Research — GeneOps

rs199971687 Pathogenic splice acceptor variant in MMAB that abolishes adenosylcobalamin synthesis, causing methylmalonic aciduria cblB type when two loss-of-function alleles are inherited

Chromosome 12 Risk Allele T Category Vitamins & Nutrient Absorption Tags Vitamin B12, B Vitamins, Carrier Status, Methylation & Detox, Metabolic

The MMAB gene encodes ATP:cob(I)alamin adenosyltransferase (ATR)(), a critical last step in the mitochondrial vitamin B12 processing pathway. When both copies of MMAB are non-functional, methylmalonyl-CoA cannot be converted to succinyl-CoA, and methylmalonic acid accumulates to toxic levels in blood, urine, and...

rs2230926 Missense variant in the A20 ubiquitin-editing enzyme that weakens NF-kB negative feedback, increasing susceptibility to autoimmune and inflammatory diseases

Chromosome 6 Risk Allele G Category TNF, NF-kB & Inflammatory Cytokines Tags Autoimmune, Inflammation, Gut Barrier, Lupus, Rheumatoid Arthritis, Immune & Gut

Your immune system maintains a delicate balance between fighting threats and attacking your own body. At the center of this balance sits A20, a protein encoded by the TNFAIP3 gene(https://pubmed.ncbi.nlm.nih.gov/19643665/) that functions as a master brake on inflammation. The F127C variant (rs2230926) weakens this...

rs2256774 Intronic IL2RA variant that modulates soluble IL-2RA shedding and Treg signaling; independently associated with psoriasis susceptibility and contributes to the IL2RA locus autoimmune risk signal

Chromosome 10 Risk Allele T Category Autoimmune Tolerance & T-Cell Regulation Tags Autoimmune, Immune & Autoimmune, Inflammation, Psoriasis, Skin, Multiple Sclerosis

The IL2RA gene(https://www.ncbi.nlm.nih.gov/gene/3559) harbors multiple independent regulatory variants that together determine how finely tuned your immune system's self-tolerance machinery is. rs2256774 is an intronic variant in IL2RA that operates in the same regulatory neighbourhood as the better-studied...

rs2268363 Intronic variant in the FSH receptor gene; identified in a genome-wide association study as associated with post-radiotherapy erectile dysfunction risk in African-American men; located in close proximity to rs2268361 and serves as an FSHR haplotype tag with potential relevance to gonadotropin signaling

Chromosome 2 Risk Allele G Category Fertility & Ovarian Function Tags Fertility, Reproductive Health, Gonadotropins, IVF, Male Fertility, Hormones

The follicle-stimulating hormone receptor (FSHR) is one of the most important genes in reproductive medicine. Encoded on chromosome 2q16.2 with the gene running on the minus strand, FSHR mediates the action of follicle-stimulating hormone (FSH) in both females — where it drives granulosa cell maturation,...

rs228918 Regulatory variant upstream of the iron-homeostasis gene TMPRSS6, associated with variation in serum iron, transferrin saturation, hemoglobin, and soluble transferrin receptor across populations

Chromosome 22 Risk Allele C Category Iron & Mineral Transport Tags Iron, Vitamins, Erythropoiesis, Minerals

The TMPRSS6 gene encodes matriptase-2(), the master regulator of hepcidin(). When matriptase-2 functions normally, it suppresses hepcidin, allowing dietary iron to cross from the gut into the bloodstream. When matriptase-2 activity is reduced — whether from coding variants like rs855791 or regulatory variants that...

rs230523 Intronic variant in the master immune transcription factor NF-κB1, associated with modestly increased susceptibility to common infections

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

Every time your body encounters a pathogen — a bacterium, virus, or fungus — a molecular alarm system fires inside your immune cells. At the heart of this alarm is NF-κB (Nuclear Factor kappa-light-chain-enhancer of activated B cells)(https://pubmed.ncbi.nlm.nih.gov/34473196/), and NFKB1 encodes its critical...

rs2364480 Synonymous coding variant in the lymphotoxin-beta receptor gene associated with altered LTBR signaling capacity and susceptibility to IgA nephropathy; the LTBR locus on chromosome 12p13 is independently implicated in ankylosing spondylitis at genome-wide significance

Chromosome 12 Risk Allele C Category Psoriasis & Spondyloarthropathy Tags Autoimmune, Inflammation, Autoimmunity, Immune Function, Lymphatic, Innate Immunity

The lymphotoxin-beta receptor (LTBR, also known as TNFRSF3) is a cell-surface receptor of the tumor necrosis factor receptor superfamily(https://www.ncbi.nlm.nih.gov/books/NBK6515/) that governs how your immune cells build and maintain organized lymphoid architecture. LTBR sits at the hub of a signaling network that...

rs2414096 Intronic CYP19A1 polymorphism associated with variation in aromatase expression and androgen-to-estrogen conversion; the G allele is linked to lower aromatase activity and elevated androgen levels in reproductive tissues, with population-specific associations to PCOS risk

Chromosome 15 Risk Allele G Category Reproductive Hormones Tags Aromatase, PCOS, Fertility, Reproductive Health, Estrogen, Steroid Hormones

Aromatase(https://www.ncbi.nlm.nih.gov/gene/1588) is expressed in the ovaries, adipose tissue, bone, brain, and adrenal glands. Because it is the only enzyme capable of estrogen synthesis in vertebrates, even small changes in its expression can meaningfully shift the androgen–estrogen balance. The rs2414096 variant...

rs244715 Intronic variant in ZNF346 (chromosome 5q35.2), a proxy SNP for the UIMC1/RAP80 DNA-repair locus; the G allele may be associated with earlier age at natural menopause and modestly increased susceptibility to primary ovarian insufficiency

Chromosome 5 Risk Allele G Category Gamete Quality & DNA Repair Tags Ovarian Reserve, Menopause, Fertility, Reproductive Health, DNA Repair

The chromosome 5q35.2 region was one of four genome-wide significant loci first identified in the landmark 2009 GWAS of 17,438 women(https://pubmed.ncbi.nlm.nih.gov/19448621/). At the center of this locus sits UIMC1 (also called RAP80) — a BRCA1 adaptor protein — and nearby, approximately 71 kb downstream, ZNF346...

rs267607326 Pathogenic missense variant in the VWF D3 domain causing von Willebrand disease type 2A/IIE — the most common D3-cluster mutation — leading to loss of high-molecular-weight multimers, impaired hemostasis, and variable mucocutaneous bleeding

Chromosome 12 Risk Allele C Category Von Willebrand & Anticoagulant Proteins Tags Blood Clotting, Cardiovascular, Thrombophilia, Carrier Status, Women's Health

Von Willebrand factor (VWF) is a multimeric glycoprotein essential for primary hemostasis. Under shear stress — in the turbulent flow of small vessels or at a wound site — ultra-large VWF multimers unfurl to capture platelets via their GPIb receptors, forming the platelet plug that stops bleeding before coagulation...