IFNG

interferon gamma, the group of Interferons

Basic information

Region (hg38): 12:68154767-68159740

Links

ENSG00000111537 ∙ NCBI:3458 ∙ OMIM:147570 ∙ HGNC:5438 ∙ Uniprot:P01579 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• immunodeficiency 69 (Limited), mode of inheritance: Unknown

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Immunodeficiency 69	AR	Allergy/Immunology/Infectious	Individuals may be susceptible to frequent and severe mycobacterial infections, and awareness and early and aggressive treatment of infections may be beneficial; Consideration of potential adverse effects of BCG vaccination in some individuals may be beneficial	Allergy/Immunology/Infectious	32163377

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the IFNG gene.

• Aplastic anemia (19 variants)
• not provided (14 variants)
• Inborn genetic diseases (2 variants)
• Immunodeficiency 69 (1 variants)
• not specified (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the IFNG gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			1	1		2
missense			4			4
nonsense			1			1
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region					2	2
non coding			11	2	3	16
Total	0	0	17	3	3

Variants in IFNG

This is a list of pathogenic ClinVar variants found in the IFNG region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
12-68154814-T-C		Aplastic anemia	Benign (Jan 13, 2018)
12-68154853-G-A		Aplastic anemia	Likely benign (Jan 13, 2018)
12-68154888-T-A		Aplastic anemia	Likely benign (Jan 13, 2018)
12-68155122-A-G		Aplastic anemia	Uncertain significance (Jan 12, 2018)
12-68155166-A-C		Aplastic anemia	Uncertain significance (Jan 13, 2018)
12-68155173-G-A		Aplastic anemia	Benign (Jan 13, 2018)
12-68155246-T-C		Aplastic anemia	Uncertain significance (Jan 13, 2018)
12-68155252-TTTGA-T		Aplastic anemia	Uncertain significance (Jun 14, 2016)
12-68155331-A-T		Aplastic anemia	Uncertain significance (Jan 12, 2018)
12-68155344-G-A		Aplastic anemia	Uncertain significance (Jan 12, 2018)
12-68155423-G-A		Aplastic anemia	Uncertain significance (Jan 12, 2018)
12-68155423-G-T		Aplastic anemia	Uncertain significance (Apr 28, 2017)
12-68155445-T-C			Uncertain significance (Nov 30, 2021)
12-68155466-G-A		not specified	Uncertain significance (Sep 28, 2022)
12-68155714-C-G			not provided (-)
12-68155769-A-T			not provided (-)
12-68155906-A-G			not provided (-)
12-68157553-C-G			not provided (-)
12-68157563-T-A			not provided (-)
12-68157629-C-T			Benign (Nov 12, 2018)
12-68157774-A-G			not provided (-)
12-68157921-TAGTC-T		Immunodeficiency 69	Pathogenic (Mar 23, 2022)
12-68157954-T-C		not specified	Uncertain significance (May 31, 2023)
12-68157994-G-A		Aplastic anemia	Uncertain significance (Jan 12, 2018)
12-68158176-G-C		Aplastic anemia	Uncertain significance (Jan 13, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
IFNG	protein_coding	protein_coding	ENST00000229135	4	4980

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.472	0.507	124075	0	2	124077	0.00000806

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.61	42	83.3	0.504	0.00000419	1111
Missense in Polyphen		8	24.482	0.32678		336
Synonymous	-0.0970	30	29.3	1.02	0.00000155	273
Loss of Function	1.84	1	5.77	0.173	2.41e-7	85

