Gene Symbol: HADHB
Description: hydroxyacyl-CoA dehydrogenase trifunctional multienzyme complex subunit beta
Alias: ECHB, MSTP029, MTPB, TP-BETA, trifunctional enzyme subunit beta, mitochondrial, 2-enoyl-Coenzyme A (CoA) hydratase, beta subunit, 3-ketoacyl-Coenzyme A (CoA) thiolase of mitochondrial trifunctional protein, beta subunit, acetyl-CoA acyltransferase, beta-ketothiolase, hydroxyacyl-CoA dehydrogenase/3-ketoacyl-CoA thiolase/enoyl-CoA hydratase (trifunctional protein), beta subunit, hydroxyacyl-Coenzyme A dehydrogenase/3-ketoacyl-Coenzyme A thiolase/enoyl-Coenzyme A hydratase (trifunctional protein), beta subunit
Species: human
Products:     HADHB

Top Publications

  1. Boutron A, Acquaviva C, Vianey Saban C, de Lonlay P, de Baulny H, Guffon N, et al. Comprehensive cDNA study and quantitative analysis of mutant HADHA and HADHB transcripts in a French cohort of 52 patients with mitochondrial trifunctional protein deficiency. Mol Genet Metab. 2011;103:341-8 pubmed publisher
    Deficiency of mitochondrial trifunctional protein (MTP) is caused by mutations in the HADHA and HADHB genes, which have been mostly delineated at the genomic DNA level and have not been always elucidated...
  2. Kamijo T, Aoyama T, Komiyama A, Hashimoto T. Structural analysis of cDNAs for subunits of human mitochondrial fatty acid beta-oxidation trifunctional protein. Biochem Biophys Res Commun. 1994;199:818-25 pubmed
    ..Expression of this cDNA in mammalian cells yielded a polypeptide with the long-chain 3-ketoacyl-CoA thiolase activity. ..
  3. Purevsuren J, Fukao T, Hasegawa Y, Kobayashi H, Li H, Mushimoto Y, et al. Clinical and molecular aspects of Japanese patients with mitochondrial trifunctional protein deficiency. Mol Genet Metab. 2009;98:372-7 pubmed publisher
    ..Herein, we describe the characterization of four missense mutations, R214C, H346R, R411K, and V422G, in the HADHB gene, which have been identified in Japanese patients, employing a newly developed, sensitive transient expression ..
  4. Spiekerkoetter U, Sun B, Khuchua Z, Bennett M, Strauss A. Molecular and phenotypic heterogeneity in mitochondrial trifunctional protein deficiency due to beta-subunit mutations. Hum Mutat. 2003;21:598-607 pubmed
    ..long-chain enoyl-CoA hydratase and long-chain L-3-hydroxyacyl-CoA dehydrogenase (LCHAD) and four beta-subunits (HADHB) harboring long-chain 3-ketoacyl-CoA thiolase (LKAT)...
  5. Xu F, Han L, Qiu W, Zhang H, Ji W, Chen T, et al. [Retrospective analysis on clinical data and genetic variations of patients with beta-ketothiolase deficiency]. Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2019;36:199-202 pubmed publisher
    ..Clinicians should consider MS/MS and GC/MS testing for those with unexplained neurological symptoms and metabolic acidosis in order to attain early diagnosis of BKD. Genetic testing should be used to confirm the diagnosis. ..
  6. Hu X, Chandler J, Orr M, Hao L, Liu K, Uppal K, et al. Selenium Supplementation Alters Hepatic Energy and Fatty Acid Metabolism in Mice. J Nutr. 2018;148:675-684 pubmed publisher
    ..Supplemental selenium in mice alters hepatic fatty acid and energy metabolism and causes increases in body mass. A lack of effect on hepatic selenium content suggests that signaling involves an extrahepatic mechanism. ..
  7. Fukao T, Mitchell G, Sass J, Hori T, Orii K, Aoyama Y. Ketone body metabolism and its defects. J Inherit Metab Dis. 2014;37:541-51 pubmed publisher
    ..We review recent data on clinical presentation, metabolite profiles and the course of these diseases in adults, including in pregnancy. ..
  8. Diebold I, Schön U, Horvath R, Schwartz O, Holinski Feder E, Kölbel H, et al. HADHA and HADHB gene associated phenotypes - Identification of rare variants in a patient cohort by Next Generation Sequencing. Mol Cell Probes. 2019;: pubmed publisher
    ..Pathogenic variants in the MTP genes (HADHA and HADHB) cause MTP deficiency, a rare autosomal recessive metabolic disorder characterized by phenotypic heterogeneity ..
