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COVID-19 research

Gene: KIR2DL2

Red List (low evidence)

KIR2DL2 (killer cell immunoglobulin-like receptor, two domains, long cytoplasmic tail, 2)
EnsemblGeneIds (GRCh37): ENSG00000215764
OMIM: 604937, Gene2Phenotype
KIR2DL2 is in 1 panel

3 reviews

Eleanor Williams (Genomics England Curator)

Ensembl identifier not available for GRCh38 (release 90). On GRCh it is on a patch chromosome so chromosome location not added.
Created: 8 Jul 2020, 3 p.m. | Last Modified: 8 Jul 2020, 3 p.m.
Panel Version: 1.59

Rebecca Foulger (Genomics England curator)

Comment on list classification: Kept rating as Red as not currently reportable- KIR2DL2 is on a non-standard (patch) chromosome.
Created: 4 Jun 2020, 12:42 p.m. | Last Modified: 4 Jun 2020, 12:42 p.m.
Panel Version: 1.6
Evidence summary from Illumina Curation Team: KIR2DL2 is a member of the KIR (killer cell immunoglobulin-like receptor) family of transmembrane proteins. KIRs, which are expressed on natural killer cells and some T cells, bind to HLA class I molecules and can influence both innate and adaptive immunity. KIR2DL2 has been shown to modulate HLA class I-restricted anti-viral immunity against hepatitis C virus and human T lymphotropic virus type 1 (Seich Al Basatena et al. 2011) and has been linked to HIV infection risk in Africans and Caucasians (Zhao et al. 2019). KIR2DL2/L3 ligand-positive pairs were also enriched among ICU patients compared to 105 H1N1-negative subjects from Canada (La et al. 2011). KIR2DL2 positive ICU patients showed lower death rates compared to KIR2DL3+/KIR2DL2- patients, further suggesting that KIR2DL2 may modulate disease severity.

PMID 22022261: Seich Al Basatena et al. (2011) - Killer cell immunoglobulin-like receptors (KIRs) are a family of transmembrane proteins that are expressed on natural killer (NK) cells and subsets of T cells. They bind HLA class I molecules and have activatory and inhibitory isoforms. KIRs influence both innate and adaptive immunity. The authors investigate whether KIR genotype (present or absent) modulates HLA-mediated anti-viral protection in vivo by focussing on HLA class I alleles that have previously been associated with disease outcome and investigated whether these effects were altered by KIR background. Four well-documented HLA class I allele-disease associations in two viral infections were studied: HLA-C*08, A*02 and B*54 in human T lymphotropic virus type 1 (HTLV-1) infection and B*57 in hepatitis C virus (HCV). KIR2DL2 enhanced the protective effect of C*08 and the detrimental effect of B*54 on HAM/TSP risk and, independently, on proviral load (Table 1). Possession of the KIR2DL2 gene also enhanced the protective effect of HBZ binding (Fig. 2), HLA class I-mediated antiviral immunity (Table 2), and the protective effect of B*57 on HCV viral load (Fig. 3). This work helps to explain why one individual infected with a virus remains healthy but another infected with the same virus develops disease.

PMID 22216211: La et al. (2011) - Investigated KIR3DL1/S1 allotype and KIR2DL2/L3 frequencies in H1N1/09 ICU patients. Also looked at frequencies in world aboriginal populations. Found that 2DL2/L3 ligand-positive pairs were enriched among ICU patients compared to 105 H1N1-negative subjects from St. Theresa Point, Manitoba. Differences in death rates were found between 2DL2+ (Rd =21%) and 2DL3+2DL2- patients (Rd= 46%) (Table 4) but there were no significant differences in disease severity between 2DL2+ (Rd=38%) and 2DL3+2DL2- (Rd=42%) patients.
PMID 31288555: Zhao et al. (2019) - Meta-analysis of the roles of KIR in HIV-1 control/susceptibility: quantitative assessment based on 25 studies [involving 3,216 HIV-1 infected subjects, 1,690 exposed uninfected subjects, 1,262 healthy controls (HCs), 748 typical progressors (TPs), and 244 long-term nonprogressors (LTNPs)] to further define the roles of the presence of 16 KIR genes (2DL1, 2DL2, 2DL3, 2DL4, 2DL5, 2DS1, 2DS2, 2DS3, 2DS4, 2DS5, 2DP1, 3DL1, 3DL2, 3DL3, 3DS1, and 3DP1), in HIV-1 control/susceptibility. Among Africans, KIR2DL2 conferred a protective role (OR = 0.664, 95% CI = 0.466–0.891, p = .008, HIV+ vs healthy controls)) (supplementary Table S1). KIR2DL2 also showed an increased risk of acquiring infection among Caucasians (OR = 1.512, 95% CI = 1.008–2.269, p = .046, HIV+ vs healthy controls) (text).
Also summarizes previous results: Under more than 5 years of follow-up, Naranbhai et al. in 2016 also reported that carriage of the KIR2DL2 was associated with lower HIV viremia and higher counts of CD4+ T cell in HIV-infected South African women. A harmful role of KIR2DL2 was observed in HIV-1-infected Polish females with exposure to HIV by Zwolinska et al. The KIR haplotype B carriers involving KIR2DL2 showed lower counts of CD4+ T cell in HIV-infected African female sex workers.
Created: 4 Jun 2020, 10:24 a.m. | Last Modified: 4 Jun 2020, 10:24 a.m.
Panel Version: 1.5

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

Green List (high evidence)

Publications

Mode of pathogenicity
Other - please provide details in the comments

Details

Mode of Inheritance
Unknown
Sources
  • Literature
Tags
currently-ngs-unreportable ensembl_ids_known_missing
OMIM
604937
Clinvar variants
Variants in KIR2DL2
Penetrance
None
Panels with this gene

History Filter Activity

4 Jun 2020, Gel status: 1

Entity classified by Genomics England curator

Rebecca Foulger (Genomics England curator)

Gene: kir2dl2 has been classified as Red List (Low Evidence).

3 Jun 2020, Gel status: 1

Added Tag, Added Tag

Eleanor Williams (Genomics England Curator)

Tag currently-ngs-unreportable tag was added to gene: KIR2DL2. Tag ensembl_ids_known_missing tag was added to gene: KIR2DL2.

3 Jun 2020, Gel status: 1

Created, Added New Source, Set mode of inheritance

Eleanor Williams (Genomics England Curator)

gene: KIR2DL2 was added gene: KIR2DL2 was added to COVID-19 research. Sources: Literature Mode of inheritance for gene: KIR2DL2 was set to Unknown