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000178	0.0000178
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Produced by lymphocytes activated by specific antigens or mitogens. IFN-gamma, in addition to having antiviral activity, has important immunoregulatory functions. It is a potent activator of macrophages, it has antiproliferative effects on transformed cells and it can potentiate the antiviral and antitumor effects of the type I interferons.
• Disease: DISEASE: Aplastic anemia (AA) [MIM:609135]: A form of anemia in which the bone marrow fails to produce adequate numbers of peripheral blood elements. It is characterized by peripheral pancytopenia and marrow hypoplasia. {ECO:0000269|PubMed:15327519}. Note=Disease susceptibility may be associated with variations affecting the gene represented in this entry.
• Pathway: Antigen processing and presentation - Homo sapiens (human);Type I diabetes mellitus - Homo sapiens (human);T cell receptor signaling pathway - Homo sapiens (human);TGF-beta signaling pathway - Homo sapiens (human);Salmonella infection - Homo sapiens (human);Allograft rejection - Homo sapiens (human);Graft-versus-host disease - Homo sapiens (human);HIF-1 signaling pathway - Homo sapiens (human);Jak-STAT signaling pathway - Homo sapiens (human);Influenza A - Homo sapiens (human);Systemic lupus erythematosus - Homo sapiens (human);Inflammatory bowel disease (IBD) - Homo sapiens (human);African trypanosomiasis - Homo sapiens (human);Amoebiasis - Homo sapiens (human);Malaria - Homo sapiens (human);Chagas disease (American trypanosomiasis) - Homo sapiens (human);Necroptosis - Homo sapiens (human);Fluid shear stress and atherosclerosis - Homo sapiens (human);Tuberculosis - Homo sapiens (human);Th17 cell differentiation - Homo sapiens (human);Th1 and Th2 cell differentiation - Homo sapiens (human);Natural killer cell mediated cytotoxicity - Homo sapiens (human);Leishmaniasis - Homo sapiens (human);IL-17 signaling pathway - Homo sapiens (human);Toxoplasmosis - Homo sapiens (human);Pathways in cancer - Homo sapiens (human);Measles - Homo sapiens (human);Rheumatoid arthritis - Homo sapiens (human);Osteoclast differentiation - Homo sapiens (human);Cytokine-cytokine receptor interaction - Homo sapiens (human);Epstein-Barr virus infection - Homo sapiens (human);Proteasome - Homo sapiens (human);Herpes simplex infection - Homo sapiens (human);JAK-STAT-Core;Selenium Micronutrient Network;Vitamin B12 Metabolism;Folate Metabolism;Proteasome Degradation;Allograft Rejection;Spinal Cord Injury;IL1 and megakaryocytes in obesity;Aryl Hydrocarbon Receptor Pathway;Nuclear Receptors Meta-Pathway;Photodynamic therapy-induced AP-1 survival signaling.;T-Cell antigen Receptor (TCR) pathway during Staphylococcus aureus infection;RIG-I-like Receptor Signaling;Development and heterogeneity of the ILC family;Protein alkylation leading to liver fibrosis;NO-cGMP-PKG mediated Neuroprotection;RUNX1 and FOXP3 control the development of regulatory T lymphocytes (Tregs);Gene and protein expression by JAK-STAT signaling after Interleukin-12 stimulation;Inflammatory Response Pathway;Hypertrophy Model;no2-dependent il-12 pathway in nk cells;Cytokines and Inflammatory Response;TGF-beta Receptor Signaling;Senescence and Autophagy in Cancer;Type II interferon signaling (IFNG);Gene expression (Transcription);il12 and stat4 dependent signaling pathway in th1 development;chaperones modulate interferon signaling pathway;ifn gamma signaling pathway;the 41bb-dependent immune response;Generic Transcription Pathway;Cytokine Signaling in Immune system;JAK STAT MolecularVariation 1;IL12 signaling mediated by STAT4;GPCR signaling-G alpha q;GPCR signaling-cholera toxin;GPCR signaling-pertussis toxin;RNA Polymerase II Transcription;Regulation of IFNG signaling;Immune System;IFN gamma signaling;ATF-2 transcription factor network;GPCR signaling-G alpha s Epac and ERK;GPCR signaling-G alpha s PKA and ERK;SHP2 signaling;Glucocorticoid receptor regulatory network;JAK STAT pathway and regulation;IL2-mediated signaling events;Interferon gamma signaling;IFN-gamma pathway;GPCR signaling-G alpha i;RUNX1 and FOXP3 control the development of regulatory T lymphocytes (Tregs);IL23-mediated signaling events;Transcriptional regulation by RUNX1;IL27-mediated signaling events;Downstream signaling in naïve CD8+ T cells;Calcineurin-regulated NFAT-dependent transcription in lymphocytes;Interferon Signaling;Regulation of Telomerase;AP-1 transcription factor network;IL12-mediated signaling events;Calcium signaling in the CD4+ TCR pathway (Consensus)

