{"gene":"ETFB","run_date":"2026-06-09T23:54:43","timeline":{"discoveries":[{"year":1992,"finding":"Mammalian ETF from pig kidney exists in two forms (ETFR and ETFB) distinguishable by their flavin semiquinone upon reduction: the normal form (ETFR) generates a red anionic semiquinone, while ETFB generates a blue neutral semiquinone. ETFB contains a substoichiometric unusual FAD analogue. Both forms have comparable catalytic activity mediating electron transfer between medium-chain acyl-CoA dehydrogenase and 2,6-dichlorophenolindophenol. ETFB can be converted to ETFR by full reduction at pH 6.5 or apoprotein reconstitution with FAD, but not the reverse.","method":"Biochemical purification, spectrophotometric reduction assays (photochemical, dithionite, enzymatic), apoprotein reconstitution","journal":"Archives of biochemistry and biophysics","confidence":"Medium","confidence_rationale":"Tier 1 / Weak — in vitro enzymatic assay and reconstitution, but single lab, single study; describes a pig kidney form","pmids":["1731621"],"is_preprint":false},{"year":2003,"finding":"ETFB missense mutation D128N (identified in a type III MADD patient) results in reduced enzyme activity that can be rescued up to 59% of wild-type when expressed in E. coli at low temperature, demonstrating that environmental temperature can modulate the ETF enzymatic phenotype caused by this missense mutation.","method":"Overexpression of mutant ETFB-D128N in E. coli at low temperature followed by activity measurement; genomic structure determination and mutation characterization","journal":"Human mutation","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — functional overexpression with activity rescue, multiple mutations characterized across patients, single lab","pmids":["12815589"],"is_preprint":false},{"year":2003,"finding":"ETFB missense mutations C42R and K202del (deletion of lysine-202) cause a late-onset mild form of MADD/GAII, establishing that beta-ETF deficiency specifically due to ETFB mutations leads to impaired palmitate/myristate oxidation in fibroblasts and abnormal acylcarnitine profiles.","method":"Mutational analysis of ETFB gene; fibroblast fatty acid oxidation assays ([3H]-palmitate and [3H]-myristate oxidation)","journal":"Molecular genetics and metabolism","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — functional cellular assay with patient-derived cells, single lab, single case","pmids":["12706375"],"is_preprint":false},{"year":2006,"finding":"Human ETF is a heterodimer of alpha (ETFA, 30 kDa) and beta (ETFB, 28 kDa) subunits encoded by separate nuclear genes; ETF activity in patient tissue samples ranges from <1 to 16% of controls and directly correlates with disease severity in MADD patients with confirmed ETF deficiency; most mutations causing ETF deficiency are in ETFA, with only two patients harboring ETFB mutations.","method":"ETF activity assay in patient tissue samples, Western blot analysis, mutation analysis","journal":"Molecular genetics and metabolism","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct enzymatic activity assay in patient samples combined with molecular analysis, multi-patient study, single lab","pmids":["16510302"],"is_preprint":false},{"year":2011,"finding":"ETFB siRNA knockdown in human fibroblasts reduces cell number specifically in mechanically stressed (attached) collagen gel culture without affecting cell number in detached (stress-free) culture, identifying ETFB as a participant in mechanoregulation of fibroblast cell number.","method":"2D gel electrophoresis differential display, MALDI-TOF-MS protein identification, siRNA knockdown, collagen gel culture assay with cell counting","journal":"Journal of dermatological science","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — siRNA KD with specific phenotypic readout in mechanically stressed culture, single lab, single study","pmids":["21903359"],"is_preprint":false},{"year":2012,"finding":"ETFB knockdown in fibroblasts attenuates TGF-β-induced alpha-SMA mRNA expression under mechanical stress conditions (attached collagen gel culture) to levels comparable to those without TGF-β, and weakens stress fiber organization induced by TGF-β, but does not affect COL1A1 mRNA levels or cell proliferation on plastic.","method":"siRNA knockdown, qRT-PCR, AlamarBlue proliferation assay, phalloidin staining of stress fibers, collagen gel contraction assay","journal":"Journal of dermatological science","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — siRNA KD with multiple molecular readouts, single lab, follows up on prior study","pmids":["23068445"],"is_preprint":false},{"year":2014,"finding":"ETFB (beta-subunit of electron transfer flavoprotein) physically interacts with glutaryl-CoA dehydrogenase (GCDH) in mitochondria, identified by affinity chromatography and visualized by YFP-based fragment complementation in living cells; ETFB serves as an electron acceptor for GCDH.","method":"Affinity chromatography pulldown of GCDH-interacting proteins, mass spectrometry identification, YFP bimolecular fluorescence complementation in living cells","journal":"PloS one","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — reciprocal affinity pulldown plus live-cell complementation assay, single lab, two orthogonal methods","pmids":["24498361"],"is_preprint":false},{"year":2016,"finding":"Connexin 43 (Cx43) interacts with ETFB in the subsarcolemmal mitochondrial fraction of mouse heart, as demonstrated by direct and reverse co-immunoprecipitation; additionally, a novel interaction between AIF and ETFB was identified, with AIF and ETFB protein content and subcellular localization being independent of Cx43 presence.","method":"Native immunoprecipitation from mitochondrial extracts, mass spectrometry identification, direct and reverse co-immunoprecipitation, subcellular fractionation","journal":"Journal of cellular and molecular medicine","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — reciprocal Co-IP with mass spectrometry identification, two binding partners established, single lab","pmids":["26915330"],"is_preprint":false},{"year":2020,"finding":"Neddylation (NEDD8 conjugation) directly targets ETFB (and ETFA) as substrates in hepatic mitochondria, stabilizing ETF proteins by inhibiting their ubiquitination and degradation. Liver-specific UBA3 (NEDD8-activating enzyme catalytic subunit) deficiency leads to decreased ETFB and ETFA protein levels, spontaneous fatty liver, and a glutaric aciduria type II-like phenotype. Certain GA-II patient mutations in ETFB hinder its neddylation.","method":"Liver-specific UBA3 and NEDD8 knockout mouse models, neddylation assays with ETF substrates, ubiquitination assays, Western blot analysis in neonatal livers and embryonic hepatocytes, pharmacological neddylation inhibition","journal":"Proceedings of the National Academy of Sciences of the United States of America","confidence":"High","confidence_rationale":"Tier 1 / Strong — in vivo knockout models + direct substrate neddylation assay + ubiquitination/degradation assay + disease mutation validation, multiple orthogonal approaches in one study","pmids":["31941714"],"is_preprint":false},{"year":2021,"finding":"Human ETF heterodimer (ETFA+ETFB) functions as an electron transfer hub accepting electrons from at least 14 flavoenzymes (including acyl-CoA dehydrogenases) in the mitochondrial matrix and relaying them to ETF:QO (ETFDH) via iron-sulfur cluster, then to ubiquinone entering the respiratory chain at complex III level. Electron transfer from donor enzymes to ETF occurs by direct flavin-to-flavin transfer regulated by a recognition loop and dynamic movement of the ETF flavin domain.","method":"Review synthesizing structural, biochemical, and mutational studies; cofactor analysis (FAD and AMP in heterodimer)","journal":"Gene","confidence":"Medium","confidence_rationale":"Tier 2 / Strong — mechanistic review consolidating established structural and biochemical findings from multiple independent studies; not primary experimental data","pmids":["33450351"],"is_preprint":false},{"year":2022,"finding":"S1P (site-1 protease/MBTPS1) is a novel mitochondrial protein that forms a trimeric complex with ETFA/ETFB. S1P enhances ETFA/ETFB flavination and maintains their stability. Patient S1P variants destabilize ETFA/ETFB, impair mitochondrial respiration and fatty acid β-oxidation, and shift OXPHOS to glycolysis. Riboflavin supplementation restored ETFA/ETFB stability and ameliorated mitochondrial dysfunction in the patient.","method":"Co-immunoprecipitation to identify S1P-ETFA/ETFB trimeric complex; functional assays for flavination, mitochondrial respiration, β-oxidation activity; patient cell studies; riboflavin rescue experiment","journal":"EMBO molecular medicine","confidence":"High","confidence_rationale":"Tier 1 / Moderate — co-IP identifying trimeric complex, direct flavination assay, functional respiration and β-oxidation assays, disease mutation validation, multiple orthogonal methods","pmids":["35362222"],"is_preprint":false},{"year":2022,"finding":"Silencing of ETFB (and ETFA) in AML cells leads to increased mitochondrial activity, mitochondrial stress, and apoptosis, but has little to no effect on normal human CD34+ cells, indicating ETFB is required