IFNGR1

Summary

IFNGR1 (interferon gamma receptor 1, HGNC:5439) is a protein-coding gene on chromosome 6q23.3, encoding Interferon gamma receptor 1 (P15260). Receptor subunit for interferon gamma/INFG that plays crucial roles in antimicrobial, antiviral, and antitumor responses by activating effector immune cells and enhancing antigen presentation. In precision oncology, IFNGR1 Loss is associated with resistance to Ipilimumab in Melanoma (CIViC Level D).

This gene (IFNGR1) encodes the ligand-binding chain (alpha) of the gamma interferon receptor. Human interferon-gamma receptor is a heterodimer of IFNGR1 and IFNGR2. A genetic variation in IFNGR1 is associated with susceptibility to Helicobacter pylori infection. In addition, defects in IFNGR1 are a cause of mendelian susceptibility to mycobacterial disease, also known as familial disseminated atypical mycobacterial infection.

Source: NCBI Gene 3459 — RefSeq curated summary.

At a glance

• Gene–disease (curated): immunodeficiency 27A (Definitive, GenCC) — +3 more curated relationships
• GWAS associations: 9
• Clinical variants (ClinVar): 445 total — 27 pathogenic, 9 likely-pathogenic
• Phenotypes (HPO): 108
• Druggable target: yes
• Precision-oncology evidence (CIViC): 1 curated variant–drug association
• MANE Select transcript: NM_000416

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:5439
Approved symbol	IFNGR1
Name	interferon gamma receptor 1
Location	6q23.3
Locus type	gene with protein product
Status	Approved
Aliases	CD119
Ensembl gene	ENSG00000027697
Ensembl biotype	protein_coding
OMIM	107470
Entrez	3459

Gene structure

Transcript identifiers

Ensembl transcripts: 23 — 19 protein_coding, 3 nonsense_mediated_decay, 1 retained_intron

ENST00000367739, ENST00000414770, ENST00000458076, ENST00000478333, ENST00000642390, ENST00000643119, ENST00000644894, ENST00000645045, ENST00000645753, ENST00000646036, ENST00000646898, ENST00000647124, ENST00000696693, ENST00000696694, ENST00000696695, ENST00000696696, ENST00000696697, ENST00000696698, ENST00000696699, ENST00000911309, ENST00000957752, ENST00000957753, ENST00000957754

RefSeq mRNA: 3 — MANE Select: NM_000416 NM_000416, NM_001363526, NM_001363527

CCDS: CCDS5185, CCDS87445, CCDS87446

Canonical transcript exons

ENST00000367739 — 7 exons

Exon	Start	End
ENSE00000764522	137206136	137206308
ENSE00000764523	137206963	137207077
ENSE00001707029	137200881	137201008
ENSE00001719673	137204332	137204504
ENSE00003788320	137203499	137203685
ENSE00003823101	137197485	137198639
ENSE00003968083	137219243	137219385

Expression profiles

Bgee: expression breadth ubiquitous, 295 present calls, max score 99.36.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 63.2240 / max 5828.7292, expressed in 1808 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
75818	61.8381	1808
75814	0.4433	129
75815	0.3975	176
75817	0.3182	145
75816	0.2269	113

Top tissues by expression

295 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
lower lobe of lung	UBERON:0008949	99.36	gold quality
epithelium of nasopharynx	UBERON:0001951	99.25	gold quality
right lung	UBERON:0002167	99.20	gold quality
jejunal mucosa	UBERON:0000399	98.79	gold quality
penis	UBERON:0000989	98.78	gold quality
pericardium	UBERON:0002407	98.78	gold quality
palpebral conjunctiva	UBERON:0001812	98.66	gold quality
skin of hip	UBERON:0001554	98.63	gold quality
monocyte	CL:0000576	98.62	gold quality
mononuclear cell	CL:0000842	98.59	gold quality
upper lobe of lung	UBERON:0008948	98.57	gold quality
leukocyte	CL:0000738	98.55	gold quality
upper lobe of left lung	UBERON:0008952	98.51	gold quality
vermiform appendix	UBERON:0001154	98.46	gold quality
upper leg skin	UBERON:0004262	98.46	gold quality
mammary duct	UBERON:0001765	98.45	gold quality
inferior vagus X ganglion	UBERON:0005363	98.36	gold quality
lymph node	UBERON:0000029	98.30	gold quality
spleen	UBERON:0002106	98.25	gold quality
blood	UBERON:0000178	98.23	gold quality
synovial joint	UBERON:0002217	98.23	gold quality
urethra	UBERON:0000057	98.16	gold quality
lung	UBERON:0002048	98.14	gold quality
caecum	UBERON:0001153	98.06	gold quality
subthalamic nucleus	UBERON:0001906	98.02	gold quality
epithelium of mammary gland	UBERON:0003244	97.97	gold quality
heart right ventricle	UBERON:0002080	97.96	gold quality
omental fat pad	UBERON:0010414	97.96	gold quality
peritoneum	UBERON:0002358	97.95	gold quality
choroid plexus epithelium	UBERON:0003911	97.94	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 5.

