UNC93B1

Chr 11AR

unc-93 homolog B1, TLR signaling regulator

NCBI Gene: 81622ENSG00000110057UniProt: Q9H1C4

Plays an important role in innate and adaptive immunity by regulating nucleotide-sensing Toll-like receptor (TLR) signaling. Required for the transport of a subset of TLRs (including TLR3, TLR7 and TLR9) from the endoplasmic reticulum to endolysosomes where they can engage pathogen nucleotides and activate signaling cascades. May play a role in autoreactive B-cells removal

Primary Disease Associations & Inheritance

{Encephalopathy, acute, infection-induced (herpes-specific), susceptibility to, 1}MIM #610551
AR
479
ClinVar variants
22
Pathogenic / LP
0.14
pLI score
0
Active trials
Clinical Summary— UNC93B1
🧬
Gene-Disease Validity (ClinGen)
systemic lupus erythematosus · SDModerate

Moderate evidence — consider for supplementary testing

⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.26) despite low pLI — interpret in context.
📋
ClinVar Variants
22 Pathogenic / Likely Pathogenic· 209 VUS of 479 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.51LOEUF
pLI 0.143
Z-score 3.31
OE 0.26 (0.14–0.51)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
1.86Z-score
OE missense 0.71 (0.64–0.79)
234 obs / 329.0 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.26 (0.14–0.51)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.71 (0.64–0.79)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.89
0≤1.21.6
LoF obs/exp: 6 / 23.2Missense obs/exp: 234 / 329.0Syn Z: 1.08

ClinVar Variant Classifications

479 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic13
Likely Pathogenic9
VUS209
Likely Benign226
Benign20
Conflicting2
13
Pathogenic
9
Likely Pathogenic
209
VUS
226
Likely Benign
20
Benign
2
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
5
0
8
0
13
Likely Pathogenic
4
2
3
0
9
VUS
7
180
19
3
209
Likely Benign
0
8
74
144
226
Benign
2
4
6
8
20
Conflicting
—2
Total18194110155479

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

UNC93B1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

{Encephalopathy, acute, infection-induced (herpes-specific), susceptibility to, 1}

MIM #610551

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Genetic variants in UNC93B1 predispose to childhood-onset systemic lupus erythematosus.
Al-Azab M et al.·Nat Immunol
2024
Melkersson-Rosenthal syndrome.
Kanerva M et al.·Otolaryngol Head Neck Surg
2008
Case Report: Novel UNC93B1 variant causes rheumatoid arthritis and interstitial pneumonia.
He T et al.·Front Immunol
2025Case report
Ferroptosis-related genes participate in the microglia-induced neuroinflammation of spinal cord injury via NF-κB signaling: evidence from integrated single-cell and spatial transcriptomic analysis.
Wang S et al.·J Transl Med
2025
Human and Murine Toll-like Receptor-Driven Disease in Systemic Lupus Erythematosus.
von Hofsten S et al.·Int J Mol Sci
2024Review
Juvenile-onset Systemic Lupus Erythematosus: Recent Advances in Pathogenesis and Treatment.
Natoli V et al.·Curr Rheumatol Rep
2025Review
UNCovering new causes of monogenic systemic lupus erythematosus.
Ellyard JI et al.·Immunol Cell Biol
2024
Unc93B1 biases Toll-like receptor responses to nucleic acid in dendritic cells toward DNA- but against RNA-sensing.
Fukui R et al.·J Exp Med
2009
Nucleic acid-sensing TLRs and autoimmunity: novel insights from structural and cell biology.
Pelka K et al.·Immunol Rev
2016Review
UNC93B1 promotes tumoral growth by controlling the secretion level of granulocyte macrophage colony-stimulating factor in human oral cancer.
Wagai S et al.·Biochem Biophys Res Commun
2019
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools