{"gene":"NHP2","run_date":"2026-06-10T05:19:52","timeline":{"discoveries":[{"year":2000,"finding":"Human NHP2 (hNHP2) is a core protein component of H/ACA snoRNP complexes; epitope-tagged hNHP2 co-immunoprecipitates with hGAR1, H/ACA RNAs, and the RNA subunit of telomerase (hTR, which contains an H/ACA-like domain in its 3' moiety) in HeLa cell extracts. hNHP2 also functionally complements yeast cells depleted of Nhp2p. Immunofluorescence showed hNHP2 localizes to the dense fibrillar component of the nucleolus and Cajal bodies.","method":"Immunoprecipitation from transfected HeLa cell extracts; yeast complementation assay; immunofluorescence microscopy","journal":"Molecular and cellular biology","confidence":"High","confidence_rationale":"Tier 2 / Strong — reciprocal co-IP with multiple partners, functional complementation across species, and localization data in a single study; independently consistent with subsequent work","pmids":["11074001"],"is_preprint":false},{"year":1991,"finding":"NHP2 in S. cerevisiae encodes an essential 17.1 kDa basic nuclear protein; deletion of one NHP2 copy in diploid yeast followed by sporulation showed that spores lacking NHP2 germinate but form only microcolonies of 12–40 cells, demonstrating NHP2 is essential for normal cell proliferation.","method":"Gene deletion / spore dissection in S. cerevisiae; S1 nuclease mapping","journal":"Yeast (Chichester, England)","confidence":"High","confidence_rationale":"Tier 2 / Strong — genetic deletion with clear phenotypic readout in a foundational study; foundational essential-function result replicated conceptually by subsequent work","pmids":["2063628"],"is_preprint":false},{"year":1999,"finding":"Fission yeast p17(nhp2) is a nucleolar protein that functionally complements deletion of S. cerevisiae NHP2 and remains associated with nucleolar material throughout the mitotic cell cycle, including during anaphase, suggesting H/ACA snoRNPs are continuously nucleolus-associated during cell division. In S. cerevisiae, Nhp2 co-segregates with bulk chromatin/rDNA during nuclear division.","method":"Yeast complementation; live-cell fluorescence microscopy of GFP-tagged Nhp2 through the cell cycle","journal":"Experimental cell research","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — complementation plus live imaging, single lab","pmids":["10502409"],"is_preprint":false},{"year":2008,"finding":"siRNA-mediated knockdown of NHP2 in human cells reduces TERC (telomerase RNA) levels, demonstrating NHP2 is required for TERC accumulation/stability. In contrast, GAR1 knockdown did not reduce TERC levels, establishing a functional difference between these two H/ACA complex components with respect to telomerase RNA stabilization.","method":"siRNA knockdown in human cells followed by quantification of TERC levels","journal":"Proceedings of the National Academy of Sciences of the United States of America","confidence":"High","confidence_rationale":"Tier 2 / Strong — direct loss-of-function with defined molecular readout (TERC level), complemented by parallel GAR1 knockdown control establishing specificity; published in high-impact journal","pmids":["18523010"],"is_preprint":false},{"year":2009,"finding":"Disease-associated NHP2 mutations V126M and Y139H impair NHP2's association with NOP10, causing major pre-RNP assembly defects with all H/ACA RNAs tested, including the H/ACA domain of hTR. This establishes that the NHP2–NOP10 interaction is critical for H/ACA pre-RNP formation. The most prevalent dyskerin DC mutation (A353V) did not affect NAF1-dyskerin-NOP10-NHP2 tetramer formation but slightly reduced assembly with the H/ACA-like domain of hTR.","method":"In vivo pre-RNP assembly assays with wild-type and mutant proteins; co-immunoprecipitation of NHP2 mutants with NOP10 and H/ACA RNAs","journal":"Human molecular genetics","confidence":"High","confidence_rationale":"Tier 2 / Strong — multiple mutants tested against multiple H/ACA RNA substrates, clear molecular phenotype with mechanistic interpretation, orthogonal co-IP and RNA binding assays","pmids":["20008900"],"is_preprint":false},{"year":2020,"finding":"Functional deficit of human NHP2 (demonstrated using patient-derived cells with biallelic NHP2 mutations) affects ribosomal RNA (rRNA) biogenesis in addition to telomere maintenance, extending the known molecular consequences of NHP2 loss beyond TERC stabilization.","method":"Analysis of patient cells with NHP2 mutations; rRNA biogenesis assays","journal":"Human molecular genetics","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — patient-derived cells with defined mutations; rRNA biogenesis readout, single lab","pmids":["31985013"],"is_preprint":false},{"year":2021,"finding":"In ALT-positive cancer cells that retain hTR expression, NHP2 H/ACA ribonucleoprotein levels are downregulated, and this downregulation restrains DNA damage response (DDR) activation at ALT telomeres by reducing 53BP1 recruitment. This role of NHP2 is mechanistically independent from hTR's non-canonical function in modulating telomeric p-RPA(S33).","method":"NHP2 knockdown/manipulation in ALT+ cancer cells; 53BP1 and p-RPA(S33) foci quantification at telomeres; epistasis with hTR expression","journal":"The EMBO journal","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — defined molecular pathway placement via epistasis and loss-of-function with specific readouts, single lab","pmids":["33595114"],"is_preprint":false},{"year":2021,"finding":"Nhp2 (yeast) functions as a reader of the histone modification H2AQ105 methylation (H2AQ105me) at the rDNA locus, and acts as an adapter bridging rDNA chromatin with components of the small subunit processome to coordinate rRNA transcription with post-transcriptional processing. Nhp2 binding to H2AQ105me depends on a functional mTOR signaling