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CYP7B1 (cytochrome P450, family 7, subfamily B, polypeptide 1)

Written2009-04Maria Norlin
Department of Pharmaceutical Biosciences, Division of Biochemistry, University of Uppsala, Sweden

(Note : for Links provided by Atlas : click)


HGNC (Hugo) CYP7B1
HGNC Previous nameSPG5A
HGNC Previous namecytochrome P450, subfamily VIIB (oxysterol 7 alpha-hydroxylase), polypeptide 1
 spastic paraplegia 5A (autosomal recessive)
 cytochrome P450, family 7, subfamily B, polypeptide 1
LocusID (NCBI) 9420
Atlas_Id 40255
Location 8q12.3  [Link to chromosome band 8q12]
Location_base_pair Starts at 64590851 and ends at 64798737 bp from pter ( according to GRCh38/hg38-Dec_2013)  [Mapping CYP7B1.png]
Fusion genes
(updated 2017)
Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands)
Note CYP7B1 is a steroid hydroxylase involved in metabolism of sex hormones, oxysterols (a type of cholesterol derivatives) and neurosteroids.


  Human CYP7B1 gene structure. Exons are represented by red bars with exon numbers at the bottom.
Description 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.
Transcription The full length CYP7B1 mRNA is 2,395 bp with an open reading rame of 1,521 bp.
Pseudogene No pseudogenes reported.


Description 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 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).
Localisation 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).
Function 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.
Homology The CYP7B1 gene is conserved in chimpanzee, dog, cow, mouse, rat, chicken, and zebrafish.


Germinal 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).

