{"gene":"H2AC14","run_date":"2026-06-10T01:55:21","timeline":{"discoveries":[{"year":1994,"finding":"A marked H2A histone protein (H2A.E, an alias for H2AC14) with an extended C-terminus (8 additional amino acids including 3 methionines) was incorporated into chromatin of HeLa cells at ~10% of total H2A. Its mRNA levels were coupled to rates of DNA and protein synthesis (replication-linked regulation), and its stability in chromatin and partitioning between soluble and nuclear fractions were indistinguishable from other histone species, demonstrating that H2AC14/H2A.E behaves as a functional replication-coupled histone.","method":"Stable transfection of HeLa cells with modified histone gene construct; two-dimensional AUT-AUC gel electrophoresis to resolve the novel protein; fractionation into soluble and nuclear compartments; mRNA stability assays correlated with DNA synthesis rates","journal":"Experimental cell research","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct biochemical fractionation and gel-based protein characterization in a single lab with multiple orthogonal methods (gel resolution, fractionation, mRNA coupling assay)","pmids":["7957682"],"is_preprint":false}],"current_model":"H2AC14 (H2A.E/H2AFE/HIST1H2AJ) encodes a replication-coupled histone H2A variant that is stably incorporated into chromatin, with mRNA levels regulated in concert with DNA replication, and whose chromatin stability and nucleocytoplasmic partitioning are equivalent to canonical H2A histones."},"narrative":{"mechanistic_narrative":"H2AC14 encodes a replication-coupled histone H2A variant that is stably incorporated into chromatin and behaves as a functional component of the nucleosome [PMID:7957682]. Expressed in HeLa cells, the protein (alias H2A.E) accumulates to roughly 10% of total H2A, carries an extended C-terminus, and exhibits chromatin stability and soluble-versus-nuclear partitioning indistinguishable from canonical H2A species; its mRNA levels are coupled to rates of DNA and protein synthesis, consistent with replication-linked regulation [PMID:7957682]. Beyond [PMID:7957682], no further mechanistic detail — partners, post-translational regulation, or distinct functional role relative to other H2A isoforms — has been characterized in the available corpus.","teleology":[{"year":1994,"claim":"Established that the H2AC14 gene product is a bona fide replication-coupled histone rather than a non-functional variant, by showing it is incorporated into chromatin and behaves like canonical H2A.","evidence":"Stable transfection of HeLa cells with a modified histone gene construct, two-dimensional AUT-AUC gel electrophoresis to resolve the protein, soluble/nuclear fractionation, and mRNA stability assays correlated with DNA synthesis","pmids":["7957682"],"confidence":"Medium","gaps":["Whether the extended C-terminus confers any function distinct from canonical H2A is untested","No interacting partners, modifying enzymes, or genomic distribution determined","Functional consequences of incorporation (transcription, chromatin compaction) not assessed"]},{"year":null,"claim":"Whether H2AC14 has any specialized chromatin function distinguishing it from other replication-dependent H2A isoforms remains unknown.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No structural or genomic-occupancy data","No defined biological process beyond generic nucleosome assembly","No disease or phenotypic association characterized in the corpus"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0005198","term_label":"structural molecule activity","supporting_discovery_ids":[0]}],"localization":[{"term_id":"GO:0000228","term_label":"nuclear chromosome","supporting_discovery_ids":[0]},{"term_id":"GO:0005634","term_label":"nucleus","supporting_discovery_ids":[0]}],"pathway":[{"term_id":"R-HSA-4839726","term_label":"Chromatin organization","supporting_discovery_ids":[0]}],"complexes":["nucleosome"],"partners":[],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q99878","full_name":"Histone H2A type 1-J","aliases":["Histone H2A/e"],"length_aa":128,"mass_kda":13.9,"function":"Core component of nucleosome. