{"gene":"CNTLN","run_date":"2026-06-09T22:57:18","timeline":{"discoveries":[{"year":2014,"finding":"Centlein (CNTLN) localizes to the proximal ends of centrioles and directly interacts with both C-Nap1 (Cep250) and Cep68, functioning as a molecular bridge between these two proteins to maintain centrosome cohesion during interphase. Depletion of centlein impairs recruitment of Cep68 to centrosomes, causing centrosome splitting.","method":"Co-immunoprecipitation, direct interaction assays, immunofluorescence localization, siRNA depletion with centrosome splitting readout","journal":"Journal of cell science","confidence":"High","confidence_rationale":"Tier 2 / Moderate — reciprocal Co-IP demonstrating direct interactions, loss-of-function (depletion) with specific cellular phenotype (centrosome splitting), and localization experiments; single lab but multiple orthogonal methods","pmids":["24554434"],"is_preprint":false},{"year":2014,"finding":"Centlein (CNTLN) is a substrate of Nek2A kinase, along with Cep68, suggesting Nek2A-mediated phosphorylation participates in regulating the C-Nap1–centlein–Cep68 cohesion complex.","method":"In vitro kinase assay identifying centlein and Cep68 as novel Nek2A substrates","journal":"Journal of cell science","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — kinase substrate identification reported in a single lab study; abstract states both are 'novel Nek2A substrates' but full mutagenesis details not described in abstract","pmids":["24554434"],"is_preprint":false}],"current_model":"Centlein (CNTLN) is a centriolar protein that localizes to the proximal ends of centrioles, where it directly bridges C-Nap1 (Cep250) and Cep68 to maintain centrosome cohesion during interphase; it is a substrate of Nek2A kinase, and its depletion causes loss of Cep68 from centrosomes and subsequent centrosome splitting."},"narrative":{"mechanistic_narrative":"Centlein (CNTLN) is a centriolar protein that maintains centrosome cohesion during interphase by acting as a molecular bridge within the proximal-end linker apparatus [PMID:24554434]. It localizes to the proximal ends of centrioles and directly interacts with both C-Nap1 (Cep250) and Cep68, physically connecting the two; its depletion impairs recruitment of Cep68 to centrosomes and causes premature centrosome splitting [PMID:24554434]. Centlein is a substrate of Nek2A kinase, placing the C-Nap1–centlein–Cep68 cohesion complex under phosphoregulatory control [PMID:24554434]. Beyond these interactions and their regulation by Nek2A, no further mechanistic detail has been characterized in the available corpus.","teleology":[{"year":2014,"claim":"Established what molecular link holds centrioles together during interphase by identifying centlein as a direct bridge between C-Nap1 and Cep68 required for centrosome cohesion.","evidence":"Reciprocal Co-IP and direct interaction assays, immunofluorescence localization to centriole proximal ends, and siRNA depletion scored for centrosome splitting in human cells","pmids":["24554434"],"confidence":"High","gaps":["Structural basis of the centlein–C-Nap1 and centlein–Cep68 interactions not resolved","Domains of centlein mediating each interaction not mapped","Single-lab study without independent replication"]},{"year":2014,"claim":"Connected the cohesion linker to cell-cycle control by showing centlein (and Cep68) are phosphorylation substrates of Nek2A kinase.","evidence":"In vitro kinase assay identifying centlein and Cep68 as novel Nek2A substrates","pmids":["24554434"],"confidence":"Medium","gaps":["Phosphorylation sites and functional mutagenesis not characterized in the report","Whether Nek2A phosphorylation disassembles the cohesion complex in cells is untested","No in vivo confirmation of the phosphorylation event"]},{"year":null,"claim":"How Nek2A phosphorylation of centlein is coupled to the timing of centrosome separation at mitotic entry remains unresolved.","evidence":"","pmids":[],"confidence":"Low","gaps":["No phosphosite-level mechanism linking centlein modification to linker dissolution","No structural model of the C-Nap1–centlein–Cep68 bridge"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0060090","term_label":"molecular adaptor activity","supporting_discovery_ids":[0]}],"localization":[{"term_id":"GO:0005815","term_label":"microtubule organizing center","supporting_discovery_ids":[0]}],"pathway":[{"term_id":"R-HSA-1640170","term_label":"Cell Cycle","supporting_discovery_ids":[0]}],"complexes":[],"partners":["CEP250","CEP68","NEK2"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q9NXG0","full_name":"Centlein","aliases":["Centrosomal