Implicated in

Entity Prostate cancer
Note High expression of CYP7B1 protein is found in high-grade prostatic intraepithelial neoplasia (PIN) and adenocarcinomas (Olsson et al., 2007). Local methylation of the CYP7B1 promoter is suggested to be important for regulation of CYP7B1 in human prostate tissue. In addition, a functional C-G polymorphism in the CYP7B1 promoter has been associated with a different allele frequency in two ethnic populations with great differences in the incidence of prostate cancer (Swedes and Koreans) (Jakobsson et al., 2004). A connection between CYP7B1 and prostate cancer may be related to the action of estrogen receptor beta (ERbeta), since metabolism by CYP7B1 is reported to affect the levels of ligands for ERbeta, which is believed to have anti-proliferative effects (Weihua et al., 2002; Martin et al., 2004). Sex hormones are important for growth of prostate and other tissues, both during normal and malignant conditions. A potential role for CYP7B1 in tissue growth is supported by data indicating that the Akt/PI3K (phosphoinositide 3-kinase) cascade, a signalling pathway important for cellular growth, affects the CYP7B1 gene (Tang et al., 2008). In human prostate cancer LNCaP cells, CYP7B1 promoter activity is affected by both androgens and estrogens, suggesting important functions in hormonal signalling (Tang and Norlin, 2006).
Entity Spastic Paraplegia Type 5A
Note Mutations in the coding region of the CYP7B1 gene has been found in patients with spastic paraplegia type 5, an upper-motor-neuron degenerative disease which affects lower limb movement and results in extremity weakness and spasticity, sometimes accompanied by additional symptoms. Hereditary spastic paraplegia (HSP) is characterized by axonal degeneration of neurons in the corticospinal tracts and dorsal columns. Sequence alterations in CYP7B1, believed to affect the functionality of the enzyme, has been associated with a pure form of autosomal-recessive HSP in several families (Tsaousidou et al., 2008). The association of an abnormal CYP7B1 gene with this neurodegenerative condition suggest that the pathogenic basis for this disease is related either to effects on cholesterol homeostasis in the brain (i e on CYP7B1-mediated control of the levels of 27-hydroxycholesterol) or to effects on the metabolism of dehydroepiandrosterone and other neurosteroids.
Entity Congenital Bile Acid Defect Type 3 (CBAS3)
Note A mutation in the CYP7B1 gene was linked to defective bile acid production, cholestasis and liver cirrhosis in an infant boy who died at the age of < 1 year due to complications following liver transplantation (Setchell et al., 1998). Other symptoms included hepatosplenomegaly, jaundice and increased bleeding. The pathological findings were consistent with accumulation of hepatotoxic unsaturated monohydroxy bile acids. The patient had 4,500 times higher levels of 27-hydroxycholesterol than normal and liver samples showed no 27-hydroxycholesterol 7alpha-hydroxylase activity. Failure to detect CYP7A1-mediated 7alpha-hydroxylase activity in this patient as well as in other infants of the same age led the authors to suggest that CYP7B1 may be more important for bile acid synthesis in early life than in adulthood (Setchell et al., 1998).
Entity Alzheimer's Disease
Note Some patients with Alzheimer's disease, a progressive neurodegenerative disease that strongly impairs cognition and memory, are reported to have altered levels of CYP7B1 expression and/or CYP7B1-formed metabolites. Some studies indicate reduced brain expression of CYP7B1 in Alzheimer's disease (Yau et al., 2003) whereas others report increased CYP7B1-formed metabolites in serum from patients with this disease (Attal-Khemis et al., 1998). The potential role(s) of CYP7B1 in connection with Alzheimer's disease remains unclear. Alzheimer's disease is associated with build-up of neuritic plaques and neurofibrillary tangles and progressive loss of neurons and synapses in several parts of the brain. The etiology of Alzheimer's disease is not well understood and the underlying mechanisms are most likely complex. It has been suggested that disturbed metabolism of neurosteroids and/or other brain lipids may be one of the contributing factors (Yau et al., 2003; Bjorkhem et al., 2006). In some types of brain cells, CYP7B1-dependent hydroxylation is the main metabolic fate for neurosteroids dehydroepiandrosterone and pregnenolone. Also, the levels of CYP7B1 are higher in the hippocampus than in other parts of the brain, supporting a potential role for this enzyme related to memory and cognition (Yau et al., 2003).
Entity Rheumatoid Arthritis and Inflammation
Note Increased production of the CYP7B1-formed metabolite 7alpha-hydroxy-DHEA has been suggested to contribute to the chronic inflammation observed in patients with rheumatoid arthritis (Dulos et al., 2005). Rheumatoid arthritis is a chronic inflammatory disorder with unclear etiology characterized by joint inflammation and progressive destruction of the joints. Other tissues also may be affected. Studies in a mouse model for collagen-induced arthritis indicate correlation of increased CYP7B1 activity with disease progression (Dulos et al., 2004). In humans, CYP7B1 is found in synovial tissues (connective tissues surrounding the joints) from patients with rheumatoid arthritis and CYP7B1 levels are up-regulated by proinflammatory cytokines in human synoviocytes (Dulos et al., 2005). Chronic inflammatory diseases including rheumatoid arthritis are known to be associated with changes in levels of several steroids. It has been proposed that the CYP7B1-formed 7alpha-hydroxy-DHEA might counteract the immunosuppressive effects of glucocorticoids, which are used in treatment of rheumatoid arthritis.


