What you carry at this position in your DNA and what research says about it.
Autoimmune Disease Risk: 10/10 evidence, 28 publications.
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Sample genotype (not yours): T/T
Typical Risk of Autoimmune Conditions
Two copies of the T allele are associated with typical, baseline susceptibility to autoimmune disorders. This genotype maintains normal expression of protective immune regulators, helping to prevent overactive inflammatory responses.
What this genotype means: Typical risk of hypothyroidism; Typical risk of rheumatoid arthritis; Typical risk of multiple sclerosis.
Sample genotype (not yours): C/C
Increased Risk of Autoimmune Conditions
Two copies of the C allele are associated with an elevated risk of developing autoimmune disorders affecting the thyroid, joints, and nervous system. This genotype reduces the expression of protective antioxidant proteins in immune cells.
What this genotype means: Increased risk of hypothyroidism; Increased risk of rheumatoid arthritis; Increased risk of multiple sclerosis.
Sample genotype (not yours): T/C
Slightly Increased Risk of Autoimmune Conditions
Carrying one copy of the C allele is linked to a slightly elevated risk of autoimmune thyroid and joint conditions. This genetic variation can lead to mild immune cell hyper-reactivity by reducing cellular antioxidant defenses.
What this genotype means: Slightly increased risk of hypothyroidism; Slightly increased risk of rheumatoid arthritis; Slightly increased risk of multiple sclerosis.
Gene function and biological role
Gene Function: The FAM76B gene encodes a nuclear speckle-localized protein that plays a key role in regulating inflammatory pathways. It interacts with other nuclear proteins to suppress inflammatory signaling, helping to maintain immune system balance. Additionally, the long non-coding RNA LNCRNA-IUR is located in this genomic region and is involved in immune cell regulation [1]. This locus is highly active in CD4-positive T cells, which are critical coordinators of the body's adaptive immune response [2]. Genetic variations in this region can alter the expression of nearby genes, including the antioxidant regulator Sestrin 3.
Variant Impact: The intergenic variant rs4409785 is located on chromosome 11 near the FAM76B and LNCRNA-IUR genes. This genetic change acts as an expression quantitative trait locus in CD4-positive T cells, where it regulates the expression of Sestrin 3. Sestrin 3 is an essential protein that helps reduce intracellular reactive oxygen species, protecting cells from oxidative stress. The C allele of this variant is associated with decreased expression of Sestrin 3, leading to higher oxidative stress and immune cell hyper-reactivity. Consequently, this variant is a recognized genetic risk factor for several autoimmune conditions, including thyroid disorders and joint inflammation [3].
Key Insight: This variant regulates Sestrin 3, an antioxidant protein that protects immune cells from oxidative stress. Lower levels of Sestrin 3 can cause immune cells to become hyper-reactive, leading them to mistakenly attack healthy tissues.
Location: FAM76B. Chromosome 11 · 11q21 · 95.6 Mb
Estimated prevalence by population
Global 76.0%; European 68.2%; African 93.6%; East Asian 82.1%; South Asian 58.8%; Americas 76.5%; Ashkenazi 62.9%; Finnish 68.2%; Middle Eastern 67.0%; Amish 42.4%.
Estimated TT genotype frequency.
Global 21.9%; European 28.7%; African 6.3%; East Asian 17.0%; South Asian 35.8%; Americas 21.9%; Ashkenazi 32.8%; Finnish 28.7%; Middle Eastern 29.7%; Amish 45.4%.
Estimated TC genotype frequency.
Global 2.2%; European 3.0%; African 0.1%; East Asian 0.9%; South Asian 5.4%; Americas 1.6%; Ashkenazi 4.3%; Finnish 3.0%; Middle Eastern 3.3%; Amish 12.2%.
Estimated CC genotype frequency.
Showing effects for T/T genotype
Endocrine & Reproductive
Hormone Levels & Endocrine Regulation
Hypothyroidism. Evidence: 10/10. Source: PMID 34594039. Typical Risk.
Immunity & Inflammation
Autoimmune Diseases
Rheumatoid Arthritis. Evidence: 8/10. Source: PMID 24390342. Typical Risk.
Multiple Sclerosis. Evidence: 8/10. Source: PMID 21833088. Typical Risk.
Graves' Disease. Evidence: 8/10. Source: PMID 22922229. Typical Risk.
Myasthenia Gravis. Evidence: 7/10. Source: PMID 35074870. Typical Risk.
Cardiovascular & Metabolic
Diabetes & Glycemic Traits
Type 1 Diabetes. Evidence: 4/10. Source: PMID 39749473. Typical Risk.
