COVID-19 research

Gene: NUP214

Red List (low evidence)

Mode of inheritance
Unknown

Publications

• 31178128

Red List (low evidence)

NUP214 was identified through an OMIM search for potential viral susceptibility genes. Initial triage by Illumina (Alison Coffey and team) was given a Tier 1 grouping (clear GDA/viral susceptibility). Illumina review: PMID 31178128: Fichtman et al. (2019) reported four patients from two unrelated families with fever-induced, partially reversible acute encephalopathy and regression, progressive microcephaly, and brain atrophy. Febrile episodes were associated with viral infections. Exome sequencing identified that both affected individuals from family A were homozygous for the NUP214 NM_005085.3; c.112C>T (p.Arg38Cys) missense variant. A frameshift variant, c.1574delC (p.Pro525LeufsTer6) and a missense variant c.1159C>T (p.Pro387Ser), found in a compound heterozygous state were identified in the NUP214 gene in the two affected individuals from family B. The missense variants affected highly conserved residues and were present at a low frequency in gnomAD. Functional studies on primary skin fibroblasts derived from one case (family A1) supported pathogenicity of the p.Arg38Cys variant; NUP214 and NUP88 protein levels were reduced in while the total number and density of nuclear pore complexes remained normal. Nuclear transport assays revealed defects in the classical protein import and mRNA export pathways in affected cells.

Created: 11 Jun 2020, 6:10 p.m. | Last Modified: 12 Jun 2020, 11:06 a.m.

Panel Version: 1.37

Viral involvement was found in 3/4 cases of susceptibility to acute infection-induced Encephalopathy 9 (OMIM 618426), caused by biallieic variants in NUP214 (PMID 31178128).

Created: 4 May 2020, 3:17 p.m. | Last Modified: 4 May 2020, 3:17 p.m.

Panel Version: 0.176

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
{Encephalopathy, acute, infection-induced, susceptibility to, 9} 618426

Publications

• 31178128