HLA-B
Major histocompatibility complex, class I, B
Gene Number: 3106
Location: 6p21.33
Key Functions: Antigen presentation, immune response activation, infection defense, autoimmunity regulation
HLA-B encodes human leukocyte antigen B, a critical component of the major histocompatibility complex (MHC) class I system, which governs the presentation of endogenous peptides to cytotoxic CD8⁺ T lymphocytes. As part of the adaptive immune system, HLA-B serves as a molecular sentinel, allowing immune surveillance mechanisms to distinguish between normal “self” cells and those harboring intracellular pathogens or malignant transformations. Its activity underpins cellular immunity and contributes to immune specificity and memory.
The HLA-B molecule is a cell surface glycoprotein composed of a heavy α-chain encoded by the HLA-B gene and a light chain (β₂-microglobulin) encoded elsewhere in the genome. The α-chain contains three extracellular domains (α1, α2, α3), a transmembrane region, and a cytoplasmic tail. The peptide-binding groove, formed by the α1 and α2 domains, accommodates short peptides (typically 8–10 amino acids) derived from intracellular proteins that have been processed by the proteasome and transported into the endoplasmic reticulum by TAP (transporter associated with antigen processing).
HLA-B polymorphism represents one of the highest degrees of genetic variability in the human genome. Thousands of allelic variants (e.g., HLA-B27, HLA-B57, HLA-B15:02) exist, differing mainly in the amino acid composition of the peptide-binding groove, thereby dictating peptide specificity and immune recognition patterns. This extraordinary diversity provides population-level resilience against pathogens but also underlies significant clinical variability in immune-related conditions.
SNP ID | Your Genotype | Alternative Alleles | Interpretation |
|---|---|---|---|
rs2395029 | Analyze your DNA to see your genotype | G | Analyze your DNA to see a personalized result. |
rs13202464 | Analyze your DNA to see your genotype | G | Analyze your DNA to see a personalized result. |
rs2395029 (HCP5 tag SNP for HLA-B57:01)
TT – Common genotype; HLA-B*57:01 allele not presente (R).
TG – Carrier of the rs2395029 (G) allele. This is ~99.9% predictive of carrying the HLA-B*57:01 allele in many Caucasian and Hispanic populations (but not all). Associated with a high risk of abacavir hypersensitivity and increased risk of flucloxacillin-induced liver injury (R).
GG – Very likely homozygous for HLA-B57:01; extremely high risk of severe reactions to abacavir and other HLA-B57:01-associated drug reactions (R).
Functional effect: rs2395029 is a SNP in the major histocompatibility complex (MHC) region. The G allele strongly tags the HLA-B*57:01 allele, which has been linked to abacavir hypersensitivity, flucloxacillin-induced liver injury, and certain autoimmune associations. While highly predictive in Europeans and Hispanics, the link is less consistent in other populations (R).
rs13202464 (tag SNP for HLA-B27)*
AA – Common genotype; HLA-B*27 allele not present (baseline risk) (R).
AG – Heterozygous for the G allele; likely carrier of HLA-B*27. Associated with a higher risk of ankylosing spondylitis (AS) and related autoimmune conditions (R).
GG – Likely homozygous HLA-B*27; strongest genetic risk factor for ankylosing spondylitis and related spondyloarthropathies (R)..
Functional effect: The G allele tags the HLA-B*27 allele, which predisposes to ankylosing spondylitis and related conditions (e.g., reactive arthritis, acute anterior uveitis). Only 1–2% of carriers actually develop disease, so penetrance is low but predictive value is strong (R).
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