rs12251249 (ADAM12): Brain FANK1 Expression Variant
Key takeaways
- rs12251249 sits in the ADAM12 gene region and was captured in a large Korean genetic study of 153,950 individuals examining 36 different health traits.
- The variant's alternate form is linked to reduced activity of the FANK1 gene across at least six brain regions, most strongly in the frontal cortex.
- Testis tissue shows the most statistically robust gene-expression effect for this variant across all tissues tested.
- The specific health trait this variant was associated with in the Korean genetic study is not specified in the available research text.
- The gene-expression data come from GTEx v11 and reflect a regulatory effect on FANK1, not an established disease outcome.
Key takeaways
- rs12251249 sits in the ADAM12 gene region and was captured in a large Korean genetic study of 153,950 individuals examining 36 different health traits.
- The variant's alternate form is linked to reduced activity of the FANK1 gene across at least six brain regions, most strongly in the frontal cortex.
- Testis tissue shows the most statistically robust gene-expression effect for this variant across all tissues tested.
- The specific health trait this variant was associated with in the Korean genetic study is not specified in the available research text.
- The gene-expression data come from GTEx v11 and reflect a regulatory effect on FANK1, not an established disease outcome.
What the research says rs12251249 falls within the ADAM12 (a disintegrin and metalloproteinase 12) gene region and was identified in a genome-wide association study (GWAS) of 36 quantitative traits conducted in 153,950 Korean participants from the KCPS2 Biobank, a study that discovered 301 previously unreported loci across East Asian samples; however, the specific phenotypic association for this locus is not stated in the available text. GTEx v11 data (953 donors) show that the alternate allele at this position reduces expression of FANK1 (fibronectin type III and ankyrin repeat domains 1) across eight tissues including six distinct brain regions, with log2-scale effect sizes ranging from -0.12 to -0.36 and p-values reaching 1.8e-14 in testis GTEx Portal.
Reported associations
- FANK1 mRNA expression - multiple brain regions: The alternate allele reduces expression in frontal cortex BA9 (slope -0.36, p=6.1e-8), putamen basal ganglia (slope -0.29, p=1.7e-6), cortex (slope -0.28, p=2.4e-5), nucleus accumbens basal ganglia (slope -0.26, p=1.3e-5), hippocampus (slope -0.17, p=1.3e-5), and hypothalamus (slope -0.16, p=2.2e-5) GTEx Portal
- FANK1 mRNA expression - testis: Reduced expression (slope -0.15, p=1.8e-14), the strongest p-value for this variant across all GTEx tissues reported GTEx Portal
- FANK1 mRNA expression - esophageal mucosa: Reduced expression (slope -0.12, p=2.7e-5) GTEx Portal
- 36 quantitative traits, Korean GWAS: Captured in a study examining anthropometric, metabolic, liver, kidney, hematological, cardiovascular, and lifestyle measures in 153,950 Koreans; the specific phenotypic link for this locus is not detailed in the available study text.
Evidence quality The GTEx eQTL (expression quantitative trait locus, meaning a genetic variant associated with changes in how actively a gene is read out in a given tissue) findings draw on 953 donors from GTEx v11. The direction of reduced FANK1 expression is consistent across six independent brain tissue types, providing cross-tissue support for the eQTL signal. The testis association reaches p=1.8e-14, the most statistically robust result reported for this variant in the GTEx data. The GWAS enrolled 153,950 Korean participants and identified 301 novel loci across 36 quantitative traits, but the specific phenotypic association for rs12251249 is not stated in the available text, limiting interpretation of its health relevance. No independent replication or conflicting findings for any specific GWAS trait association are available in the provided sources. Evidence for clinical significance is not established.
Tissue-specific expression effects
- FANK1: The alternate allele reduces expression of this gene in six brain regions - most strongly in frontal cortex (BA9), followed by putamen basal ganglia, cortex, nucleus accumbens basal ganglia, hippocampus, and hypothalamus - and also reduces expression in testis (where the statistical association is the strongest across all tissues) and in esophageal mucosa GTEx Portal
Lifestyle considerations No lifestyle considerations on file for this variant.
Frequently asked questions
What is rs12251249?
rs12251249 is a genetic variant located in the ADAM12 gene region. GTEx data show it reduces activity of a nearby gene called FANK1 across multiple brain regions and in testis. It was also identified in a large Korean population genetic study of 36 quantitative health traits.
What does the ADAM12 gene do?
ADAM12 encodes a disintegrin and metalloproteinase enzyme involved in cell surface remodeling and signaling. The rs12251249 variant sits in this gene's region, though GTEx expression data show the variant's measured effects on a neighboring gene, FANK1, rather than on ADAM12 itself.
What is FANK1 and why is its expression affected by this variant?
FANK1 (fibronectin type III and ankyrin repeat domains 1) is a gene expressed broadly in brain tissue and testis. GTEx data indicate that rs12251249 acts as a regulatory variant that reduces FANK1 expression across multiple tissues, though the downstream functional or health consequences are not established by the available sources.
Is rs12251249 linked to any disease?
The available sources do not link rs12251249 to any specific disease. It was identified in a Korean GWAS of 36 quantitative traits, but the specific phenotypic association is not stated in the available text. The GTEx data describe gene expression effects, not disease outcomes.
In which populations has this variant been studied?
The GWAS study that captured rs12251249 was conducted in 153,950 Korean participants from the KCPS2 Biobank, representing an East Asian population. The GTEx expression data draw on a multi-ancestry cohort of 953 donors. No population-specific allele frequency comparisons are provided in the available sources.