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External IDs OMIM143450 MGI3651143 HomoloGene153 GeneCards: HADHB Gene
EC number
Species Human Mouse
Entrez 3032 231086
Ensembl ENSG00000138029 ENSMUSG00000059447
UniProt P55084 Q99JY0
RefSeq (mRNA) NM_000183 NM_001289798
RefSeq (protein) NP_000174 NP_001276727
Location (UCSC) Chr 2:
26.24 – 26.29 Mb
Chr 5:
30.16 – 30.18 Mb
PubMed search [1] [2]




The HADHB gene is located on chromosome 2, with its specific location being 2p23.[1] The gene contains 17 exons. HADHB encodes a 51.2 kDa protein that is composed of 474 amino acids; 124 peptides have been observed through mass spectrometry data.[2][3]


Enzymatic activity of HADHB in beta-oxidation

This gene encodes the beta subunit of the mitochondrial trifunctional protein, a catalyst of mitochondrial beta-oxidation of long chain fatty acids. The HADHB protein catalyzes the final step of beta-oxidation, in which 3-ketoacyl CoA is cleaved by the thiol group of another molecule of Coenzyme A. The thiol is inserted between C-2 and C-3, which yields an acetyl CoA molecule and an acyl CoA molecule, which is two carbons shorter.


Clinical significance[edit]

Mutations in this gene, along with mutations in HADHA, result in trifunctional protein deficiency.[1] Mutations in either gene have similar clinical presentations.[4] Trifunctional protein deficiency is characterized by decreased activity of long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD), long-chain enoyl-CoA hydratase, and long-chain thiolase. This deficiency can be classified into 3 main clinical phenotypes: neonatal onset of a severe, lethal condition resulting in sudden infant death syndrome (SIDS),[5] infantile onset of a hepatic Reye-like syndrome, and late-adolescent onset of primarily a skeletal myopathy.[6] Additionally, some presents showed symptoms associated with myopathy, recurrent and episodic rhabdomyolysis, and sensorimotor axonal neuropathy.[7] In some cases, symptoms of the deficiency can present as dilated cardiomyopathy, congestive heart failure, and respiratory failure. The deficiency has presented as hydrops fetalis and HELLP syndrome in fetuses.[8] A compound heterozygous mutation of the HADHB gene can causes axonal Charcot-Marie-tooth disease, which is a neurological disorder, which shows that mutations in this gene can result in deficiencies that present in new forms not currently described.[9]


HADHB is a functional molecular target of ERα in the mitochondria, and the interaction may play an important role in the estrogen-mediated lipid metabolism in animals and humans.[10] Additionally, HADHB has been shown to bind to the distal 3’ untranslated region of renin mRNA, thereby regulating renin protein expression.[11]


  1. ^ a b c d "Entrez Gene: hydroxyacyl-Coenzyme A dehydrogenase/3-ketoacyl-Coenzyme A thiolase/enoyl-Coenzyme A hydratase (trifunctional protein)". 
  2. ^ ]Zong NC, Li H, Li H, Lam MP, Jimenez RC, Kim CS, Deng N, Kim AK, Choi JH, Zelaya I, Liem D, Meyer D, Odeberg J, Fang C, Lu HJ, Xu T, Weiss J, Duan H, Uhlen M, Yates JR, Apweiler R, Ge J, Hermjakob H, Ping P (Oct 2013). "Integration of cardiac proteome biology and medicine by a specialized knowledgebase". Circulation Research 113 (9): 1043–53. doi:10.1161/CIRCRESAHA.113.301151. PMC 4076475. PMID 23965338. 
  3. ^ "Trifunctional enzyme subunit beta, mitochondrial". Cardiac Organellar Protein Atlas Knowledgebase (COPaKB). 
  4. ^ Spiekerkoetter, U; Khuchua, Z; Yue, Z; Bennett, MJ; Strauss, AW (February 2004). "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.". Pediatric research 55 (2): 190–6. doi:10.1203/01.pdr.0000103931.80055.06. PMID 14630990. 
  5. ^ Sonta, SI; Sandberg, AA (1977). "Chromosomes and causation of human cancer and leukemia: XXVIII. Value of detailed chromosome studies on large numbers of cells in CML.". American journal of hematology 3: 121–6. doi:10.1002/ajh.2830030202. PMID 272120. 
  6. ^ Spiekerkoetter, U; Sun, B; Khuchua, Z; Bennett, MJ; Strauss, AW (June 2003). "Molecular and phenotypic heterogeneity in mitochondrial trifunctional protein deficiency due to beta-subunit mutations.". Human mutation 21 (6): 598–607. doi:10.1002/humu.10211. PMID 12754706. 
  7. ^ den Boer, ME; Dionisi-Vici, C; Chakrapani, A; van Thuijl, AO; Wanders, RJ; Wijburg, FA (June 2003). "Mitochondrial trifunctional protein deficiency: a severe fatty acid oxidation disorder with cardiac and neurologic involvement.". The Journal of pediatrics 142 (6): 684–9. doi:10.1067/mpd.2003.231. PMID 12838198. 
  8. ^ Jackson, S; Kler, RS; Bartlett, K; Briggs, H; Bindoff, LA; Pourfarzam, M; Gardner-Medwin, D; Turnbull, DM (October 1992). "Combined enzyme defect of mitochondrial fatty acid oxidation.". The Journal of clinical investigation 90 (4): 1219–25. doi:10.1172/jci115983. PMID 1401059. 
  9. ^ Hong, YB; Lee, JH; Park, JM; Choi, YR; Hyun, YS; Yoon, BR; Yoo, JH; Koo, H; Jung, SC; Chung, KW; Choi, BO (5 December 2013). "A compound heterozygous mutation in HADHB gene causes an axonal Charcot-Marie-tooth disease.". BMC medical genetics 14: 125. doi:10.1186/1471-2350-14-125. PMID 24314034. 
  10. ^ Zhou, Z; Zhou, J; Du, Y (July 2012). "Estrogen receptor alpha interacts with mitochondrial protein HADHB and affects beta-oxidation activity.". Molecular & cellular proteomics : MCP 11 (7): M111.011056. doi:10.1074/mcp.m111.011056. PMID 22375075. 
  11. ^ Adams, DJ; Beveridge, DJ; van der Weyden, L; Mangs, H; Leedman, PJ; Morris, BJ (7 November 2003). "HADHB, HuR, and CP1 bind to the distal 3'-untranslated region of human renin mRNA and differentially modulate renin expression.". The Journal of biological chemistry 278 (45): 44894–903. doi:10.1074/jbc.m307782200. PMID 12933794. 

Further reading[edit]

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