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The gene UNC93B1 (UniProt: Q9H1C4) encodes a protein designated as "Unc-93 homolog B1" (Unc-93B1 or hUNC93B1) in humans (ishida2021cryoemstructuresof pages 1-2). This protein belongs to the unc-93 family and contains the characteristic UNC93B1 domain (IPR043268) (klammer2023expressionundfunktion pages 19-22, ishida2021cryoemstructuresof pages 1-2). The gene identity matches the UniProt record provided, confirming we are researching the correct human protein.
UNC93B1 functions primarily as a non-enzymatic, multipass transmembrane chaperone protein that regulates intracellular nucleic-acid-sensing Toll-like receptors (TLRs) (song2022nglycosylationofunc93b1 pages 1-2, ishida2021cryoemstructuresof pages 1-2, rael2024largescalemutationalanalysis pages 17-18). It is not a transporter with conventional small-molecule substrates but rather a protein-protein interaction partner whose "substrates" are membrane receptor clients (ishida2021cryoemstructuresof pages 1-2, ishida2021cryoemstructuresof pages 5-6). The protein acts as an essential trafficking factor that mediates the exit of TLR3, TLR7, TLR8, and TLR9 from the endoplasmic reticulum (ER) and their subsequent delivery to endosomal compartments where these receptors detect microbial or viral nucleic acids (ishida2021cryoemstructuresof pages 1-2, song2022nglycosylationofunc93b1 pages 1-2, mielcarska2021cellsurfaceexpression pages 2-4).
UNC93B1 is a 12-transmembrane (TM) domain protein with structural similarity to atypical major facilitator superfamily (MFS) members (ishida2021cryoemstructuresof pages 1-2, ishida2021cryoemstructuresof pages 2-3). High-resolution cryo-electron microscopy structures of TLR3–UNC93B1 and TLR7–UNC93B1 complexes, published in 2021, revealed that UNC93B1 comprises two pseudo-symmetrical six-helix bundles (TM1–TM6 and TM7–TM12) that create an outward-facing, solvent-accessible central cavity (ishida2021cryoemstructuresof pages 2-3, ishida2021cryoemstructuresof pages 5-6). The N-terminal six-helix bundle provides the principal TLR-binding interface, contacting TLR transmembrane helices and luminal juxtamembrane regions (ishida2021cryoemstructuresof pages 1-2, ishida2021cryoemstructuresof pages 2-3, ishida2021cryoemstructuresof pages 3-4).
Key structural features include:
- Luminal loops: The TM5–TM6 loop (residues 245–280) extends across the luminal surface and contains conserved N-glycosylation sites at Asn251 and Asn272 (ishida2021cryoemstructuresof pages 2-3, ishida2021cryoemstructuresof pages 6-8).
- Intracellular elements: The TM6–TM7 connecting region forms membrane-associated helices that mediate UNC93B1 oligomerization and contains Lys333, which is subject to ubiquitylation (ishida2021cryoemstructuresof pages 3-4, ishida2021cryoemstructuresof pages 6-8).
- Regulatory regions: The N-terminal disordered region contains D34, and the C-terminal region includes a YxxF sorting motif and phosphorylation sites that recruit adaptors such as syntenin-1 (song2022nglycosylationofunc93b1 pages 1-2, ishida2021cryoemstructuresof pages 6-8).
UNC93B1 directly binds nucleic-acid-sensing endosomal TLRs, including TLR3, TLR7, TLR8, and TLR9 (ishida2021cryoemstructuresof pages 1-2, mielcarska2021cellsurfaceexpression pages 2-4, rael2024largescalemutationalanalysis pages 17-18). TLR5 has also been reported as an UNC93B1-associated receptor, whereas TLR4, a cell-surface receptor, does not detectably associate with UNC93B1 in pull-down experiments (ishida2021cryoemstructuresof pages 1-2). The structural basis of TLR recognition involves contacts between TLR transmembrane helices (especially near UNC93B1 TM3 and TM6) and luminal juxtamembrane β-turn-like regions that insert into pockets formed by UNC93B1 loops (ishida2021cryoemstructuresof pages 2-3, ishida2021cryoemstructuresof pages 3-4). TLR3 forms a 1:1 complex with UNC93B1, while TLR7 assembles into a preformed 2:2 (TLR7)₂–(UNC93B1)₂ dimer (ishida2021cryoemstructuresof pages 6-8, ishida2021cryoemstructuresof pages 2-3, ishida2021cryoemstructuresof pages 5-6).
Beyond TLRs, UNC93B1 also binds STING (stimulator of interferon genes) and regulates its stability through an independent mechanism discussed below (zhu2022unc93b1attenuatesthe pages 1-1, zhu2022unc93b1attenuatesthe pages 4-4).
| Functional module | Molecular activity | Principal partners or clients | Functional location | Pathway/output | Key regulatory mechanism and evidence |
|---|---|---|---|---|---|
| Core identity | Non-enzymatic, 12-transmembrane trafficking chaperone; no demonstrated transported small-molecule substrate | Nucleic-acid-sensing TLRs | Primarily ER membrane; subsequently accompanies clients along the secretory/endosomal route | Establishes signaling competence of intracellular TLRs | MFS-like fold comprises two pseudo-symmetrical six-helix bundles and a central cavity; the N-terminal bundle provides the major TLR-binding surface (ishida2021cryoemstructuresof pages 1-2, ishida2021cryoemstructuresof pages 2-3) |
| TLR recognition | Directly binds and stabilizes membrane-receptor clients | TLR3, TLR7, TLR8 and TLR9; association with TLR5 has also been reported, whereas TLR4 was not detectably associated in one pull-down analysis | ER and trafficking intermediates | Enables receptor maturation, stability and delivery to ligand-recognition compartments | TLR transmembrane helices and luminal juxtamembrane regions contact UNC93B1's N-terminal six-helix bundle; cryo-EM resolved 1:1 TLR3–UNC93B1 and 2:2 TLR7–UNC93B1 assemblies (ishida2021cryoemstructuresof pages 1-2, ishida2021cryoemstructuresof pages 2-3) |
| ER export and endosomal delivery | Escorts client TLRs from the ER through COPII-dependent export to endosomes/endolysosomes | TLR3, TLR7, TLR8 and TLR9; COPII trafficking machinery | ER → Golgi/secretory pathway → endosome/endolysosome | Positions receptors for nucleic-acid sensing while limiting activation by self nucleic acids outside the appropriate compartment | Without functional UNC93B1, major client TLRs remain in the ER and fail to signal normally; the trafficking-defective H412R substitution prevents UNC93B1 and associated TLRs from reaching endosomes (song2022nglycosylationofunc93b1 pages 1-2, ishida2021cryoemstructuresof pages 6-8) |
| TLR3 regulation | Positively supports trafficking and signaling competence while structurally maintaining a pre-activation state | TLR3, which senses double-stranded RNA and signals through TRIF | ER-to-endosomal route | TRIF-dependent IRF3/type I interferon and NF-κB responses | The TLR3–UNC93B1 structure is incompatible with the ligand-induced active TLR3 dimer, implying that release or rearrangement is needed for activation (ishida2021cryoemstructuresof pages 5-6, ishida2021cryoemstructuresof pages 6-8) |
| TLR7 regulation | Enables endosomal delivery but also imposes post-delivery negative regulation | TLR7, syntenin-1/SDCBP and sorting machinery | Endosomes and multivesicular bodies | MyD88-dependent NF-κB and type I interferon signaling in response to single-stranded RNA-derived ligands | Unlike TLR9, TLR7 can remain associated with UNC93B1 in endosomes. Phosphorylated C-terminal regions recruit syntenin-1, and Lys333 ubiquitylation supports sorting of the complex into intraluminal vesicles to terminate signaling (rael2024largescalemutationalanalysis pages 1-2, ishida2021cryoemstructuresof pages 6-8) |
| TLR8 regulation | Supports localization and calibrates human TLR8 responses | TLR8; disease-associated variants can alter UNC93B1–TLR8 association | ER-to-endosomal route | MyD88–NF-κB inflammatory signaling in response to RNA degradation products | Human gain-of-function variants can selectively or preferentially enhance TLR8 signaling; G325C, L330R and R466S showed enhanced TLR8 interaction, while several variants caused chilblain or systemic lupus phenotypes (david2024gainoffunctionhumanunc93b1 pages 1-2) |
| TLR9 regulation | Promotes trafficking, receptor release and signaling-complex assembly | TLR9, CpG DNA and MyD88 | ER-to-endosome route; signaling in acidified endosomes | MyD88-dependent NF-κB and inflammatory cytokine responses to DNA | TLR9 normally dissociates from UNC93B1 in endosomes. S282A strengthens association and can prevent productive release; UNC93B1 glycosylation at Asn272 is specifically required for MyD88 recruitment and TLR9 signaling despite normal receptor localization and ligand binding (song2022nglycosylationofunc93b1 pages 1-2, song2022nglycosylationofunc93b1 pages 4-6, ishida2021cryoemstructuresof pages 6-8) |
| TLR7–TLR9 balance | Receptor-specific signal calibration rather than uniform chaperoning | TLR7 and TLR9 | Endosomal system | Balances RNA versus DNA sensing and limits TLR7-driven autoimmunity | TLR9 is released after delivery, whereas TLR7 remains associated and undergoes continued UNC93B1-dependent control. Accordingly, UNC93B1 mutations can enhance TLR7/8 without increasing TLR9 responses; Asn272 glycosylation is required for TLR9 but dispensable for TLR7 signaling (rael2024largescalemutationalanalysis pages 1-2, song2022nglycosylationofunc93b1 pages 1-2) |
| Sorting motifs and post-translational control | Couples receptor complexes to intracellular sorting and signaling machinery | AP-2, syntenin-1, MyD88 and client TLRs | Cytosolic face of endosomal/trafficking membranes and luminal glycosylated loops | Controls receptor localization, signal initiation and termination | A C-terminal YxxF motif supports adaptor-mediated sorting; phosphorylation and Lys333 ubiquitylation regulate syntenin-1-dependent TLR7 termination; luminal Asn251 and Asn272 are N-glycosylated, with Asn272 having a selective TLR9-signaling role (song2022nglycosylationofunc93b1 pages 1-2, ishida2021cryoemstructuresof pages 6-8) |
| Structural restraint of activation | Holds client receptors in pre-activation assemblies in addition to transporting them | TLR3 and TLR7, with analogous release behavior implicated for TLR9 | ER and endosomal membranes | Prevents premature receptor dimerization and signaling | Cryo-EM superposition shows steric incompatibility between UNC93B1-bound complexes and activated TLR dimers; release or conformational rearrangement therefore provides a compartmental activation checkpoint (ishida2021cryoemstructuresof pages 5-6) |
| cGAS–STING regulation | Negative trafficking regulator that lowers STING protein stability; does not act as an enzyme on cGAS | STING directly; no detected interaction with cGAS | ER-associated trafficking pathway and autophagy–lysosome system | Attenuates STING–TBK1–IRF3 signaling, IFN-β production and interferon-stimulated gene expression | UNC93B1 binds/colocalizes with STING and directs it to autophagy–lysosome degradation. Chloroquine or NH4Cl, but not proteasome inhibition, blocks degradation; UNC93B1 loss increases TBK1 phosphorylation, IRF3 nuclear translocation and IFN/ISG output (zhu2022unc93b1attenuatesthe pages 1-1, zhu2022unc93b1attenuatesthe pages 4-5, zhu2022unc93b1attenuatesthe pages 4-4) |
| Functional consequence of gain-of-function variants | Hyperactivates selected endosomal TLR pathways without necessarily increasing receptor transport | Predominantly TLR7 and TLR8; variant-dependent effects on TLR3/TLR9 | Endosomal signaling compartments in immune cells | Excess NF-κB/type I interferon signaling and monogenic autoimmunity | 2024 human studies linked distinct UNC93B1 variants to childhood-onset systemic or cutaneous lupus; variants frequently enhanced TLR7/8 responses, demonstrating that UNC93B1 is an active signaling checkpoint rather than merely a passive escort (david2024gainoffunctionhumanunc93b1 pages 1-2, alazab2024geneticvariantsin pages 1-4, rael2024largescalemutationalanalysis pages 1-2) |
Table: This table integrates UNC93B1’s structural, trafficking and signaling functions, emphasizing receptor-specific regulation of TLR3/7/8/9 and lysosomal control of STING. It distinguishes the protein’s primary chaperone role from its non-catalytic regulatory effects.
