rs3197999

This is a protein-altering variant in the APEH gene.

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GWAS Catalog Trait Associations (20)

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

protein measurement

Western D et al. “Proteogenomic analysis of human cerebrospinal fluid identifies neurologically relevant regulation and implicates causal proteins for Alzheimer's disease.” Nature Genetics 56(12):2672-2684 (2024)
Allele A
OR 1.20
p —
N 3,506
Large GWAS
European
Hartley AE et al. “Deciphering tissue-specific protein regulation for insights into cardiometabolic disease.” Molecular Metabolism 104:102314 (2026)
Allele A
OR —
p 1.0e-8
N 272
Small GWAS
European

hepatocyte growth factor-like protein level

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 A
OR 1.21
p 4.0e-303
N 2,935
Large GWAS
Greater Middle Eastern (Middle Eastern, North African or Persian)
Suhre K et al. “A genome-wide association study of mass spectrometry proteomics using a nanoparticle enrichment platform.” Nature Genetics 57(12):2987-2996 (2025)
Allele A
OR 0.78
p 2.0e-119
N 1,255
Large GWAS
multi-ancestry

blood protein amount

Gudjonsson A et al. “A genome-wide association study of serum proteins reveals shared loci with common diseases.” Nature Communications 13(1):480 (2022)
Allele A
OR 0.62
p 1.0e-258
N 5,361
Large GWAS
European

indoleamine 2,3-dioxygenase 1 measurement

Pietzner M et al. “Mapping the proteo-genomic convergence of human diseases.” Science (new York, N.y.) 374(6569):eabj1541 (2021)
Allele A
OR 0.38
p 1.0e-155
N 10,708
Large GWAS
European

leukocyte cell-derived chemotaxin 1 measurement

Pietzner M et al. “Mapping the proteo-genomic convergence of human diseases.” Science (new York, N.y.) 374(6569):eabj1541 (2021)
Allele A
OR 0.35
p 3.0e-131
N 10,708
Large GWAS
European

transmembrane protease serine 11D measurement

Sun BB et al. “Genomic atlas of the human plasma proteome.” Nature 558(7708):73-79 (2018)
Allele A
OR —
β 0.530
p 3.0e-96
N 3,301
Large GWAS
European

interleukin-23 receptor measurement

Pietzner M et al. “Mapping the proteo-genomic convergence of human diseases.” Science (new York, N.y.) 374(6569):eabj1541 (2021)
Allele A
OR 0.28
p 5.0e-90
N 10,708
Large GWAS
European

tensin-2 measurement

Pietzner M et al. “Mapping the proteo-genomic convergence of human diseases.” Science (new York, N.y.) 374(6569):eabj1541 (2021)
Allele A
OR 0.22
p 8.0e-49
N 10,708
Large GWAS
European
Sun BB et al. “Genomic atlas of the human plasma proteome.” Nature 558(7708):73-79 (2018)
Allele A
OR —
β 0.380
p 4.0e-48
N 3,301
Large GWAS
European

inflammatory bowel disease

Jostins L et al. “Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease.” Nature 491(7422):119-24 (2012)
Allele A
OR 1.18
p 1.0e-47
N 34,366
Large GWAS
European

level of regenerating islet-derived protein 3-alpha in blood serum

Kuliesius J et al. “Efficient candidate drug target discovery through proteogenomics in a Scottish cohort.” Communications Biology 8(1):1300 (2025)
Allele A
OR 1.20
p 3.0e-46
N 199
Small GWAS
European
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Research that mentions this SNP (4)

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Genome-Wide Association Analysis in Primary Sclerosing Cholangitis And Ulcerative Colitis Identifies Risk Loci at Gpr35 And Tcf4
AssociationN=28,868David Ellinghaus et al.(2013)· Hepatology

This dense genotyping study identified 12 genome-wide significant susceptibility loci for primary sclerosing cholangitis (PSC) outside the HLA complex in 3,789 European PSC cases and 25,079 controls using the Immunochip array. Nine loci were novel, including rs7426056 (CD28; OR=1.30), rs3197999 (MST1; OR=1.33), rs13140464 (IL2/IL21; OR=1.30), rs56258221 (BACH2; OR=1.23), and rs2836883 (PSMG1; OR=1.28). The study found overlapping yet distinct genetic architecture between PSC and inflammatory bowel disease, with PSC being genetically more similar to ulcerative colitis than Crohn's disease.

