{"gene":"NBPF3","run_date":"2026-06-10T05:19:52","timeline":{"discoveries":[{"year":2007,"finding":"NBPF3, which lacks an intronic HERV(K) LTR insertion, is transcriptionally active and expressed in a variety of tissues, demonstrating that the HERV(K) LTR insertion is not required for transcriptional activity of NBPF genes.","method":"RT-PCR expression analysis across multiple tissues","journal":"Virology","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — direct transcriptional activity assay in multiple tissues, single lab, single method","pmids":["17391723"],"is_preprint":false},{"year":2011,"finding":"NBPF3 (AL592309/NBPF3), an LTR-lacking gene of the KIAA1245/NBPF subfamily, is transcriptionally active at the pre-mRNA level, but shows significantly lower transcription levels compared to LTR-containing paralogs, suggesting that intronic HERV-K LTRs enhance transcriptional activity without being strictly required.","method":"RT-PCR analysis of non-spliced pre-mRNA in cell lines and tissues","journal":"Genetica","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — direct pre-mRNA RT-PCR distinguishing splicing effects, replicated finding across two studies (PMIDs 17391723 and 21544646)","pmids":["21544646"],"is_preprint":false}],"current_model":"NBPF3 is a transcriptionally active member of the NBPF/KIAA1245 gene family that does not require an intronic HERV(K) LTR insertion for its expression, though LTR-containing paralogs show higher transcription levels; beyond its expression characteristics, no biochemical function, binding partners, enzymatic activity, or specific cellular role has been mechanistically established for the NBPF3 protein."},"narrative":{"mechanistic_narrative":"NBPF3 is a transcriptionally active member of the KIAA1245/NBPF gene family whose expression has been characterized at the level of transcription rather than protein function [PMID:17391723, PMID:21544646]. Unlike many NBPF paralogs, NBPF3 lacks an intronic HERV(K) LTR insertion yet is transcribed across a variety of tissues, establishing that the LTR insertion is not required for NBPF gene transcriptional activity [PMID:17391723]. Quantitative comparison at the pre-mRNA level shows NBPF3 is transcribed at significantly lower levels than its LTR-containing paralogs, indicating that intronic HERV-K LTRs enhance transcription without being strictly required [PMID:21544646]. Beyond these expression characteristics, no biochemical function, enzymatic activity, binding partners, subcellular localization, or specific cellular role has been mechanistically established for the NBPF3 protein in the available corpus.","teleology":[{"year":2007,"claim":"It was unknown whether an intronic HERV(K) LTR insertion was required for NBPF gene expression; demonstrating that the LTR-lacking NBPF3 is transcribed established that the LTR is dispensable for transcriptional activity.","evidence":"RT-PCR expression analysis of NBPF3 across multiple tissues","pmids":["17391723"],"confidence":"Medium","gaps":["Single lab and single method; no protein-level expression demonstrated","No functional or biochemical role assigned to the NBPF3 product","Quantitative contribution of the LTR to expression not addressed"]},{"year":2011,"claim":"Whether LTR insertions modulate rather than gate NBPF transcription was unresolved; pre-mRNA quantification showed LTR-lacking NBPF3 is transcribed but at significantly lower levels than LTR-containing paralogs, establishing the LTR as an enhancer of transcription rather than a requirement.","evidence":"RT-PCR of non-spliced pre-mRNA in cell lines and tissues, distinguishing transcription from splicing","pmids":["21544646"],"confidence":"Medium","gaps":["Mechanism by which the LTR enhances transcription not defined","No protein function, localization, or interaction data","Tissue-by-tissue regulatory differences not resolved"]},{"year":null,"claim":"The biochemical function, binding partners, enzymatic activity, subcellular localization, and cellular role of the NBPF3 protein remain entirely uncharacterized.