rs10743889 (KLRK1-AS1): Gene Expression Variant

Key takeaways

• This variant increases expression of KLRK1-AS1 (an antisense RNA gene) in esophageal, skin, and testicular tissue.
• The same variant also raises expression of KLRC2, a natural killer cell receptor gene, in several brain regions including the hypothalamus.
• It was identified in a genome-wide study of childhood obesity-related traits in 815 Hispanic children.
• The brain expression effects are mechanistic findings - they show what the variant does in tissue, not a confirmed disease outcome.
• Overall evidence is preliminary, with no independent replication studies available in the provided data.

What the research says rs10743889 sits in KLRK1-AS1, an antisense RNA gene (one that produces RNA running in the opposite direction to a neighboring coding gene) located adjacent to KLRC2, which encodes a natural killer cell activating receptor involved in immune surveillance. Gene expression data from GTEx (953 donors across multiple tissues, FDR-corrected) shows that the alternate allele is associated with increased expression of KLRK1-AS1 in esophageal mucosa, testis, and skin, and separately with increased expression of KLRC2 in multiple brain regions and lung GTEx Portal. This locus also falls within the scope of the VIVA LA FAMILIA Study, a genome-wide association study (GWAS) of 1.1 million SNPs in 815 Hispanic children aged 4-19 from 263 families, which examined obesity-related traits including anthropometry, energy expenditure, metabolites, hormones, and inflammation.

Reported associations

• KLRK1-AS1 expression (esophagus mucosa): The alternate allele is associated with increased expression of KLRK1-AS1 in esophageal mucosa (slope +0.74, p=1.2e-54) GTEx Portal
• KLRK1-AS1 expression (testis): Increased KLRK1-AS1 expression in testis (slope +0.56, p=2.4e-38) GTEx Portal
• KLRK1-AS1 expression (skin, non-sun-exposed suprapubic): Increased KLRK1-AS1 expression in suprapubic skin (slope +0.45, p=5.8e-28) GTEx Portal
• KLRC2 expression (anterior cingulate cortex): The alternate allele is associated with increased KLRC2 expression in the anterior cingulate cortex, a brain region involved in decision-making and autonomic regulation (slope +0.80, p=5.1e-16) GTEx Portal
• KLRC2 expression (hypothalamus): Increased KLRC2 expression in the hypothalamus, which regulates metabolism and appetite (slope +0.78, p=4.2e-16) GTEx Portal
• KLRC2 expression (nucleus accumbens basal ganglia): Increased KLRC2 expression in the nucleus accumbens, a brain region involved in reward processing (slope +0.72, p=1.0e-16) GTEx Portal
• KLRC2 expression (testis): Increased KLRC2 expression in testis (slope +0.71, p=1.3e-19) GTEx Portal
• KLRC2 expression (lung): Increased KLRC2 expression in lung tissue (slope +0.56, p=4.3e-21) GTEx Portal
• Childhood obesity-related traits (Hispanic children): rs10743889 falls within a locus examined in the VIVA LA FAMILIA GWAS of 815 Hispanic children from 263 families (1.1 million SNPs genotyped); the specific trait association and effect size for this variant from that study are not detailed in the available study text.

Evidence quality The eQTL associations from GTEx are based on 953 donors and reach p-values as low as 1.2e-54 for the esophageal mucosa effect, making the gene expression findings statistically robust GTEx Portal. The VIVA LA FAMILIA Study represents a well-characterized GWAS (n=815, 1.1 million SNPs) in a pediatric Hispanic cohort that is underrepresented in most genetic research, but the specific association statistic for rs10743889 in that study is not available in the provided text. No independent replication studies for disease associations are present in the provided data. The GTEx eQTL evidence is mechanistic, describing changes in gene expression levels rather than confirmed health outcomes, and clinical relevance should be considered preliminary.

Tissue-specific expression effects

• KLRK1-AS1: The alternate allele is associated with increased expression in esophageal mucosa, testis, and non-sun-exposed suprapubic skin, with the largest effect in esophageal tissue GTEx Portal
• KLRC2: The alternate allele is associated with increased expression in the anterior cingulate cortex, hypothalamus, and nucleus accumbens basal ganglia, as well as in testis and lung GTEx Portal

Lifestyle considerations No lifestyle considerations on file for this variant.