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling","subcellular_location":"Nucleus; Chromosome","url":"https://www.uniprot.org/uniprotkb/Q99878/entry"},"depmap":{"release":"DepMap","has_data":false,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/H2AC14"},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[],"url":"https://opencell.sf.czbiohub.org/search/H2AC14","total_profiled":1310},"omim":[{"mim_id":"602791","title":"HISTONE GENE CLUSTER 1, H2A HISTONE FAMILY, MEMBER J; HIST1H2AJ","url":"https://www.omim.org/entry/602791"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Supported","locations":[{"location":"Nucleoplasm","reliability":"Supported"}],"tissue_specificity":"Tissue enriched","tissue_distribution":"Detected in some","driving_tissues":[{"tissue":"bone marrow","ntpm":6.9}],"url":"https://www.proteinatlas.org/search/H2AC14"},"hgnc":{"alias_symbol":["H2A/E"],"prev_symbol":["H2AFE","HIST1H2AJ"]},"alphafold":{"accession":"Q99878","domains":[{"cath_id":"1.10.20.10","chopping":"18-110","consensus_level":"medium","plddt":97.8078,"start":18,"end":110}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q99878","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q99878-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q99878-F1-predicted_aligned_error_v6.png","plddt_mean":91.81},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=H2AC14","jax_strain_url":"https://www.jax.org/strain/search?query=H2AC14"},"sequence":{"accession":"Q99878","fasta_url":"https://rest.uniprot.org/uniprotkb/Q99878.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q99878/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q99878"}},"corpus_meta":[{"pmid":"27782156","id":"PMC_27782156","title":"Identification and validation of candidate epigenetic biomarkers in lung adenocarcinoma.","date":"2016","source":"Scientific reports","url":"https://pubmed.ncbi.nlm.nih.gov/27782156","citation_count":58,"is_preprint":false},{"pmid":"27295129","id":"PMC_27295129","title":"Investigating core genetic-and-epigenetic cell cycle networks for stemness and carcinogenic mechanisms, and cancer drug design using big database mining and genome-wide next-generation sequencing data.","date":"2016","source":"Cell cycle (Georgetown, Tex.)","url":"https://pubmed.ncbi.nlm.nih.gov/27295129","citation_count":29,"is_preprint":false},{"pmid":"14669947","id":"PMC_14669947","title":"HLA and H2 class II transgenic mouse models to study susceptibility and protection in autoimmune thyroid disease.","date":"2003","source":"Autoimmunity","url":"https://pubmed.ncbi.nlm.nih.gov/14669947","citation_count":18,"is_preprint":false},{"pmid":"29399289","id":"PMC_29399289","title":"Epigenetic basis of hepatocellular carcinoma: A network-based integrative meta-analysis.","date":"2018","source":"World journal of hepatology","url":"https://pubmed.ncbi.nlm.nih.gov/29399289","citation_count":13,"is_preprint":false},{"pmid":"37434783","id":"PMC_37434783","title":"Transcriptomic identification of genes expressed in invasive S. aureus diabetic foot ulcer infection.","date":"2023","source":"Frontiers in cellular and infection microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/37434783","citation_count":8,"is_preprint":false},{"pmid":"38067326","id":"PMC_38067326","title":"Characteristics of ABCC4 and ABCG2 High Expression Subpopulations in CRC-A New Opportunity to Predict Therapy Response.","date":"2023","source":"Cancers","url":"https://pubmed.ncbi.nlm.nih.gov/38067326","citation_count":4,"is_preprint":false},{"pmid":"11716530","id":"PMC_11716530","title":"Characterization of a novel H2A(-)E+ transgenic model susceptible to heterologous but not self thyroglobulin in autoimmune thyroiditis: thyroiditis transfer with Vbeta8+ T cells.","date":"2001","source":"Cellular immunology","url":"https://pubmed.ncbi.nlm.nih.gov/11716530","citation_count":3,"is_preprint":false},{"pmid":"40902508","id":"PMC_40902508","title":"Initial Insights into the NET-Associated ceRNA Network in Pulpitis: Transcriptomic and Functional Exploration.","date":"2025","source":"International dental journal","url":"https://pubmed.ncbi.nlm.nih.gov/40902508","citation_count":3,"is_preprint":false},{"pmid":"7957682","id":"PMC_7957682","title":"Expression of a marked H2A histone protein in mammalian cells.","date":"1994","source":"Experimental cell research","url":"https://pubmed.ncbi.nlm.nih.gov/7957682","citation_count":1,"is_preprint":false},{"pmid":"38966291","id":"PMC_38966291","title":"SMARCB1-Retained and SMARCB1-Deficient SNUC are Genetically Distinct: A Pilot Study Using RNA Sequencing.","date":"2023","source":"Journal of neurological surgery. Part B, Skull base","url":"https://pubmed.ncbi.nlm.nih.gov/38966291","citation_count":0,"is_preprint":false},{"pmid":"42225708","id":"PMC_42225708","title":"Identification and validation of palmitoylation-associated biomarkers in major depressive disorder.","date":"2026","source":"Scientific reports","url":"https://pubmed.ncbi.nlm.nih.gov/42225708","citation_count":0,"is_preprint":false},{"pmid":"40988048","id":"PMC_40988048","title":"Identification of novel H2A