rs10890404 (KNCN/MKNK1-AS1): Height and Brain eQTL

Key takeaways

• rs10890404 is one of 12,111 common variants linked to adult height in a study of over 5.4 million people.
• The alternate allele reduces expression of the KNCN gene in two brain cortex regions.
• MKNK1 expression increases in heart tissue with the same allele, showing multi-tissue regulatory effects.
• No individual effect size for this specific SNP is available in current published sources.
• All gene-expression signals come from tissue data and do not directly indicate disease risk.

What the research says rs10890404, in the MKNK1-AS1 / KNCN region, was captured among 12,111 independent SNPs significantly associated with adult height in a genome-wide association study (a method that scans the entire genome for variants correlated with a trait) of approximately 5,380,080 individuals across European, East Asian, Hispanic, African, and South Asian ancestries; those 12,111 SNPs collectively account for approximately 40% of phenotypic variance in European-ancestry populations (45% when all HapMap 3 reference panel SNPs are included) and roughly 10-20% in non-European populations. GTEx eQTL analysis (expression quantitative trait loci - statistical links between a genetic variant and gene activity levels) across 953 donors at FDR less than 0.05 links the alternate allele to reduced expression of MKNK1-AS1 in testis and reduced expression of KNCN in two cortical brain regions GTEx Portal. Additional eQTL signals from the same dataset associate this allele with increased MKNK1 expression in heart tissue, reduced MKNK1 expression in esophagus, reduced TMEM275 expression in brain nucleus accumbens, and reduced EFCAB14 expression in esophagus mucosa GTEx Portal.

Reported associations

• Adult height: Identified as one of 12,111 height-associated common variants in a genome-wide study of approximately 5.4 million individuals; the full set of identified SNPs explains roughly 40-45% of height variance in European-ancestry cohorts, though no individual effect size for this locus is provided in the available source.

Evidence quality The height association derives from a single, very large genome-wide study of 5,380,080 individuals spanning five ancestry groups, which identified 12,111 independent height-associated SNPs that together account for nearly all common-variant heritability of adult height. No p-value or beta coefficient specific to rs10890404 is available in the provided study text, so the per-SNP contribution to height cannot be quantified. Prediction accuracy for height drops to 10-20% in non-European populations, reflecting differences in linkage disequilibrium (the tendency for nearby genetic variants to be inherited together) and allele frequency across ancestries rather than an absence of the underlying biology. The GTEx eQTL signals for MKNK1-AS1, KNCN, MKNK1, TMEM275, and EFCAB14 are statistically significant at FDR less than 0.05 across 953 donors and span multiple tissue types, but eQTL status alone does not establish a causal link to any clinical outcome. No independent replication study specifically targeting this SNP appears in the available sources, so all associations should be considered preliminary.

Tissue-specific expression effects

• MKNK1-AS1: The alternate allele is associated with reduced expression in testis GTEx Portal.
• KNCN: The alternate allele is associated with reduced expression in brain cortex and frontal cortex (Brodmann area 9) GTEx Portal.
• MKNK1: The alternate allele is associated with increased expression in left ventricle and atrial appendage of the heart, and reduced expression in esophagus mucosa GTEx Portal.
• TMEM275: The alternate allele is associated with reduced expression in nucleus accumbens (a brain region within the basal ganglia) GTEx Portal.
• EFCAB14: The alternate allele is associated with reduced expression in esophagus mucosa GTEx Portal.

Lifestyle considerations No lifestyle considerations on file for this variant.