Gene details

Additional test information

Learn more about the genes covered by our tests.

COMT

The COMT gene, residing on chromosome 22, encodes the enzyme catechol-O-methyltransferase, which degrades catecholamines such as the neurotransmitters dopamine, epinephrine, and norepinephrine. COMT enzyme activity is modulated by genetic variants, one of the best characterized being rs4680 (also known as Val158Met variant or c.322G>A).

CYP1A2

Located on the plus strand of chromosome 15, CYP1A2 encodes the cytochrome P450 family 1 subfamily A type 2 enzyme, which mediates liver metabolism of 9% of clinically important drugs, procarcinogens, and endogenous substrates. For many drugs CYP1A2 is not the sole metabolizing enzyme, nor is it active at the rate-limiting step. The genetic component of variation in CYP1A2 activity is estimated at up to 75%, with environmental factors (e.g., smoking) making up the remaining difference.

CYP2B6

Located on the plus strand of chromosome 19, CYP2B6 encodes the cytochrome P450 family 2, subfamily B type 6 enzyme, which mediates liver and brain metabolism of 4% of the top 200 prescribed medications. CYP2B6 is highly inducible by several drugs and other xenobiotics. CYP2B6 expression varies over a 20-250-fold range, due to differences in transcriptional regulation and genetic variations. Pharmacogenomic guidelines published by professional associations exist for this gene and a certain medication.

CYP2C9

Located on the plus strand of chromosome 10, CYP2C9 encodes the cytochrome P450 family 2 subfamily C type 9 enzyme, which is primarily expressed in the liver and mediates metabolic clearance of 15-20% of all drugs undergoing phase I metabolism. The gene coding for the CYP2C9 enzyme is highly polymorphic, including functional variants of major pharmacogenetic importance. Pharmacogenomic guidelines published by professional associations exist for this gene and certain medications.

CYP2C19

CYP2C19, located on the plus strand of chromosome 10, encodes the cytochrome P450 family 2 subfamily C type 19 enzyme, which mediates liver (and small intestinal) metabolic oxidation of 10-15% of clinically relevant drugs and drug classes. Variants in the gene include loss-of-function alleles (e.g., *2, *3) and a promoter variant that causes increased gene expression (e.g., *17). Pharmacogenomic guidelines published by professional associations exist for this gene and certain medications.

CYP2C Cluster

The single nucleotide polymorphism (SNP) rs12777823 is located in the CYP2C Cluster near the CYP2C18 gene on chromosome 10. This SNP is of therapeutic interest in combination with genotypes from CYP2C9, VKORC1, and CYP4F2. Pharmacogenomic guidelines published by a professional association exist for this gene and a certain medication.

CYP2D6

CYP2D6, located on the minus strand of chromosome 22, encodes the cytochrome P450 family 2 subfamily D type 6 enzyme, which mediates hepatic first-pass metabolic oxidation of numerous drugs. Phenotypes for this gene range from poor to ultrarapid, as variants may result in reduced or abolished enzyme function, and variations in copy number and pseudogene rearrangements are also possible. Pharmacogenomic guidelines published by professional associations exist for this gene and certain medications.

CYP3A4

Cytochrome P450 family 3 subfamily A type 4 enzyme (CYP3A4) is encoded by the CYP3A4 gene located on the minus strand of chromosome 7. Along with CYP3A5, CYP3A4 is the predominant cytochrome P450 enzyme expressed in the adult human liver. CYP3A4 activity predominates in Caucasians and CYP3A5 predominates in individuals of African descent. CYP3A is involved in the metabolism of about 50% of all drugs.

CYP3A5

Cytochrome P450 family 3 subfamily A type 5 (CYP3A5) is encoded by the CYP3A5 gene, located on the minus strand of chromosome 7. Along with CYP3A4, CYP3A5 is the predominant cytochrome P450 enzyme expressed in the adult human liver. CYP3A4 activity predominates in Caucasians and CYP3A5 predominates in individuals of African descent. Most medications metabolized by CYP3A4 are also metabolized by CYP3A5, with a few exceptions. CYP3A5 poor metabolizer phenotype was the most prevalent phenotype in studies used to define standard dosing of medications. CYP3A5 normal metabolizers have increased enzyme activity relative to the poor metabolizer phenotype. Pharmacogenomic guidelines published by professional associations exist for this gene and a certain medication.