Experiment	Marker?	Max mean expression
E-MTAB-9388	yes	1391.06
E-HCAD-1	yes	49.91
E-MTAB-8410	yes	14.42
E-MTAB-10042	yes	8.04
E-ANND-3	no	0.00

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

1 targets.

Target	Regulation
BACE1	Activation

Upstream regulators (CollecTRI, top): EGR1, EGR3, GLI2, IRF1, IRF2, RARA, SP1, STAT1, TFAP2A

miRNA regulators (miRDB)

26 targeting IFNGR1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-548AR-3P	99.85	71.26	3889
HSA-MIR-548AZ-3P	99.82	70.56	3549
HSA-MIR-548BC	99.82	70.61	3524
HSA-MIR-548E-3P	99.82	70.59	3514
HSA-MIR-548F-3P	99.82	70.59	3540
HSA-MIR-4659A-3P	99.80	72.62	4248
HSA-MIR-4659B-3P	99.80	72.62	4248
HSA-MIR-548A-3P	99.76	70.58	3524
HSA-MIR-5580-3P	99.70	69.41	2052
HSA-MIR-33A-3P	99.70	70.27	3362
HSA-MIR-7154-5P	99.69	70.52	1900
HSA-MIR-3609	99.52	69.89	2587
HSA-MIR-548AH-5P	99.52	69.73	2626
HSA-MIR-183-3P	99.41	69.41	1598
HSA-MIR-3675-3P	99.09	67.70	968
HSA-MIR-12135	98.99	70.26	1814
HSA-MIR-8060	98.61	66.93	1187
HSA-MIR-499B-5P	98.35	68.39	988
HSA-MIR-216B-5P	97.16	66.76	1126
HSA-MIR-1243	97.07	65.44	719
HSA-MIR-3914	94.91	65.77	643
HSA-MIR-4315	94.78	64.86	112

Literature-anchored findings (GeneRIF, showing 40)

