Research — GeneOps

rs2531693353 Rare splice acceptor variant disrupting intron 9 of D-bifunctional protein; biallelic carriers develop peroxisomal fatty acid oxidation failure causing either severe neonatal DBP deficiency or Perrault syndrome; heterozygous carriers are clinically unaffected but carry reproductive risk

Chromosome 5 Risk Allele A Category Metabolic Enzymes & Rare Disorders Tags Carrier Status, Fat Metabolism, Neurological Risk, Hearing Loss, Ovarian Reserve, Genetic Counseling

The peroxisome is a cellular organelle dedicated in part to processing the fatty acids that mitochondria cannot — very long chains (more than 20 carbons), branched-chain fatty acids such as phytanic acid, and the bile acid precursors derived from cholesterol. D-bifunctional protein (DBP), encoded by HSD17B4,...

rs25531 Promoter SNP near 5-HTTLPR that modifies serotonin transporter expression and antidepressant response

Chromosome 17 Risk Allele C Category Mood & Behavior Tags Mental Health, Neurotransmitters, Antidepressants, Mood, Anxiety, Pharmacogenomics

Important Limitation: According to 23andMe's own geneticists, rs25531 is not reliably genotyped on consumer platforms(https://www.snpedia.com/index.php/Rs25531). This SNP requires specialized genotyping methods. If your 23andMe data shows AA for rs25531, it is likely a technical artifact rather than your true...

rs28940580 Exon 10 missense variant in the inflammasome regulator pyrin; one of five founder FMF mutations at codon 680 — a severity hotspot alongside codon 694. M680I homozygotes develop moderate-to-severe FMF, and M680I/M694V compound heterozygotes can have severe, colchicine- resistant disease comparable to M694V homozygosity.

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

Familial Mediterranean fever (FMF) is the most common hereditary autoinflammatory disease, driven by gain-of-function variants in MEFV that destabilize pyrin's normally tight control over the inflammasome. Pyrin(https://www.ncbi.nlm.nih.gov/gene/4210) operates as a conditional alarm sensor — active only when genuine...

rs30021 Intronic variant in SNX24 (sorting nexin 24) with roles in vascular endothelial inflammation and platelet alpha-granule biogenesis, including VWF and P-selectin trafficking; G allele is minor and may reduce SNX24 expression efficiency in endothelial and megakaryocyte lineages

Chromosome 5 Risk Allele G Category Coronary Artery Disease & Atherosclerosis Tags Angiogenesis, Cardiovascular, Heart Disease, Inflammation, Blood Clotting, Endothelial Health, Thrombophilia

Inside every vascular endothelial cell and platelet-producing megakaryocyte, a molecular sorting system routes proteins to exactly where they need to go. SNX24 — sorting nexin 24(https://www.ncbi.nlm.nih.gov/gene/28966) — is one component of this system, specifically required for building platelet alpha-granules and...

rs3134883 Intronic IL2RA variant independently associated with rheumatoid arthritis risk and part of the IL-2 receptor locus haplotype architecture modulating Treg-driven immune tolerance

Chromosome 10 Risk Allele A Category Autoimmune Tolerance & T-Cell Regulation Tags Autoimmune, Immune & Autoimmune, Inflammation, Rheumatoid Arthritis, Type 1 Diabetes, Vitamin D

The IL2RA locus(https://www.ncbi.nlm.nih.gov/gene/3559) is one of the most replicated non-HLA autoimmune susceptibility regions in the human genome. While rs2104286 is the most commonly cited variant at this locus, fine-mapping studies have established that multiple independent genetic signals coexist in the same...

rs36211723 Rare pathogenic missense variant at the last nucleotide of MYBPC3 exon 23, causing aberrant splicing and haploinsufficiency; strongly associated with hypertrophic cardiomyopathy (autosomal dominant)

Chromosome 11 Risk Allele T Category Cardiomyopathy & Structural Heart Tags Cardiovascular, Heart Disease, Genetic Counseling, RNA Splicing, Carrier Status, Congenital

The MYBPC3 gene encodes cardiac myosin-binding protein C (cMyBP-C)(https://www.ncbi.nlm.nih.gov/snp/rs36211723). Functioning like a molecular brake on sarcomeric contraction, cMyBP-C is also phosphorylated in response to beta-adrenergic stimulation, allowing the heart to increase its output during exertion....

rs369296618 Nonsense variant in MMAB creating a premature stop codon (Q234*) that impairs adenosylcobalamin synthesis; pathogenic for methylmalonic aciduria cblB type in biallelic state; heterozygous carriers are asymptomatic.

Chromosome 12 Risk Allele A Category Vitamins & Nutrient Absorption Tags Vitamin B12, Carrier Status, B Vitamins, Methylation, Genetic Counseling, Metabolic

The MMAB gene encodes ATP:cob(I)alamin adenosyltransferase (ATR)(https://www.ncbi.nlm.nih.gov/gene/326625), the final enzyme in the pathway that converts dietary vitamin B12 into its active mitochondrial form, adenosylcobalamin (AdoCbl). Without AdoCbl, methylmalonyl-CoA mutase(https://omim.org/entry/251000) stalls,...

rs3764880 X-linked initiator codon variant in TLR8 that fine-tunes the ratio of two TLR8 protein isoforms, producing sex-specific effects on innate immune responses to RNA viruses and mycobacteria

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

Toll-like receptor 8 (TLR8) is an endosomal sentinel of the innate immune system that detects single-stranded RNA from invading pathogens — including RNA viruses and the RNA-rich debris shed by mycobacteria such as Mycobacterium tuberculosis. TLR8(https://www.ncbi.nlm.nih.gov/gene/51311) sits inside the membranes of...

rs3805435 Intronic variant in the GPX3/TNIP1 regulatory locus on chromosome 5; the C allele is protective against generalized pustular psoriasis (OR≈0.61 per C allele) by tagging a haplotype associated with maintained ABIN-1/NF-κB regulatory capacity

Chromosome 5 Risk Allele T Category Psoriasis & Spondyloarthropathy Tags Autoimmune, Inflammation, Psoriasis, Skin, Anti-TNF Biologics, Oxidative Stress

Two adjacent genes on chromosome 5 occupy opposite ends of the same molecular story. GPX3(https://www.ncbi.nlm.nih.gov/gene/2878) sits upstream on the forward strand. Downstream on the reverse strand lies TNIP1(https://pubmed.ncbi.nlm.nih.gov/19169254/). The two genes are separated by roughly 100 kilobases but share...

rs3827103 Common MC3R missense variant that reduces receptor expression and shifts nutrient partitioning toward fat storage, particularly when co-inherited with the Thr6Lys variant (rs3746619)

Chromosome 20 Risk Allele A Category Appetite & Obesity Tags Fat Metabolism, Obesity, Insulin, Diet, Lean Mass

The melanocortin-3 receptor(https://pubmed.ncbi.nlm.nih.gov/16123355/) serves a fundamentally different role from its better-known cousin MC4R. While MC4R primarily governs appetite and energy expenditure, MC3R acts as a feed-efficiency rheostat(https://pubmed.ncbi.nlm.nih.gov/26818770/) — determining where calories...