for AML cell survival and mitochondrial function.","method":"siRNA/shRNA silencing, mitochondrial activity assays, apoptosis assays in AML cell lines vs. normal CD34+ cells; quantitative mass spectrometry and RNAseq showing ETFB upregulated at protein but not transcript level in AML","journal":"Leukemia","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — loss-of-function with specific cellular phenotype readout, single lab, AML model","pmids":["35177813"],"is_preprint":false},{"year":2015,"finding":"Electron transfer flavoprotein subunit beta (ETFB) was identified as a candidate endothelial cell autoantigen in Behçet's disease: ETFB was detected by Western blotting and mass spectrometry from endothelial cell extracts probed with BD patient sera, recombinant ETFB was cloned and expressed, and ELISA showed positive reactivity in 41% of BD patients versus 1% of healthy controls.","method":"Western blotting with patient sera, LC-MALDI-TOF/TOF mass spectrometry identification, recombinant protein expression/purification, ELISA with patient cohort","journal":"PloS one","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — antigen identification by MS plus ELISA validation in large patient cohort, single lab, multiple orthogonal methods","pmids":["25915519"],"is_preprint":false},{"year":1994,"finding":"The human ETFB gene maps to chromosome 19q13.4, within approximately 40 kb of the LIM2 gene, as demonstrated by identifying a cosmid containing sequences from both genes.","method":"Cosmid cloning, chromosomal mapping by somatic cell genetics and FISH","journal":"Somatic cell and molecular genetics","confidence":"Low","confidence_rationale":"Tier 3 / Weak — chromosomal localization by cosmid mapping, single study, no functional information","pmids":["8197479"],"is_preprint":false}],"current_model":"Human ETFB encodes the beta subunit of the mitochondrial electron transfer flavoprotein (ETF) heterodimer (with ETFA), which accepts electrons from at least 14 flavoenzyme dehydrogenases (including acyl-CoA dehydrogenases) via direct flavin-to-flavin transfer and relays them to ETF:QO (ETFDH) and thence to ubiquinone; the ETF heterodimer is stabilized by neddylation (NEDD8 conjugation) that suppresses its ubiquitination/degradation, and is further chaperoned by a trimeric interaction with S1P/MBTPS1 that promotes FAD loading; ETFB physically interacts with GCDH (as electron acceptor), with mitochondrial Cx43 and AIF, and acts as an autoantigen in Behçet's disease; loss of ETFB causes fatty acid oxidation failure (MADD/glutaric aciduria type II), and ETFB knockdown in fibroblasts attenuates TGF-β-induced alpha-SMA expression and mechanoregulated cell number under mechanical stress."},"narrative":{"mechanistic_narrative":"ETFB encodes the beta subunit of the mitochondrial electron transfer flavoprotein (ETF), which together with ETFA forms a heterodimeric electron-transfer hub that accepts electrons from at least 14 matrix flavoenzymes, including acyl-CoA dehydrogenases, by direct flavin-to-flavin transfer and relays them to ETF:QO (ETFDH) and onward to ubiquinone at the respiratory chain [PMID:33450351]. ETFB physically interacts with glutaryl-CoA dehydrogenase (GCDH), for which it serves as electron acceptor [PMID:24498361], and is found in complex with mitochondrial connexin 43 and AIF in cardiac subsarcolemmal mitochondria [PMID:26915330]. The ETF heterodimer is post-translationally stabilized: neddylation (NEDD8 conjugation) of ETFB and ETFA suppresses their ubiquitination and degradation, with loss of this modification producing a glutaric aciduria type II–like phenotype [PMID:31941714], and a trimeric interaction with S1P/MBTPS1 promotes ETF flavination and stability [PMID:35362222]. Loss-of-function ETFB mutations cause multiple acyl-CoA dehydrogenation deficiency (MADD/glutaric aciduria type II), impairing fibroblast fatty acid oxidation and yielding abnormal acylcarnitine profiles, with residual ETF activity correlating with disease severity [PMID:12706375, PMID:16510302]. ETFB is required for the survival of AML cells but not normal CD34+ cells [PMID:35177813], and is detected as an endothelial autoantigen in Behçet's disease [PMID:25915519]; beyond its canonical bioenergetic role, ETFB also participates in mechanoregulation of fibroblast cell number and TGF-β-induced alpha-SMA expression under mechanical stress [PMID:21903359, PMID:23068445].","teleology":[{"year":1992,"claim":"Established that mammalian ETF exists in interconvertible redox/cofactor forms while retaining catalytic competence as an electron shuttle between acyl-CoA dehydrogenase and an artificial acceptor, defining its core biochemical activity.","evidence":"Biochemical purification and spectrophotometric reduction/reconstitution assays of pig kidney ETF","pmids":["1731621"],"confidence":"Medium","gaps":["Does not resolve which subunit carries the FAD analogue","Performed on a non-human ortholog","Physiological relevance of the ETFB-vs-ETFR distinction unclear"]},{"year":1994,"claim":"Localized the human ETFB gene to chromosome 19q13.4, providing the genomic anchor for subsequent mutation analysis.","evidence":"Cosmid cloning and chromosomal mapping by somatic cell genetics and FISH","pmids":["8197479"],"confidence":"Low","gaps":["Mapping only, no functional data","No gene structure or regulatory information"]},{"year":2003,"claim":"Demonstrated that specific ETFB missense and deletion mutations cause MADD/glutaric aciduria type II by impairing fatty acid oxidation, directly linking the beta subunit to disease.","evidence":"Mutational analysis plus fibroblast [3H]-palmitate/myristate oxidation assays and bacterial expression with activity rescue","pmids":["12706375","12815589"],"confidence":"Medium","gaps":["Limited number of patients/mutations","Mechanism by which mutations destabilize the heterodimer not resolved","Temperature-sensitive rescue shown only in E. coli"]},{"year":2006,"claim":"Confirmed the alpha/beta heterodimeric architecture of human ETF and quantified that residual ETF activity correlates with MADD severity, establishing genotype-to-phenotype gradation.","evidence":"ETF activity assays, Western blot, and mutation analysis in patient tissues","pmids":["16510302"],"confidence":"Medium","gaps":["ETFB mutations rare relative to ETFA in this cohort","Does not address structural basis of activity loss"]},{"year":2012,"claim":"Revealed a non-canonical role for ETFB in fibroblast mechanobiology, showing it is required for stress-dependent cell number control and TGF-β-induced myofibroblast marker expression.","evidence":"siRNA knockdown with collagen gel culture, qRT-PCR, proliferation and stress-fiber assays in human fibroblasts","pmids":["21903359","23068445"],"confidence":"Medium","gaps":["Molecular link between mitochondrial ETF function and mechanosignaling unknown","Single lab, no in vivo confirmation","Whether effect is metabolic or moonlighting unresolved"]},{"year":2014,"claim":"Identified a direct physical interaction with GCDH, establishing ETFB as the electron-accepting partner for a specific matrix dehydrogenase.","evidence":"Affinity chromatography pulldown, mass spectrometry, and YFP bimolecular fluorescence complementation in living cells","pmids":["24498361"],"confidence":"Medium","gaps":["Stoichiometry and structural interface not defined","Generalizability to other dehydrogenase partners not tested"]},{"year":2015,"claim":"Identified ETFB as an endothelial autoantigen recognized by Behçet's disease patient sera, implicating it in autoimmune reactivity.","evidence":"Western blotting and mass spectrometry from endothelial extracts probed with patient sera, plus ELISA in a patient cohort","pmids":["25915519"],"confidence":"Medium","gaps":["Pathogenic role of anti-ETFB antibodies unknown","Mechanism of surface/extracellular exposure of a mitochondrial protein unexplained"]},{"year":2016,"claim":"Placed ETFB in a cardiac mitochondrial protein complex with connexin 43 and AIF, expanding its interactome beyond electron-transfer substrates.","evidence":"Native and reciprocal co-immunoprecipitation with mass spectrometry from mouse heart subsarcolemmal mitochondria","pmids":["26915330"],"confidence":"Medium","gaps":["Functional consequence of Cx43/AIF association undefined","Direct vs indirect binding not distinguished"]},{"year":2020,"claim":"Defined neddylation as a post-translational mechanism that stabilizes ETFB/ETFA by blocking their ubiquitin-mediated degradation, with loss causing a GA-II-like phenotype in vivo.","evidence":"Liver-specific UBA3/NEDD8 knockout mice, direct neddylation and ubiquitination assays, and disease-mutation validation","pmids":["31941714"],"confidence":"High","gaps":["Site(s) of NEDD8 conjugation on ETFB not mapped","Upstream signals controlling ETF neddylation unknown"]},{"year":2022,"claim":"Showed that S1P/MBTPS1 forms a trimeric complex with ETFA/ETFB to promote flavination and stability, and that ETFB is selectively required for AML cell mitochondrial function and survival.","evidence":"Co-IP, flavination and respiration/β-oxidation assays with riboflavin rescue in patient cells; siRNA/shRNA silencing with mitochondrial and apoptosis assays in AML vs CD34+ cells","pmids":["35362222","35177813"],"confidence":"High","gaps":["Mechanism by which S1P facilitates FAD loading not structurally resolved","Basis of AML-selective dependence on ETFB unclear"]},{"year":null,"claim":"How ETFB's canonical electron-transfer role mechanistically connects to its reported moonlighting functions in mechanotransduction, autoimmunity, and AML dependence remains unresolved.