Research — GeneOps

rs2241879 Intronic ATG16L1 variant in tight LD with the T300A coding variant; the G risk allele tags a haplotype that sensitizes the ATG16L1 protein to caspase-3-mediated degradation, impairing autophagy and Paneth cell antimicrobial function, raising risk for Crohn's disease

Chromosome 2 Risk Allele G Category IBD & Mucosal Immunity Tags Autophagy, Crohn's Disease, Inflammatory Bowel Disease, Paneth Cells, Immune & Gut, Gut Microbiome

ATG16L1 (Autophagy Related 16 Like 1)(https://www.ncbi.nlm.nih.gov/gene/55054) is one of the strongest and most replicated genetic risk loci for Crohn's disease(https://en.wikipedia.org/wiki/Crohn%27sdisease). rs2241879 is an intronic variant within ATG16L1 on chromosome 2q37.1 that sits in tight linkage...

rs2298566 Missense variant in sorting nexin 19 that alters endolysosomal positioning at the ER membrane; the A allele was associated with elevated coronary heart disease risk in a prospective cohort study and confirmed as one of five common risk variants in the ARIC validation

Chromosome 11 Risk Allele A Category Coronary Artery Disease & Atherosclerosis Tags Heart Disease, Atherosclerosis, Cardiovascular, Inflammation, Lipid Metabolism

Deep inside every cell, a network of membrane-bound organelles sorts, degrades, and recycles proteins and lipids(https://pubmed.ncbi.nlm.nih.gov/34315878/). SNX19 — Sorting Nexin 19 — is a molecular tether that anchors endolysosomes to the endoplasmic reticulum (ER), keeping them clustered near the cell nucleus...

rs2371365 Intronic variant in the presynaptic scaffold gene PCLO linked to altered monoaminergic neurotransmission, increased depression and anxiety risk, and heightened amygdala reactivity to emotional stimuli

Chromosome 7 Risk Allele C Category Mood & Behavior Tags Depression, Anxiety, Mood, Neurotransmitters, Brain Health, Antidepressants

Every time a neuron signals its neighbor, a precisely choreographed event unfolds at the presynaptic terminal: calcium floods in, synaptic vesicles fuse with the membrane, and neurotransmitters flood the synapse. Orchestrating this entire process is a giant scaffolding protein called...

rs2488457 Promoter variant in PTPN22 that alters gene expression and modulates autoimmune susceptibility, particularly in Asian populations where it acts independently of the R620W coding variant

Chromosome 1 Risk Allele G Category Autoimmune Tolerance & T-Cell Regulation Tags Autoimmune, T-Cell Regulation, Immune System, Rheumatoid Arthritis, Type 1 Diabetes, Ancestry-Specific

The PTPN22 gene is best known for its coding variant rs2476601 (R620W), the strongest non-HLA risk factor for autoimmunity in Europeans. But the gene harbors a second clinically relevant variant in its promoter region: -1123GC (rs2488457), located 1,123 base pairs upstream of the transcription start site. Unlike...

rs28940578 Exon 10 missense variant in the inflammasome regulator pyrin, converting methionine to isoleucine at codon 694; one of five founder FMF mutations, associated with mild-to-moderate familial Mediterranean fever, colchicine responsiveness, and lower amyloidosis risk than M694V — particularly prevalent in East Asian FMF patients and Lebanese founder lineages

Chromosome 16 Risk Allele T Category TNF, NF-kB & Inflammatory Cytokines Tags Innate Immunity, Inflammation, Autoimmune, Ancestry-Specific, Amyloidosis, Carrier Status

Familial Mediterranean fever(https://pubmed.ncbi.nlm.nih.gov/11464238/) is the most common hereditary periodic fever in the world. The MEFV gene encodes pyrin, a protein expressed in myeloid cells that normally suppresses inflammasome activation in the absence of microbial toxins. Of the hundreds of documented MEFV...

rs28942074 Pathogenic missense variant in the hepatic copper transporter ATP7B that abolishes protein trafficking to the trans-Golgi network; the most common Wilson disease mutation in East Asian populations, accounting for ~29% of pathogenic ATP7B alleles in Chinese patients; homozygotes and compound heterozygotes develop progressive copper accumulation causing liver disease, neurological symptoms, and Kayser-Fleischer rings; heterozygous carriers are asymptomatic but can transmit the disease if their reproductive partner also carries an ATP7B pathogenic variant

Chromosome 13 Risk Allele A Category Vitamins & Nutrient Absorption Tags Metal Metabolism, Liver Disease, Carrier Status, Genetic Counseling, Minerals, Liver

Copper is an essential mineral — a cofactor for enzymes involved in energy production, antioxidant defence, and neurotransmitter synthesis — yet it is toxic when it accumulates. The liver is the body's copper thermostat: it absorbs dietary copper from the portal circulation, uses what is needed, loads the rest onto...

rs2922126 Upstream regulatory variant near the ghrelin receptor gene; the A allele is associated with abdominal adiposity and metabolic syndrome risk in women through altered GHSR expression

Chromosome 3 Risk Allele A Category Appetite & Obesity Tags Appetite, Obesity, Metabolic Health, Hormones, Fat Distribution, Satiety

Every time your stomach empties, it sends a chemical distress signal — a 28-amino-acid peptide called ghrelin — up the bloodstream and into the brain. Ghrelin(https://pubmed.ncbi.nlm.nih.gov/24100676/) docks onto its receptor, GHSR-1a (growth hormone secretagogue receptor type 1a), triggering appetite and promoting...

rs3213094 Intronic IL12B variant in linkage with the promoter-regulatory haplotype; T allele is protective against psoriasis and associated with better ustekinumab (anti-p40) response

Chromosome 5 Risk Allele C Category Psoriasis & Spondyloarthropathy Tags Immune & Autoimmune, Psoriasis, Inflammation, Inflammatory Bowel Disease, Biologic Therapy, Skin

The IL12B gene(https://www.omim.org/entry/161561). IL-12 drives Th1 differentiation and IFN-γ production; IL-23 expands Th17 cells and IL-17 production. Both pathways converge on psoriatic skin inflammation and inflammatory bowel disease. rs3213094 is an intronic variant at chr5:159323761 (GRCh38) within the IL12B...

rs35947132 Common perforin variant that reduces cytolytic activity by ~50%, acting as a susceptibility factor for HLH when combined with a second PRF1 loss-of-function allele

Chromosome 10 Risk Allele A Category Innate Immunity & Infection Defense Tags Innate Immunity, Immune Defense, Immune Response, Autoimmune, Infection Risk, Cancer Risk

Perforin is the immune system's master assassin molecule. When a cytotoxic T lymphocyte (CTL) or natural killer (NK) cell locks onto a virus-infected cell or tumor cell, it releases perforin from secretory granules. Perforin polymerizes on the target cell membrane, punching transmembrane...

rs3750243 Regulatory variant 2 kb upstream of EIF4EBP1 (encoding 4E-BP1, a direct mTOR effector); the C allele is associated with later age at menopause (beta +0.376 years per allele) and higher circulating AMH, consistent with slower primordial follicle activation through attenuated mTOR signalling

Chromosome 8 Risk Allele G Category Fertility & Ovarian Function Tags Fertility, Menopause, Ovarian Reserve, mTOR Pathway, Reproductive Health, Women's Health

Inside every ovary sits a dormant population of primordial follicles — the finite reserve of egg precursors you are born with. How quickly this pool depletes determines when your fertility naturally declines and when menopause arrives. One of the most important molecular gatekeepers of this process is...