rs1172147 (TMCC2): Blood Cell Variant & eQTL Effects
Key takeaways
- rs1172147 was found in a 563,000-person study of 29 blood cell traits
- The ALT allele increases TMCC2 gene activity in body fat and skeletal muscle
- The same variant raises DSTYK expression in arteries, nerves, and skin
- CNTN2 expression in skin and TMEM81 expression in immune cells are both lowered by the ALT allele
- No drug response or lifestyle connections have been established for this variant
Key takeaways
- rs1172147 was identified in a 563,000-person genome-wide study of blood cell traits covering 29 distinct hematopoietic phenotypes
- The ALT allele increases TMCC2 (Transmembrane and Coiled-Coil Domains 2) gene activity in subcutaneous fat and skeletal muscle
- The same variant also raises DSTYK expression in arteries, nerves, and skin, while lowering CNTN2 expression in skin and TMEM81 expression in immune cells
- These tissue-specific expression effects are drawn from GTEx v11 data (953 donors) at a false discovery rate below 0.05
- No drug response or lifestyle connections have been established for this variant
What the research says rs1172147, located near the TMCC2 locus, was among 5,106 newly identified genetic variants linked to 29 blood cell phenotypes in a study of 563,085 European ancestry participants that integrated UK Biobank and international consortium data. The study characterized the genetic architecture of hematopoiesis (the biological process of blood cell formation) using functional genomic annotations to map variants to regulatory regions active in blood-forming cells. In parallel, GTEx v11 data show that this locus acts as a cis-eQTL (a variant that influences expression of nearby genes within the same chromosomal neighborhood) for at least four genes across multiple tissue types GTEx Portal.
Reported associations
- Blood cell phenotypes (29 traits): rs1172147 was identified as one of 5,106 newly discovered variants associated with hematopoietic phenotypes in a study of 563,085 European ancestry participants, covering red cell, white cell, and platelet measures; specific per-trait effect sizes for this variant are not reported in the provided study text
- TMCC2 gene expression - subcutaneous fat and skeletal muscle: The ALT allele is associated with increased expression of TMCC2 in subcutaneous adipose tissue and skeletal muscle GTEx Portal
- DSTYK gene expression - multiple tissues: The ALT allele is associated with increased DSTYK expression in subcutaneous adipose tissue, tibial artery, tibial nerve, and sun-exposed lower leg skin GTEx Portal
- CNTN2 gene expression - sun-exposed skin: The ALT allele is associated with decreased CNTN2 (Contactin-2) expression in sun-exposed lower leg skin GTEx Portal
- TMEM81 gene expression - immune cells: The ALT allele is associated with decreased TMEM81 expression in EBV-transformed lymphocytes, a laboratory model of immune B cells GTEx Portal
Evidence quality The blood cell trait association derives from a large, well-powered GWAS with 563,085 European ancestry participants using UK Biobank and multi-cohort consortium data, with fine-mapping analyses applied to identify likely causal variants in regulatory regions relevant to hematopoietic cell states. Specific per-variant effect sizes for blood cell traits are not available in the provided study text, limiting assessment of this variant's individual contribution to trait variance. The GTEx eQTL findings are based on 953 donors (v11) at FDR below 0.05, covering four affected genes across several tissues, which represents a robust expression dataset. The study population is predominantly of European ancestry, which may limit generalizability to other populations. No independent replication studies specific to rs1172147 were provided.
Tissue-specific expression effects
- TMCC2: The ALT allele is associated with increased expression in subcutaneous adipose tissue and skeletal muscle GTEx Portal
- DSTYK: The ALT allele is associated with increased expression in subcutaneous adipose tissue, tibial artery, tibial nerve, and sun-exposed lower leg skin GTEx Portal
- CNTN2: The ALT allele is associated with reduced expression in sun-exposed lower leg skin GTEx Portal
- TMEM81: The ALT allele is associated with reduced expression in EBV-transformed lymphocytes, a laboratory model of immune B cells GTEx Portal
Lifestyle considerations No lifestyle considerations on file for this variant.
Frequently asked questions
What is the TMCC2 gene and what does it do?
TMCC2 stands for Transmembrane and Coiled-Coil Domains 2 and encodes a protein embedded in cell membranes. The rs1172147 variant influences how actively this gene is expressed, with the ALT allele associated with higher TMCC2 activity in subcutaneous fat and skeletal muscle.
What blood traits is rs1172147 linked to?
The variant was identified in a genome-wide study examining 29 blood cell phenotypes, including measures of red blood cells, white blood cells, and platelets, in over 563,000 participants. Specific per-trait effect sizes for rs1172147 were not reported in the available study text.
What does rs1172147 do to gene expression?
GTEx data show that the ALT allele increases TMCC2 expression in fat and muscle and raises DSTYK expression in arteries, nerves, and skin. It also decreases CNTN2 expression in skin and TMEM81 expression in immune B cells. These are called eQTL effects, meaning the variant influences how much of each nearby gene product is produced.
Is rs1172147 linked to any disease?
The variant was identified through a study of normal blood cell trait variation in over half a million people. The provided research does not link it to a specific blood disease, only to variation in hematopoietic measures across the general population.
What is an eQTL and why does it matter for rs1172147?
An eQTL (expression quantitative trait locus) is a genetic variant that influences how much of a nearby gene's product is made in a given tissue. rs1172147 acts as an eQTL for four genes, suggesting it may affect biological processes in fat, muscle, blood vessels, skin, and immune cells, though eQTL effects indicate a potential mechanism rather than a confirmed clinical outcome.