{"gene":"ABHD14B","run_date":"2026-06-09T22:02:37","timeline":{"discoveries":[{"year":2019,"finding":"ABHD14B was annotated as a lysine deacetylase (KDAC) that transfers an acetyl group from a post-translationally acetylated protein lysine residue to coenzyme A (CoA), yielding acetyl-CoA and regenerating the free amine on the lysine. This activity was validated by in vitro biochemical assays with recombinant human ABHD14B and by cellular knockdown experiments. A putative substrate binding site was also identified.","method":"In vitro biochemical assay with recombinant protein, mammalian cell knockdown, active-site analysis","journal":"Biochemistry","confidence":"High","confidence_rationale":"Tier 1 / Moderate — in vitro reconstitution of enzymatic activity with recombinant protein plus cellular validation by knockdown; two orthogonal methods in a focused mechanistic study","pmids":["31478652"],"is_preprint":false},{"year":2022,"finding":"Loss of ABHD14B in mammalian cells results in significantly decreased flux of glucose through glycolysis and the citric acid cycle, as determined by combined transcriptomics and metabolomics. Hepatic depletion of ABHD14B in mice additionally causes defective systemic glucose metabolism, particularly during fasting, establishing ABHD14B as a regulator of glucose metabolism in vivo.","method":"siRNA knockdown in mammalian cells combined with transcriptomics and metabolomics; hepatic ABHD14B depletion in mice with metabolic phenotyping","journal":"The Journal of biological chemistry","confidence":"High","confidence_rationale":"Tier 2 / Moderate — loss-of-function in cells and in vivo mouse model with two orthogonal readouts (transcriptomics + metabolomics); specific metabolic phenotype defined","pmids":["35700823"],"is_preprint":false},{"year":2023,"finding":"Bioinformatics coupled with biochemical experiments identified key sequence determinants that distinguish ABHD14B from the closely related ABHD14A, enabling correct classification of each enzyme. The study mapped both enzymes on an evolutionary timescale and showed that despite high sequence similarity, ABHD14B has KDAC activity while ABHD14A remains functionally unannotated.","method":"Bioinformatics sequence analysis combined with biochemical experiments","journal":"Proteins","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — bioinformatics plus biochemical experiments distinguishing ABHD14B from ABHD14A; single lab, partial mechanistic detail from abstract","pmids":["37974539"],"is_preprint":false},{"year":2025,"finding":"ABHD14B was identified as a host protein that interacts with hepatitis B virus covalently closed circular DNA (cccDNA) via TFII-I, a protein that binds cccDNA in a sequence-dependent manner. ABHD14B decreases acetylation levels of histone proteins associated with cccDNA, thereby inhibiting HBV RNA transcription from cccDNA. Knockout of ABHD14B confirmed its suppressor role in HBV transcription.","method":"CRISPR-based proximity labeling (dCas9-BioID2) to identify cccDNA-interacting proteins; gene knockout; HBV RNA transcription assay; histone acetylation measurement","journal":"Hepatology communications","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — proximity labeling plus gene knockout with specific transcriptional readout; single lab, single study, mechanistic chain partially inferred from abstract","pmids":["40658808"],"is_preprint":false},{"year":2019,"finding":"ABHD14B was originally identified as associated with the transcription initiation factor TFIID (CCG1/TAFII250-interacting factor B), and its crystal structure was determined, though its endogenous substrates remained elusive prior to the KDAC annotation in this same paper.","method":"Crystal structure determination (prior to this paper); co-purification with TFIID reported in prior literature as noted in abstract","journal":"Biochemistry","confidence":"Low","confidence_rationale":"Tier 3 / Weak — structural and interaction data referenced historically in the abstract but not directly demonstrated as new experiments in this paper; context-dependent","pmids":["31478652"],"is_preprint":false}],"current_model":"ABHD14B is a serine hydrolase that functions as a lysine deacetylase (KDAC), transferring acetyl groups from post-translationally acetylated protein lysine residues to coenzyme A to produce acetyl-CoA; loss of ABHD14B impairs glucose flux through glycolysis and the TCA cycle in mammalian cells and causes defective systemic glucose metabolism in mice, and ABHD14B also localizes to cccDNA of hepatitis B virus via TFII-I, where it deacetylates cccDNA-associated histones to suppress HBV RNA transcription."