{"gene":"PRR14L","run_date":"2026-06-10T06:43:36","timeline":{"discoveries":[{"year":2018,"finding":"ShRNA knockdown of PRR14L in human CD34+ cells followed by in vitro differentiation assays showed an increase in monocytes and decrease in neutrophils, consistent with a CMML-like phenotype, indicating PRR14L loss-of-function drives a specific hematopoietic differentiation defect. Cellular localization studies also suggested a role for PRR14L in cell division.","method":"ShRNA knockdown in human CD34+ cells, in vitro growth and differentiation assays, cellular localization studies","journal":"Leukemia","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — defined cellular phenotype from KD with specific readout, single lab, single method set","pmids":["30573780"],"is_preprint":false},{"year":2025,"finding":"Proximity labeling of PRR14L using TurboID identified the PP2A-B56 phosphatase complex and the spindle assembly factor TACC3 as PRR14L-interacting proteins, establishing PRR14L as a scaffold linking the PP2A-TACC3 axis.","method":"TurboID proximity labeling mass spectrometry","journal":"Molecular biology of the cell","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — proximity labeling MS replicated across preprint and peer-reviewed publication by same lab; single lab but published in two forms","pmids":["41279925","42160513"],"is_preprint":false},{"year":2025,"finding":"Loss of PRR14L prolongs spindle assembly checkpoint (SAC)-dependent mitotic arrest in response to microtubule depolymerization, demonstrating that PRR14L normally limits the duration of SAC-mediated arrest.","method":"CRISPR/Cas9 loss-of-function, live-cell mitotic arrest assays with microtubule depolymerizing agents","journal":"Molecular biology of the cell","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — CRISPR KO with defined mitotic phenotype, replicated across preprint and peer-reviewed publication","pmids":["41279925","42160513"],"is_preprint":false},{"year":2025,"finding":"Loss of PRR14L leads to catastrophic mitotic errors upon SAC abrogation by MPS1 inhibitors, indicating that PRR14L is required for mitotic fidelity when checkpoint signaling is compromised.","method":"CRISPR/Cas9 loss-of-function combined with MPS1 inhibitor (NMS-P715) treatment, genome-wide CRISPR screen","journal":"Molecular biology of the cell","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — genome-wide CRISPR screen plus targeted KO with defined mitotic error phenotype, replicated across preprint and peer-reviewed publication","pmids":["41279925","42160513"],"is_preprint":false}],"current_model":"PRR14L is a scaffold protein that interacts with the PP2A-B56 phosphatase complex and the spindle assembly factor TACC3 to regulate mitotic fidelity; its loss prolongs SAC-dependent mitotic arrest but causes catastrophic mitotic errors when the SAC is abrogated by MPS1 inhibition, and in hematopoietic cells its loss-of-function skews differentiation toward monocytes at the expense of neutrophils."},"narrative":{"mechanistic_narrative":"PRR14L is a scaffold protein that supports mitotic fidelity and constrains the spindle assembly checkpoint (SAC) [PMID:41279925, PMID:42160513]. Proximity labeling places PRR14L in physical proximity to the PP2A-B56 phosphatase complex and the spindle assembly factor TACC3, defining it as a scaffold linking a PP2A-TACC3 axis during cell division [PMID:41279925, PMID:42160513]. Consistent with this role, loss of PRR14L prolongs SAC-dependent mitotic arrest upon microtubule depolymerization, indicating that PRR14L normally limits the duration of checkpoint-mediated arrest [PMID:41279925, PMID:42160513]; when the checkpoint is abrogated by MPS1 inhibition, PRR14L-deficient cells instead undergo catastrophic mitotic errors, showing that PRR14L is required to maintain mitotic fidelity when checkpoint signaling is compromised [PMID:41279925, PMID:42160513]. In the hematopoietic lineage, PRR14L loss-of-function skews CD34+ differentiation toward monocytes at the expense of neutrophils, a CMML-like phenotype [PMID:30573780]. Beyond these mitotic and differentiation observations, the molecular logic by which PRR14L coordinates PP2A-B56 and TACC3 has not been resolved in the available corpus.","teleology":[{"year":2018,"claim":"Established that PRR14L loss-of-function has a defined cellular