• IL-12R beta 1- and IFN-gamma R1 signals co-ordinately regulate IFN-gamma production, but only IL-12 negatively controls IL-4 production. IL-12 and IFN-gamma signals are each sufficient for IFN-gamma production but both are needed for optimal production. (PMID:11857344)
• partial IFNGR1 mutations in Japanese patients with BCG osteomyelitis (PMID:11865431)
• IFNGR1 gene promoter polymorphisms may be assocaited with susceptibility to cerebral malaria (PMID:12023780)
• Mutations in interferon-gamma receptor 1. (PMID:12027427)
• This study identified a further role of IFN-gamma on IL-4 responses, including reduced IL-4R surface expression by human monocytes. (PMID:12034035)
• Lipid microdomains are required sites for the selective endocytosis and nuclear translocation of IFN-gamma receptor-1. (PMID:12165521)
• Partial deficiency of IFN-gamma receptor 1 results in abrogation of IFN-gamma-induced killing of Salmonella typhimurium and Toxoplasma gondii due to IFN-gamma unresponsiveness of patients’ cells of the monocyte/macrophage lineage. (PMID:12244188)
• FRET was used to demonstrate that the IFNGR chains were preassembled on the cell membrane. (PMID:12438563)
• suppressed by 2- to 3-fold in B-cell chronic lymphocytic leukemia cells, which is expected to increase CLL cell survival (PMID:12454749)
• Genome analysis identified polymorphism in the human interferon gamma receptor affecting Helicobacter pylori infection. (PMID:12516030)
• MHC Class II proteins, interferon-alpha, interferon-gamma receptor and the capacity to present antigen may be crucial in HIV-associated nephropathy pathogenesis. (PMID:12543882)
• Mutations have no association with the susceptibility to lepromatous leprosy in the Korean population. (PMID:12743658)
• Unidentified allelic variations in the IFNGR1 gene might elevate or decrease the risk in the Croatian population, as a part of the multigenic predisposition to tuberculosis. (PMID:12753505)
• In this study, although IFN-gamma production in the allergic patients with L467P was equivalent to that in the non-allergic subjects, their serum IgE levels were high and they had allergic diseases (PMID:12851715)
• IFN-gamma receptor deficiency alters the epitope hierarchy of the pool of lymphocytic choriomeningitis virus-specific memory CD8 T cells without significantly affecting the immunodominance of the primary CD8 T cell response in an acute infection. (PMID:14734726)
• disease susceptibility in Schistosoma mansoni infection to hepatic fibrosis is linked to a SNP in the interferon gamma receptor locus (P=0.000001). (PMID:15756299)
• The IFN-GammaR2 Arg64/Arg64 genotype does not determine susceptibility to SLE in Chinese people, and the combination of IFN-Gamma R2 Arg64/Arg64 genotype and IFN-Gamma R1 Val14/Val14 genotype does not, either. (PMID:15952126)
• IFNG T874A, IFNGR1 C-56T and IFNGR2 A839G genotypes were not associated with the incidence of angiographic and clinical restenosis (P>0.23). (PMID:16115485)
• The relationship between polymorphisms at IFNGR1 and susceptibility to pulmonary tuberculosis is reported in Iranian patients. (PMID:16233916)
• IFNGR1 does not contribute to susceptibility to rheumatoid arthritis in Caucasians, although a single nucleotide polymorphisms exist in this disease. (PMID:16563189)
• Novel tuberculosis association was found with the 56CC genotype of the IFNGR1 promotor. (PMID:16690980)
• Interferon (IFN)-gamma and its receptor subunit IFNGR1 bind to the IFN-gamma-activated sequence (GAS) response element in the promoter region of IFN-gamma-activated genes. This binding results in enhanced activation of IFN-gamma-induced genes. (PMID:16785527)
• no statistically significant association with susceptibility to persistent HBV infection was observed with the IFN-gamma, IFNGR-1 and 2, and IRF-1 gene polymorphisms under the codominant, dominant, and recessive models (PMID:16944293)
• Infection of HEK 293 cells with C. psittaci increased IFN-gammaR expression only in cells expressing either TLR2 or TLR4 and the adaptor protein MD-2. (PMID:17030574)
• The results suggest a complex pattern of haplotypic variation at the IFNGR1 promoter locus associated with post-kala-azar dermal leishmanaisis susceptibility. (PMID:17136124)
• The K3 and K5 proteins of Kaposi’s sarcoma-associated herpesvirus (KSHV) both specifically target IFN-gammaR1 and induce its ubiquitination, endocytosis, and degradation. (PMID:17166914)
• The -56T allele in the IFNGR1 promoter results in higher IFNGR1 transcriptional activity and represents a genetic risk factor for atopic cataracts. (PMID:17251453)
• expression downregulated by Mycobacterium tuberculosis in human cells as immune evasion mechanism. (PMID:17339358)
• analyzed candidate genes related to TNFalpha regulation and found that interleukin (IL)-10, interferon-gamma receptor 1 (IFNGR1), and TNFalpha receptor 1 (TNFR1) genes were linked and associated to both tuberculosis and TNFalpha (PMID:17431682)
• A deletion in this receptor produces a truncated form of IFNgammaR1, which has a dominant-negative effect on IFNgamma signal transduction through altered receptor stability. (PMID:17513528)
• Variation in transcriptional activity of genes encoding INF-gamma receptor subunits may affect function of microvasculature and thereby participate in the pathology of cardiac syndrome X (PMID:17546485)
• IFNGR polymorphisms (Val14Met and Gln64Arg) are protective in systemic lupus erythematosus in Chinese patients (PMID:17618444)
• expressed IFNgamma and IFNgamma-Ralpha together with the nuclear localization of IFNgamma-Rbeta, could be a tumoral cell response (PMID:17697357)
• The IFN-gamma receptor 1 gene polymorphism does not appear to be responsible for host susceptibility to pulmonary tuberculosis in the Korean population. (PMID:17986123)
• Frequent mutations in microsatellite-instable (MSI-H) tumours and cell lines of a conserved A14 repeat within the 3’-untranslated region of the interferon-gamma receptor 1 gene (IFNGR1). (PMID:18414508)
• The polymorphisms in the IFNG and IFNGR1 genes were studied with the aim of clarifying the relationships among these polymorphisms, penicillin allergy and anti-penicillin antibodies. (PMID:18548239)
• Regulation of the IFN-gamma R and its signaling response in human endometrial stromal cells during decidualization. (PMID:18555234)
• results indicate that the IFNGR1 -56C/T polymorphism is a relevant host susceptibility factor for Gastric Carcinoma development. (PMID:18593809)
• with progression of HIV-1 infection, interferon-gamma production declines whereas expression of interferon-gamma receptors (R1 and R2) increases (PMID:18620489)
• allele (CA)(25)of the interferon gamma receptor 1 gene appeared to be susceptible to TB, while the allele (CA)(26) was protective towards TB (PMID:18702743)

