Table 1.
Descriptions of selected host genes and their functions relevant to COVID-19 susceptibility and severity.
| Gene | Location | Function | Discovery | Reference(s) |
|---|---|---|---|---|
| CCR2 | 3p21.31 | The C-C Motif Chemokine Receptor 2 gene encodes the receptor for monocyte chemoattractant protein-1, a chemokine which mediates monocyte chemotaxis. CCR2-associated diseases include human immunodeficiency virus type 1 and idiopathic anterior uveitis. | GWAS/TWAS (differential predicted expression in lung tissue) | Pairo-Castineira et al. https://doi.org/10.1101/2020.09.24.20200048 |
| CCR3 | 3p21.31 | The C-C Motif Chemokine Receptor 3 gene encodes a receptor for C-C type chemokines. It belongs to family 1 of the G protein-coupled receptors. This receptor may contribute to the accumulation and activation of eosinophils and other inflammatory cells in the allergic airway. CCR3-associated diseases include aids dementia complex and folliculotropic mycosis fungoides. | GWAS/TWAS (differential predicted expression in lung tissue) | Pairo-Castineira et al. https://doi.org/10.1101/2020.09.24.20200048 |
| CCR9 | 3p21.31 | The C-C Motif Chemokine Receptor 9 gene encodes a member of the beta chemokine receptor family. Chemokines and their receptors are key regulators of the thymocytes migration and maturation in normal and inflammation conditions. CCR9-associated diseases include ileitis and celiac disease 1. | GWAS | PubMed ID: 32558485 |
| CXCR6 | 3p21.31 | The C-X-C Motif Chemokine Receptor 6 gene encodes a protein with G protein-coupled receptor activity and C-X-C chemokine receptor activity functioning in GPCR signaling and CCR5 pathway in macrophages. CXCR6-associated diseases include sarcoidosis 1 and immune deficiency disease. | GWAS/TWAS (differential predicted expression in lung tissue) | PubMed ID: 32558485; Pairo-Castineira et al. https://doi.org/10.1101/2020.09.24.20200048 |
| FYCO1 | 3p21.31 | The FYVE And Coiled-Coil Domain Autophagy Adaptor 1 gene encodes a protein with a role in microtubule plus end-directed transport of autophagic vesicles through interactions with the small GTPase Rab7, phosphatidylinositol-3-phosphate (PI3P) and the autophagosome marker LC3. FYCO1-associated diseases include autosomal recessive congenital cataract-2. | GWAS | PubMed ID: 32558485; Pairo-Castineira et al. https://doi.org/10.1101/2020.09.24.20200048 |
| LZTFL1 | 3p21.31 | The Leucine Zipper Transcription Factor Like 1 gene encodes an ubiquitously expressed protein localized in the cytoplasm. LZTFL1 regulates protein trafficking to the ciliary membrane via interactions with Bardet-Biedl Syndrome (BBS) proteins. It may also function as a tumor suppressor by interacting with E-cadherin and the actin cytoskeleton to regulate the transition of epithelial cells to mesenchymal cells. LZTFL-associated diseases include Bardet-Biedl Syndrome 17 and Bardet-Biedl Syndrome 1. | GWAS | PubMed ID: 32558485; Pairo-Castineira et al. https://doi.org/10.1101/2020.09.24.20200048 |
| SLC6A20 | 3p21.31 | The Solute Carrier Family 6 Member 20 gene encodes a membrane transporter with unidentified substrates within the Na+ and Cl- coupled transporter family. It is expressed in the kidneys. SLC6A20-associated diseases include iminoglycinuria and hyperglycinuria. | GWAS | PubMed ID: 32558485; Pairo-Castineira et al. https://doi.org/10.1101/2020.09.24.20200048 |
| XCR1 | 3p21.31 | The X-C Motif Chemokine Receptor 1 gene encodes a chemokine receptor belonging to the G protein-coupled receptor superfamily. It transduces a signal by increasing the intracellular calcium ions level. The viral macrophage inflammatory protein-II is an antagonist of this receptor. XCR-associated diseases include Leber plus disease. | GWAS | PubMed ID: 32558485 |
| NOTCH4 | 6p21.32 | The Notch receptor 4 gene encodes a member of the NOTCH family of proteins. Notch signaling is an evolutionarily conserved intercellular signaling pathway that regulates interactions between physically adjacent cells. This receptor may play a role in vascular, renal and hepatic development. NOTCH4-associated diseases include arteriovenous malformation and schizoaffective disorder. | GWAS | Pairo-Castineira et al. https://doi.org/10.1101/2020.09.24.20200048 |
| CCHCR1 | 6p21.33 | The Coiled-Coil Alpha-Helical Rod Protein 1 gene encodes a protein with five coiled-coil alpha-helical rod domains acting as a regulator of mRNA metabolism through its interaction with mRNA-decapping protein 4. CCHCR1-associated diseases include autoimmune psoriasis. | GWAS | Pairo-Castineira et al. https://doi.org/10.1101/2020.09.24.20200048 |
| HLA-G | 6p22.1 | Human Leukocyte Antigen (HLA) G belongs to the HLA class I heavy chain paralogues on chromosome 6. HLA-G is expressed on fetal derived placental cells. HLA-G-associated diseases include asthma and severe pre-eclampsia. | GWAS | Pairo-Castineira et al. https://doi.org/10.1101/2020.09.24.20200048 |
