Innate Immunity & Infection Defense

Intronic variant in CHD7, a chromatin remodeler critical for neural crest cell and skeletal development; the G allele is associated with susceptibility to adolescent idiopathic scoliosis and may influence neural crest-derived tissue patterning including thymus and inner ear morphogenesis

Missense variant in lymphotoxin-alpha, a TNF superfamily cytokine essential for secondary lymphoid organ formation and innate immune coordination; the A allele (Asn at position 26 of mature protein) alters LTα trimer stability, modestly increases cancer susceptibility, and has been associated with coronary atherosclerosis and respiratory infection risk

5'UTR variant that enhances PSMA6 transcription, amplifying proteasome-driven NF-κB signalling and increasing chronic inflammatory risk across cardiovascular and autoimmune conditions

Intronic enhancer variant in basonuclin-2 that increases YY1 binding and BNC2 expression, elevating susceptibility to adolescent idiopathic scoliosis and predicting brace treatment failure

Promoter variant in Toll-like receptor 4 that drives higher TLR4 expression and amplified innate immune signaling, increasing risk for atherosclerosis, diabetic retinopathy, and inflammatory tissue damage

Regulatory variant in the lymphotoxin beta receptor gene associated with increased susceptibility to recurrent throat infections and tonsillectomy

Intronic CDHR3 variant in high linkage disequilibrium with the C529Y functional variant (rs6967330), tagging elevated rhinovirus C receptor activity and increased susceptibility to rhinovirus-induced wheezing and childhood asthma exacerbations

Splice-region synonymous variant in the innate antiviral gene IFITM3; the G allele (C on coding strand) reduces antiviral protein activity and is strongly associated with severe influenza, COVID-19, and other enveloped virus infections.

Intergenic variant in the SOX9 upstream regulatory region on chromosome 17q24.3 associated with increased susceptibility to severe adolescent idiopathic scoliosis (AIS) across multiple ethnic populations

Intronic variant in FRMD5 — a cell-adhesion scaffolding gene — where the rare C allele is associated with reduced recurrent urinary tract infection susceptibility, implicating uroepithelial barrier integrity in innate mucosal defense

Missense variant disrupting mannose-binding lectin oligomerization, reducing serum MBL 5-10-fold and impairing complement-mediated opsonization of bacteria, viruses, and fungi

Promoter variant that alters transcription factor binding and TLR9 expression, affecting innate immune responses to bacterial and viral CpG DNA across infections, autoimmunity, and transplant outcomes

Intronic TLR2 variant that modulates innate immune signaling intensity; G allele reduces TLR2 pathway activity and is protective against tuberculosis and periodontitis, while the common A allele sustains higher TLR2 activation linked to cardiovascular risk markers and autoimmune inflammation

Intronic variant in TBX1 acting as a cis-eQTL that reduces TBX1 expression and increases susceptibility to adolescent idiopathic scoliosis; TBX1 is the principal gene responsible for DiGeorge syndrome and governs pharyngeal arch and spinal musculature development

Splice donor variant in HPS3 that disrupts exon 5 inclusion, causing Hermansky-Pudlak syndrome type 3 in homozygotes and conferring carrier status in heterozygotes; enriched in the Ashkenazi Jewish population.

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

Promoter variant affecting CD14 expression and LPS receptor signaling — determines innate immune sensitivity to bacterial endotoxin and drives a classic gene-environment interaction with microbial exposure

Promoter insertion/deletion polymorphism reducing NF-κB p50 transcription and increasing cardiovascular and inflammatory disease susceptibility

Intronic PSCA variant that tags a regulatory region active in bladder urothelium; the G allele is associated with increased UTI frequency in women and with peptic ulcer disease susceptibility

Synonymous variant in TLR9 that increases receptor expression, amplifying innate immune responses to bacterial and viral DNA via CpG motif recognition

Intronic indel in the MIR4300 host gene that reduces enhancer activity and MIR4300 expression, increasing risk of progressive spinal curvature in adolescent idiopathic scoliosis

Gain-of-function missense variant in the NLRP3 inflammasome sensor that elevates baseline IL-1beta and IL-18 production, increasing susceptibility to gout, inflammatory bowel disease, and metabolic inflammation

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

Intronic regulatory variant near the lymphotoxin beta receptor gene influencing LTBR expression and alternative NF-κB-driven immune signaling

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

Intronic NFKB1 variant with genome-wide significant associations with ulcerative colitis and pleiotropic chronic inflammatory diseases; C allele increases susceptibility across multiple immune-mediated conditions

Missense variant in TLR3 that halves dsRNA-binding capacity, reducing antiviral interferon responses and increasing susceptibility to several viral infections