UNC93B1 is primarily an ER-resident membrane protein that functions along the ER-to-endosome trafficking route (klammer2023expressionundfunktion pages 19-22, mielcarska2021cellsurfaceexpression pages 2-4, song2022nglycosylationofunc93b1 pages 1-2, ishida2021cryoemstructuresof pages 1-2). Under resting conditions, it resides in the ER where it binds nascent TLR clients and supports their folding, stabilization, and quality control (mielcarska2021cellsurfaceexpression pages 2-4, song2022nglycosylationofunc93b1 pages 1-2). UNC93B1 then escorts TLRs through COPII-dependent ER export vesicles, via the Golgi apparatus, to endosomal and endolysosomal compartments (song2022nglycosylationofunc93b1 pages 1-2, robinson2025recentinsightsinto pages 7-8). This compartmentalization is functionally critical because it restricts TLR activation to specialized intracellular locations, preventing inappropriate recognition of extracellular or plasma-membrane-accessible self-nucleic acids (ishida2021cryoemstructuresof pages 1-2).
UNC93B1 also participates in the autophagy–lysosome system, where it delivers STING for degradation (zhu2022unc93b1attenuatesthe pages 6-6, zhu2022unc93b1attenuatesthe pages 9-9, zhu2022unc93b1attenuatesthe pages 1-1, zhu2022unc93b1attenuatesthe pages 4-5).
UNC93B1 regulates multiple branches of nucleic-acid-sensing TLR signaling, which converge on NF-κB-driven inflammatory cytokine production and IRF-mediated type I interferon (IFN-α/β) responses (han2024anovelunc93b1 pages 4-6, song2022nglycosylationofunc93b1 pages 1-2, rael2024largescalemutationalanalysis pages 1-2, robinson2025recentinsightsinto pages 7-8). Each TLR exhibits distinct ligand specificity and signaling outcomes:
UNC93B1 does not uniformly activate all client TLRs; rather, it exerts receptor-specific positive (trafficking, stabilization) and negative (signal termination, competitive inhibition) regulatory effects (rael2024largescalemutationalanalysis pages 17-18, rael2024largescalemutationalanalysis pages 1-2).
A major discovery in UNC93B1 biology is its differential regulation of TLR7 and TLR9 after endosomal delivery (rael2024largescalemutationalanalysis pages 1-2, song2022nglycosylationofunc93b1 pages 1-2, ishida2021cryoemstructuresof pages 6-8). TLR9 is released from UNC93B1 in endosomes, permitting DNA binding and downstream signaling (song2022nglycosylationofunc93b1 pages 1-2, ishida2021cryoemstructuresof pages 6-8). In contrast, TLR7 remains associated with UNC93B1 in endosomes, exposing it to additional regulatory mechanisms (rael2024largescalemutationalanalysis pages 1-2, ishida2021cryoemstructuresof pages 6-8). Phosphorylation of UNC93B1 C-terminal regions recruits the adaptor syntenin-1 (SDCBP), which directs the TLR7–UNC93B1 complex into intraluminal vesicles of multivesicular bodies, terminating signaling (ishida2021cryoemstructuresof pages 6-8). This mechanism depends on ubiquitylation of UNC93B1 Lys333 (ishida2021cryoemstructuresof pages 6-8).
Post-translational modifications further differentiate TLR regulation. N-glycosylation of UNC93B1 at Asn272 is specifically required for TLR9 signaling—apparently by enabling recruitment of the MyD88 adaptor—but is dispensable for TLR7 responses (song2022nglycosylationofunc93b1 pages 1-2, song2022nglycosylationofunc93b1 pages 4-6, song2022nglycosylationofunc93b1 pages 12-13). The S282A mutation in UNC93B1 strengthens TLR9 binding and prevents productive receptor release, impairing TLR9 function without affecting TLR3 or TLR7 (zhu2022unc93b1attenuatesthe pages 9-9, ishida2021cryoemstructuresof pages 6-8).
This differential regulation helps balance RNA versus DNA sensing and prevents excessive TLR7-driven autoimmunity (rael2024largescalemutationalanalysis pages 17-18, rael2024largescalemutationalanalysis pages 1-2).
Cryo-EM structures reveal that UNC93B1 binding is sterically incompatible with the ligand-induced activated dimeric states of TLR3 and TLR7 (ishida2021cryoemstructuresof pages 5-6). This structural restraint implies that UNC93B1 holds receptors in pre-activation conformations during trafficking, and that receptor release or conformational rearrangement provides a compartmental activation checkpoint (ishida2021cryoemstructuresof pages 5-6, ishida2021cryoemstructuresof pages 6-8).
In addition to TLR regulation, UNC93B1 negatively regulates the cytosolic DNA-sensing cGAS–STING pathway (zhu2022unc93b1attenuatesthe pages 1-1, zhu2022unc93b1attenuatesthe pages 6-7). UNC93B1 physically interacts with STING and promotes its degradation through the autophagy–lysosome pathway, thereby attenuating downstream TBK1–IRF3 signaling, IFN-β production, and interferon-stimulated gene (ISG) expression (zhu2022unc93b1attenuatesthe pages 1-1, zhu2022unc93b1attenuatesthe pages 4-5, zhu2022unc93b1attenuatesthe pages 4-4, zhu2022unc93b1attenuatesthe pages 8-9). Pharmacological experiments using chloroquine and ammonium chloride (lysosome inhibitors), but not MG132 (a proteasome inhibitor), demonstrated that STING degradation occurs via the autophagy–lysosome system (zhu2022unc93b1attenuatesthe pages 4-5, zhu2022unc93b1attenuatesthe pages 9-9, zhu2022unc93b1attenuatesthe pages 5-5). Loss of UNC93B1 enhances cGAS–STING-mediated antiviral responses, reduces STING degradation, and increases TBK1 phosphorylation and IRF3 nuclear translocation (zhu2022unc93b1attenuatesthe pages 1-1, zhu2022unc93b1attenuatesthe pages 6-7, zhu2022unc93b1attenuatesthe pages 8-9). In vivo, Unc93b1-deficient mice showed enhanced interferon responses and improved survival against herpes simplex virus-1 (HSV-1) infection (zhu2022unc93b1attenuatesthe pages 8-9, zhu2022unc93b1attenuatesthe pages 9-9).
UNC93B1 does not interact with cGAS, indicating that its effect on the cGAS–STING pathway is mediated exclusively through STING (zhu2022unc93b1attenuatesthe pages 4-4).
Beginning in 2023–2024, multiple independent studies identified rare human UNC93B1 coding variants that cause monogenic autoimmune and autoinflammatory diseases (han2024anovelunc93b1 pages 26-31, he2025casereportnovel pages 5-7, david2024gainoffunctionhumanunc93b1 pages 1-2, alazab2024geneticvariantsin pages 1-4, rael2024largescalemutationalanalysis pages 4-6, he2025casereportnovel pages 2-5, rael2024largescalemutationalanalysis pages 1-2). These gain-of-function mutations typically enhance TLR7 and/or TLR8 signaling without correspondingly increasing TLR9 responses, demonstrating that UNC93B1 is an active signaling regulator rather than a passive trafficking escort (rael2024largescalemutationalanalysis pages 1-2, david2024gainoffunctionhumanunc93b1 pages 1-2, alazab2024geneticvariantsin pages 1-4).