Cross-species orthologs

10 orthologs

Organism	Symbol	Gene ID
danio_rerio	il22ra2	ENSDARG00000039439
danio_rerio	ifngr2	ENSDARG00000067795
danio_rerio	ifngr1l	ENSDARG00000074488
danio_rerio	ifngr1	ENSDARG00000074771
danio_rerio	crfb16	ENSDARG00000075181
danio_rerio	ifnlr1	ENSDARG00000087131
danio_rerio	crfb15	ENSDARG00000099342
danio_rerio	il10ra	ENSDARG00000100383
mus_musculus	Ifngr1	ENSMUSG00000020009
rattus_norvegicus	Ifngr1	ENSRNOG00000012074

Paralogs (11): IL20RA (ENSG00000016402), IL10RA (ENSG00000110324), F3 (ENSG00000117525), IFNAR1 (ENSG00000142166), IL22RA1 (ENSG00000142677), IFNAR2 (ENSG00000159110), IFNGR2 (ENSG00000159128), IL22RA2 (ENSG00000164485), IL20RB (ENSG00000174564), IFNLR1 (ENSG00000185436), IL10RB (ENSG00000243646)

Protein

Protein identifiers

Interferon gamma receptor 1 — P15260 (reviewed: P15260)

Alternative names: CDw119, Interferon gamma receptor alpha-chain

All UniProt accessions (13): A0A0S2Z3Y2, A0A2R8Y4U4, A0A2R8Y792, A0A2R8Y7R1, A0A2R8YFL3, A0A8Q3SIW7, P15260, A0A8Q3SJ27, A0A8Q3SJH3, A0A8Q3WLG6, A0A8Q3WLI2, A0A8Q3WLI6, Q5TFC9

UniProt curated annotations — full annotation on UniProt →

Function. Receptor subunit for interferon gamma/INFG that plays crucial roles in antimicrobial, antiviral, and antitumor responses by activating effector immune cells and enhancing antigen presentation. Associates with transmembrane accessory factor IFNGR2 to form a functional receptor. Upon ligand binding, the intracellular domain of IFNGR1 opens out to allow association of downstream signaling components JAK1 and JAK2. In turn, activated JAK1 phosphorylates IFNGR1 to form a docking site for STAT1. Subsequent phosphorylation of STAT1 leads to dimerization, translocation to the nucleus, and stimulation of target gene transcription. STAT3 can also be activated in a similar manner although activation seems weaker. IFNGR1 intracellular domain phosphorylation also provides a docking site for SOCS1 that regulates the JAK-STAT pathway by competing with STAT1 binding to IFNGR1.

Subunit / interactions. Monomer. Heterodimer with IFNGR2, to form the IFNG receptor complex. Interacts with JAK1. Interacts (when phosphorylated) with STAT1. Interacts with SOCS1.

Subcellular location. Cell membrane.

Post-translational modifications. Phosphorylated at Ser/Thr residues. Phosphorylation of Tyr-457 is required for IFNG receptor signal transduction. Influenza virus infection leads to phosphorylation in a CSNK1A1-dependent manner. Ubiquitinated after phosphorylation in a CSNK1A1-dependent manner, leading to the lysosome-dependent degradation. Proteasomally degraded through ‘Lys-48’-mediated ubiquitination. Ubiquitination is necessary for efficient IFNGR1 signaling.