Increased total 7 alpha-hydroxy-dehydroepiandrosterone in serum of patients with Alzheimer's disease.
Attal-Khemis S, Dalmeyda V, Michot JL, Roudier M, Morfin R.
J Gerontol A Biol Sci Med Sci. 1998 Mar;53(2):B125-32.
PMID 9520908
Cholesterol is converted to 7 alpha-hydroxy-3-oxo-4-cholestenoic acid in liver mitochondria. Evidence for a mitochondrial sterol 7 alpha-hydroxylase.
Axelson M, Shoda J, Sjovall J, Toll A, Wikvall K.
J Biol Chem. 1992 Jan 25;267(3):1701-4.
PMID 1730713
Oxysterols and Alzheimer's disease.
Bjorkhem I, Heverin M, Leoni V, Meaney S, Diczfalusy U.
Acta Neurol Scand Suppl. 2006;185:43-9.
PMID 16866910
Severity of murine collagen-induced arthritis correlates with increased CYP7B activity: enhancement of dehydroepiandrosterone metabolism by interleukin-1beta.
Dulos J, Verbraak E, Bagchus WM, Boots AM, Kaptein A.
Arthritis Rheum. 2004 Oct;50(10):3346-53.
PMID 15476247
CYP7B expression and activity in fibroblast-like synoviocytes from patients with rheumatoid arthritis: regulation by proinflammatory cytokines.
Dulos J, van der Vleuten MA, Kavelaars A, Heijnen CJ, Boots AM.
Arthritis Rheum. 2005 Mar;52(3):770-8.
PMID 15751070
A functional C-G polymorphism in the CYP7B1 promoter region and its different distribution in Orientals and Caucasians.
Jakobsson J, Karypidis H, Johansson JE, Roh HK, Rane A, Ekstrom L.
Pharmacogenomics J. 2004;4(4):245-50.
PMID 15007371
CYP7B generates a selective estrogen receptor beta agonist in human prostate.
Martin C, Ross M, Chapman KE, Andrew R, Bollina P, Seckl JR, Habib FK.
J Clin Endocrinol Metab. 2004 Jun;89(6):2928-35.
PMID 15181079
Enzymes in the conversion of cholesterol into bile acids.
Norlin M, Wikvall K.
Curr Mol Med. 2007 Mar;7(2):199-218. (REVIEW)
PMID 17346171
Regulation and expression of human CYP7B1 in prostate: overexpression of CYP7B1 during progression of prostatic adenocarcinoma.
Olsson M, Gustafsson O, Skogastierna C, Tolf A, Rietz BD, Morfin R, Rane A, Ekstrom L.
Prostate. 2007 Sep 15;67(13):1439-46.
PMID 17639508
Regulation of oxysterol 7alpha-hydroxylase (CYP7B1) in primary cultures of rat hepatocytes.
Pandak WM, Hylemon PB, Ren S, Marques D, Gil G, Redford K, Mallonee D, Vlahcevic ZR.
Hepatology. 2002 Jun;35(6):1400-8.
PMID 12029625
Cyp7b, a novel brain cytochrome P450, catalyzes the synthesis of neurosteroids 7alpha-hydroxy dehydroepiandrosterone and 7alpha-hydroxy pregnenolone.
Rose KA, Stapleton G, Dott K, Kieny MP, Best R, Schwarz M, Russell DW, Bjorkhem I, Seckl J, Lathe R.
Proc Natl Acad Sci U S A. 1997 May 13;94(10):4925-30.
PMID 9144166
Analysis of CYP7B1 in non-consanguineous cases of hereditary spastic paraplegia.
