What you carry at this position in your DNA and what research says about it.
Multiple Sclerosis Risk: 8/10 evidence, 26 publications.
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Sample genotype (not yours): T/T
Typical Multiple Sclerosis Risk
This genotype is associated with baseline risk for multiple sclerosis and other autoimmune conditions. It is the most common genetic profile globally.
What this genotype means: Baseline risk for multiple sclerosis; Slightly higher baseline C-reactive protein levels.
Sample genotype (not yours): C/C
Increased Multiple Sclerosis Risk
Carrying two copies of the variant C allele is linked to an increased risk of developing multiple sclerosis and primary biliary cholangitis.
What this genotype means: Increased risk of multiple sclerosis; Increased risk of primary biliary cholangitis; Slightly lower baseline C-reactive protein levels.
Sample genotype (not yours): T/C
Slightly Increased Multiple Sclerosis Risk
Carrying one copy of the variant C allele is linked to a slightly higher risk of developing multiple sclerosis and primary biliary cholangitis.
What this genotype means: Slightly increased risk of multiple sclerosis; Slightly increased risk of primary biliary cholangitis.
Gene function and biological role
Gene Function: The TNFRSF1A gene encodes a key subunit of the tumor necrosis factor receptor 1, which plays a central role in regulating inflammation and cell survival [1]. This receptor binds to tumor necrosis factor alpha, a powerful signaling protein that coordinates the body's immune response [2]. When this pathway is altered, it can lead to chronic inflammatory states or autoimmune diseases where the immune system mistakenly attacks healthy tissues [1] [3]. Interestingly, while blocking this receptor is highly effective for treating some autoimmune conditions like rheumatoid arthritis, it can actually trigger or worsen multiple sclerosis [4].
Variant Impact: This variant is located within an intron of the TNFRSF1A gene and alters how the genetic code is spliced together [4]. Specifically, the variant allele promotes the skipping of exon 6, which leads to the production of a shortened, soluble form of the receptor [4] [5]. This soluble receptor acts as a natural decoy, binding to and neutralizing tumor necrosis factor alpha in the bloodstream [4]. While this natural blockade mimics the effects of anti-inflammatory medications, it paradoxically increases the risk of developing multiple sclerosis [4] [6].
Key Insight: The genetic variant mimics the biological effect of anti-TNF medications, which are highly effective for arthritis but can trigger multiple sclerosis relapses.
Location: TNFRSF1A. Chromosome 12 · 12p13.31 · 6.3 Mb
Estimated prevalence by population
Global 39.3%; European 34.5%; African 42.5%; East Asian 74.7%; South Asian 48.7%; Americas 41.8%; Ashkenazi 34.5%; Finnish 34.3%; Middle Eastern 36.2%; Amish 39.2%.
Estimated TT genotype frequency.
Global 46.3%; European 48.5%; African 45.4%; East Asian 23.5%; South Asian 42.2%; Americas 45.7%; Ashkenazi 48.5%; Finnish 48.5%; Middle Eastern 47.9%; Amish 46.8%.
Estimated TC genotype frequency.
Global 14.4%; European 17.0%; African 12.1%; East Asian 1.8%; South Asian 9.1%; Americas 12.5%; Ashkenazi 17.0%; Finnish 17.2%; Middle Eastern 15.8%; Amish 14.0%.
Estimated CC genotype frequency.
Showing effects for T/T genotype
Immunity & Inflammation
Autoimmune Diseases
Multiple Sclerosis. Evidence: 8/10. Source: PMID 19525953. Typical Risk.
Inflammatory & Circulating Protein Markers
C-Reactive Protein. Evidence: 8/10. Source: PMID 35459240. Slightly Higher.
Infection Susceptibility & Resistance
Pneumonia. Evidence: 4/10. Source: PMID 28928442. Typical.
Organ Systems
Liver Function & Disease
Biliary Cholangitis. Evidence: 7/10. Source: PMID 22961000. Typical Risk.