Disease relevance. Immunodeficiency 27A (IMD27A) [MIM:209950] A form of Mendelian susceptibility to mycobacterial disease, a rare condition caused by impairment of interferon-gamma mediated immunity. It is characterized by predisposition to illness caused by moderately virulent mycobacterial species, such as Bacillus Calmette-Guerin (BCG) vaccine, environmental non-tuberculous mycobacteria, and by the more virulent Mycobacterium tuberculosis. Other microorganisms rarely cause severe clinical disease in individuals with susceptibility to mycobacterial infections, with the exception of Salmonella which infects less than 50% of these individuals. Clinical outcome severity depends on the degree of impairment of interferon-gamma mediated immunity. Some patients die of overwhelming mycobacterial disease with lepromatous-like lesions in early childhood, whereas others develop, later in life, disseminated but curable infections with tuberculoid granulomas. The disease is caused by variants affecting the gene represented in this entry. Immunodeficiency 27B (IMD27B) [MIM:615978] A form of Mendelian susceptibility to mycobacterial disease, a rare condition caused by impairment of interferon-gamma mediated immunity. It is characterized by predisposition to illness caused by moderately virulent mycobacterial species, such as Bacillus Calmette-Guerin (BCG) vaccine, environmental non-tuberculous mycobacteria, and by the more virulent Mycobacterium tuberculosis. Other microorganisms rarely cause severe clinical disease in individuals with susceptibility to mycobacterial infections, with the exception of Salmonella which infects less than 50% of these individuals. Clinical outcome severity depends on the degree of impairment of interferon-gamma mediated immunity. Some patients die of overwhelming mycobacterial disease with lepromatous-like lesions in early childhood, whereas others develop, later in life, disseminated but curable infections with tuberculoid granulomas. IMD27B commonly presents with recurrent, moderately severe infections with environmental mycobacteria or BCG. Salmonellosis is present in about 5% of patients. The disease is caused by variants affecting the gene represented in this entry.

Polymorphism. A genetic variation in the IFNGR1 gene is associated with susceptibility to Helicobacter pylori infection [MIM:600263].

Similarity. Belongs to the type II cytokine receptor family.

Isoforms (2)

UniProt ID	Names	Canonical?
P15260-1	1	yes
P15260-2	2

RefSeq proteins (3): NP_000407, NP_001350455, NP_001350456 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003961	FN3_dom	Domain
IPR008355	Interferon_gamma_rcpt_asu	Family
IPR013783	Ig-like_fold	Homologous_superfamily
IPR021126	IFN_gamma_rc_D2_pox/mammal	Domain
IPR036116	FN3_sf	Homologous_superfamily
IPR050650

Pfam: PF01108, PF07140, PF20634

UniProt features (75 total): sequence variant 24, strand 14, compositionally biased region 5, modified residue 5, glycosylation site 5, disulfide bond 4, mutagenesis site 4, splice variant 3, helix 3, topological domain 2, turn 2, signal peptide 1, chain 1, transmembrane region 1, region of interest 1

Structure

Experimental structures (PDB)

5 structures.

PDB	Method	Resolution (Å)
1FYH	X-RAY DIFFRACTION	2.04
1JRH	X-RAY DIFFRACTION	2.8
1FG9	X-RAY DIFFRACTION	2.9
6E3K	X-RAY DIFFRACTION	3.25
6E3L	X-RAY DIFFRACTION	3.8

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P15260-F1	66.67	0.37

Antibody-complex structures (SAbDab): 1 — 1JRH

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (5): 369, 372, 378, 403, 457

Disulfide bonds (4): 77–85, 122–167, 195–200, 214–235

Glycosylation sites (5): 34, 79, 86, 179, 240

Mutagenesis-validated functional residues (4):

Position	Phenotype
61	loss of function in the interferon-gamma-mediated signaling pathway.
277	strong decreased level of ubiquitination; when associated with r-279 and r-285.
279	strong decreased level of ubiquitination; when associated with r-277 and r-285.
285	strong decreased level of ubiquitination; when associated with r-277 and r-279.

Function

Pathways and Gene Ontology

Reactome pathways

11 pathways

ID	Pathway
R-HSA-877300	Interferon gamma signaling
R-HSA-877312	Regulation of IFNG signaling
R-HSA-9679191	Potential therapeutics for SARS
R-HSA-9732724	IFNG signaling activates MAPKs
R-HSA-1280215	Cytokine Signaling in Immune system
R-HSA-1643685	Disease
R-HSA-168256	Immune System
R-HSA-5663205	Infectious disease
R-HSA-913531	Interferon Signaling
R-HSA-9679506	SARS-CoV Infections
R-HSA-9824446	Viral Infection Pathways

