Research — GeneOps

rs397507563 Frameshift deletion in the third filaggrin repeat domain — the third most common European FLG null allele, causing filaggrin haploinsufficiency in carriers and complete filaggrin deficiency in compound heterozygotes with R501X or 2282del4

Chromosome 1 Risk Allele D Category Skin & Eyes Tags Skin Health, Immune & Gut, Inflammation, Food Sensitivity, Asthma, Immune System

A single protein — filaggrin — is responsible for assembling the skin's outermost waterproof layer and generating the natural moisturizing factor (NMF)(https://pubmed.ncbi.nlm.nih.gov/16810297/) that protects against allergen penetration, infection, and water loss. The FLG gene encodes a massive precursor —...

rs403016 Rare missense variant in Fc gamma receptor IIIa (CD16a) causing an Arg36Ser substitution, associated with systemic lupus erythematosus susceptibility in Chinese family-based studies

Chromosome 1 Risk Allele G Category B-Cell Immunity & Antibody-Mediated Disease Tags Innate Immunity, Autoimmune, Lupus, Immune Response, Immune System

Your immune system deploys natural killer (NK) cells(https://pubmed.ncbi.nlm.nih.gov/21370226/) as front-line defenders. On the surface of NK cells sits a receptor called FcgammaRIIIa (CD16a), encoded by the FCGR3A gene. This receptor grabs the tail end (Fc region) of IgG antibodies already bound to target cells —...

rs419788 Intronic SKIV2L variant in the MHC class III region; the T allele tags an independent susceptibility signal for systemic lupus erythematosus separate from HLA-DRB1

Chromosome 6 Risk Allele T Category Interferon Signaling & Systemic Autoimmune Tags Lupus, Autoimmune, MHC Antigen Presentation, Inflammation, HLA, Complement, SLE, MHC Class III

The major histocompatibility complex (MHC) on chromosome 6 is the most gene-dense immune region in the human genome, and its class III segment — wedged between the complement genes and the classical HLA loci — contains a cluster of RNA surveillance genes that few people know about. One of them, SKIV2L (Superkiller...

rs4473653 Intronic SLC2A9 variant in a third independent haplotype block within the GLUT9 urate transporter locus; the A allele (reference, ~57% European frequency) is associated with elevated serum uric acid, while the protective G allele (~43% European) improves renal urate clearance — with stronger effects in women — and reduces dietary fructose-induced urate spikes

Chromosome 4 Risk Allele A Category Uric Acid & Kidney Function Tags Gout, Uric Acid, Cardiovascular, Diet, Kidney Function

The SLC2A9 gene is the single largest genetic determinant of serum uric acid levels in humans, encoding GLUT9(https://pubmed.ncbi.nlm.nih.gov/18327257/). What is less widely appreciated is that the SLC2A9 locus contains several genetically independent signals — distinct intronic haplotype blocks, each contributing...

rs55714927 Synonymous coding variant (Lys89Lys) in the asialoglycoprotein receptor 1 gene that acts as an sQTL and eQTL, reducing ASGR1 expression and associating with lower LDL and non-HDL cholesterol at genome-wide significance and reduced coronary artery disease risk

Chromosome 17 Risk Allele T Category Atherogenic Lipoproteins Tags Cardiovascular, LDL Cholesterol, Cholesterol, Atherosclerosis, Liver, Heart Disease

The liver's job includes clearing old and damaged glycoproteins from the bloodstream. This housekeeping task is performed by the asialoglycoprotein receptor (ASGR)(https://pubmed.ncbi.nlm.nih.gov/27192541/). One of its subunits, encoded by ASGR1 on chromosome 17, turns out to be a key modulator of plasma cholesterol...

rs5985 Missense variant in Factor XIII A subunit; the Leu34 allele accelerates thrombin-driven FXIII activation, producing finer and more fibrinolysis-susceptible fibrin clots — moderately protective against venous thromboembolism and myocardial infarction, with context-dependent effects at elevated fibrinogen

Chromosome 6 Risk Allele A Category Coagulation & Clotting Factors Tags Blood Clotting, Thrombosis, Fibrinolysis, Cardiovascular, Thrombophilia, Venous Health

Every blood clot is a scaffold of cross-linked fibrin, and the enzyme that builds that scaffold is Factor XIII-A (F13A1)(https://pubmed.ncbi.nlm.nih.gov/22197181/). The Val34Leu variant sits just three amino acids upstream of Factor XIII's thrombin cleavage site — close enough that the single valine-to-leucine swap...

rs6536991 Intronic UCP1 variant — the C allele is associated with reduced overweight risk and lower BMI, likely by influencing UCP1 expression in brown adipose tissue

Chromosome 4 Risk Allele T Category Liver Fat Tags Thermogenesis, Brown Fat, Fat Metabolism, Obesity, Energy Metabolism

Brown adipose tissue (BAT) is one of the body's most metabolically active organs. Unlike white fat, which stores energy, brown fat burns calories to generate heat — a process called non-shivering thermogenesis(). The master effector of this process is uncoupling protein 1...

rs72755295 Intronic regulatory variant in EXO1 (exonuclease 1) that increases EXO1 enhancer activity; the G allele is associated with earlier age at natural menopause (ovarian ageing) and elevated breast cancer risk through upregulated EXO1 expression

Chromosome 1 Risk Allele G Category Gamete Quality & DNA Repair Tags Fertility, Ovarian Reserve, Menopause, DNA Repair, Mismatch Repair, Breast Cancer

Exonuclease 1 (EXO1) is a multifunctional nuclease that participates in two of the most consequential DNA maintenance processes in human biology: mismatch repair (MMR)(https://pubmed.ncbi.nlm.nih.gov/26686657/) and meiotic recombination — the process that generates genetic diversity and ensures proper chromosome...

rs7940244 Intronic NADSYN1 variant in the DHCR7/NADSYN1 vitamin D locus; T allele tags the lower-vitamin-D haplotype, reducing 7-dehydrocholesterol availability for skin vitamin D3 synthesis

Chromosome 11 Risk Allele T Category Vitamin D Metabolism Tags Vitamin D, Bone Health, Immune System, Cholesterol, Cardiovascular

Every cell in your skin can convert sunlight into vitamin D — but only if it has enough 7-dehydrocholesterol (7-DHC) to work with. The problem is that 7-DHC is a shared substrate: the same molecule that becomes vitamin D3 in sunlight can also be converted to cholesterol by the enzyme DHCR7 (7-dehydrocholesterol...

rs944289 Regulatory variant near FOXE1 at 14q13.3 that reduces PTCSC3 tumor suppressor expression, increasing risk of papillary thyroid cancer

Chromosome 14 Risk Allele T Category Cancer Risk Tags Thyroid, Cancer Risk, Hormones & Thyroid

Tucked into the intergenic region of chromosome 14q13.3, rs944289 was one of the first common variants identified as a thyroid cancer susceptibility locus. Discovered in a landmark Icelandic GWAS(https://pubmed.ncbi.nlm.nih.gov/19198613/) alongside rs965513 on chromosome 9, this variant does not sit within a...