What you carry at this position in your DNA and what research says about it.
Autoimmune Disease Risk: 10/10 evidence, 61 publications.
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Sample genotype (not yours): A/A
Typical Risk of Autoimmune Diseases
This genotype is associated with normal levels of CTLA-4 protein on immune cells. It provides a baseline, typical risk for autoimmune conditions like thyroiditis and alopecia.
What this genotype means: Typical risk of autoimmune thyroiditis; Typical risk of alopecia areata; Slightly higher risk of certain cancers.
Sample genotype (not yours): A/G
Increased Risk of Autoimmune Diseases
Carrying one copy of the G allele is associated with reduced CTLA-4 protein on immune cells. This reduction moderately increases the risk of developing autoimmune thyroiditis and other inflammatory conditions.
What this genotype means: Moderately increased risk of autoimmune thyroiditis; Moderately increased risk of alopecia areata; Slightly lower risk of certain cancers.
Sample genotype (not yours): G/G
Higher Risk of Autoimmune Diseases
Carrying two copies of the G allele significantly reduces CTLA-4 receptor levels on immune cells. This reduction is linked to a higher risk of autoimmune thyroiditis, Graves' disease, and other autoimmune disorders.
What this genotype means: Significantly increased risk of Hashimoto's thyroiditis; Increased risk of alopecia areata; Lower risk of certain cancers.
Gene function and biological role
Gene Function: Cytotoxic T-lymphocyte associated protein 4, encoded by the CTLA4 gene, acts as an essential immune checkpoint that downregulates T-cell activation [1]. By binding to co-stimulatory ligands on antigen-presenting cells, it prevents the immune system from attacking the body's own tissues [1]. Genetic variations in this gene can alter its expression levels and impair its inhibitory function [2]. This impairment often leads to an imbalance in immune homeostasis, promoting autoimmune responses [2]. Conversely, high expression of this protein can suppress the immune system's ability to detect and destroy malignant cells [3].
Variant Impact: The rs231775 variant, also known as +49A>G or Thr17Ala, is a missense mutation in the first exon of the CTLA4 gene [4]. This nucleotide substitution replaces the amino acid threonine with alanine in the signal peptide region of the protein [4]. The alanine substitution causes incomplete glycosylation of the protein in the endoplasmic reticulum [2]. Consequently, a portion of the newly synthesized protein is targeted for retrograde transport and cytoplasmic degradation [2]. This process significantly reduces the abundance of functional CTLA-4 receptors on the cell surface, diminishing their capacity to control T-cell activation [2].
Key Insight: The same genetic variant that increases the risk of autoimmune diseases like thyroiditis actually helps the immune system fight off cancer cells.
Location: CTLA4. Chromosome 2 · 2q33.2 · 203.9 Mb
Estimated prevalence by population
Global 36.4%; European 37.7%; African 39.2%; East Asian 12.6%; South Asian 46.0%; Americas 34.5%; Ashkenazi 49.0%; Finnish 22.1%; Middle Eastern 51.2%; Amish 32.6%.
Estimated AA genotype frequency.
Global 47.2%; European 47.4%; African 46.8%; East Asian 45.8%; South Asian 43.6%; Americas 48.5%; Ashkenazi 42.0%; Finnish 49.8%; Middle Eastern 40.7%; Amish 49.0%.
Estimated AG genotype frequency.
Global 16.4%; European 14.9%; African 14.0%; East Asian 41.5%; South Asian 10.3%; Americas 17.0%; Ashkenazi 9.0%; Finnish 28.1%; Middle Eastern 8.1%; Amish 18.4%.
Estimated GG genotype frequency.
Showing effects for A/A genotype
Immunity & Inflammation
Autoimmune Diseases
Autoimmune Thyroiditis. Evidence: 10/10. Source: PMID 32581359. Typical Risk.
Organ Systems
Skin & Hair Conditions
Alopecia Areata. Evidence: 6/10. Source: PMID 25608926. Typical Risk.
Dental & Oral Health
Gum Overgrowth. Evidence: 5/10. Source: PMID 18021981. Increased Risk.
Cardiovascular & Metabolic
Diabetes & Glycemic Traits
Autoimmune Diabetes. Evidence: 4/10. Source: PMID 25005490. Typical Risk.
Cancer & Oncology
General Cancer Risk
Cancer Susceptibility. Evidence: 4/10. Source: PMID 29794444. Higher Risk.