MSigDB gene sets: 641 (showing top): PID_SHP2_PATHWAY, GSE45365_NK_CELL_VS_CD8A_DC_MCMV_INFECTION_UP, GSE45365_NK_CELL_VS_CD8A_DC_UP, GOBP_CELLULAR_RESPONSE_TO_VIRUS, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, GOBP_INFLAMMATORY_RESPONSE, KAAB_FAILED_HEART_ATRIUM_DN, GOBP_RESPONSE_TO_PEPTIDE, GOBP_POSITIVE_REGULATION_OF_AMIDE_METABOLIC_PROCESS, MODULE_45, MODULE_64, GOBP_GLIAL_CELL_DEVELOPMENT, KYNG_DNA_DAMAGE_DN, GOBP_NEUROGENESIS, GOBP_POSITIVE_REGULATION_OF_CYTOKINE_PRODUCTION

GO Biological Process (16): microglial cell activation (GO:0001774), signal transduction (GO:0007165), response to virus (GO:0009615), positive regulation of gene expression (GO:0010628), cytokine-mediated signaling pathway (GO:0019221), positive regulation of tumor necrosis factor production (GO:0032760), type III interferon-mediated signaling pathway (GO:0038196), astrocyte activation (GO:0048143), defense response to virus (GO:0051607), type II interferon-mediated signaling pathway (GO:0060333), cellular response to virus (GO:0098586), negative regulation of amyloid-beta clearance (GO:1900222), positive regulation of amyloid-beta formation (GO:1902004), immune system process (GO:0002376), cell surface receptor signaling pathway via JAK-STAT (GO:0007259), defense response to other organism (GO:0098542)

GO Molecular Function (4): cytokine receptor activity (GO:0004896), type II interferon receptor activity (GO:0004906), cytokine binding (GO:0019955), protein binding (GO:0005515)

GO Cellular Component (2): plasma membrane (GO:0005886), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-8 pathways:

Category	Pathways
Interferon gamma signaling	2
Interferon Signaling	1
SARS-CoV Infections	1
Immune System	1
Disease	1
Cytokine Signaling in Immune system	1
Viral Infection Pathways	1
Infectious disease	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
glial cell activation	2
response to other organism	2
interferon-mediated signaling pathway	2
defense response	2
response to virus	2
leukocyte activation involved in inflammatory response	1
macrophage activation	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
gene expression	1
regulation of gene expression	1
positive regulation of macromolecule biosynthetic process	1
cell surface receptor signaling pathway	1
cellular response to cytokine stimulus	1
tumor necrosis factor production	1
regulation of tumor necrosis factor production	1
positive regulation of tumor necrosis factor superfamily cytokine production	1
cellular response to type III interferon	1
astrocyte development	1
cellular response to type II interferon	1
negative regulation of multicellular organismal process	1
amyloid-beta clearance	1
regulation of amyloid-beta clearance	1
amyloid-beta formation	1
regulation of amyloid-beta formation	1
positive regulation of amyloid precursor protein catabolic process	1
biological_process	1
cell surface receptor signaling pathway via STAT	1
transmembrane signaling receptor activity	1
cytokine-mediated signaling pathway	1
cytokine binding	1
immune receptor activity	1
interferon receptor activity	1
type II interferon binding	1
type II interferon-mediated signaling pathway	1
protein binding	1
binding	1

Protein interactions and networks

STRING

2085 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
IFNGR1	IFNGR2	P38484	999
IFNGR1	IFNG	P01579	998
IFNGR1	JAK1	P23458	997
IFNGR1	JAK2	O60674	993
IFNGR1	STAT1	P42224	977
IFNGR1	SOCS1	O15524	934
IFNGR1	IFNAR2	P48551	918
IFNGR1	IFNA13	P01562	897
IFNGR1	IFNAR1	P17181	863
IFNGR1	IL12RB1	P42701	859
IFNGR1	STAT3	P40763	821
IFNGR1	IL10RB	Q08334	806
IFNGR1	IFNB1	P01574	790
IFNGR1	IL6	P05231	788
IFNGR1	TNFRSF1A	P19438	786

IntAct

121 interactions, top by confidence:

