The human CYP7A1 DNA maps to NM_000780 (Entrez Gene) and spans a region of 9.98 kB. CYP7A1 is located on chromosome 8 and consists of six exons.

The full length CYP7A1 mRNA is 2,875 bp with an open reading frame of 1,512 bp (Noshiro and Okuda, 1990).

No pseudogenes reported.

The human CYP7A1 protein consists of 504 amino acids and has a molecular weight of 57,630 Da (Noshiro and Okuda, 1990). Human CYP7A1 shares 40% sequence identity with CYP7B1, the other member of the CYP7 family.

Most reports indicate exclusive liver specific expression. One study reports expression of CYP7A1 also in human prostate (Steckelbroeck et al., 2002). The expression of hepatic CYP7A1 in several species has been reported to be low in early life and to increase severalfold with age (Norlin, 2002; Massimi et al., 1998).

CYP7A1 is a endoplasmic reticulum membrane enzyme.

CYP7A1 is a cholesterol 7alpha-hydroxylase, catalyzing the first and rate-limiting step in the neutral or classic pathway for bile acid biosynthesis. Bile acid biosynthesis is the predominant pathway for cholesterol catabolism. The enzyme also 7alpha-hydroxylates 27-hydroxycholesterol and other oxysterols (Norlin et al., 2000a, b). Results supporting a role for CYP7A1 as an oxysterol 7alpha-hydroxylase are also reported by others (Dueland et al., 1992; Pandak et al., 2002). Studies on mice with a disruption in the Cyp7a1 gene (Ishibashi et al., 1996; Schwarz et al., 1996) demonstrated a crucial role for this enzyme in bile acid biosynthesis. Mice and humans with cholesterol 7alpha-hydroxylase deficiency exhibit, however, different phenotypes (Norlin and Wikvall, 2007).
Several mechanisms for regulation of CYP7A1 have been described (Chiang, 2004). Bile acids inhibit CYP7A1 gene transcription via negative feedback control. The feedback inhibition by bile acids involve several nuclear receptors such as liver receptor homolog 1 (LRH-1), hepatocyte nuclear factor 4alpha (HNF4alpha), small heterodimer partner (SHP) and the bile acid receptor farnesyl X receptor (FXR). Also the pregnane X receptor (PXR) and the vitamin D receptor (VDR) have been identified as bile acid-activated receptors (Staudinger et al., 2001; Han and Chiang, 2009). Bile acids are also reported to suppress CYP7A1 via stimulation of inflammatory cytokines (tumor necrosis factor alpha and IL-1beta) and mitogen-activated protein kinase (MAPK) signaling pathways leading to the activation of cJun N-terminus kinase (JNK). JNK may phosphorylate and inactivate transcription factors crucial for stimulating the hepatic expression of CYP7A1 (Chiang, 2004; Gupta et al., 2004). Cholestyramine, a drug used in the treatment of hyperlipoproteinemia, induces cholesterol 7alpha-hydroxylase by binding to bile acids in the intestine and preventing their reabsorption to the liver (Brown and Boyd, 1974). Evidence for a posttranscriptional regulation of cholesterol 7alpha-hydroxylase has been reported, but most of the data available suggest that the regulation is predominantly on a transcriptional level (Chiang, 2004; Stroup and Ramsaran, 2005).

The CYP7A1 gene is conserved in many species, such as chimpanzee, dog, cow, mouse, rat, chicken, and zebrafish.

A metabolic disorder presenting with elevated plasma cholesterol levels caused by a homozygous deletion mutation in the CYP7A1 gene in a family of English and Celtic origin has been described (Pullinger et al., 2002). The mutation leads to a frameshift resulting in the synthesis of a truncated protein with no enzymatic activity. High levels of LDL cholesterol were seen in three homozygous subjects. The high levels of LDL cholesterol in the CYP7A1-deficient subjects were found to be resistant to treatment with hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase inhibitors. Two male subjects had hypertriglyceridemia and premature gallstone disease. One subject had premature coronary and peripheral vascular disease. Individuals that are heterozygous for the mutation were also found to be hyperlipidemic, indicating that the disorder is inherited in a codominant fashion (Pullinger et al., 2002). The authors concluded that CYP7A1 deficiency in humans causes hypercholesterolemia. This conclusion is consistent with studies showing an association between cholesterol levels and polymorphisms at the CYP7A1 locus (Wang et al., 1998; Couture et al., 1999).