Clinical phenotypes associated with UNC93B1 gain-of-function variants include:
Childhood-onset systemic lupus erythematosus (SLE): Multiple variants (I317M, G325C, T314A, V117L, R95L) cause early-onset SLE with features including antinuclear antibodies (ANA), anti-dsDNA antibodies, hypocomplementemia, proteinuria, and lupus nephritis (han2024anovelunc93b1 pages 26-31, david2024gainoffunctionhumanunc93b1 pages 1-2, alazab2024geneticvariantsin pages 1-4).
Cutaneous lupus: Chilblain lupus has been linked to L330R, R466S, and R525P variants, which preferentially enhance TLR8 signaling (he2025casereportnovel pages 5-7, david2024gainoffunctionhumanunc93b1 pages 1-2). Tumid lupus was reported in families carrying the T93I variant (rael2024largescalemutationalanalysis pages 4-6, rael2024largescalemutationalanalysis pages 1-2).
Rheumatoid arthritis and juvenile arthritis: The novel R336H variant was associated with rheumatoid arthritis, polyarthritis, and interstitial pneumonia across four affected family members (he2025casereportnovel pages 5-7, he2025casereportnovel pages 2-5). The R336C variant caused juvenile idiopathic arthritis with neuroinflammatory manifestations (rael2024largescalemutationalanalysis pages 4-6, rael2024largescalemutationalanalysis pages 1-2).
Other manifestations: Reported cases include immune thrombocytopenia (ITP), autoimmune hemolytic anemia, pulmonary artery hypertension, and interstitial lung disease (he2025casereportnovel pages 5-7, he2025casereportnovel pages 2-5).
The inheritance pattern varies by allele: some variants (e.g., I317M, R95L) are homozygous/recessive, while others (e.g., G325C, T93I, R336C) are heterozygous/dominant (david2024gainoffunctionhumanunc93b1 pages 1-2, alazab2024geneticvariantsin pages 1-4, rael2024largescalemutationalanalysis pages 4-6, rael2024largescalemutationalanalysis pages 1-2). The V117L variant represents a rare susceptibility allele with incomplete penetrance rather than a fully Mendelian mutation (alazab2024geneticvariantsin pages 1-4).
Mechanistically, these variants disrupt negative regulatory regions in UNC93B1, leading to excessive TLR7/8-dependent NF-κB and type I interferon signaling (han2024anovelunc93b1 pages 4-6, rael2024largescalemutationalanalysis pages 1-2, david2024gainoffunctionhumanunc93b1 pages 1-2, alazab2024geneticvariantsin pages 1-4). Patient-derived cells and engineered mouse models confirmed that the variants cause hyperresponsiveness to TLR7/8 agonists, elevated inflammatory cytokines (IL-6, TNF, IFN-α), and increased interferon-stimulated gene expression (han2024anovelunc93b1 pages 4-6, han2024anovelunc93b1 pages 26-31, rael2024largescalemutationalanalysis pages 9-11).
In contrast to gain-of-function autoimmune alleles, loss-of-function UNC93B1 mutations cause primary immunodeficiency with susceptibility to severe viral infections, particularly herpes simplex encephalitis (alazab2024geneticvariantsin pages 1-4). The H412R trafficking-defective mutation disrupts the hydrophobic core of TM9, preventing UNC93B1 and associated TLRs from reaching endosomes (ishida2021cryoemstructuresof pages 6-8). Without functional UNC93B1, TLR3, TLR7, TLR8, and TLR9 remain trapped in the ER and cannot mount effective antiviral responses (mielcarska2021cellsurfaceexpression pages 2-4). Human patients with biallelic UNC93B1 deficiency show impaired TLR3-driven interferon production and recurrent herpesvirus infections (alazab2024geneticvariantsin pages 1-4).
| Variant / mutation | Functional class | Inheritance pattern | Clinical phenotype(s) | Affected TLR pathway(s) | Key clinical or experimental features | 2023–2024 references |
|---|---|---|---|---|---|---|
| p.T93I | Gain of function; loss of negative regulation | Heterozygous, autosomal dominant familial segregation | Cutaneous tumid lupus; systemic inflammatory/autoimmune disease in engineered mice | Predominantly increased TLR7/8 signaling; some weak TLR3 enhancement in mice | Familial early-childhood tumid lupus; genome-edited heterozygous mice developed splenomegaly, expanded germinal-center and age-associated B cells, plasma cells and inflammatory monocytes; homozygous mice were not recovered, suggesting embryonic or perinatal lethality (rael2024largescalemutationalanalysis pages 9-11, rael2024largescalemutationalanalysis pages 1-2) | Rael et al., Journal of Experimental Medicine, published May 2024, DOI: 10.1084/jem.20232005 |
| p.R336C | Gain of function; loss of negative regulation | Heterozygous; familial variant consistent with dominant disease | Juvenile idiopathic arthritis and neuroinflammatory disease; systemic autoimmunity in engineered mice | Selective or predominant enhancement of TLR7/8 | Engineered mice showed reduced body weight, splenomegaly, antinuclear antibodies, expansion of age-associated B cells, plasma cells and monocytes, elevated CXCL1/CXCL10, and glomerulonephritis-like kidney lesions (rael2024largescalemutationalanalysis pages 9-11, rael2024largescalemutationalanalysis pages 1-2) | Rael et al., Journal of Experimental Medicine, published May 2024, DOI: 10.1084/jem.20232005 |
| p.I317M | Gain of function / hypermorphic | Homozygous; autosomal recessive in the reported family | Childhood-onset systemic lupus erythematosus | Increased TLR7, with lesser TLR8 enhancement | Part of a set of rare missense substitutions shown by cellular and patient-derived assays to produce receptor-selective hyperresponsiveness and monogenic lupus (david2024gainoffunctionhumanunc93b1 pages 1-2) | David et al., Journal of Experimental Medicine, published June 2024, DOI: 10.1084/jem.20232066 |
| p.G325C | Gain of function / hypermorphic | Heterozygous; autosomal dominant in the reported family | Systemic lupus erythematosus | Strongly increased TLR7 and more modestly increased TLR8 | Hyperresponsiveness was demonstrated both in vitro and ex vivo; the variant also enhanced UNC93B1 interaction with TLR8 (david2024gainoffunctionhumanunc93b1 pages 1-2) | David et al., Journal of Experimental Medicine, published June 2024, DOI: 10.1084/jem.20232066 |
| p.L330R | Gain of function / hypermorphic | Heterozygous; autosomal dominant familial disease | Chilblain lupus | Preferentially increased TLR8, without increased TLR7 in the tested systems | Cutaneous lupus phenotype associated with enhanced UNC93B1–TLR8 interaction, supporting receptor-selective dysregulation rather than generalized failure of TLR trafficking (david2024gainoffunctionhumanunc93b1 pages 1-2) | David et al., Journal of Experimental Medicine, published June 2024, DOI: 10.1084/jem.20232066 |
| p.R466S | Gain of function / hypermorphic | Heterozygous; autosomal dominant familial disease | Chilblain lupus | Preferentially increased TLR8 | Enhanced interaction with TLR8 was observed; TLR7 hyperactivation was not detected in the reported test systems (david2024gainoffunctionhumanunc93b1 pages 1-2) | David et al., Journal of Experimental Medicine, published June 2024, DOI: 10.1084/jem.20232066 |
| p.R525P | Gain of function / hypermorphic | Heterozygous; autosomal dominant familial disease | Chilblain lupus | Preferentially increased TLR8 | Enhanced TLR8 activity was observed, including ex vivo, although increased physical interaction with TLR8 was not detected—indicating that altered signaling need not result from tighter receptor binding (david2024gainoffunctionhumanunc93b1 pages 1-2) | David et al., Journal of Experimental Medicine, published June 2024, DOI: 10.1084/jem.20232066 |
| p.T314A | Gain of function / hypermorphic | Rare heterozygous variant; inheritance not specified in the available evidence | Childhood-onset systemic lupus erythematosus | Increased TLR7/8; no corresponding enhancement of TLR3 or TLR9 | Associated with type-I-interferon and NF-κB activation; reported clinical features across the cohort included ANA and anti-dsDNA antibodies, hypocomplementemia, proteinuria and lupus nephritis (alazab2024geneticvariantsin pages 1-4) | Al-Azab et al., Nature Immunology 25:969–980, 2024, DOI record: 10.1101/2023.10.15.23296507 |
| p.V117L | Risk-enhancing hypermorphic allele | Heterozygous susceptibility allele; not established as a fully penetrant Mendelian mutation | Predisposition to childhood-onset systemic lupus erythematosus | Increased TLR7/8; TLR3 and TLR9 not enhanced | Found in seven East Asian patients in the reported cohort; associated with increased type-I-interferon and NF-κB cytokine signatures. The orthologous mouse p.V138L allele caused spontaneous, dose-dependent lupus-like disease (alazab2024geneticvariantsin pages 1-4) | Al-Azab et al., Nature Immunology 25:969–980, 2024, DOI record: 10.1101/2023.10.15.23296507 |
| p.R95L | Gain of function / hypermorphic | Homozygous; recessive presentation, with unaffected heterozygous parents | Early-onset systemic lupus erythematosus | Hyperactivation of TLR7/8; reported receptor assays showed little or no comparable TLR3 enhancement | Patient PBMCs exhibited increased NF-κB, type-I-interferon and inflammatory cytokine programs; engineered cells and mice supported a TLR7/8-dependent mechanism. Evidence was initially reported as a 2024 preprint and therefore warrants peer-reviewed confirmation (han2024anovelunc93b1 pages 4-6, han2024anovelunc93b1 pages 9-12) | Han et al., medRxiv, posted September 2024, DOI: 10.1101/2024.09.11.24313360 |
| p.H412R | Loss of function; trafficking-defective | Classically associated with biallelic/recessive UNC93B1 deficiency | Innate immunodeficiency with susceptibility to severe herpesvirus infection, especially herpes simplex encephalitis | Impaired TLR3, TLR7, TLR8 and TLR9 trafficking/signaling | The substitution disrupts the hydrophobic TM9 core and prevents UNC93B1–TLR complexes from reaching endosomes; recent literature contrasts such loss-of-function immunodeficiency with TLR7/8-hyperactive autoimmune alleles (ishida2021cryoemstructuresof pages 6-8, alazab2024geneticvariantsin pages 1-4) | Mechanistic context summarized in Al-Azab et al., Nature Immunology, 2024; structural mechanism from Ishida et al., Nature Structural & Molecular Biology, 2021, DOI: 10.1038/s41594-020-00542-w |
| Other deleterious or partial loss-of-function UNC93B1 missense variants | Loss or reduction of function; pathogenicity may depend on genetic background | Variable or unresolved | Recurrent or severe viral infection, including HSV-associated disease; broader innate immunodeficiency | Reduced endosomal TLR signaling, particularly the TLR3–IRF3/type-I-IFN antiviral axis | Recent human observations support impaired TLR3-driven interferon responses, but individual variants require functional validation because coexisting variants in other antiviral genes can complicate causal attribution; loss of UNC93B1 generally traps client TLRs in the ER (mielcarska2021cellsurfaceexpression pages 2-4, alazab2024geneticvariantsin pages 1-4) | Contemporary functional context from 2023–2024 human and mechanistic studies; variant-level causality should be interpreted conservatively |
Table: Summary of human UNC93B1 gain- and loss-of-function variants, their inheritance, receptor-selective signaling effects, and associated autoimmune or infectious phenotypes. The table emphasizes 2023–2024 genetic studies while distinguishing causal mutations from susceptibility alleles and incompletely resolved variants.