  9. Fukao T, Maruyama S, Ohura T, Hasegawa Y, Toyoshima M, Haapalainen A, et al. Three Japanese Patients with Beta-Ketothiolase Deficiency Who Share a Mutation, c.431A>C (H144P) in ACAT1 : Subtle Abnormality in Urinary Organic Acid Analysis and Blood Acylcarnitine Analysis Using Tandem Mass Spectrometry. JIMD Rep. 2012;3:107-15 pubmed publisher
    ..T2-deficient patients with "mild" mutations have severe ketoacidotic crises but their chemical phenotypes may be subtle even during acute crises. ..

More Information


  1. Downie Ruiz Velasco A, Welten S, Goossens E, Quax P, Rappsilber J, Michlewski G, et al. Posttranscriptional Regulation of 14q32 MicroRNAs by the CIRBP and HADHB during Vascular Regeneration after Ischemia. Mol Ther Nucleic Acids. 2018;14:329-338 pubmed publisher
    ..of cold-inducible RBP (CIRBP) and hydroxyacyl-CoA dehydrogenase trifunctional multienzyme complex subunit beta (HADHB) to the precursors of late-upregulated miR-329-3p and unaffected miR-495-3p...
  2. Fukao T, Sasai H, Aoyama Y, Otsuka H, Ago Y, Matsumoto H, et al. Recent advances in understanding beta-ketothiolase (mitochondrial acetoacetyl-CoA thiolase, T2) deficiency. J Hum Genet. 2019;64:99-111 pubmed publisher
  3. Gao T, Li M, Mu G, Hou T, Zhu W, Yang Y. PKCζ Phosphorylates SIRT6 to Mediate Fatty Acid β-Oxidation in Colon Cancer Cells. Neoplasia. 2019;21:61-73 pubmed publisher
    ..In the functional study, we find that the expression of ACSL1, CPT1, CACT, and HADHB, the genes related to fatty acid β-oxidation, increases after PA stimulation...
  4. de la Rosa Rodriguez M, Sugahara G, Hooiveld G, Ishida Y, Tateno C, Kersten S. The whole transcriptome effects of the PPARα agonist fenofibrate on livers of hepatocyte humanized mice. BMC Genomics. 2018;19:443 pubmed publisher
    ..significantly higher in the fenofibrate-treated mice, including many established PPARα targets such as FABP1, HADHB, HADHA, VNN1, PLIN2, ACADVL and HMGCS2...
  5. Vasilescu C, Ojala T, Brilhante V, Ojanen S, Hinterding H, Palin E, et al. Genetic Basis of Severe Childhood-Onset Cardiomyopathies. J Am Coll Cardiol. 2018;72:2324-2338 pubmed publisher
    ..The disease genes converge on metabolic causes (PRKAG2, MRPL44, AARS2, HADHB, DNAJC19, PPA2, TAZ, BAG3), MAPK pathways (HRAS, PTPN11, RAF1, TAB2), development (NEK8 and TBX20), calcium ..
  6. Lu Y, Wu R, Meng L, Lv H, Liu J, Zuo Y, et al. HADHB mutations cause infantile-onset axonal Charcot-Marie-Tooth disease: A report of two cases. Clin Neuropathol. 2018;37:232-238 pubmed publisher
    Mitochondrial trifunctional protein deficiency (MTPD) is a rare disorder caused by mutations in the HADHA and HADHB genes...
  7. Law C, Lam C, Ching C, Yau K, Ho T, Lai C, et al. NMR-based urinalysis for beta-ketothiolase deficiency. Clin Chim Acta. 2015;438:222-5 pubmed publisher
    ..We envisage that NMR analysis will become more available in clinical laboratories and will play an important role in acute pediatric care. ..
  8. Sodhi S, Ghosh M, Song K, Sharma N, Kim J, Kim N, et al. An approach to identify SNPs in the gene encoding acetyl-CoA acetyltransferase-2 (ACAT-2) and their proposed role in metabolic processes in pig. PLoS ONE. 2014;9:e102432 pubmed publisher
    ..Further associations of SNPs in ACAT2 with production traits might guide efforts to improve growth performance in Jeju native pigs. ..
  9. Kobayashi T, Minami S, Mitani A, Tanizaki Y, Booka M, Okutani T, et al. Acute fatty liver of pregnancy associated with fetal mitochondrial trifunctional protein deficiency. J Obstet Gynaecol Res. 2015;41:799-802 pubmed publisher
    ..Gene analysis demonstrated homozygous mutation in exon 13 of HADHB, the gene responsible for mitochondrial TFP deficiency...
