IFNG
Interferon gamma
Also known as: IFNG_HUMAN
Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene
Protein identityUniProt · HPA
- UniProt accession
- P01579
- Gene
- IFNG
- Ensembl
- ENSG00000111537
- Chromosome
- 12
- Canonical length
- 166 aa
- Protein class
- Cancer-related genes, Disease related genes, FDA approved drug targets, Human disease related genes, Plasma proteins, Predicted secreted proteins
- Secretome location
- Secreted to blood
- Quaternary structure
- Homodimer
OverviewNCBI Gene
This gene encodes a soluble cytokine that is a member of the type II interferon class. The encoded protein is secreted by cells of both the innate and adaptive immune systems. The active protein is a homodimer that binds to the interferon gamma receptor which triggers a cellular response to viral and microbial infections. Mutations in this gene are associated with an increased susceptibility to viral, bacterial and parasitic infections and to several autoimmune diseases. [provided by RefSeq, Dec 2015]
Canonical amino-acid sequenceUniProt
166 residues, UniProt reviewed canonical sequence.
>P01579|IFNG
1 MKYTSYILAF QLCIVLGSLG CYCQDPYVKE AENLKKYFNA GHSDVADNGT LFLGILKNWK
61 EESDRKIMQS QIVSFYFKLF KNFKDDQSIQ KSVETIKEDM NVKFFNSNKK KRDDFEKLTN
121 YSVTDLNVQR KAIHELIQVM AELSPAAKTG KRKRSQMLFR GRRASQLocalizationUniProt · AlphaFold · HPA
Whether an antibody against IFNG can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.
- Antibody reachability
- Secreted
- Secreted
- Yes
- Transmembrane segments
- 0
- Mean surface accessibility (rSASA)
- 0.47
- Highest tissue expression
- 11 nTPM
Expression across tissuesHPA
Tissue
- bone marrow: 11 nTPM
- lymph node: 7 nTPM
- appendix: 3.3 nTPM
- lung: 1.7 nTPM
- liver: 1.6 nTPM
- spleen: 1.4 nTPM
Single-cell type
- t-cells: 232 nCPM
- nk-cells: 232 nCPM
- pdcs: 40 nCPM
- plasma cells: 11 nCPM
- cdc: 8.3 nCPM
- innate lymphoid cells: 6.7 nCPM
Immune cell
- memory CD8 T-cell: 6.6 nTPM
- gdT-cell: 5.5 nTPM
- naive CD8 T-cell: 3.7 nTPM
- memory CD4 T-cell: 2.4 nTPM
- NK-cell: 0.9 nTPM
- total PBMC: 0.9 nTPM
Brain region
- basal ganglia: 0.5 nTPM
- choroid plexus: 0.5 nTPM
- thalamus: 0.4 nTPM
- cerebral cortex: 0.3 nTPM
- hippocampal formation: 0.3 nTPM
- hypothalamus: 0.3 nTPM
DiseaseUniProt · ClinVar · IEDB · PubMed
Four sources answering four different questions about IFNG.
Disease | AllUniProt
Conditions IFNG is implicated in, by any mechanism.
- Aplastic anemia (AA) MIM:609135
- Immunodeficiency 69 (IMD69) MIM:618963
Disease | GeneticClinVar
2 pathogenic / likely-pathogenic of 44 ClinVar records.
Conditions with pathogenic or likely-pathogenic variants.
- Acquired immunodeficiency syndrome, rapid progression to
- Immunodeficiency 69
Disease | ImmuneIEDB
Conditions an epitope on IFNG was assayed in.
- autoimmune disease B cell
Disease | AutoantibodyPubMed
Conditions in which antibodies against IFNG are reported. Each links to that disease's full target list.
- HIV Infections 21
- Lupus Erythematosus, Systemic 8
- Diabetes Mellitus, Type 1 6
- Acquired Immunodeficiency Syndrome 5
- Psoriasis 5
- Sjogren's Syndrome 5
- Arthritis, Rheumatoid 4
- COVID-19 4
- Cytomegalovirus Infections 3
- Lung Neoplasms 3
- Multiple Sclerosis 3
- Skin Diseases, Vesiculobullous 3
Showing 12 of 20 — disease pages carrying at least 10 antigens.
ReferencesPubMed · IEDB
Publications for IFNG from three distinct lines of evidence, kept separate because they answer different questions: whether antibodies are directed at the protein, whether a B-cell epitope has been mapped on it, and whether a T-cell epitope has. Each is labelled with its source.
Reference: AutoantibodyPubMed
364 publications
- Adult-onset immunodeficiency in Thailand and Taiwan.
2012 · N Engl J Med · RCR 13.4 · 464 citations - Talaromyces (Penicillium) marneffei infection in non-HIV-infected patients.