| ABO blood group locus | 9q34.2 | This locus encodes proteins related to the first discovered blood group system, ABO. Variations in the ABO gene determines the ABO blood groups. ABO-associated diseases include epiglottis cancer and orbital tenonitis. | GWAS | PubMed ID: 32558485; Replicated by the 23andMe (unpublished) and Zhao et al. https://doi.org/10.1101/2020.03.11.20031096 |
| OAS1, OAS2, OAS3 gene cluster | 12q24.13 | The 2'-5'-Oligoadenylate Synthetase gene cluster encode the antiviral restriction enzyme activators, essential proteins involved in the innate immune response to viral infection. These enzymes are induced by interferons and catalyze reactions to activate RNase L, which results in viral RNA degradation and the inhibition of viral replication. This enzyme family plays a significant role in the inhibition of cellular protein synthesis, and hence, viral infection resistance. OAS-associated diseases include chikungunya, tick-borne encephalitis, microphthalmia with limb anomalies and pulmonary alveolar proteinosis with hypogammaglobulinemia. | GWAS/TWAS | Pairo-Castineira et al. https://doi.org/10.1101/2020.09.24.20200048 |
| TYK2 | 19p13.2 | The tyrosine kinase 2 gene encodes a member of the tyrosine kinase and the Janus kinase (JAK) protein families. It interacts with the cytoplasmic domain of type I and type II cytokine receptors and promote cytokine signals by phosphorylating receptor subunits. It is also a component of both the type I and type III interferon signaling pathways playing a potential role in anti-viral immunity. TYK2-associated diseases include hyperimmunoglobulin E syndrome (HIES) - a primary immunodeficiency characterized by elevated serum immunoglobulin E - and lymphomatoid papulosis as well as autoimmune diseases. | GWAS | Pairo-Castineira et al. https://doi.org/10.1101/2020.09.24.20200048 |
| DPP9 | 19p13.3 | The Dipeptidyl peptidase 9 gene encodes a protein that is a member of the S9B family in clan SC of the serine proteases. It has been shown to have post-proline dipeptidyl aminopeptidase activity. Dipeptidyl peptidases are involved in the regulation of the activity of their substrates and have been linked to a variety of diseases including type 2 diabetes, obesity and cancer. Other diseases associated with DPP9 include pulmonary fibrosis and nasopharyngitis. | GWAS | Pairo-Castineira et al. https://doi.org/10.1101/2020.09.24.20200048 |
| APOE | 19q13.32 | The Apolipoprotein E gene encodes an apoprotein of the chylomicron, which binds to a specific liver and peripheral cell receptor and is essential for the normal catabolism of triglyceride-rich lipoprotein constituents. Located on chromosome 19 in a cluster with the related apolipoprotein C1 and C2 genes. APOE-associated diseases include lipoprotein glomerulopathy, familial dysbetalipoproteinemia and type III hyperlipoproteinemia leading to increased blood triglyceride and cholesterol levels. | Observational candidate | PubMed ID: 32451547 |
| IFNAR2 | 21q22.1 | The Interferon Alpha And Beta Receptor Subunit 2 gene encodes a type I membrane protein that forms one of the two chains of a receptor for interferons alpha and beta. Binding and activation of the receptor stimulates Janus protein kinases, which in turn phosphorylate several proteins including STAT1 and STAT2. IFNAR2-associated diseases include immunodeficiency 45 and measles. | GWAS | Pairo-Castineira et al. https://doi.org/10.1101/2020.09.24.20200048 |
| TMPRSS2 | 21q22.3 | The Transmembrane Serine Protease 2 gene encodes a member of the serine protease family known to be involved in many physiological and pathological processes. It is upregulated by androgenic hormones in prostate cancer cells and downregulated in androgen-independent prostate cancer tissue. TMPRSS2-associated diseases include influenza. | Observational candidate | PubMed IDs: 32658335, 32664879, 32582302 |
| ACE2 | Xp22.2 | The Angiotensin I Converting Enzyme 2 gene encodes a member of the angiotensin-converting enzyme family of dipeptidyl carboxydipeptidases. It has significant homology to human angiotensin 1 converting enzyme. It catalyzes the cleavage of angiotensin I into angiotensin 1-9, and angiotensin II into the vasodilator angiotensin 1-7. It also functions as a receptor for the spike glycoprotein of the human coronaviruses SARS and HCoV-NL63. ACE2-associated diseases include severe acute respiratory syndrome. | Observational candidate | PubMed IDs: 32341442, 32221983, 32658335, 32664879, 32582302 |
Literature search performed using the LitCovid hub for COVID-19 using the keywords ‘COVID-19 host genetics’ (https://www.ncbi.nlm.nih.gov/research/coronavirus/, access date 10 July 2020). GWAS, Genome-wide association study; TWAS, transcriptome-wide association study).