Schule R, Brandt E, Karle KN, Tsaousidou M, Klebe S, Klimpe S, Auer-Grumbach M, Crosby AH, Hubner CA, Schols L, Deufel T, Beetz C.
Neurogenetics. 2009 Apr;10(2):97-104. Epub 2008 Oct 15.
PMID 18855023
Identification of a new inborn error in bile acid synthesis: mutation of the oxysterol 7alpha-hydroxylase gene causes severe neonatal liver disease.
Setchell KD, Schwarz M, O'Connell NC, Lund EG, Davis DL, Lathe R, Thompson HR, Weslie Tyson R, Sokol RJ, Russell DW.
J Clin Invest. 1998 Nov 1;102(9):1690-703.
PMID 9802883
Regulation of steroid hydroxylase CYP7B1 by androgens and estrogens in prostate cancer LNCaP cells.
Tang W, Norlin M.
Biochem Biophys Res Commun. 2006 Jun 2;344(2):540-6. Epub 2006 Apr 4.
PMID 16630558
Involvement of the PI3K/Akt pathway in estrogen-mediated regulation of human CYP7B1: identification of CYP7B1 as a novel target for PI3K/Akt and MAPK signalling.
Tang W, Pettersson H, Norlin M.
J Steroid Biochem Mol Biol. 2008 Nov;112(1-3):63-73. Epub 2008 Aug 26.
PMID 18790053
7 alpha hydroxylation of 25-hydroxycholesterol in liver microsomes. Evidence that the enzyme involved is different from cholesterol 7 alpha-hydroxylase.
Toll A, Wikvall K, Sudjana-Sugiaman E, Kondo KH, Bjorkhem I.
Eur J Biochem. 1994 Sep 1;224(2):309-16.
PMID 7925343
Sequence alterations within CYP7B1 implicate defective cholesterol homeostasis in motor-neuron degeneration.
Tsaousidou MK, Ouahchi K, Warner TT, Yang Y, Simpson MA, Laing NG, Wilkinson PA, Madrid RE, Patel H, Hentati F, Patton MA, Hentati A, Lamont PJ, Siddique T, Crosby AH.
Am J Hum Genet. 2008 Feb;82(2):510-5. Epub 2008 Jan 18.
PMID 18252231
An endocrine pathway in the prostate, ERbeta, AR, 5alpha-androstane-3beta,17beta-diol, and CYP7B1, regulates prostate growth.
Weihua Z, Lathe R, Warner M, Gustafsson JA.
Proc Natl Acad Sci U S A. 2002 Oct 15;99(21):13589-94. Epub 2002 Oct 7.
PMID 12370428
Structure and functions of human oxysterol 7alpha-hydroxylase cDNAs and gene CYP7B1.
Wu Z, Martin KO, Javitt NB, Chiang JY.
J Lipid Res. 1999 Dec;40(12):2195-203.
PMID 10588945
Central administration of a cytochrome P450-7B product 7 alpha-hydroxypregnenolone improves spatial memory retention in cognitively impaired aged rats.
Yau JL, Noble J, Graham M, Seckl JR.
J Neurosci. 2006 Oct 25;26(43):11034-40.
PMID 17065445
Dehydroepiandrosterone 7-hydroxylase CYP7B: predominant expression in primate hippocampus and reduced expression in Alzheimer's disease.
Yau JL, Rasmuson S, Andrew R, Graham M, Noble J, Olsson T, Fuchs E, Lathe R, Seckl JR.
Neuroscience. 2003;121(2):307-14.
PMID 14521990