  10. Magdeldin S, Blaser R, Yamamoto T, Yates J. Behavioral and proteomic analysis of stress response in zebrafish (Danio rerio). J Proteome Res. 2015;14:943-52 pubmed publisher
    ..changes in protein abundance following shock exposure, eight proteins were significantly up-regulated (HADHB, hspa8, hspa5, actb1, mych4, atp2a1, zgc:86709, and zgc:86725)...
  11. Wang Q, Liu M, Xu L, Wu Y, Huang Y. Transcriptome analysis reveals the molecular mechanism of hepatic fat metabolism disorder caused by Muscovy duck reovirus infection. Avian Pathol. 2018;47:127-139 pubmed publisher
  12. Song Y, Tan X, Pan Y, Zhang L, Chen Q. Fatty Acid ?-Oxidation Is Essential in Leptin-Mediated Oocytes Maturation of Yellow Catfish Pelteobagrus fulvidraco. Int J Mol Sci. 2018;19: pubmed publisher
    ..of genes, including twenty-five up-regulated genes (CPT1, Acsl, Acadl, Acadm, Hadhb, Echsl, Hsd17b4, Acca, PPAR?, CYP8B1, ACOX1, ACBP, MAPK..
  13. Weichler M, Kurteva Yaneva N, Przybylski D, Schuster J, Müller R, Harms H, et al. Thermophilic Coenzyme B12-Dependent Acyl Coenzyme A (CoA) Mutase from Kyrpidia tusciae DSM 2912 Preferentially Catalyzes Isomerization of (R)-3-Hydroxybutyryl-CoA and 2-Hydroxyisobutyryl-CoA. Appl Environ Microbiol. 2015;81:4564-72 pubmed publisher
    ..7 mM. Measures to improve production in E. coli, such as coexpression of the chaperone MeaH and repression of thioesterase II, are discussed. ..
  14. Xu W, Yang X, Li D, Zheng K, Qiu P, Zhang W, et al. Up-regulation of fatty acid oxidation in the ligament as a contributing factor of ankylosing spondylitis: A comparative proteomic study. J Proteomics. 2015;113:57-72 pubmed publisher
    ..GO and pathway analyses showed that six fatty acid β-oxidation-related proteins (HADHB, ECHS1, ACSL4, ACADM, ACSL1 and HADH) were up-regulated in FLL cells, which was consistent with the results ..
  15. Bo R, Yamada K, Kobayashi H, Jamiyan P, Hasegawa Y, Taketani T, et al. Clinical and molecular investigation of 14 Japanese patients with complete TFP deficiency: a comparison with Caucasian cases. J Hum Genet. 2017;62:809-814 pubmed publisher
    ..361C>T, and HADHA-HADHB: g.26233880_ 26248855del), although no common mutations were found...
  16. Li Y, Liu X, Niu L, Li Q. Proteomics Analysis Reveals an Important Role for the PPAR Signaling Pathway in DBDCT-Induced Hepatotoxicity Mechanisms. Molecules. 2017;22: pubmed publisher
    ..Our studies indicated that DBDCT may serve as a modulator of PPAR-λ, further up-regulating CD36, FABP4 and EHHADH on the PPAR signal pathway. ..
  17. van Vliet P, Berden A, VAN Schie M, Bakker J, Heringhaus C, De Coo I, et al. Peripheral Neuropathy, Episodic Rhabdomyolysis, and Hypoparathyroidism in a Patient with Mitochondrial Trifunctional Protein Deficiency. JIMD Rep. 2018;38:101-105 pubmed publisher
    ..Sequence analysis of the HADHB gene showed two heterozygous variants: c.209+1G>C (splicing defect) and c.980T>C (p.Leu327Leu)...
  18. Chen Y, Su Z. Reveal genes functionally associated with ACADS by a network study. Gene. 2015;569:294-302 pubmed publisher
    ..ACADS web retrieved from both STRING and GeneMANIA, ACADS is effectively conjoined with 4 genes including HAHDA, HADHB, ECHS1 and ACAT1. The functional analysis is done via ontological briefing and candidate disease identification...
  19. Ojala T, Nupponen I, Saloranta C, Sarkola T, Sekar P, Breilin A, et al. Fetal left ventricular noncompaction cardiomyopathy and fatal outcome due to complete deficiency of mitochondrial trifunctional protein. Eur J Pediatr. 2015;174:1689-92 pubmed publisher
    We report a fetal case with fatal outcome having a novel mutation in the HADHB gene, coding the beta-subunit of the mitochondrial trifunctional protein. Parents had a previous pregnancy loss due to fetal heart failure and hydrops...
