IFNG (interferon gamma)

Gene

• Entrez ID: 3458
• Gene name: Interferon gamma
• Gene symbol: IFNG
• Synonyms: IFG, IFI, IMD69
• Chromosome: 12
• Chromosome location: 12q15
• Summary: 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]

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs2069707	G>A,C	Drug-response	Upstream transcript variant
rs34079299	TGTGTGTGTGTG>-,TG,TGTG,TGTGTG,TGTGTGTG,TGTGTGTGTG,TGTGTGTGTGTGTG,TGTGTGTGTGTGTGTG,TGTGTGTGTGTGTGTGTG,TGTGTGTGTGTGTGTGTGTG,TGTGTGTGTGTGTGTGTGTGTG,TGTGTGTGTGTGTGTGTGTGTGTG,TGTGTGTGTGTGTGTGTGTGTGTGTG	Risk-factor	Intron variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT006912	hsa-miR-16-5p	Luciferase reporter assay, qRT-PCR	22379033
MIRT006913	hsa-miR-15a-5p	Luciferase reporter assay, qRT-PCR	22379033
MIRT006914	hsa-miR-15b-5p	Luciferase reporter assay, qRT-PCR	22379033
MIRT007034	hsa-miR-29b-3p	Luciferase reporter assay	22772450
MIRT007034	hsa-miR-29b-3p	Luciferase reporter assay	27812842
MIRT007285	hsa-miR-409-3p	Luciferase reporter assay	23360331
MIRT029122	hsa-miR-26b-5p	Microarray	19088304
MIRT437825	hsa-miR-125a-5p	ELISA, Microarray, qRT-PCR, Western blot, silico analysis	24759737
MIRT437945	hsa-miR-27a-3p	ChIP-seq, qRT-PCR, Luciferase reporter assay, Western blot	24725595
MIRT437969	hsa-miR-181a-5p	qRT-PCR, Luciferase reporter assay, Western blot	24704866
MIRT437970	hsa-miR-24-3p	qRT-PCR, Luciferase reporter assay, Western blot	24704866

Transcription factors

Transcription factor	Regulation	Reference
ATF2	Activation	12836278;18641343;20006311;20304822
ATF3	Activation	20304822
CREB1	Activation	20006311;20685939
CREB1	Repression	11907114
CREB1	Unknown	7759501
EGR1	Unknown	8900159
EOMES	Unknown	20056084
EP300	Activation	12836278
GATA1	Unknown	12836278
GATA3	Unknown	21507199
IRF1	Activation	13678429
JUN	Activation	12626576;18641343;20006311;20304822
JUN	Unknown	12836278;7759501
MSC	Activation	19561533
MYCN	Unknown	9570357
NFATC1	Unknown	12836278
NFATC2	Unknown	12836278
NFIL3	Unknown	7565758
NFKB1	Activation	17407192;18690006
NFKB1	Unknown	21243522;9374532
PARP1	Unknown	17177976
PROX1	Repression	20064070
RELA	Activation	17407192;18690006
RELA	Unknown	21243522;9374532
RFX5	Unknown	12968017
STAT1	Activation	13678429
STAT1	Repression	15055356;18616672
STAT1	Unknown	16195385;20004484
STAT3	Repression	18616672
STAT4	Unknown	9558063;9642277
STAT5A	Activation	15528362
STAT5B	Unknown	15528362
TBX21	Activation	17541280;19348920;20977921;21540308
TBX21	Unknown	12938094;16498264;16737784;17705132;19879772;20056084;21507199;22521571;24752800
TFAP4	Unknown	12836278
USF1	Unknown	8900159
YY1	Activation	8756632
YY1	Repression	8756632
YY1	Unknown	12836278