consequence, linking the gene to hematopoietic differentiation control and hinting at a cell-division role.","evidence":"shRNA knockdown in human CD34+ cells with in vitro differentiation assays and cellular localization studies","pmids":["30573780"],"confidence":"Medium","gaps":["No molecular mechanism connecting PRR14L to the differentiation skew","Localization role in cell division only suggested, not defined","Single lab, single method set"]},{"year":2025,"claim":"Identified the physical interaction network of PRR14L, placing it as a scaffold proximal to the PP2A-B56 phosphatase and TACC3.","evidence":"TurboID proximity labeling mass spectrometry","pmids":["41279925","42160513"],"confidence":"Medium","gaps":["Proximity labeling does not establish direct binding or stable complex stoichiometry","Functional consequence of the PP2A-TACC3 link not dissected","Single lab"]},{"year":2025,"claim":"Defined PRR14L as a negative regulator of SAC-dependent arrest duration and as a guardian of mitotic fidelity when the checkpoint is bypassed.","evidence":"CRISPR/Cas9 loss-of-function with live-cell mitotic arrest assays, MPS1 inhibitor treatment, and a genome-wide CRISPR screen","pmids":["41279925","42160513"],"confidence":"Medium","gaps":["Mechanism by which PRR14L limits arrest duration unresolved","How PRR14L loss produces catastrophic errors under MPS1 inhibition not mechanistically mapped","Connection between the mitotic role and the hematopoietic phenotype untested"]},{"year":null,"claim":"How PRR14L mechanistically coordinates PP2A-B56 phosphatase activity and TACC3 to control checkpoint timing and segregation fidelity, and whether this explains its hematopoietic differentiation role, remains unresolved.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No structural or biochemical model of the scaffold function","Direct substrates/dephosphorylation targets of the PRR14L-PP2A axis unknown","Causal link between mitotic defects and CMML-like differentiation skew not established"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0060090","term_label":"molecular adaptor activity","supporting_discovery_ids":[1]}],"localization":[],"pathway":[{"term_id":"R-HSA-1640170","term_label":"Cell Cycle","supporting_discovery_ids":[2,3]}],"complexes":[],"partners":["TACC3","PPP2R5"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q5THK1","full_name":"Protein PRR14L","aliases":["Proline rich 14-like protein"],"length_aa":2151,"mass_kda":237.3,"function":"","subcellular_location":"","url":"https://www.uniprot.org/uniprotkb/Q5THK1/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/PRR14L","classification":"Not Classified","n_dependent_lines":6,"n_total_lines":1208,"dependency_fraction":0.004966887417218543},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[{"gene":"ALDH16A1","stoichiometry":0.2},{"gene":"FKBP5","stoichiometry":0.2},{"gene":"HSPA4","stoichiometry":0.2},{"gene":"PPP2CA","stoichiometry":0.2},{"gene":"PTGES3","stoichiometry":0.2},{"gene":"TNPO1","stoichiometry":0.2}],"url":"https://opencell.sf.czbiohub.org/search/PRR14L","total_profiled":1310},"omim":[{"mim_id":"621035","title":"PROLINE-RICH PROTEIN 14-LIKE PROTEIN; PRR14L","url":"https://www.omim.org/entry/621035"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Approved","locations":[{"location":"Nucleoplasm","reliability":"Approved"}],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in all","driving_tissues":[],"url":"https://www.proteinatlas.org/search/PRR14L"},"hgnc":{"alias_symbol":["MGC50372"],"prev_symbol":["C22orf30"]},"alphafold":{"accession":"Q5THK1","domains":[],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q5THK1","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q5THK1-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q5THK1-F1-predicted_aligned_error_v6.png","plddt_mean":35.5},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=PRR14L","jax_strain_url":"https://www.jax.org/strain/search?query=PRR14L"},"sequence":{"accession":"Q5THK1","fasta_url":"https://rest.uniprot.org/uniprotkb/Q5THK1.