protein"],"length_aa":1405,"mass_kda":161.6,"function":"Required for centrosome cohesion and recruitment of CEP68 to centrosomes","subcellular_location":"Cytoplasm, cytoskeleton, microtubule organizing center, centrosome, centriole","url":"https://www.uniprot.org/uniprotkb/Q9NXG0/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/CNTLN","classification":"Not Classified","n_dependent_lines":5,"n_total_lines":1208,"dependency_fraction":0.0041390728476821195},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[],"url":"https://opencell.sf.czbiohub.org/search/CNTLN","total_profiled":1310},"omim":[{"mim_id":"618291","title":"SPINAL MUSCULAR ATROPHY, LOWER EXTREMITY-PREDOMINANT, 2B, PRENATAL ONSET, AUTOSOMAL DOMINANT; SMALED2B","url":"https://www.omim.org/entry/618291"},{"mim_id":"616889","title":"CENTROSOMAL PROTEIN, 68-KD; CEP68","url":"https://www.omim.org/entry/616889"},{"mim_id":"615290","title":"SPINAL MUSCULAR ATROPHY, LOWER EXTREMITY-PREDOMINANT, 2A, CHILDHOOD ONSET, AUTOSOMAL DOMINANT; SMALED2A","url":"https://www.omim.org/entry/615290"},{"mim_id":"611870","title":"CENTLEIN; CNTLN","url":"https://www.omim.org/entry/611870"},{"mim_id":"609797","title":"BICD CARGO ADAPTOR 2; BICD2","url":"https://www.omim.org/entry/609797"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Approved","locations":[{"location":"Centrosome","reliability":"Approved"},{"location":"Nucleoplasm","reliability":"Additional"},{"location":"Cytosol","reliability":"Additional"}],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in all","driving_tissues":[],"url":"https://www.proteinatlas.org/search/CNTLN"},"hgnc":{"alias_symbol":["FLJ20276","bA340N12.1","OTTHUMG00000019597"],"prev_symbol":["C9orf101","C9orf39"]},"alphafold":{"accession":"Q9NXG0","domains":[{"cath_id":"-","chopping":"96-329","consensus_level":"medium","plddt":87.8529,"start":96,"end":329},{"cath_id":"1.20.5","chopping":"1318-1372","consensus_level":"high","plddt":73.6656,"start":1318,"end":1372}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q9NXG0","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q9NXG0-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q9NXG0-F1-predicted_aligned_error_v6.png","plddt_mean":70.25},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=CNTLN","jax_strain_url":"https://www.jax.org/strain/search?query=CNTLN"},"sequence":{"accession":"Q9NXG0","fasta_url":"https://rest.uniprot.org/uniprotkb/Q9NXG0.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q9NXG0/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q9NXG0"}},"corpus_meta":[{"pmid":"24554434","id":"PMC_24554434","title":"Centlein mediates an interaction between C-Nap1 and Cep68 to maintain centrosome cohesion.","date":"2014","source":"Journal of cell science","url":"https://pubmed.ncbi.nlm.nih.gov/24554434","citation_count":55,"is_preprint":false},{"pmid":"34827207","id":"PMC_34827207","title":"Transcriptomic Profile of New Gene Markers Encoding Proteins Responsible for Structure of Porcine Ovarian Granulosa Cells.","date":"2021","source":"Biology","url":"https://pubmed.ncbi.nlm.nih.gov/34827207","citation_count":30,"is_preprint":false},{"pmid":"27743375","id":"PMC_27743375","title":"Genetic resilience to amyloid related cognitive decline.","date":"2017","source":"Brain imaging and behavior","url":"https://pubmed.ncbi.nlm.nih.gov/27743375","citation_count":27,"is_preprint":false},{"pmid":"26035058","id":"PMC_26035058","title":"Genome-wide copy-number variation study of psychosis in Alzheimer's disease.","date":"2015","source":"Translational psychiatry","url":"https://pubmed.ncbi.nlm.nih.gov/26035058","citation_count":24,"is_preprint":false},{"pmid":"17668870","id":"PMC_17668870","title":"Novel aphidicolin-inducible common fragile site FRA9G maps to 9p22.2, within the C9orf39 gene.","date":"2007","source":"Genes, chromosomes & cancer","url":"https://pubmed.ncbi.nlm.nih.gov/17668870","citation_count":23,"is_preprint":false},{"pmid":"27270507","id":"PMC_27270507","title":"Genetic variations associated with six-white-point coat pigmentation in Diannan small-ear pigs.","date":"2016","source":"Scientific reports","url":"https://pubmed.ncbi.nlm.nih.gov/27270507","citation_count":22,"is_preprint":false},{"pmid":"33405298","id":"PMC_33405298","title":"iTRAQ-based proteomic analysis of the molecular mechanisms and downstream effects of fatty acid synthase in osteosarcoma cells.","date":"2021","source":"Journal of clinical laboratory