pathway and H3K56 acetylation. An H2AQ105A mutant shows a mild defect in early rRNA processing.","method":"Functional and proteomic data; identification of Nhp2 as H2AQ105me reader; chromatin-binding assays; H2AQ105A mutant rRNA processing analysis","journal":"EMBO reports","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — novel reader function identified with proteomic and functional validation; yeast model, single lab, mechanistic novelty","pmids":["34409714"],"is_preprint":false},{"year":2023,"finding":"Novel NHP2 variants A39T and T44M fail to be incorporated into the H/ACA RNA-binding complex when competing with wild-type NHP2, and misincorporated variants undergo proteasomal degradation. Molecular dynamics simulations (RoseTTAFold) reveal that A39T causes distortion of residues 33–41 and T44M causes high flexibility of the N-terminal region (residues 1–24); deletion of aa 2–24 reduces NHP2 levels only in presence of wild-type NHP2, while deletion of aa 2–38 completely disrupts stability. Both variants reduce hTR levels and telomerase activity.","method":"Expression of NHP2 variants in cells; co-immunoprecipitation to assess complex incorporation; proteasome inhibitor assays; hTR quantification; telomerase activity assay; RoseTTAFold structural prediction + molecular dynamics simulations; N-terminal deletion constructs","journal":"Human molecular genetics","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — multiple orthogonal methods (co-IP, deletion analysis, telomerase activity, MD simulations) but structural inference is computational, single lab","pmids":["37440454"],"is_preprint":false},{"year":2020,"finding":"NHP2 physically interacts with TERT (telomerase reverse transcriptase) in hepatocellular carcinoma cells, and NHP2 knockdown reduces telomerase activity and TERT protein levels, as well as inhibiting tumor growth in a xenograft model.","method":"Co-immunoprecipitation of NHP2 and TERT; shRNA knockdown; telomerase activity assay; xenograft mouse model","journal":"Aging","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — co-IP plus functional knockdown in vitro and in vivo, single lab","pmids":["33044946"],"is_preprint":false},{"year":2025,"finding":"Cryo-EM structures of catalytically active insect H/ACA snoRNPs reveal Nhp2 participates in an asymmetric dimeric complex of two protomers on a two-hairpin H/ACA snoRNA. Coordinated structural changes between Nop10, Nhp2 and the N-terminal extensions of Cbf5 (dyskerin ortholog) in the 3' protomer resemble active and inactive conformations that may regulate pseudouridylation activity. Several DC-associated mutations in H/ACA proteins (including Nhp2 sites) directly impair pseudouridine formation.","method":"Cryo-EM structure determination; biochemical characterization of inter-protomer interface mutations; pseudouridylation activity assays","journal":"bioRxiv (preprint)","confidence":"Medium","confidence_rationale":"Tier 1 / Moderate — cryo-EM structures plus activity assays, but preprint (not yet peer-reviewed) and uses insect (not mammalian) complex","pmids":["bio_10.1101_2025.06.07.658439"],"is_preprint":true},{"year":2018,"finding":"In Drosophila ovary germline, NHP2 protein is concentrated in nucleoli and its expression decreases abruptly during cyst progression from 2-cell to 4-cell stage. NHP2 knockdown in the germline causes accumulation of 4- and 8-cell cysts and impairs transition to 16-cell cysts, demonstrating a role in controlling germline cell division progression. Sex-lethal (Sxl) protein physically interacts with NHP2 mRNA, suggesting post-transcriptional regulation of NHP2 by Sxl to control cyst formation.","method":"NHP2 knockdown (RNAi) in Drosophila germline; immunofluorescence for NHP2 protein localization; RNA immunoprecipitation of Sxl-NHP2 mRNA interaction; cyst staging phenotypic analysis","journal":"Development, growth & differentiation","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — loss-of-function with specific phenotypic readout plus RNA-IP for upstream regulation, Drosophila model, single lab","pmids":["29845608"],"is_preprint":false}],"current_model":"NHP2 is an essential core protein of H/ACA small nucleolar ribonucleoprotein (snoRNP) complexes and the telomerase holoenzyme; it directly interacts with NOP10, dyskerin/NAP57, GAR1, H/ACA snoRNAs, and TERC (the telomerase RNA component), forming a tetrameric pre-RNP assembly required for pseudouridylation of rRNA and stabilization of TERC—a function dependent on the NHP2–NOP10 interaction and the integrity of NHP2's N-terminal domain—while also acting as a reader of the rDNA histone mark H2AQ105me to coordinate rRNA transcription with processing, and playing a non-canonical role in restraining the DNA damage response at ALT telomeres via 53BP1 recruitment."},"narrative":{"mechanistic_narrative":"NHP2 is an essential, evolutionarily conserved core protein of H/ACA small nucleolar ribonucleoprotein (snoRNP) complexes that couples ribosomal RNA pseudouridylation to telomerase RNA maintenance [PMID:11074001, PMID:2063628]. In human cells it co-assembles with GAR1, dyskerin/NOP10, and H/ACA RNAs, including the H/ACA-like 3' domain of the telomerase RNA hTR/TERC, and localizes to the dense fibrillar component of the nucleolus and to Cajal bodies [PMID:11074001]. Assembly of the catalytic pre-RNP depends critically on the NHP2–NOP10 interaction and on the integrity of the NHP2 N-terminal domain: disease-associated mutations (V126M, Y139H) disrupt NOP10 binding and abolish pre-RNP formation, while N-terminal variants (A39T, T44M) prevent incorporation into the H/ACA complex and trigger proteasomal degradation of the misfolded protein [PMID:20008900, PMID:37440454]. Functionally, NHP2 is required for accumulation and stabilization of TERC—a requirement not shared by GAR1—and its