This paper should be referenced as such :
Norlin, M
CYP7B1 (cytochrome P450, family 7, subfamily B, polypeptide 1)
Atlas Genet Cytogenet Oncol Haematol. 2010;14(3):275-278.
Free journal version : [ pdf ]   [ DOI ]

External links

HGNC (Hugo)CYP7B1   2652
Entrez_Gene (NCBI)CYP7B1    cytochrome P450 family 7 subfamily B member 1
AliasesCBAS3; CP7B; SPG5A
GeneCards (Weizmann)CYP7B1
Ensembl hg19 (Hinxton)ENSG00000172817 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000172817 [Gene_View]  ENSG00000172817 [Sequence]  chr8:64590851-64798737 [Contig_View]  CYP7B1 [Vega]
ICGC DataPortalENSG00000172817
TCGA cBioPortalCYP7B1
AceView (NCBI)CYP7B1
Genatlas (Paris)CYP7B1
SOURCE (Princeton)CYP7B1
Genetics Home Reference (NIH)CYP7B1
Genomic and cartography
GoldenPath hg38 (UCSC)CYP7B1  -     chr8:64590851-64798737 -  8q12.3   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)CYP7B1  -     8q12.3   [Description]    (hg19-Feb_2009)
GoldenPathCYP7B1 - 8q12.3 [CytoView hg19]  CYP7B1 - 8q12.3 [CytoView hg38]
genome Data Viewer NCBICYP7B1 [Mapview hg19]  
OMIM270800   603711   613812   
Gene and transcription
Genbank (Entrez)AF029403 AF127090 BC029155 BC136574 BM729103
RefSeq transcript (Entrez)NM_001324112 NM_004820
Consensus coding sequences : CCDS (NCBI)CYP7B1
Alternative Splicing GalleryENSG00000172817
Gene ExpressionCYP7B1 [ NCBI-GEO ]   CYP7B1 [ EBI - ARRAY_EXPRESS ]   CYP7B1 [ SEEK ]   CYP7B1 [ MEM ]
Gene Expression Viewer (FireBrowse)CYP7B1 [ Firebrowse - Broad ]
GenevisibleExpression of CYP7B1 in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)9420
GTEX Portal (Tissue expression)CYP7B1
Human Protein AtlasENSG00000172817-CYP7B1 [pathology]   [cell]   [tissue]
Protein : pattern, domain, 3D structure
UniProt/SwissProtO75881   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtO75881  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProO75881
Domains : Interpro (EBI)Cyt_P450    Cyt_P450_CYP7A1-type    Cyt_P450_E_grp-IV    Cyt_P450_sf   
Domain families : Pfam (Sanger)p450 (PF00067)   
Domain families : Pfam (NCBI)pfam00067   
Conserved Domain (NCBI)CYP7B1
AlphaFold pdb e-kbO75881   
Human Protein Atlas [tissue]ENSG00000172817-CYP7B1 [tissue]
Protein Interaction databases
IntAct (EBI)O75881
Ontologies - Pathways
Ontology : AmiGOiron ion binding  endoplasmic reticulum membrane  bile acid biosynthetic process  bile acid biosynthetic process  bile acid biosynthetic process  cholesterol metabolic process  steroid hydroxylase activity  oxysterol 7-alpha-hydroxylase activity  oxysterol 7-alpha-hydroxylase activity  integral component of membrane  sterol metabolic process  heme binding  negative regulation of intracellular estrogen receptor signaling pathway  25-hydroxycholesterol 7alpha-hydroxylase activity  B cell chemotaxis  cholesterol homeostasis  27-hydroxycholesterol 7-alpha-monooxygenase activity  positive regulation of epithelial cell proliferation  prostate gland epithelium morphogenesis  
Ontology : EGO-EBIiron ion binding  endoplasmic reticulum membrane  bile acid biosynthetic process  bile acid biosynthetic process  bile acid biosynthetic process  cholesterol metabolic process  steroid hydroxylase activity  oxysterol 7-alpha-hydroxylase activity  oxysterol 7-alpha-hydroxylase activity  integral component of membrane  sterol metabolic process  heme binding  negative regulation of intracellular estrogen receptor signaling pathway  25-hydroxycholesterol 7alpha-hydroxylase activity  B cell chemotaxis  cholesterol homeostasis  27-hydroxycholesterol 7-alpha-monooxygenase activity  positive regulation of epithelial cell proliferation  prostate gland epithelium morphogenesis  
Pathways : KEGGPrimary bile acid biosynthesis    Steroid hormone biosynthesis   
REACTOMEO75881 [protein]
REACTOME PathwaysR-HSA-5579013 [pathway]   
NDEx NetworkCYP7B1
Atlas of Cancer Signalling NetworkCYP7B1
Wikipedia pathwaysCYP7B1
Orthology - Evolution
GeneTree (enSembl)ENSG00000172817
Phylogenetic Trees/Animal Genes : TreeFamCYP7B1
Homologs : HomoloGeneCYP7B1
Homology/Alignments : Family Browser (UCSC)CYP7B1
Gene fusions - Rearrangements
Fusion : FusionGDB1.14.14.29   
Fusion : QuiverCYP7B1
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerCYP7B1 [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)CYP7B1
Exome Variant ServerCYP7B1
GNOMAD BrowserENSG00000172817
Varsome BrowserCYP7B1
Genomic Variants (DGV)CYP7B1 [DGVbeta]
DECIPHERCYP7B1 [patients]   [syndromes]   [variants]   [genes]  
CONAN: Copy Number AnalysisCYP7B1 
ICGC Data PortalCYP7B1 
TCGA Data PortalCYP7B1 
Broad Tumor PortalCYP7B1
OASIS PortalCYP7B1 [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICCYP7B1  [overview]  [genome browser]  [tissue]  [distribution]  
Somatic Mutations in Cancer : COSMIC3DCYP7B1
Mutations and Diseases : HGMDCYP7B1
LOVD (Leiden Open Variation Database)[gene] [transcripts] [variants]
BioMutasearch CYP7B1
DgiDB (Drug Gene Interaction Database)CYP7B1
DoCM (Curated mutations)CYP7B1 (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)CYP7B1 (select a term)
NCG6 (London) select CYP7B1
Cancer3DCYP7B1(select the gene name)
Impact of mutations[PolyPhen2] [Provean] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
OMIM270800    603711    613812   
Orphanet11328    14697   
Genetic Testing Registry CYP7B1
NextProtO75881 [Medical]
Target ValidationCYP7B1
Huge Navigator CYP7B1 [HugePedia]
Clinical trials, drugs, therapy
Protein Interactions : CTDCYP7B1
Pharm GKB GenePA27124
Clinical trialCYP7B1
DataMed IndexCYP7B1
PubMed60 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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