},"narrative":{"mechanistic_narrative":"ABHD14B is a serine hydrolase that functions as a lysine deacetylase (KDAC), transferring an acetyl group from post-translationally acetylated protein lysine residues onto coenzyme A to generate acetyl-CoA while regenerating the free lysine amine [PMID:31478652]. Through this deacetylation/acetyl-transfer activity it acts as a regulator of central carbon metabolism: loss of ABHD14B reduces flux of glucose through glycolysis and the citric acid cycle in mammalian cells, and hepatic depletion in mice produces defective systemic glucose metabolism that is most pronounced during fasting [PMID:35700823]. The same KDAC activity is deployed in an antiviral context, where ABHD14B is recruited to hepatitis B virus covalently closed circular DNA (cccDNA) via the cccDNA-binding factor TFII-I and deacetylates cccDNA-associated histones to suppress HBV RNA transcription [PMID:40658808]. Sequence determinants that distinguish ABHD14B from the closely related, functionally unannotated ABHD14A have been defined, supporting its specific assignment as the KDAC-active enzyme of the pair [PMID:37974539].","teleology":[{"year":2019,"claim":"Established the molecular activity of ABHD14B, resolving a previously orphan serine hydrolase into a defined lysine deacetylase that channels protein acetyl groups onto CoA to make acetyl-CoA.","evidence":"In vitro biochemical assay with recombinant human protein plus mammalian cell knockdown and active-site analysis","pmids":["31478652"],"confidence":"High","gaps":["Endogenous physiological substrate lysines not identified","Substrate binding site described as putative, not structurally validated against a bound substrate"]},{"year":2022,"claim":"Connected the KDAC activity to a physiological output by showing ABHD14B controls glucose flux, demonstrating its enzymatic role is metabolically consequential at the cellular and organismal level.","evidence":"siRNA knockdown with transcriptomics/metabolomics in cells, and hepatic depletion with metabolic phenotyping in mice","pmids":["35700823"],"confidence":"High","gaps":["Direct substrate(s) linking deacetylation to glycolytic/TCA flux not pinpointed","Mechanism by which acetyl-CoA generation drives the metabolic phenotype not dissected"]},{"year":2023,"claim":"Resolved the ambiguity between two highly similar paralogs, defining sequence determinants that assign KDAC activity specifically to ABHD14B and not ABHD14A.","evidence":"Bioinformatics sequence analysis combined with biochemical experiments","pmids":["37974539"],"confidence":"Medium","gaps":["Function of ABHD14A remains unannotated","Single-lab classification, partial mechanistic detail"]},{"year":2025,"claim":"Extended ABHD14B function to host antiviral defense, showing its deacetylase activity acts on chromatinized viral cccDNA to repress transcription via a defined recruitment factor.","evidence":"CRISPR dCas9-BioID2 proximity labeling, gene knockout, HBV RNA transcription and histone acetylation assays","pmids":["40658808"],"confidence":"Medium","gaps":["Single-lab, single study with mechanistic chain partly inferred","Specific histone lysine residues deacetylated on cccDNA not mapped","TFII-I-ABHD14B interaction not independently validated"]},{"year":null,"claim":"The endogenous protein substrate repertoire that links ABHD14B deacetylation to glucose metabolism remains undefined.","evidence":"","pmids":[],"confidence":"Low","gaps":["No physiological substrate lysines identified","Structural basis of substrate selectivity unresolved","Relationship between metabolic and antiviral roles unexplored"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0140096","term_label":"catalytic activity, acting on a protein","supporting_discovery_ids":[0,3]},{"term_id":"GO:0016787","term_label":"hydrolase activity","supporting_discovery_ids":[0]},{"term_id":"GO:0016740","term_label":"transferase