Genes with known somatic GEI
| Gene (protein) . | Chr . | Disease . | Mechanism . | VAF in affected cell types . | Method of discovery . | References . |
|---|---|---|---|---|---|---|
| Somatic GEI that are phenocopies of germline GEI | ||||||
| FADD | chr11 | ALPS | LOF | NA | ES, SS, PS | Pellé et al. (2024) |
| FAS | chr10 | ALPS | LOF | 1–50% in DNTs | PS, SS | Dowdell et al. (2010), Holzelova et al. (2004), López-Nevado et al. (2021) |
| KRAS | chr12 | RAS-associated autoimmune leukoproliferative disease (RALD) | GOF | NA | ES, SS | Moritake et al. (2016), Niemela et al. (2011) |
| NRAS | chr1 | RALD | GOF | 49–67% in blood | ES, pyro, AS | Mensa-Vilaró et al. (2019), Shiota et al. (2015) |
| MEFV (Pyrin) | chr16 | Familial mediterranean fever (FMF) | GOF | 46% in PMNs and blood | SS, AS | Shinar et al. (2015) |
| NLRP3 | chr1 | CAPS | GOF | 4–36% in blood | ES, SC, AS, SS | Saito et al. (2005), Tanaka et al. (2011), Zhou et al. (2015) |
| NOD2 | chr16 | Blau syndrome | GOF | 7–13% in blood | SS, AS | de Inocencio et al. (2015), Mensa-Vilaró et al. (2019) |
| TMEM173 (STING) | chr5 | STING-associated vasculopathy, infantile onset (SAVI) | GOF | NA | SS | Clarke et al. (2016) |
| TNFRSF1A | chr12 | TNF receptor-associated periodic fever syndrome (TRAPS) | GOF | 21–30% in blood and immune cells | PS, SS | Kontzias et al. (2019), Rowczenio (2016) |
| JAK1 | chr1 | JAK1 GOF | GOF | 27% in blood | ES | Gruber et al. (2020) |
| CYBB (gp91-phox) | chrX | XL chronic granulomatous disease (XL-CGD) | LOF | NA | SS | Wolach et al. (2005) |
| Somatic GEI that are partial phenocopies of germline GEI | ||||||
| NLRC4 | chr2 | NLRC4 GOF | GOF | ∼45% in blood | ES | De Langhe et al. (2023) |
| RAP1B | chr12 | Immunodeficiency and thrombocytopenia | GOF | 40% in blood | ES | Benavides-Nieto et al. (2024) |
| STAT3 | chr17 | AD hyper-IgE syndrome (AD-HIES) | LOF/DN | NA | SS | Hsu et al. (2013) |
| Somatic GEI with a distinct clinical phenotype from germline GEI in the same gene | ||||||
| IL6ST (gp130) | chr5 | Neonatal onset immunodeficiency with autoinflammation and dysmorphy | GOF | 10% in blood | ES, AS | Materna-Kiryluk et al. (2021) |
| PIK3R1 (p85) | chr5 | Sweet syndrome | GOF | 50% in neutrophils | GS | Bhattacharya et al. (2023) |
| Primarily somatic GEI | ||||||
| UBA1 | chrX | Vacuoles, E1-enzyme, XL, autoinflammatory, somatic (VEXAS) | LOF | 35–80% in blood; 60–95% in myeloid cells | ES | Beck et al. (2020) |
| STAT5B | chr17 | STAT5B GOF | GOF | ∼10% B cells; ∼45% T cells | PS | Ma et al. (2017b) |
| TLR8 | chrX | Inflammation, neutropenia, bone marrow failure and lymphoproliferation associated with TLR8 (INFLTR8) | GOF | 8–26% in blood and sorted immune cells | ES | Aluri et al. (2021a) |
| Gene (protein) . | Chr . | Disease . | Mechanism . | VAF in affected cell types . | Method of discovery . | References . |
|---|---|---|---|---|---|---|
| Somatic GEI that are phenocopies of germline GEI | ||||||
| FADD | chr11 | ALPS | LOF | NA | ES, SS, PS | Pellé et al. (2024) |
| FAS | chr10 | ALPS | LOF | 1–50% in DNTs | PS, SS | Dowdell et al. (2010), Holzelova et al. (2004), López-Nevado et al. (2021) |
| KRAS | chr12 | RAS-associated autoimmune leukoproliferative disease (RALD) | GOF | NA | ES, SS | Moritake et al. (2016), Niemela et al. (2011) |
| NRAS | chr1 | RALD | GOF | 49–67% in blood | ES, pyro, AS | Mensa-Vilaró et al. (2019), Shiota et al. (2015) |
| MEFV (Pyrin) | chr16 | Familial mediterranean fever (FMF) | GOF | 46% in PMNs and blood | SS, AS | Shinar et al. (2015) |
| NLRP3 | chr1 | CAPS | GOF | 4–36% in blood | ES, SC, AS, SS | Saito et al. (2005), Tanaka et al. (2011), Zhou et al. (2015) |
| NOD2 | chr16 | Blau syndrome | GOF | 7–13% in blood | SS, AS | de Inocencio et al. (2015), Mensa-Vilaró et al. (2019) |
| TMEM173 (STING) | chr5 | STING-associated vasculopathy, infantile onset (SAVI) | GOF | NA | SS | Clarke et al. (2016) |
| TNFRSF1A | chr12 | TNF receptor-associated periodic fever syndrome (TRAPS) | GOF | 21–30% in blood and immune cells | PS, SS | Kontzias et al. (2019), Rowczenio (2016) |
| JAK1 | chr1 | JAK1 GOF | GOF | 27% in blood | ES | Gruber et al. (2020) |
| CYBB (gp91-phox) | chrX | XL chronic granulomatous disease (XL-CGD) | LOF | NA | SS | Wolach et al. (2005) |
| Somatic GEI that are partial phenocopies of germline GEI | ||||||
| NLRC4 | chr2 | NLRC4 GOF | GOF | ∼45% in blood | ES | De Langhe et al. (2023) |
| RAP1B | chr12 | Immunodeficiency and thrombocytopenia | GOF | 40% in blood | ES | Benavides-Nieto et al. (2024) |
| STAT3 | chr17 | AD hyper-IgE syndrome (AD-HIES) | LOF/DN | NA | SS | Hsu et al. (2013) |
| Somatic GEI with a distinct clinical phenotype from germline GEI in the same gene | ||||||
| IL6ST (gp130) | chr5 | Neonatal onset immunodeficiency with autoinflammation and dysmorphy | GOF | 10% in blood | ES, AS | Materna-Kiryluk et al. (2021) |
| PIK3R1 (p85) | chr5 | Sweet syndrome | GOF | 50% in neutrophils | GS | Bhattacharya et al. (2023) |
| Primarily somatic GEI | ||||||
| UBA1 | chrX | Vacuoles, E1-enzyme, XL, autoinflammatory, somatic (VEXAS) | LOF | 35–80% in blood; 60–95% in myeloid cells | ES | Beck et al. (2020) |
| STAT5B | chr17 | STAT5B GOF | GOF | ∼10% B cells; ∼45% T cells | PS | Ma et al. (2017b) |
| TLR8 | chrX | Inflammation, neutropenia, bone marrow failure and lymphoproliferation associated with TLR8 (INFLTR8) | GOF | 8–26% in blood and sorted immune cells | ES | Aluri et al. (2021a) |
NA, not available; PMN, polymorphonuclear cells; ES, exome sequencing; SS, Sanger sequencing; SC, subcloning; AS, amplicon sequencing; GS, genome sequencing; PS, panel sequencing; pyro, pyrosequencing.