The functional characterization of UNC93B1 has employed diverse experimental approaches:
Human cell lines: HEK293T cells with transient or stable expression of UNC93B1 and TLRs, THP-1 monocytic cells, and engineered knockout/knockdown lines have been used for luciferase reporter assays, qPCR, Western blotting, co-immunoprecipitation, and flow cytometry (zhu2022unc93b1attenuatesthe pages 6-6, han2024anovelunc93b1 pages 4-6, david2024gainoffunctionhumanunc93b1 pages 22-22, zhu2022unc93b1attenuatesthe pages 5-5, zhu2022unc93b1attenuatesthe pages 4-5).
Primary cells: Patient-derived PBMCs, fibroblasts, and peritoneal macrophages from Unc93b1-deficient mice have been analyzed using single-cell transcriptomics, ELISA, viral infection assays, and signaling pathway readouts (zhu2022unc93b1attenuatesthe pages 9-9, han2024anovelunc93b1 pages 4-6, han2024anovelunc93b1 pages 26-31).
Genome-edited mice: CRISPR-engineered mice carrying human disease variants (T93I, R336C, R95L, V138L) developed spontaneous autoimmune phenotypes including splenomegaly, lymphoid expansion, autoantibodies, glomerulonephritis, and enhanced TLR7 responses (rael2024largescalemutationalanalysis pages 9-11, alazab2024geneticvariantsin pages 1-4, han2024anovelunc93b1 pages 4-6, rael2024largescalemutationalanalysis pages 1-2).
Mutagenesis screens: Large-scale alanine-scanning mutagenesis of all cytosolic and luminal UNC93B1 residues identified receptor-specific positive and negative regulatory regions (rael2024largescalemutationalanalysis pages 1-2).
TLR-specific stimulation with R848 (TLR7/8), CL307 (TLR7), TL8-506 (TLR8), CpG DNA (TLR9), and poly(I:C) (TLR3) in conjunction with NF-κB and IRF reporter assays, cytokine ELISAs, and transcriptional profiling (han2024anovelunc93b1 pages 4-6, david2024gainoffunctionhumanunc93b1 pages 22-22).
Inhibitor experiments using chloroquine, ammonium chloride, MG132, and TLR7/8 inhibitors to distinguish degradation pathways and validate receptor dependence (zhu2022unc93b1attenuatesthe pages 4-5, han2024anovelunc93b1 pages 4-6).
HSV-1 infection models in cells and mice to assess antiviral immunity and STING regulation (zhu2022unc93b1attenuatesthe pages 8-9, zhu2022unc93b1attenuatesthe pages 9-9).
UNC93B1 is a 12-transmembrane endoplasmic reticulum chaperone protein that serves as a master regulator of intracellular nucleic-acid-sensing innate immunity (ishida2021cryoemstructuresof pages 1-2, rael2024largescalemutationalanalysis pages 17-18, robinson2025recentinsightsinto pages 7-8). Its primary molecular function is to bind, stabilize, and traffic endosomal Toll-like receptors (TLR3, TLR7, TLR8, TLR9) from the ER to endolysosomal compartments, where these receptors detect viral and microbial nucleic acids and initiate antiviral and inflammatory responses (song2022nglycosylationofunc93b1 pages 1-2, mielcarska2021cellsurfaceexpression pages 2-4, ishida2021cryoemstructuresof pages 1-2, rael2024largescalemutationalanalysis pages 17-18). Beyond simple trafficking, UNC93B1 exerts receptor-specific regulatory control: it differentially regulates TLR7 versus TLR9 through post-delivery retention, N-glycosylation-dependent adaptor recruitment, and syntenin-1-mediated signal termination (rael2024largescalemutationalanalysis pages 1-2, song2022nglycosylationofunc93b1 pages 1-2, ishida2021cryoemstructuresof pages 6-8). UNC93B1 also negatively regulates the cGAS–STING DNA-sensing pathway by targeting STING for autophagy–lysosome degradation (zhu2022unc93b1attenuatesthe pages 1-1, zhu2022unc93b1attenuatesthe pages 4-5, zhu2022unc93b1attenuatesthe pages 4-4).
Recent human genetic studies (2023–2024) have identified gain-of-function UNC93B1 variants as causes of monogenic childhood-onset systemic lupus erythematosus, chilblain lupus, rheumatoid arthritis, and other autoimmune diseases, underscoring the protein's critical role in preventing TLR7/8-driven autoimmunity (han2024anovelunc93b1 pages 26-31, david2024gainoffunctionhumanunc93b1 pages 1-2, alazab2024geneticvariantsin pages 1-4, rael2024largescalemutationalanalysis pages 4-6, he2025casereportnovel pages 2-5, rael2024largescalemutationalanalysis pages 1-2). Conversely, loss-of-function mutations cause immunodeficiency with susceptibility to herpes simplex virus and other infections (alazab2024geneticvariantsin pages 1-4). These findings establish UNC93B1 as a dual checkpoint regulator that balances protective antiviral immunity against inappropriate recognition of self nucleic acids, with dysregulation leading to either immunodeficiency or autoimmunity depending on the functional direction of the variant (rael2024largescalemutationalanalysis pages 1-2, rael2024largescalemutationalanalysis pages 17-18).
References
(ishida2021cryoemstructuresof pages 1-2): Hanako Ishida, Jinta Asami, Zhikuan Zhang, Tomohiro Nishizawa, Hideki Shigematsu, Umeharu Ohto, and Toshiyuki Shimizu. Cryo-em structures of toll-like receptors in complex with unc93b1. Nature Structural & Molecular Biology, 28:173-180, Jan 2021. URL: https://doi.org/10.1038/s41594-020-00542-w, doi:10.1038/s41594-020-00542-w. This article has 99 citations and is from a highest quality peer-reviewed journal.
(klammer2023expressionundfunktion pages 19-22): Markus Klammer. Expression und funktion von unc93b1 im zentralen nervensystem. Text, Jan 2023. URL: https://doi.org/10.17169/refubium-38796, doi:10.17169/refubium-38796. This article has 0 citations and is from a peer-reviewed journal.
(song2022nglycosylationofunc93b1 pages 1-2): Hyun-Sup Song, Soeun Park, Ji-Won Huh, Yu-Ran Lee, Da-Jung Jung, Chorong Yang, So Hyun Kim, Ho Min Kim, and You-Me Kim. N-glycosylation of unc93b1 at a specific asparagine residue is required for tlr9 signaling. Frontiers in Immunology, Jul 2022. URL: https://doi.org/10.3389/fimmu.2022.875083, doi:10.3389/fimmu.2022.875083. This article has 6 citations and is from a peer-reviewed journal.