Recessive Scores

• pRec: 0.999

Intolerance Scores

• loftool: 0.512
• rvis_EVS: -0.03
• rvis_percentile_EVS: 51.04

Haploinsufficiency Scores

• pHI: 0.133
• hipred: N
• hipred_score: 0.275
• ghis: 0.459

Essentials

• essential_gene_CRISPR: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.955

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Low	Low	Low
Primary Immunodeficiency	Medium	Low	Medium
Cancer	Low	Low	Low

Mouse Genome Informatics

• Gene name: Ifng
• Phenotype: endocrine/exocrine gland phenotype; growth/size/body region phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); homeostasis/metabolism phenotype; cellular phenotype; craniofacial phenotype; digestive/alimentary phenotype; muscle phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); neoplasm; hematopoietic system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); normal phenotype; reproductive system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); respiratory system phenotype; liver/biliary system phenotype; embryo phenotype; renal/urinary system phenotype; skeleton phenotype; immune system phenotype; vision/eye phenotype

Zebrafish Information Network

• Gene name: ifng1r
• Affected structure: defense response to bacterium
• Phenotype tag: abnormal
• Phenotype quality: disrupted

Gene ontology

• Biological process: obsolete protein import into nucleus, translocation;negative regulation of transcription by RNA polymerase II;positive regulation of protein phosphorylation;adaptive immune response;apoptotic process;humoral immune response;cell cycle arrest;cell surface receptor signaling pathway;positive regulation of cell population proliferation;response to virus;regulation of signaling receptor activity;positive regulation of autophagy;positive regulation of gene expression;negative regulation of gene expression;positive regulation of epithelial cell migration;regulation of protein ADP-ribosylation;negative regulation of epithelial cell differentiation;positive regulation of protein complex assembly;negative regulation of interleukin-17 production;positive regulation of interleukin-12 production;positive regulation of interleukin-23 production;positive regulation of CD4-positive, CD25-positive, alpha-beta regulatory T cell differentiation involved in immune response;positive regulation of peptidyl-serine phosphorylation of STAT protein;obsolete positive regulation of protein import into nucleus, translocation;positive regulation of smooth muscle cell apoptotic process;interleukin-12-mediated signaling pathway;regulation of growth;positive regulation of tyrosine phosphorylation of STAT protein;positive regulation of nitric oxide biosynthetic process;regulation of regulatory T cell differentiation;positive regulation of osteoclast differentiation;negative regulation of transcription, DNA-templated;negative regulation of smooth muscle cell proliferation;regulation of insulin secretion;positive regulation of membrane protein ectodomain proteolysis;defense response to virus;positive regulation of killing of cells of other organism;interferon-gamma-mediated signaling pathway;regulation of interferon-gamma-mediated signaling pathway;positive regulation of fructose 1,6-bisphosphate 1-phosphatase activity;positive regulation of fructose 1,6-bisphosphate metabolic process;positive regulation of vitamin D biosynthetic process;positive regulation of calcidiol 1-monooxygenase activity;positive regulation of protein serine/threonine kinase activity;positive regulation of protein deacetylation;extrinsic apoptotic signaling pathway;positive regulation of protein localization to plasma membrane;positive regulation of exosomal secretion;positive regulation of core promoter binding;positive regulation of tumor necrosis factor (ligand) superfamily member 11 production
• Cellular component: extracellular region;extracellular space;cell
• Molecular function: cytokine activity;interferon-gamma receptor binding;protein binding