  20. Liu R, Wang H, Liu J, Wang J, Zheng M, Tan X, et al. Uncovering the embryonic development-related proteome and metabolome signatures in breast muscle and intramuscular fat of fast-and slow-growing chickens. BMC Genomics. 2017;18:816 pubmed publisher
    ..For IMF, several rate-limiting enzymes for beta-oxidation of fatty acid (ACADL, ACAD9, HADHA and HADHB) were identified as candidate biomarkers for IMF deposition in both breeds...
  21. Wen P, Chen Z, Wang G, Su Z, Zhang X, Tang G, et al. [Analysis of clinical phenotype and ACAT1 gene mutation in a family affected with beta-ketothiolase deficiency]. Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2016;33:286-91 pubmed publisher
    ..Urine organic acid and blood acylcarnitine analyses play an important role in the diagnosis of the disease. The compound heterozygous of ACAT1 gene mutations probably underlie the BKTD in our patient. ..
  22. Abdelkreem E, Akella R, Dave U, Sane S, Otsuka H, Sasai H, et al. Clinical and Mutational Characterizations of Ten Indian Patients with Beta-Ketothiolase Deficiency. JIMD Rep. 2017;35:59-65 pubmed publisher
    ..Expression analyses confirmed pathogenicity of these mutations. T2 deficiency has a likely high incidence in India and p.Met193Arg may be a common mutation in the Indian population. ..
  23. Chen J, Young M, Chatham J, Crossman D, Dell Italia L, Shalev A. TXNIP regulates myocardial fatty acid oxidation via miR-33a signaling. Am J Physiol Heart Circ Physiol. 2016;311:H64-75 pubmed publisher
    ..palmitoyl transferase 1 (CPT1), hydroxyacyl-CoA dehydrogenase/3-ketoacyl-CoA thiolase/enoyl-CoA hydratase-? (HADHB), and AMPK? and is associated with an increase in phospho-AMPK? and phosphorylation/inactivation of acetyl-CoA-..
  24. Asghari A, Marashi S, Ansari Pour N. A sperm-specific proteome-scale metabolic network model identifies non-glycolytic genes for energy deficiency in asthenozoospermia. Syst Biol Reprod Med. 2017;63:100-112 pubmed publisher
    ..dehydrogenase; HADHA: hydroxyacyl-CoA dehydrogenase/3-ketoacyl-CoA thiolase/enoyl-CoA hydratase, subunit A; HADHB: hydroxyacyl-CoA dehydrogenase/3-ketoacyl-CoA thiolase/enoyl-CoA hydratase, subunit B; PPA2: pyrophosphatase (..
  25. Zheng Y, Jiang S, Zhang Y, Zhang R, Gong D. Detection of miR-33 Expression and the Verification of Its Target Genes in the Fatty Liver of Geese. Int J Mol Sci. 2015;16:12737-52 pubmed publisher
    ..O-octanoyltransferase (CROT), cyl-CoA dehydrogenase/3-ketoacyl-CoA thiolase/enoyl-CoA hydratase, beta subunit (HADHB), AMP-activated protein kinase, alpha subunit 1 (AMPKα1), insulin receptor substrate 2, glutamic pyruvate ..
  26. Shahrokhi M, Shafiei M, Galehdari H, Shariati G. Identification of a Novel HADHB Gene Mutation in an Iranian Patient with Mitochondrial Trifunctional Protein Deficiency. Arch Iran Med. 2017;20:22-27 pubmed publisher
    ..After isolation of DNA and Amplification of all exons of the HADHA and HADHB, directly Sequence analyses of all exons and the flanking introns both of genes were performed...
  27. Choo J, Kim H. Production of (R)-Ethyl-4-Chloro-3-Hydroxybutanoate Using Saccharomyces cerevisiae YOL151W Reductase Immobilized onto Magnetic Microparticles. J Microbiol Biotechnol. 2015;25:1810-8 pubmed publisher
    ..Among them, (R)-ethyl-4-chloro-3-hydroxybutanoate ((R)-ECHB) is an important building block for the synthesis of L-carnitine...