(rael2024largescalemutationalanalysis pages 17-18): Victoria E. Rael, Julian A. Yano, John P. Huizar, Leianna C. Slayden, Madeleine A. Weiss, Elizabeth A. Turcotte, Jacob M. Terry, Wenqi Zuo, Isabelle Thiffault, Tomi Pastinen, Emily G. Farrow, Janda L. Jenkins, Mara L. Becker, Stephen C. Wong, Anne M. Stevens, Catherine Otten, Eric J. Allenspach, Devon E. Bonner, Jonathan A. Bernstein, Matthew T. Wheeler, Robert A. Saxton, Maria T. Acosta, David R. Adams, Raquel L. Alvarez, Justin Alvey, Aimee Allworth, Ashley Andrews, Euan A. Ashley, Ben Afzali, Carlos A. Bacino, Guney Bademci, Ashok Balasubramanyam, Dustin Baldridge, Jim Bale, Michael Bamshad, Deborah Barbouth, Pinar Bayrak-Toydemir, Anita Beck, Alan H. Beggs, Edward Behrens, Gill Bejerano, Hugo J. Bellen, Jimmy Bennett, Jonathan A. Bernstein, Gerard T. Berry, Anna Bican, Stephanie Bivona, Elizabeth Blue, John Bohnsack, Devon Bonner, Lorenzo Botto, Lauren C. Briere, Gabrielle Brown, Elizabeth A. Burke, Lindsay C. Burrage, Manish J. Butte, Peter Byers, William E. Byrd, John Carey, Thomas Cassini, Sirisak Chanprasert, Hsiao-Tuan Chao, Ivan Chinn, Gary D. Clark, Terra R. Coakley, Laurel A. Cobban, Joy D. Cogan, Matthew Coggins, F. Sessions Cole, Heather A. Colley, Rosario Corona, William J. Craigen, Andrew B. Crouse, Michael Cunningham, Precilla D’Souza, Hongzheng Dai, Surendra Dasari, Joie Davis, Jyoti G. Dayal, Margaret Delgado, Esteban C. Dell’Angelica, Katrina Dipple, Daniel Doherty, Naghmeh Dorrani, Argenia L. Doss, Emilie D. Douine, Dawn Earl, David J. Eckstein, Lisa T. Emrick, Christine M. Eng, Marni Falk, Elizabeth L. Fieg, Paul G. Fisher, Brent L. Fogel, Jiayu Fu, William A. Gahl, Ian Glass, Page C. Goddard, Rena A. Godfrey, Andrea Gropman, Meghan C. Halley, Rizwan Hamid, Neal Hanchard, Kelly Hassey, Nichole Hayes, Frances High, Anne Hing, Fuki M. Hisama, Ingrid A. Holm, Jason Hom, Martha Horike-Pyne, Alden Huang, Yan Huang, Sarah Hutchison, Wendy Introne, Kosuke Izumi, Gail P. Jarvik, Jeffrey Jarvik, Suman Jayadev, Orpa Jean-Marie, Vaidehi Jobanputra, Emerald Kaitryn, Shamika Ketkar, Dana Kiley, Gonench Kilich, Shilpa N. Kobren, Isaac S. Kohane, Jennefer N. Kohler, Susan Korrick, Deborah Krakow, Donna M. Krasnewich, Elijah Kravets, Seema R. Lalani, Christina Lam, Brendan C. Lanpher, Ian R. Lanza, Kimberly LeBlanc, Brendan H. Lee, Richard A. Lewis, Pengfei Liu, Nicola Longo, Sandra K. Loo, Joseph Loscalzo, Richard L. Maas, Ellen F. Macnamara, Calum A. MacRae, Valerie V. Maduro, AudreyStephannie Maghiro, Rachel Mahoney, May Christine V. Malicdan, Laura A. Mamounas, Teri A. Manolio, Rong Mao, Ronit Marom, Gabor Marth, Beth A. Martin, Martin G. Martin, Julian A. Martínez-Agosto, Shruti Marwaha, Allyn McConkie-Rosell, Alexa T. McCray, Elisabeth McGee, Matthew Might, Mohamad Mikati, Danny Miller, Ghayda Mirzaa, Eva Morava, Paolo Moretti, Marie Morimoto, John J. Mulvihill, Mariko Nakano-Okuno, Stanley F. Nelson, Shirley Nieves-Rodriguez, Donna Novacic, Devin Oglesbee, James P. Orengo, Laura Pace, Stephen Pak, J. Carl Pallais, Jeanette C. Papp, Neil H. Parker, Leoyklang Petcharet, John A. Phillips, Jennifer E. Posey, Lorraine Potocki, Barbara N. Pusey Swerdzewski, Aaron Quinlan, Deepak A. Rao, Anna Raper, Wendy Raskind, Genecee Renteria, Chloe M. Reuter, Lynette Rives, Amy K. Robertson, Lance H. Rodan, Jill A. Rosenfeld, Elizabeth Rosenthal, Francis Rossignol, Maura Ruzhnikov, Marla Sabaii, Jacinda B. Sampson, Timothy Schedl, Kelly Schoch, Daryl A. Scott, Elaine Seto, Prashant Sharma, Vandana Shashi, Emily Shelkowitz, Sam Sheppeard, Jimann Shin, Edwin K. Silverman, Janet S. Sinsheimer, Kathy Sisco, Kevin S. Smith, Lilianna Solnica-Krezel, Ben Solomon, Rebecca C. Spillmann, Andrew Stergachis, Joan M. Stoler, Kathleen Sullivan, Shirley Sutton, David A. Sweetser, Virginia Sybert, Holly K. Tabor, Queenie K.-G. Tan, Amelia L.M. Tan, Arjun Tarakad, Herman Taylor, Mustafa Tekin, Willa Thorson, Cynthia J. Tifft, Camilo Toro, Alyssa A. Tran, Rachel A. Ungar, Tiina K. Urv, Adeline Vanderver, Matt Velinder, Dave Viskochil, Tiphanie P. Vogel, Colleen E. Wahl, Melissa Walker, Nicole M. Walley, Jennifer Wambach, Jijun Wan, Lee-kai Wang, Michael F. Wangler, Patricia A. Ward, Daniel Wegner, Monika Weisz Hubshman, Mark Wener, Tara Wenger, Monte Westerfield, Matthew T. Wheeler, Jordan Whitlock, Lynne A. Wolfe, Kim Worley, Shinya Yamamoto, Zhe Zhang, Stephan Zuchner, Bo Liu, Olivia Majer, and Gregory M. Barton. Large-scale mutational analysis identifies unc93b1 variants that drive tlr-mediated autoimmunity in mice and humans. The Journal of Experimental Medicine, May 2024. URL: https://doi.org/10.1084/jem.20232005, doi:10.1084/jem.20232005. This article has 51 citations.
(ishida2021cryoemstructuresof pages 5-6): Hanako Ishida, Jinta Asami, Zhikuan Zhang, Tomohiro Nishizawa, Hideki Shigematsu, Umeharu Ohto, and Toshiyuki Shimizu. Cryo-em structures of toll-like receptors in complex with unc93b1. Nature Structural & Molecular Biology, 28:173-180, Jan 2021. URL: https://doi.org/10.1038/s41594-020-00542-w, doi:10.1038/s41594-020-00542-w. This article has 99 citations and is from a highest quality peer-reviewed journal.
(mielcarska2021cellsurfaceexpression pages 2-4): Matylda Barbara Mielcarska, Magdalena Bossowska-Nowicka, and Felix Ngosa Toka. Cell surface expression of endosomal toll-like receptors—a necessity or a superfluous duplication? Frontiers in Immunology, Feb 2021. URL: https://doi.org/10.3389/fimmu.2020.620972, doi:10.3389/fimmu.2020.620972. This article has 81 citations and is from a peer-reviewed journal.
(ishida2021cryoemstructuresof pages 2-3): Hanako Ishida, Jinta Asami, Zhikuan Zhang, Tomohiro Nishizawa, Hideki Shigematsu, Umeharu Ohto, and Toshiyuki Shimizu. Cryo-em structures of toll-like receptors in complex with unc93b1. Nature Structural & Molecular Biology, 28:173-180, Jan 2021. URL: https://doi.org/10.1038/s41594-020-00542-w, doi:10.1038/s41594-020-00542-w. This article has 99 citations and is from a highest quality peer-reviewed journal.
(ishida2021cryoemstructuresof pages 3-4): Hanako Ishida, Jinta Asami, Zhikuan Zhang, Tomohiro Nishizawa, Hideki Shigematsu, Umeharu Ohto, and Toshiyuki Shimizu. Cryo-em structures of toll-like receptors in complex with unc93b1. Nature Structural & Molecular Biology, 28:173-180, Jan 2021. URL: https://doi.org/10.1038/s41594-020-00542-w, doi:10.1038/s41594-020-00542-w. This article has 99 citations and is from a highest quality peer-reviewed journal.
(ishida2021cryoemstructuresof pages 6-8): Hanako Ishida, Jinta Asami, Zhikuan Zhang, Tomohiro Nishizawa, Hideki Shigematsu, Umeharu Ohto, and Toshiyuki Shimizu. Cryo-em structures of toll-like receptors in complex with unc93b1. Nature Structural & Molecular Biology, 28:173-180, Jan 2021. URL: https://doi.org/10.1038/s41594-020-00542-w, doi:10.1038/s41594-020-00542-w. This article has 99 citations and is from a highest quality peer-reviewed journal.
(zhu2022unc93b1attenuatesthe pages 1-1): Huifang Zhu, Rongzhao Zhang, Li Yi, Yan‐Dong Tang, and Chunfu Zheng. Unc93b1 attenuates the cgas–sting signaling pathway by targeting sting for autophagy–lysosome degradation. May 2022. URL: https://doi.org/10.1002/jmv.27860, doi:10.1002/jmv.27860. This article has 84 citations and is from a peer-reviewed journal.
(zhu2022unc93b1attenuatesthe pages 4-4): Huifang Zhu, Rongzhao Zhang, Li Yi, Yan‐Dong Tang, and Chunfu Zheng. Unc93b1 attenuates the cgas–sting signaling pathway by targeting sting for autophagy–lysosome degradation. May 2022. URL: https://doi.org/10.1002/jmv.27860, doi:10.1002/jmv.27860. This article has 84 citations and is from a peer-reviewed journal.