Traits studied:Inflammatory bowel diseasePrimary sclerosing cholangitis
PubMedDOIMetascience Observatory
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Distinct and overlapping genetic loci in crohnʼs disease and ulcerative colitis: Correlations with pathogenesis
AssociationN=3,431Matti Waterman et al.(2011)· Inflammatory Bowel Diseases

This study examined 40 SNPs (34 CD-associated and 6 UC-associated) in 2374 Canadian IBD patients (1144 CD, 1230 UC/IBDU) and 1057 healthy controls. While most immune-related variants showed similar frequencies between CD and UC, the two diseases diverged significantly in genes related to innate immunity and autophagy (NOD2, ATG16L1, IRGM), which were more prevalent in CD. In patients with colon-only CD, genetic overlap with UC was nearly complete, suggesting a shared genetic basis for colonic disease.

Traits studied:Crohn's diseaseInflammatory bowel disease (IBD)Ulcerative colitis
PubMedDOIMetascience Observatory
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Identification of candidate loci at 6p21 and 21q22 in a genome‐wide association study of cardiac manifestations of neonatal lupus
AssociationN=3,467Robert M. Clancy et al.(2010)· Arthritis &amp; Rheumatism

Genome-wide association study of 116 children with cardiac neonatal lupus (116 cases, 3,351 controls) identified 17 significant SNPs in the HLA region at 6p21, with the strongest association at rs3099844 (OR 3.34, P=4.52×10⁻¹⁰) near the MICB gene. Non-HLA associations were found at rs743446 (21q22, OR 2.40, P=5.45×10⁻⁶), rs2403106 (12q21, OR 2.48, P=2.62×10⁻⁶), rs1391511 (10p15, OR 1.84, P=6.6×10⁻⁶), and rs1890645 (1q31, OR 2.98, P=3.52×10⁻⁶). Results suggest genetic polymorphisms in inflammatory and apoptotic pathways contribute to cardiac injury in fetuses exposed to maternal anti-Ro/SSA antibodies.

Traits studied:Atrioventricular blockCardiac neonatal lupusCardiomyopathyCongenital heart blockNeonatal lupus erythematosus
PubMedDOIMetascience Observatory
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Association of IL23R, TNFRSF1A, and HLA-DRB1*0103 allele variants with inflammatory bowel disease phenotypes in the Finnish population
AssociationN=7,457Maarit Lappalainen et al.(2008)· Inflammatory Bowel Diseases

PhD thesis describing comprehensive genome-wide association studies of acute anterior uveitis (AAU) in European (2,752 cases, 3,836 controls) and East Asian (821 cases, 4,898 controls) populations. European descent GWAS identified HLA-B at genome-wide significance plus 11 suggestive loci (ERAP1, NOS2, MERTK). East Asian GWAS identified HLA-B and ERAP1 at genome-wide significance plus 12 suggestive loci (GPR68, RHBDD2). Mendelian randomization confirmed ERAP1 as functionally relevant and showed genetically predicted CRP levels positively associated with AAU risk.

Traits studied:Acute anterior uveitis (AAU)Ankylosing spondylitis (AS)Spondyloarthropathies
PubMedDOIMetascience Observatory

About APEH

This gene encodes the enzyme acylpeptide hydrolase, which catalyzes the hydrolysis of the terminal acetylated amino acid preferentially from small acetylated peptides. The acetyl amino acid formed by this hydrolase is further processed to acetate and a free amino acid by an aminoacylase. This gene is located within the same region of chromosome 3 (3p21) as the aminoacylase gene, and deletions at this locus are also associated with a decrease in aminoacylase activity. The acylpeptide hydrolase is a homotetrameric protein of 300 kDa with each subunit consisting of 732 amino acid residues. It can play an important role in destroying oxidatively damaged proteins in living cells. Deletions of this gene locus are found in various types of carcinomas, including small cell lung carcinoma and renal cell carcinoma. [provided by RefSeq, Jul 2008]

View all APEH variants →

Gene information from NCBI Gene. Variant classifications from ClinVar.

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