rs2292884

This is a variant in the MLPH gene that changes a histidine to an arginine.

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GWAS Catalog Trait Associations (1)

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

prostate carcinoma

Conti DV et al. “Trans-ancestry genome-wide association meta-analysis of prostate cancer identifies new susceptibility loci and informs genetic risk prediction.” Nature Genetics 53(1):65-75 (2021)
Allele G
OR 1.06
p 6.0e-16
N 234,253
Meta-analysisLarge GWAS
multi-ancestry
Schumacher FR et al. “Association analyses of more than 140,000 men identify 63 new prostate cancer susceptibility loci.” Nature Genetics 50(7):928-936 (2018)
Allele G
OR 1.06
p 4.0e-11
N 140,254
Large GWAS
European
Schumacher FR et al. “Genome-wide association study identifies new prostate cancer susceptibility loci.” Human Molecular Genetics 20(19):3867-75 (2011)
Allele G
OR 1.14
p 4.0e-8
N 7,240
Large GWAS
European
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ClinVar annotation

Benign★★★☆
3 submitters2 publications
View on ClinVar →
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Research that mentions this SNP (2)

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Putative Prostate Cancer Risk SNP in an Androgen Receptor‐Binding Site of the Melanophilin Gene Illustrates Enrichment of Risk SNPs in Androgen Receptor Target Sites
FunctionalN=126Huajie Bu et al.(2016)· Human Mutation

This study integrated ChIP-seq analysis of androgen receptor-binding sites in prostate cancer cells with GWAS data and found that rs11891426:T>G in the melanophilin gene (MLPH) lies within a functional AR-binding motif, with the risk G allele attenuating transcriptional activity. Expression analysis showed MLPH was significantly lower in tumors carrying the G allele, suggesting a tumor-suppressive role weakened by this functional variant.

Traits studied:Biochemical recurrencePathological stageProstate cancerProstate cancer susceptibilityTumor grade (Gleason score)
PubMedDOIMetascience Observatory
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A genome-wide association study of prostate cancer in West African men
AssociationN=932Michael Blaise Cook et al.(2014)· Human Genetics

Genome-wide association study of 474 prostate cancer cases and 458 controls from West African men identified a novel prostate cancer susceptibility locus at 10p14 marked by rs7918885 (p=1.29×10⁻⁷), localized to an intron of the lncRNA gene RP11-543F8.2. A stratified analysis by Gleason score revealed additional associations including rs34575154 in PCDHA1 at 5q31.3 (p=3.66×10⁻⁸) for high-grade disease and rs985081 at Xq28 (p=8.66×10⁻⁹) for low-grade disease. Validation in the African Ancestry Prostate Cancer GWAS Consortium showed limited replication, with only rs2993385 at 10p14 reaching nominal significance (p<0.05), highlighting population-specific genetic architecture.

Traits studied:Prostate cancerProstate cancer (high-grade/Gleason score ≥7)Prostate cancer (low-grade/Gleason score <7)
PubMedDOIMetascience Observatory

About MLPH

This gene encodes a member of the exophilin subfamily of Rab effector proteins. The protein forms a ternary complex with the small Ras-related GTPase Rab27A in its GTP-bound form and the motor protein myosin Va. A similar protein complex in mouse functions to tether pigment-producing organelles called melanosomes to the actin cytoskeleton in melanocytes, and is required for visible pigmentation in the hair and skin. A mutation in this gene results in Griscelli syndrome type 3, which is characterized by a silver-gray hair color and abnormal pigment distribution in the hair shaft. Several alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2013]

View all MLPH variants →

Gene information from NCBI Gene. Variant classifications from ClinVar.

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