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000122	Process	Negative regulation of transcription by RNA polymerase II	ISS
GO:0001774	Process	Microglial cell activation	IGI	7715705, 19808651
GO:0001774	Process	Microglial cell activation	ISS
GO:0001819	Process	Positive regulation of cytokine production	IDA	30634164
GO:0001934	Process	Positive regulation of protein phosphorylation	IDA	22504299
GO:0002250	Process	Adaptive immune response	IBA	21873635
GO:0002281	Process	Macrophage activation involved in immune response	IDA	30634164
GO:0005125	Function	Cytokine activity	IBA	21873635
GO:0005133	Function	Interferon-gamma receptor binding	IEA
GO:0005515	Function	Protein binding	IPI	7617032, 11250200, 18252829, 28514442
GO:0005576	Component	Extracellular region	IDA	20041150
GO:0005576	Component	Extracellular region	TAS
GO:0005615	Component	Extracellular space	IBA	21873635
GO:0006915	Process	Apoptotic process	IGI	7828849
GO:0006959	Process	Humoral immune response	IBA	21873635
GO:0007050	Process	Cell cycle arrest	IDA	16942485
GO:0007166	Process	Cell surface receptor signaling pathway	TAS	10477596
GO:0007259	Process	Receptor signaling pathway via JAK-STAT	ISS
GO:0008284	Process	Positive regulation of cell population proliferation	ISS
GO:0009615	Process	Response to virus	IDA	16280321
GO:0010508	Process	Positive regulation of autophagy	IDA	23629966, 26347139
GO:0010628	Process	Positive regulation of gene expression	HDA	11487543
GO:0010628	Process	Positive regulation of gene expression	IDA	19423618, 20164187, 20209097, 22504299, 23817958
GO:0010628	Process	Positive regulation of gene expression	IGI	19808651
GO:0010628	Process	Positive regulation of gene expression	IMP	20889566
GO:0010628	Process	Positive regulation of gene expression	ISS
GO:0010629	Process	Negative regulation of gene expression	IDA	23817958
GO:0010629	Process	Negative regulation of gene expression	ISS
GO:0010634	Process	Positive regulation of epithelial cell migration	IDA	11698262
GO:0010835	Process	Regulation of protein ADP-ribosylation	IDA	22504299
GO:0030225	Process	Macrophage differentiation	IDA	30634164
GO:0030857	Process	Negative regulation of epithelial cell differentiation	ISS
GO:0031334	Process	Positive regulation of protein-containing complex assembly	IDA	22504299
GO:0032700	Process	Negative regulation of interleukin-17 production	IDA	18501882
GO:0032722	Process	Positive regulation of chemokine production	IDA	19423618
GO:0032731	Process	Positive regulation of interleukin-1 beta production	ISS
GO:0032735	Process	Positive regulation of interleukin-12 production	IDA	7605994, 8557999
GO:0032747	Process	Positive regulation of interleukin-23 production	IDA	20027291
GO:0032755	Process	Positive regulation of interleukin-6 production	IDA	30634164
GO:0032760	Process	Positive regulation of tumor necrosis factor production	ISS	7715705
GO:0032834	Process	Positive regulation of CD4-positive, CD25-positive, alpha-beta regulatory T cell differentiation involved in immune response	IDA	20209097
GO:0033141	Process	Positive regulation of peptidyl-serine phosphorylation of STAT protein	IDA	16280321
GO:0033141	Process	Positive regulation of peptidyl-serine phosphorylation of STAT protein	NAS	21268089
GO:0034393	Process	Positive regulation of smooth muscle cell apoptotic process	IDA	16942485
GO:0035722	Process	Interleukin-12-mediated signaling pathway	TAS
GO:0040008	Process	Regulation of growth	IEA
GO:0042307	Process	Positive regulation of protein import into nucleus	IDA	22504299
GO:0042531	Process	Positive regulation of tyrosine phosphorylation of STAT protein	IDA	15604419, 16280321
GO:0045348	Process	Positive regulation of MHC class II biosynthetic process	ISS
GO:0045429	Process	Positive regulation of nitric oxide biosynthetic process	IDA	8383325
GO:0045589	Process	Regulation of regulatory T cell differentiation	TAS
GO:0045672	Process	Positive regulation of osteoclast differentiation	IDA	16220542
GO:0045821	Process	Positive regulation of glycolytic process	ISS
GO:0045892	Process	Negative regulation of transcription, DNA-templated	IDA	23629966
GO:0048143	Process	Astrocyte activation	IDA	18375019
GO:0048143	Process	Astrocyte activation	ISS
GO:0048662	Process	Negative regulation of smooth muscle cell proliferation	IDA	16942485
GO:0050729	Process	Positive regulation of inflammatory response	IDA	30634164
GO:0050766	Process	Positive regulation of phagocytosis	ISS
GO:0050769	Process	Positive regulation of neurogenesis	IGI	19808651
GO:0050796	Process	Regulation of insulin secretion	IDA	8383325
GO:0051044	Process	Positive regulation of membrane protein ectodomain proteolysis	IDA	18373975
GO:0051173	Process	Positive regulation of nitrogen compound metabolic process	IGI	7715705
GO:0051607	Process	Defense response to virus	IEA
GO:0051712	Process	Positive regulation of killing of cells of other organism	IDA	7544003
GO:0051770	Process	Positive regulation of nitric-oxide synthase biosynthetic process	ISS
GO:0060333	Process	Interferon-gamma-mediated signaling pathway	IDA	22504299, 23629966
GO:0060333	Process	Interferon-gamma-mediated signaling pathway	TAS
GO:0060334	Process	Regulation of interferon-gamma-mediated signaling pathway	TAS
GO:0060550	Process	Positive regulation of fructose 1,6-bisphosphate 1-phosphatase activity	IDA	9282826
GO:0060552	Process	Positive regulation of fructose 1,6-bisphosphate metabolic process	IDA	9282826
GO:0060557	Process	Positive regulation of vitamin D biosynthetic process	IDA	9282826
GO:0060559	Process	Positive regulation of calcidiol 1-monooxygenase activity	IDA	9282826
GO:0071902	Process	Positive regulation of protein serine/threonine kinase activity	IDA	22504299
GO:0090312	Process	Positive regulation of protein deacetylation	IDA	23629966
GO:0097191	Process	Extrinsic apoptotic signaling pathway	IDA	16942485
GO:0150076	Process	Neuroinflammatory response	ISS
GO:1900222	Process	Negative regulation of amyloid-beta clearance	ISS
GO:1901216	Process	Positive regulation of neuron death	IGI	7715705
GO:1901857	Process	Positive regulation of cellular respiration	ISS
GO:1902004	Process	Positive regulation of amyloid-beta formation	IGI	19808651
GO:1902004	Process	Positive regulation of amyloid-beta formation	ISS
GO:1902948	Process	Negative regulation of tau-protein kinase activity	IGI	19808651
GO:1903078	Process	Positive regulation of protein localization to plasma membrane	HDA	11487543
GO:1903543	Process	Positive regulation of exosomal secretion	HDA	11487543
GO:1904440	Process	Positive regulation of iron ion import across plasma membrane	ISS
GO:1904783	Process	Positive regulation of NMDA glutamate receptor activity	ISS
GO:1904798	Process	Positive regulation of core promoter binding	IDA	23629966
GO:2000273	Process	Positive regulation of signaling receptor activity	ISS
GO:2000309	Process	Positive regulation of tumor necrosis factor (ligand) superfamily member 11 production	IDA	16220542