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q5THK1/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q5THK1"}},"corpus_meta":[{"pmid":"30573780","id":"PMC_30573780","title":"PRR14L mutations are associated with chromosome 22 acquired uniparental disomy, age-related clonal hematopoiesis and myeloid neoplasia.","date":"2018","source":"Leukemia","url":"https://pubmed.ncbi.nlm.nih.gov/30573780","citation_count":11,"is_preprint":false},{"pmid":"37810911","id":"PMC_37810911","title":"Next-Generation Sequencing Analysis of 3 Uterine Adenosarcomas with Heterogeneously Differentiated Genomic Mutations.","date":"2023","source":"International journal of analytical chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/37810911","citation_count":1,"is_preprint":false},{"pmid":"41279925","id":"PMC_41279925","title":"The scaffold protein PRR14L links the PP2A-TACC3 axis to mitotic fidelity and sensitivity to MPS1 inhibition.","date":"2025","source":"bioRxiv : the preprint server for biology","url":"https://pubmed.ncbi.nlm.nih.gov/41279925","citation_count":0,"is_preprint":false},{"pmid":"42160513","id":"PMC_42160513","title":"The scaffold protein PRR14L is linked to mitotic fidelity and sensitivity to MPS1 inhibition.","date":"2026","source":"Molecular biology of the cell","url":"https://pubmed.ncbi.nlm.nih.gov/42160513","citation_count":0,"is_preprint":false},{"pmid":null,"id":"bio_10.1101_2025.11.14.25340228","title":"Tandem Repeat Polymorphisms Are Associated with Brain Structure: Results of Two Large Population-based Studies","date":"2025-11-19","source":"bioRxiv","url":"https://doi.org/10.1101/2025.11.14.25340228","citation_count":0,"is_preprint":true}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":4355,"output_tokens":967,"usd":0.013785,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":7491,"output_tokens":1534,"usd":0.037902,"stage2_stop_reason":"end_turn"},"total_usd":0.051687,"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\": 2018,\n      \"finding\": \"ShRNA knockdown of PRR14L in human CD34+ cells followed by in vitro differentiation assays showed an increase in monocytes and decrease in neutrophils, consistent with a CMML-like phenotype, indicating PRR14L loss-of-function drives a specific hematopoietic differentiation defect. Cellular localization studies also suggested a role for PRR14L in cell division.\",\n      \"method\": \"ShRNA knockdown in human CD34+ cells, in vitro growth and differentiation assays, cellular localization studies\",\n      \"journal\": \"Leukemia\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — defined cellular phenotype from KD with specific readout, single lab, single method set\",\n      \"pmids\": [\"30573780\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"Proximity labeling of PRR14L using TurboID identified the PP2A-B56 phosphatase complex and the spindle assembly factor TACC3 as PRR14L-interacting proteins, establishing PRR14L as a scaffold linking the PP2A-TACC3 axis.\",\n      \"method\": \"TurboID proximity labeling mass spectrometry\",\n      \"journal\": \"Molecular biology of the cell\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — proximity labeling MS replicated across preprint and peer-reviewed publication by same lab; single lab but published in two forms\",\n      \"pmids\": [\"41279925\", \"42160513\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"Loss of PRR14L prolongs spindle assembly checkpoint (SAC)-dependent mitotic arrest in response to microtubule depolymerization, demonstrating that PRR14L normally limits the duration of SAC-mediated arrest.\",\n      \"method\": \"CRISPR/Cas9 loss-of-function, live-cell mitotic arrest assays with microtubule depolymerizing agents\",\n      \"journal\": \"Molecular biology of the cell\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — CRISPR KO with defined mitotic phenotype, replicated across preprint and peer-reviewed publication\",\n      \"pmids\": [\"41279925\", \"42160513\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"Loss of PRR14L leads to catastrophic mitotic errors upon SAC abrogation by MPS1 inhibitors, indicating that PRR14L is required for mitotic fidelity when checkpoint signaling is compromised.\",\n      \"method\": \"CRISPR/Cas9 loss-of-function combined with MPS1 inhibitor (NMS-P715) treatment, genome-wide CRISPR screen\",\n      \"journal\": \"Molecular biology of the cell\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — genome-wide CRISPR screen plus targeted KO with defined mitotic error phenotype, replicated across preprint and peer-reviewed publication\",\n      \"pmids\": [\"41279925\", \"42160513\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"PRR14L is a scaffold protein that interacts with the PP2A-B56 phosphatase complex and the spindle assembly factor TACC3 to regulate mitotic fidelity; its loss prolongs SAC-dependent mitotic arrest but causes catastrophic mitotic errors when the SAC is abrogated by MPS1 inhibition, and in hematopoietic cells its loss-of-function skews differentiation toward monocytes at the expense of neutrophils.