Table 2.
The main altered genes described in the monogenic forms of SLE and corresponding phenotype.
| Locus | Gene location | Protein | Inheritance | Pathway | Phenotype |
|---|---|---|---|---|---|
|
C1QA
C1QB C1QC |
1p36.12 | C1q | AR | Complement—Classic pathway | Nephritis, CNS involvement, photosensibility, arthritis, infectious susceptibility |
| C1R | 12p13.31 | C1r | AR | Complement—Classic pathway | Poliarthicular arthritis, upper and lower respiratory tract infections |
| C1S | 12p13.31 | C1s | AR | Complement—Classic pathway | Hashimoto's thyroiditis, autoimmune epatitis |
| C2 | 6p21.33 | C2 | AR | Complement—Classic pathway | Arthritis, malar rash, discoid rash, and photosensibility. Rare neurological and renal involvement |
| C4A-B | 6p21.33 | C4 | AR | Complement—Classic pathway | Multiorgan involvement with severe nephritis and photosensibility |
| C3 | 6p21.33 | C4 | AR | Complement—Classic and no classic pathway | Complement deficiencies with upper and lower respiratory tract infection, SLE in a minority of affected individuals |
| DNASE 1 | 16p13.3 | DNASE1 | AD | Extracellular acid nucleic degradation | Sjogren syndrome, high level of antinucleosomal autoantibodies |
| DNASE1L3 | 3p14.3 | DNASE1L3 | AR | Extracellular acid nucleic degradation | Early onset, nephritis, ANCA positive hypocomplementemic urticarial vasculitis syndrome (HUVS) |
| ACP5 | 2q24.2 | TRAP | AD | Type-I IFN—regulation of Opn | Cytopenia (also implied in SMS) |
| IFIHI | 2q24.3 | MDA-5 | AD | Type-I IFN Cytosolic sensor for dsRNA | IgA deficiency, mild lower limb Spasticity (also implied in SMS and AGS) |
| TREX1 | 3p21.31 | TREX1 | AD | Type-I IFN degradation of intracellular ds-ss DNA | FCL (also implied in AGS) |
| SAMHD1 | 20q11.23 | SAMHD1 | AR | Type I IFN cytoplasmic ssRNA/DNA sensor | FCL (also implied in AGS) |
| PRKCD | 3p21.2 | PRKCD | AR | Self-tolerance-B-cell survival and proliferation | Renal involvement, CNS vasculitis, lymphoproliferative syndromes |
| RAG2 | 11p12 | RAG2 | AR/AD | Self-tolerance | Immune-mediated cytopenias to localized destructive vasculitis |
| TNFRSF6 | 10q23.31 | CD95 | AR | Self-tolerance- apoptosis | Marked lymphadenopathy |
AD, autosomal dominant; AR, autosomal recessive; ACP5-TRAP, Acid Phosphatase 5 Tartrate Resistant; IFIH1, IFN-induced helicase C domain-containing protein 1; MDA5, melanoma differentiation-associated protein 5; TREX1, DNA 3′ repair exonuclease; SAMHD1, deoxynucleoside triphosphate triphosphohydrolase SAM domain and HD domain 1; PRKCD, Protein Kinase C Delta; RAG 2, recombination-activating genes 2; TNFRSF6, Truncated tumor necrosis factor receptor superfamily member 6; FLC, familial chilblain lupus.