CYP3A5
Cytochrome P450 3A5 is a protein that in humans is encoded by the CYP3A5 gene.
Tissue distribution
CYP3A5 encodes a member of the cytochrome P450 superfamily of enzymes. Like most of the cytochrome P450, the CYP3A5 is expressed in the prostate and the liver. It is also expressed in epithelium of the small intestine and large intestine for uptake and in small amounts in the bile duct, nasal mucosa, kidney, adrenal cortex, epithelium of the gastric mucosa with intestinal metaplasia, gallbladder, intercalated ducts of the pancreas, chief cells of the parathyroid and the corpus luteum of the ovary.Clinical significance
The cytochrome P450 proteins are monooxygenases which catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids and other lipids. This protein localizes to the endoplasmic reticulum and its expression is induced by glucocorticoids and some pharmacological agents. The enzyme metabolizes drugs such as nifedipine and cyclosporine as well as the steroid hormones testosterone, progesterone and androstenedione. This gene is part of a cluster of cytochrome P450 genes on chromosome 7q21.1. This cluster includes a pseudogene, CYP3A5P1, which is very similar to CYP3A5. This similarity has caused some difficulty in determining whether cloned sequences represent the gene or the pseudogene.CYP3A4/3A5 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Immunoblot analysis of liver microsomes showed that CYP3A5 is expressed as a 52.5-kD protein, whereas CYP3A4 migrates as a 52.0-kD protein. The human CYP3A subfamily, CYP3A4, CYP3A5, CYP3A7 and CYP3A43, is one of the most versatile of the biotransformation systems that facilitate the elimination of drugs (37% of the 200 most frequently prescribed drugs in the U.S.
CYP3A4 and CYP3A5 together account for approximately 30% of hepatic cytochrome P450, and approximately half of medications that are oxidatively metabolized by P450 are CYP3A substrates. Both CYP3A4 and CYP3A5 are expressed in liver and intestine, with CYP3A5 being the predominant form expressed in extrahepatic tissues.
Allele distribution
The CYP3A5 gene has several functional variants, which vary depending on ethnicity. The CYP3A5*1 allele is associated with a normal metabolization of medication. It is most common among individuals native to Sub-Equatorial Africa, though the mutation also occurs at low frequencies in other populations. The CYP3A5*3 allele is linked with a poor metabolization of medication. It is near fixation in Europe, and is likewise found at high frequencies in West Asia and Central Asia, as well as among Afro-Asiatic speaking populations in North Africa and the Horn of Africa. Additionally, the mutation occurs at moderate-to-high frequencies in South Asia, Southeast Asia and East Asia, and at low frequencies in Sub-Equatorial Africa.Global distribution of the CYP3A5 alleles:
| Population | CYP3A5*1 | CYP3A5*3 | CYP3A5*6 | CYP3A5*7 |
| Adygei | 12% | 88% | ||
| Afar | 35% | 65% | 18% | 0% |
| African Americans | 63% | 37% | 12% | 21% |
| Algerians | 19% | 81% | 5% | 1% |
| Amhara | 33% | 67% | 15% | 0% |
| Anatolian Turks | 9% | 91% | 0% | 0% |
| Armenians | 5% | 95% | 0% | 0% |
| Asante | 89% | 11% | 22% | 7% |
| Ashkenazi Jews | 3% | 97% | 0% | 0% |
| Balochi | 20% | 80% | ||
| Bantu | 83% | 17% | ||
| Bantu | 74% | 26% | 18% | 10% |
| Bantu | 96% | 4% | 22% | 21% |