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No structural model of the S1P-ETF trimeric complex","Neddylation site on ETFB unmapped","Link between mitochondrial ETF activity and TGF-β/mechanosignaling unknown"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0016491","term_label":"oxidoreductase activity","supporting_discovery_ids":[0,6,9]},{"term_id":"GO:0140104","term_label":"molecular carrier activity","supporting_discovery_ids":[9]},{"term_id":"GO:0008289","term_label":"lipid binding","supporting_discovery_ids":[10]}],"localization":[{"term_id":"GO:0005739","term_label":"mitochondrion","supporting_discovery_ids":[6,7,8,9,10]}],"pathway":[{"term_id":"R-HSA-1430728","term_label":"Metabolism","supporting_discovery_ids":[2,9]},{"term_id":"R-HSA-1643685","term_label":"Disease","supporting_discovery_ids":[2,3,8,10]}],"complexes":["electron transfer flavoprotein (ETFA/ETFB) heterodimer","S1P-ETFA-ETFB trimeric complex"],"partners":["ETFA","ETFDH","GCDH","MBTPS1","GJA1","AIFM1","NEDD8","UBA3"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"P38117","full_name":"Electron transfer flavoprotein subunit beta","aliases":[],"length_aa":255,"mass_kda":27.8,"function":"Heterodimeric electron transfer flavoprotein that accepts electrons from several mitochondrial dehydrogenases, including acyl-CoA dehydrogenases, glutaryl-CoA and sarcosine dehydrogenase (PubMed:15159392, PubMed:15975918, PubMed:25416781). It transfers the electrons to the main mitochondrial respiratory chain via ETF-ubiquinone oxidoreductase (Probable). Required for normal mitochondrial fatty acid oxidation and normal amino acid metabolism (PubMed:12815589, PubMed:7912128). ETFB binds an AMP molecule that probably has a purely structural role (PubMed:15159392, PubMed:15975918, PubMed:8962055)","subcellular_location":"Mitochondrion matrix","url":"https://www.uniprot.org/uniprotkb/P38117/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/ETFB","classification":"Not Classified","n_dependent_lines":4,"n_total_lines":1208,"dependency_fraction":0.0033112582781456954},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[{"gene":"ASS1","stoichiometry":0.2},{"gene":"BLVRB","stoichiometry":0.2},{"gene":"CLIP1","stoichiometry":0.2},{"gene":"HEATR3","stoichiometry":0.2},{"gene":"PHGDH","stoichiometry":0.2},{"gene":"RER1","stoichiometry":0.2}],"url":"https://opencell.sf.czbiohub.org/search/ETFB","total_profiled":1310},"omim":[{"mim_id":"621252","title":"CATARACT, ALOPECIA, ORAL MUCOSAL DISORDER, AND PSORIASIS-LIKE SYNDROME; CAOP","url":"https://www.omim.org/entry/621252"},{"mim_id":"615256","title":"ELECTRON TRANSFER FLAVOPROTEIN BETA-SUBUNIT LYSINE METHYLTRANSFERASE; ETFBKMT","url":"https://www.omim.org/entry/615256"},{"mim_id":"610528","title":"CHROMODOMAIN HELICASE DNA-BINDING PROTEIN 8; CHD8","url":"https://www.omim.org/entry/610528"},{"mim_id":"608053","title":"ELECTRON TRANSFER FLAVOPROTEIN, ALPHA POLYPEPTIDE; ETFA","url":"https://www.omim.org/entry/608053"},{"mim_id":"603355","title":"MEMBRANE-BOUND TRANSCRIPTION FACTOR PROTEASE, SITE 1; MBTPS1","url":"https://www.omim.org/entry/603355"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Enhanced","locations":[{"location":"Mitochondria","reliability":"Enhanced"}],"tissue_specificity":"Tissue enhanced","tissue_distribution":"Detected in all","driving_tissues":[{"tissue":"liver","ntpm":489.9}],"url":"https://www.proteinatlas.org/search/ETFB"},"hgnc":{"alias_symbol":[],"prev_symbol":[]},"alphafold":{"accession":"P38117","domains":[{"cath_id":"3.40.50.620","chopping":"6-231","consensus_level":"high","plddt":96.9635,"start":6,"end":231}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/P38117","model_url":"https://alphafold.ebi.ac.uk/files/AF-P38117-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-P38117-F1-predicted_aligned_error_v6.png","plddt_mean":96.12},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=ETFB","jax_strain_url":"https://www.jax.org/strain/search?query=ETFB"},"sequence":{"accession":"P38117","fasta_url":"https://rest.uniprot.org/uniprotkb/P38117.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/P38117/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/P38117"}},"corpus_meta":[{"pmid":"18060402","id":"PMC_18060402","title":"Expression of Clostridium acetobutylicum butanol synthetic genes in Escherichia coli.","date":"2007","source":"Applied microbiology and biotechnology","url":"https://pubmed.ncbi.nlm.nih.gov/18060402","citation_count":198,"is_preprint":false},{"pmid":"12815589","id":"PMC_12815589","title":"Clear relationship between ETF/ETFDH genotype and phenotype in patients with multiple acyl-CoA dehydrogenation deficiency.","date":"2003","source":"Human mutation","url":"https://pubmed.ncbi.nlm.nih.gov/12815589","citation_count":191,"is_preprint":false},{"pmid":"18288265","id":"PMC_18288265","title":"Comprehensive analysis of PPARalpha-dependent regulation of hepatic lipid metabolism by expression profiling.","date":"2007","source":"PPAR research","url":"https://pubmed.ncbi.nlm.nih.gov/18288265","citation_count":184,"is_preprint":false},{"pmid":"18448419","id":"PMC_18448419","title":"The identification of potential factors associated with the development of type 2 diabetes: a quantitative proteomics approach.","date":"2008","source":"Molecular & cellular proteomics : MCP","url":"https://pubmed.ncbi.nlm.nih.gov/18448419","citation_count":163,"is_preprint":false},{"pmid":"32711556","id":"PMC_32711556","title":"Integrated analysis of ultra-deep proteomes in cortex, cerebrospinal fluid and serum reveals a mitochondrial signature in Alzheimer's disease.","date":"2020","source":"Molecular neurodegeneration","url":"https://pubmed.ncbi.nlm.nih.gov/32711556","citation_count":162,"is_preprint":false},{"pmid":"25200064","id":"PMC_25200064","title":"Clinical and genetical heterogeneity of late-onset multiple acyl-coenzyme A dehydrogenase deficiency.","date":"2014","source":"Orphanet journal of rare diseases","url":"https://pubmed.ncbi.nlm.nih.gov/25200064","citation_count":150,"is_preprint":false},{"pmid":"33450351","id":"PMC_33450351","title":"Electron transfer flavoprotein and its role in mitochondrial energy metabolism in health and disease.","date":"2021","source":"Gene","url":"https://pubmed.ncbi.nlm.nih.gov/33450351","citation_count":101,"is_preprint":false},{"pmid":"8655474","id":"PMC_8655474","title":"Cloning, sequencing, and expression of clustered genes encoding beta-hydroxybutyryl-coenzyme A (CoA) dehydrogenase, crotonase, and butyryl-CoA dehydrogenase from Clostridium acetobutylicum ATCC 824.","date":"1996","source":"Journal of bacteriology","url":"https://pubmed.ncbi.nlm.nih.gov/8655474","citation_count":100,"is_preprint":false},{"pmid":"20195860","id":"PMC_20195860","title":"Reconstructing the clostridial n-butanol metabolic pathway in Lactobacillus brevis.","date":"2010","source":"Applied microbiology and biotechnology","url":"https://pubmed.ncbi.nlm.nih.gov/20195860","citation_count":94,"is_preprint":false},{"pmid":"19758981","id":"PMC_19758981","title":"Riboflavin-responsive lipid-storage myopathy caused by ETFDH gene mutations.","date":"2009","source":"Journal of neurology, neurosurgery, and psychiatry","url":"https://pubmed.ncbi.nlm.nih.gov/19758981","citation_count":92,"is_preprint":false},{"pmid":"16510302","id":"PMC_16510302","title":"Electron transfer flavoprotein deficiency: functional and molecular aspects.","date":"2006","source":"Molecular genetics and metabolism","url":"https://pubmed.ncbi.nlm.nih.gov/16510302","citation_count":90,"is_preprint":false},{"pmid":"17189250","id":"PMC_17189250","title":"Organization and function of the YsiA regulon of Bacillus subtilis involved in fatty acid degradation.","date":"2006","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/17189250","citation_count":87,"is_preprint":false},{"pmid":"21347544","id":"PMC_21347544","title":"Molecular analysis of 51 unrelated pedigrees with late-onset multiple acyl-CoA dehydrogenation deficiency (MADD) in southern China confirmed the most common ETFDH mutation and high carrier frequency of c.250G>A.","date":"2011","source":"Journal of molecular medicine (Berlin, Germany)","url":"https://pubmed.ncbi.nlm.nih.gov/21347544","citation_count":81,"is_preprint":false},{"pmid":"33886098","id":"PMC_33886098","title":"Riboflavin in Neurological Diseases: A Narrative Review.","date":"2021","source":"Clinical drug investigation","url":"https://pubmed.ncbi.nlm.nih.gov/33886098","citation_count":73,"is_preprint":false},{"pmid":"17085570","id":"PMC_17085570","title":"Bacillus subtilis gene cluster involved in calcium carbonate biomineralization.","date":"2006","source":"Journal of bacteriology","url":"https://pubmed.ncbi.nlm.nih.gov/17085570","citation_count":66,"is_preprint":false},{"pmid":"25956767","id":"PMC_25956767","title":"Energy Conservation Model Based on Genomic and Experimental Analyses of a Carbon Monoxide-Utilizing, Butyrate-Forming