Research — GeneOps

rs11842874 Intronic variant in MCF2L that acts as a synovial eQTL — A allele carriers have higher MCF2L expression in joint tissue and elevated osteoarthritis risk across large joints

Chromosome 13 Risk Allele A Category Fitness & Body Tags Joints, Injury Risk, Inflammation, Fitness, Cartilage, Bone & Joint, Chronic Pain

Your joints don't simply wear down mechanically — they're governed by complex molecular signals that determine how the tissues lining them respond to stress, injury, and inflammation. MCF2L, a gene encoding a guanine nucleotide exchange factor(https://www.ncbi.nlm.nih.gov/gene/23263), turns out to be one of those...

rs121434282 Pathogenic missense variant in the MCAD enzyme causing medium-chain acyl-CoA dehydrogenase deficiency — an autosomal recessive disorder of mitochondrial fatty acid oxidation leading to hypoketotic hypoglycemia and metabolic crisis during fasting or illness

Chromosome 1 Risk Allele C Category Metabolic Enzymes & Rare Disorders Tags Fat Metabolism, Energy Metabolism, Carrier Status, Metabolic, Mitochondria, Genetic Counseling

Every cell that depends on fat for fuel must first strip two-carbon acetyl groups from fatty acids inside mitochondria, a process called beta-oxidation(). The medium-chain step of this pathway — handling fatty acids with 6–12 carbons — is catalysed exclusively by medium-chain acyl-CoA dehydrogenase (MCAD), the...

rs121918384 Frameshift deletion in APOB causing truncated apolipoprotein B-100, reducing LDL production and impairing fat-soluble vitamin absorption; pathogenic for familial hypobetalipoproteinemia

Chromosome 2 Risk Allele D Category Cholesterol & Lipoproteins Tags Fat Metabolism, Cholesterol, Cardiovascular, Liver Health, Vitamins, Carrier Status

Apolipoprotein B-100 (ApoB-100)(https://pubmed.ncbi.nlm.nih.gov/1619387/) is one of the largest proteins in the human body, spanning 4,536 amino acids. The rs121918384 variant deletes two nucleotides (CA) at coding position c.5566–5567 of the APOB gene, shifting the reading frame at amino acid 1856 and generating a...

rs121918393 Ultra-rare APOE3 missense variant that dramatically reduces HSPG binding and tau propagation, conferring near-complete resistance to Alzheimer's disease in the homozygous state and a modest protective delay in heterozygotes

Chromosome 19 Risk Allele C Category Longevity & Aging Tags Alzheimer's, Longevity, Aging, Cardiovascular, Cholesterol, Inflammation

Apolipoprotein E (ApoE) is the most powerful common genetic determinant of Alzheimer's disease risk in the human genome. The APOE4 allele increases lifetime risk 3–4 fold in heterozygotes and 8–12 fold in homozygotes; APOE2 is modestly protective. But in 2019, a third piece of the puzzle emerged: an ultra-rare...

rs121918476 Pathogenic PROS1 missense variant in the SHBG-like domain that impairs protein S secretion; heterozygotes have reduced protein S activity and a substantially elevated risk of venous thromboembolism requiring specialist evaluation

Chromosome 3 Risk Allele A Category Von Willebrand & Anticoagulant Proteins Tags Thrombophilia, Blood Clotting, Cardiovascular, Blood Thinners, Thrombosis

Protein S is one of the body's key natural anticoagulants. It works as a cofactor for activated protein C, which inactivates the clotting factors that would otherwise sustain a thrombus. When protein S is reduced or absent, activated protein C loses much of its braking power over the coagulation cascade — the...

rs12478601 Intronic variant in THADA (thyroid adenoma associated) on chromosome 2p21; the C allele is a PCOS risk allele at the THADA locus (companion tag SNP to rs13429458, the original Han Chinese GWAS lead), tagging a haplotype that reduces THADA-mediated SERCA uncoupling, impairing ER calcium homeostasis in pancreatic beta cells and predisposing to PCOS and insulin secretion defects

Chromosome 2 Risk Allele C Category Fertility & Ovarian Function Tags PCOS, Fertility, Insulin Resistance, Reproductive Health, Hormones, Metabolic Syndrome

At chromosome 2p21, a gene called THADA(https://www.ncbi.nlm.nih.gov/gene/63892) harbours one of the most robustly replicated genetic loci for polycystic ovary syndrome (PCOS). The rs12478601 C allele was first identified as a PCOS risk variant in 2011 and has since been confirmed across multiple ethnic groups,...

rs12730735 Intronic PTPN22 haplotype tag variant that refines autoimmune risk stratification beyond R620W and associates independently with Hashimoto's thyroiditis in Asian populations

Chromosome 1 Risk Allele C Category Autoimmune Tolerance & T-Cell Regulation Tags Autoimmune, Immune System, Rheumatoid Arthritis, Thyroid, T-Cell Regulation, B-Cell Signaling

PTPN22 encodes lymphoid tyrosine phosphatase (LYP), the master negative regulator of T-cell and B-cell activation. While the R620W missense variant (rs2476601) is the most studied variant in this gene, the PTPN22 locus harbors additional variation that modifies autoimmune risk in ways R620W alone cannot capture....

rs1279683 Intronic variant in the SVCT2 vitamin C transporter — G allele associated with lower plasma vitamin C, higher glaucoma risk, and modified cognitive decline risk in APOE4 carriers

Chromosome 20 Risk Allele G Category Vitamins & Nutrient Absorption Tags Vitamin C, Vitamins, Eye Health, Micronutrients, Cognition

Vitamin C cannot synthesize itself — it must be obtained from food, absorbed by the gut, and then actively transported into individual cells. That last step is controlled by SVCT2(). A common intronic variant at rs1279683 in SLC23A2 has been associated with meaningfully lower plasma vitamin C concentrations and a...

rs12870438 Intronic variant in the immune-response gene EPSTI1, associated in recessive models with reduced sperm concentration, total sperm count, sperm motility, and azoospermia/oligospermia risk in men.

Chromosome 13 Risk Allele A Category Endometriosis & Uterine Health Tags Male Fertility, Sperm Quality, Fertility, Reproductive Health, Immune & Gut

The testes occupy a paradoxical position in the immune system: they must shield developing sperm — which display "foreign" surface antigens not seen by the immune system before puberty — from attack, while still defending against microbial infection. EPSTI1 (epithelial stromal interaction 1) is an...

rs12917707 Uromodulin promoter variant — strongest GWAS signal for chronic kidney disease risk, affecting salt handling and blood pressure via NKCC2

Chromosome 16 Risk Allele G Category Uric Acid & Kidney Function Tags Kidney Function, Hypertension, Cardiovascular, Kidney Stones, Salt Sensitivity

The UMOD gene encodes uromodulin(https://pubmed.ncbi.nlm.nih.gov/19430482/), a glycoprotein that plays central roles in kidney tubular function, salt handling, innate immunity, and protection against urinary tract infections. The rs12917707 variant sits in the promoter...