What you carry at this position in your DNA and what research says about it.
Cholesterol and Crohn's Risk: 5/10 evidence, 32 publications.
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Sample genotype (not yours): T/T
Higher Cholesterol but Lower Crohn's Risk
Carrying two copies of the T allele is associated with elevated blood lipid levels alongside a reduced risk of chronic inflammatory bowel conditions.
What this genotype means: Elevated LDL and HDL cholesterol levels; Lower risk of Crohn's disease; Lower risk of major depressive disorder.
Sample genotype (not yours): C/C
Lower Cholesterol but Higher Crohn's Risk
Carrying two copies of the C allele is associated with lower circulating cholesterol levels but an increased risk of Crohn's disease and depression.
What this genotype means: Lower LDL and HDL cholesterol levels; Increased risk of Crohn's disease; Higher susceptibility to major depressive disorder.
Sample genotype (not yours): T/C
Typical Cholesterol and Inflammatory Risk
Carrying one T and one C allele results in balanced lipid levels and a typical risk profile for inflammatory bowel and mood disorders.
What this genotype means: Typical circulating cholesterol levels; Standard baseline risk for Crohn's disease; Average susceptibility to mood disorders.
Gene function and biological role
Gene Function: The TMEM258 gene encodes transmembrane protein 258, which is localized to the endoplasmic reticulum membrane. This protein plays a critical role in maintaining endoplasmic reticulum homeostasis and regulating cellular stress responses. It is highly expressed in the intestinal epithelium, where it helps maintain the mucosal barrier. Genetic variation in this genomic region is tightly linked to the adjacent FADS gene cluster, which regulates the desaturation of polyunsaturated fatty acids. Consequently, alterations in this gene are associated with systemic lipid levels and inflammatory bowel conditions [1].
Variant Impact: The rs102275 variant is an intronic change located within the TMEM258 gene. This genetic variation influences the expression of both TMEM258 and neighboring lipid-metabolizing genes. The T allele is associated with significantly higher circulating levels of total cholesterol, LDL cholesterol, and HDL cholesterol [2]. Conversely, the C allele is linked to an increased susceptibility to chronic inflammatory conditions such as Crohn's disease [1] and major depressive disorder [3]. This variant represents a key genetic link between systemic lipid metabolism and immune system regulation.
Key Insight: This genetic variant acts as a metabolic pivot, where the version of the gene that protects against inflammatory bowel disease simultaneously raises circulating cholesterol levels.
Location: TMEM258. Chromosome 11 · 11q12.2 · 61.8 Mb
Estimated prevalence by population
Global 31.2%; European 43.0%; African 11.5%; East Asian 19.8%; South Asian 64.0%; Americas 18.8%; Ashkenazi 47.1%; Finnish 33.3%; Middle Eastern 34.6%; Amish 54.9%.
Estimated TT genotype frequency.
Global 45.4%; European 45.1%; African 44.8%; East Asian 49.4%; South Asian 32.0%; Americas 49.1%; Ashkenazi 43.1%; Finnish 48.8%; Middle Eastern 48.4%; Amish 38.4%.
Estimated TC genotype frequency.
Global 23.5%; European 11.8%; African 43.6%; East Asian 30.8%; South Asian 4.0%; Americas 32.1%; Ashkenazi 9.8%; Finnish 17.9%; Middle Eastern 16.9%; Amish 6.7%.
Estimated CC genotype frequency.
Showing effects for T/T genotype
Immunity & Inflammation
Chronic Inflammatory Diseases
Crohn's Disease. Evidence: 5/10. Source: PMID 21102463. Lower Risk.
Cardiovascular & Metabolic
Lipids & Cholesterol
LDL Cholesterol. Evidence: 9/10. Source: PMID 35213538. Increased Levels.
HDL Cholesterol. Evidence: 10/10. Source: PMID 20694148. Increased Levels.
Blood Cell & Iron Traits
Red Blood Cell Count. Evidence: 9/10. Source: PMID 30595370. Typical Count.
Neurology & Mental Health
Mood Disorders
Depression. Evidence: 8/10. Source: PMID 31926635. Lower Risk.