(rael2024largescalemutationalanalysis pages 1-2): Victoria E. Rael, Julian A. Yano, John P. Huizar, Leianna C. Slayden, Madeleine A. Weiss, Elizabeth A. Turcotte, Jacob M. Terry, Wenqi Zuo, Isabelle Thiffault, Tomi Pastinen, Emily G. Farrow, Janda L. Jenkins, Mara L. Becker, Stephen C. Wong, Anne M. Stevens, Catherine Otten, Eric J. Allenspach, Devon E. Bonner, Jonathan A. Bernstein, Matthew T. Wheeler, Robert A. Saxton, Maria T. Acosta, David R. Adams, Raquel L. Alvarez, Justin Alvey, Aimee Allworth, Ashley Andrews, Euan A. Ashley, Ben Afzali, Carlos A. Bacino, Guney Bademci, Ashok Balasubramanyam, Dustin Baldridge, Jim Bale, Michael Bamshad, Deborah Barbouth, Pinar Bayrak-Toydemir, Anita Beck, Alan H. Beggs, Edward Behrens, Gill Bejerano, Hugo J. Bellen, Jimmy Bennett, Jonathan A. Bernstein, Gerard T. Berry, Anna Bican, Stephanie Bivona, Elizabeth Blue, John Bohnsack, Devon Bonner, Lorenzo Botto, Lauren C. Briere, Gabrielle Brown, Elizabeth A. Burke, Lindsay C. Burrage, Manish J. Butte, Peter Byers, William E. Byrd, John Carey, Thomas Cassini, Sirisak Chanprasert, Hsiao-Tuan Chao, Ivan Chinn, Gary D. Clark, Terra R. Coakley, Laurel A. Cobban, Joy D. Cogan, Matthew Coggins, F. Sessions Cole, Heather A. Colley, Rosario Corona, William J. Craigen, Andrew B. Crouse, Michael Cunningham, Precilla D’Souza, Hongzheng Dai, Surendra Dasari, Joie Davis, Jyoti G. Dayal, Margaret Delgado, Esteban C. Dell’Angelica, Katrina Dipple, Daniel Doherty, Naghmeh Dorrani, Argenia L. Doss, Emilie D. Douine, Dawn Earl, David J. Eckstein, Lisa T. Emrick, Christine M. Eng, Marni Falk, Elizabeth L. Fieg, Paul G. Fisher, Brent L. Fogel, Jiayu Fu, William A. Gahl, Ian Glass, Page C. Goddard, Rena A. Godfrey, Andrea Gropman, Meghan C. Halley, Rizwan Hamid, Neal Hanchard, Kelly Hassey, Nichole Hayes, Frances High, Anne Hing, Fuki M. Hisama, Ingrid A. Holm, Jason Hom, Martha Horike-Pyne, Alden Huang, Yan Huang, Sarah Hutchison, Wendy Introne, Kosuke Izumi, Gail P. Jarvik, Jeffrey Jarvik, Suman Jayadev, Orpa Jean-Marie, Vaidehi Jobanputra, Emerald Kaitryn, Shamika Ketkar, Dana Kiley, Gonench Kilich, Shilpa N. Kobren, Isaac S. Kohane, Jennefer N. Kohler, Susan Korrick, Deborah Krakow, Donna M. Krasnewich, Elijah Kravets, Seema R. Lalani, Christina Lam, Brendan C. Lanpher, Ian R. Lanza, Kimberly LeBlanc, Brendan H. Lee, Richard A. Lewis, Pengfei Liu, Nicola Longo, Sandra K. Loo, Joseph Loscalzo, Richard L. Maas, Ellen F. Macnamara, Calum A. MacRae, Valerie V. Maduro, AudreyStephannie Maghiro, Rachel Mahoney, May Christine V. Malicdan, Laura A. Mamounas, Teri A. Manolio, Rong Mao, Ronit Marom, Gabor Marth, Beth A. Martin, Martin G. Martin, Julian A. Martínez-Agosto, Shruti Marwaha, Allyn McConkie-Rosell, Alexa T. McCray, Elisabeth McGee, Matthew Might, Mohamad Mikati, Danny Miller, Ghayda Mirzaa, Eva Morava, Paolo Moretti, Marie Morimoto, John J. Mulvihill, Mariko Nakano-Okuno, Stanley F. Nelson, Shirley Nieves-Rodriguez, Donna Novacic, Devin Oglesbee, James P. Orengo, Laura Pace, Stephen Pak, J. Carl Pallais, Jeanette C. Papp, Neil H. Parker, Leoyklang Petcharet, John A. Phillips, Jennifer E. Posey, Lorraine Potocki, Barbara N. Pusey Swerdzewski, Aaron Quinlan, Deepak A. Rao, Anna Raper, Wendy Raskind, Genecee Renteria, Chloe M. Reuter, Lynette Rives, Amy K. Robertson, Lance H. Rodan, Jill A. Rosenfeld, Elizabeth Rosenthal, Francis Rossignol, Maura Ruzhnikov, Marla Sabaii, Jacinda B. Sampson, Timothy Schedl, Kelly Schoch, Daryl A. Scott, Elaine Seto, Prashant Sharma, Vandana Shashi, Emily Shelkowitz, Sam Sheppeard, Jimann Shin, Edwin K. Silverman, Janet S. Sinsheimer, Kathy Sisco, Kevin S. Smith, Lilianna Solnica-Krezel, Ben Solomon, Rebecca C. Spillmann, Andrew Stergachis, Joan M. Stoler, Kathleen Sullivan, Shirley Sutton, David A. Sweetser, Virginia Sybert, Holly K. Tabor, Queenie K.-G. Tan, Amelia L.M. Tan, Arjun Tarakad, Herman Taylor, Mustafa Tekin, Willa Thorson, Cynthia J. Tifft, Camilo Toro, Alyssa A. Tran, Rachel A. Ungar, Tiina K. Urv, Adeline Vanderver, Matt Velinder, Dave Viskochil, Tiphanie P. Vogel, Colleen E. Wahl, Melissa Walker, Nicole M. Walley, Jennifer Wambach, Jijun Wan, Lee-kai Wang, Michael F. Wangler, Patricia A. Ward, Daniel Wegner, Monika Weisz Hubshman, Mark Wener, Tara Wenger, Monte Westerfield, Matthew T. Wheeler, Jordan Whitlock, Lynne A. Wolfe, Kim Worley, Shinya Yamamoto, Zhe Zhang, Stephan Zuchner, Bo Liu, Olivia Majer, and Gregory M. Barton. Large-scale mutational analysis identifies unc93b1 variants that drive tlr-mediated autoimmunity in mice and humans. The Journal of Experimental Medicine, May 2024. URL: https://doi.org/10.1084/jem.20232005, doi:10.1084/jem.20232005. This article has 51 citations.
(david2024gainoffunctionhumanunc93b1 pages 1-2): Clémence David, Carlos A. Arango-Franco, Mihaly Badonyi, Julien Fouchet, Gillian I. Rice, Blaise Didry-Barca, Lucie Maisonneuve, Luis Seabra, Robin Kechiche, Cécile Masson, Aurélie Cobat, Laurent Abel, Estelle Talouarn, Vivien Béziat, Caroline Deswarte, Katie Livingstone, Carle Paul, Gulshan Malik, Alison Ross, Jane Adam, Jo Walsh, Sathish Kumar, Damien Bonnet, Christine Bodemer, Brigitte Bader-Meunier, Joseph A. Marsh, Jean-Laurent Casanova, Yanick J. Crow, Bénédicte Manoury, Marie-Louise Frémond, Jonathan Bohlen, and Alice Lepelley. Gain-of-function human unc93b1 variants cause systemic lupus erythematosus and chilblain lupus. The Journal of Experimental Medicine, Jun 2024. URL: https://doi.org/10.1084/jem.20232066, doi:10.1084/jem.20232066. This article has 69 citations.
(song2022nglycosylationofunc93b1 pages 4-6): Hyun-Sup Song, Soeun Park, Ji-Won Huh, Yu-Ran Lee, Da-Jung Jung, Chorong Yang, So Hyun Kim, Ho Min Kim, and You-Me Kim. N-glycosylation of unc93b1 at a specific asparagine residue is required for tlr9 signaling. Frontiers in Immunology, Jul 2022. URL: https://doi.org/10.3389/fimmu.2022.875083, doi:10.3389/fimmu.2022.875083. This article has 6 citations and is from a peer-reviewed journal.
(zhu2022unc93b1attenuatesthe pages 4-5): Huifang Zhu, Rongzhao Zhang, Li Yi, Yan‐Dong Tang, and Chunfu Zheng. Unc93b1 attenuates the cgas–sting signaling pathway by targeting sting for autophagy–lysosome degradation. May 2022. URL: https://doi.org/10.1002/jmv.27860, doi:10.1002/jmv.27860. This article has 84 citations and is from a peer-reviewed journal.
(alazab2024geneticvariantsin pages 1-4): Mahmoud Al-Azab, Elina Idiiatullina, Ziyang Liu, Meng Lin, K. Hrovat-Schaale, Huifang Xian, Jianheng Zhu, Mandy Yang, Bingtai Lu, Zhiyao Zhao, Yiyi Liu, Jingjie Chang, Xiaotian Li, Caiqin Guo, Yunfeng Liu, Qi Wu, Jiazhang Chen, Chaoting Lan, Ping Zeng, Jun Cui, Xia Gao, Wenhao Zhou, Yan Zhang, Yuxia Zhang, and Seth L Masters. Genetic variants in unc93b1 predispose to childhood-onset systemic lupus erythematosus. Nature Immunology, 25:969-980, Oct 2024. URL: https://doi.org/10.1101/2023.10.15.23296507, doi:10.1101/2023.10.15.23296507. This article has 66 citations and is from a highest quality peer-reviewed journal.
(robinson2025recentinsightsinto pages 7-8): Lauren A. Robinson and Virginia Pascual. Recent insights into the role of innate immunity in lupus. Human molecular genetics, Jun 2025. URL: https://doi.org/10.1093/hmg/ddaf066, doi:10.1093/hmg/ddaf066. This article has 7 citations and is from a domain leading peer-reviewed journal.
(zhu2022unc93b1attenuatesthe pages 6-6): Huifang Zhu, Rongzhao Zhang, Li Yi, Yan‐Dong Tang, and Chunfu Zheng. Unc93b1 attenuates the cgas–sting signaling pathway by targeting sting for autophagy–lysosome degradation. May 2022. URL: https://doi.org/10.1002/jmv.27860, doi:10.1002/jmv.27860. This article has 84 citations and is from a peer-reviewed journal.