Pharmacogenomics
Adverse Drug Reactions
NSAID Allergy Risk. Evidence: 5/10. Source: PMID 28750137. Typical Risk.
Showing effects for A/G genotype
Autoimmune Thyroiditis. Evidence: 10/10. Source: PMID 32581359. ~1.5x Risk.
Alopecia Areata. Evidence: 6/10. Source: PMID 25608926. Increased Risk.
Autoimmune Diabetes. Evidence: 4/10. Source: PMID 25005490. Increased Risk.
Cancer Susceptibility. Evidence: 4/10. Source: PMID 29794444. Lower Risk.
NSAID Allergy Risk. Evidence: 5/10. Source: PMID 28750137. Decreased Risk.
Showing effects for G/G genotype
Autoimmune Thyroiditis. Evidence: 10/10. Source: PMID 32581359. ~2.3x Risk.
Alopecia Areata. Evidence: 6/10. Source: PMID 25608926. Higher Risk.
Gum Overgrowth. Evidence: 5/10. Source: PMID 18021981. Typical Risk.
Autoimmune Diabetes. Evidence: 4/10. Source: PMID 25005490. Higher Risk.
What this genotype means for the people who carry it
Sample genotype: AA (Homozygous)
Normal expression of the CTLA-4 receptor on the surface of regulatory T-cells helps maintain immune tolerance [1]. Lacking the G variant means the receptor undergoes proper glycosylation and trafficking, allowing it to effectively suppress overactive immune responses [1]. Consequently, there is no elevated risk for autoimmune thyroid diseases, such as Hashimoto's thyroiditis or Graves' disease [2]. However, higher levels of functional CTLA-4 can sometimes overly suppress the immune system, which has been linked to a slightly higher susceptibility to certain cancers [3]. Additionally, kidney transplant recipients with this genotype who take cyclosporine may have an increased likelihood of developing gum overgrowth [4].
Typical risk of autoimmune thyroiditis; Typical risk of alopecia areata; Slightly higher risk of certain cancers.
Sample genotype: AG (Heterozygous)
A single copy of the G allele leads to partial degradation of the CTLA-4 protein during its synthesis [1]. With fewer receptors reaching the cell surface, the immune system has a slightly harder time putting the brakes on T-cell activation [1]. This cellular change translates to a roughly 1.5-fold increased risk of autoimmune thyroiditis and Graves' disease [2]. It also moderately elevates susceptibility to other immune-mediated conditions, such as alopecia areata and latent autoimmune diabetes in adults [3] [4]. On the positive side, the reduced immune suppression associated with this genotype may offer a protective effect against certain cancers [5]. Furthermore, individuals with this genotype may experience a decreased risk of drug allergies to NSAIDs and a lower risk of anemia during certain antiviral therapies [6] [7].
Moderately increased risk of autoimmune thyroiditis; Moderately increased risk of alopecia areata; Slightly lower risk of certain cancers.
Sample genotype: GG (Homozygous)
Having two copies of the G allele causes substantial retrograde transport and degradation of the CTLA-4 protein [1]. The resulting shortage of functional receptors on T-cells impairs the body's ability to maintain self-tolerance [1]. Clinical studies show this genotype is associated with a 2.3-fold higher risk of Hashimoto's thyroiditis and a 1.47-fold higher risk of Graves' disease [2]. It is also linked to an increased susceptibility to alopecia areata and latent autoimmune diabetes in adults [3] [4]. Interestingly, the lower levels of immune checkpoint activity in this genotype can enhance the immune system's ability to target tumor cells, resulting in a lower overall risk for several cancers [5]. Additionally, individuals with this genotype exhibit a decreased risk of developing cross-reactive hypersensitivity reactions to NSAIDs [6].
Significantly increased risk of Hashimoto's thyroiditis; Increased risk of alopecia areata; Lower risk of certain cancers.
Variants with shared genetic architecture
rs3087243 · CTLA4 Gene · Chr 2 · Autoimmune and Cancer Risk
rs5742909 · CTLA4 Gene · Chr 2 · Immune System Balance
rs16840252 · CTLA4 Gene · Chr 2 · Autoimmune and Cancer Risk
FLT3 stop mutation increases FLT3 ligand level and risk of autoimmune thyroid disease.
Content updated August 2026.
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