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"PRR14L is a scaffold protein that supports mitotic fidelity and constrains the spindle assembly checkpoint (SAC) [#2, #3]. Proximity labeling places PRR14L in physical proximity to the PP2A-B56 phosphatase complex and the spindle assembly factor TACC3, defining it as a scaffold linking a PP2A-TACC3 axis during cell division [#1]. Consistent with this role, loss of PRR14L prolongs SAC-dependent mitotic arrest upon microtubule depolymerization, indicating that PRR14L normally limits the duration of checkpoint-mediated arrest [#2]; when the checkpoint is abrogated by MPS1 inhibition, PRR14L-deficient cells instead undergo catastrophic mitotic errors, showing that PRR14L is required to maintain mitotic fidelity when checkpoint signaling is compromised [#3]. In the hematopoietic lineage, PRR14L loss-of-function skews CD34+ differentiation toward monocytes at the expense of neutrophils, a CMML-like phenotype [#0]. Beyond these mitotic and differentiation observations, the molecular logic by which PRR14L coordinates PP2A-B56 and TACC3 has not been resolved in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2018,\n      \"claim\": \"Established that PRR14L loss-of-function has a defined cellular consequence, linking the gene to hematopoietic differentiation control and hinting at a cell-division role.\",\n      \"evidence\": \"shRNA knockdown in human CD34+ cells with in vitro differentiation assays and cellular localization studies\",\n      \"pmids\": [\"30573780\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No molecular mechanism connecting PRR14L to the differentiation skew\", \"Localization role in cell division only suggested, not defined\", \"Single lab, single method set\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Identified the physical interaction network of PRR14L, placing it as a scaffold proximal to the PP2A-B56 phosphatase and TACC3.\",\n      \"evidence\": \"TurboID proximity labeling mass spectrometry\",\n      \"pmids\": [\"41279925\", \"42160513\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Proximity labeling does not establish direct binding or stable complex stoichiometry\", \"Functional consequence of the PP2A-TACC3 link not dissected\", \"Single lab\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Defined PRR14L as a negative regulator of SAC-dependent arrest duration and as a guardian of mitotic fidelity when the checkpoint is bypassed.\",\n      \"evidence\": \"CRISPR/Cas9 loss-of-function with live-cell mitotic arrest assays, MPS1 inhibitor treatment, and a genome-wide CRISPR screen\",\n      \"pmids\": [\"41279925\", \"42160513\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Mechanism by which PRR14L limits arrest duration unresolved\", \"How PRR14L loss produces catastrophic errors under MPS1 inhibition not mechanistically mapped\", \"Connection between the mitotic role and the hematopoietic phenotype untested\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How PRR14L mechanistically coordinates PP2A-B56 phosphatase activity and TACC3 to control checkpoint timing and segregation fidelity, and whether this explains its hematopoietic differentiation role, remains unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No structural or biochemical model of the scaffold function\", \"Direct substrates/dephosphorylation targets of the PRR14L-PP2A axis unknown\", \"Causal link between mitotic defects and CMML-like differentiation skew not established\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0060090\", \"supporting_discovery_ids\": [1]}\n    ],\n    \"localization\": [],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-1640170\", \"supporting_discovery_ids\": [2, 3]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\"TACC3\", \"PPP2R5\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"faith_supported":4,"faith_total":4,"faith_pct":100.0}}