(zhu2022unc93b1attenuatesthe pages 9-9): Huifang Zhu, Rongzhao Zhang, Li Yi, Yan‐Dong Tang, and Chunfu Zheng. Unc93b1 attenuates the cgas–sting signaling pathway by targeting sting for autophagy–lysosome degradation. May 2022. URL: https://doi.org/10.1002/jmv.27860, doi:10.1002/jmv.27860. This article has 84 citations and is from a peer-reviewed journal.
(han2024anovelunc93b1 pages 4-6): Xu Han, Ruoran Wang, Seza Ozen, Qintao Wang, Wei Dong, Yi Zeng, Ouyuan Xu, Seher Şener, Li Guo, Ying Gu, Huanming Yang, Xiaomin Yu, Panfeng Tao, and Qing Zhou. A novel unc93b1 gain-of-function mutation leads to tlr7 and tlr8 hyperactivation and systemic lupus erythematosus. MedRxiv, Sep 2024. URL: https://doi.org/10.1101/2024.09.11.24313360, doi:10.1101/2024.09.11.24313360. This article has 0 citations.
(song2022nglycosylationofunc93b1 pages 12-13): Hyun-Sup Song, Soeun Park, Ji-Won Huh, Yu-Ran Lee, Da-Jung Jung, Chorong Yang, So Hyun Kim, Ho Min Kim, and You-Me Kim. N-glycosylation of unc93b1 at a specific asparagine residue is required for tlr9 signaling. Frontiers in Immunology, Jul 2022. URL: https://doi.org/10.3389/fimmu.2022.875083, doi:10.3389/fimmu.2022.875083. This article has 6 citations and is from a peer-reviewed journal.
(zhu2022unc93b1attenuatesthe pages 6-7): Huifang Zhu, Rongzhao Zhang, Li Yi, Yan‐Dong Tang, and Chunfu Zheng. Unc93b1 attenuates the cgas–sting signaling pathway by targeting sting for autophagy–lysosome degradation. May 2022. URL: https://doi.org/10.1002/jmv.27860, doi:10.1002/jmv.27860. This article has 84 citations and is from a peer-reviewed journal.
(zhu2022unc93b1attenuatesthe pages 8-9): Huifang Zhu, Rongzhao Zhang, Li Yi, Yan‐Dong Tang, and Chunfu Zheng. Unc93b1 attenuates the cgas–sting signaling pathway by targeting sting for autophagy–lysosome degradation. May 2022. URL: https://doi.org/10.1002/jmv.27860, doi:10.1002/jmv.27860. This article has 84 citations and is from a peer-reviewed journal.
(zhu2022unc93b1attenuatesthe pages 5-5): Huifang Zhu, Rongzhao Zhang, Li Yi, Yan‐Dong Tang, and Chunfu Zheng. Unc93b1 attenuates the cgas–sting signaling pathway by targeting sting for autophagy–lysosome degradation. May 2022. URL: https://doi.org/10.1002/jmv.27860, doi:10.1002/jmv.27860. This article has 84 citations and is from a peer-reviewed journal.
(han2024anovelunc93b1 pages 26-31): Xu Han, Ruoran Wang, Seza Ozen, Qintao Wang, Wei Dong, Yi Zeng, Ouyuan Xu, Seher Şener, Li Guo, Ying Gu, Huanming Yang, Xiaomin Yu, Panfeng Tao, and Qing Zhou. A novel unc93b1 gain-of-function mutation leads to tlr7 and tlr8 hyperactivation and systemic lupus erythematosus. MedRxiv, Sep 2024. URL: https://doi.org/10.1101/2024.09.11.24313360, doi:10.1101/2024.09.11.24313360. This article has 0 citations.
(he2025casereportnovel pages 5-7): Ting-Yan He, Junbin Ou, Li-Juan Huang, Xinyi Zhou, Linlin Wang, Xiao-Lin Li, and Jun Yang. Case report: novel unc93b1 variant causes rheumatoid arthritis and interstitial pneumonia. Frontiers in Immunology, Oct 2025. URL: https://doi.org/10.3389/fimmu.2025.1671984, doi:10.3389/fimmu.2025.1671984. This article has 5 citations and is from a peer-reviewed journal.
(rael2024largescalemutationalanalysis pages 4-6): Victoria E. Rael, Julian A. Yano, John P. Huizar, Leianna C. Slayden, Madeleine A. Weiss, Elizabeth A. Turcotte, Jacob M. Terry, Wenqi Zuo, Isabelle Thiffault, Tomi Pastinen, Emily G. Farrow, Janda L. Jenkins, Mara L. Becker, Stephen C. Wong, Anne M. Stevens, Catherine Otten, Eric J. Allenspach, Devon E. Bonner, Jonathan A. Bernstein, Matthew T. Wheeler, Robert A. Saxton, Maria T. Acosta, David R. Adams, Raquel L. Alvarez, Justin Alvey, Aimee Allworth, Ashley Andrews, Euan A. Ashley, Ben Afzali, Carlos A. Bacino, Guney Bademci, Ashok Balasubramanyam, Dustin Baldridge, Jim Bale, Michael Bamshad, Deborah Barbouth, Pinar Bayrak-Toydemir, Anita Beck, Alan H. Beggs, Edward Behrens, Gill Bejerano, Hugo J. Bellen, Jimmy Bennett, Jonathan A. Bernstein, Gerard T. Berry, Anna Bican, Stephanie Bivona, Elizabeth Blue, John Bohnsack, Devon Bonner, Lorenzo Botto, Lauren C. Briere, Gabrielle Brown, Elizabeth A. Burke, Lindsay C. Burrage, Manish J. Butte, Peter Byers, William E. Byrd, John Carey, Thomas Cassini, Sirisak Chanprasert, Hsiao-Tuan Chao, Ivan Chinn, Gary D. Clark, Terra R. Coakley, Laurel A. Cobban, Joy D. Cogan, Matthew Coggins, F. Sessions Cole, Heather A. Colley, Rosario Corona, William J. Craigen, Andrew B. Crouse, Michael Cunningham, Precilla D’Souza, Hongzheng Dai, Surendra Dasari, Joie Davis, Jyoti G. Dayal, Margaret Delgado, Esteban C. Dell’Angelica, Katrina Dipple, Daniel Doherty, Naghmeh Dorrani, Argenia L. Doss, Emilie D. Douine, Dawn Earl, David J. Eckstein, Lisa T. Emrick, Christine M. Eng, Marni Falk, Elizabeth L. Fieg, Paul G. Fisher, Brent L. Fogel, Jiayu Fu, William A. Gahl, Ian Glass, Page C. Goddard, Rena A. Godfrey, Andrea Gropman, Meghan C. Halley, Rizwan Hamid, Neal Hanchard, Kelly Hassey, Nichole Hayes, Frances High, Anne Hing, Fuki M. Hisama, Ingrid A. Holm, Jason Hom, Martha Horike-Pyne, Alden Huang, Yan Huang, Sarah Hutchison, Wendy Introne, Kosuke Izumi, Gail P. Jarvik, Jeffrey Jarvik, Suman Jayadev, Orpa Jean-Marie, Vaidehi Jobanputra, Emerald Kaitryn, Shamika Ketkar, Dana Kiley, Gonench Kilich, Shilpa N. Kobren, Isaac S. Kohane, Jennefer N. Kohler, Susan Korrick, Deborah Krakow, Donna M. Krasnewich, Elijah Kravets, Seema R. Lalani, Christina Lam, Brendan C. Lanpher, Ian R. Lanza, Kimberly LeBlanc, Brendan H. Lee, Richard A. Lewis, Pengfei Liu, Nicola Longo, Sandra K. Loo, Joseph Loscalzo, Richard L. Maas, Ellen F. Macnamara, Calum A. MacRae, Valerie V. Maduro, AudreyStephannie Maghiro, Rachel Mahoney, May Christine V. Malicdan, Laura A. Mamounas, Teri A. Manolio, Rong Mao, Ronit Marom, Gabor Marth, Beth A. Martin, Martin G. Martin, Julian A. Martínez-Agosto, Shruti Marwaha, Allyn McConkie-Rosell, Alexa T. McCray, Elisabeth McGee, Matthew Might, Mohamad Mikati, Danny Miller, Ghayda Mirzaa, Eva Morava, Paolo Moretti, Marie Morimoto, John J. Mulvihill, Mariko Nakano-Okuno, Stanley F. Nelson, Shirley Nieves-Rodriguez, Donna Novacic, Devin Oglesbee, James P. Orengo, Laura Pace, Stephen Pak, J. Carl Pallais, Jeanette C. Papp, Neil H. Parker, Leoyklang Petcharet, John A. Phillips, Jennifer E. Posey, Lorraine Potocki, Barbara N. Pusey Swerdzewski, Aaron Quinlan, Deepak A. Rao, Anna Raper, Wendy Raskind, Genecee Renteria, Chloe M. Reuter, Lynette Rives, Amy K. Robertson, Lance H. Rodan, Jill A. Rosenfeld, Elizabeth Rosenthal, Francis Rossignol, Maura Ruzhnikov, Marla Sabaii, Jacinda B. Sampson, Timothy Schedl, Kelly Schoch, Daryl A. Scott, Elaine Seto, Prashant Sharma, Vandana Shashi, Emily Shelkowitz, Sam Sheppeard, Jimann Shin, Edwin K. Silverman, Janet S. Sinsheimer, Kathy Sisco, Kevin S. Smith, Lilianna Solnica-Krezel, Ben Solomon, Rebecca C. Spillmann, Andrew Stergachis, Joan M. Stoler, Kathleen Sullivan, Shirley Sutton, David A. Sweetser, Virginia Sybert, Holly K. Tabor, Queenie K.-G. Tan, Amelia L.M. Tan, Arjun Tarakad, Herman Taylor, Mustafa Tekin, Willa Thorson, Cynthia J. Tifft, Camilo Toro, Alyssa A. Tran, Rachel A. Ungar, Tiina K. Urv, Adeline Vanderver, Matt Velinder, Dave Viskochil, Tiphanie P. Vogel, Colleen E. Wahl, Melissa Walker, Nicole M. Walley, Jennifer Wambach, Jijun Wan, Lee-kai Wang, Michael F. Wangler, Patricia A. Ward, Daniel Wegner, Monika Weisz Hubshman, Mark Wener, Tara Wenger, Monte Westerfield, Matthew T. Wheeler, Jordan Whitlock, Lynne A. Wolfe, Kim Worley, Shinya Yamamoto, Zhe Zhang, Stephan Zuchner, Bo Liu, Olivia Majer, and Gregory M. Barton. Large-scale mutational analysis identifies unc93b1 variants that drive tlr-mediated autoimmunity in mice and humans. The Journal of Experimental Medicine, May 2024. URL: https://doi.org/10.1084/jem.20232005, doi:10.1084/jem.20232005. This article has 51 citations.
