rs112401631 (CCR7/SMARCE1): Immune and Skin Variant

Key takeaways

• rs112401631 lies between CCR7, an immune cell navigation receptor that routes T cells and dendritic cells to lymph nodes, and SMARCE1, a gene activity regulator involved in chromatin remodeling
• The alternative allele reduces SMARCE1 expression in non-sun-exposed skin and thyroid tissue based on GTEx eQTL data
• Large GWAS studies of atopic dermatitis, eczema, and asthma covering hundreds of thousands of participants have studied this chromosomal region
• The skin and thyroid gene expression finding is the most specific evidence available for this particular variant
• No clinical utility is established; all associations are population-level statistical signals

What the research says rs112401631 sits in the CCR7-SMARCE1 locus; CCR7 encodes a G protein-coupled chemokine receptor (a cell-surface sensor directing immune cells such as T cells and dendritic cells into lymph nodes) while SMARCE1 encodes a subunit of the SWI/SNF chromatin remodeling complex (a protein machine that reorganizes DNA packaging to govern gene accessibility). Large-scale multi-ancestry GWAS meta-analyses covering this region include an atopic dermatitis study of 56,146 cases and 602,280 controls across five ancestry groups, an asthma meta-analysis of 69,189 cases and 702,199 controls, and blood cell phenotype analyses spanning up to 746,667 participants. The most specific evidence for this variant comes from GTEx v11 eQTL data showing the alternative allele reduces SMARCE1 transcription in two distinct tissues GTEx Portal.

Reported associations

• SMARCE1 expression in non-sun-exposed skin: The alternative allele reduces SMARCE1 expression (effect: -0.35 log2 units, p=1.3e-4) in suprapubic skin, based on GTEx v11 data from 953 donors GTEx Portal
• SMARCE1 expression in thyroid: The alternative allele reduces SMARCE1 expression (effect: -0.31 log2 units, p=2.2e-4) in thyroid tissue GTEx Portal
• Atopic dermatitis: This locus was studied in a multi-ancestry GWAS meta-analysis of 12 cohorts (56,146 cases, 602,280 controls, five ancestry groups) that identified 101 associated genomic loci; fine-mapping implicated keratinocytes and immune cell types as disease-relevant
• Eczema: A rare variant meta-analysis of 20,016 cases and 380,433 controls found rare and low-frequency variants account for over 20% of single nucleotide variant-based heritability, with prioritized genes significantly up-regulated in skin
• Asthma: A GWAS meta-analysis of 69,189 cases and 702,199 controls identified 88 independent associations at 56 loci, implicating T cell regulation and airway remodeling genes - pathways in which CCR7-mediated trafficking is involved

Evidence quality The most directly supported evidence for rs112401631 is the GTEx v11 eQTL resource (953 donors, FDR<0.05), showing reduced SMARCE1 expression in non-sun-exposed skin (p=1.3e-4) and thyroid (p=2.2e-4) GTEx Portal. These p-values satisfy the GTEx FDR<0.05 threshold but fall short of conventional genome-wide significance (5e-8); the eQTL signals are preliminary. The associated GWAS studies are well-powered: the atopic dermatitis meta-analysis covered 658,426 participants, the asthma analysis 771,388, and the VA Million Veteran Program 635,969 participants (29% non-European) across 2,068 traits. The available study texts do not report a specific p-value or effect size for rs112401631 in any disease trait, so direct variant-to-disease contribution cannot be confirmed from the excerpts provided. Consistent direction across two tissues modestly supports a genuine SMARCE1 regulatory effect.

Tissue-specific expression effects

• SMARCE1: The alternative allele is associated with reduced expression in both non-sun-exposed skin (suprapubic, -0.35 log2 units) and thyroid (-0.31 log2 units); direction is consistent across both tissues GTEx Portal

Lifestyle considerations No lifestyle considerations on file for this variant.