UNC93B1

Chr 11AR

unc-93B1 regulator of TLR signaling

Also known as: IIAE1, UNC-93B, UNC93, UNC93B, Unc-93B1

NCBI Gene: 81622 ENSG00000110057 UniProt: Q9H1C4 OMIM: 608204

The protein traffics nucleotide-sensing toll-like receptors from the endoplasmic reticulum to endolysosomes, enabling innate and adaptive immune responses to pathogens. Autosomal recessive mutations cause susceptibility to herpes simplex encephalitis, resulting in acute infection-induced encephalopathy primarily affecting the central nervous system. The gene shows moderate constraint against loss-of-function variants (LOEUF 0.51), consistent with its critical role in antiviral immunity.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a protein that is involved in innate and adaptive immune response by regulating toll-like receptor signaling. The encoded protein traffics nucleotide sensing toll-like receptors to the endolysosome from the endoplasmic reticulum. Deficiency of the encoded protein has been associated with herpes simplex encephalitis. [provided by RefSeq, Feb 2014]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

{Encephalopathy, acute, infection-induced (herpes-specific), susceptibility to, 1}MIM #610551

Clinical highlights

Gene–disease validity (ClinGen)

Moderate · systemic lupus erythematosus · SD · ClinGen 2025

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.51

LOEUF

Multiple*

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

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?

1.86Z-score

OE missense 0.71 (0.64–0.79)

234 obs / 329.0 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.26 (0.14–0.51)

0≤0.351.4

Missense OE?0.71 (0.64–0.79)

0≤0.61.4

Synonymous OE?0.89

0≤1.21.6

LoF obs/exp: 6 / 23.2Missense obs/exp: 234 / 329.0Syn Z: 1.08

Background carrier burden — how many people carry a rare variant somewhere in UNC93B1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 76

733 rare PASS variants

Rare truncating (LoF)

1 in 1,900

79 rare PASS variants

Rare synonymous (reference)

1 in 120

363 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for UNC93B1. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 99	1 in 2,000
South Asian	~43k	1 in 82	1 in 1,400
Remaining (unassigned)	~30k	1 in 57	1 in 3,200
European (Finnish)	~27k	1 in 210	≈ 1 in 6,600
Admixed American	~22k	1 in 55	≈ 1 in 5,200
African / African American	~21k	1 in 79	1 in 2,400
East Asian	~20k	1 in 140	1 in 1,600
Ashkenazi Jewish	~13k	1 in 310	≈ 1 in 6,400
Middle Eastern	~2,884	1 in 120	≈ 1 in 2,600

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 9 of 11 coding exons well covered in gnomAD exomes; exon 10 poorly covered; exon 1 marginal. Genomes: 10 of 11 (exon 9 below).? see exons ↓