Methylation & Detox

Catalase promoter variant affecting hydrogen peroxide clearance and antioxidants defense capacity

DAO structural variant affecting enzyme activity and histamine degradation

Missense variant in methionine synthase reductase that impairs B12 reactivation, elevating homocysteine and reducing methylation capacity

Intronic variant near QDPR that affects BH4 recycling efficiency, influencing neurotransmitter synthesis and nitric oxide production

Phase I detoxification enzyme that activates polycyclic aromatic hydrocarbons and metabolizes estrogens; the Val variant increases catalytic activity, producing more reactive intermediates

Missense variant in the diamine oxidase enzyme that contributes to reduced histamine clearance from dietary sources

DAO structural variant near the catalytic domain affecting histamine degradation

Selenium-dependent antioxidant enzyme that neutralizes hydrogen peroxide; the Leu variant reduces enzyme activity and responsiveness to selenium

Histamine breakdown in blood and tissues - uses methyl groups from SAM

Folate transporter — how well folate gets into your cells

3'UTR variant in the reduced folate carrier that affects miR-595 binding, altering cellular folate and methotrexate uptake efficiency

3'UTR variant in the folate transporter gene affecting pemetrexed toxicity risk and potentially SLC19A1 expression

Phase I detoxification enzyme that hydroxylates estradiol to potentially genotoxic 4-hydroxyestradiol and activates environmental procarcinogens including PAHs

Vitamin D activation — converts D3 to 25(OH)D in the liver

Deep intronic MTR variant associated with reduced cleft lip/palate risk via lower methionine synthase expression

Deep intronic MTR variant associated with reduced cleft lip/palate risk via lower methionine synthase expression

Intronic MTR variant associated with altered methionine synthase expression and neural tube defect risk

Second functional variant in glutathione S-transferase Pi 1, reducing enzyme activity to ~80% of normal and defining key GSTP1 haplotypes that affect detoxification capacity and cancer susceptibility

Promoter variant that increases GGH expression, accelerating hydrolysis of intracellular folate polyglutamates and reducing cellular folate retention

HNMT structural variant - reduces enzyme stability and histamine clearance in tissues

Intronic variant in the cytoplasmic trifunctional folate enzyme MTHFD1, associated with increased risk of congenital heart defects and neural tube defects — particularly under low dietary folate conditions

Intronic variant in the de novo DNA methyltransferase DNMT3A, associated with altered stress-response methylation patterns and immune cell ratios

NAT2 acetylation speed tag SNP - marks rapid vs slow acetylator haplotypes

Synonymous variant in the folate transporter SLC19A1 — a haplotype tag linked to altered methotrexate response

3' UTR variant in the de novo DNA methyltransferase DNMT3A, associated with altered DNMT3A expression, modestly reduced gastric cancer risk in some populations, and interaction effects with folate intake and H. pylori infection on cancer and cardiovascular risk

Missense variant in methionine synthase reductase that raises homocysteine when vitamin B12 is low, affecting B12-dependent methylation efficiency

Vitamin D receptor — affects how well vitamin D activates cellular processes

MTRR cobalamin-reactivation variant — reduces B12 recycling efficiency and modulates folate-therapy response

Intronic MTRR tag SNP in a haplotype block where the C-allele variant associates with attenuated colorectal cancer survival benefit, modulated by pre-diagnostic alcohol intake

Intronic MTRR variant associated with reduced enzyme expression and impaired B12-dependent homocysteine remethylation

Phase II detoxification enzyme that conjugates glutathione to carcinogens, drugs, and oxidative stress products; this variant alters the active site geometry, changing substrate specificity

Downstream regulatory variant of glutathione synthetase (GSS) associated with reduced glutathione production capacity and poorer survival in chemotherapy-treated lung cancer patients

Slow acetylator variant affecting Phase II detoxification capacity

Nitric oxide production - reduced activity increases cardiovascular risk and oxidative stress

Phase II detoxification enzyme that reduces quinones and recycles CoQ10 to its active ubiquinol form; variant causes near-complete loss of enzyme activity

Signal-peptide missense variant that alters GGH subcellular targeting; C allele carriers show modestly lower plasma homocysteine and altered methotrexate pharmacokinetics

Second MTHFR variant affecting enzyme activity in the regulatory domain

Key enzyme for converting folate to its active methylfolate form

A synonymous variant in CBS affecting homocysteine metabolism and associated with modest changes in transsulfuration pathway activity