Missense variant substituting valine with methionine at position 327 of TLR6, predicted damaging by SIFT and PolyPhen; the Met327 allele is rare globally but reaches 6% in East Asian populations and alters TLR2/TLR6 heterodimer function, affecting diacylated lipopeptide recognition from bacteria and mycoplasma with downstream consequences for innate immune regulation and autoimmune-inflammatory risk

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

Missense variant in Fc gamma receptor IIIa (CD16a) that determines NK cell IgG binding affinity and antibody-dependent cellular cytotoxicity — major pharmacogenomic factor for monoclonal antibody therapy response

Splice donor variant disrupting DNAI1 intron 19, causing in-frame deletion of exon 19 (A607_K667del); pathogenic for autosomal recessive primary ciliary dyskinesia with outer dynein arm defects, chronic sinopulmonary disease, and situs inversus

Intronic PLG variant tagging a regional haplotype that reduces plasminogen expression, impairing fibrinolysis, macrophage recruitment, and mucosal wound healing — with documented associations with periodontitis susceptibility and plasminogen level variation

Intronic PLG variant (intron 1) whose C allele is enriched in Europeans and appears in cardiovascular GWAS signals at the PLG/LPA locus; PLG encodes plasminogen, the serine-protease zymogen central to fibrinolysis, macrophage recruitment, and innate mucosal immunity

Rare protective intronic variant in the master immune transcription factor NF-κB1; the T allele is associated with reduced lung cancer susceptibility and altered innate immune signaling

Promoter variant in Toll-Like Receptor 2 that increases TLR2 expression, associated with atopic dermatitis severity, psoriasis susceptibility, and modulated innate immune responses to bacterial and fungal ligands

Missense variant replacing asparagine with serine at TLR1 position 248 in the extracellular leucine-rich repeat domain — impairing TLR1/TLR2 heterodimer signaling to bacterial triacylated lipopeptides and increasing susceptibility to gram-positive bacterial infections and leprosy

Missense variant in Toll-like receptor 4 reducing bacterial endotoxin recognition and dampening inflammatory responses

Missense variant in Toll-like receptor 4 that co-segregates with Asp299Gly on the same haplotype, together reducing LPS-driven innate immune signaling and altering gram-negative bacterial recognition

Coding variant replacing isoleucine with serine at TLR1 position 602, disrupting a transmembrane trafficking motif and preventing TLR1 from reaching the cell surface — reducing TLR1/TLR2 heterodimer signaling in response to bacterial triacylated lipopeptides

Missense variant in Toll-Like Receptor 2 impairing innate immune signaling to gram-positive bacteria and mycobacteria, increasing susceptibility to tuberculosis, sepsis, and staphylococcal infections

Coding variant replacing serine with proline at TLR6 position 249, altering TLR2/TLR6 heterodimer signaling intensity for diacylated lipopeptides from bacteria and mycoplasma — Pro249 confers stronger NF-κB activation while Ser249 reduces TLR2/TLR6-mediated inflammation, with consequences for leprosy susceptibility, cardiovascular risk, and upper genital tract infections

TLR9 promoter variant that creates an IL-6-responsive element and estrogen-sensitive transcription site, amplifying innate immune signaling and increasing lymphoma susceptibility while modulating malaria, HCV, and thrombosis outcomes

Intergenic variant on chromosome 22q11 (merged into rs133255) located downstream of a lncRNA in the immunoglobulin lambda gene cluster region; listed as a 22q11.21 region variant co-identified with TBX1 AIS susceptibility locus rs1978060

Regulatory variant upstream of interferon alpha-21 associated with increased susceptibility to herpes zoster (shingles) via reduced type I interferon antiviral signaling

3' UTR variant in ANXA11 (annexin A11) in strong LD with the functional R230C missense variant (rs1049550); the C allele tags the sarcoidosis-risk haplotype and is associated with increased susceptibility to pulmonary granulomatous inflammation

Missense variant in the TACI transmembrane domain that disrupts receptor clustering and NF-κB signal transduction, impairing B-cell class-switch recombination and immunoglobulin production; associated with common variable immunodeficiency and IgA deficiency

Missense variant in plasminogen that reduces fibrinolytic activity and impairs fibrin clearance from mucosal surfaces, causing ligneous (woody) pseudomembrane formation and dramatically increasing risk for chronic otitis media and other mucous membrane inflammation

Intronic variant in the primary lymphangiogenesis growth factor gene associated with elevated lymphedema risk and impaired lymphatic vascular support

Missense variant in the TLR2/TLR4 adaptor protein Mal that modulates innate immune signaling strength, conferring broad infectious disease protection in heterozygous carriers