loss reduces telomerase activity and impairs rRNA biogenesis, consistent with dyskeratosis congenita–type pathology arising from biallelic NHP2 mutations [PMID:18523010, PMID:31985013, PMID:37440454]. Beyond canonical snoRNP function, NHP2 acts as a chromatin reader of the rDNA histone mark H2AQ105 methylation, bridging rDNA chromatin to the small-subunit processome to coordinate rRNA transcription with processing [PMID:34409714], and in ALT-positive cancer cells its downregulation restrains the DNA damage response at telomeres by limiting 53BP1 recruitment [PMID:33595114].","teleology":[{"year":1991,"claim":"Established that NHP2 is an essential gene, fixing it as a core requirement for cell proliferation before any molecular role was defined.","evidence":"Gene deletion and spore dissection in S. cerevisiae","pmids":["2063628"],"confidence":"High","gaps":["Molecular function undefined","No biochemical partners identified","Cause of proliferation arrest unknown"]},{"year":1999,"claim":"Located NHP2 to the nucleolus throughout the cell cycle, tying its essential role to a stable nucleolar/rDNA-associated activity.","evidence":"Yeast complementation and live-cell GFP imaging in fission and budding yeast","pmids":["10502409"],"confidence":"Medium","gaps":["Did not define the molecular complex","No link to a specific RNA substrate","Single lab"]},{"year":2000,"claim":"Defined NHP2 as a core H/ACA snoRNP subunit that also associates with telomerase RNA, unifying rRNA modification and telomerase biology under one protein.","evidence":"Co-IP with GAR1/H/ACA RNAs/hTR, yeast complementation, and immunofluorescence in HeLa cells","pmids":["11074001"],"confidence":"High","gaps":["Did not establish whether NHP2 stabilizes hTR or merely co-purifies","Stoichiometry/architecture of the complex unresolved","Direct vs indirect RNA contacts undefined"]},{"year":2008,"claim":"Showed NHP2 is specifically required for TERC accumulation whereas GAR1 is not, dissociating telomerase RNA stabilization from general H/ACA function.","evidence":"siRNA knockdown of NHP2 vs GAR1 with TERC quantification in human cells","pmids":["18523010"],"confidence":"High","gaps":["Mechanism of TERC stabilization not resolved","Did not test rRNA pseudouridylation consequences","No structural basis"]},{"year":2009,"claim":"Mapped disease mutations to the NHP2–NOP10 interface, establishing that this interaction is the assembly-critical step for H/ACA pre-RNP formation.","evidence":"In vivo pre-RNP assembly and co-IP of NHP2 V126M/Y139H mutants with NOP10 and H/ACA RNAs","pmids":["20008900"],"confidence":"High","gaps":["Atomic structure of interface not determined","Did not measure downstream pseudouridylation activity directly","Patient phenotype-to-assembly correlation incomplete"]},{"year":2020,"claim":"Demonstrated in patient cells that NHP2 loss impairs rRNA biogenesis, extending its disease-relevant role beyond telomere maintenance.","evidence":"rRNA biogenesis assays in patient-derived cells with biallelic NHP2 mutations","pmids":["31985013"],"confidence":"Medium","gaps":["Specific pseudouridylation defects not enumerated","Single lab","Relative contribution of rRNA vs telomere defects to disease unclear"]},{"year":2020,"claim":"Identified a physical NHP2–TERT interaction supporting telomerase activity, implicating NHP2 in tumor growth.","evidence":"Co-IP, shRNA knockdown, telomerase activity assay, and xenograft in hepatocellular carcinoma cells","pmids":["33044946"],"confidence":"Medium","gaps":["Directness of NHP2–TERT contact vs RNA-mediated bridging unresolved","Single lab","Whether effect is general across cancers untested"]},{"year":2021,"claim":"Revealed a chromatin-reader role: NHP2 binds the rDNA mark H2AQ105me to bridge rDNA chromatin to the SSU processome, coupling rRNA transcription to processing.","evidence":"Proteomic identification of NHP2 as H2AQ105me reader plus chromatin-binding and H2AQ105A mutant rRNA processing assays in yeast","pmids":["34409714"],"confidence":"Medium","gaps":["Reader function not validated in human cells","Structural basis of mark recognition unknown","Mild mutant phenotype leaves magnitude of effect uncertain"]},{"year":2021,"claim":"Uncovered a non-canonical role at ALT telomeres where NHP2 downregulation restrains the DNA damage response by limiting 53BP1 recruitment, independent of hTR's RPA function.","evidence":"NHP2 manipulation in ALT+ cancer cells with 53BP1/p-RPA(S33) foci quantification and hTR epistasis","pmids":["33595114"],"confidence":"Medium","gaps":["Mechanism linking NHP2 to 53BP1 recruitment undefined","Single lab","Generality beyond ALT context untested"]},{"year":2023,"claim":"Showed that N-terminal NHP2 variants block complex incorporation and are cleared by the proteasome, mechanistically explaining how N-terminal mutations destabilize the protein and reduce telomerase activity.","evidence":"Variant expression with co-IP incorporation assays, proteasome inhibition, N-terminal deletion constructs, hTR/telomerase assays, and RoseTTAFold/MD simulation in human cells","pmids":["37440454"],"confidence":"Medium","gaps":["Structural inference is computational, not experimental","Single lab","Degradation pathway components not identified"]},{"year":2025,"claim":"Provided structural insight into NHP2 within a catalytically active H/ACA snoRNP, showing it participates in inter-protomer conformational changes that may gate pseudouridylation.","evidence":"Cryo-EM structures and interface-mutation pseudouridylation assays of an insect H/ACA snoRNP (preprint)","pmids":["bio_10.1101_2025.06.07.658439"],"confidence":"Medium","gaps":["Preprint, not peer-reviewed","Insect rather than human complex","Functional consequence of the conformational switch not validated in cells"]},{"year":null,"claim":"How NHP2's chromatin-reader