CYP4F2

Cytochrome P450 family 4 subfamily F member 2 (CYP4F2) is encoded by the CYP4F2 gene, located on chromosome 19. CYP4F2 catalyzes the NADPH-dependent oxidation of the terminal carbon of long and very long-chain fatty acids, the side chains of vitamin K (K1, K2) and vitamin E (tocopherols and tocotrienols), arachidonic acid (AA), and leukotriene B4 (LTB4). Through its role as a vitamin K1 oxidase, the CYP4F2 variant rs2108622 is of therapeutic interest in combination with genotypes from CYP2C9, VKORC1, and rs12777823. Pharmacogenomic guidelines published by a professional association exist for this gene and a certain medication.

DPYD

The DPYD gene, located on the minus strand of chromosome 1, encodes dihydropyrimidine dehydrogenase (DPD) enzyme, which is involved in the degradation pathway of certain medications. Decreased activity of DPD can lead to severe or fatal toxicity induced by these medications. Pharmacogenomic guidelines published by professional associations exist for this gene and certain medications.

DRD2

The DRD2 gene, residing on the minus strand of chromosome 11, encodes dopamine receptor D2. Dopamine receptor D2 is a G protein-coupled receptor highly expressed in the pituitary gland and central nervous system. This receptor is targeted by certain medications. In particular, rs1799978 A>G is a promoter variant that influences receptor expression.

F2

The F2 gene, residing on chromosome 11, encodes prothrombin (coagulation factor II), which is cleaved to form the serine protease thrombin during blood clotting. Genotyping F2 may be useful in identifying an increased risk of thrombosis due to prothrombin thrombophilia.

F5

The F5 gene, residing on the minus strand of chromosome 1, encodes the coagulation cofactor Factor 5. Genetic variations of F5 can lead to the formation of the Factor V Leiden protein, which cannot be inactivated normally by activated protein C (APC). The prolonged time for APC to inactivate Factor V Leiden leads to a prolonged clotting process, increasing the chance of developing abnormal blood clots. Genotyping F5 may be useful in identifying an increased risk of thrombosis due to Factor V Leiden thrombophilia.

GRIK4

The GRIK4 gene, residing on chromosome 11, encodes the glutamate receptor, ionotropic, kainate 4. It is involved in glutamate neurotransmission, with glutamate being the main neurotransmitter in the human brain.

HLA-A

The HLA-A gene, located at chromosome 6p22.1, codes for the major histocompatibility complex (MHC), class I, A molecules. This group of proteins, also called human leukocyte antigens (HLAs), are major players in normal immune response, specifically in adaptive immunity as their role is to present antigen peptides to T lymphocytes. Certain alleles are associated with severe allergic drug reactions. The HLA-A*31:01 allele has been associated with hypersensitivity reactions including Stevens-Johnson syndrome (SJS), maculopapular exanthema (MEP), and toxic epidermal necrolysis (TEN) following administration of certain drugs, particularly in Japanese, Korean and Caucasian populations. Pharmacogenomic guidelines published by professional associations exist for this gene and certain medications.

HLA-B

The HLA-B gene, located at chromosome 6p21.33, codes for the major histocompatibility complex (MHC) class I, B molecules. This group of proteins, also called human leukocyte antigens (HLAs) are major players in normal immune response, specifically in adaptive immunity as their role is to present antigen peptides to T lymphocytes. Certain alleles are associated with allergic drug reactions. In particular, HLA-B*15:02, HLA-B*57:01, and HLA-B*58:01 have been reported to be strongly associated with adverse reactions induced by certain medications. The HLA-B*15:02 allele has been strongly associated with drug-induced Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). Pharmacogenomic guidelines published by professional associations exist for this gene and certain medications.

HTR2A

The HTR2A gene, residing on chromosome 13, encodes the 5-hydroxytryptamine (serotonin) receptor 2A. This metabotropic receptor is found to be downregulated as a pharmacodynamic effect of certain medications. Variants in this gene are of therapeutic interest, in particular rs7997012 A>G.

HTR2C

The HTR2C gene, residing on the X chromosome, encodes the 5-hydroxytryptamine (serotonin) receptor 2C. Many agonists or antagonists of this metabotropic receptor cause downregulation.

IFNL4

The IFNL4 gene, residing on the minus strand of chromosome 19, encodes interferon, lambda 4, and was recently identified as important to the immune response to hepatitis C. The IFNL4 gene encodes the functional protein interferon, lambda 4 in most people from African origin; in about half of people from European origin and most of people from Asian origin, IFNL4 exhibits a variant that renders the gene non functional. Another variant in this gene, rs12979860 C>T, is associated with variability in hepatitis C sustained virologic response (SVR) rate. Until recently, rs12979860 C>T was thought to be located in a regulatory region upstream of IFNL3 (also referred to as IL28B). Therefore, this gene may also be referred to as IL28B or IFNL3. Pharmacogenomic guidelines published by professional associations exist for this gene and certain medications.

