\n      \"journal\": \"Leukemia research\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — molecularly characterized fusion gene in a single patient case using LDI-PCR; establishes the translocation but no functional mechanism of the fusion protein was tested\",\n      \"pmids\": [\"25205603\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2026,\n      \"finding\": \"shRNA-mediated knockdown of PRRC1 in GBM cells reduces proliferation, clonogenic survival, anchorage-independent growth, and 3D spheroid formation; under genotoxic stress, PRRC1-deficient cells show enhanced γ-H2AX accumulation, indicating PRRC1 supports DNA damage response and stress-adaptive programs in glioblastoma cells.\",\n      \"method\": \"shRNA knockdown in U87 and patient-derived GBM cells, clonogenic survival assay, γ-H2AX immunofluorescence under genotoxic stress, 3D spheroid assay\",\n      \"journal\": \"DNA repair\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2–3 / Weak — clean KD with multiple defined cellular phenotypes (proliferation, DNA damage signaling) in two cell models, but single lab and no direct biochemical mechanism elucidated for PRRC1 in DDR\",\n      \"pmids\": [\"41932066\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"MUC5AC interacts and colocalizes with PRRC1 in the Golgi, suggesting a role for PRRC1 in MUC5AC glycosylation.\",\n      \"method\": \"Co-localization/interaction assay (biochemical/proteomic analysis) in LUAD cells\",\n      \"journal\": \"The Journal of clinical investigation\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single co-localization/interaction observation in a study focused on ST6GalNAc-I; PRRC1's role in MUC5AC glycosylation is proposed but not functionally validated\",\n      \"pmids\": [\"40371640\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"PRRC1 is a proline-rich cytosolic protein that functions at multiple steps of vesicular trafficking: it is recruited to ER exit sites where it interacts with the inner COPII coat and negatively regulates COPII membrane association, and it also acts as an accessory factor required for AP-4-mediated export from the trans-Golgi network; additionally, PRRC1 supports DNA damage response and proliferative fitness in glioblastoma cells, and its locus is subject to MLL translocation in secondary leukemia.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"PRRC1 is a cytosolic accessory factor that operates at multiple steps of the secretory pathway. At ER exit sites it is recruited to the inner COPII coat and limits COPII membrane association, thereby tuning anterograde ER-to-Golgi transport [#0]. At the trans-Golgi network it acts as an essential cytosolic regulator of AP-4-mediated vesicle biogenesis, functioning independently of clathrin to support AP-4-dependent export [#1]. Beyond trafficking, loss of PRRC1 in glioblastoma cells impairs proliferation, clonogenic survival, and anchorage-independent growth and elevates γ-H2AX under genotoxic stress, linking PRRC1 to proliferative fitness and the DNA damage response in these cells [#3]. A t(5;11) chromosomal translocation can fuse PRRC1 in-frame to MLL (KMT2A) in secondary acute lymphoblastic leukemia [#2]. The molecular basis connecting PRRC1's trafficking functions to its DNA-damage and oncogenic roles has not been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2014,\n      \"claim\": \"Before any biochemical function was known, characterizing a leukemia breakpoint established that the PRRC1 locus can be rearranged, identifying it as an MLL fusion partner.\",\n      \"evidence\": \"Banding cytogenetics, FISH, and LDI-PCR breakpoint mapping in a secondary ALL patient case\",\n      \"pmids\": [\"25205603\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Single patient case; recurrence not established\",\n        \"No functional test of the 5'MLL-3'PRRC1 fusion protein\",\n        \"Does not address normal PRRC1 cellular function\"\n      ]\n    },\n    {\n      \"year\": 2021,\n      \"claim\": \"The first mechanistic assignment placed PRRC1 at ER exit sites as a regulator of COPII, answering what cellular process it participates in.\",\n      \"evidence\": \"In vitro vesicle formation assay, quantitative MS, co-IP, and siRNA knockdown reading out COPII membrane association\",\n      \"pmids\": [\"34433667\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Precise binding interface within the inner COPII coat not defined\",\n        \"Structural basis for negative regulation of COPII membrane association unresolved\"\n      ]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Extending its trafficking role, PRRC1 was shown to be required at a distinct compartment, the TGN, as an accessory factor for AP-4 vesicle biogenesis.\",\n      \"evidence\": \"In vitro vesicle formation assay in AP4ε-deficient HeLa cells with label-free quantitative MS and genetic epistasis\",\n      \"pmids\": [\"41032520\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Direct physical contact between PRRC1 and AP-4 not structurally defined\",\n        \"Whether the COPII and AP-4 roles share a common biochemical activity is unknown\"\n      ]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"A Golgi colocalization observation tentatively extended PRRC1 into cargo glycosylation, raising whether it influences MUC5AC processing.\",\n      \"evidence\": \"Co-localization/interaction assay in LUAD cells within a study focused on ST6GalNAc-I\",\n      \"pmids\": [\"40371640\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"Single co-localization observation without functional validation\",\n        \"No reciprocal or biochemical confirmation of the interaction\",\n        \"Role in MUC5AC glycosylation is inferred, not demonstrated\"\n      ]\n    },\n    {\n      \"year\": 2026,\n      \"claim\": \"Loss-of-function studies connected PRRC1 to cancer cell fitness and stress adaptation, beyond its trafficking roles.\",\n      \"evidence\": \"shRNA knockdown in U87 and patient-derived GBM cells with clonogenic, anchorage-independent growth, spheroid, and γ-H2AX assays under genotoxic stress\",\n      \"pmids\": [\"41932066\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No direct biochemical mechanism linking PRRC1 to the DNA damage response\",\n        \"Single-lab finding without orthogonal genetic validation\",\n        \"Whether the DDR phenotype is secondary to trafficking defects is unknown\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"It remains unknown what unifying molecular activity allows PRRC1 to act at both COPII and AP-4 vesicle steps and whether this relates to its proliferative and DNA-damage roles in cancer.\",\n      \"evidence\": null,\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No defined catalytic or adaptor activity established\",\n        \"No structural model of PRRC1 or its interaction interfaces\",\n        \"Mechanistic link between trafficking function and DDR/oncogenic phenotypes absent\"\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0098772\", \"supporting_discovery_ids\": [0, 1]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005829\", \"supporting_discovery_ids\": [0, 1]},\n      {\"term_id\": \"GO:0005783\", \"supporting_discovery_ids\": [0]},\n      {\"term_id\": \"GO:0005794\", \"supporting_discovery_ids\": [1]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-5653656\", \"supporting_discovery_ids\": [0, 1]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\"AP4E1\", \"MUC5AC\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":4,"faith_total":4,"faith_pct":100.0}}