Research — GeneOps

rs1064608 Missense variant in MTCH2 that reduces mitochondrial metabolic efficiency, increasing risk for obesity and sleep disruption through impaired energy substrate switching

Chromosome 11 Risk Allele C Category Hormones & Sleep Tags Sleep, Mitochondria, Obesity, Energy Metabolism, Metabolic, Cardiovascular

The mitochondria in your cells do not burn a fixed fuel. Depending on what you have eaten, your activity level, and the time of day, they switch between glucose and fatty acids — a flexibility that is central to healthy metabolism and, it turns out, to restorative sleep. MTCH2 (mitochondrial carrier homolog...

rs1064793917 Frameshift deletion in SERPING1 (p.Lys390fs) abolishing C1-inhibitor production — causes hereditary angioedema Type I with recurrent life-threatening swelling attacks via uncontrolled bradykinin release

Chromosome 11 Risk Allele D Category B-Cell Immunity & Antibody-Mediated Disease Tags Complement System, Complement, Autoimmune, Inflammation, Genetic Counseling, Innate Immunity, Hereditary Angioedema

The SERPING1 gene encodes C1-inhibitor (C1-INH)(https://www.ncbi.nlm.nih.gov/gene/710), keeping the body's inflammatory cascade under strict control. When C1-INH is absent or non-functional, the contact activation pathway generates bradykinin — a potent peptide that opens vascular endothelial junctions and forces...

rs10773771 A 3' UTR variant in PIWIL1 that alters miRNA binding to the transcript and modifies PIWIL1 expression; the T allele is associated with decreased epithelial ovarian cancer susceptibility in southern Chinese women, consistent with PIWIL1's role in piRNA-mediated genome stability in ovarian follicular cells

Chromosome 12 Risk Allele C Category Fertility & Ovarian Function Tags Fertility, Ovarian Reserve, Cancer Risk, Genomic Stability, Women's Health, Reproductive Health

PIWIL1 (also known as HIWI) is one of four human PIWI proteins, a conserved family of RNA-guided genome guardians that silence transposable elements in germ cells. These mobile genetic elements(https://pubmed.ncbi.nlm.nih.gov/34489571/) are particularly threatening in the ovary, where follicular cells and their...

rs10794648 Intergenic regulatory variant near IFNLR1 that contacts GRHL3 via chromatin looping in keratinocytes — the C (risk) allele is associated with psoriasis susceptibility, linking type III interferon receptor signaling and epidermal barrier transcription factor control at the same locus

Chromosome 1 Risk Allele C Category Interferon Signaling & Systemic Autoimmune Tags Autoimmune, Psoriasis, Skin Health, Interferon, Innate Immunity, Skin

A regulatory variant on chromosome 1p36.11 sits quietly 3,757 base pairs upstream of IFNLR1(https://pubmed.ncbi.nlm.nih.gov/26200010/). For years this locus was attributed to IFNLR1 based on proximity alone. Then a 2021 chromatin interactome study(https://pubmed.ncbi.nlm.nih.gov/33607115/) rewrote the story: in...

rs10984447 Intronic variant in DBC1 (DBCCR1/BRINP1) at 9q33.1 associated with multiple sclerosis susceptibility; the common A allele increases MS risk, while the minor G allele is protective

Chromosome 9 Risk Allele A Category TNF, NF-kB & Inflammatory Cytokines Tags Multiple Sclerosis, Autoimmune, Immune & Autoimmune, Inflammation, Neuroinflammation, Neurological Risk

The DBC1 gene(https://www.ncbi.nlm.nih.gov/gene/1620) sits at one of the genomic regions repeatedly flagged by multiple sclerosis genome-wide association studies. Its most common variant, rs10984447, illustrates an unusual feature of MS genetics: the reference (major) allele is the susceptibility allele, and rarer...

rs11057830 Intronic variant in SCARB1 that affects SR-BI receptor function and the intestinal and hepatic uptake of fat-soluble vitamin E (alpha-tocopherol) and carotenoids from HDL particles

Chromosome 12 Risk Allele G Category Cholesterol & Lipoproteins Tags Vitamin E, Vitamins, Fat Metabolism, Antioxidants, Cardiovascular, HDL Cholesterol

Every fat-soluble micronutrient you absorb --- vitamin E, beta-carotene, lutein, zeaxanthin --- faces a double barrier: the intestinal wall and then the liver. At both sites, a single receptor protein called SR-BI() (scavenger receptor class B type I, encoded by SCARB1) acts as the primary gateway. SR-BI is...

rs11265611 Intronic IL6R variant in LD with the IL-6 receptor signaling locus; G allele associates with higher IL-6 pathway activity, elevated CRP, and increased atrial fibrillation risk

Chromosome 1 Risk Allele G Category Coronary Artery Disease & Atherosclerosis Tags Arrhythmia, Inflammation, Cardiovascular, Heart Disease

The interleukin-6 receptor (IL-6R) encoded by IL6R is the gateway through which interleukin-6, one of the body's primary inflammatory messengers, communicates its instructions to target cells. When IL-6 binds its receptor, it triggers STAT3 phosphorylation(https://pubmed.ncbi.nlm.nih.gov/), driving the liver to...

rs1148259 Synonymous variant in the 3′ UTR of ANKRD30A associated with altered circulating sphingolipid levels in a metabolomics genome-wide association study

Chromosome 10 Risk Allele C Category Metabolic Enzymes & Rare Disorders Tags Micronutrients, Lipid Metabolism, Metabolic, Cardiovascular, Cholesterol

When geneticists search for the DNA variants that shape our metabolic chemistry, they sometimes find signals in unexpected places. rs1148259 sits in the 3′ untranslated region() of the ANKRD30A gene on chromosome 10 — technically a synonymous position that leaves the encoded protein unchanged, yet it emerged as one...

rs1155563 Third independent intronic tag SNP in the vitamin D binding protein gene, influencing circulating 25-hydroxyvitamin D levels and supplementation response

Chromosome 4 Risk Allele C Category Vitamin D Metabolism Tags Vitamin D, Bone Health, Micronutrients, Diet, Mineral Metabolism

The GC gene() has long been known as the dominant genetic determinant of circulating vitamin D levels in the blood. Most research has focused on two functional missense variants — rs7041 (Asp432Glu) and rs4588 (Thr436Lys) — and one intronic GWAS tag (rs2282679). rs1155563 is a fourth GC region variant that behaves...

rs116098458 Rare intronic variant in a lncRNA antisense to KIF2B (chromosome 17q22), identified in the Ruth et al. 2021 Nature GWAS as associated with age at natural menopause; KIF2B encodes a kinesin-13 microtubule depolymerase essential for bipolar spindle assembly during oocyte meiosis

Chromosome 17 Risk Allele T Category Gamete Quality & DNA Repair Tags Fertility, Ovarian Reserve, Reproductive Health, Menopause, Apoptosis, Women's Health

The fidelity of chromosome segregation during female meiosis depends critically on the construction and function of the meiotic spindle — the microtubule apparatus that physically moves chromosomes to opposite poles of the oocyte. KIF2B (Kinesin Family Member 2B) is a member of the kinesin-13 family of microtubule...