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No protein-level study of NBPF3 in the corpus","No identified molecular activity or interaction partners","No phenotype or pathway association established"]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":[],"partners":[],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q9H094","full_name":"NBPF family member NBPF3","aliases":["Neuroblastoma breakpoint family member 3","Protein AE2","Protein SHIIIa4"],"length_aa":633,"mass_kda":73.0,"function":"","subcellular_location":"Cytoplasm","url":"https://www.uniprot.org/uniprotkb/Q9H094/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/NBPF3","classification":"Not Classified","n_dependent_lines":83,"n_total_lines":1208,"dependency_fraction":0.06870860927152318},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[],"url":"https://opencell.sf.czbiohub.org/search/NBPF3","total_profiled":1310},"omim":[{"mim_id":"612992","title":"NEUROBLASTOMA BREAKPOINT FAMILY, MEMBER 3; NBPF3","url":"https://www.omim.org/entry/612992"},{"mim_id":"612957","title":"VITAMIN B6 PLASMA LEVEL QUANTITATIVE TRAIT LOCUS 1; B6QTL1","url":"https://www.omim.org/entry/612957"},{"mim_id":"612367","title":"ALKALINE PHOSPHATASE, PLASMA LEVEL OF, QUANTITATIVE TRAIT LOCUS 2","url":"https://www.omim.org/entry/612367"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Approved","locations":[{"location":"Nucleoplasm","reliability":"Approved"},{"location":"Cytosol","reliability":"Approved"},{"location":"Nuclear speckles","reliability":"Additional"}],"tissue_specificity":"Tissue enriched","tissue_distribution":"Detected in many","driving_tissues":[{"tissue":"testis","ntpm":9.1}],"url":"https://www.proteinatlas.org/search/NBPF3"},"hgnc":{"alias_symbol":["AE2"],"prev_symbol":[]},"alphafold":{"accession":"Q9H094","domains":[],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q9H094","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q9H094-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q9H094-F1-predicted_aligned_error_v6.png","plddt_mean":47.16},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=NBPF3","jax_strain_url":"https://www.jax.org/strain/search?query=NBPF3"},"sequence":{"accession":"Q9H094","fasta_url":"https://rest.uniprot.org/uniprotkb/Q9H094.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q9H094/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q9H094"}},"corpus_meta":[{"pmid":"35578825","id":"PMC_35578825","title":"Population Genetics and Signatures of Selection in Early Neolithic European Farmers.","date":"2022","source":"Molecular biology and evolution","url":"https://pubmed.ncbi.nlm.nih.gov/35578825","citation_count":33,"is_preprint":false},{"pmid":"17391723","id":"PMC_17391723","title":"Insertion of an HERV(K) LTR in the intron of NBPF3 is not required for its transcriptional activity.","date":"2007","source":"Virology","url":"https://pubmed.ncbi.nlm.nih.gov/17391723","citation_count":7,"is_preprint":false},{"pmid":"40157598","id":"PMC_40157598","title":"Landscape of sex differences in obesity and type 2 diabetes in subcutaneous adipose tissue: a systematic review and meta-analysis of transcriptomics studies.","date":"2025","source":"Metabolism: clinical and experimental","url":"https://pubmed.ncbi.nlm.nih.gov/40157598","citation_count":7,"is_preprint":false},{"pmid":"35346016","id":"PMC_35346016","title":"Vitamin B-related Gene Polymorphisms and Cardiovascular Disease.","date":"2022","source":"Endocrine, metabolic & immune disorders drug targets","url":"https://pubmed.ncbi.nlm.nih.gov/35346016","citation_count":4,"is_preprint":false},{"pmid":"21544646","id":"PMC_21544646","title":"Different transcription activity of HERV-K LTR-containing and LTR-lacking genes of the KIAA1245/NBPF gene subfamily.","date":"2011","source":"Genetica","url":"https://pubmed.ncbi.nlm.nih.gov/21544646","citation_count":1,"is_preprint":false},{"pmid":"41778435","id":"PMC_41778435","title":"Potential Therapeutic Targets for Neuroblastoma Screened through Mendelian Randomization Analysis.","date":"2025","source":"Archives of Iranian medicine","url":"https://pubmed.ncbi.nlm.nih.gov/41778435","citation_count":0,"is_preprint":false},{"pmid":"41158885","id":"PMC_41158885","title":"Novel Insights From In Silico Analysis of Biallelic ALPL (c.1001G/A and c.571G/A) in Two Mennonite Families Leading to Hypophosphatasia.","date":"2025","source":"Cureus","url":"https://pubmed.ncbi.nlm.nih.gov/41158885","citation_count":0,"is_preprint":false},{"pmid":null,"id":"bio_10.1101_2024.09.18.613678","title":"Transcriptomic landscape of sex differences in obesity and type 2 diabetes in subcutaneous adipose tissue","date":"2024-09-19","source":"bioRxiv","url":"https://doi.org/10.1101/2024.09.18.613678","citation_count":0,"is_preprint":true}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":6545,"output_tokens":531,"usd":0.0138,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":6834,"output_tokens":1111,"usd":0.030973,"stage2_stop_reason":"end_turn"},"total_usd":0.044773,"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\": 2007,\n      \"finding\": \"NBPF3, which lacks an intronic HERV(K) LTR insertion, is transcriptionally active and expressed in a variety of tissues, demonstrating that the HERV(K) LTR insertion is not required for transcriptional activity of NBPF genes.