Acetogen, Eubacterium limosum KIST612.","date":"2015","source":"Applied and environmental microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/25956767","citation_count":65,"is_preprint":false},{"pmid":"18289905","id":"PMC_18289905","title":"Clinical and molecular investigations of Japanese cases of glutaric acidemia type 2.","date":"2008","source":"Molecular genetics and metabolism","url":"https://pubmed.ncbi.nlm.nih.gov/18289905","citation_count":64,"is_preprint":false},{"pmid":"17873051","id":"PMC_17873051","title":"Dissection of the caffeate respiratory chain in the acetogen Acetobacterium woodii: identification of an Rnf-type NADH dehydrogenase as a potential coupling site.","date":"2007","source":"Journal of bacteriology","url":"https://pubmed.ncbi.nlm.nih.gov/17873051","citation_count":57,"is_preprint":false},{"pmid":"22231380","id":"PMC_22231380","title":"Update on clinical aspects and treatment of selected vitamin-responsive disorders II (riboflavin and CoQ 10).","date":"2012","source":"Journal of inherited metabolic disease","url":"https://pubmed.ncbi.nlm.nih.gov/22231380","citation_count":56,"is_preprint":false},{"pmid":"26915330","id":"PMC_26915330","title":"New protein-protein interactions of mitochondrial connexin 43 in mouse heart.","date":"2016","source":"Journal of cellular and molecular medicine","url":"https://pubmed.ncbi.nlm.nih.gov/26915330","citation_count":53,"is_preprint":false},{"pmid":"24291725","id":"PMC_24291725","title":"Comparative study of the neurotrophic effects elicited by VEGF-B and GDNF in preclinical in vivo models of Parkinson's disease.","date":"2013","source":"Neuroscience","url":"https://pubmed.ncbi.nlm.nih.gov/24291725","citation_count":51,"is_preprint":false},{"pmid":"21962126","id":"PMC_21962126","title":"Single-nucleotide resolution analysis of the transcriptome structure of Clostridium beijerinckii NCIMB 8052 using RNA-Seq.","date":"2011","source":"BMC genomics","url":"https://pubmed.ncbi.nlm.nih.gov/21962126","citation_count":49,"is_preprint":false},{"pmid":"31941714","id":"PMC_31941714","title":"Hepatic neddylation targets and stabilizes electron transfer flavoproteins to facilitate fatty acid β-oxidation.","date":"2020","source":"Proceedings of the National Academy of Sciences of the United States of America","url":"https://pubmed.ncbi.nlm.nih.gov/31941714","citation_count":46,"is_preprint":false},{"pmid":"19265687","id":"PMC_19265687","title":"Novel mutations in ETFDH gene in Chinese patients with riboflavin-responsive multiple acyl-CoA dehydrogenase deficiency.","date":"2009","source":"Clinica chimica acta; international journal of clinical chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/19265687","citation_count":44,"is_preprint":false},{"pmid":"33279678","id":"PMC_33279678","title":"Disorders of flavin adenine dinucleotide metabolism: MADD and related deficiencies.","date":"2020","source":"The international journal of biochemistry & cell biology","url":"https://pubmed.ncbi.nlm.nih.gov/33279678","citation_count":42,"is_preprint":false},{"pmid":"23785301","id":"PMC_23785301","title":"Multi-organ abnormalities and mTORC1 activation in zebrafish model of multiple acyl-CoA dehydrogenase deficiency.","date":"2013","source":"PLoS genetics","url":"https://pubmed.ncbi.nlm.nih.gov/23785301","citation_count":39,"is_preprint":false},{"pmid":"30311138","id":"PMC_30311138","title":"A Novel Truncating FLAD1 Variant, Causing Multiple Acyl-CoA Dehydrogenase Deficiency (MADD) in an 8-Year-Old Boy.","date":"2018","source":"JIMD reports","url":"https://pubmed.ncbi.nlm.nih.gov/30311138","citation_count":32,"is_preprint":false},{"pmid":"30003820","id":"PMC_30003820","title":"Coenzyme Q10 serves to couple mitochondrial oxidative phosphorylation and fatty acid β-oxidation, and attenuates NLRP3 inflammasome activation.","date":"2018","source":"Free radical research","url":"https://pubmed.ncbi.nlm.nih.gov/30003820","citation_count":32,"is_preprint":false},{"pmid":"16527485","id":"PMC_16527485","title":"So doctor, what exactly is wrong with my muscles? Glutaric aciduria type II presenting in a teenager.","date":"2006","source":"Neuromuscular disorders : NMD","url":"https://pubmed.ncbi.nlm.nih.gov/16527485","citation_count":31,"is_preprint":false},{"pmid":"27000805","id":"PMC_27000805","title":"Significant clinical heterogeneity with similar ETFDH genotype in three Chinese patients with late-onset multiple acyl-CoA dehydrogenase deficiency.","date":"2016","source":"Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology","url":"https://pubmed.ncbi.nlm.nih.gov/27000805","citation_count":29,"is_preprint":false},{"pmid":"12706375","id":"PMC_12706375","title":"Late-onset form of beta-electron transfer flavoprotein deficiency.","date":"2003","source":"Molecular genetics and metabolism","url":"https://pubmed.ncbi.nlm.nih.gov/12706375","citation_count":29,"is_preprint":false},{"pmid":"28913729","id":"PMC_28913729","title":"Exome array analysis identifies ETFB as a novel susceptibility gene for anthracycline-induced cardiotoxicity in cancer patients.","date":"2017","source":"Breast cancer research and treatment","url":"https://pubmed.ncbi.nlm.nih.gov/28913729","citation_count":28,"is_preprint":false},{"pmid":"31997039","id":"PMC_31997039","title":"Multiple acyl-COA dehydrogenase deficiency in elderly carriers.","date":"2020","source":"Journal of neurology","url":"https://pubmed.ncbi.nlm.nih.gov/31997039","citation_count":28,"is_preprint":false},{"pmid":"34782606","id":"PMC_34782606","title":"Multiple acyl-CoA dehydrogenase deficiency kills Mycobacterium tuberculosis in vitro and during infection.","date":"2021","source":"Nature communications","url":"https://pubmed.ncbi.nlm.nih.gov/34782606","citation_count":27,"is_preprint":false},{"pmid":"35362222","id":"PMC_35362222","title":"S1P defects cause a new entity of cataract, alopecia, oral mucosal disorder, and psoriasis-like syndrome.","date":"2022","source":"EMBO molecular medicine","url":"https://pubmed.ncbi.nlm.nih.gov/35362222","citation_count":25,"is_preprint":false},{"pmid":"35309592","id":"PMC_35309592","title":"Diagnostic Challenges in Late Onset Multiple Acyl-CoA Dehydrogenase Deficiency: Clinical, Morphological, and Genetic Aspects.","date":"2022","source":"Frontiers in neurology","url":"https://pubmed.ncbi.nlm.nih.gov/35309592","citation_count":23,"is_preprint":false},{"pmid":"31331668","id":"PMC_31331668","title":"Determinants of Riboflavin Responsiveness in Multiple Acyl-CoA Dehydrogenase Deficiency.","date":"2019","source":"Pediatric neurology","url":"https://pubmed.ncbi.nlm.nih.gov/31331668","citation_count":21,"is_preprint":false},{"pmid":"21131487","id":"PMC_21131487","title":"A caffeyl-coenzyme A synthetase initiates caffeate activation prior to caffeate reduction in the acetogenic bacterium Acetobacterium woodii.","date":"2010","source":"Journal of bacteriology","url":"https://pubmed.ncbi.nlm.nih.gov/21131487","citation_count":21,"is_preprint":false},{"pmid":"30115820","id":"PMC_30115820","title":"Putative Iron Acquisition Systems in Stenotrophomonas maltophilia.","date":"2018","source":"Molecules (Basel, Switzerland)","url":"https://pubmed.ncbi.nlm.nih.gov/30115820","citation_count":21,"is_preprint":false},{"pmid":"27113712","id":"PMC_27113712","title":"Functional characterization of electron-transferring flavoprotein and its dehydrogenase required for fungal development and plant infection by the rice blast fungus.","date":"2016","source":"Scientific reports","url":"https://pubmed.ncbi.nlm.nih.gov/27113712","citation_count":21,"is_preprint":false},{"pmid":"23453982","id":"PMC_23453982","title":"Fermentation approach for enhancing 1-butanol production using engineered butanologenic Escherichia coli.","date":"2013","source":"Bioresource technology","url":"https://pubmed.ncbi.nlm.nih.gov/23453982","citation_count":21,"is_preprint":false},{"pmid":"35748623","id":"PMC_35748623","title":"Structure-based electron-confurcation mechanism of the Ldh-EtfAB complex.","date":"2022","source":"eLife","url":"https://pubmed.ncbi.nlm.nih.gov/35748623","citation_count":20,"is_preprint":false},{"pmid":"35177813","id":"PMC_35177813","title":"Multi-omics reveals mitochondrial metabolism proteins susceptible for drug discovery in AML.","date":"2022","source":"Leukemia","url":"https://pubmed.ncbi.nlm.nih.gov/35177813","citation_count":20,"is_preprint":false},{"pmid":"30982706","id":"PMC_30982706","title":"Flavin adenine dinucleotide synthase deficiency due to FLAD1 mutation presenting as multiple acyl-CoA dehydrogenation deficiency-like disease: A case report.","date":"2019","source":"Brain & development","url":"https://pubmed.ncbi.nlm.nih.gov/30982706","citation_count":20,"is_preprint":false},{"pmid":"21398533","id":"PMC_21398533","title":"Catabolite repression of the Bacillus subtilis FadR regulon, which is involved in fatty acid catabolism.","date":"2011","source":"Journal of bacteriology","url":"https://pubmed.ncbi.nlm.nih.gov/21398533","citation_count":20,"is_preprint":false},{"pmid":"24498361","id":"PMC_24498361","title":"Interaction of glutaric aciduria type 1-related glutaryl-CoA dehydrogenase with mitochondrial matrix proteins.","date":"2014","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/24498361","citation_count":19,"is_preprint":false},{"pmid":"28709933","id":"PMC_28709933","title":"Identification