  28. Miltiadou D, Hager Theodorides A, Symeou S, Constantinou C, Psifidi A, Banos G, et al. Variants in the 3' untranslated region of the ovine acetyl-coenzyme A acyltransferase 2 gene are associated with dairy traits and exhibit differential allelic expression. J Dairy Sci. 2017;100:6285-6297 pubmed publisher
    ..This is the first study reporting differential allelic imbalance expression of a candidate gene associated with milk production traits in dairy sheep. ..
  29. Balasubramaniam S, Lewis B, Greed L, Meili D, Flier A, Yamamoto R, et al. Heterozygous Monocarboxylate Transporter 1 (MCT1, SLC16A1) Deficiency as a Cause of Recurrent Ketoacidosis. JIMD Rep. 2016;29:33-38 pubmed
    ..Early diagnosis may enable improved disease management. Careful identification of potential triggers of metabolic decompensations in individuals even with single heterozygous mutations in the SLC16A1 gene is indicated. ..
  30. Zorc M, Kunej T. In silico screening of the chicken genome for overlaps between genomic regions: microRNA genes, coding and non-coding transcriptional units, QTL, and genetic variations. Chromosome Res. 2016;24:225-30 pubmed publisher
    ..miRNA in a chicken genome, an overlap between the miRNA gene and the exon of the protein-coding gene (gga-miR-6578/HADHB), and the first report of a missense polymorphism located within a mature miRNA seed region...
  31. Otsuka H, Sasai H, Nakama M, Aoyama Y, Abdelkreem E, Ohnishi H, et al. Exon 10 skipping in ACAT1 caused by a novel c.949G>A mutation located at an exonic splice enhancer site. Mol Med Rep. 2016;14:4906-4910 pubmed publisher
    ..The present study demonstrates that a missense mutation, or even a synonymous substitution, may disrupt enzyme function by interference with splicing. ..
  32. Nguyen K, Abdelkreem E, Colombo R, Hasegawa Y, Can N, Bui T, et al. Characterization and outcome of 41 patients with beta-ketothiolase deficiency: 10 years' experience of a medical center in northern Vietnam. J Inherit Metab Dis. 2017;40:395-401 pubmed publisher
    ..The direct management and long-term follow-up of a large number of T2-deficient patients enabled us to study the natural history of this rare disease. ..
  33. Ribeiro A, de Lacerda R, Correia D, Brunialti Godard A, de Miranda D, Campos V, et al. Possible involvement of ACSS2 gene in alcoholism. J Neural Transm (Vienna). 2017;124:1151-1158 pubmed publisher
    ..Seven genes were picked out (Acss2, Acss3, Acat1, Acsl1, Acaa2, Hadh, and Hadhb) and the mRNA level of the Acss2 gene was increased only in the "compulsive-like" group (p = 0.004)...
  34. Fan Q, Long B, Yan G, Wang Z, Shi M, Bao X, et al. Dietary leucine supplementation alters energy metabolism and induces slow-to-fast transitions in longissimus dorsi muscle of weanling piglets. Br J Nutr. 2017;117:1222-1234 pubmed publisher
    ..For further confirmation, we identified that SDHB, ATP5F1, ACADM and HADHB were significantly down-regulated (P<0·01, except ATP5F1, P<0·05), whereas the glycolytic enzyme pyruvate ..
  35. Fisher L, Davies C, Al Dirbashi O, Ten Brink H, Chakraborty P, Lepage N. A novel method for quantitation of acylglycines in human dried blood spots by UPLC-tandem mass spectrometry. Clin Biochem. 2018;54:131-138 pubmed publisher
    ..This method shows potential application as a second tier screen in order to reduce the false positive rate for a number of IEM targeted by newborn screening. ..
  36. Yamamoto Y, Matsui N, Hiramatsu Y, Miyazaki Y, Nodera H, Izumi Y, et al. Mitochondrial trifunctional protein deficiency: an adult patient with similar progress to Charcot-Marie-Tooth disease. Rinsho Shinkeigaku. 2017;57:82-87 pubmed publisher
    ..We re-examined variants obtained via exome sequencing and found a mutation in HADHB. Mitochondrial trifunctional protein (MTP) deficiency is a rare autosomal recessive disorder of mitochondrial ..
  37. Karunakaran D, Richards L, Geoffrion M, Barrette D, Gotfrit R, Harper M, et al. Therapeutic Inhibition of miR-33 Promotes Fatty Acid Oxidation but Does Not Ameliorate Metabolic Dysfunction in Diet-Induced Obesity. Arterioscler Thromb Vasc Biol. 2015;35:2536-43 pubmed publisher
    ..Hepatic expression of miR-33 targets Abca1 and Hadhb were derepressed on miR-33 inhibition...