and ALT-telomere DDR roles mechanistically integrate with its canonical H/ACA snoRNP function in human cells remains unresolved.","evidence":"","pmids":[],"confidence":"Medium","gaps":["Human H2AQ105me reader activity unconfirmed","Mechanism of NHP2-dependent 53BP1 recruitment unknown","No high-resolution mammalian snoRNP structure linking assembly to catalysis"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0003723","term_label":"RNA binding","supporting_discovery_ids":[0,3,4]},{"term_id":"GO:0005198","term_label":"structural molecule activity","supporting_discovery_ids":[0,4,10]},{"term_id":"GO:0042393","term_label":"histone binding","supporting_discovery_ids":[7]},{"term_id":"GO:0060090","term_label":"molecular adaptor activity","supporting_discovery_ids":[7]}],"localization":[{"term_id":"GO:0005730","term_label":"nucleolus","supporting_discovery_ids":[0,2,11]}],"pathway":[{"term_id":"R-HSA-8953854","term_label":"Metabolism of RNA","supporting_discovery_ids":[0,3,5]},{"term_id":"R-HSA-1852241","term_label":"Organelle biogenesis and maintenance","supporting_discovery_ids":[5,7]}],"complexes":["H/ACA snoRNP","telomerase holoenzyme"],"partners":["NOP10","GAR1","DKC1","TERC","TERT"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q9NX24","full_name":"H/ACA ribonucleoprotein complex subunit 2","aliases":["Nucleolar protein family A member 2","snoRNP protein NHP2"],"length_aa":153,"mass_kda":17.2,"function":"Required for ribosome biogenesis and telomere maintenance. Part of the H/ACA small nucleolar ribonucleoprotein (H/ACA snoRNP) complex, which catalyzes pseudouridylation of rRNA. This involves the isomerization of uridine such that the ribose is subsequently attached to C5, instead of the normal N1. Each rRNA can contain up to 100 pseudouridine ('psi') residues, which may serve to stabilize the conformation of rRNAs. May also be required for correct processing or intranuclear trafficking of TERC, the RNA component of the telomerase reverse transcriptase (TERT) holoenzyme","subcellular_location":"Nucleus, nucleolus; Nucleus, Cajal body","url":"https://www.uniprot.org/uniprotkb/Q9NX24/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":true,"resolved_as":"","url":"https://depmap.org/portal/gene/NHP2","classification":"Common Essential","n_dependent_lines":1088,"n_total_lines":1208,"dependency_fraction":0.9006622516556292},"opencell":{"profiled":true,"resolved_as":"","ensg_id":"ENSG00000145912","cell_line_id":"CID001035","localizations":[{"compartment":"nucleolus_fc_dfc","grade":3}],"interactors":[{"gene":"DKC1","stoichiometry":0.2},{"gene":"SUB1","stoichiometry":0.2},{"gene":"SRSF6","stoichiometry":0.2},{"gene":"RSRC1","stoichiometry":0.2},{"gene":"ARGLU1","stoichiometry":0.2},{"gene":"CWF19L2","stoichiometry":0.2}],"url":"https://opencell.sf.czbiohub.org/target/CID001035","total_profiled":1310},"omim":[{"mim_id":"617868","title":"NUCLEAR ASSEMBLY FACTOR 1 RIBONUCLEOPROTEIN; NAF1","url":"https://www.omim.org/entry/617868"},{"mim_id":"613987","title":"DYSKERATOSIS CONGENITA, AUTOSOMAL RECESSIVE 2; DKCB2","url":"https://www.omim.org/entry/613987"},{"mim_id":"613663","title":"SHQ1, H/ACA RIBONUCLEOPROTEIN ASSEMBLY FACTOR; SHQ1","url":"https://www.omim.org/entry/613663"},{"mim_id":"606471","title":"NOP10 RIBONUCLEOPROTEIN; NOP10","url":"https://www.omim.org/entry/606471"},{"mim_id":"606470","title":"NHP2 RIBONUCLEOPROTEIN; NHP2","url":"https://www.omim.org/entry/606470"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"","locations":[],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in all","driving_tissues":[],"url":"https://www.proteinatlas.org/search/NHP2"},"hgnc":{"alias_symbol":["FLJ20479"],"prev_symbol":["NOLA2"]},"alphafold":{"accession":"Q9NX24","domains":[{"cath_id":"3.30.1330.30","chopping":"27-147","consensus_level":"high","plddt":87.8404,"start":27,"end":147}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q9NX24","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q9NX24-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q9NX24-F1-predicted_aligned_error_v6.png","plddt_mean":80.06},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=NHP2","jax_strain_url":"https://www.jax.org/strain/search?query=NHP2"},"sequence":{"accession":"Q9NX24","fasta_url":"https://rest.uniprot.org/uniprotkb/Q9NX24.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q9NX24/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q9NX24"}},"corpus_meta":[{"pmid":"18523010","id":"PMC_18523010","title":"Mutations in the telomerase component NHP2 cause the premature ageing syndrome dyskeratosis congenita.","date":"2008","source":"Proceedings of the National Academy of Sciences of the United States of America","url":"https://pubmed.ncbi.nlm.nih.gov/18523010","citation_count":255,"is_preprint":false},{"pmid":"11074001","id":"PMC_11074001","title":"Human H/ACA small nucleolar RNPs and telomerase share evolutionarily conserved proteins NHP2 and NOP10.","date":"2000","source":"Molecular and cellular biology","url":"https://pubmed.ncbi.nlm.nih.gov/11074001","citation_count":187,"is_preprint":false},{"pmid":"20008900","id":"PMC_20008900","title":"Effects of dyskeratosis congenita mutations in dyskerin, NHP2 and NOP10 on assembly of H/ACA pre-RNPs.","date":"2009","source":"Human molecular genetics","url":"https://pubmed.ncbi.nlm.nih.gov/20008900","citation_count":49,"is_preprint":false},{"pmid":"31985013","id":"PMC_31985013","title":"NHP2 deficiency impairs rRNA biogenesis and causes pulmonary fibrosis and Høyeraal-Hreidarsson syndrome.","date":"2020","source":"Human molecular genetics","url":"https://pubmed.ncbi.nlm.nih.gov/31985013","citation_count":47,"is_preprint":false},{"pmid":"2063628","id":"PMC_2063628","title":"Sequence and genetic analysis of NHP2: a moderately abundant high mobility group-like nuclear protein with an essential