analysis","url":"https://pubmed.ncbi.nlm.nih.gov/33405298","citation_count":14,"is_preprint":false},{"pmid":"23827040","id":"PMC_23827040","title":"The use of redberry juniper (Juniperus pinchotii) to reduce Haemonchus contortus fecal egg counts and increase ivermectin efficacy.","date":"2013","source":"Veterinary parasitology","url":"https://pubmed.ncbi.nlm.nih.gov/23827040","citation_count":13,"is_preprint":false},{"pmid":"36788602","id":"PMC_36788602","title":"Ultra-low-coverage genome-wide association study-insights into gestational age using 17,844 embryo samples with preimplantation genetic testing.","date":"2023","source":"Genome medicine","url":"https://pubmed.ncbi.nlm.nih.gov/36788602","citation_count":6,"is_preprint":false},{"pmid":"36090173","id":"PMC_36090173","title":"Transcriptome sequencing reveals differences between leydig cells and sertoli cells of yak.","date":"2022","source":"Frontiers in veterinary science","url":"https://pubmed.ncbi.nlm.nih.gov/36090173","citation_count":4,"is_preprint":false},{"pmid":"40646437","id":"PMC_40646437","title":"Bivariate GWAS performed on rabbits divergently selected for intramuscular fat content reveals pleiotropic genomic regions and genes related to meat and carcass quality traits.","date":"2025","source":"Genetics, selection, evolution : GSE","url":"https://pubmed.ncbi.nlm.nih.gov/40646437","citation_count":1,"is_preprint":false},{"pmid":"22940680","id":"PMC_22940680","title":"Variant on chromosome 9p is associated with left ventricular mass: results from two cohorts of essential hypertensive individuals.","date":"2012","source":"Journal of hypertension","url":"https://pubmed.ncbi.nlm.nih.gov/22940680","citation_count":1,"is_preprint":false},{"pmid":"39640822","id":"PMC_39640822","title":"High heritability of human facial traits reveals associations with CNTLN, BRCA1, and TMPRSS6 loci in Korean families.","date":"2024","source":"Heliyon","url":"https://pubmed.ncbi.nlm.nih.gov/39640822","citation_count":0,"is_preprint":false},{"pmid":"41681505","id":"PMC_41681505","title":"GWAS-Identified SNPs and Candidate Genes Influencing Sex in Loach (Misgurnus anguillicaudatus).","date":"2026","source":"Animals : an open access journal from MDPI","url":"https://pubmed.ncbi.nlm.nih.gov/41681505","citation_count":0,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":9487,"output_tokens":1127,"usd":0.022683,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":6909,"output_tokens":1151,"usd":0.03166,"stage2_stop_reason":"end_turn"},"total_usd":0.054343,"stage1_batch_id":"msgbatch_01ACAxJQabDsht39JXeWG22d","stage2_batch_id":"msgbatch_01QEU22A9U5sbPTgsMzTmvSf","note":"batch pricing = 50% of standard"},"stage1_raw":"Looking at the papers, I need to identify which ones describe mechanistic findings about the canonical human CNTLN protein (centlein, centrosomal protein).\n\n**Paper-by-paper classification:**\n\n1. PMID:24554434 - Direct mechanistic study of CNTLN (centlein) protein. **INCLUDE**\n2. PMID:34827207 - Expression/transcriptomics in granulosa cells. EXCLUDE (expression correlation)\n3. PMID:27743375 - GWAS/predicted expression analysis. EXCLUDE (no direct mechanism)\n4. PMID:26035058 - CNV association study. EXCLUDE (genetic association only)\n5. PMID:17668870 - Maps common fragile site FRA9G within C9orf39 (=CNTLN). This is about chromosomal fragility at the DNA level, not the protein's mechanism. EXCLUDE (not mechanistic for the protein)\n6. PMID:27270507 - Pig coat color GWAS. EXCLUDE (genetic association)\n7. PMID:33405298 - Proteomics screen; CNTLN listed as downregulated protein. EXCLUDE (catalog/screen)\n8. PMID:23827040 - Veterinary parasitology; \"CNTL\" = control group abbreviation, not the gene. EXCLUDE (symbol collision/abbreviation)\n9. PMID:36788602 - GWAS gestational age. EXCLUDE (genetic association)\n10. PMID:36090173 - Transcriptome in yak cells; CNTLN mentioned as expression difference. EXCLUDE (expression correlation)\n11. PMID:40646437 - Rabbit GWAS. EXCLUDE (genetic association)\n12. PMID:22940680 - SNP association with LVM. EXCLUDE (genetic association)\n13. PMID:39640822 - GWAS facial traits. EXCLUDE (genetic association)\n14. PMID:41681505 - Loach GWAS; cntln mentioned as candidate gene. EXCLUDE (genetic association, fish)\n\nOnly PMID:24554434 contains direct mechanistic findings about CNTLN protein.\n\n```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2014,\n      \"finding\": \"Centlein (CNTLN) localizes to the proximal ends of centrioles and directly interacts with both C-Nap1 (Cep250) and Cep68, functioning as a molecular bridge between these two proteins to maintain centrosome cohesion during interphase. Depletion of centlein impairs recruitment of Cep68 to centrosomes, causing centrosome splitting.