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Rs2395029

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Geno Mag Summary
(G;G) 4 HLA-B*5701 homozygote; high risk for hypersensitivity to various drugs including abacavir; 2x psoriasis risk; see details
(G;T) 3.1 HLA-B*5701 carrier
(T;T) 0 common
ReferenceGRCh38 38.1/141
Chromosome6
Position31464003
GeneHCP5
is asnp
is mentioned by
dbSNPrs2395029
PheGenIrs2395029
nextbiors2395029
hapmaprs2395029
1000 genomesrs2395029
hgdprs2395029
ensemblrs2395029
gopubmedrs2395029
geneviewrs2395029
scholarrs2395029
googlers2395029
pharmgkbrs2395029
gwascentralrs2395029
openSNPrs2395029
23andMers2395029
23andMe allrs2395029
SNP Nexus

SNPshotrs2395029
SNPdbers2395029
MSV3drs2395029
GMAF0.02663
Max Magnitude4
? (G;G) (G;T) (T;T) 28
rs2395029 is a SNP in the major histocompatibility complex (MHC) region, and several studies have shown that the rs2395029(G) allele is 99.9% predictive of the presence of an HLA-B*5701 allele. This HLA allele, in turn, has been associated with several conditions.

A study of 51 cases of flucloxacillin drug-induced liver injury (DILI), an important cause of serious liver disease, along with a replication study of another 23 cases, found that the rs2395029(G) carriers were at highly increased risk (odds ratio 80, p=8.7x10(-33)).[PMID 19483685]

[PMID 17641165OA-icon.png] This SNP is thought to be involved in determining the HIV viral load set point during the asymptomatic period of infection. This SNP is estimated to explain 9.6% of the total variation in the viral set point.

Humans show remarkable variation in vulnerability to infection by HIV-1 and especially in the clinical outcome following infection. One striking and largely unexplained difference is the level of circulating virus in the plasma during the non-symptomatic phase preceding progression to AIDS. This is known as the viral set point and can vary among individuals by as much as 4 to 5 logs.

The HCP5 (HLA complex P5) gene is located 100 kb centromeric from HLAB on chromosome 6. HCP5 is a good candidate to interact with HIV-1, possibly through an antisense mechanism. Moreover, HCP5 is predicted to encode two proteins, and the associated polymorphism results in an amino acid substitution in one of these.

rs9264942 is also reported to be associated with reduced HIV viral load set point.

In European populations, the rs2395029(G) allele is in tight linkage disequilibrium (r2 = 1) with the HLA-B*5701 allele, and therefore is predictive of hypersensitivity to the drug abacavir, an antiviral used to treat HIV+ individuals.[PMID 18684101]

nature Abacavir hypersensitivity rs2395029

[PMID 18369459OA-icon.png] rs2395029 reported to be associated with psoriasis in a large US/UK study

[PMID 24270849OA-icon.png] rs2395029 was found to be associated with psoriasis based on a study by the eMERGE network in which electronic medical records were searched to find clinical associations associated with selected SNPs.

[PMID 19115949] HIV-1 nonprogressors (odds ratio, 3.47)

Marker HLA-B*5701 hypersensitivity to the HIV drug abacavir; FDA warning here

OMIM142830
DescMAJOR HISTOCOMPATIBILITY COMPLEX, CLASS I, B; HLA-B
Variant
Relatedalso


GWAS snp
PMID [PMID 20041166OA-icon.png]
Trait HIV-1 control
Title Common Genetic Variation and the Control of HIV-1 in Human
Risk Allele
P-val 1E-11
Odds Ratio NR NR
OMIM604676
DescHLA COMPLEX P5 GENE; HCP5
Variant
Relatedalso





GWAS snp
PMID [PMID 21051598OA-icon.png]
Trait
Title The Major Genetic Determinants of HIV-1 Control Affect HLA Class I Peptide Presentation
Risk Allele G
P-val 1E-25
Odds Ratio 5.3000 [NR]


[PMID 18256235OA-icon.png] WGAViewer: software for genomic annotation of whole genome association studies.


[PMID 18982067OA-icon.png] HIV-1 disease-influencing effects associated with ZNRD1, HCP5 and HLA-C alleles are attributable mainly to either HLA-A10 or HLA-B*57 alleles.


[PMID 19050382] Association of HLA-C and HCP5 gene regions with the clinical course of HIV-1 infection.


[PMID 19107206OA-icon.png] Distinct genetic loci control plasma HIV-RNA and cellular HIV-DNA levels in HIV-1 infection: the ANRS Genome Wide Association 01 study.


[PMID 19182814OA-icon.png] New insights into the pathogenesis and genetics of psoriatic arthritis.


[PMID 19276793OA-icon.png] Host genetics and HIV-1 viral load set-point in African-Americans.


[PMID 19474294OA-icon.png] Potential etiologic and functional implications of genome-wide association loci for human diseases and traits.


[PMID 19679225OA-icon.png] X chromosomal variation is associated with slow progression to AIDS in HIV-1-infected women.


[PMID 19935381OA-icon.png] A polymorphism in the HCP5 gene associated with HLA-B*5701 does not restrict HIV-1 in vitro.


[PMID 20487506OA-icon.png] A whole genome association study of mother-to-child transmission of HIV in Malawi.


[PMID 20534626] Use of the HCP5 single nucleotide polymorphism to predict hypersensitivity reactions to abacavir: correlation with HLA-B*5701.


[PMID 20552027OA-icon.png] Host and viral genetic correlates of clinical definitions of HIV-1 disease progression.


[PMID 21107268OA-icon.png] Screening low-frequency SNPS from genome-wide association study reveals a new risk allele for progression to AIDS.


[PMID 21221856OA-icon.png] The search for host genetic factors of HIV/AIDS pathogenesis in the post-genome era: progress to date and new avenues for discovery.


[PMID 21253569OA-icon.png] Genome-wide association study SNPs in the human genome diversity project populations: does selection affect unlinked SNPs with shared trait associations?


[PMID 21514285] Rapid HCP5 single-nucleotide polymorphism genotyping: a simple allele-specific PCR method for prediction of hypersensitivity reaction to Abacavir.


[PMID 21854194] Distribution of polymorphisms in cytochrome P450 2B6, histocompatibility complex P5, chemokine coreceptor 5, and interleukin 28B genes in inhabitants from the central area of Argentina.


[PMID 21860345] Rising HIV-1 viral load set point at a population level coincides with a fading impact of host genetic factors on HIV-1 control.


[PMID 22474614OA-icon.png] Host Genes Important to HIV Replication and Evolution.


GET Evidence
HCP5-V112G
aa_change Val112Gly
aa_change_short V112G
impact pathogenic
qualified_impact Insufficiently evaluated pathogenic
overall_frequency 0.015625
summary GWAS association with AIDS progression.



HIV Progression

Abacavir Hypersensitivity

Floxacillin Toxicity


[PMID 23403273] Novel genetic association of TNF-alpha-238 and PDCD1-7209 polymorphisms with long-term non-progressive HIV-1 infection.


[PMID 24861233] Development of multiplex pyrosequencing for HLA-B*57:01 screening using single nucleotide polymorphism haplotype