activity","supporting_discovery_ids":[0]}],"localization":[],"pathway":[{"term_id":"R-HSA-1430728","term_label":"Metabolism","supporting_discovery_ids":[1]},{"term_id":"R-HSA-4839726","term_label":"Chromatin organization","supporting_discovery_ids":[3]}],"complexes":[],"partners":["GTF2I"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q96IU4","full_name":"Putative protein-lysine deacylase ABHD14B","aliases":["Alpha/beta hydrolase domain-containing protein 14B","Abhydrolase domain-containing protein 14B","CCG1-interacting factor B"],"length_aa":210,"mass_kda":22.3,"function":"Acts as an atypical protein-lysine deacetylase in vitro (PubMed:31478652). Catalyzes the deacetylation of lysine residues using CoA as substrate, generating acetyl-CoA and the free amine of protein-lysine residues (PubMed:31478652). Additional experiments are however required to confirm the protein-lysine deacetylase activity in vivo (Probable). Has hydrolase activity towards various surrogate p-nitrophenyl (pNp) substrates, such as pNp-butyrate, pNp-acetate and pNp-octanoate in vitro, with a strong preference for pNp-acetate (PubMed:14672934, PubMed:31478652). May activate transcription (PubMed:14672934)","subcellular_location":"Cytoplasm; Nucleus","url":"https://www.uniprot.org/uniprotkb/Q96IU4/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/ABHD14B","classification":"Not Classified","n_dependent_lines":1,"n_total_lines":1208,"dependency_fraction":0.0008278145695364238},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[{"gene":"SAR1B","stoichiometry":0.2}],"url":"https://opencell.sf.czbiohub.org/search/ABHD14B","total_profiled":1310},"omim":[{"mim_id":"621040","title":"ABHYDROLASE DOMAIN-CONTAINING PROTEIN 14B; ABHD14B","url":"https://www.omim.org/entry/621040"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Supported","locations":[{"location":"Nucleoplasm","reliability":"Supported"},{"location":"Nucleoli","reliability":"Supported"},{"location":"Cytosol","reliability":"Additional"}],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in all","driving_tissues":[],"url":"https://www.proteinatlas.org/search/ABHD14B"},"hgnc":{"alias_symbol":["MGC15429","CIB"],"prev_symbol":[]},"alphafold":{"accession":"Q96IU4","domains":[{"cath_id":"3.40.50.1820","chopping":"4-207","consensus_level":"high","plddt":97.5749,"start":4,"end":207}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q96IU4","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q96IU4-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q96IU4-F1-predicted_aligned_error_v6.png","plddt_mean":96.94},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=ABHD14B","jax_strain_url":"https://www.jax.org/strain/search?query=ABHD14B"},"sequence":{"accession":"Q96IU4","fasta_url":"https://rest.uniprot.org/uniprotkb/Q96IU4.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q96IU4/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q96IU4"}},"corpus_meta":[{"pmid":"31593922","id":"PMC_31593922","title":"Tumor expression of environmental chemical-responsive genes and breast cancer mortality.","date":"2019","source":"Endocrine-related cancer","url":"https://pubmed.ncbi.nlm.nih.gov/31593922","citation_count":19,"is_preprint":false},{"pmid":"35700823","id":"PMC_35700823","title":"A multi-omics analysis reveals that the lysine deacetylase ABHD14B influences glucose metabolism in mammals.","date":"2022","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/35700823","citation_count":17,"is_preprint":false},{"pmid":"31478652","id":"PMC_31478652","title":"Functional Annotation of ABHD14B, an Orphan Serine Hydrolase Enzyme.","date":"2019","source":"Biochemistry","url":"https://pubmed.ncbi.nlm.nih.gov/31478652","citation_count":17,"is_preprint":false},{"pmid":"36995894","id":"PMC_36995894","title":"In-depth proteomic signature of parathyroid carcinoma.","date":"2023","source":"European journal of endocrinology","url":"https://pubmed.ncbi.nlm.nih.gov/36995894","citation_count":10,"is_preprint":false},{"pmid":"30121252","id":"PMC_30121252","title":"Effect of biphenyl hydrolase-like (BPHL) gene disruption on the intestinal stability, permeability and absorption of valacyclovir in wildtype and Bphl knockout mice.","date":"2018","source":"Biochemical pharmacology","url":"https://pubmed.ncbi.nlm.nih.gov/30121252","citation_count":6,"is_preprint":false},{"pmid":"39272995","id":"PMC_39272995","title":"Effects