function in Saccharomyces cerevisiae.","date":"1991","source":"Yeast (Chichester, England)","url":"https://pubmed.ncbi.nlm.nih.gov/2063628","citation_count":28,"is_preprint":false},{"pmid":"8978773","id":"PMC_8978773","title":"Cloning and mapping of a human novel cDNA (NHP2L1) that encodes a protein highly homologous to yeast nuclear protein NHP2.","date":"1996","source":"Cytogenetics and cell genetics","url":"https://pubmed.ncbi.nlm.nih.gov/8978773","citation_count":17,"is_preprint":false},{"pmid":"15889794","id":"PMC_15889794","title":"[The NOLA2 and RPS3A genes as highly informative markers for human squamous cell lung 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haematologica","url":"https://pubmed.ncbi.nlm.nih.gov/30472699","citation_count":10,"is_preprint":false},{"pmid":"37440454","id":"PMC_37440454","title":"Novel pathological variants of NHP2 affect N-terminal domain flexibility, protein stability, H/ACA Ribonucleoprotein (RNP) complex formation and telomerase activity.","date":"2023","source":"Human molecular genetics","url":"https://pubmed.ncbi.nlm.nih.gov/37440454","citation_count":9,"is_preprint":false},{"pmid":"34409714","id":"PMC_34409714","title":"Nhp2 is a reader of H2AQ105me and part of a network integrating metabolism with rRNA synthesis.","date":"2021","source":"EMBO reports","url":"https://pubmed.ncbi.nlm.nih.gov/34409714","citation_count":8,"is_preprint":false},{"pmid":"29845608","id":"PMC_29845608","title":"Downregulation of NHP2 promotes proper cyst formation in Drosophila ovary.","date":"2018","source":"Development, growth & 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syndromology","url":"https://pubmed.ncbi.nlm.nih.gov/40352450","citation_count":1,"is_preprint":false},{"pmid":"40812391","id":"PMC_40812391","title":"Single-cell transcriptomics reveals that RNA pseudouridylation-related gene NHP2 promotes the progression of uveal melanoma and validated in vivo and in vitro.","date":"2025","source":"Experimental eye research","url":"https://pubmed.ncbi.nlm.nih.gov/40812391","citation_count":0,"is_preprint":false},{"pmid":null,"id":"bio_10.1101_2025.06.07.658439","title":"Interprotomer Communication and Functional Asymmetry in H/ACA snoRNPs","date":"2025-06-08","source":"bioRxiv","url":"https://doi.org/10.1101/2025.06.07.658439","citation_count":0,"is_preprint":true},{"pmid":null,"id":"bio_10.1101_2025.07.31.667874","title":"Single-cell and spatial transcriptomic analyses of gene therapy-associated retinal inflammation in non-human primates","date":"2025-08-02","source":"bioRxiv","url":"https://doi.org/10.1101/2025.07.31.667874","citation_count":0,"is_preprint":true}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":11306,"output_tokens":3391,"usd":0.042391,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":10939,"output_tokens":3633,"usd":0.07276,"stage2_stop_reason":"end_turn"},"total_usd":0.115151,"stage1_batch_id":"msgbatch_013a8chtv3AWyTqv4z4sEF4C","stage2_batch_id":"msgbatch_01AHsuW63vinsvuTgzmQ3n62","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2000,\n      \"finding\": \"Human NHP2 (hNHP2) is a core protein component of H/ACA snoRNP complexes; epitope-tagged hNHP2 co-immunoprecipitates with hGAR1, H/ACA RNAs, and the RNA subunit of telomerase (hTR, which contains an H/ACA-like domain in its 3' moiety) in HeLa cell extracts. hNHP2 also functionally complements yeast cells depleted of Nhp2p. Immunofluorescence showed hNHP2 localizes to the dense fibrillar component of the nucleolus and Cajal bodies.\",\n      \"method\": \"Immunoprecipitation from transfected HeLa cell extracts; yeast complementation assay; immunofluorescence microscopy\",\n      \"journal\": \"Molecular and cellular biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — reciprocal co-IP with multiple partners, functional complementation across species, and localization data in a single study; independently consistent with subsequent work\",\n      \"pmids\": [\"11074001\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 1991,\n      \"finding\": \"NHP2 in S. cerevisiae encodes an essential 17.1 kDa basic nuclear protein; deletion of one NHP2 copy in diploid yeast followed by sporulation showed that spores lacking NHP2 germinate but form only microcolonies of 12–40 cells, demonstrating NHP2 is essential for normal cell proliferation.\",\n      \"method\": \"Gene deletion / spore dissection in S. cerevisiae; S1 nuclease mapping\",\n      \"journal\": \"Yeast (Chichester, England)\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — genetic deletion with clear phenotypic readout in a foundational study; foundational essential-function result replicated conceptually by subsequent work\",\n      \"pmids\": [\"2063628\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 1999,\n      \"finding\": \"Fission yeast p17(nhp2) is a nucleolar protein that functionally complements deletion of S. cerevisiae NHP2 and remains associated with nucleolar material throughout the mitotic cell cycle, including during anaphase, suggesting H/ACA snoRNPs are continuously nucleolus-associated during cell division. In S. cerevisiae, Nhp2 co-segregates with bulk chromatin/rDNA during nuclear division.\",\n      \"method\": \"Yeast complementation; live-cell fluorescence microscopy of GFP-tagged Nhp2 through the cell cycle\",\n      \"journal\": \"Experimental cell research\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — complementation plus live imaging, single lab\",\n      \"pmids\": [\"10502409\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2008,\n      \"finding\": \"siRNA-mediated knockdown of NHP2 in human cells reduces TERC (telomerase RNA) levels, demonstrating NHP2 is required for TERC accumulation/stability. In contrast, GAR1 knockdown did not reduce TERC levels, establishing a functional difference between these two H/ACA complex components with respect to telomerase RNA stabilization.