Genes in panel
STRs in panel
Prev Next

COVID-19 research

Gene: IFNG

Green List (high evidence)

IFNG (interferon gamma)
EnsemblGeneIds (GRCh38): ENSG00000111537
EnsemblGeneIds (GRCh37): ENSG00000111537
OMIM: 147570, Gene2Phenotype
IFNG is in 5 panels

2 reviews

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

Green List (high evidence)

Mode of inheritance
Unknown

Publications

Sarah Leigh (Genomics England Curator)

I don't know

Comment on list classification: Associated with relevant phenotype in OMIM, but not associated with phenotype in Gen2Phen. Two promoter variants are associated with viral susceptibility and response to therapy; c.-179G>T (RCV000015845.26) with accelerated progression to AIDS (PMID 12854077) and c.-764C>G (rs2069707) with enhanced promoter activity and increased viral clearance and treatment response in hepatitis C virus infection (PMID 17215375). The A allele of rs2430561 is associate with susceptibility to Hepatitis B virus infection (PMID 26458193).
Created: 15 Jun 2020, 4:47 p.m. | Last Modified: 15 Jun 2020, 4:47 p.m.
Panel Version: 1.54
IFNG was identified through an OMIM search for potential viral susceptibility genes. Initial triage by Illumina (Alison Coffey and team) was given a Tier 3 grouping (experimental evidence and association data consistent with viral susceptibility). Illumina review: From OMIM: Interferon-gamma (IFNG), or type II interferon, is a cytokine critical for innate and adaptive immunity against viral and intracellular bacterial infections and for tumor control. The importance of IFNG in the immune system stems in part from its ability to inhibit viral replication directly, but most importantly derives from its immunostimulatory and immunomodulatory effects. IFNG is produced predominantly by natural killer (NK) and natural killer T (NKT) cells as part of the innate immune response, and by CD4 (186940) and CD8 (see 186910) cytotoxic T lymphocyte (CTL) effector T cells once antigen-specific immunity develops (PMID: 17981204; Schoenborn and Wilson, 2007). From OMIM: PMID: 17215375: Huang et al. (2007) The IFNG gene SNP, -764 C>G (rs2069707) in the proximal promoter region next to the binding motif for HSF1 , was significantly associated with sustained virologic response to IFNA therapy in a cohort of hepatitis C virus-positive patients compared to a cohorts who had spontaneously cleared HCV infection or who had chronic HCV infection. Luciferase reporter and EMSA analyses showed that the -764G allele had 2- to 3-fold higher promoter activity and stronger binding affinity for HSF1 than the -764C allele. Huang et al. (2007) concluded that the -764C-G SNP is functionally important in determining viral clearance and treatment response in HCV-infected patients.
From OMIM PMID: 12854077: An et al. (2003) reported an association between a SNP in the IFNG promoter region, -173 G>T, and progression to AIDS. In individuals with the rare -179T allele, but not in those with the -179G allele, IFNG is inducible by TNF. An et al. (2003) studied 298 African American HIV-1 seroconverters and found that the -179T allele was associated with accelerated progression to a CD4 cell count below 200 and to AIDS. They noted that the SNP is present in 4% of African Americans and in only 0.02% of European Americans.
PMID: 26458193 Wei et al. (2017) Eleven independent case-control studies were selected for the meta-analysis, comprising a total of 1527 HBV cases and 1467 healthy subjects. carriers of the IFN-γ A allele were more likely to develop HBV infection than those without in all five genetic models (all p < 0.05). According to the ethnicity-based sub-group analysis, a significant difference of the IFN-γ rs2430561 T > A (IFN-γ +874T/A) polymorphism was detected associated with the increased risk of HBV infection in Asians and European-derived populations in the majority of the groups.
Created: 11 Jun 2020, 6:10 p.m. | Last Modified: 15 Jun 2020, 1 p.m.
Panel Version: 1.52
IFNG c.-179G>T (RCV000015845.26) is associated with progression to AIDS (PMID 12854077).
Created: 4 May 2020, 3:17 p.m. | Last Modified: 4 May 2020, 3:17 p.m.
Panel Version: 0.176

Mode of inheritance
Unknown

Phenotypes
AIDS, rapid progression to} 609423

Publications

Details

Sources
  • Expert Review Green
  • OMIM
Phenotypes
  • {AIDS, rapid progression to} 609423
  • {Hepatitis C virus, response to therapy of} 609532
OMIM
147570
Clinvar variants
Variants in IFNG
Penetrance
None
Publications
Panels with this gene

History Filter Activity

15 Jun 2020, Gel status: 3

Entity classified by Genomics England curator

Sarah Leigh (Genomics England Curator)

Gene: ifng has been classified as Green List (High Evidence).

15 Jun 2020, Gel status: 1

Set Phenotypes

Sarah Leigh (Genomics England Curator)

Phenotypes for gene: IFNG were changed from {AIDS, rapid progression to} 609423 to {AIDS, rapid progression to} 609423; {Hepatitis C virus, response to therapy of} 609532

15 Jun 2020, Gel status: 1

Set publications

Sarah Leigh (Genomics England Curator)

Publications for gene: IFNG were set to 178981204; 17215375; 12854077; 26458193

12 Jun 2020, Gel status: 1

Set publications

Sarah Leigh (Genomics England Curator)

Publications for gene: IFNG were set to

4 May 2020, Gel status: 1

Set Phenotypes

Sarah Leigh (Genomics England Curator)

Phenotypes for gene: IFNG were changed from to {AIDS, rapid progression to} 609423

21 Apr 2020, Gel status: 1

Created, Added New Source, Set mode of inheritance

Sarah Leigh (Genomics England Curator)

gene: IFNG was added gene: IFNG was added to Viral susceptibility. Sources: OMIM Mode of inheritance for gene: IFNG was set to