Systemic lupus erythematosus: genes and variants
Systemic lupus erythematosus is linked to 12 analyzed proteins (TLR7, TREX1, CTLA4, STAT4, IFNAR1, IL10, NCF2, PTPN22 and 4 more). 3 DNA variants are known to cause it; 12 more are uncertain, and 0 of those already look disease-causing on computable evidence.
Last updated 2026-09-30. Research information, not medical advice.
Also known as: systemic lupus erythematosus 17; Systemic lupus erythematosus, susceptibility to, 11
Genes linked to Systemic lupus erythematosus
TLR7: Toll-like receptor 7
It detects single-stranded viral RNA in endosomes and drives type I interferon and inflammatory responses, particularly in plasmacytoid dendritic cells and B cells. Loss-of-function variants can predispose to severe viral infection, whereas gain-of-function variants cause immune dysregulation and autoimmunity.
1 disease-causing and 2 uncertain variants in TLR7 are linked to Systemic lupus erythematosus.
TREX1: Three-prime repair exonuclease 1
It degrades aberrant cytosolic DNA and prevents inappropriate activation of the cGAS-STING interferon pathway. Pathogenic variants cause interferon-mediated diseases including Aicardi-Goutieres syndrome and familial chilblain lupus, and certain alleles cause retinal vasculopathy with cerebral leukoencephalopathy.
0 disease-causing and 7 uncertain variants in TREX1 are linked to Systemic lupus erythematosus.
CTLA4: Cytotoxic T-lymphocyte protein 4
It restrains T-cell activation by competing with CD28 for CD80 and CD86 and by delivering inhibitory signals after immune activation. Haploinsufficiency causes immune dysregulation with autoimmunity and lymphoproliferation, while therapeutic blockade enhances antitumor immunity.
0 disease-causing and 2 uncertain variants in CTLA4 are linked to Systemic lupus erythematosus.
STAT4: Signal transducer and activator of transcription 4
It transduces signals from IL-12 and related cytokines to promote Th1 differentiation and IFN-gamma production. Common variants strongly influence susceptibility to autoimmune diseases such as rheumatoid arthritis and systemic lupus erythematosus.
0 disease-causing and 1 uncertain variants in STAT4 are linked to Systemic lupus erythematosus.
IFNAR1: Interferon alpha/beta receptor 1
Together with IFNAR2, it detects type I interferons and activates JAK-STAT antiviral and immunoregulatory programs. Loss-of-function can impair antiviral defense, while excessive pathway activation contributes to interferon-driven inflammatory disease.
0 disease-causing and 0 uncertain variants in IFNAR1 are linked to Systemic lupus erythematosus.
IL10: Interleukin-10
It suppresses excessive inflammatory cytokine production and restrains antigen-presenting cells and effector lymphocytes, protecting tissues from immune-mediated damage. Loss of IL-10 signaling causes severe early-onset intestinal inflammation and inflammatory bowel disease.
0 disease-causing and 0 uncertain variants in IL10 are linked to Systemic lupus erythematosus.
NCF2: Neutrophil cytosol factor 2
It helps activate the phagocyte NADPH oxidase by assembling with membrane and cytosolic partners during the respiratory burst. Biallelic loss-of-function variants cause chronic granulomatous disease and impaired killing of catalase-positive bacteria and fungi.
0 disease-causing and 0 uncertain variants in NCF2 are linked to Systemic lupus erythematosus.
PTPN22: Tyrosine-protein phosphatase non-receptor type 22
It tunes antigen-receptor signaling thresholds in T and B cells and helps maintain immune tolerance. The common R620W variant is a major non-HLA genetic risk factor for several autoimmune diseases, including type 1 diabetes and rheumatoid arthritis.
0 disease-causing and 0 uncertain variants in PTPN22 are linked to Systemic lupus erythematosus.
TLR9: Toll-like receptor 9
It detects unmethylated CpG-rich DNA in endosomes and activates innate immune and type I interferon responses. Dysregulated signaling can contribute to autoimmunity, while agonists and antagonists of the pathway are being developed for cancer and inflammatory disease.