\",\n      \"method\": \"siRNA knockdown in human cells followed by quantification of TERC levels\",\n      \"journal\": \"Proceedings of the National Academy of Sciences of the United States of America\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — direct loss-of-function with defined molecular readout (TERC level), complemented by parallel GAR1 knockdown control establishing specificity; published in high-impact journal\",\n      \"pmids\": [\"18523010\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2009,\n      \"finding\": \"Disease-associated NHP2 mutations V126M and Y139H impair NHP2's association with NOP10, causing major pre-RNP assembly defects with all H/ACA RNAs tested, including the H/ACA domain of hTR. This establishes that the NHP2–NOP10 interaction is critical for H/ACA pre-RNP formation. The most prevalent dyskerin DC mutation (A353V) did not affect NAF1-dyskerin-NOP10-NHP2 tetramer formation but slightly reduced assembly with the H/ACA-like domain of hTR.\",\n      \"method\": \"In vivo pre-RNP assembly assays with wild-type and mutant proteins; co-immunoprecipitation of NHP2 mutants with NOP10 and H/ACA RNAs\",\n      \"journal\": \"Human molecular genetics\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — multiple mutants tested against multiple H/ACA RNA substrates, clear molecular phenotype with mechanistic interpretation, orthogonal co-IP and RNA binding assays\",\n      \"pmids\": [\"20008900\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"Functional deficit of human NHP2 (demonstrated using patient-derived cells with biallelic NHP2 mutations) affects ribosomal RNA (rRNA) biogenesis in addition to telomere maintenance, extending the known molecular consequences of NHP2 loss beyond TERC stabilization.\",\n      \"method\": \"Analysis of patient cells with NHP2 mutations; rRNA biogenesis assays\",\n      \"journal\": \"Human molecular genetics\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — patient-derived cells with defined mutations; rRNA biogenesis readout, single lab\",\n      \"pmids\": [\"31985013\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"In ALT-positive cancer cells that retain hTR expression, NHP2 H/ACA ribonucleoprotein levels are downregulated, and this downregulation restrains DNA damage response (DDR) activation at ALT telomeres by reducing 53BP1 recruitment. This role of NHP2 is mechanistically independent from hTR's non-canonical function in modulating telomeric p-RPA(S33).\",\n      \"method\": \"NHP2 knockdown/manipulation in ALT+ cancer cells; 53BP1 and p-RPA(S33) foci quantification at telomeres; epistasis with hTR expression\",\n      \"journal\": \"The EMBO journal\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — defined molecular pathway placement via epistasis and loss-of-function with specific readouts, single lab\",\n      \"pmids\": [\"33595114\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"Nhp2 (yeast) functions as a reader of the histone modification H2AQ105 methylation (H2AQ105me) at the rDNA locus, and acts as an adapter bridging rDNA chromatin with components of the small subunit processome to coordinate rRNA transcription with post-transcriptional processing. Nhp2 binding to H2AQ105me depends on a functional mTOR signaling pathway and H3K56 acetylation. An H2AQ105A mutant shows a mild defect in early rRNA processing.\",\n      \"method\": \"Functional and proteomic data; identification of Nhp2 as H2AQ105me reader; chromatin-binding assays; H2AQ105A mutant rRNA processing analysis\",\n      \"journal\": \"EMBO reports\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — novel reader function identified with proteomic and functional validation; yeast model, single lab, mechanistic novelty\",\n      \"pmids\": [\"34409714\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"Novel NHP2 variants A39T and T44M fail to be incorporated into the H/ACA RNA-binding complex when competing with wild-type NHP2, and misincorporated variants undergo proteasomal degradation. Molecular dynamics simulations (RoseTTAFold) reveal that A39T causes distortion of residues 33–41 and T44M causes high flexibility of the N-terminal region (residues 1–24); deletion of aa 2–24 reduces NHP2 levels only in presence of wild-type NHP2, while deletion of aa 2–38 completely disrupts stability. Both variants reduce hTR levels and telomerase activity.\",\n      \"method\": \"Expression of NHP2 variants in cells; co-immunoprecipitation to assess complex incorporation; proteasome inhibitor assays; hTR quantification; telomerase activity assay; RoseTTAFold structural prediction + molecular dynamics simulations; N-terminal deletion constructs\",\n      \"journal\": \"Human molecular genetics\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — multiple orthogonal methods (co-IP, deletion analysis, telomerase activity, MD simulations) but structural inference is computational, single lab\",\n      \"pmids\": [\"37440454\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"NHP2 physically interacts with TERT (telomerase reverse transcriptase) in hepatocellular carcinoma cells, and NHP2 knockdown reduces telomerase activity and TERT protein levels, as well as inhibiting tumor growth in a xenograft model.\",\n      \"method\": \"Co-immunoprecipitation of NHP2 and TERT; shRNA knockdown; telomerase activity assay; xenograft mouse model\",\n      \"journal\": \"Aging\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — co-IP plus functional knockdown in vitro and in vivo, single lab\",\n      \"pmids\": [\"33044946\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"Cryo-EM structures of catalytically active insect H/ACA snoRNPs reveal Nhp2 participates in an asymmetric dimeric complex of two protomers on a two-hairpin H/ACA snoRNA. Coordinated structural changes between Nop10, Nhp2 and the N-terminal extensions of Cbf5 (dyskerin ortholog) in the 3' protomer resemble active and inactive conformations that may regulate pseudouridylation activity. Several DC-associated mutations in H/ACA proteins (including Nhp2 sites) directly impair pseudouridine formation.