| Gene . | Protein function . | Sensing/activation pathway related to type I interferon signaling . | Mutation effect . | Major patient phenotypes . |
|---|---|---|---|---|
| TREX1 | Deoxyribonuclease | Cytosolic DNA | LOF (recessive or dominant-negative) | AGS, FCL, SLE |
| SAMHD1 | Control of dNTP pool (±nuclease) | Cytosolic DNA (±cytosolic RNA) | LOF (recessive) | AGS, FCL, CVD |
| TMEM173 | Transduction of cytosolic type I interferon signal | Cytosolic DNA (±cytosolic RNA) | GOF (dominant) | SAVI, FCL |
| RNASEH2A | Ribonuclease | Cytosolic RNA:DNA hybrids | LOF (recessive) | AGS |
| RNASEH2B | Ribonuclease | Cytosolic RNA:DNA hybrids | LOF (recessive) | AGS, SP |
| RNASEH2C | Ribonuclease | Cytosolic RNA:DNA hybrids | LOF (recessive) | AGS |
| POLA1 | Polymerase | Cytosolic RNA:DNA hybrids | X-linked recessive | XLPDR |
| ADAR1 | RNA editing | Cytosolic RNA | LOF (recessive or dominant-negative) | AGS, DSH, BSN, SP |
| IFIH1 | dsRNA sensor | Cytosolic RNA | GOF (dominant) | AGS, SP, SMS |
| RIG-I | dsRNA sensor | Cytosolic RNA | GOF (dominant) | Atypical SMS |
| SKIV2L | RNA helicase | Cytosolic RNA | LOF (recessive) | THES |
| UPS18 | Inhibition of ISG transcription | IFNAR1 signaling | LOF (recessive) | pseudo-TORCH |
| ISG15 | Inhibition of ISG transcription | IFNAR1 signaling | LOF (recessive) | MSMD, ICC |
| PSMB8 | Proteasome | Unknown | LOF (recessive) | PRAAS |
| PSMB4 | Proteasome | Unknown | LOF (recessive) | PRAAS |
| PSMA3 | Proteasome | Unknown | LOF (recessive) | PRAAS |
| ACP5 | Phosphatase activity related to osteopontin | Unknown | LOF (recessive) | SPENCD, SLE, cytopenias |
| C1q | Alternative complement pathway activity | Unknown | LOF (recessive) | SLE |
| Gene . | Protein function . | Sensing/activation pathway related to type I interferon signaling . | Mutation effect . | Major patient phenotypes . |
|---|---|---|---|---|
| TREX1 | Deoxyribonuclease | Cytosolic DNA | LOF (recessive or dominant-negative) | AGS, FCL, SLE |
| SAMHD1 | Control of dNTP pool (±nuclease) | Cytosolic DNA (±cytosolic RNA) | LOF (recessive) | AGS, FCL, CVD |
| TMEM173 | Transduction of cytosolic type I interferon signal | Cytosolic DNA (±cytosolic RNA) | GOF (dominant) | SAVI, FCL |
| RNASEH2A | Ribonuclease | Cytosolic RNA:DNA hybrids | LOF (recessive) | AGS |
| RNASEH2B | Ribonuclease | Cytosolic RNA:DNA hybrids | LOF (recessive) | AGS, SP |
| RNASEH2C | Ribonuclease | Cytosolic RNA:DNA hybrids | LOF (recessive) | AGS |
| POLA1 | Polymerase | Cytosolic RNA:DNA hybrids | X-linked recessive | XLPDR |
| ADAR1 | RNA editing | Cytosolic RNA | LOF (recessive or dominant-negative) | AGS, DSH, BSN, SP |
| IFIH1 | dsRNA sensor | Cytosolic RNA | GOF (dominant) | AGS, SP, SMS |
| RIG-I | dsRNA sensor | Cytosolic RNA | GOF (dominant) | Atypical SMS |
| SKIV2L | RNA helicase | Cytosolic RNA | LOF (recessive) | THES |
| UPS18 | Inhibition of ISG transcription | IFNAR1 signaling | LOF (recessive) | pseudo-TORCH |
| ISG15 | Inhibition of ISG transcription | IFNAR1 signaling | LOF (recessive) | MSMD, ICC |
| PSMB8 | Proteasome | Unknown | LOF (recessive) | PRAAS |
| PSMB4 | Proteasome | Unknown | LOF (recessive) | PRAAS |
| PSMA3 | Proteasome | Unknown | LOF (recessive) | PRAAS |
| ACP5 | Phosphatase activity related to osteopontin | Unknown | LOF (recessive) | SPENCD, SLE, cytopenias |
| C1q | Alternative complement pathway activity | Unknown | LOF (recessive) | SLE |
BSN, bilateral striatal necrosis; CVD, cerebrovascular disease; DSH, dyschromatosis symmetrica hereditaria; FCL, familial chilblain lupus; GOF, gain-of-function; ICC, intracranial calcification; LOF, loss-of-function; MSMD, Mendelian susceptibility to mycobacterial disease; PRAAS, proteasome-associated autoinflammatory syndrome; SAVI, STING-associated vasculopathy with onset in infancy; SMS, Singleton-Merten syndrome; SP, spastic paraparesis; SPENCD, spondyloenchondrodysplasia; XLPDR, X-linked reticulate pigmentary disorder.