\",\n      \"method\": \"RT-PCR expression analysis across multiple tissues\",\n      \"journal\": \"Virology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — direct transcriptional activity assay in multiple tissues, single lab, single method\",\n      \"pmids\": [\"17391723\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2011,\n      \"finding\": \"NBPF3 (AL592309/NBPF3), an LTR-lacking gene of the KIAA1245/NBPF subfamily, is transcriptionally active at the pre-mRNA level, but shows significantly lower transcription levels compared to LTR-containing paralogs, suggesting that intronic HERV-K LTRs enhance transcriptional activity without being strictly required.\",\n      \"method\": \"RT-PCR analysis of non-spliced pre-mRNA in cell lines and tissues\",\n      \"journal\": \"Genetica\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — direct pre-mRNA RT-PCR distinguishing splicing effects, replicated finding across two studies (PMIDs 17391723 and 21544646)\",\n      \"pmids\": [\"21544646\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"NBPF3 is a transcriptionally active member of the NBPF/KIAA1245 gene family that does not require an intronic HERV(K) LTR insertion for its expression, though LTR-containing paralogs show higher transcription levels; beyond its expression characteristics, no biochemical function, binding partners, enzymatic activity, or specific cellular role has been mechanistically established for the NBPF3 protein.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"NBPF3 is a transcriptionally active member of the KIAA1245/NBPF gene family whose expression has been characterized at the level of transcription rather than protein function [#0, #1]. Unlike many NBPF paralogs, NBPF3 lacks an intronic HERV(K) LTR insertion yet is transcribed across a variety of tissues, establishing that the LTR insertion is not required for NBPF gene transcriptional activity [#0]. Quantitative comparison at the pre-mRNA level shows NBPF3 is transcribed at significantly lower levels than its LTR-containing paralogs, indicating that intronic HERV-K LTRs enhance transcription without being strictly required [#1]. Beyond these expression characteristics, no biochemical function, enzymatic activity, binding partners, subcellular localization, or specific cellular role has been mechanistically established for the NBPF3 protein in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2007,\n      \"claim\": \"It was unknown whether an intronic HERV(K) LTR insertion was required for NBPF gene expression; demonstrating that the LTR-lacking NBPF3 is transcribed established that the LTR is dispensable for transcriptional activity.\",\n      \"evidence\": \"RT-PCR expression analysis of NBPF3 across multiple tissues\",\n      \"pmids\": [\"17391723\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Single lab and single method; no protein-level expression demonstrated\",\n        \"No functional or biochemical role assigned to the NBPF3 product\",\n        \"Quantitative contribution of the LTR to expression not addressed\"\n      ]\n    },\n    {\n      \"year\": 2011,\n      \"claim\": \"Whether LTR insertions modulate rather than gate NBPF transcription was unresolved; pre-mRNA quantification showed LTR-lacking NBPF3 is transcribed but at significantly lower levels than LTR-containing paralogs, establishing the LTR as an enhancer of transcription rather than a requirement.\",\n      \"evidence\": \"RT-PCR of non-spliced pre-mRNA in cell lines and tissues, distinguishing transcription from splicing\",\n      \"pmids\": [\"21544646\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Mechanism by which the LTR enhances transcription not defined\",\n        \"No protein function, localization, or interaction data\",\n        \"Tissue-by-tissue regulatory differences not resolved\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The biochemical function, binding partners, enzymatic activity, subcellular localization, and cellular role of the NBPF3 protein remain entirely uncharacterized.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No protein-level study of NBPF3 in the corpus\",\n        \"No identified molecular activity or interaction partners\",\n        \"No phenotype or pathway association established\"\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [],\n    \"localization\": [],\n    \"pathway\": [],\n    \"complexes\": [],\n    \"partners\": [],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"faith_supported":3,"faith_total":3,"faith_pct":100.0}}