0 disease-causing and 0 uncertain variants in TLR9 are linked to Systemic lupus erythematosus.
TNFAIP3: Tumor necrosis factor alpha-induced protein 3
Its A20 ubiquitin-editing activity terminates NF-kappaB signaling after inflammatory receptor activation and helps prevent excessive immune responses. Haploinsufficiency causes early-onset autoinflammatory disease, while somatic loss occurs in several lymphoid malignancies.
0 disease-causing and 0 uncertain variants in TNFAIP3 are linked to Systemic lupus erythematosus.
TYK2: Non-receptor tyrosine-protein kinase TYK2
It transmits signals from type I interferon, IL-12, IL-23, and related cytokine receptors. Severe loss-of-function can cause immunodeficiency, common variants influence autoimmune susceptibility, and partial pharmacologic inhibition is effective in inflammatory disease.
0 disease-causing and 0 uncertain variants in TYK2 are linked to Systemic lupus erythematosus.
SOCS1: Suppressor of cytokine signaling 1
It provides inducible negative feedback on cytokine signaling by inhibiting JAK kinases and promoting degradation of signaling components. Haploinsufficiency can cause early-onset autoimmunity and immune dysregulation, while somatic loss contributes to some lymphomas.
2 disease-causing and 0 uncertain variants in SOCS1 are linked to Systemic lupus erythematosus.
Known disease-causing variants in Systemic lupus erythematosus
| Variant | Position | Protein part | Clinical label |
|---|---|---|---|
| SOCS1 Y154H | 154 | SH2 | Disease-causing |
| TLR7 F507L | 507 | LRR 16 | Disease-causing |
| SOCS1 R22W | 22 | Disease-causing |
Diseases related to Systemic lupus erythematosus
- Type 1 diabetes mellitus, also linked to CTLA4, IL10, PTPN22 and TYK2
- Hypothyroidism, also linked to CTLA4, PTPN22 and TYK2
- Malaria, also linked to TLR7 and TLR9
- Melanoma, also linked to CTLA4 and IFNAR1
- Basal cell carcinoma, also linked to CTLA4 and TLR7
- Acquired polycythemia vera, also linked to IFNAR1 and TYK2
- Non-small cell lung carcinoma, also linked to CTLA4
- Autoimmune lymphoproliferative syndrome due to CTLA4 haploinsufficiency, also linked to CTLA4
- Inherited Immunodeficiency Diseases, also linked to CTLA4
- Fetal anomalies with a likely genetic cause, also linked to TREX1
- Hyperthyroidism, also linked to CTLA4
- Granulomatous disease, chronic, autosomal recessive, cytochrome b-positive, type 2, also linked to NCF2
Frequently asked questions
Which genes are linked to Systemic lupus erythematosus?
In CATVariant, Systemic lupus erythematosus is linked to 12 analyzed proteins: TLR7 (Toll-like receptor 7), TREX1 (Three-prime repair exonuclease 1), CTLA4 (Cytotoxic T-lymphocyte protein 4), STAT4 (Signal transducer and activator of transcription 4), IFNAR1 (Interferon alpha/beta receptor 1), IL10 (Interleukin-10) and 6 more.
How many genetic variants are linked to Systemic lupus erythematosus?
27 variants: 3 are classified as disease-causing (pathogenic or likely pathogenic) in ClinVar and 12 are of uncertain significance or have conflicting reports.
Which uncertain variants in Systemic lupus erythematosus look disease-causing?
None of the uncertain variants currently reaches the likely-pathogenic range on computable evidence alone.
About this data
Variant–disease links come from ClinVar, Open Targets and UniProt, pooled from the latest public CATVariant analysis of each human protein. Evidence scores use the ACMG/AMP Bayesian points scale with computable criteria only (position among known disease variants, rarity in gnomAD, calibrated predictors, deep mutational scanning); there is no family or patient data, so they prioritise variants for expert review and never classify them.
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