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COVID-19 research

Gene: NECTIN1

Amber List (moderate evidence)

NECTIN1 (nectin cell adhesion molecule 1)
EnsemblGeneIds (GRCh38): ENSG00000110400
EnsemblGeneIds (GRCh37): ENSG00000110400
OMIM: 600644, Gene2Phenotype
NECTIN1 is in 7 panels

2 reviews

Alison Coffey (Illumina Clinical Services Laboratory, Illumina Inc.)

I don't know

Publications

Rebecca Foulger (Genomics England curator)

Evidence Summary from Illumina curation team (Alison Coffey and Julie Taylor): Amino acid substitutions in nectin-1 showed impaired entry of Herpes simplex virus (HSV) into CHO-K1 cells (PMID:1175687;12072525). Nectin-1 knockout mice inoculated with HSV in the hippocampus demonstrated that nectin-1 is necessary for neurologic disease caused by HSV (PMID:19805039).

PMID 11756979 - Struyf et al. (2002) - Searched for polymorphisms in HVEM, nectin-1, and nectin-2 via sequencing in individuals shown to immune seronegative for herpes simplex virus (HSV). These individuals showed T cell responses to HSV antigens and did not have anti-HSV antibodies detected in their serum. There were three individuals that were immune seronegative, three with no signs of cellular or humoral immunity, and three with frequent reactivations of HSV who had antibody and T cell responses to HSV. One individual in the study (true seronegative as demonstrated by negative testing for HSV-1 and HSV-2 and no HSV-specific T cell immunity) was identified to have a variant in nectin-1 (c.752G>A, p.Arg199Gln) in addition to one missense variant in HVEM (table 2). This variant was screened for 644 healthy White individuals and 17 were shown to be heterozygous for the p.Arg199Gln variant and one individual had a different missense variant at the same residue. The p.Arg199Gln variant occurs in the first constant-like domain for the protein. A different domain, the N-terminal variable-like domain, has previously been shown as important for virus entry into the cell.

PMID 12072525 - Martinez and Spear (2002) - Investigated whether residues 75-77 and 85 of nectin-1 (homologous to regions A and B of nectin-2) are necessary for HSV-1 entry into CHO-K1 cells (which are resistant to the entry of alphaherpesviruses unless they are created to express a gD receptor). When there were mutants involving both residues 77 and 85, there was severely diminished ability of HSV-1 or HSV-2 to enter the cell and was unable to find to soluble forms of HSV-1 and HSV-2 (table 1; fig. 3). Note that these mutants allowed entry of PRV and BHV-1.

PMID 19805039 - Kopp et al. (2009) - Nectin-1 knockout (KO) mice were inoculated intracranially and into the hippocampus with herpes simplex virus (HSV) and infection of neurons compared to HVEM KO mice, HVEM/nectin-1 KO mice, and controls. Nectin-1 KO mice were resistant to disease, as were the double KO mice at doses of the virus up to 100x needed to cause disease as compared to the wildtype and HVEM KO mice (Fig. 1). Nectin-1 is necessary for neurologic disease caused by HSV. Viral antigen was not detected in brain sections from double KO mice, but could be detected for nectin-1 KO mice (limited regions), HVEM-KO mice and wildtype (more widespread) (Fig. 2A). HSV was shown to be located to the ventricular surfaces in nectin-1 KO mice and confirmed as non-parenchymal cells (Fig. 2B).
Created: 28 May 2020, 3:23 p.m. | Last Modified: 28 May 2020, 3:23 p.m.
Panel Version: 0.348
Identified through an OMIM search for potential viral susceptibility genes, and subsequently triaged/reviewed by Illumina curation team.
Created: 28 May 2020, 12:36 p.m. | Last Modified: 28 May 2020, 12:36 p.m.
Panel Version: 0.336

History Filter Activity

28 May 2020, Gel status: 2

Created, Added New Source, Set mode of inheritance

Rebecca Foulger (Genomics England curator)

gene: NECTIN1 was added gene: NECTIN1 was added to COVID-19 research. Sources: Expert list,OMIM,Expert Review Amber Mode of inheritance for gene: NECTIN1 was set to Unknown