of novel biomarker and therapeutic target candidates for diagnosis and treatment of follicular carcinoma.","date":"2017","source":"Journal of proteomics","url":"https://pubmed.ncbi.nlm.nih.gov/28709933","citation_count":19,"is_preprint":false},{"pmid":"31392824","id":"PMC_31392824","title":"FLAD1-associated multiple acyl-CoA dehydrogenase deficiency identified by newborn screening.","date":"2019","source":"Molecular genetics & genomic medicine","url":"https://pubmed.ncbi.nlm.nih.gov/31392824","citation_count":17,"is_preprint":false},{"pmid":"33869202","id":"PMC_33869202","title":"Melatonin Modulates Lipid Metabolism in Porcine Cumulus-Oocyte Complex via Its Receptors.","date":"2021","source":"Frontiers in cell and developmental biology","url":"https://pubmed.ncbi.nlm.nih.gov/33869202","citation_count":14,"is_preprint":false},{"pmid":"24565692","id":"PMC_24565692","title":"Cellular responses in Bacillus thuringiensis CS33 during bacteriophage BtCS33 infection.","date":"2014","source":"Journal of proteomics","url":"https://pubmed.ncbi.nlm.nih.gov/24565692","citation_count":13,"is_preprint":false},{"pmid":"26586044","id":"PMC_26586044","title":"Transcriptional analysis of micronutrient zinc-associated response for enhanced carbohydrate utilization and earlier solventogenesis in Clostridium acetobutylicum.","date":"2015","source":"Scientific reports","url":"https://pubmed.ncbi.nlm.nih.gov/26586044","citation_count":13,"is_preprint":false},{"pmid":"32393189","id":"PMC_32393189","title":"A novel electron transfer flavoprotein dehydrogenase (ETFDH) gene mutation identified in a newborn with glutaric acidemia type II: a case report of a Chinese family.","date":"2020","source":"BMC medical genetics","url":"https://pubmed.ncbi.nlm.nih.gov/32393189","citation_count":13,"is_preprint":false},{"pmid":"1731621","id":"PMC_1731621","title":"A new form of mammalian electron-transferring flavoprotein.","date":"1992","source":"Archives of biochemistry and biophysics","url":"https://pubmed.ncbi.nlm.nih.gov/1731621","citation_count":12,"is_preprint":false},{"pmid":"8197479","id":"PMC_8197479","title":"Assignment of the human lens fiber cell MP19 gene (LIM2) to chromosome 19q13.4, and adjacent to ETFB.","date":"1994","source":"Somatic cell and molecular genetics","url":"https://pubmed.ncbi.nlm.nih.gov/8197479","citation_count":11,"is_preprint":false},{"pmid":"38941880","id":"PMC_38941880","title":"Molecular genetic analysis of candidate genes for glutaric aciduria type II in a cohort of patients from Queensland, Australia.","date":"2024","source":"Molecular genetics and metabolism","url":"https://pubmed.ncbi.nlm.nih.gov/38941880","citation_count":11,"is_preprint":false},{"pmid":"37041202","id":"PMC_37041202","title":"Proteomics reveals specific biological changes induced by the normothermic machine perfusion of donor kidneys with a significant up-regulation of Latexin.","date":"2023","source":"Scientific reports","url":"https://pubmed.ncbi.nlm.nih.gov/37041202","citation_count":11,"is_preprint":false},{"pmid":"34764427","id":"PMC_34764427","title":"Hypoketotic hypoglycemia without neuromuscular complications in patients with SLC25A32 deficiency.","date":"2021","source":"European journal of human genetics : EJHG","url":"https://pubmed.ncbi.nlm.nih.gov/34764427","citation_count":11,"is_preprint":false},{"pmid":"31418342","id":"PMC_31418342","title":"Molecular and Clinical Investigations on Portuguese Patients with Multiple acyl-CoA Dehydrogenase Deficiency.","date":"2019","source":"Current molecular medicine","url":"https://pubmed.ncbi.nlm.nih.gov/31418342","citation_count":10,"is_preprint":false},{"pmid":"39318848","id":"PMC_39318848","title":"MADD-like pattern of acylcarnitines associated with sertraline use.","date":"2024","source":"Molecular genetics and metabolism reports","url":"https://pubmed.ncbi.nlm.nih.gov/39318848","citation_count":10,"is_preprint":false},{"pmid":"20736750","id":"PMC_20736750","title":"Role of postmortem genetic testing demonstrated in a case of glutaric aciduria type II.","date":"2010","source":"Diagnostic molecular pathology : the American journal of surgical pathology, part B","url":"https://pubmed.ncbi.nlm.nih.gov/20736750","citation_count":10,"is_preprint":false},{"pmid":"32804429","id":"PMC_32804429","title":"Mitochondrial energetic impairment in a patient with late-onset glutaric acidemia Type 2.","date":"2020","source":"American journal of medical genetics. Part A","url":"https://pubmed.ncbi.nlm.nih.gov/32804429","citation_count":9,"is_preprint":false},{"pmid":"38183079","id":"PMC_38183079","title":"Identification of key genes in chronic intermittent hypoxia-induced lung cancer progression based on transcriptome sequencing.","date":"2024","source":"BMC cancer","url":"https://pubmed.ncbi.nlm.nih.gov/38183079","citation_count":8,"is_preprint":false},{"pmid":"22776992","id":"PMC_22776992","title":"Engineering a homobutanol fermentation pathway in Escherichia coli EG03.","date":"2012","source":"Journal of industrial microbiology & biotechnology","url":"https://pubmed.ncbi.nlm.nih.gov/22776992","citation_count":8,"is_preprint":false},{"pmid":"21903359","id":"PMC_21903359","title":"Identification of ETFB as a candidate protein that participates in the mechanoregulation of fibroblast cell number in collagen gel culture.","date":"2011","source":"Journal of dermatological science","url":"https://pubmed.ncbi.nlm.nih.gov/21903359","citation_count":7,"is_preprint":false},{"pmid":"24918489","id":"PMC_24918489","title":"A proteomics approach to identify the differential protein level in cardiac muscle of diabetic rat.","date":"2014","source":"Acta biochimica Polonica","url":"https://pubmed.ncbi.nlm.nih.gov/24918489","citation_count":7,"is_preprint":false},{"pmid":"34025022","id":"PMC_34025022","title":"Transcriptome profiling analysis of the response to walnut polyphenol extract in Helicobacter pylori-infected cells.","date":"2021","source":"Journal of clinical biochemistry and nutrition","url":"https://pubmed.ncbi.nlm.nih.gov/34025022","citation_count":7,"is_preprint":false},{"pmid":"25915519","id":"PMC_25915519","title":"Electron Transfer Flavoprotein Subunit Beta Is a Candidate Endothelial Cell Autoantigen in Behçet's Disease.","date":"2015","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/25915519","citation_count":7,"is_preprint":false},{"pmid":"34704421","id":"PMC_34704421","title":"Screening of multiple acyl-CoA dehydrogenase deficiency in newborns and follow-up of patients.","date":"2021","source":"Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences","url":"https://pubmed.ncbi.nlm.nih.gov/34704421","citation_count":6,"is_preprint":false},{"pmid":"23068445","id":"PMC_23068445","title":"Knockdown of electron transfer flavoprotein β subunit reduced TGF-β-induced α-SMA mRNA expression but not COL1A1 in fibroblast-populated three-dimensional collagen gel cultures.","date":"2012","source":"Journal of dermatological science","url":"https://pubmed.ncbi.nlm.nih.gov/23068445","citation_count":6,"is_preprint":false},{"pmid":"37599631","id":"PMC_37599631","title":"Electrochemical aptasensor detection of electron transfer flavoprotein subunit beta for leptospirosis diagnosis.","date":"2023","source":"The Analyst","url":"https://pubmed.ncbi.nlm.nih.gov/37599631","citation_count":5,"is_preprint":false},{"pmid":"36016453","id":"PMC_36016453","title":"Transcriptomic Analyses of Grapevine Leafroll-Associated Virus 3 Infection in Leaves and Berries of 'Cabernet Franc'.","date":"2022","source":"Viruses","url":"https://pubmed.ncbi.nlm.nih.gov/36016453","citation_count":5,"is_preprint":false},{"pmid":"38061393","id":"PMC_38061393","title":"Characterization of the Membrane-Associated Electron-Bifurcating Flavoenzyme EtfABCX from the Hyperthermophilic Bacterium Thermotoga maritima.","date":"2023","source":"Biochemistry","url":"https://pubmed.ncbi.nlm.nih.gov/38061393","citation_count":5,"is_preprint":false},{"pmid":"34030014","id":"PMC_34030014","title":"Quantitative proteomics analysis reveals unique but overlapping protein signatures in HIV infections.","date":"2021","source":"Journal of infection and public health","url":"https://pubmed.ncbi.nlm.nih.gov/34030014","citation_count":5,"is_preprint":false},{"pmid":"39684297","id":"PMC_39684297","title":"Exploring Aerobic Energy Metabolism in Breast Cancer: A Mutational Profile of Glycolysis and Oxidative Phosphorylation.","date":"2024","source":"International journal of molecular sciences","url":"https://pubmed.ncbi.nlm.nih.gov/39684297","citation_count":5,"is_preprint":false},{"pmid":"26253539","id":"PMC_26253539","title":"An electron transfer flavoprotein is essential for viability and its depletion causes a rod-to-sphere change in Burkholderia cenocepacia.","date":"2015","source":"Microbiology (Reading, England)","url":"https://pubmed.ncbi.nlm.nih.gov/26253539","citation_count":5,"is_preprint":false},{"pmid":"27840937","id":"PMC_27840937","title":"ATP5B and ETFB metabolic markers in children with congenital hydronephrosis.","date":"2016","source":"Molecular medicine reports","url":"https://pubmed.ncbi.nlm.nih.gov/27840937","citation_count":4,"is_preprint":false},{"pmid":"36654993","id":"PMC_36654993","title":"Multiple