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COVID-19 research

Gene: UNC93B1

Green List (high evidence)

UNC93B1 (unc-93 homolog B1, TLR signaling regulator)
EnsemblGeneIds (GRCh38): ENSG00000110057
EnsemblGeneIds (GRCh37): ENSG00000110057
OMIM: 608204, Gene2Phenotype
UNC93B1 is in 4 panels

7 reviews

Abdelazeem Elhabyan (Arizona State University)

Green List (high evidence)

Autosomal recessive , Loss of function , 3 unrelated patients. 2 of them reported in 2006 and 1 in 2015

UNC-93B deficiency was implicated in Herpes simplex encephalitis(HSE) - a rare complication of herpes simplex virus(HSV) infection- and this is supported by many studies of related patients from unrelated families with HSE. In two unrelated patients in two unrelated families whose parents are first cousins, it has been demonstrated that their peripheral blood mononuclear cells lack the ability to produce IFN alpha and beta in response to HSV and ten other viruses. Those patients also showed decreased response to stimulation of TLR7, 8, and 9 which are important in intracellular detection of viruses. On the contrary, TLR4 (cell surface receptor for viral detection) and INF gamma response were not affected9. The fact that the loss of function mutation of the gene is involved in IFN response to many viruses indicates possible involvement in SARS-CoV-2 host immune response. The deficient response described above is similar to a mouse model described by Tabeta et al(10). Patients’ relatives and parents carried heterozygous mutations of the same gene but never developed HSE as a complication of HSV infection, nor their cells lacked IFN response indicating that the mode of inheritance is autosomal recessive (9). This study proves also therapeutic indications for some patients indicated by the proven efficacy of recombinant IFN alpha in the treatment of infected mice models(11)Another patient was reported to be homozygous for SNP at exon 4 of the gene which affected the expression of UNC93B1 which increased susceptibility to HSE and had a harmful effect on the long term prognosis(12)


9.Casrouge A, Zhang SY, Eidenschenk C, et al. Herpes simplex virus encephalitis in human UNC-93B deficiency. Science. 2006;314(5797):308–312. doi:10.1126/science.1128346

10.Tabeta K, Hoebe K, Janssen EM, et al. The Unc93b1 mutation 3d disrupts exogenous antigen presentation and signaling via Toll-like receptors 3, 7 and 9. Nat Immunol. 2006;7(2):156–164. doi:10.1038/ni1297

11.Wintergerst U, Gangemi JD, Whitley RJ, Chatterjee S, Kern ER. Effect of recombinant human interferon alpha B/D (rHu-IFN-alpha B/D) in combination with acyclovir in experimental HSV-1 encephalitis. Antiviral Res. 1999;44(1):75–78. doi:10.1016/s0166-3542(99)00055-8

12.Feng W, Chen T, Hu B, Wan J, Liu G. Zhonghua Er Ke Za Zhi. 2015;53(9):701–706.
Created: 24 Apr 2020, 12:52 a.m. | Last Modified: 24 Apr 2020, 12:52 a.m.
Panel Version: 0.160

Mode of inheritance
Other

Kimberly Gilmour (Great Ormond Street Hopsital)

Green List (high evidence)

agree with green gene
Created: 17 Sep 2019, 3:18 p.m. | Last Modified: 17 Sep 2019, 3:18 p.m.
Panel Version: 1.94

Tracy Briggs (Manchester Genomic Medicine Centre)

Green List (high evidence)

YES- this is covered on our targeted exome
Created: 17 Sep 2019, 3:18 p.m. | Last Modified: 17 Sep 2019, 3:18 p.m.
Panel Version: 1.94

Sophie Hambleton (Newcastle University)

Green List (high evidence)

Eleanor Williams (Genomics England Curator)

Comment on list classification: 3 unrelated cases with plausible disease causing mutations.
Created: 21 Jun 2018, 2:44 p.m.
Comment on phenotypes: Added OMIM phenotype
Created: 21 Jun 2018, 2:34 p.m.
Comment on publications: Added relevant publications
Created: 21 Jun 2018, 2:21 p.m.
In OMIM UNC93B1 is associated with {Encephalopathy, acute, infection-induced (herpes-specific), susceptibility to, 1}. OMIM evidence comes from Casrouge et al. (2006) (PMID: 16973841) who reports 2 individuals with herpes simplex encephalitis (HSE) caused by deficiency of UNC93B1. Both patients were the products of consanguineous unions. One patient was homozygous for a frameshift mutation resulting in barely detectable UNC93B1 RNA. The other was homozygous for a splice site mutation at the end of exon 6 resulting in skipping of exon 6 of UNC93B1. Neither of these variants were identified in 100 healthy European controls. Feng et al 2015 (PMID: 26757972) report a Chinese patient homozygous for a single-nucleotide substitution at position C.414C>G in exon 4 of UNC93B1 which affected the expression of UNC93B1. PubMed, Clinvar and JensenLab Disease (https://diseases.jensenlab.org/) searches have not found published studies of further cases. No pathogenic variants reported in ClinVar. A mouse model with a missense allele of Unc93b1 exists (Tabeta et al. (2006)(PMID: 16415873) and functional studies show the role of UNC93B1 in regulating Toll-like receptors that play a key role in the innate immune system e.g. Pelka et al. 2018 (PMID: 29768176).
Created: 21 Jun 2018, 2:19 p.m.

