What you carry at this position in your DNA and what research says about it.
Autoimmune Disease Risk: 8/10 evidence, 14 publications.
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Sample genotype (not yours): T/T
Higher Celiac Risk but Lower Multiple Sclerosis Risk
This genotype increases susceptibility to celiac disease while offering protection against multiple sclerosis and rheumatoid arthritis.
What this genotype means: Increased susceptibility to celiac disease; Lower risk of multiple sclerosis; Lower risk of rheumatoid arthritis.
Sample genotype (not yours): C/C
Higher Multiple Sclerosis Risk but Lower Celiac Risk
This genotype increases the risk of multiple sclerosis and rheumatoid arthritis while protecting against celiac disease.
What this genotype means: Increased risk of multiple sclerosis; Increased risk of rheumatoid arthritis; Lower risk of celiac disease.
Sample genotype (not yours): T/C
Typical Autoimmune Disease Risk
This genotype carries one protective and one risk allele, resulting in typical baseline risks for several autoimmune conditions.
What this genotype means: Typical risk for celiac disease; Typical risk for multiple sclerosis; Typical risk for rheumatoid arthritis.
Gene function and biological role
Gene Function: The TAGAP gene encodes the T cell activation RhoGTPase activating protein, which plays a vital role in regulating the transmission of signals within T cells [1]. These immune cells are responsible for identifying and targeting foreign invaders, but their dysregulation can lead to autoimmune conditions [2]. By modulating Rho GTPase activity, this protein helps control the cytoskeletal changes necessary for T cell activation and migration [1]. Consequently, genetic variations that alter how this gene is expressed can shift the balance of the immune system, predisposing individuals to various inflammatory and autoimmune disorders [2].
Variant Impact: The rs1738074 variant is located in the 5 prime untranslated region of the TAGAP gene, a regulatory area that influences gene expression [3]. The T allele at this position acts as an expression quantitative trait locus, leading to decreased expression of the TAGAP protein in immune cells [4]. This reduction in protein levels alters T cell activation pathways, creating a complex trade-off in autoimmune susceptibility [4]. While lower expression dampens certain inflammatory responses, it simultaneously increases the risk of other immune-mediated conditions [3].
Key Insight: This variant presents an evolutionary trade-off where protecting against one autoimmune disease directly increases the risk of developing another.
Location: TAGAP. Chromosome 6 · 6q25.3 · 159.0 Mb
Estimated prevalence by population
Global 27.0%; European 17.4%; African 45.8%; East Asian 34.1%; South Asian 14.7%; Americas 29.2%; Ashkenazi 16.8%; Finnish 18.0%; Middle Eastern 22.0%; Amish 16.6%.
Estimated TT genotype frequency.
Global 47.4%; European 48.6%; African 43.8%; East Asian 48.6%; South Asian 47.3%; Americas 49.7%; Ashkenazi 48.4%; Finnish 48.8%; Middle Eastern 49.8%; Amish 48.3%.
Estimated TC genotype frequency.
Global 25.7%; European 34.0%; African 10.5%; East Asian 17.3%; South Asian 38.0%; Americas 21.2%; Ashkenazi 34.8%; Finnish 33.2%; Middle Eastern 28.2%; Amish 35.1%.
Estimated CC genotype frequency.
Showing effects for T/T genotype
Immunity & Inflammation
Autoimmune Diseases
Multiple Sclerosis. Evidence: 8/10. Source: PMID 21833088. Lower Risk.
Celiac Disease. Evidence: 6/10. Source: PMID 18311140. ~1.17x Higher Risk.
Rheumatoid Arthritis. Evidence: 6/10. Source: PMID 38368726. Lower Risk.
Endocrine & Reproductive
Hormone Levels & Endocrine Regulation
Hypothyroidism. Evidence: 8/10. Source: PMID 38368726. Lower Risk.
Cardiovascular & Metabolic
Blood Cell & Iron Traits
Myeloid White Cell Count. Evidence: 7/10. Source: PMID 32888493. Higher Count.
Showing effects for C/C genotype
Multiple Sclerosis. Evidence: 8/10. Source: PMID 21833088. ~1.13x Higher Risk.
Celiac Disease. Evidence: 6/10. Source: PMID 18311140. Lower Risk.
Rheumatoid Arthritis. Evidence: 6/10. Source: PMID 38368726. Increased Risk.
Hypothyroidism. Evidence: 8/10. Source: PMID 38368726. Increased Risk.
Myeloid White Cell Count. Evidence: 7/10. Source: PMID 32888493. Lower Count.
Showing effects for T/C genotype
Multiple Sclerosis. Evidence: 8/10. Source: PMID 21833088. Typical Risk.
Celiac Disease. Evidence: 6/10. Source: PMID 18311140. Typical Risk.
Rheumatoid Arthritis. Evidence: 6/10. Source: PMID 38368726. Typical Risk.
Hypothyroidism. Evidence: 8/10. Source: PMID 38368726. Typical Risk.
Myeloid White Cell Count. Evidence: 7/10. Source: PMID 32888493. Typical Count.
What this genotype means for the people who carry it
Sample genotype: TT (Homozygous)
Inheriting two copies of the T allele leads to reduced expression of the TAGAP gene in immune cells [1]. This altered immune signaling is associated with an approximate 1.17-fold increase in the risk of developing celiac disease [2]. However, this same reduction in gene expression appears to protect the body from overactive autoimmune attacks in other tissues. Consequently, this genotype is linked to a significantly lower risk of multiple sclerosis, rheumatoid arthritis, and hypothyroidism [3]. It is also associated with a slightly higher baseline count of myeloid leukocytes, which are essential white blood cells involved in the innate immune response [4].
Increased susceptibility to celiac disease; Lower risk of multiple sclerosis; Lower risk of rheumatoid arthritis.
Sample genotype: CC (Homozygous)
Inheriting two copies of the C allele maintains higher levels of TAGAP expression, which influences how T cells respond to inflammatory signals [1]. This heightened immune activity is associated with an approximate 1.13-fold increase in the risk of multiple sclerosis [2]. It also elevates the risk of developing rheumatoid arthritis and hypothyroidism [3]. On the positive side, this active immune state provides strong protection against celiac disease, resulting in a significantly lower risk of gluten-induced autoimmune damage [4]. Additionally, this genotype is associated with a slightly lower baseline count of myeloid leukocytes [5].
Increased risk of multiple sclerosis; Increased risk of rheumatoid arthritis; Lower risk of celiac disease.
Sample genotype: TC (Heterozygous)
Carrying one T allele and one C allele establishes an intermediate level of TAGAP gene expression in the immune system [1]. Because the two alleles have opposing effects on different autoimmune pathways, they effectively balance each other out [2]. This results in a typical baseline risk for celiac disease, multiple sclerosis, rheumatoid arthritis, and hypothyroidism [3]. Baseline levels of myeloid leukocytes also remain within the standard average range [4]. No specific dietary or lifestyle adjustments are typically suggested based on this balanced genetic profile.
Typical risk for celiac disease; Typical risk for multiple sclerosis; Typical risk for rheumatoid arthritis.
Variants with shared genetic architecture
rs3890745 · MMEL1 Gene · Chr 1 · Autoimmune Disease Risk
rs1893592 · UBASH3A Gene · Chr 21 · Autoimmune Disease Risk
rs1980422 · CD28 Gene · Chr 2 · Autoimmune Disease Risk
Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis.
Genome-wide meta-analysis identifies novel multiple sclerosis susceptibility loci.
Multiple common variants for celiac disease influencing immune gene expression.
Newly identified genetic risk variants for celiac disease related to the immune response.
Content updated August 2026.
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