2016 · Emerg Microbes Infect · RCR 12.2 · 237 citations - Identification of T helper type 1-like, Foxp3+ regulatory T cells in human autoimmune disease.
2011 · Nat Med · RCR 9.1 · 425 citations - Host susceptibility to non-tuberculous mycobacterial infections.
2015 · Lancet Infect Dis · RCR 7.5 · 196 citations - Natural History and Evolution of Anti-Interferon-γ Autoantibody-Associated Immunodeficiency Syndrome in Thailand and the United States.
2020 · Clin Infect Dis · RCR 5.8 · 106 citations
Show 20 more of 364 total
- Functional assay of type I interferon in systemic lupus erythematosus plasma and association with anti-RNA binding protein autoantibodies.
2006 · Arthritis Rheum · RCR 5.6 · 265 citations - Anti-IFN-γ autoantibodies in adults with disseminated nontuberculous mycobacterial infections are associated with HLA-DRB1*16:02 and HLA-DQB1*05:02 and the reactivation of latent varicella-zoster virus infection.
2013 · Blood · RCR 5.3 · 167 citations - Anti-IFN-γ autoantibodies underlie disseminated Talaromyces marneffei infections.
2020 · J Exp Med · RCR 4.9 · 113 citations - Anti-CD20 (rituximab) therapy for anti-IFN-γ autoantibody-associated nontuberculous mycobacterial infection.
2012 · Blood · RCR 4.6 · 160 citations - Clinical manifestations, course, and outcome of patients with neutralizing anti-interferon-γ autoantibodies and disseminated nontuberculous mycobacterial infections.
2016 · Medicine (Baltimore) · RCR 4.6 · 124 citations - Anti-interferon-γ autoantibody-associated immunodeficiency.
2021 · Curr Opin Immunol · RCR 4.4 · 76 citations - Autoantibodies to interferon-gamma in a patient with selective susceptibility to mycobacterial infection and organ-specific autoimmunity.
2004 · Clin Infect Dis · RCR 4.3 · 228 citations - Acquired predisposition to mycobacterial disease due to autoantibodies to IFN-gamma.
2005 · J Clin Invest · RCR 3.9 · 198 citations - Naturally occurring anti-IFN-gamma autoantibody and severe infections with Mycobacterium cheloneae and Burkholderia cocovenenans.
2004 · Blood · RCR 3.9 · 199 citations - Characteristics and Outcomes of Anti-interferon Gamma Antibody-Associated Adult Onset Immunodeficiency.
2023 · J Clin Immunol · RCR 3.8 · 32 citations - Anti-IFN-gamma autoantibodies in disseminated nontuberculous mycobacterial infections.
2005 · J Immunol · RCR 3.8 · 184 citations - Pathogen spectrum and immunotherapy in patients with anti-IFN-γ autoantibodies: A multicenter retrospective study and systematic review.
2022 · Front Immunol · RCR 3.7 · 42 citations - Clinical Significance of Interferon-γ Neutralizing Autoantibodies Against Disseminated Nontuberculous Mycobacterial Disease.
2018 · Clin Infect Dis · RCR 3.7 · 89 citations - Involvement of ILC1-like innate lymphocytes in human autoimmunity, lessons from alopecia areata.
2023 · Elife · RCR 3.6 · 22 citations - Experimental therapy of systemic lupus erythematosus: the treatment of NZB/W mice with mouse soluble interferon-gamma receptor inhibits the onset of glomerulonephritis.
1995 · Eur J Immunol · RCR 3.4 · 158 citations - Distinct Functions of Autoantibodies Against Interferon in Systemic Lupus Erythematosus: A Comprehensive Analysis of Anticytokine Autoantibodies in Common Rheumatic Diseases.
2016 · Arthritis Rheumatol · RCR 3.2 · 112 citations - IFN-gamma receptor deletion prevents autoantibody production and glomerulonephritis in lupus-prone (NZB x NZW)F1 mice.
1998 · J Immunol · RCR 3.2 · 160 citations - Clinical Characteristics and Mortality of Non-tuberculous Mycobacterial Infection in Immunocompromised vs. Immunocompetent Hosts.
2022 · Front Med (Lausanne) · RCR 3.1 · 30 citations - Identification of a major epitope by anti-interferon-γ autoantibodies in patients with mycobacterial disease.
2016 · Nat Med · RCR 3 · 93 citations - Anti-cytokine autoantibodies in autoimmunity: preponderance of neutralizing autoantibodies against interferon-alpha, interferon-omega and interleukin-12 in patients with thymoma and/or myasthenia gravis.
2003 · Clin Exp Immunol · RCR 3 · 158 citations
Reference: B cellIEDB
1 publication
- The impact of neutralizing anti-IFN-γ autoantibodies on GBP5 expression and monocyte dysfunction in adult-onset immunodeficiency.