(he2025casereportnovel pages 2-5): Ting-Yan He, Junbin Ou, Li-Juan Huang, Xinyi Zhou, Linlin Wang, Xiao-Lin Li, and Jun Yang. Case report: novel unc93b1 variant causes rheumatoid arthritis and interstitial pneumonia. Frontiers in Immunology, Oct 2025. URL: https://doi.org/10.3389/fimmu.2025.1671984, doi:10.3389/fimmu.2025.1671984. This article has 5 citations and is from a peer-reviewed journal.
(rael2024largescalemutationalanalysis pages 9-11): Victoria E. Rael, Julian A. Yano, John P. Huizar, Leianna C. Slayden, Madeleine A. Weiss, Elizabeth A. Turcotte, Jacob M. Terry, Wenqi Zuo, Isabelle Thiffault, Tomi Pastinen, Emily G. Farrow, Janda L. Jenkins, Mara L. Becker, Stephen C. Wong, Anne M. Stevens, Catherine Otten, Eric J. Allenspach, Devon E. Bonner, Jonathan A. Bernstein, Matthew T. Wheeler, Robert A. Saxton, Maria T. Acosta, David R. Adams, Raquel L. Alvarez, Justin Alvey, Aimee Allworth, Ashley Andrews, Euan A. Ashley, Ben Afzali, Carlos A. Bacino, Guney Bademci, Ashok Balasubramanyam, Dustin Baldridge, Jim Bale, Michael Bamshad, Deborah Barbouth, Pinar Bayrak-Toydemir, Anita Beck, Alan H. Beggs, Edward Behrens, Gill Bejerano, Hugo J. Bellen, Jimmy Bennett, Jonathan A. Bernstein, Gerard T. Berry, Anna Bican, Stephanie Bivona, Elizabeth Blue, John Bohnsack, Devon Bonner, Lorenzo Botto, Lauren C. Briere, Gabrielle Brown, Elizabeth A. Burke, Lindsay C. Burrage, Manish J. Butte, Peter Byers, William E. Byrd, John Carey, Thomas Cassini, Sirisak Chanprasert, Hsiao-Tuan Chao, Ivan Chinn, Gary D. Clark, Terra R. Coakley, Laurel A. Cobban, Joy D. Cogan, Matthew Coggins, F. Sessions Cole, Heather A. Colley, Rosario Corona, William J. Craigen, Andrew B. Crouse, Michael Cunningham, Precilla D’Souza, Hongzheng Dai, Surendra Dasari, Joie Davis, Jyoti G. Dayal, Margaret Delgado, Esteban C. Dell’Angelica, Katrina Dipple, Daniel Doherty, Naghmeh Dorrani, Argenia L. Doss, Emilie D. Douine, Dawn Earl, David J. Eckstein, Lisa T. Emrick, Christine M. Eng, Marni Falk, Elizabeth L. Fieg, Paul G. Fisher, Brent L. Fogel, Jiayu Fu, William A. Gahl, Ian Glass, Page C. Goddard, Rena A. Godfrey, Andrea Gropman, Meghan C. Halley, Rizwan Hamid, Neal Hanchard, Kelly Hassey, Nichole Hayes, Frances High, Anne Hing, Fuki M. Hisama, Ingrid A. Holm, Jason Hom, Martha Horike-Pyne, Alden Huang, Yan Huang, Sarah Hutchison, Wendy Introne, Kosuke Izumi, Gail P. Jarvik, Jeffrey Jarvik, Suman Jayadev, Orpa Jean-Marie, Vaidehi Jobanputra, Emerald Kaitryn, Shamika Ketkar, Dana Kiley, Gonench Kilich, Shilpa N. Kobren, Isaac S. Kohane, Jennefer N. Kohler, Susan Korrick, Deborah Krakow, Donna M. Krasnewich, Elijah Kravets, Seema R. Lalani, Christina Lam, Brendan C. Lanpher, Ian R. Lanza, Kimberly LeBlanc, Brendan H. Lee, Richard A. Lewis, Pengfei Liu, Nicola Longo, Sandra K. Loo, Joseph Loscalzo, Richard L. Maas, Ellen F. Macnamara, Calum A. MacRae, Valerie V. Maduro, AudreyStephannie Maghiro, Rachel Mahoney, May Christine V. Malicdan, Laura A. Mamounas, Teri A. Manolio, Rong Mao, Ronit Marom, Gabor Marth, Beth A. Martin, Martin G. Martin, Julian A. Martínez-Agosto, Shruti Marwaha, Allyn McConkie-Rosell, Alexa T. McCray, Elisabeth McGee, Matthew Might, Mohamad Mikati, Danny Miller, Ghayda Mirzaa, Eva Morava, Paolo Moretti, Marie Morimoto, John J. Mulvihill, Mariko Nakano-Okuno, Stanley F. Nelson, Shirley Nieves-Rodriguez, Donna Novacic, Devin Oglesbee, James P. Orengo, Laura Pace, Stephen Pak, J. Carl Pallais, Jeanette C. Papp, Neil H. Parker, Leoyklang Petcharet, John A. Phillips, Jennifer E. Posey, Lorraine Potocki, Barbara N. Pusey Swerdzewski, Aaron Quinlan, Deepak A. Rao, Anna Raper, Wendy Raskind, Genecee Renteria, Chloe M. Reuter, Lynette Rives, Amy K. Robertson, Lance H. Rodan, Jill A. Rosenfeld, Elizabeth Rosenthal, Francis Rossignol, Maura Ruzhnikov, Marla Sabaii, Jacinda B. Sampson, Timothy Schedl, Kelly Schoch, Daryl A. Scott, Elaine Seto, Prashant Sharma, Vandana Shashi, Emily Shelkowitz, Sam Sheppeard, Jimann Shin, Edwin K. Silverman, Janet S. Sinsheimer, Kathy Sisco, Kevin S. Smith, Lilianna Solnica-Krezel, Ben Solomon, Rebecca C. Spillmann, Andrew Stergachis, Joan M. Stoler, Kathleen Sullivan, Shirley Sutton, David A. Sweetser, Virginia Sybert, Holly K. Tabor, Queenie K.-G. Tan, Amelia L.M. Tan, Arjun Tarakad, Herman Taylor, Mustafa Tekin, Willa Thorson, Cynthia J. Tifft, Camilo Toro, Alyssa A. Tran, Rachel A. Ungar, Tiina K. Urv, Adeline Vanderver, Matt Velinder, Dave Viskochil, Tiphanie P. Vogel, Colleen E. Wahl, Melissa Walker, Nicole M. Walley, Jennifer Wambach, Jijun Wan, Lee-kai Wang, Michael F. Wangler, Patricia A. Ward, Daniel Wegner, Monika Weisz Hubshman, Mark Wener, Tara Wenger, Monte Westerfield, Matthew T. Wheeler, Jordan Whitlock, Lynne A. Wolfe, Kim Worley, Shinya Yamamoto, Zhe Zhang, Stephan Zuchner, Bo Liu, Olivia Majer, and Gregory M. Barton. Large-scale mutational analysis identifies unc93b1 variants that drive tlr-mediated autoimmunity in mice and humans. The Journal of Experimental Medicine, May 2024. URL: https://doi.org/10.1084/jem.20232005, doi:10.1084/jem.20232005. This article has 51 citations.
(han2024anovelunc93b1 pages 9-12): Xu Han, Ruoran Wang, Seza Ozen, Qintao Wang, Wei Dong, Yi Zeng, Ouyuan Xu, Seher Şener, Li Guo, Ying Gu, Huanming Yang, Xiaomin Yu, Panfeng Tao, and Qing Zhou. A novel unc93b1 gain-of-function mutation leads to tlr7 and tlr8 hyperactivation and systemic lupus erythematosus. MedRxiv, Sep 2024. URL: https://doi.org/10.1101/2024.09.11.24313360, doi:10.1101/2024.09.11.24313360. This article has 0 citations.
(david2024gainoffunctionhumanunc93b1 pages 22-22): Clémence David, Carlos A. Arango-Franco, Mihaly Badonyi, Julien Fouchet, Gillian I. Rice, Blaise Didry-Barca, Lucie Maisonneuve, Luis Seabra, Robin Kechiche, Cécile Masson, Aurélie Cobat, Laurent Abel, Estelle Talouarn, Vivien Béziat, Caroline Deswarte, Katie Livingstone, Carle Paul, Gulshan Malik, Alison Ross, Jane Adam, Jo Walsh, Sathish Kumar, Damien Bonnet, Christine Bodemer, Brigitte Bader-Meunier, Joseph A. Marsh, Jean-Laurent Casanova, Yanick J. Crow, Bénédicte Manoury, Marie-Louise Frémond, Jonathan Bohlen, and Alice Lepelley. Gain-of-function human unc93b1 variants cause systemic lupus erythematosus and chilblain lupus. The Journal of Experimental Medicine, Jun 2024. URL: https://doi.org/10.1084/jem.20232066, doi:10.1084/jem.20232066. This article has 69 citations.