Showing effects for C/C genotype
Multiple Sclerosis. Evidence: 8/10. Source: PMID 19525953. ~1.4x Increased Risk.
C-Reactive Protein. Evidence: 8/10. Source: PMID 35459240. Slightly Lower.
Pneumonia. Evidence: 4/10. Source: PMID 28928442. Altered Risk.
Biliary Cholangitis. Evidence: 7/10. Source: PMID 22961000. ~1.27x Increased Risk.
Showing effects for T/C genotype
Multiple Sclerosis. Evidence: 8/10. Source: PMID 19525953. ~1.2x Increased Risk.
C-Reactive Protein. Evidence: 8/10. Source: PMID 35459240. Typical.
Biliary Cholangitis. Evidence: 7/10. Source: PMID 22961000. ~1.2x Increased Risk.
What this genotype means for the people who carry it
Sample genotype: TT (Homozygous)
Having two copies of the major T allele means your body produces typical levels of the full-length tumor necrosis factor receptor [1]. This maintains standard immune signaling pathways and is not associated with an elevated risk of developing multiple sclerosis [2]. Large-scale genomic studies confirm that this profile represents the baseline risk for autoimmune conditions like primary biliary cholangitis [3]. However, this genotype is associated with slightly higher baseline levels of C-reactive protein, a common marker of systemic inflammation [4]. ClinVar database entries classify this common genetic profile as harmless and benign [1]. It is the most frequent genotype across almost all ancestral populations.
Baseline risk for multiple sclerosis; Slightly higher baseline C-reactive protein levels.
Sample genotype: CC (Homozygous)
Having two copies of the C allele significantly increases the production of a soluble, truncated form of the tumor necrosis factor receptor [1]. This soluble receptor acts as a natural inhibitor of tumor necrosis factor alpha, mimicking the biological effects of anti-TNF medications [1] [2]. While this can lower some markers of systemic inflammation like C-reactive protein, it increases susceptibility to autoimmune attacks on the central nervous system [3] [4]. Large-scale genetic studies show that this genotype is associated with a 1.3-fold to 1.4-fold increase in the risk of developing multiple sclerosis [5]. It is also linked to a higher risk of primary biliary cholangitis [6]. However, because this variant is very common and has a low overall impact on its own, clinical databases like ClinVar classify it as benign rather than a direct disease-causing mutation [1].
Increased risk of multiple sclerosis; Increased risk of primary biliary cholangitis; Slightly lower baseline C-reactive protein levels.
Sample genotype: TC (Heterozygous)
Carrying one copy of the C allele alters the splicing of the TNFRSF1A gene, leading to the production of a soluble receptor isoform [1]. This soluble receptor can neutralize tumor necrosis factor alpha, which paradoxically increases susceptibility to certain autoimmune diseases [1] [2]. Large genome-wide association studies have linked this single-copy profile to a roughly 1.15-fold to 1.2-fold increase in the risk of multiple sclerosis [3]. It is also associated with a slightly elevated risk of primary biliary cholangitis, a chronic autoimmune liver disease [4]. Despite these statistical associations, ClinVar classifies this variant as benign because it does not cause disease on its own and is highly common in the general population [1]. Most people with this genotype never develop any autoimmune conditions.
Slightly increased risk of multiple sclerosis; Slightly increased risk of primary biliary cholangitis.
Variants with shared genetic architecture
rs1800692 · TNFRSF1A Gene · Chr 12 · Blood Cell Levels
rs4149577 · TNFRSF1A Gene · Chr 12 · Ankylosing Spondylitis Risk
rs4149584 · TNFRSF1A Gene · Chr 12 · Multiple Sclerosis Risk
Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis.
TNF receptor 1 genetic risk mirrors outcome of anti-TNF therapy in multiple sclerosis.
Multiple sclerosis genomic map implicates peripheral immune cells and microglia in susceptibility.
Genetic analysis of over half a million people characterises C-reactive protein loci.
Content updated August 2026.
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