  38. Liu F, Wang Y, Xu J, Liu F, Hu R, Deng H. Effects of Porphyromonas gingivalis lipopolysaccharide on the expression of key genes involved in cholesterol metabolism in macrophages. Arch Med Sci. 2016;12:959-967 pubmed
    ..CD36, lectin-like oxidized LDL receptor-1 (LOX-1), ATP-binding cassette G1 (ABCG1), and acetyl CoA acyltransferase 1 (ACAT1) expression levels were measured by western blot and qRT-PCR...
  39. Vega Badillo J, Gutiérrez Vidal R, Hernández Pérez H, Villamil Ramírez H, León Mimila P, Sánchez Muñoz F, et al. Hepatic miR-33a/miR-144 and their target gene ABCA1 are associated with steatohepatitis in morbidly obese subjects. Liver Int. 2016;36:1383-91 pubmed publisher
    ..genes regulated by miR-33 (carnitine O-octanoyltransferase, CROT and hydroxyacyl-CoA-dehydrogenase β-subunit, HADHB) and miR-144 (toll-like receptor-2, TLR2)...
  40. Meguro S, Hasumura T. Fish Oil Suppresses Body Fat Accumulation in Zebrafish. Zebrafish. 2018;15:27-32 pubmed publisher
    ..In the intestine, expression of genes for the alpha (hadhaa) and beta (hadhb) subunits of the beta-oxidation enzyme hydroxyacyl-Coenzyme A dehydrogenase/3-ketoacyl-Coenzyme A thiolase/enoyl-..
  41. Ibdah J, Tein I, Dionisi Vici C, Bennett M, Ijlst L, Gibson B, et al. Mild trifunctional protein deficiency is associated with progressive neuropathy and myopathy and suggests a novel genotype-phenotype correlation. J Clin Invest. 1998;102:1193-9 pubmed
  42. Djouadi F, Habarou F, Le Bachelier C, Ferdinandusse S, Schlemmer D, Benoist J, et al. Mitochondrial trifunctional protein deficiency in human cultured fibroblasts: effects of bezafibrate. J Inherit Metab Dis. 2016;39:47-58 pubmed publisher
    Mitochondrial trifunctional protein (MTP) deficiency caused by HADHA or HADHB gene mutations exhibits substantial molecular, biochemical, and clinical heterogeneity and ranks among the more severe fatty acid oxidation (FAO) disorders, ..
  43. Milan E, Perini T, Resnati M, Orfanelli U, Oliva L, Raimondi A, et al. A plastic SQSTM1/p62-dependent autophagic reserve maintains proteostasis and determines proteasome inhibitor susceptibility in multiple myeloma cells. Autophagy. 2015;11:1161-78 pubmed publisher
  44. Hong Y, Lee J, Park J, Choi Y, Hyun Y, Yoon B, et al. A compound heterozygous mutation in HADHB gene causes an axonal Charcot-Marie-tooth disease. BMC Med Genet. 2013;14:125 pubmed publisher
    ..hydroxyacyl-CoA dehydrogenase/3-ketoacyl-CoA thiolase/enoyl-CoA hydratase (trifunctional protein), beta subunit (HADHB) gene exhibit three distinctive phenotypes: severe neonatal presentation with cardiomyopathy, hepatic form with ..
  45. Zhou Z, Zhou J, Du Y. Estrogen receptor beta interacts and colocalizes with HADHB in mitochondria. Biochem Biophys Res Commun. 2012;427:305-8 pubmed publisher
    ..We previously found that ER? interacted with mitochondrial protein HADHB and affected the thiolytic cleavage activity of HADHB in ?-oxidation. It is known that ER? binds to ER?...
  46. Zhou Z, Zhou J, Du Y. Estrogen receptor alpha interacts with mitochondrial protein HADHB and affects beta-oxidation activity. Mol Cell Proteomics. 2012;11:M111.011056 pubmed publisher
    ..One of the proteins identified was trifunctional protein ?-subunit (HADHB), a mitochondrial protein that is required for ?-oxidation of fatty acids in mitochondria...
  47. Orii K, Aoyama T, Wakui K, Fukushima Y, Miyajima H, Yamaguchi S, et al. Genomic and mutational analysis of the mitochondrial trifunctional protein beta-subunit (HADHB) gene in patients with trifunctional protein deficiency. Hum Mol Genet. 1997;6:1215-24 pubmed
    ..the enoyl-CoA hydratase and 3-hydroxyacyl-CoA dehydrogenase domains and four molecules of the beta-subunit (HADHB) containing the 3-ketoacyl-CoA thiolase domain...
