The human CYP7B1 DNA maps to NM_004820 (Entrez-Gene) and spans a region of 202.66 kB. CYP7B1 is located on chromosome 8 and consists of six exons.

The full length CYP7B1 mRNA is 2,395 bp with an open reading rame of 1,521 bp.

No pseudogenes reported.

The human CYP7B1 protein consists of 506 amino acids and has a molecular weight of 58,256. The N-terminal membrane-binding domain (residues 1 to 38) is highly hydrophobic. The ATG start codon is located 204 nucleotides downstream of the transcription start site (Wu et al., 1999). Similarly as other members of the cytochrome P450 (CYP) enzyme superfamily, CYP7B1 contains heme iron as a cofactor. Human CYP7B1 shares 40% sequence identity with human CYP7A1, the other member of the CYP7 family.

Expression of CYP7B1 is reported in many human tissues including brain, kidney, liver, lung, heart, prostate, testis, ovary, placenta, pancreas, intestine, colon and thymus (Wu et al., 1999).

Most reports indicated localization to the membrane of the endoplasmic reticulum. There are some data indicating possible CYP7B1-related activity also in mitochondria but it is unclear whether this activity represents CYP7B1 or another enzyme species (Axelson et al., 1992; Pandak et al., 2002).

CYP7B1 converts a number of steroids into their 7alpha-hydroxyderivatives (Toll et al., 1994; Rose et al., 1997; Yau et al., 2006; Norlin and Wikvall, 2007). In addition to 7alpha-hydroxylation, formation of 6alpha, 6beta-, and 7beta-hydroxyderivatives also has been reported for this enzyme. Some well-known substrates for CYP7B1 are: 27-hydroxycholesterol and 25-hydroxycholesterol (cholesterol derivatives); dehydroepiandrosterone (DHEA) and pregnenolone (sex hormone precursors and neurosteroids); 5alpha-androstane-3beta,17beta-diol and 5-androstene-3beta,17beta-diol (estrogen receptor ligands). The catalytic reactions performed by CYP7B1 may lead to elimination of the steroids from the cell and thereby reduce the cellular levels of the substrates for this enzyme. Also, several of the products formed by CYP7B1 are reported to have physiological effects. Thus, CYP7B1 may in some cases be part of biosynthetic pathways to form active compounds.

The CYP7B1 gene is conserved in chimpanzee, dog, cow, mouse, rat, chicken, and zebrafish.

A homozygous mutation in the CYP7B1 gene (R388X) was identified in an infant boy with defective bile acid synthesis and severe cholestasis (Setchell et al., 1998). The patient was the offspring of first cousins. Mutations in the CYP7B1 gene (S363F, G57R, R417H, F216S, R388X) have been associated with a form of hereditary spastic paraplegia (HSP type 5) characterized by motor neuron degeneration in affected individuals of several families (Tsaousidou et al., 2008). S363F and F216S was predicted to affect phosphorylation of the mature protein. In addition, studies on non-consanguineous cases of hereditary spastic paraplegia indicate that a coding CYP7B1 polymorphism (c.971G>A) is associated with a phenotype of cerebellar signs believed to complicate a primary HSP phenotype (Schule et al., 2009).
A functional polymorphism was reported in the human CYP7B1 promoter consisting of a C-G change located -104 nucleotides from the transcription start site (Jakobsson et al., 2004). The C-G alteration at -104 creates a putative C/EBPbeta binding site and was shown to result in higher transcriptional activity. In a study comparing allele frequency in an Oriental (Korean) population and a Caucasian (Swedish) population, the frequency of the uncommon G-allele was found to be much lower in the Oriental population (Jakobsson et al., 2004).