rs9264942

mixedMag 5.5

This is a intergenic variant variant in the HLA-C gene.

Key Literature Trait Associations

HIV-1 Viral Load Control

The C allele at rs9264942, located 35 kb upstream of HLA-C, is associated with lower HIV-1 viral load set point. In a GWAS of 2,362 HIV-1-infected individuals, this variant showed the strongest association with viral load control outside of HLA-B (p = 9.36e-26). The protective effect is mediated through higher HLA-C surface expression, enhancing cytotoxic T-lymphocyte responses against HIV-infected cells.

Fellay J et al. “Common genetic variation and the control of HIV-1 in humans.” Plos Genetics 5(12):e1000791 (2009)

Allele T

OR —

β -0.300

p 6.0e-32

N 2,554

Large GWAS

European

Fellay J et al. “A whole-genome association study of major determinants for host control of HIV-1.” Science (new York, N.y.) 317(5840):944-947 (2007)

Allele T

OR —

β -0.500

p 9.4e-26

Large GWAS

Thørner LW et al. “Impact of polymorphisms in the HCP5 and HLA-C, and ZNRD1 genes on HIV viral load.” Infection, Genetics and Evolution : Journal of Molecular Epidemiology and Evolutionary Genetics in Infectious Diseases (2016)

Allele T

OR —

p 1.0e-4

N 1,897

Preliminary work

European

van Manen D et al. “Association of HLA-C and HCP5 gene regions with the clinical course of HIV-1 infection.” Aids (london, England) (2009)

Allele T

OR —

p —

N 335

Candidate gene study

European

Herráiz-Nicuesa L et al. “Impact of the Polymorphism rs9264942 near the HLA-C Gene on HIV-1 DNA Reservoirs in Asymptomatic Chronically Infected Patients Initiating Antiviral Therapy.” Journal of Immunology Research (2017)

Allele T

OR —

p —

N 183

Candidate gene study

European

Psoriasis

The C allele at rs9264942, which tags high HLA-C expression, is also associated with increased susceptibility to psoriasis vulgaris. Majorczyk et al. (2014) found an OR of 5.04 for the C allele in a Polish cohort, though this effect is substantially weaker than that of HLA-Cw*06 (OR=15.61) and is largely dependent on HLA-Cw*06 co-carriage due to strong linkage disequilibrium. The dual role of this SNP in HIV protection and psoriasis risk is thought to reflect the pleiotropic consequences of elevated HLA-C expression on immune regulation in different tissue contexts.

Majorczyk E et al. “A single nucleotide polymorphism -35 kb T>C (rs9264942) is strongly associated with psoriasis vulgaris depending on HLA-Cw(∗)06.” Human Immunology (2014)

Allele C

OR 5.04

p —

N 546

Preliminary work

European

Nititham J et al. “Psoriasis risk SNPs and their association with HIV-1 control.” Human Immunology (2017)

Allele C

OR —

p —

N 2,028

Preliminary work

multi-ancestry

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GWAS Catalog Trait Associations (4)

Genome-wide significant associations (p < 5×10⁻⁸) from the NHGRI-EBI GWAS Catalog.

HIV-1 infection

Pereyra F et al. “The major genetic determinants of HIV-1 control affect HLA class I peptide presentation.” Science (new York, N.y.) 330(6010):1551-7 (2010)

Allele C

OR 2.90

p 3.0e-35

N 3,622

Large GWAS

multi-ancestry

Fellay J et al. “Common genetic variation and the control of HIV-1 in humans.” Plos Genetics 5(12):e1000791 (2009)

Allele C

OR 5.30

p 6.0e-32

N 2,362

Large GWAS

European

Crohn's disease

Jostins L et al. “Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease.” Nature 491(7422):119-24 (2012)

Allele C

OR 1.15

p 5.0e-28

N 34,366

Large GWAS

European

MHC class I polypeptide-related sequence A measurement

Thareja G et al. “Differences and commonalities in the genetic architecture of protein quantitative trait loci in European and Arab populations.” Human Molecular Genetics 32(6):907-916 (2023)

Allele C

OR 0.27

p 1.0e-20

N 2,935

Large GWAS

Greater Middle Eastern (Middle Eastern, North African or Persian)

amount of leukocyte immunoglobulin-like receptor subfamily A member 5 (human) in blood

Loya H et al. “A scalable variational inference approach for increased mixed-model association power.” Nature Genetics 57(2):461-468 (2025)

Allele C

OR 0.04

p 1.0e-12

N 47,745

Large GWAS

European

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ClinVar annotation

Risk Factor

1 submitter1 publication

HIV-1 VIREMIA, SUSCEPTIBILITY TO

View on ClinVar →

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Research that mentions this SNP (1)

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Quantity of HLA-C surface expression and licensing of KIR2DL+ natural killer cells

FunctionalN=66Hojjatollah Nozad Charoudeh et al.(2012)· Immunogenetics

This functional study of 66 healthy donors investigated whether HLA-C surface expression variants (rs9264942 and rs67384697) influence NK cell licensing through altered HLA-C quantity. While the number of HLA-C ligands dose-dependently increased NK cell degranulation and cytokine production, neither polymorphism nor absolute HLA-C surface quantity significantly affected NK cell function. Notably, HLA-Cw7, which has low surface expression, strongly licensed KIR2DL3+ NK cells more effectively than other C1 ligands.

rs9264942

Key Literature Trait Associations

HIV-1 Viral Load Control

Psoriasis

GWAS Catalog Trait Associations (4)

HIV-1 infection

Crohn's disease

MHC class I polypeptide-related sequence A measurement

amount of leukocyte immunoglobulin-like receptor subfamily A member 5 (human) in blood

ClinVar annotation

Research that mentions this SNP (1)

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