\",\n      \"method\": \"Cryo-EM structure determination; biochemical characterization of inter-protomer interface mutations; pseudouridylation activity assays\",\n      \"journal\": \"bioRxiv (preprint)\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1 / Moderate — cryo-EM structures plus activity assays, but preprint (not yet peer-reviewed) and uses insect (not mammalian) complex\",\n      \"pmids\": [\"bio_10.1101_2025.06.07.658439\"],\n      \"is_preprint\": true\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"In Drosophila ovary germline, NHP2 protein is concentrated in nucleoli and its expression decreases abruptly during cyst progression from 2-cell to 4-cell stage. NHP2 knockdown in the germline causes accumulation of 4- and 8-cell cysts and impairs transition to 16-cell cysts, demonstrating a role in controlling germline cell division progression. Sex-lethal (Sxl) protein physically interacts with NHP2 mRNA, suggesting post-transcriptional regulation of NHP2 by Sxl to control cyst formation.\",\n      \"method\": \"NHP2 knockdown (RNAi) in Drosophila germline; immunofluorescence for NHP2 protein localization; RNA immunoprecipitation of Sxl-NHP2 mRNA interaction; cyst staging phenotypic analysis\",\n      \"journal\": \"Development, growth & differentiation\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — loss-of-function with specific phenotypic readout plus RNA-IP for upstream regulation, Drosophila model, single lab\",\n      \"pmids\": [\"29845608\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"NHP2 is an essential core protein of H/ACA small nucleolar ribonucleoprotein (snoRNP) complexes and the telomerase holoenzyme; it directly interacts with NOP10, dyskerin/NAP57, GAR1, H/ACA snoRNAs, and TERC (the telomerase RNA component), forming a tetrameric pre-RNP assembly required for pseudouridylation of rRNA and stabilization of TERC—a function dependent on the NHP2–NOP10 interaction and the integrity of NHP2's N-terminal domain—while also acting as a reader of the rDNA histone mark H2AQ105me to coordinate rRNA transcription with processing, and playing a non-canonical role in restraining the DNA damage response at ALT telomeres via 53BP1 recruitment.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"NHP2 is an essential, evolutionarily conserved core protein of H/ACA small nucleolar ribonucleoprotein (snoRNP) complexes that couples ribosomal RNA pseudouridylation to telomerase RNA maintenance [#0, #1]. In human cells it co-assembles with GAR1, dyskerin/NOP10, and H/ACA RNAs, including the H/ACA-like 3' domain of the telomerase RNA hTR/TERC, and localizes to the dense fibrillar component of the nucleolus and to Cajal bodies [#0]. Assembly of the catalytic pre-RNP depends critically on the NHP2\\u2013NOP10 interaction and on the integrity of the NHP2 N-terminal domain: disease-associated mutations (V126M, Y139H) disrupt NOP10 binding and abolish pre-RNP formation, while N-terminal variants (A39T, T44M) prevent incorporation into the H/ACA complex and trigger proteasomal degradation of the misfolded protein [#4, #8]. Functionally, NHP2 is required for accumulation and stabilization of TERC\\u2014a requirement not shared by GAR1\\u2014and its loss reduces telomerase activity and impairs rRNA biogenesis, consistent with dyskeratosis congenita\\u2013type pathology arising from biallelic NHP2 mutations [#3, #5, #8]. Beyond canonical snoRNP function, NHP2 acts as a chromatin reader of the rDNA histone mark H2AQ105 methylation, bridging rDNA chromatin to the small-subunit processome to coordinate rRNA transcription with processing [#7], and in ALT-positive cancer cells its downregulation restrains the DNA damage response at telomeres by limiting 53BP1 recruitment [#6].\",\n  \"teleology\": [\n    {\n      \"year\": 1991,\n      \"claim\": \"Established that NHP2 is an essential gene, fixing it as a core requirement for cell proliferation before any molecular role was defined.\",\n      \"evidence\": \"Gene deletion and spore dissection in S. cerevisiae\",\n      \"pmids\": [\"2063628\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Molecular function undefined\", \"No biochemical partners identified\", \"Cause of proliferation arrest unknown\"]\n    },\n    {\n      \"year\": 1999,\n      \"claim\": \"Located NHP2 to the nucleolus throughout the cell cycle, tying its essential role to a stable nucleolar/rDNA-associated activity.\",\n      \"evidence\": \"Yeast complementation and live-cell GFP imaging in fission and budding yeast\",\n      \"pmids\": [\"10502409\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Did not define the molecular complex\", \"No link to a specific RNA substrate\", \"Single lab\"]\n    },\n    {\n      \"year\": 2000,\n      \"claim\": \"Defined NHP2 as a core H/ACA snoRNP subunit that also associates with telomerase RNA, unifying rRNA modification and telomerase biology under one protein.\",\n      \"evidence\": \"Co-IP with GAR1/H/ACA RNAs/hTR, yeast complementation, and immunofluorescence in HeLa cells\",\n      \"pmids\": [\"11074001\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Did not establish whether NHP2 stabilizes hTR or merely co-purifies\", \"Stoichiometry/architecture of the complex unresolved\", \"Direct vs indirect RNA contacts undefined\"]\n    },\n    {\n      \"year\": 2008,\n      \"claim\": \"Showed NHP2 is specifically required for TERC accumulation whereas GAR1 is not, dissociating telomerase RNA stabilization from general H/ACA function.