A	B	Type	Score
IFNGR1	IFNG	psi-mi:“MI:0407”(direct interaction)	0.880
IFNG	IFNGR1	psi-mi:“MI:0407”(direct interaction)	0.880
IFNG	IFNGR1	psi-mi:“MI:0914”(association)	0.880
IFNG	IFNGR1	psi-mi:“MI:0915”(physical association)	0.880
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
STAT1	IFNGR1	psi-mi:“MI:0914”(association)	0.690
IFNGR1	STAT1	psi-mi:“MI:0914”(association)	0.690
IFNGR1	RUSF1	psi-mi:“MI:0915”(physical association)	0.670
PDGFRB	PIK3R2	psi-mi:“MI:0914”(association)	0.610
IFNGR1	CD93	psi-mi:“MI:0407”(direct interaction)	0.600
CD93	IFNGR1	psi-mi:“MI:0407”(direct interaction)	0.600
CD93	IFNGR1	psi-mi:“MI:0403”(colocalization)	0.600
IFNGR1	AQP6	psi-mi:“MI:0915”(physical association)	0.560
IFNGR1	NINJ2	psi-mi:“MI:0915”(physical association)	0.560
IFNGR1	TMEM237	psi-mi:“MI:0915”(physical association)	0.560
IFNGR1	TMEM100	psi-mi:“MI:0915”(physical association)	0.560
IFNGR1	SLC9A6	psi-mi:“MI:0915”(physical association)	0.560
IFNGR1	STIM1	psi-mi:“MI:0915”(physical association)	0.560
TMEM30B	KLRG2	psi-mi:“MI:0914”(association)	0.530
ADGRG5	KLRG2	psi-mi:“MI:0914”(association)	0.530
SLC9A6	MAP1LC3B2	psi-mi:“MI:0914”(association)	0.530
FBXO2	TMEM131L	psi-mi:“MI:0914”(association)	0.530

BioGRID (147): IFNGR1 (Affinity Capture-RNA), IFNGR1 (Affinity Capture-RNA), IFNGR1 (Affinity Capture-RNA), IFNGR1 (Affinity Capture-MS), IFNGR1 (Affinity Capture-MS), IFNGR1 (Affinity Capture-MS), MAD2L2 (Affinity Capture-MS), BMPR1A (Affinity Capture-MS), NDFIP1 (Affinity Capture-MS), CD320 (Affinity Capture-MS), RHOU (Affinity Capture-MS), IFNGR1 (Affinity Capture-MS), IFNGR1 (Affinity Capture-MS), SRC (Affinity Capture-MS), IFNGR1 (Affinity Capture-MS)

ESM2 similar proteins: A0MSX9, A5HJM1, C8AW46, C8AW47, K9JA28, O02671, O35664, O46561, O70458, P05710, P14787, P15260, P15261, P16297, P16471, P16871, P16872, P16882, P26896, P48356, P48357, P48551, P97378, Q08501, Q13651, Q28172, Q28235, Q38IC7, Q38J85, Q3SYS8, Q4W815, Q5VWK5, Q61727, Q62959, Q63257, Q65Z14, Q6JTA8, Q6PHB0, Q80VH0, Q80XZ4

Diamond homologs: P15260, P15261, Q9UHF4, K9JA28, Q04790, Q08334, Q28589, Q6PHB0, Q80XF5, Q969J5

SIGNOR signaling

14 interactions.

A	Effect	B	Mechanism
IFNGR1	up-regulates	JAK1	binding
IFNGR1	up-regulates	JAK2	binding
SOCS1	down-regulates	IFNGR1	binding
IFNG	“up-regulates activity”	IFNGR1	binding
IFNGR1	“form complex”	IFNGR2/INFGR1	binding
JAK1	“up-regulates activity”	IFNGR1	phosphorylation
JAK2	“up-regulates activity”	IFNGR1	phosphorylation
IFNGR1	“up-regulates activity”	JAK2	binding
GSK3B	“up-regulates quantity by stabilization”	IFNGR1	phosphorylation
JAK1	up-regulates	IFNGR1	phosphorylation
IFNG	up-regulates	IFNGR1	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 99 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Signaling by phosphorylated juxtamembrane, extracellular and kinase domain KIT mutants	6	45.1×	6e-07
Downstream signal transduction	7	38.6×	2e-07
NCAM signaling for neurite out-growth	6	23.6×	1e-05
Signaling by SCF-KIT	6	21.6×	2e-05
Signaling by FGFR1 in disease	5	21.2×	1e-04
Cardiac conduction	5	7.9×	3e-03
Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell	6	7.6×	1e-03
RAF/MAP kinase cascade	7	6.2×	1e-03

Disease & clinical

Cancer significance

Clinical variants and AI predictions

ClinVar

445 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	27
Likely pathogenic	9
Uncertain significance	245
Likely benign	107
Benign	20