Showing effects for C/C genotype
Hypothyroidism. Evidence: 10/10. Source: PMID 34594039. ~1.25x Risk.
Rheumatoid Arthritis. Evidence: 8/10. Source: PMID 24390342. ~1.2x Risk.
Multiple Sclerosis. Evidence: 8/10. Source: PMID 21833088. ~1.2x Risk.
Graves' Disease. Evidence: 8/10. Source: PMID 22922229. ~1.46x Risk.
Myasthenia Gravis. Evidence: 7/10. Source: PMID 35074870. Increased Risk.
Type 1 Diabetes. Evidence: 4/10. Source: PMID 39749473. ~1.2x Risk.
Showing effects for T/C genotype
Hypothyroidism. Evidence: 10/10. Source: PMID 34594039. ~1.12x Risk.
Rheumatoid Arthritis. Evidence: 8/10. Source: PMID 24390342. ~1.1x Risk.
Multiple Sclerosis. Evidence: 8/10. Source: PMID 21833088. ~1.1x Risk.
Graves' Disease. Evidence: 8/10. Source: PMID 22922229. ~1.21x Risk.
Type 1 Diabetes. Evidence: 4/10. Source: PMID 39749473. ~1.1x Risk.
What this genotype means for the people who carry it
Sample genotype: TT (Homozygous)
Carrying two copies of the T allele represents the most common genetic profile globally, providing a baseline level of protection against autoimmune diseases. This genotype is associated with normal expression of Sestrin 3 in CD4-positive T cells, which helps keep cellular oxidative stress in check. Large-scale genetic studies show that individuals with this profile have a lower risk of developing hypothyroidism compared to those carrying the C allele [1]. Similarly, this genotype is linked to a typical, non-elevated risk of rheumatoid arthritis [2] and multiple sclerosis [3]. Maintaining a healthy lifestyle, managing stress, and supporting thyroid health through proper nutrition remain excellent general strategies. Regular checkups can help monitor thyroid function and joint health over time.
Typical risk of hypothyroidism; Typical risk of rheumatoid arthritis; Typical risk of multiple sclerosis.
Sample genotype: CC (Homozygous)
Carrying two copies of the C allele is linked to the highest genetic susceptibility at this locus for multiple autoimmune conditions. This genotype significantly decreases the expression of Sestrin 3 in CD4-positive T cells, leading to increased cellular oxidative stress and a tendency toward immune system overactivation. Genome-wide association studies have consistently linked this genetic profile to an increased risk of hypothyroidism [1] and rheumatoid arthritis [2]. It is also associated with a higher risk of multiple sclerosis [3], Graves disease [1], and type 1 diabetes [4]. While genetics play a role, environmental factors and lifestyle choices are also critical in determining whether an autoimmune condition develops. Prioritizing stress reduction, getting adequate sleep, and eating a nutrient-rich diet can help support overall immune balance. It is helpful to be aware of common symptoms like chronic fatigue, joint pain, or unexplained weight changes, and to discuss them with a doctor.
Increased risk of hypothyroidism; Increased risk of rheumatoid arthritis; Increased risk of multiple sclerosis; Increased risk of type 1 diabetes.
Sample genotype: TC (Heterozygous)
Having one copy of the C allele is associated with a modest increase in susceptibility to several autoimmune disorders. This genetic change slightly reduces the expression of Sestrin 3 in key immune cells, which can elevate oxidative stress and promote inflammatory pathways. Research indicates that carriers of this allele have a slightly higher likelihood of developing hypothyroidism [1] and rheumatoid arthritis [2]. There is also a small associated increase in the risk of multiple sclerosis [3] and Graves disease [1]. Because these risks are only moderately elevated, many people with this genotype never develop any autoimmune conditions. Supporting the immune system through an anti-inflammatory diet, regular exercise, and stress management can be highly beneficial. Discussing any symptoms of fatigue, cold sensitivity, or joint stiffness with a healthcare provider is a proactive way to manage health.
Slightly increased risk of hypothyroidism; Slightly increased risk of rheumatoid arthritis; Slightly increased risk of multiple sclerosis.
Variants with shared genetic architecture
rs3761959 · FCRL3 Gene · Chr 1 · Autoimmune Disease Risk
rs7731626 · ANKRD55 Gene · Chr 5 · Autoimmune Disease Risk
rs1738074 · TAGAP Gene · Chr 6 · Autoimmune Disease Risk
Seven newly identified loci for autoimmune thyroid disease.
Multiple sclerosis genomic map implicates peripheral immune cells and microglia in susceptibility.
A cross-population atlas of genetic associations for 220 human phenotypes.
Content updated August 2026.
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