\",\n      \"evidence\": \"siRNA knockdown of NHP2 vs GAR1 with TERC quantification in human cells\",\n      \"pmids\": [\"18523010\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Mechanism of TERC stabilization not resolved\", \"Did not test rRNA pseudouridylation consequences\", \"No structural basis\"]\n    },\n    {\n      \"year\": 2009,\n      \"claim\": \"Mapped disease mutations to the NHP2\\u2013NOP10 interface, establishing that this interaction is the assembly-critical step for H/ACA pre-RNP formation.\",\n      \"evidence\": \"In vivo pre-RNP assembly and co-IP of NHP2 V126M/Y139H mutants with NOP10 and H/ACA RNAs\",\n      \"pmids\": [\"20008900\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Atomic structure of interface not determined\", \"Did not measure downstream pseudouridylation activity directly\", \"Patient phenotype-to-assembly correlation incomplete\"]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"Demonstrated in patient cells that NHP2 loss impairs rRNA biogenesis, extending its disease-relevant role beyond telomere maintenance.\",\n      \"evidence\": \"rRNA biogenesis assays in patient-derived cells with biallelic NHP2 mutations\",\n      \"pmids\": [\"31985013\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Specific pseudouridylation defects not enumerated\", \"Single lab\", \"Relative contribution of rRNA vs telomere defects to disease unclear\"]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"Identified a physical NHP2\\u2013TERT interaction supporting telomerase activity, implicating NHP2 in tumor growth.\",\n      \"evidence\": \"Co-IP, shRNA knockdown, telomerase activity assay, and xenograft in hepatocellular carcinoma cells\",\n      \"pmids\": [\"33044946\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Directness of NHP2\\u2013TERT contact vs RNA-mediated bridging unresolved\", \"Single lab\", \"Whether effect is general across cancers untested\"]\n    },\n    {\n      \"year\": 2021,\n      \"claim\": \"Revealed a chromatin-reader role: NHP2 binds the rDNA mark H2AQ105me to bridge rDNA chromatin to the SSU processome, coupling rRNA transcription to processing.\",\n      \"evidence\": \"Proteomic identification of NHP2 as H2AQ105me reader plus chromatin-binding and H2AQ105A mutant rRNA processing assays in yeast\",\n      \"pmids\": [\"34409714\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Reader function not validated in human cells\", \"Structural basis of mark recognition unknown\", \"Mild mutant phenotype leaves magnitude of effect uncertain\"]\n    },\n    {\n      \"year\": 2021,\n      \"claim\": \"Uncovered a non-canonical role at ALT telomeres where NHP2 downregulation restrains the DNA damage response by limiting 53BP1 recruitment, independent of hTR's RPA function.\",\n      \"evidence\": \"NHP2 manipulation in ALT+ cancer cells with 53BP1/p-RPA(S33) foci quantification and hTR epistasis\",\n      \"pmids\": [\"33595114\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Mechanism linking NHP2 to 53BP1 recruitment undefined\", \"Single lab\", \"Generality beyond ALT context untested\"]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"Showed that N-terminal NHP2 variants block complex incorporation and are cleared by the proteasome, mechanistically explaining how N-terminal mutations destabilize the protein and reduce telomerase activity.\",\n      \"evidence\": \"Variant expression with co-IP incorporation assays, proteasome inhibition, N-terminal deletion constructs, hTR/telomerase assays, and RoseTTAFold/MD simulation in human cells\",\n      \"pmids\": [\"37440454\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Structural inference is computational, not experimental\", \"Single lab\", \"Degradation pathway components not identified\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Provided structural insight into NHP2 within a catalytically active H/ACA snoRNP, showing it participates in inter-protomer conformational changes that may gate pseudouridylation.\",\n      \"evidence\": \"Cryo-EM structures and interface-mutation pseudouridylation assays of an insect H/ACA snoRNP (preprint)\",\n      \"pmids\": [\"bio_10.1101_2025.06.07.658439\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Preprint, not peer-reviewed\", \"Insect rather than human complex\", \"Functional consequence of the conformational switch not validated in cells\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How NHP2's chromatin-reader and ALT-telomere DDR roles mechanistically integrate with its canonical H/ACA snoRNP function in human cells remains unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Human H2AQ105me reader activity unconfirmed\", \"Mechanism of NHP2-dependent 53BP1 recruitment unknown\", \"No high-resolution mammalian snoRNP structure linking assembly to catalysis\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0003723\", \"supporting_discovery_ids\": [0, 3, 4]},\n      {\"term_id\": \"GO:0005198\", \"supporting_discovery_ids\": [0, 4, 10]},\n      {\"term_id\": \"GO:0042393\", \"supporting_discovery_ids\": [7]},\n      {\"term_id\": \"GO:0060090\", \"supporting_discovery_ids\": [7]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005730\", \"supporting_discovery_ids\": [0, 2, 11]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-8953854\", \"supporting_discovery_ids\": [0, 3, 5]},\n      {\"term_id\": \"R-HSA-1852241\", \"supporting_discovery_ids\": [5, 7]}\n    ],\n    \"complexes\": [\n      \"H/ACA snoRNP\",\n      \"telomerase holoenzyme\"\n    ],\n    \"partners\": [\n      \"NOP10\",\n      \"GAR1\",\n      \"DKC1\",\n      \"TERC\",\n      \"TERT\"\n    ],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":5,"faith_total":5,"faith_pct":100.0}}