Expressive

rs11712964 (KLF15/ALDH1L1-AS2): Gene Expression Variant

Key takeaways

  • rs11712964 at the KLF15 and ALDH1L1-AS2 locus was identified in the VA Million Veteran Program GWAS, one of the largest US genomic studies with 635,969 participants across four ancestry groups.
  • The alternate allele is linked to increased expression of a gene at this locus in the brain nucleus accumbens, based on GTEx v11 expression data from 953 tissue donors.
  • A second expression effect was found in colon sigmoid tissue, where the alternate allele is associated with higher ALDH1L1 expression.
  • Evidence is based on expression-QTL data (GTEx v11, FDR < 0.05); phenotypic trait associations for this specific variant are not detailed in the available study text.

Key takeaways

  • rs11712964 at the KLF15 and ALDH1L1-AS2 locus was identified in the VA Million Veteran Program (MVP) GWAS, one of the largest US genomic studies, with 635,969 participants across four ancestry groups.
  • The alternate allele is linked to increased expression of ENSG00000250934 (a gene at this locus) in the brain nucleus accumbens, based on GTEx v11 expression data from 953 tissue donors.
  • A second expression effect was found in colon sigmoid tissue, where the alternate allele is associated with higher ALDH1L1 expression.
  • Evidence is based on expression-QTL data (GTEx v11, FDR < 0.05); phenotypic trait associations for this specific variant are not detailed in the available study text.

What the research says rs11712964 at the ALDH1L1-AS2 and KLF15 locus was captured in a genome-wide association study of 2,068 traits across 635,969 participants in the VA Million Veteran Program, published in Science in 2024; that study identified 26,049 variant-trait associations, with statistical fine-mapping locating 15,045 signals to single high-confidence variants. Expression-quantitative trait locus (eQTL) data from GTEx v11 (953 donors, FDR < 0.05) shows the alternate allele is associated with increased expression of ENSG00000250934 in the brain nucleus accumbens basal ganglia (effect slope +0.51, p=2.5e-5) GTEx Portal. The same allele is associated with increased expression of ALDH1L1 in colon sigmoid tissue (effect slope +0.17, p=2.3e-5) GTEx Portal.

Reported associations

  • ENSG00000250934 expression in brain nucleus accumbens (basal ganglia): The alternate allele is associated with increased expression of this gene at the locus in the brain nucleus accumbens basal ganglia (slope +0.51, p=2.5e-5, GTEx v11) GTEx Portal.
  • ALDH1L1 expression in colon sigmoid: The alternate allele is associated with increased expression of ALDH1L1 in the colon sigmoid (slope +0.17, p=2.3e-5, GTEx v11) GTEx Portal.

Evidence quality The eQTL evidence for rs11712964 comes from GTEx v11 (953 donors, FDR < 0.05), a well-established reference dataset that applies stringent multiple-testing correction across tissues. The brain nucleus accumbens signal for ENSG00000250934 (slope +0.51, p=2.5e-5) is larger in magnitude than the colon sigmoid signal for ALDH1L1 (slope +0.17, p=2.3e-5); both pass the GTEx FDR threshold GTEx Portal. The MVP GWAS (635,969 participants drawn from African, Admixed American, East Asian, and European ancestry groups) provides large-scale population context for this locus, but the specific phenotypic trait associations reported for rs11712964 in that study are not detailed in the available study text, which limits characterization of clinical effect sizes and replication status for this variant. No conflicting findings are present within the provided evidence.

Tissue-specific expression effects

  • ENSG00000250934: Increased expression in the brain nucleus accumbens basal ganglia with the alternate allele; this is the larger of the two expression signals at this locus, with a slope of +0.51 GTEx Portal.
  • ALDH1L1: Increased expression in colon sigmoid tissue with the alternate allele, with a slope of +0.17 GTEx Portal.

Lifestyle considerations No lifestyle considerations on file for this variant.

Frequently asked questions

What is rs11712964?

rs11712964 is a genetic variant at the ALDH1L1-AS2 and KLF15 gene locus, cataloged in the VA Million Veteran Program genome-wide association study of 635,969 participants across African, Admixed American, East Asian, and European ancestry groups.

What does rs11712964 do to gene expression?

Based on GTEx v11 data from 953 tissue donors, the alternate allele is associated with increased expression of ENSG00000250934 in the brain nucleus accumbens basal ganglia (slope +0.51) and with increased expression of ALDH1L1 in colon sigmoid tissue (slope +0.17). Both effects pass a stringent false discovery rate threshold.

What genes are near rs11712964?

rs11712964 is located at the ALDH1L1-AS2 and KLF15 gene locus. Expression data from GTEx v11 indicates the variant influences the expression of ENSG00000250934 at this locus as well as ALDH1L1 in colon tissue.

Where was rs11712964 discovered?

rs11712964 was cataloged in the VA Million Veteran Program genome-wide association study, published in Science in 2024, which analyzed 2,068 traits across 635,969 participants from four ancestry groups and identified 26,049 variant-trait associations.

Is rs11712964 associated with any diseases?

The available evidence for rs11712964 primarily shows tissue-specific gene expression effects in the brain nucleus accumbens and colon sigmoid. Phenotypic disease associations from the large MVP GWAS are not detailed in the available study text, so disease-level conclusions cannot be drawn from the provided evidence.