Other IDs

• MIM: 147570
• HGNC: 5438
• e!Ensembl: ENSG00000111537

Protein

• UniProt ID: P01579
• Protein name: Interferon gamma (IFN-gamma) (Immune interferon)
• Protein function: Type II interferon produced by immune cells such as T-cells and NK cells that plays crucial roles in antimicrobial, antiviral, and antitumor responses by activating effector immune cells and enhancing antigen presentation (PubMed:16914093, PubMed:8666937). Primarily signals through the JAK-STAT pathway after interaction with its receptor IFNGR1 to affect gene regulation (PubMed:8349687). Upon IFNG binding, IFNGR1 intracellular domain opens out to allow association of downstream signaling components JAK2, JAK1 and STAT1, leading to STAT1 activation, nuclear translocation and transcription of IFNG-regulated genes. Many of the induced genes are transcription factors such as IRF1 that are able to further drive regulation of a next wave of transcription (PubMed:16914093). Plays a role in class I antigen presentation pathway by inducing a replacement of catalytic proteasome subunits with immunoproteasome subunits (PubMed:8666937). In turn, increases the quantity, quality, and repertoire of peptides for class I MHC loading (PubMed:8163024). Increases the efficiency of peptide generation also by inducing the expression of activator PA28 that associates with the proteasome and alters its proteolytic cleavage preference (PubMed:11112687). Up-regulates as well MHC II complexes on the cell surface by promoting expression of several key molecules such as cathepsins B/CTSB, H/CTSH, and L/CTSL (PubMed:7729559). Participates in the regulation of hematopoietic stem cells during development and under homeostatic conditions by affecting their development, quiescence, and differentiation (By similarity).
• PDB: 1EKU, 1FG9, 1FYH, 1HIG, 3BES, 6E3K, 6E3L
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00714	IFN-gamma	15 → 153	Interferon gamma	Domain

• Sequence:

  MKYTSYILAFQLCIVLGSLGCYCQDPYVKEAENLKKYFNAGHSDVADNGTLFLGILKNWK
  EESDRKIMQSQIVSFYFKLFKNFKDDQSIQKSVETIKEDMNVKFFNSNKKKRDDFEKLTN
  YSVTDLNVQRKAIHELIQVMAELSPAAKTGKRKRSQMLFRGRRASQ

• Sequence length: 166