Showing effects for C/C genotype
Crohn's Disease. Evidence: 5/10. Source: PMID 21102463. Increased Risk.
LDL Cholesterol. Evidence: 9/10. Source: PMID 35213538. Decreased Levels.
HDL Cholesterol. Evidence: 10/10. Source: PMID 20694148. Decreased Levels.
Red Blood Cell Count. Evidence: 9/10. Source: PMID 30595370. Slightly Higher.
Depression. Evidence: 8/10. Source: PMID 31926635. Increased Risk.
Showing effects for T/C genotype
Crohn's Disease. Evidence: 5/10. Source: PMID 21102463. Typical Risk.
LDL Cholesterol. Evidence: 9/10. Source: PMID 35213538. Typical Levels.
HDL Cholesterol. Evidence: 10/10. Source: PMID 20694148. Typical Levels.
Depression. Evidence: 8/10. Source: PMID 31926635. Typical Risk.
What this genotype means for the people who carry it
Sample genotype: TT (Homozygous)
Inheriting two copies of the T allele leads to a distinct metabolic profile characterized by elevated circulating lipids. Large-scale genetic studies show that this genotype is associated with significantly higher levels of total cholesterol, LDL cholesterol, and apolipoprotein B [1]. Interestingly, it also correlates with higher levels of protective HDL cholesterol [2]. While these lipid elevations might suggest cardiovascular caution, the T/T genotype offers a protective advantage against several inflammatory and mood-related conditions. Research indicates that individuals with this genotype have a lower risk of developing Crohn's disease [3]. Additionally, this genetic makeup is associated with a reduced susceptibility to major depressive disorder [4]. The biological mechanism likely involves altered fatty acid desaturation, which influences systemic inflammation and cellular membrane composition.
Elevated LDL and HDL cholesterol levels; Lower risk of Crohn's disease; Lower risk of major depressive disorder.
Sample genotype: CC (Homozygous)
Carrying two copies of the C allele results in a metabolic trade-off characterized by favorable lipid profiles but higher inflammatory susceptibility. Clinical data demonstrate that this genotype is linked to lower levels of total cholesterol, LDL cholesterol, and apolipoprotein B [1]. However, this lipid-lowering effect is accompanied by a decrease in protective HDL cholesterol [2]. On the immunological side, the C/C genotype is associated with a higher risk of developing Crohn's disease, a chronic inflammatory bowel condition [3]. This genetic variation is also linked to an increased susceptibility to major depressive disorder [4]. Furthermore, individuals with this genotype tend to exhibit slightly higher red blood cell and reticulocyte counts [5]. These diverse effects are driven by changes in fatty acid metabolism that can influence both systemic inflammation and brain chemistry.
Lower LDL and HDL cholesterol levels; Increased risk of Crohn's disease; Higher susceptibility to major depressive disorder.
Sample genotype: TC (Heterozygous)
Possessing one copy of each allele establishes an intermediate biological baseline for both lipid transport and inflammatory pathways. Circulating levels of LDL cholesterol, HDL cholesterol, and total cholesterol generally remain within the typical population average [1]. This balanced state extends to the immune system, where the risk of developing chronic inflammatory bowel conditions like Crohn's disease is not significantly elevated or reduced [2]. Similarly, the likelihood of experiencing major depressive disorder aligns with standard baseline statistics [3]. Because this genotype represents a blend of the lipid-elevating T allele and the inflammation-prone C allele, the opposing genetic forces tend to neutralize each other. Cellular membranes maintain a standard distribution of polyunsaturated fatty acids, supporting normal physiological function without extreme metabolic shifts.
Typical circulating cholesterol levels; Standard baseline risk for Crohn's disease; Average susceptibility to mood disorders.
Variants with shared genetic architecture
rs174538 · TMEM258 Gene · Chr 11 · Fatty Acid Metabolism
rs740006 · TMEM258 Gene · Chr 11 · Blood Lipid Balance
rs1077835 · LIPC Gene · Chr 15 · HDL Cholesterol Levels
The Polygenic and Monogenic Basis of Blood Traits and Diseases.
Content updated August 2026.
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