2025 · Immunobiology · 1 citations
Sources: PubMed — antigen-level antibody evidence from a custom retrieval. Records matching a controlled set of autoantibody terms (the MeSH descriptors Autoantibodies and Autoantigens, with title and abstract term variants) were obtained through NCBI E-utilities, and their titles and abstracts parsed for constructions that direct an antibody at a named protein rather than for co-occurrence. Captured names were resolved against UniProt nomenclature and each antigen adjudicated individually against the source text. IEDB — curated epitope assays from the Immune Epitope Database (Vita et al., Nucleic Acids Research 2019). Bibliographic records from PubMed and MeSH, U.S. National Library of Medicine; citation metrics from NIH iCite (Hutchins et al., PLoS Biology 2016). Titles link to PubMed; abstracts are not reproduced here. The NLM does not endorse this analysis.
Genetic constraint and essentialitygnomAD · DepMap
Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.
- gnomAD LOEUF (loss-of-function intolerance)
- 0.82
- gnomAD pLI
- 0.47
- gnomAD missense Z
- 1.61
- DepMap mean gene effect
- 0.1
- DepMap dependency class
- none
Cancer expressionTCGA
Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).
OntologyGO
Biological processes
- adaptive immune response
- apoptotic process
- astrocyte activation
- cell surface receptor signaling pathway
- cell surface receptor signaling pathway via JAK-STAT
- cell surface receptor signaling pathway via STAT
- cellular response to virus
- defense response to virus
- extrinsic apoptotic signaling pathway
- Fc-gamma receptor signaling pathway involved in phagocytosis
- humoral immune response
- macrophage activation involved in immune response
- macrophage differentiation
- microglial cell activation
- negative regulation of amyloid-beta clearance
- negative regulation of DNA-templated transcription
- negative regulation of epithelial cell differentiation
- negative regulation of gene expression
- negative regulation of interleukin-17 production
- negative regulation of smooth muscle cell proliferation
- negative regulation of transcription by RNA polymerase II
- neuroinflammatory response
- positive regulation of amyloid-beta formation
- positive regulation of autophagy
- positive regulation of CD4-positive, CD25-positive, alpha-beta regulatory T cell differentiation involved in immune response
- positive regulation of cell population proliferation
- positive regulation of cellular respiration
- positive regulation of chemokine production
- positive regulation of cytokine production
- positive regulation of epithelial cell migration
- positive regulation of exosomal secretion
- positive regulation of gene expression
- positive regulation of glutamate receptor signaling pathway
- positive regulation of glycolytic process
- positive regulation of inflammatory response
- positive regulation of interleukin-1 beta production
- positive regulation of interleukin-12 production
- positive regulation of interleukin-23 production
- positive regulation of interleukin-6 production
- positive regulation of iron ion import across plasma membrane
- positive regulation of membrane protein ectodomain proteolysis
- positive regulation of MHC class II biosynthetic process
- positive regulation of neurogenesis
- positive regulation of nitric oxide biosynthetic process
- positive regulation of osteoclast differentiation
- positive regulation of phagocytosis
- positive regulation of protein localization to plasma membrane
- positive regulation of smooth muscle cell apoptotic process
- positive regulation of transcription by RNA polymerase II
- positive regulation of tumor necrosis factor (ligand) superfamily member 11 production
- positive regulation of tumor necrosis factor production
- positive regulation of tyrosine phosphorylation of STAT protein
- positive regulation of vitamin D biosynthetic process
- regulation of insulin secretion
- response to virus
- type II interferon-mediated signaling pathway
- type III interferon-mediated signaling pathway
- positive regulation of fructose 1,6-bisphosphate metabolic process
- positive regulation of peptidyl-serine phosphorylation of STAT protein
Molecular functions
Cellular components
Protein domainsUniProt · Pfam · InterPro
- Four-helical cytokine-like, core
- Interferon gamma
- Interferon gamma
KeywordsUniProt
InteractionsUniProt · HPA
Protein binding partners of IFNG in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.
Antibody and autoantibody relevanceSeroatlas analysis
Seroatlas reads IFNG as an antibody target. Whether an autoantibody or antibody against IFNG could matter depends on whether native IFNG is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.
IFNG is annotated as secreted, so native IFNG circulates and is directly accessible to antibodies. Secreted and cell-surface proteins are the autoantibody targets most likely to act like drugs, blocking or depleting the native protein.
Source-annotated serology context
The source annotations explicitly mention antibody, autoantibody, autoantigen, or autoimmune context. This is biological context, not study-specific reactivity.
- Mutations in this gene are associated with an increased susceptibility to viral, bacterial and parasitic infections and to several autoimmune diseases.
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