of Continuous Prenatal Low Dose Rate Irradiation on Neurobehavior, Hippocampal Cellularity, Messenger RNA and MicroRNA Expression on B6C3F1 Mice.","date":"2024","source":"Cells","url":"https://pubmed.ncbi.nlm.nih.gov/39272995","citation_count":5,"is_preprint":false},{"pmid":"38633108","id":"PMC_38633108","title":"Epigenome-wide association study identifies DNA methylation loci associated with handgrip strength in Chinese monozygotic twins.","date":"2024","source":"Frontiers in cell and developmental biology","url":"https://pubmed.ncbi.nlm.nih.gov/38633108","citation_count":4,"is_preprint":false},{"pmid":"32549867","id":"PMC_32549867","title":"Activity-based protein profiling guided identification of urine proteinase 3 activity in subclinical rejection after renal transplantation.","date":"2020","source":"Clinical proteomics","url":"https://pubmed.ncbi.nlm.nih.gov/32549867","citation_count":4,"is_preprint":false},{"pmid":"37974539","id":"PMC_37974539","title":"Identification of sequence determinants for the ABHD14 enzymes.","date":"2023","source":"Proteins","url":"https://pubmed.ncbi.nlm.nih.gov/37974539","citation_count":2,"is_preprint":false},{"pmid":"40426217","id":"PMC_40426217","title":"Spontaneous brain activity in patients with type 2 diabetes: linking serum neuroproteins to cognitive ability.","date":"2025","source":"Diabetology & metabolic syndrome","url":"https://pubmed.ncbi.nlm.nih.gov/40426217","citation_count":2,"is_preprint":false},{"pmid":"40658808","id":"PMC_40658808","title":"CRISPR-mediated proximity labeling unveils ABHD14B as a host factor to regulate HBV cccDNA transcriptional activity.","date":"2025","source":"Hepatology communications","url":"https://pubmed.ncbi.nlm.nih.gov/40658808","citation_count":1,"is_preprint":false},{"pmid":"41774615","id":"PMC_41774615","title":"Genome-wide DNA methylation profiles and ribosomal DNA copy number at birth.","date":"2026","source":"Epigenetics","url":"https://pubmed.ncbi.nlm.nih.gov/41774615","citation_count":0,"is_preprint":false},{"pmid":"40890957","id":"PMC_40890957","title":"Exploring Novel Biomarkers for Rosacea Through Cohort Study and Mendelian Randomisation.","date":"2025","source":"Experimental dermatology","url":"https://pubmed.ncbi.nlm.nih.gov/40890957","citation_count":0,"is_preprint":false},{"pmid":"41422660","id":"PMC_41422660","title":"GCHFR-gut microbiota axis in gout: an integrative multi-omics and Mendelian randomization study with clinical and molecular validation.","date":"2025","source":"International immunopharmacology","url":"https://pubmed.ncbi.nlm.nih.gov/41422660","citation_count":0,"is_preprint":false},{"pmid":"40181221","id":"PMC_40181221","title":"Mediators of the causal associations between protein ratios and ischemic stroke: a two-step Mendelian randomization study.","date":"2025","source":"Neurological research","url":"https://pubmed.ncbi.nlm.nih.gov/40181221","citation_count":0,"is_preprint":false},{"pmid":null,"id":"bio_10.1101_2025.11.28.691245","title":"Biochemical characterization of ABHD14A, an outlying member of the metabolic serine hydrolase family","date":"2025-11-29","source":"bioRxiv","url":"https://doi.org/10.1101/2025.11.28.691245","citation_count":0,"is_preprint":true}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":11525,"output_tokens":1362,"usd":0.027502,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":8061,"output_tokens":1727,"usd":0.04174,"stage2_stop_reason":"end_turn"},"total_usd":0.069242,"stage1_batch_id":"msgbatch_0179Z2pxRYBsXi2xADneafRw","stage2_batch_id":"msgbatch_01LaY9ZaVdgjWArcZo9eqQE5","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2019,\n      \"finding\": \"ABHD14B was annotated as a lysine deacetylase (KDAC) that transfers an acetyl group from a post-translationally acetylated protein lysine residue to coenzyme A (CoA), yielding acetyl-CoA and regenerating the free amine on the lysine. This activity was validated by in vitro biochemical assays with recombinant human ABHD14B and by cellular knockdown experiments. A putative substrate binding site was also identified.