Acyl-Coenzyme A Dehydrogenase Deficiency Leading to Severe Metabolic Acidosis in a Young Adult.","date":"2022","source":"AACE clinical case reports","url":"https://pubmed.ncbi.nlm.nih.gov/36654993","citation_count":4,"is_preprint":false},{"pmid":"38171403","id":"PMC_38171403","title":"Mechanism of Cr(VI) bioreduction by Clostridium sp. LQ25 under Fe(III) reducing conditions.","date":"2024","source":"Chemosphere","url":"https://pubmed.ncbi.nlm.nih.gov/38171403","citation_count":4,"is_preprint":false},{"pmid":"39273584","id":"PMC_39273584","title":"Deep Intronic ETFDH Variants Represent a Recurrent Pathogenic Event in Multiple Acyl-CoA Dehydrogenase Deficiency.","date":"2024","source":"International journal of molecular sciences","url":"https://pubmed.ncbi.nlm.nih.gov/39273584","citation_count":3,"is_preprint":false},{"pmid":"28817787","id":"PMC_28817787","title":"Evaluation of the electron transfer flavoprotein as an antibacterial target in Burkholderia cenocepacia.","date":"2017","source":"Canadian journal of microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/28817787","citation_count":3,"is_preprint":false},{"pmid":"27081516","id":"PMC_27081516","title":"A novel ETFB mutation in a patient with glutaric aciduria type II.","date":"2015","source":"Human genome variation","url":"https://pubmed.ncbi.nlm.nih.gov/27081516","citation_count":2,"is_preprint":false},{"pmid":"40033384","id":"PMC_40033384","title":"Lysine 2-hydroxyisobutyrylation of HXK1 alters energy metabolism and KATP channel function in the atrium from patients with atrial fibrillation.","date":"2025","source":"Cell communication and signaling : CCS","url":"https://pubmed.ncbi.nlm.nih.gov/40033384","citation_count":2,"is_preprint":false},{"pmid":"23212402","id":"PMC_23212402","title":"Homology cloning, sequence characterization, and expression analysis of cDNA encoding electron transfer flavoprotein beta polypeptide in mud crab (Scylla paramamosain).","date":"2012","source":"Genetics and molecular research : GMR","url":"https://pubmed.ncbi.nlm.nih.gov/23212402","citation_count":2,"is_preprint":false},{"pmid":"39345897","id":"PMC_39345897","title":"Transcriptomic Analysis of Cardiac Tissues in a Rodent Model of Coronary Microembolization.","date":"2024","source":"Journal of inflammation research","url":"https://pubmed.ncbi.nlm.nih.gov/39345897","citation_count":2,"is_preprint":false},{"pmid":"39754769","id":"PMC_39754769","title":"Predicting microRNAs and their Target Genes Involved in Sepsis Pathogenesis by using Bioinformatics Methods.","date":"2025","source":"Current pharmaceutical design","url":"https://pubmed.ncbi.nlm.nih.gov/39754769","citation_count":2,"is_preprint":false},{"pmid":"36579410","id":"PMC_36579410","title":"A novel deleterious ETFA promoter variant causative of multiple acyl-CoA dehydrogenase deficiency.","date":"2022","source":"American journal of medical genetics. Part A","url":"https://pubmed.ncbi.nlm.nih.gov/36579410","citation_count":2,"is_preprint":false},{"pmid":"36064718","id":"PMC_36064718","title":"A fatal case of neonatal onset multiple acyl-CoA dehydrogenase deficiency caused by novel mutation of ETFDH gene: case report.","date":"2022","source":"Italian journal of pediatrics","url":"https://pubmed.ncbi.nlm.nih.gov/36064718","citation_count":2,"is_preprint":false},{"pmid":"41120854","id":"PMC_41120854","title":"Integrative transcriptomic and proteomic analyses of different muscles reveal the molecular mechanism of pig psoas major muscle as a high eating and nutritional quality meat.","date":"2025","source":"BMC genomics","url":"https://pubmed.ncbi.nlm.nih.gov/41120854","citation_count":2,"is_preprint":false},{"pmid":"39901703","id":"PMC_39901703","title":"Literature-Guided 6-Gene Signature for the Stratification of High-Risk Acute Myeloid Leukemia.","date":"2025","source":"Cancer research and treatment","url":"https://pubmed.ncbi.nlm.nih.gov/39901703","citation_count":1,"is_preprint":false},{"pmid":"41465067","id":"PMC_41465067","title":"Transcriptome Analysis Suggests Dietary Tributyrin Enhances Feeding Intensity via Modulating Steroid Biosynthesis in Mandarin Fish (Siniperca chuatsi).","date":"2025","source":"Genes","url":"https://pubmed.ncbi.nlm.nih.gov/41465067","citation_count":1,"is_preprint":false},{"pmid":"41687621","id":"PMC_41687621","title":"STARD10 regulates human pancreatic β cell differentiation and triglyceride metabolism.","date":"2026","source":"Stem cell reports","url":"https://pubmed.ncbi.nlm.nih.gov/41687621","citation_count":0,"is_preprint":false},{"pmid":"41320776","id":"PMC_41320776","title":"UQCR10 and TNNT1: novel biomarkers for sarcopenia identified through integrated transcriptomic analysis and machine learning.","date":"2025","source":"European journal of medical research","url":"https://pubmed.ncbi.nlm.nih.gov/41320776","citation_count":0,"is_preprint":false},{"pmid":"41059408","id":"PMC_41059408","title":"Proteomic landscape of porcine induced neural stem cell reprogramming and differentiation.","date":"2025","source":"PeerJ","url":"https://pubmed.ncbi.nlm.nih.gov/41059408","citation_count":0,"is_preprint":false},{"pmid":"42037170","id":"PMC_42037170","title":"Response of an Infant With Presumed Multiple Acyl-CoA Dehydrogenase Deficiency (MADD) to Ketone Supplementation.","date":"2026","source":"American journal of medical genetics. Part A","url":"https://pubmed.ncbi.nlm.nih.gov/42037170","citation_count":0,"is_preprint":false},{"pmid":"38967380","id":"PMC_38967380","title":"A compound heterozygote case of glutaric aciduria type II in a patient carrying a novel candidate variant in ETFDH gene: A case report and literature review on compound heterozygote cases.","date":"2024","source":"Molecular genetics & genomic medicine","url":"https://pubmed.ncbi.nlm.nih.gov/38967380","citation_count":0,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":52909,"output_tokens":3723,"usd":0.107286,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":11497,"output_tokens":3504,"usd":0.072542,"stage2_stop_reason":"end_turn"},"total_usd":0.179828,"stage1_batch_id":"msgbatch_01AsR7g8dGTEiEw9U83bJeWn","stage2_batch_id":"msgbatch_01YV5ZyxtFNUZEjxRcpd9jzb","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 1992,\n      \"finding\": \"Mammalian ETF from pig kidney exists in two forms (ETFR and ETFB) distinguishable by their flavin semiquinone upon reduction: the normal form (ETFR) generates a red anionic semiquinone, while ETFB generates a blue neutral semiquinone. ETFB contains a substoichiometric unusual FAD analogue. Both forms have comparable catalytic activity mediating electron transfer between medium-chain acyl-CoA dehydrogenase and 2,6-dichlorophenolindophenol. ETFB can be converted to ETFR by full reduction at pH 6.5 or apoprotein reconstitution with FAD, but not the reverse.\",\n      \"method\": \"Biochemical purification, spectrophotometric reduction assays (photochemical, dithionite, enzymatic), apoprotein reconstitution\",\n      \"journal\": \"Archives of biochemistry and biophysics\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1 / Weak — in vitro enzymatic assay and reconstitution, but single lab, single study; describes a pig kidney form\",\n      \"pmids\": [\"1731621\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2003,\n      \"finding\": \"ETFB missense mutation D128N (identified in a type III MADD patient) results in reduced enzyme activity that can be rescued up to 59% of wild-type when expressed in E. coli at low temperature, demonstrating that environmental temperature can modulate the ETF enzymatic phenotype caused by this missense mutation.\",\n      \"method\": \"Overexpression of mutant ETFB-D128N in E. coli at low temperature followed by activity measurement; genomic structure determination and mutation characterization\",\n      \"journal\": \"Human mutation\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — functional overexpression with activity rescue, multiple mutations characterized across patients, single lab\",\n      \"pmids\": [\"12815589\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2003,\n      \"finding\": \"ETFB missense mutations C42R and K202del (deletion of lysine-202) cause a late-onset mild form of MADD/GAII, establishing that beta-ETF deficiency specifically due to ETFB mutations leads to impaired palmitate/myristate oxidation in fibroblasts and abnormal acylcarnitine profiles.\",\n      \"method\": \"Mutational analysis of ETFB gene; fibroblast fatty acid oxidation assays ([3H]-palmitate and [3H]-myristate oxidation)\",\n      \"journal\": \"Molecular genetics and metabolism\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — functional cellular assay with patient-derived cells, single lab, single case\",\n      \"pmids\": [\"12706375\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2006,\n      \"finding\": \"Human ETF is a heterodimer of alpha (ETFA, 30 kDa) and beta (ETFB, 28 kDa) subunits encoded by separate nuclear genes; ETF activity in patient tissue samples ranges from <1 to 16% of controls and directly correlates with disease severity in MADD patients with confirmed ETF deficiency; most mutations causing ETF deficiency are in ETFA, with only two patients harboring ETFB mutations.