| Basques | 4% | 96% | ||
| Bedouin | 17% | 83% | ||
| Berbers | 20% | 80% | 4% | 1% |
| Biaka Pygmies | 89% | 11% | ||
| Brahui | 12% | 88% | ||
| Britons | 35% | 65% | 0% | |
| Bulsa | 81% | 19% | 16% | 13% |
| Burusho | 22% | 78% | ||
| Cameroonian | 76% | 24% | 32% | 7% |
| Canadian Caucasians | 7% | 93% | 0% | 0% |
| Chagga | 74% | 26% | 14% | 9% |
| Chewa | 85% | 15% | 16% | 17% |
| Chinese | 25% | 75% | 0% | |
| Chinese | 25% | 75% | ||
| Colombians | 15% | 85% | ||
| Colombians | 48% | 52% | 2% | |
| Congolese | 80% | 20% | 12% | 9% |
| Dai | 45% | 55% | ||
| Druze | 8% | 92% | ||
| Daur | 15% | 85% | ||
| East Asian | 31% | 69% | 0% | 0% |
| European | 2% | 98% | 0% | 0% |
| Finns | 45% | 55% | 0% | |
| French | 8%-9% | 91%-92% | 0% | 0% |
| Gabonese | 79% | 21% | 19% | 19% |
| Gambians | 79% | 21% | 20% | 12% |
| Germans | 7% | 93% | ||
| Gujarati | 25% | 75% | ||
| Han | 25% | 75% | ||
| Han | 28% | 72% | 0% | |
| Han | 47% | 53% | 0% | |
| Hazara | 25% | 75% | ||
| Hezhen | 15% | 85% | ||
| Hispanic | 25% | 75% | 0% | 0% |
| Iberians | 39% | 61% | 0% | |
| Igbo | 87% | 13% | 18% | 9% |
| Indians | 41% | 59% | 0% | |
| Italians | 18% | 82% | ||
| Italians | 5% | 95% | ||
| Italians | 5%-6% | 94%-95% | 0.5% | |
| Japanese | 23% | 77% | 0% | |
| Japanese | 26% | 74% | 0.004% | |
| Kalash | 24% | 76% | ||
| Karitiana | 23% | 77% | ||
| Kasena | 78% | 22% | 17% | 13% |
| Khmer | 27% | 73% | ||
| Koreans | 19% | 81% | 0% | |
| Kotoko | 73% | 27% | 23% | 5% |
| Lahu | 25% | 75% | ||
| Lemba | 87% | 13% | 25% | 15% |
| Lomwe | 83% | 17% | 22% | 11% |
| Luhya | 86% | 14% | 26% | |
| Maale | 51% | 49% | 15% | 1% |
| Maasai | 51% | 49% | 14% | |
| Makrani | 14% | 86% | ||
| Malay | 39% | 61% | 0% | |
| Malawians | 79% | 21% | 14% | 14% |
| Mandenka | 69% | 31% | ||
| Manjak | 79% | 21% | 23% | 7% |
| Maya | 29% | 71% | ||
| Mayo Darle | 73% | 27% | 25% | 6% |
| Mbuti Pygmies | 93% | 7% | ||
| Melanesians | 18% | 82% | ||
| Mestizo | 24% | 76% | ||
| Mestizo | 12% | 88% | ||
| Mexicans | 25% | 75% | 2% | |
| Miaozu | 35% | 65% | ||
| Mongola | 35% | 65% | ||
| Mozabite | 16% | 84% | ||
| Naxi | 28% | 72% | ||
| Ngoni | 89% | 11% | 33% | 6% |
| North American Caucasians | 9% | 90% | ||
| Orogen | 10% | 90% | ||
| Orcadians | 16% | 84% | ||
| Oromo | 35% | 65% | 14% | 0% |
| Papuans | 21% | 79% | ||
| Palestinians | 18% | 82% | ||
| Pathan | 12% | 88% | ||
| Pima | 54% | 46% | ||
| Puerto Ricans | 56% | 44% | 5% | |
| Russians | 8% | 92% | ||
| San | 93% | 7% | ||
| Sena | 84% | 16% | 23% | 16% |
| Sephardi Jews | 11% | 89% | 0% | 0% |
| She | 45% | 55% | ||
| Shewa Arabs | 60% | 40% | 22% | 7% |
| Shona | 22% | 78% | 22% | 10% |
| Sindhi | 18% | 82% | ||
| Somie | 77% | 23% | 18% | 10% |
| Southern Sudanese | 76% | 24% | 33% | 3% |
| Spaniard | 9% | 91% | ||
| Sudanese | 40% | 60% | 11% | 0% |
| Sudanese | 55% | 45% | 20% | 2% |
| Surui | 17% | 83% | ||
| Swedes | 7% | 93% | 0% | 0% |
| Tanzanians | 81% | 19% | 19% | 12% |
| Tu | 10% | 90% | ||
| Tujia | 35% | 65% | ||
| Tunisian | 19% | 81% | 1% | 0% |
| Uygur | 5% | 95% | ||
| Wolof | 73% | 27% | 18% | 9% |
| Xibo | 22% | 78% | ||
| Yao | 82% | 18% | 13% | 9% |
| Yakuts | 10% | 90% | ||
| Yemeni | 15% | 85% | 3% | 1% |
| Yemeni | 42% | 58% | 12% | 3% |
| Yizu | 20% | 80% | ||
| Yoruba | 83%-94% | 6%-17% | 17%-75% | 0% |
| Zimbabweans | 84% | 16% | 16% | 19% |