MTHFR (Available to providers as an optional, complimentary add-on to the RightMed test. MTHFR is not available to patients who purchase the test online (ordered through the independent physician network).)

The MTHFR gene, residing on the minus strand of chromosome 1, encodes the enzyme methylenetetrahydrofolate reductase. This enzyme is integrally involved in the DNA synthesis pathway, specifically the conversion of homocysteine to methionine through the methylation cycle of folic acid. Common variants in this gene, namely 677C>T (rs1801133) and 1298A>C (rs1801131), can disrupt this pathway, altering folic acid metabolism and/or leading to hyperhomocysteinemia. However, the American College of Medical Genetics and Genomics (ACMG) determined that MTHFR genotyping has minimal clinical utility as part of the routine evaluation for thrombophilia.

NUDT15

The NUDT15 gene, residing on the plus strand of chromosome 13, encodes nucleotide diphosphate linked moiety X (nudix)-type hydrolase motif 15. This type of protein catalyzes the hydrolysis of nucleoside diphosphates that are oxidized bases that can result in base mispairing during nucleic acid synthesis, and thereby cause translational errors. NUDT15 also inactivates thiopurine metabolites. Variants causing impaired NUDT15 activity, specifically rs116855232 C>T, are associated with a higher risk of thiopurine-related toxicities. Pharmacogenomic guidelines published by professional associations exist for this gene and certain medications.

OPRM1

The OPRM1 gene, residing on chromosome 6, encodes the mu-1 opioid receptor, a G protein-coupled receptor highly expressed in the spinal cord and other areas of the central nervous system. The rs1799971 A>G variant has been linked to sensitivity to the effects of certain substrates that act on the mu-1 opioid receptor.

SLC6A4

The SLC6A4 gene, residing on chromosome 17, encodes the serotonin transporter (SERT), or 5HTT, which is primarily involved in serotonin reuptake. A 44 base pair insertion in the promoter region of SLC6A4 gives rise to two variants: the "L" or long variant and the "S" or short variant. The L variant is associated with increased transcriptional activity of the serotonin transporter and is also linked to the rs25531 A>G variant, which further modulates transcription. The minor allele substitution A>G is almost always in phase with the L allele and has been postulated to decrease the transcriptional activity comparable to that of the S allele.

SLCO1B1

Located on the plus strand of chromosome 19, SLCO1B1 encodes the OATP1B1 transporter, which mediates the transport of substrates from the blood into the liver. SLCO1B1 variants affect transporter function, which may impact substrates of OATP1B1. Pharmacogenomic guidelines published by professional associations exist for this gene and certain medications.

TPMT

The TPMT gene, residing on the minus strand of chromosome 6, encodes the thiopurine S-methyltransferase enzyme that catalyzes S-methylation of heterocyclic sulfhydryl compounds in thiopurine metabolites. The methylation of these metabolites is the inactivation pathway, so decreased activity of this enzyme leads to toxicity due to overexposure to active medication. The 3A allele is comprised of the two SNPs rs1800460 and rs1142345, which are in high linkage disequilibrium, though may occur as individual variations, denoted as 3B and 3C respectively. Pharmacogenomic guidelines published by professional associations exist for this gene and certain medications.

UGT1A1

The UGT1A1 gene, located on chromosome 2, belongs to the family of UDP-glucuronosyltransferases, which mediate glucuronidation of target substrates. Glucuronidation renders the substrates water soluble, thus making them available for renal elimination. UGT1A1 is expressed in the liver, colon, intestine, and stomach. In the liver, it is the sole enzyme responsible for the metabolism of bilirubin, the hydrophobic breakdown product of heme catabolism. UGT1A1 also is involved in the metabolism of some medications. Pharmacogenomic guidelines published by professional associations exist for this gene and certain medications.

VKORC1

The VKORC1 gene, residing on the minus strand of chromosome 16, encodes vitamin K epoxide reductase (VKOR), which is a key enzyme in the Vitamin K cycle. VKOR mediates conversion of vitamin K-epoxide to Vitamin K, which is the rate-limiting step in physiological Vitamin K recycling. The availability of reduced Vitamin K is of particular importance for several coagulation factor proteins that require it as a cofactor. A single variant in VKORC1 promoter, rs9923231 G>A is of therapeutic interest.

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