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COVID-19 research

Gene: POLR3C

Green List (high evidence)

POLR3C (RNA polymerase III subunit C)
EnsemblGeneIds (GRCh38): ENSG00000186141
EnsemblGeneIds (GRCh37): ENSG00000186141
OMIM: 617454, Gene2Phenotype
POLR3C is in 2 panels

4 reviews

Sophie Hambleton (Newcastle University)

Green List (high evidence)

May contribute to viral susceptibility in a non-Mendelian way
Created: 1 May 2020, 12:17 p.m. | Last Modified: 1 May 2020, 12:17 p.m.
Panel Version: 0.171

Ivone Leong (Genomics England Curator)

Green List (high evidence)

IUIS: categorised under the Predisposition to severe viral infection section. Inheritance: AD. Affects Leukocytes and other cells and causes impaired viral recognition and IFN induction in response to VZVor poly I:C. The associated features is severe VZV infection.
Created: 15 Apr 2020, 12:09 p.m. | Last Modified: 15 Apr 2020, 12:09 p.m.
Panel Version: 0.103

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Phenotypes
Defects in intrinsic and innate immunity; Predisposition to severe viral infection; RNA polymerase III deficiency

Publications

Abdelazeem Elhabyan (Arizona State University)

Red List (low evidence)

This gene is responsible for A subunit of Polymerase which senses DNA viruses especially AT-rich regions eg Varicella Zoster. SARS-CoV-2 is an RNA virus.


Inborn errors in RNA polymerase III underlie severe varicella zoster virus infections(PMID: 28783042)

We report 4 cases of acute severe VZV infection affecting the central nervous system or the lungs in unrelated, otherwise healthy children who are heterozygous for rare missense mutations in POLR3A (one patient), POLR3C (one patient), or both (two patients). POLR3A and POLR3C encode subunits of RNA polymerase III. Leukocytes from all 4 patients tested exhibited poor IFN induction in response to synthetic or VZV-derived DNA. Moreover, leukocytes from 3 of the patients displayed defective IFN production upon VZV infection and reduced control of VZV replication. These phenotypes were rescued by transduction with relevant WT alleles. This work demonstrates that monogenic or digenic POLR3A and POLR3C deficiencies confer increased susceptibility to severe VZV disease in otherwise healthy children, providing evidence for an essential role of a DNA sensor in human immunity
Different classes of PRRs are involved in recognition of virus infections, including membrane-associated TLRs; cytosolic retinoic acid–inducible gene 1–like (RIG-I–like) receptors, which sense RNA; and DNA sensors (24). Each of these classes of PRRs stimulates production of IFNs, which exhibit antiviral activity through their ability to induce IFN-stimulated genes (ISGs). With respect to DNA sensors, TLR9 detects unmethylated DNA, RNA polymerase III (POL III) recognizes AT-rich DNA, while gamma-interferon-inducible protein 16 (IFI16) and cyclic GMP-AMP synthase (cGAS) sense double-stranded DNA in a sequence-independent manner (25–29).
Created: 10 Apr 2020, 12:34 p.m. | Last Modified: 10 Apr 2020, 12:34 p.m.
Panel Version: 0.81

Publications

Rebecca Foulger (Genomics England curator)

Added POLR3C to panel based on presence on VCGS 'Susceptibility to Viral Infections' panel V0.22: https://panelapp.agha.umccr.org/panels/237/
Created: 9 Apr 2020, 4:16 p.m. | Last Modified: 9 Apr 2020, 4:18 p.m.
Panel Version: 0.76

Details

Mode of Inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • IUIS Classification December 2019
  • Expert Review Green
Phenotypes
  • RNA polymerase III deficiency
  • Severe VZV infection
  • Predisposition to severe viral infection
  • Defects in intrinsic and innate immunity
OMIM
617454
Clinvar variants
Variants in POLR3C
Penetrance
None
Publications
Panels with this gene

History Filter Activity

15 Apr 2020, Gel status: 3

Set publications

Ivone Leong (Genomics England Curator)

Publications for gene: POLR3C were set to 28783042

15 Apr 2020, Gel status: 3

Added New Source, Added New Source, Set Phenotypes, Status Update

Ivone Leong (Genomics England Curator)

Source Expert Review Green was added to POLR3C. Source IUIS Classification December 2019 was added to POLR3C. Added phenotypes RNA polymerase III deficiency; Defects in intrinsic and innate immunity; Predisposition to severe viral infection for gene: POLR3C Rating Changed from Amber List (moderate evidence) to Green List (high evidence)

9 Apr 2020, Gel status: 2

Created, Added New Source, Set mode of inheritance, Set publications, Set Phenotypes

Rebecca Foulger (Genomics England curator)

gene: POLR3C was added gene: POLR3C was added to Viral susceptibility. Sources: Victorian Clinical Genetics Services,Expert list,Expert Review Amber Mode of inheritance for gene: POLR3C was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: POLR3C were set to 28783042 Phenotypes for gene: POLR3C were set to Severe VZV infection