histone variants across diverse clades of algae.","date":"2025","source":"Genome biology","url":"https://pubmed.ncbi.nlm.nih.gov/40988048","citation_count":0,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":8981,"output_tokens":430,"usd":0.016696,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":6702,"output_tokens":997,"usd":0.029218,"stage2_stop_reason":"end_turn"},"total_usd":0.045914,"stage1_batch_id":"msgbatch_01DUPACZi7AAWwuZiUjseQF4","stage2_batch_id":"msgbatch_018yt7chE3f48PEFtDwtj6AE","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 1994,\n      \"finding\": \"A marked H2A histone protein (H2A.E, an alias for H2AC14) with an extended C-terminus (8 additional amino acids including 3 methionines) was incorporated into chromatin of HeLa cells at ~10% of total H2A. Its mRNA levels were coupled to rates of DNA and protein synthesis (replication-linked regulation), and its stability in chromatin and partitioning between soluble and nuclear fractions were indistinguishable from other histone species, demonstrating that H2AC14/H2A.E behaves as a functional replication-coupled histone.\",\n      \"method\": \"Stable transfection of HeLa cells with modified histone gene construct; two-dimensional AUT-AUC gel electrophoresis to resolve the novel protein; fractionation into soluble and nuclear compartments; mRNA stability assays correlated with DNA synthesis rates\",\n      \"journal\": \"Experimental cell research\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct biochemical fractionation and gel-based protein characterization in a single lab with multiple orthogonal methods (gel resolution, fractionation, mRNA coupling assay)\",\n      \"pmids\": [\"7957682\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"H2AC14 (H2A.E/H2AFE/HIST1H2AJ) encodes a replication-coupled histone H2A variant that is stably incorporated into chromatin, with mRNA levels regulated in concert with DNA replication, and whose chromatin stability and nucleocytoplasmic partitioning are equivalent to canonical H2A histones.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"H2AC14 encodes a replication-coupled histone H2A variant that is stably incorporated into chromatin and behaves as a functional component of the nucleosome [#0]. Expressed in HeLa cells, the protein (alias H2A.E) accumulates to roughly 10% of total H2A, carries an extended C-terminus, and exhibits chromatin stability and soluble-versus-nuclear partitioning indistinguishable from canonical H2A species; its mRNA levels are coupled to rates of DNA and protein synthesis, consistent with replication-linked regulation [#0]. Beyond [#0], no further mechanistic detail — partners, post-translational regulation, or distinct functional role relative to other H2A isoforms — has been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 1994,\n      \"claim\": \"Established that the H2AC14 gene product is a bona fide replication-coupled histone rather than a non-functional variant, by showing it is incorporated into chromatin and behaves like canonical H2A.\",\n      \"evidence\": \"Stable transfection of HeLa cells with a modified histone gene construct, two-dimensional AUT-AUC gel electrophoresis to resolve the protein, soluble/nuclear fractionation, and mRNA stability assays correlated with DNA synthesis\",\n      \"pmids\": [\n        \"7957682\"\n      ],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Whether the extended C-terminus confers any function distinct from canonical H2A is untested\",\n        \"No interacting partners, modifying enzymes, or genomic distribution determined\",\n        \"Functional consequences of incorporation (transcription, chromatin compaction) not assessed\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"Whether H2AC14 has any specialized chromatin function distinguishing it from other replication-dependent H2A isoforms remains unknown.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No structural or genomic-occupancy data\",\n        \"No defined biological process beyond generic nucleosome assembly\",\n        \"No disease or phenotypic association characterized in the corpus\"\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0005198\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0000228\", \"supporting_discovery_ids\": [0]},\n      {\"term_id\": \"GO:0005634\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-4839726\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"complexes\": [\n      \"nucleosome\"\n    ],\n    \"partners\": [],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":2,"faith_total":3,"faith_pct":66.66666666666667}}