rs111351217 (IFI35/VAT1): Gene Expression Variant
Key takeaways
- rs111351217 alters activity of at least three nearby genes across peripheral nerve, lung, non-sun-exposed skin, skeletal muscle, and aortic tissue.
- The alternate allele reduces expression of ENSG00000304661 in tibial nerve, lung, and non-sun-exposed skin.
- The same allele increases expression of NBR2 in tibial nerve, non-sun-exposed skin, skeletal muscle, and lung.
- TMEM106A expression in the aorta is increased in alternate allele carriers.
- No direct clinical trait associations are documented in the provided evidence for this variant.
Key takeaways
- rs111351217 alters activity of at least three nearby genes across peripheral nerve, lung, non-sun-exposed skin, skeletal muscle, and aortic tissue.
- The alternate allele reduces expression of ENSG00000304661 in tibial nerve, lung, and non-sun-exposed skin.
- The same allele increases expression of NBR2 in tibial nerve, non-sun-exposed skin, skeletal muscle, and lung.
- TMEM106A expression in the aorta is increased in alternate allele carriers.
- No direct clinical trait associations are documented in the provided evidence for this variant.
What the research says GTEx v11 data from 953 donors identifies rs111351217 as an expression quantitative trait locus (eQTL, a variant that influences how much a nearby gene is expressed in a given tissue) for three genes in the IFI35/VAT1 genomic region, with effects in tibial nerve, lung, non-sun-exposed skin, skeletal muscle, and aortic tissue GTEx Portal. The alternate allele simultaneously reduces expression of ENSG00000304661 and increases expression of NBR2 in an overlapping set of tissues, representing opposing directional effects from a single variant GTEx Portal. A Mendelian randomization study of lipid-modifying drug targets, examining up to 115,082 UK Biobank participants across 249 metabolic traits, provides methodological context for how genetic variants are used to characterize biological pathway effects, though it does not report a direct association for this variant.
Reported associations
- ENSG00000304661 expression (eQTL): The alternate allele is associated with reduced expression in tibial nerve (slope -0.57, p=2.7e-5), lung (slope -0.49, p=5.9e-5), and non-sun-exposed skin (slope -0.45, p=2.5e-4) GTEx Portal.
- NBR2 expression (eQTL): The alternate allele is associated with increased expression in tibial nerve (slope +0.51, p=5.0e-5), non-sun-exposed skin (slope +0.48, p=7.4e-6), skeletal muscle (slope +0.40, p=1.4e-4), and lung (slope +0.35, p=4.0e-5) GTEx Portal.
- TMEM106A expression (eQTL): The alternate allele is associated with increased expression in aortic tissue (slope +0.29, p=5.4e-5) GTEx Portal.
Evidence quality The three eQTL associations are drawn from GTEx v11 (953 donors, cis-window analysis, FDR < 0.05), a well-characterized reference dataset for tissue-specific gene expression. Nominal p-values for individual tissue-gene pairs range from 7.4e-6 for NBR2 in non-sun-exposed skin to 2.5e-4 for ENSG00000304661 in non-sun-exposed skin, each meeting the FDR threshold for the dataset. No independent replication is available from the provided evidence. A Mendelian randomization study of up to 115,082 UK Biobank participants across 249 metabolic traits provides context for genetic variant-based inference in lipid-relevant pathways but reports no clinical trait associations for this variant. Evidence is limited to tissue-specific expression effects, which represent preliminary mechanistic signals rather than established links to clinical outcomes.
Tissue-specific expression effects
- ENSG00000304661: The alternate allele is associated with reduced expression in tibial nerve, lung, and non-sun-exposed skin GTEx Portal.
- NBR2: The alternate allele is associated with increased expression in tibial nerve, non-sun-exposed skin, skeletal muscle, and lung GTEx Portal.
- TMEM106A: The alternate allele is associated with increased expression in aortic tissue GTEx Portal.
Lifestyle considerations No lifestyle considerations on file for this variant.
Frequently asked questions
What is rs111351217 associated with?
Based on GTEx v11 data, rs111351217 is linked to altered expression of three nearby genes: ENSG00000304661 (reduced expression), NBR2 (increased expression), and TMEM106A (increased expression), across tissues including tibial nerve, lung, skin, skeletal muscle, and aorta. No clinical health outcome associations are reported in the provided evidence.
Which tissues are affected by rs111351217?
GTEx v11 data shows gene expression changes associated with this variant in tibial nerve, lung, non-sun-exposed skin, skeletal muscle, and aortic tissue.
What is an eQTL and why does it matter?
An eQTL (expression quantitative trait locus) is a genetic variant that affects how much a nearby gene is expressed in a cell or tissue. rs111351217 is classified as an eQTL, meaning its effect is on gene activity levels rather than on a protein's structure directly.
Is rs111351217 linked to any diseases?
The provided evidence does not document direct associations between this variant and any specific diseases or clinical health outcomes. Its known effects in the provided data are limited to influencing gene expression levels in certain tissues.
What are the IFI35 and VAT1 genes?
IFI35 and VAT1 are the primary genes in the chromosomal region where rs111351217 is located. The provided studies do not describe their specific functional roles in relation to this variant.