UNC93B1

unc-93 homolog B1, TLR signaling regulator

Basic information

Region (hg38): 11:67991100-68004982

Links

ENSG00000110057 ∙ NCBI:81622 ∙ OMIM:608204 ∙ HGNC:13481 ∙ Uniprot:Q9H1C4 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• herpes simplex encephalitis, susceptibility to, 1 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Encephalopathy, acute, infection-induced (herpes-specific), susceptibility to, 1	AR	Allergy/Immunology/Infectious	Individuals may be susceptible to severe HSV infections, which can result in lethal sequlae or severe chronic impairment, and recognition may allow preventive measures as well as prompt treatment with anti-HSV medications (eg, acyclovir), which may improve outcome	Allergy/Immunology/Infectious	16973841

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the UNC93B1 gene.

• Herpes_simplex_encephalitis,_susceptibility_to,_1 (387 variants)
• not_specified (52 variants)
• not_provided (31 variants)
• UNC93B1-related_disorder (4 variants)
• Type_1_interferonopathy (1 variants)
• Immunodeficiency (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the UNC93B1 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000030930.4. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			2	126	6	134
missense		3	176	8	4	191
nonsense	2					2
start loss			1			1
frameshift	5	1	5		2	13
splice donor/acceptor (+/-2bp)		3	1			4
Total	7	7	185	134	12

Highest pathogenic variant AF is 0.00004963323

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
UNC93B1	protein_coding	protein_coding	ENST00000227471	12	13878

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.143	0.857	3071	121565	0	124636	0.843

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.86	234	329	0.711	0.0000205	3740
Missense in Polyphen		60	130.99	0.45803		1534
Synonymous	1.08	134	151	0.889	0.0000105	1203
Loss of Function	3.31	6	23.2	0.258	9.93e-7	294

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	2.00	1.93
Ashkenazi Jewish	1.00	0.944
East Asian	1.00	0.970
Finnish	1.00	0.500
European (Non-Finnish)	1.00	0.930
Middle Eastern	1.00	0.970
South Asian	1.00	0.992
Other	1.00	0.904

dbNSFP

Source: dbNSFP

• Function: FUNCTION: 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. {ECO:0000269|PubMed:19006693}.
• Disease: DISEASE: Encephalopathy, acute, infection-induced, Herpes- specific, 1 (IIAE1) [MIM:610551]: A rare complication of human herpesvirus 1 (HHV-1) infection, occurring in only a small minority of HHV-1 infected individuals. It is characterized by hemorrhagic necrosis of parts of the temporal and frontal lobes. Onset is over several days and involves fever, headache, seizures, stupor, and often coma, frequently with a fatal outcome. {ECO:0000269|PubMed:16973841}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry. Mutations in UNC93B1 resulting in autosomal recessive UNC93B1 deficieny predispose otherwise healthy individuals to isolated herpes simplex encephalitis due to impaired IFNs production. UNC93B1 deficieny, however, does not compromise immunity to most pathogens, unlike most known primary immunodeficiencies.
• Pathway: miR-targeted genes in epithelium - TarBase;miR-targeted genes in leukocytes - TarBase;miR-targeted genes in lymphocytes - TarBase;Trafficking and processing of endosomal TLR;Toll-Like Receptors Cascades;Innate Immune System;Immune System (Consensus)

Recessive Scores

• pRec: 0.176

Haploinsufficiency Scores

• hipred: Y
• hipred_score: 0.519
• ghis: 0.482

Essentials

• essential_gene_CRISPR2: S
• gene_indispensability_pred: N
• gene_indispensability_score: 0.283

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Unc93b1
• Phenotype: mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); hematopoietic system phenotype; liver/biliary system phenotype; skeleton phenotype; renal/urinary system phenotype; immune system phenotype; homeostasis/metabolism phenotype

Gene ontology

• Biological process: toll-like receptor signaling pathway;adaptive immune response;intracellular protein transport;toll-like receptor 3 signaling pathway;toll-like receptor 7 signaling pathway;toll-like receptor 9 signaling pathway;innate immune response;defense response to virus
• Cellular component: Golgi membrane;lysosome;endosome;endoplasmic reticulum;endoplasmic reticulum membrane;integral component of membrane;early phagosome
• Molecular function: protein transporter activity;Toll-like receptor binding