Phase II detoxification - acetylation of aromatic amines and certain medications

B12 recycling enzyme — regenerates active B12 for the methylation cycle

Synonymous MTRR variant (c.1911G>A) associated with congenital heart disease risk in offspring and maternal carriers, likely through regulatory effects on B12 recycling capacity

Methionine synthase — uses B12 to convert homocysteine to methionine

Intronic NOS3 variant associated with ankle-brachial index and peripheral arterial disease risk in hypertensive adults; G allele linked to lower peripheral blood flow

Alters one-carbon metabolism and folate distribution; influences cancer risk, folate levels, and cardiovascular disease in combination with MTHFR variants

Reduces intestinal folate hydrolase activity, impairing absorption of dietary polyglutamyl folates and lowering circulating folate available for methylation

Intronic variant in the intestinal folate-cleaving enzyme FOLH1 (GCPII); the C allele may reduce dietary folate bioavailability by altering GCPII expression or splicing

Histamine breakdown in gut - reduced activity means dietary histamine accumulates

NOS3 expression - controls how much eNOS enzyme is produced for nitric oxide synthesis

Intronic variant in the mitochondrial folate enzyme MTHFD1L, associated with altered one-carbon metabolism and Alzheimer's disease risk

Intronic tag variant in MTHFD1 in strong LD with the R653Q missense variant, affecting folate-dependent purine synthesis and maternal neural tube defect risk

Folate processing enzyme — reduced stability increases choline need

Intronic MTR variant associated with elevated homocysteine and B12-dependent methylation stress

Common synonymous variant in the CBS gene associated with reduced cardiovascular disease risk and enhanced response to folate supplementation

Intronic SLC19A1 variant that tags a haplotype affecting reduced folate carrier expression or splicing, influencing methotrexate transport efficiency and folate uptake across cell membranes

Intronic MTRR variant associated with colorectal cancer survival in interaction with alcohol consumption

Tag SNP proxy for GSTM1 gene deletion status — the most common pharmacogenomic variant worldwide, eliminating a Phase II detoxification enzyme that conjugates glutathione to environmental carcinogens

Missense variant in betaine-homocysteine methyltransferase that reduces enzyme throughput and influences homocysteine, betaine, and choline metabolite levels

Intronic MTRR variant associated with altered folate-pathway cancer risk and B12-dependent homocysteine metabolism

Intronic MTRR variant with sex-specific association with DNA methylation patterning in one-carbon metabolism

Intronic variant in the folate transporter gene associated with pemetrexed treatment outcomes and folate pathway efficiency in antifolate chemotherapy

Intronic SLC19A1 tag variant in strong LD with the G80A folate-transporter coding variant — marks reduced folate carrier efficiency

Intronic marker in the folate transporter gene; tags SLC19A1 haplotype variation associated with folate-dependent disease risk

Missense/splicing variant in sepiapterin reductase that reduces BH4 biosynthesis to ~15% of normal, impairing dopamine and serotonin production; causes dopa-responsive dystonia in biallelic carriers

Intronic MTR variant that tags the folate/B12-dependent remethylation locus and associates with altered one-carbon metabolic balance

Dopamine/catecholamine breakdown — affects stress response and methyl donor tolerance

Intronic variant in the histamine H1 receptor gene associated with altered receptor expression and histamine sensitivity

Primary mitochondrial antioxidant enzyme - variant reduces superoxide detoxification in mitochondria

Lactase persistence - ability to digest lactose (milk sugar) in adulthood

Intronic variant in betaine-homocysteine methyltransferase gene associated with selenium levels but no known disease risk

Pathogenic missense variant in the cobalamin-processing enzyme; homozygosity causes cobalamin C (cblC) disease with severe methylation and detoxification failure

Reduces intestinal GCPII enzyme activity by 53%, paradoxically raising circulating folate and lowering homocysteine by slowing folate catabolism in the gut

Complete deletion of the GSTT1 gene eliminating glutathione conjugation capacity for industrial solvents and certain carcinogens

Phosphatidylcholine production — affects dietary choline requirements

Regulatory variant affecting S-adenosylhomocysteine hydrolase expression, influencing methylation cycle balance and SAH clearance

Intronic variant in the mitochondrial folate enzyme MTHFD2, influencing one-carbon metabolism and linked to folate receptor autoantibody levels and embryonic development risk

Intronic NOS3 variant that alters splicing factor binding and is associated with blood pressure and cardiovascular risk, with effects that are amplified by physical activity

Regulatory variant that reduces reduced folate carrier protein expression, impairing folate uptake into cells