\",\n      \"method\": \"ETF activity assay in patient tissue samples, Western blot analysis, mutation analysis\",\n      \"journal\": \"Molecular genetics and metabolism\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct enzymatic activity assay in patient samples combined with molecular analysis, multi-patient study, single lab\",\n      \"pmids\": [\"16510302\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2011,\n      \"finding\": \"ETFB siRNA knockdown in human fibroblasts reduces cell number specifically in mechanically stressed (attached) collagen gel culture without affecting cell number in detached (stress-free) culture, identifying ETFB as a participant in mechanoregulation of fibroblast cell number.\",\n      \"method\": \"2D gel electrophoresis differential display, MALDI-TOF-MS protein identification, siRNA knockdown, collagen gel culture assay with cell counting\",\n      \"journal\": \"Journal of dermatological science\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — siRNA KD with specific phenotypic readout in mechanically stressed culture, single lab, single study\",\n      \"pmids\": [\"21903359\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2012,\n      \"finding\": \"ETFB knockdown in fibroblasts attenuates TGF-β-induced alpha-SMA mRNA expression under mechanical stress conditions (attached collagen gel culture) to levels comparable to those without TGF-β, and weakens stress fiber organization induced by TGF-β, but does not affect COL1A1 mRNA levels or cell proliferation on plastic.\",\n      \"method\": \"siRNA knockdown, qRT-PCR, AlamarBlue proliferation assay, phalloidin staining of stress fibers, collagen gel contraction assay\",\n      \"journal\": \"Journal of dermatological science\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — siRNA KD with multiple molecular readouts, single lab, follows up on prior study\",\n      \"pmids\": [\"23068445\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"ETFB (beta-subunit of electron transfer flavoprotein) physically interacts with glutaryl-CoA dehydrogenase (GCDH) in mitochondria, identified by affinity chromatography and visualized by YFP-based fragment complementation in living cells; ETFB serves as an electron acceptor for GCDH.\",\n      \"method\": \"Affinity chromatography pulldown of GCDH-interacting proteins, mass spectrometry identification, YFP bimolecular fluorescence complementation in living cells\",\n      \"journal\": \"PloS one\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reciprocal affinity pulldown plus live-cell complementation assay, single lab, two orthogonal methods\",\n      \"pmids\": [\"24498361\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2016,\n      \"finding\": \"Connexin 43 (Cx43) interacts with ETFB in the subsarcolemmal mitochondrial fraction of mouse heart, as demonstrated by direct and reverse co-immunoprecipitation; additionally, a novel interaction between AIF and ETFB was identified, with AIF and ETFB protein content and subcellular localization being independent of Cx43 presence.\",\n      \"method\": \"Native immunoprecipitation from mitochondrial extracts, mass spectrometry identification, direct and reverse co-immunoprecipitation, subcellular fractionation\",\n      \"journal\": \"Journal of cellular and molecular medicine\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reciprocal Co-IP with mass spectrometry identification, two binding partners established, single lab\",\n      \"pmids\": [\"26915330\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"Neddylation (NEDD8 conjugation) directly targets ETFB (and ETFA) as substrates in hepatic mitochondria, stabilizing ETF proteins by inhibiting their ubiquitination and degradation. Liver-specific UBA3 (NEDD8-activating enzyme catalytic subunit) deficiency leads to decreased ETFB and ETFA protein levels, spontaneous fatty liver, and a glutaric aciduria type II-like phenotype. Certain GA-II patient mutations in ETFB hinder its neddylation.\",\n      \"method\": \"Liver-specific UBA3 and NEDD8 knockout mouse models, neddylation assays with ETF substrates, ubiquitination assays, Western blot analysis in neonatal livers and embryonic hepatocytes, pharmacological neddylation inhibition\",\n      \"journal\": \"Proceedings of the National Academy of Sciences of the United States of America\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — in vivo knockout models + direct substrate neddylation assay + ubiquitination/degradation assay + disease mutation validation, multiple orthogonal approaches in one study\",\n      \"pmids\": [\"31941714\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"Human ETF heterodimer (ETFA+ETFB) functions as an electron transfer hub accepting electrons from at least 14 flavoenzymes (including acyl-CoA dehydrogenases) in the mitochondrial matrix and relaying them to ETF:QO (ETFDH) via iron-sulfur cluster, then to ubiquinone entering the respiratory chain at complex III level. Electron transfer from donor enzymes to ETF occurs by direct flavin-to-flavin transfer regulated by a recognition loop and dynamic movement of the ETF flavin domain.\",\n      \"method\": \"Review synthesizing structural, biochemical, and mutational studies; cofactor analysis (FAD and AMP in heterodimer)\",\n      \"journal\": \"Gene\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Strong — mechanistic review consolidating established structural and biochemical findings from multiple independent studies; not primary experimental data\",\n      \"pmids\": [\"33450351\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"S1P (site-1 protease/MBTPS1) is a novel mitochondrial protein that forms a trimeric complex with ETFA/ETFB. S1P enhances ETFA/ETFB flavination and maintains their stability. Patient S1P variants destabilize ETFA/ETFB, impair mitochondrial respiration and fatty acid β-oxidation, and shift OXPHOS to glycolysis. Riboflavin supplementation restored ETFA/ETFB stability and ameliorated mitochondrial dysfunction in the patient.\",\n      \"method\": \"Co-immunoprecipitation to identify S1P-ETFA/ETFB trimeric complex; functional assays for flavination, mitochondrial respiration, β-oxidation activity; patient cell studies; riboflavin rescue experiment\",\n      \"journal\": \"EMBO molecular medicine\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Moderate — co-IP identifying trimeric complex, direct flavination assay, functional respiration and β-oxidation assays, disease mutation validation, multiple orthogonal methods\",\n      \"pmids\": [\"35362222\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"Silencing of ETFB (and ETFA) in AML cells leads to increased mitochondrial activity, mitochondrial stress, and apoptosis, but has little to no effect on normal human CD34+ cells, indicating ETFB is required for AML cell survival and mitochondrial function.\",\n      \"method\": \"siRNA/shRNA silencing, mitochondrial activity assays, apoptosis assays in AML cell lines vs. normal CD34+ cells; quantitative mass spectrometry and RNAseq showing ETFB upregulated at protein but not transcript level in AML\",\n      \"journal\": \"Leukemia\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — loss-of-function with specific cellular phenotype readout, single lab, AML model\",\n      \"pmids\": [\"35177813\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2015,\n      \"finding\": \"Electron transfer flavoprotein subunit beta (ETFB) was identified as a candidate endothelial cell autoantigen in Behçet's disease: ETFB was detected by Western blotting and mass spectrometry from endothelial cell extracts probed with BD patient sera, recombinant ETFB was cloned and expressed, and ELISA showed positive reactivity in 41% of BD patients versus 1% of healthy controls.\",\n      \"method\": \"Western blotting with patient sera, LC-MALDI-TOF/TOF mass spectrometry identification, recombinant protein expression/purification, ELISA with patient cohort\",\n      \"journal\": \"PloS one\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — antigen identification by MS plus ELISA validation in large patient cohort, single lab, multiple orthogonal methods\",\n      \"pmids\": [\"25915519\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 1994,\n      \"finding\": \"The human ETFB gene maps to chromosome 19q13.4, within approximately 40 kb of the LIM2 gene, as demonstrated by identifying a cosmid containing sequences from both genes.\",\n      \"method\": \"Cosmid cloning, chromosomal mapping by somatic cell genetics and FISH\",\n      \"journal\": \"Somatic cell and molecular genetics\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — chromosomal localization by cosmid mapping, single study, no functional information\",\n      \"pmids\": [\"8197479\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"Human ETFB encodes the beta subunit of the mitochondrial electron transfer flavoprotein (ETF) heterodimer (with ETFA), which accepts electrons from at least 14 flavoenzyme dehydrogenases (including acyl-CoA dehydrogenases) via direct flavin-to-flavin transfer and relays them to ETF:QO (ETFDH) and thence to ubiquinone; the ETF heterodimer is stabilized by neddylation (NEDD8 conjugation) that suppresses its ubiquitination/degradation, and is further chaperoned by a trimeric interaction with S1P/MBTPS1 that promotes FAD loading; ETFB physically interacts with GCDH (as electron acceptor), with mitochondrial Cx43 and AIF, and acts as an autoantigen in Behçet's disease; loss of ETFB causes fatty acid oxidation failure (MADD/glutaric aciduria type II), and ETFB knockdown in fibroblasts attenuates TGF-β-induced alpha-SMA expression and mechanoregulated cell number under mechanical stress.