Louise Daugherty (Genomics England Curator)

Green List (high evidence)

Gene rating submitted by Kimberly Gilmour and Austen Worth on behalf of London North GLH for the GMS Immunology specialist test group. As discussed with the GMS Immunology Specialist Test Group during webex call 28th March 2019 and confirmed in follow up email 6th September the Specialist Test Group all agreed there is enough evidence to rate this gene Green.
Created: 17 Sep 2019, 3:18 p.m. | Last Modified: 17 Sep 2019, 3:18 p.m.
Panel Version: 1.94
Gene rating submitted by Tracy Briggs, David Gokhale and Abigal Rousseau on behalf of North West GLH for the GMS Immunology specialist test group. As discussed with the GMS Immunology Specialist Test Group during webex call 28th March 2019 and confirmed in follow up email on 20th June the Specialist Test Group all agreed there is enough evidence to rate this gene Green.
Created: 17 Sep 2019, 3:18 p.m. | Last Modified: 17 Sep 2019, 3:18 p.m.
Panel Version: 1.94
OriginaI Metadata from IUIS classification table (February, 2018) downloaded 20180614. IUIS Genetic defect (original gene symbol in IUIS download): UNC93B1 .PanelApp HGNC gene symbol check: UNC93B1 . IUIS Disease: UNC93B1 deficiency . IUIS Inheritance: AR , .B cells: N/A, .IUIS Other affected cells: CNS resident cells and fibroblasts. IUIS Associated features: Herpes simplex virus 1 encephalitis. IUIS Major category: Defects in Intrinsic and Innate Immunity. IUIS Subcategory: Herpes Simplex Encephalitis (HSE)
Created: 2 Jul 2018, 10:35 a.m.
This gene was absent from the original PanelApp PID panel dataset (review April 2018). However it was listed in external expert immunodeficiency diagnostic gene list(s)
GOSH or GRID. In this combined PID panel, this gene has been rated as AMBER and needs further curational review to assess pertinence prior to v1.
Created: 19 Apr 2018, 10:49 a.m.
Original metadata downloaded from ESID Registry. ESID_Gene_original: UNC93, PanelApp HGNC gene symbol check: UNC93B1, ESID classification: Main_category/ Sub_category/ PID_Diagnosis Defects in innate immunity / Herpetic encephalitis / Herpetic encephalitis (HSE)
Created: 17 Apr 2018, 12:29 p.m.
Original metadata supplied by GRID. GRID Gene Symbol HGNC PanelApp check: UNC93B1, GRID_Gene_Symbol: UNC93B1, GRID_Transcript_ENS_Community submitted: ENST00000227471, GRID_Transcript_RefSeq: NM_030930.2, GRID_Transcript_ENS_used_on_Production: ENST00000227471
Created: 17 Apr 2018, 12:12 p.m.

Ellen McDonagh (Genomics England Curator)

Mode of inheritance
Unknown

Phenotypes
Herpes simplex encephalitis

Publications

Details

Mode of Inheritance
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Literature
Phenotypes
  • Herpetic encephalitis (HSE)
  • Herpes simplex virus 1 encephalitis
  • Herpes simplex encephalitis, susceptibility to, 1
  • {Encephalopathy, acute, infection-induced (herpes-specific), susceptibility to, 1} 610551
  • Herpes simplex encephalitis
  • Defects in Intrinsic and Innate Immunity
OMIM
608204
Clinvar variants
Variants in UNC93B1
Penetrance
Complete
Publications
Panels with this gene

History Filter Activity

1 Apr 2020, Gel status: 3

Set mode of inheritance, Set Phenotypes, Set publications

Ellen McDonagh (Genomics England Curator)

Mode of inheritance for gene UNC93B1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal Added phenotypes Herpetic encephalitis (HSE); Herpes simplex virus 1 encephalitis; Herpes simplex encephalitis, susceptibility to, 1; {Encephalopathy, acute, infection-induced (herpes-specific), susceptibility to, 1} 610551; Defects in Intrinsic and Innate Immunity for gene: UNC93B1 Publications for gene UNC93B1 were updated from 26621750 to 16973841; 16415873; 29768176; 26621750

31 Mar 2020, Gel status: 3

Added New Source, Added New Source, Added New Source, Status Update

Ellen McDonagh (Genomics England Curator)

Source Melbourne Genomics Health Alliance Immunology Flagship was added to UNC93B1. Source Victorian Clinical Genetics Services was added to UNC93B1. Source Expert Review Green was added to UNC93B1. Rating Changed from Red List (low evidence) to Green List (high evidence)

14 Mar 2017, Gel status: 0

Created

Ellen McDonagh (Genomics England Curator)

UNC93B1 was created by ellenmcdonagh

14 Mar 2017, Gel status: 0

Added New Source

Ellen McDonagh (Genomics England Curator)

UNC93B1 was added to Monogenic viral susceptibilitypanel. Sources: Literature