Research — GeneOps

rs34579341 Intronic tag SNP in NEGR1 affecting neuronal cell adhesion, hippocampal neurogenesis, and monoaminergic neurotransmission — the G allele is associated with increased risk of major depression, anxiety disorders, and elevated BMI through shared hypothalamic circuits

Chromosome 1 Risk Allele G Category Mood & Behavior Tags Depression, Anxiety, Neuroplasticity, Mood, Appetite, Cognition

At the intersection of brain chemistry and body weight lies a gene most people have never heard of. NEGR1() encodes a molecular "social glue" that neurons use to recognize and bond with each other. Variants in NEGR1 have been replicated across virtually every major depression genome-wide association study (GWAS) of...

rs3790565 Intronic IL12RB2 variant associated with IL-12 signaling pathway variation and susceptibility to Th1-mediated autoimmune conditions including primary biliary cholangitis, allergic rhinitis, and endometriosis

Chromosome 1 Risk Allele C Category IBD & Mucosal Immunity Tags Autoimmune, Immune Function, T-Cell Regulation, Inflammation, Type 1 Diabetes, Autoimmunity

Interleukin-12 (IL-12) (https://pubmed.ncbi.nlm.nih.gov/10651948/) is one of the master switches of adaptive immunity. Its receptor on T and NK cells consists of two subunits: IL-12Rβ1 (encoded by IL12RB1) and IL-12Rβ2 (encoded by IL12RB2). The β2 subunit is the key signaling component — it carries the intracellular...

rs3804099 Synonymous variant in Toll-Like Receptor 2 affecting mRNA stability and splicing, associated with pulmonary tuberculosis susceptibility, cancer risk modification, and anti-TNF treatment response in inflammatory bowel disease

Chromosome 4 Risk Allele C Category Innate Immunity & Infection Defense Tags Innate Immunity, Infectious Disease, Immune & Gut, Inflammation, Immune System

Not all genetic variants that matter change an amino acid. Toll-Like Receptor 2 (TLR2)(https://www.ncbi.nlm.nih.gov/gene/7097) carries a synonymous variant — rs3804099, also written as T597C or 19216T/C — where a single nucleotide change in the coding sequence leaves the encoded amino acid identical but may not...

rs3816769 Intronic STAT3 variant where the T allele (reference, ~66%) increases risk for autoimmune thyroid disease, Crohn's disease, and lung cancer while the protective C allele correlates with higher STAT3 expression

Chromosome 17 Risk Allele T Category TNF, NF-kB & Inflammatory Cytokines Tags Autoimmune, Inflammation, JAK-STAT Signaling, IBD, Thyroid

STAT3(https://www.ncbi.nlm.nih.gov/gene/6774) occupies one of the most contested positions in immunology: it is simultaneously required for anti-inflammatory resolution and for driving the Th17 cell differentiation that underlies autoimmune pathology. This intronic variant at position 42,346,255 on chromosome 17...

rs3825942 Missense variant in the elastin-crosslinking enzyme LOXL1; the common G allele is one of the strongest known genetic risk factors for exfoliation syndrome and exfoliation glaucoma, a leading cause of secondary glaucoma worldwide

Chromosome 15 Risk Allele G Category Coronary Artery Disease & Atherosclerosis Tags Eye Health, Glaucoma, Connective Tissue, Extracellular Matrix, Cardiovascular, Inflammation, Aortic Wall, Elastin

Buried in the structure of every elastic tissue in your body — blood vessels, lungs, skin, eyes — is a protein called LOXL1 (Lysyl Oxidase-Like 1)(https://omim.org/entry/153700). Without functional LOXL1, elastin fibers fail to assemble properly, accumulating as disorganized fibrillar material in tissues throughout...

rs396514912 Protein-truncating frameshift deletion in obscurin; homozygous or compound heterozygous carriers lose functional obscurin in muscle, predisposing to recurrent, exercise-triggered rhabdomyolysis.

Chromosome 1 Risk Allele D Category Cardiomyopathy & Structural Heart Tags Muscle, Cardiovascular, Heart Disease, Exercise Recovery, Carrier Status, Genetic Counseling

Obscurin — encoded by OBSCN on chromosome 1q42 — is one of the largest proteins in the human body, a giant sarcomeric scaffold of nearly 800 kDa expressed in both cardiac and skeletal muscle. At the M-band and Z-disks of each sarcomere, obscurin tethers the sarcoplasmic reticulum to the...

rs397507172 Rare missense variant near the BTD active site (p.Val89Gly) that likely reduces biotinidase enzyme activity; heterozygous carriers have partial enzyme reduction while biallelic inheritance causes biotinidase deficiency

Chromosome 3 Risk Allele G Category Vitamins & Nutrient Absorption Tags B Vitamins, Micronutrients, Carrier Status, Genetic Counseling, Metabolism, Congenital

Every time your body breaks down a protein that used biotin as a cofactor, it produces biocytin — a biotin molecule still attached to a lysine residue. Recovering that biotin for reuse is the job of biotinidase(https://www.ncbi.nlm.nih.gov/books/NBK1322/). When biotinidase activity falls too low, biotin cannot be...

rs41295061 Regulatory variant in the IL2RA locus altering LEF1 transcription factor binding and soluble IL-2 receptor levels — the C allele increases type 1 diabetes susceptibility while the minor A allele raises Graves' disease risk

Chromosome 10 Risk Allele C Category Autoimmune Tolerance & T-Cell Regulation Tags Autoimmune, Type 1 Diabetes, T-Cell Regulation, Inflammation, Thyroid, Immune & Autoimmune

The interleukin-2 receptor alpha chain (IL-2Rα, also called CD25) sits at a critical junction in immune regulation. When IL-2 binds to its receptor on T cells, it triggers proliferation of both effector T cells that drive immune responses and regulatory T cells (Tregs) that shut them down. The balance between these...

rs490683 Promoter variant in the ghrelin receptor gene that disrupts NF-1 transcription factor binding; the G allele preserves the binding site and elevates GHSR expression, increasing appetite drive and resistance to dietary weight loss intervention

Chromosome 3 Risk Allele G Category Appetite & Obesity Tags Appetite, Obesity, Satiety, Metabolic Health, Hormones, Fat Metabolism

Ghrelin is the stomach's hunger signal — it rises before meals and drives appetite through the growth hormone secretagogue receptor (GHSR-1a)(https://pubmed.ncbi.nlm.nih.gov/28134808/). How much GHSR protein is available in the brain determines how strongly ghrelin can drive eating behavior. rs490683 sits in the...

rs519664 Intronic variant in TTC39B (9p22) that increases endometriosis susceptibility; the T allele carries an OR of 1.29 for endometriosis, with a stronger effect on stage III/IV disease (OR 1.35). TTC39B is a regulator of LXR protein stability that controls HDL cholesterol metabolism, suggesting the endometriosis association may act through lipid-mediated inflammatory signalling in the peritoneal environment.

Chromosome 9 Risk Allele T Category Endometriosis & Uterine Health Tags Endometriosis, Fertility, Women's Health, Inflammation, Lipid Metabolism, HDL Cholesterol

On the short arm of chromosome 9, an intronic variant in TTC39B(https://www.ncbi.nlm.nih.gov/gene/158865) has emerged as one of only a handful of robustly confirmed genetic risk factors for endometriosis. The rs519664 T allele increases endometriosis risk by approximately 29% and carries an even stronger association...