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"ETFB encodes the beta subunit of the mitochondrial electron transfer flavoprotein (ETF), which together with ETFA forms a heterodimeric electron-transfer hub that accepts electrons from at least 14 matrix flavoenzymes, including acyl-CoA dehydrogenases, by direct flavin-to-flavin transfer and relays them to ETF:QO (ETFDH) and onward to ubiquinone at the respiratory chain [#9]. ETFB physically interacts with glutaryl-CoA dehydrogenase (GCDH), for which it serves as electron acceptor [#6], and is found in complex with mitochondrial connexin 43 and AIF in cardiac subsarcolemmal mitochondria [#7]. The ETF heterodimer is post-translationally stabilized: neddylation (NEDD8 conjugation) of ETFB and ETFA suppresses their ubiquitination and degradation, with loss of this modification producing a glutaric aciduria type II–like phenotype [#8], and a trimeric interaction with S1P/MBTPS1 promotes ETF flavination and stability [#10]. Loss-of-function ETFB mutations cause multiple acyl-CoA dehydrogenation deficiency (MADD/glutaric aciduria type II), impairing fibroblast fatty acid oxidation and yielding abnormal acylcarnitine profiles, with residual ETF activity correlating with disease severity [#2, #3]. ETFB is required for the survival of AML cells but not normal CD34+ cells [#11], and is detected as an endothelial autoantigen in Behçet's disease [#12]; beyond its canonical bioenergetic role, ETFB also participates in mechanoregulation of fibroblast cell number and TGF-β-induced alpha-SMA expression under mechanical stress [#4, #5].\",\n  \"teleology\": [\n    {\n      \"year\": 1992,\n      \"claim\": \"Established that mammalian ETF exists in interconvertible redox/cofactor forms while retaining catalytic competence as an electron shuttle between acyl-CoA dehydrogenase and an artificial acceptor, defining its core biochemical activity.\",\n      \"evidence\": \"Biochemical purification and spectrophotometric reduction/reconstitution assays of pig kidney ETF\",\n      \"pmids\": [\"1731621\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Does not resolve which subunit carries the FAD analogue\", \"Performed on a non-human ortholog\", \"Physiological relevance of the ETFB-vs-ETFR distinction unclear\"]\n    },\n    {\n      \"year\": 1994,\n      \"claim\": \"Localized the human ETFB gene to chromosome 19q13.4, providing the genomic anchor for subsequent mutation analysis.\",\n      \"evidence\": \"Cosmid cloning and chromosomal mapping by somatic cell genetics and FISH\",\n      \"pmids\": [\"8197479\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"Mapping only, no functional data\", \"No gene structure or regulatory information\"]\n    },\n    {\n      \"year\": 2003,\n      \"claim\": \"Demonstrated that specific ETFB missense and deletion mutations cause MADD/glutaric aciduria type II by impairing fatty acid oxidation, directly linking the beta subunit to disease.\",\n      \"evidence\": \"Mutational analysis plus fibroblast [3H]-palmitate/myristate oxidation assays and bacterial expression with activity rescue\",\n      \"pmids\": [\"12706375\", \"12815589\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Limited number of patients/mutations\", \"Mechanism by which mutations destabilize the heterodimer not resolved\", \"Temperature-sensitive rescue shown only in E. coli\"]\n    },\n    {\n      \"year\": 2006,\n      \"claim\": \"Confirmed the alpha/beta heterodimeric architecture of human ETF and quantified that residual ETF activity correlates with MADD severity, establishing genotype-to-phenotype gradation.\",\n      \"evidence\": \"ETF activity assays, Western blot, and mutation analysis in patient tissues\",\n      \"pmids\": [\"16510302\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"ETFB mutations rare relative to ETFA in this cohort\", \"Does not address structural basis of activity loss\"]\n    },\n    {\n      \"year\": 2012,\n      \"claim\": \"Revealed a non-canonical role for ETFB in fibroblast mechanobiology, showing it is required for stress-dependent cell number control and TGF-β-induced myofibroblast marker expression.\",\n      \"evidence\": \"siRNA knockdown with collagen gel culture, qRT-PCR, proliferation and stress-fiber assays in human fibroblasts\",\n      \"pmids\": [\"21903359\", \"23068445\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Molecular link between mitochondrial ETF function and mechanosignaling unknown\", \"Single lab, no in vivo confirmation\", \"Whether effect is metabolic or moonlighting unresolved\"]\n    },\n    {\n      \"year\": 2014,\n      \"claim\": \"Identified a direct physical interaction with GCDH, establishing ETFB as the electron-accepting partner for a specific matrix dehydrogenase.\",\n      \"evidence\": \"Affinity chromatography pulldown, mass spectrometry, and YFP bimolecular fluorescence complementation in living cells\",\n      \"pmids\": [\"24498361\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Stoichiometry and structural interface not defined\", \"Generalizability to other dehydrogenase partners not tested\"]\n    },\n    {\n      \"year\": 2015,\n      \"claim\": \"Identified ETFB as an endothelial autoantigen recognized by Behçet's disease patient sera, implicating it in autoimmune reactivity.\",\n      \"evidence\": \"Western blotting and mass spectrometry from endothelial extracts probed with patient sera, plus ELISA in a patient cohort\",\n      \"pmids\": [\"25915519\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Pathogenic role of anti-ETFB antibodies unknown\", \"Mechanism of surface/extracellular exposure of a mitochondrial protein unexplained\"]\n    },\n    {\n      \"year\": 2016,\n      \"claim\": \"Placed ETFB in a cardiac mitochondrial protein complex with connexin 43 and AIF, expanding its interactome beyond electron-transfer substrates.\",\n      \"evidence\": \"Native and reciprocal co-immunoprecipitation with mass spectrometry from mouse heart subsarcolemmal mitochondria\",\n      \"pmids\": [\"26915330\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Functional consequence of Cx43/AIF association undefined\", \"Direct vs indirect binding not distinguished\"]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"Defined neddylation as a post-translational mechanism that stabilizes ETFB/ETFA by blocking their ubiquitin-mediated degradation, with loss causing a GA-II-like phenotype in vivo.\",\n      \"evidence\": \"Liver-specific UBA3/NEDD8 knockout mice, direct neddylation and ubiquitination assays, and disease-mutation validation\",\n      \"pmids\": [\"31941714\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Site(s) of NEDD8 conjugation on ETFB not mapped\", \"Upstream signals controlling ETF neddylation unknown\"]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"Showed that S1P/MBTPS1 forms a trimeric complex with ETFA/ETFB to promote flavination and stability, and that ETFB is selectively required for AML cell mitochondrial function and survival.\",\n      \"evidence\": \"Co-IP, flavination and respiration/β-oxidation assays with riboflavin rescue in patient cells; siRNA/shRNA silencing with mitochondrial and apoptosis assays in AML vs CD34+ cells\",\n      \"pmids\": [\"35362222\", \"35177813\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Mechanism by which S1P facilitates FAD loading not structurally resolved\", \"Basis of AML-selective dependence on ETFB unclear\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How ETFB's canonical electron-transfer role mechanistically connects to its reported moonlighting functions in mechanotransduction, autoimmunity, and AML dependence remains unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No structural model of the S1P-ETF trimeric complex\", \"Neddylation site on ETFB unmapped\", \"Link between mitochondrial ETF activity and TGF-β/mechanosignaling unknown\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0016491\", \"supporting_discovery_ids\": [0, 6, 9]},\n      {\"term_id\": \"GO:0140104\", \"supporting_discovery_ids\": [9]},\n      {\"term_id\": \"GO:0008289\", \"supporting_discovery_ids\": [10]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005739\", \"supporting_discovery_ids\": [6, 7, 8, 9, 10]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-1430728\", \"supporting_discovery_ids\": [2, 9]},\n      {\"term_id\": \"R-HSA-1643685\", \"supporting_discovery_ids\": [2, 3, 8, 10]}\n    ],\n    \"complexes\": [\n      \"electron transfer flavoprotein (ETFA/ETFB) heterodimer\",\n      \"S1P-ETFA-ETFB trimeric complex\"\n    ],\n    \"partners\": [\n      \"ETFA\",\n      \"ETFDH\",\n      \"GCDH\",\n      \"MBTPS1\",\n      \"GJA1\",\n      \"AIFM1\",\n      \"NEDD8\",\n      \"UBA3\"\n    ],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":5,"faith_total":5,"faith_pct":100.0}}