  48. Aoyama T, Wakui K, Orii K, Hashimoto T, Fukushima Y. Fluorescence in situ hybridization mapping of the alpha and beta subunits (HADHA and HADHB) of human mitochondrial fatty acid beta-oxidation multienzyme complex to 2p23 and their evolution. Cytogenet Cell Genet. 1997;79:221-4 pubmed
    ..The alpha and beta subunits (HADHA and HADHB) are members of the enoyl-CoA hydratase/3-hydroxyacyl-CoA dehydrogenase and 3-ketoacyl-CoA thiolase families, ..
  49. Kao Y, Chang B, Liang J, Tsai H, Lee Y, Lin R, et al. Japanese encephalitis virus nonstructural protein NS5 interacts with mitochondrial trifunctional protein and impairs fatty acid β-oxidation. PLoS Pathog. 2015;11:e1004750 pubmed publisher
    ..We identified a novel function of JEV NS5 in viral pathogenesis by impairing LCFA β-oxidation and inducing cytokine expression by association with MTP. ..
  50. Grünert S, Schmitt R, Schlatter S, Gemperle Britschgi C, Balci M, Berg V, et al. Clinical presentation and outcome in a series of 32 patients with 2-methylacetoacetyl-coenzyme A thiolase (MAT) deficiency. Mol Genet Metab. 2017;122:67-75 pubmed publisher
    ..Our study underlines that the prognosis in MAT deficiency is good and MAT deficient individuals may remain asymptomatic, if diagnosed early and preventive measures are applied. ..
  51. Ushikubo S, Aoyama T, Kamijo T, Wanders R, Rinaldo P, Vockley J, et al. Molecular characterization of mitochondrial trifunctional protein deficiency: formation of the enzyme complex is important for stabilization of both alpha- and beta-subunits. Am J Hum Genet. 1996;58:979-88 pubmed
  52. Seo J, Yaneva R, Hinson E, Cresswell P. Human cytomegalovirus directly induces the antiviral protein viperin to enhance infectivity. Science. 2011;332:1093-7 pubmed publisher
    ..This function of viperin, which was previously attributed to vMIA, suggests that HCMV has coopted viperin to facilitate the infectious process. ..
  53. Spiekerkoetter U, Khuchua Z, Yue Z, Bennett M, Strauss A. General mitochondrial trifunctional protein (TFP) deficiency as a result of either alpha- or beta-subunit mutations exhibits similar phenotypes because mutations in either subunit alter TFP complex expression and subunit turnover. Pediatr Res. 2004;55:190-6 pubmed
    ..Both alpha- and beta-subunit mutations result in TFP complex instability, demonstrating that the mechanism of disease is the same in alpha- or beta-mutation-derived disease and explaining the biochemical and clinical similarities. ..
  54. Middleton B. The mitochondrial long-chain trifunctional enzyme: 2-enoyl-CoA hydratase, 3-hydroxyacyl-CoA dehydrogenase and 3-oxoacyl-CoA thiolase. Biochem Soc Trans. 1994;22:427-31 pubmed
  55. Carpenter K, Pollitt R, Middleton B. Human liver long-chain 3-hydroxyacyl-coenzyme A dehydrogenase is a multifunctional membrane-bound beta-oxidation enzyme of mitochondria. Biochem Biophys Res Commun. 1992;183:443-8 pubmed
    ..coli, but unique in its membrane location and substrate specificity. We propose that its existence explains the repeated failure to detect any intermediates of mitochondrial beta-oxidation. ..
  56. Kamijo T, Wanders R, Saudubray J, Aoyama T, Komiyama A, Hashimoto T. Mitochondrial trifunctional protein deficiency. Catalytic heterogeneity of the mutant enzyme in two patients. J Clin Invest. 1994;93:1740-7 pubmed
    ..Taken together, the results obtained show that in both patients, long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency is caused by an abnormality in the trifunctional protein, even though there is a heterogeneity in both patients. ..
  57. Adams D, Beveridge D, van der Weyden L, Mangs H, Leedman P, Morris B. HADHB, HuR, and CP1 bind to the distal 3'-untranslated region of human renin mRNA and differentially modulate renin expression. J Biol Chem. 2003;278:44894-903 pubmed
    ..Yeast three-hybrid screening with the REN 3'-UTR as bait isolated HADHB (hydroxyacyl-CoA dehydrogenase/3-ketoacyl-CoA thiolase/enoyl-CoA hydratase (trifunctional protein) beta-subunit) ..