\",\n      \"method\": \"In vitro biochemical assay with recombinant protein, mammalian cell knockdown, active-site analysis\",\n      \"journal\": \"Biochemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Moderate — in vitro reconstitution of enzymatic activity with recombinant protein plus cellular validation by knockdown; two orthogonal methods in a focused mechanistic study\",\n      \"pmids\": [\"31478652\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"Loss of ABHD14B in mammalian cells results in significantly decreased flux of glucose through glycolysis and the citric acid cycle, as determined by combined transcriptomics and metabolomics. Hepatic depletion of ABHD14B in mice additionally causes defective systemic glucose metabolism, particularly during fasting, establishing ABHD14B as a regulator of glucose metabolism in vivo.\",\n      \"method\": \"siRNA knockdown in mammalian cells combined with transcriptomics and metabolomics; hepatic ABHD14B depletion in mice with metabolic phenotyping\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — loss-of-function in cells and in vivo mouse model with two orthogonal readouts (transcriptomics + metabolomics); specific metabolic phenotype defined\",\n      \"pmids\": [\"35700823\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"Bioinformatics coupled with biochemical experiments identified key sequence determinants that distinguish ABHD14B from the closely related ABHD14A, enabling correct classification of each enzyme. The study mapped both enzymes on an evolutionary timescale and showed that despite high sequence similarity, ABHD14B has KDAC activity while ABHD14A remains functionally unannotated.\",\n      \"method\": \"Bioinformatics sequence analysis combined with biochemical experiments\",\n      \"journal\": \"Proteins\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — bioinformatics plus biochemical experiments distinguishing ABHD14B from ABHD14A; single lab, partial mechanistic detail from abstract\",\n      \"pmids\": [\"37974539\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"ABHD14B was identified as a host protein that interacts with hepatitis B virus covalently closed circular DNA (cccDNA) via TFII-I, a protein that binds cccDNA in a sequence-dependent manner. ABHD14B decreases acetylation levels of histone proteins associated with cccDNA, thereby inhibiting HBV RNA transcription from cccDNA. Knockout of ABHD14B confirmed its suppressor role in HBV transcription.\",\n      \"method\": \"CRISPR-based proximity labeling (dCas9-BioID2) to identify cccDNA-interacting proteins; gene knockout; HBV RNA transcription assay; histone acetylation measurement\",\n      \"journal\": \"Hepatology communications\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — proximity labeling plus gene knockout with specific transcriptional readout; single lab, single study, mechanistic chain partially inferred from abstract\",\n      \"pmids\": [\"40658808\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"ABHD14B was originally identified as associated with the transcription initiation factor TFIID (CCG1/TAFII250-interacting factor B), and its crystal structure was determined, though its endogenous substrates remained elusive prior to the KDAC annotation in this same paper.\",\n      \"method\": \"Crystal structure determination (prior to this paper); co-purification with TFIID reported in prior literature as noted in abstract\",\n      \"journal\": \"Biochemistry\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — structural and interaction data referenced historically in the abstract but not directly demonstrated as new experiments in this paper; context-dependent\",\n      \"pmids\": [\"31478652\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"ABHD14B is a serine hydrolase that functions as a lysine deacetylase (KDAC), transferring acetyl groups from post-translationally acetylated protein lysine residues to coenzyme A to produce acetyl-CoA; loss of ABHD14B impairs glucose flux through glycolysis and the TCA cycle in mammalian cells and causes defective systemic glucose metabolism in mice, and ABHD14B also localizes to cccDNA of hepatitis B virus via TFII-I, where it deacetylates cccDNA-associated histones to suppress HBV RNA transcription.