\",\n      \"method\": \"Co-immunoprecipitation, direct interaction assays, immunofluorescence localization, siRNA depletion with centrosome splitting readout\",\n      \"journal\": \"Journal of cell science\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reciprocal Co-IP demonstrating direct interactions, loss-of-function (depletion) with specific cellular phenotype (centrosome splitting), and localization experiments; single lab but multiple orthogonal methods\",\n      \"pmids\": [\"24554434\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"Centlein (CNTLN) is a substrate of Nek2A kinase, along with Cep68, suggesting Nek2A-mediated phosphorylation participates in regulating the C-Nap1–centlein–Cep68 cohesion complex.\",\n      \"method\": \"In vitro kinase assay identifying centlein and Cep68 as novel Nek2A substrates\",\n      \"journal\": \"Journal of cell science\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — kinase substrate identification reported in a single lab study; abstract states both are 'novel Nek2A substrates' but full mutagenesis details not described in abstract\",\n      \"pmids\": [\"24554434\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"Centlein (CNTLN) is a centriolar protein that localizes to the proximal ends of centrioles, where it directly bridges C-Nap1 (Cep250) and Cep68 to maintain centrosome cohesion during interphase; it is a substrate of Nek2A kinase, and its depletion causes loss of Cep68 from centrosomes and subsequent centrosome splitting.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"Centlein (CNTLN) is a centriolar protein that maintains centrosome cohesion during interphase by acting as a molecular bridge within the proximal-end linker apparatus [#0]. It localizes to the proximal ends of centrioles and directly interacts with both C-Nap1 (Cep250) and Cep68, physically connecting the two; its depletion impairs recruitment of Cep68 to centrosomes and causes premature centrosome splitting [#0]. Centlein is a substrate of Nek2A kinase, placing the C-Nap1–centlein–Cep68 cohesion complex under phosphoregulatory control [#1]. Beyond these interactions and their regulation by Nek2A, no further mechanistic detail has been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2014,\n      \"claim\": \"Established what molecular link holds centrioles together during interphase by identifying centlein as a direct bridge between C-Nap1 and Cep68 required for centrosome cohesion.\",\n      \"evidence\": \"Reciprocal Co-IP and direct interaction assays, immunofluorescence localization to centriole proximal ends, and siRNA depletion scored for centrosome splitting in human cells\",\n      \"pmids\": [\"24554434\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Structural basis of the centlein–C-Nap1 and centlein–Cep68 interactions not resolved\",\n        \"Domains of centlein mediating each interaction not mapped\",\n        \"Single-lab study without independent replication\"\n      ]\n    },\n    {\n      \"year\": 2014,\n      \"claim\": \"Connected the cohesion linker to cell-cycle control by showing centlein (and Cep68) are phosphorylation substrates of Nek2A kinase.\",\n      \"evidence\": \"In vitro kinase assay identifying centlein and Cep68 as novel Nek2A substrates\",\n      \"pmids\": [\"24554434\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Phosphorylation sites and functional mutagenesis not characterized in the report\",\n        \"Whether Nek2A phosphorylation disassembles the cohesion complex in cells is untested\",\n        \"No in vivo confirmation of the phosphorylation event\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How Nek2A phosphorylation of centlein is coupled to the timing of centrosome separation at mitotic entry remains unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No phosphosite-level mechanism linking centlein modification to linker dissolution\",\n        \"No structural model of the C-Nap1–centlein–Cep68 bridge\"\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0060090\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005815\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-1640170\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\"CEP250\", \"CEP68\", \"NEK2\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":3,"faith_total":3,"faith_pct":100.0}}