  58. Wang R, Yang Z, Zhu J, Wang J, Yang H, Wang Q, et al. [Screening for G1528C mutation in mitochondrial trifunctional protein gene in pregnant women with severe preeclampsia and new born infant]. Zhonghua Fu Chan Ke Za Zhi. 2006;41:672-5 pubmed
    ..Further study is needed to expand the sample size among HELLP syndrome and maternal liver diseases in Chinese population. ..
  59. Nedoszytko B, Sieminska A, Strapagiel D, Dabrowski S, Słomka M, Sobalska Kwapis M, et al. High prevalence of carriers of variant c.1528G>C of HADHA gene causing long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency (LCHADD) in the population of adult Kashubians from North Poland. PLoS ONE. 2017;12:e0187365 pubmed publisher
    ..Mutations in MTP genes (HADHA and HADHB), both located on chromosome 2p23, cause MTP deficiency, a rare autosomal recessive metabolic disorder ..
  60. Yagi M, Lee T, Awano H, Tsuji M, Tajima G, Kobayashi H, et al. A patient with mitochondrial trifunctional protein deficiency due to the mutations in the HADHB gene showed recurrent myalgia since early childhood and was diagnosed in adolescence. Mol Genet Metab. 2011;104:556-9 pubmed publisher
    ..MTP is an ?4?4 hetero-octomer encoded by two different genes: HADHA (OMIM 600890) and HADHB (OMIM 143450)...
  61. Zhao Y, Meng X, Wei Y, Zhao X, Liu D, Cao H, et al. Cloning and characterization of a novel cardiac-specific kinase that interacts specifically with cardiac troponin I. J Mol Med (Berl). 2003;81:297-304 pubmed
    ..Our data suggest that TNNI3K is a cardiac-specific kinase and play important roles in cardiac system. ..
  62. Frackowiak J, Mazur Kolecka B, Kaczmarski W, Dickson D. Deposition of Alzheimer's vascular amyloid-beta is associated with decreased expression of brain L-3-hydroxyacyl-coenzyme A dehydrogenase (ERAB). Brain Res. 2001;907:44-53 pubmed
    ..Explanation of the association between low levels of HADH and deposition of Abeta by brain smooth muscle cells requires further studies. ..
  63. Orii K, Orii K, Souri M, Orii T, Kondo N, Hashimoto T, et al. Genes for the human mitochondrial trifunctional protein alpha- and beta-subunits are divergently transcribed from a common promoter region. J Biol Chem. 1999;274:8077-84 pubmed
    Human HADHA and HADHB genes encode the subunits of an enzyme complex, the trifunctional protein, involved in mitochondrial beta-oxidation of fatty acids. Both genes are located in the same region of chromosome 2p23...
  64. Chiou F, Ong C, Phua K, Chedid F, Kader A. Conjugated hyperbilirubinemia presenting in first fourteen days in term neonates. World J Hepatol. 2017;9:1108-1114 pubmed publisher
    To describe the etiology and characteristics of early-onset conjugated hyperbilirubinemia (ECHB) presenting within 14 d of life in term neonates.
  65. Yang B, Heng H, Ding J, Roe C. The genes for the alpha and beta subunits of the mitochondrial trifunctional protein are both located in the same region of human chromosome 2p23. Genomics. 1996;37:141-3 pubmed
  66. Wojcik M, Wierenga K, Rodan L, Sahai I, Ferdinandusse S, Genetti C, et al. Beta-Ketothiolase Deficiency Presenting with Metabolic Stroke After a Normal Newborn Screen in Two Individuals. JIMD Rep. 2018;39:45-54 pubmed publisher
  67. Fould B, Garlatti V, Neumann E, Fenel D, Gaboriaud C, Arlaud G. Structural and functional characterization of the recombinant human mitochondrial trifunctional protein. Biochemistry. 2010;49:8608-17 pubmed publisher
    ..This study provides the first detailed structural and functional characterization of a recombinant human TFP preparation and opens the way to in-depth analyses through site-directed mutagenesis. ..
  68. Naiki M, Ochi N, Kato Y, Purevsuren J, Yamada K, Kimura R, et al. Mutations in HADHB, which encodes the ?-subunit of mitochondrial trifunctional protein, cause infantile onset hypoparathyroidism and peripheral polyneuropathy. Am J Med Genet A. 2014;164A:1180-7 pubmed publisher
    ..HADHA and HADHB encode the ?-subunit and the ?-subunit of MTP, respectively...