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Gene Review

CYB5R4  -  cytochrome b5 reductase 4

Homo sapiens

Synonyms: Cytochrome b5 reductase 4, Flavohemoprotein b5/b5R, N-terminal cytochrome b5 and cytochrome b5 oxidoreductase domain-containing protein, NCB5OR, b5+b5R, ...
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Disease relevance of CYB5R4

  • A genetic approach, using BLAST searches against DBEST for FAD-, NAD(P)H-binding sequences followed by reverse transcription-PCR, was used to clone the complete cDNA sequence of human b5+b5R from the hepatoma cell line Hep 3B [1].
  • Variation in NCB5OR: studies of relationships to type 2 diabetes, maturity-onset diabetes of the young, and gestational diabetes mellitus [2].

High impact information on CYB5R4


Biological context of CYB5R4

  • Furthermore, genome-wide scans have reported linkage to the chromosome 6q14.2 region close to the human NCB5OR [2].
  • The subcellular localization and redox properties of NCB5OR provide important insights into the biology of NCB5OR and the phenotype of the Ncb5or-null mouse [4].

Anatomical context of CYB5R4


Associations of CYB5R4 with chemical compounds


Other interactions of CYB5R4

  • The recombinant b5+b5R protein can be reduced by NAD(P)H, generating spectrum typical of reduced cytochrome b with alpha, beta, and Soret peaks at 557, 527, and 425 nm, respectively [1].
  • NCB5OR is the first example of an animal flavohemoprotein containing cytochrome b5 and chrome b5 reductase cytodomains [4].
  • Kinetic measurements showed that full-length and truncated NCB5OR reduce cytochrome c actively in vitro [4].

Analytical, diagnostic and therapeutic context of CYB5R4

  • The redox potential at the heme center of NCB5OR is -108 mV, as determined by potentiometric titrations [4].
  • Resonance Raman spectroscopy of NCB5OR presents typical signatures of a six-coordinate low-spin heme similar to those found in other cytochrome b5 proteins [4].
  • We therefore considered NCB5OR to be a biological and positional candidate gene and examined the coding region of NCB5OR in 120 type 2 diabetic patients and 63 patients with maturity-onset diabetes of the young using denaturing high-performance liquid chromatography [2].


  1. Identification of a cytochrome b-type NAD(P)H oxidoreductase ubiquitously expressed in human cells. Zhu, H., Qiu, H., Yoon, H.W., Huang, S., Bunn, H.F. Proc. Natl. Acad. Sci. U.S.A. (1999) [Pubmed]
  2. Variation in NCB5OR: studies of relationships to type 2 diabetes, maturity-onset diabetes of the young, and gestational diabetes mellitus. Andersen, G., Wegner, L., Rose, C.S., Xie, J., Zhu, H., Larade, K., Johansen, A., Ek, J., Lauenborg, J., Drivsholm, T., Borch-Johnsen, K., Damm, P., Hansen, T., Bunn, H.F., Pedersen, O. Diabetes (2004) [Pubmed]
  3. Absence of a reductase, NCB5OR, causes insulin-deficient diabetes. Xie, J., Zhu, H., Larade, K., Ladoux, A., Seguritan, A., Chu, M., Ito, S., Bronson, R.T., Leiter, E.H., Zhang, C.Y., Rosen, E.D., Bunn, H.F. Proc. Natl. Acad. Sci. U.S.A. (2004) [Pubmed]
  4. NCB5OR is a novel soluble NAD(P)H reductase localized in the endoplasmic reticulum. Zhu, H., Larade, K., Jackson, T.A., Xie, J., Ladoux, A., Acker, H., Berchner-Pfannschmidt, U., Fandrey, J., Cross, A.R., Lukat-Rodgers, G.S., Rodgers, K.R., Bunn, H.F. J. Biol. Chem. (2004) [Pubmed]
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