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"ABHD14B is a serine hydrolase that functions as a lysine deacetylase (KDAC), transferring an acetyl group from post-translationally acetylated protein lysine residues onto coenzyme A to generate acetyl-CoA while regenerating the free lysine amine [#0]. Through this deacetylation/acetyl-transfer activity it acts as a regulator of central carbon metabolism: loss of ABHD14B reduces flux of glucose through glycolysis and the citric acid cycle in mammalian cells, and hepatic depletion in mice produces defective systemic glucose metabolism that is most pronounced during fasting [#1]. The same KDAC activity is deployed in an antiviral context, where ABHD14B is recruited to hepatitis B virus covalently closed circular DNA (cccDNA) via the cccDNA-binding factor TFII-I and deacetylates cccDNA-associated histones to suppress HBV RNA transcription [#3]. Sequence determinants that distinguish ABHD14B from the closely related, functionally unannotated ABHD14A have been defined, supporting its specific assignment as the KDAC-active enzyme of the pair [#2].\",\n  \"teleology\": [\n    {\n      \"year\": 2019,\n      \"claim\": \"Established the molecular activity of ABHD14B, resolving a previously orphan serine hydrolase into a defined lysine deacetylase that channels protein acetyl groups onto CoA to make acetyl-CoA.\",\n      \"evidence\": \"In vitro biochemical assay with recombinant human protein plus mammalian cell knockdown and active-site analysis\",\n      \"pmids\": [\"31478652\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Endogenous physiological substrate lysines not identified\", \"Substrate binding site described as putative, not structurally validated against a bound substrate\"]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"Connected the KDAC activity to a physiological output by showing ABHD14B controls glucose flux, demonstrating its enzymatic role is metabolically consequential at the cellular and organismal level.\",\n      \"evidence\": \"siRNA knockdown with transcriptomics/metabolomics in cells, and hepatic depletion with metabolic phenotyping in mice\",\n      \"pmids\": [\"35700823\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Direct substrate(s) linking deacetylation to glycolytic/TCA flux not pinpointed\", \"Mechanism by which acetyl-CoA generation drives the metabolic phenotype not dissected\"]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"Resolved the ambiguity between two highly similar paralogs, defining sequence determinants that assign KDAC activity specifically to ABHD14B and not ABHD14A.\",\n      \"evidence\": \"Bioinformatics sequence analysis combined with biochemical experiments\",\n      \"pmids\": [\"37974539\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Function of ABHD14A remains unannotated\", \"Single-lab classification, partial mechanistic detail\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Extended ABHD14B function to host antiviral defense, showing its deacetylase activity acts on chromatinized viral cccDNA to repress transcription via a defined recruitment factor.\",\n      \"evidence\": \"CRISPR dCas9-BioID2 proximity labeling, gene knockout, HBV RNA transcription and histone acetylation assays\",\n      \"pmids\": [\"40658808\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Single-lab, single study with mechanistic chain partly inferred\", \"Specific histone lysine residues deacetylated on cccDNA not mapped\", \"TFII-I-ABHD14B interaction not independently validated\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The endogenous protein substrate repertoire that links ABHD14B deacetylation to glucose metabolism remains undefined.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"No physiological substrate lysines identified\", \"Structural basis of substrate selectivity unresolved\", \"Relationship between metabolic and antiviral roles unexplored\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0140096\", \"supporting_discovery_ids\": [0, 3]},\n      {\"term_id\": \"GO:0016787\", \"supporting_discovery_ids\": [0]},\n      {\"term_id\": \"GO:0016740\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"localization\": [],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-1430728\", \"supporting_discovery_ids\": [1]},\n      {\"term_id\": \"R-HSA-4839726\", \"supporting_discovery_ids\": [3]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\"GTF2I\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":4,"faith_total":4,"faith_pct":100.0}}