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1284946	NM_000416.3(IFNGR1):c.373+1G>T	Pathogenic
1450358	NC_000006.11:g.(?137143759)(138202456_?)del	Pathogenic
1451799	NM_000416.3(IFNGR1):c.805del (p.Tyr269fs)	Pathogenic
1454131	NM_000416.3(IFNGR1):c.781del (p.Ser262fs)	Pathogenic
17942	NM_000416.3(IFNGR1):c.446C>A (p.Ser149Ter)	Pathogenic
17943	NM_000416.3(IFNGR1):c.131del (p.Pro44fs)	Pathogenic
17945	NM_000416.3(IFNGR1):c.104_107dup (p.Ile37fs)	Pathogenic
17946	NM_000416.3(IFNGR1):c.200+1G>A	Pathogenic
17947	NM_000416.3(IFNGR1):c.819_822del (p.Asn274fs)	Pathogenic
17948	NM_000416.3(IFNGR1):c.295_306del (p.Trp99_Val102del)	Pathogenic
17949	NM_000416.3(IFNGR1):c.230G>A (p.Cys77Tyr)	Pathogenic
17950	NM_000416.3(IFNGR1):c.182T>A (p.Val61Glu)	Pathogenic
17952	NM_000416.3(IFNGR1):c.819del (p.Asn274fs)	Pathogenic
17954	NM_000416.3(IFNGR1):c.794del (p.Phe265fs)	Pathogenic
2082580	NM_000416.3(IFNGR1):c.643_644del (p.Val215fs)	Pathogenic
208588	NM_000416.3(IFNGR1):c.523del (p.Tyr175fs)	Pathogenic
2734959	NM_000416.3(IFNGR1):c.672G>A (p.Trp224Ter)	Pathogenic
29607	NM_000416.3(IFNGR1):c.2T>A (p.Met1Lys)	Pathogenic
3026973	NM_000416.3(IFNGR1):c.218G>A (p.Trp73Ter)	Pathogenic
3893292	NM_000416.3(IFNGR1):c.817del (p.Ile273fs)	Pathogenic
4292897	NM_000416.3(IFNGR1):c.573_574dup (p.Glu192fs)	Pathogenic
462774	NM_000416.3(IFNGR1):c.373+2T>C	Pathogenic
4720494	NM_000416.3(IFNGR1):c.588_592del (p.Glu197fs)	Pathogenic
4725529	NM_000416.3(IFNGR1):c.811A>T (p.Lys271Ter)	Pathogenic
652535	NM_000416.3(IFNGR1):c.641_644delinsCC (p.Cys214fs)	Pathogenic
802277	NM_000416.3(IFNGR1):c.86-1_93del	Pathogenic
830065	NM_000416.3(IFNGR1):c.476del (p.Val159fs)	Pathogenic
1488138	NM_000416.3(IFNGR1):c.733+2T>C	Likely pathogenic
2440869	NM_000416.3(IFNGR1):c.585T>A (p.Cys195Ter)	Likely pathogenic
2585538	NM_000416.3(IFNGR1):c.85+1G>T	Likely pathogenic

SpliceAI

1245 predictions. Top by Δscore:

Variant	Effect	Δscore
6:137203496:TACC:T	donor_loss	1.0000
6:137203497:ACCT:A	donor_loss	1.0000
6:137203498:C:CG	donor_loss	1.0000
6:137203684:ATC:A	acceptor_loss	1.0000
6:137203686:C:CC	acceptor_gain	1.0000
6:137204329:TA:T	donor_loss	1.0000
6:137204330:A:AC	donor_gain	1.0000
6:137204331:C:CC	donor_gain	1.0000
6:137204331:CCT:C	donor_gain	1.0000
6:137204331:CCTCA:C	donor_gain	1.0000
6:137204338:T:TA	donor_gain	1.0000
6:137204405:T:TA	donor_gain	1.0000
6:137204500:TTTTC:T	acceptor_gain	1.0000
6:137204501:TTTC:T	acceptor_gain	1.0000
6:137204502:TTC:T	acceptor_gain	1.0000
6:137204502:TTCC:T	acceptor_loss	1.0000
6:137204503:TC:T	acceptor_gain	1.0000
6:137204504:CC:C	acceptor_gain	1.0000
6:137204505:C:CC	acceptor_gain	1.0000
6:137206128:CTACT:C	donor_loss	1.0000
6:137206130:ACT:A	donor_loss	1.0000
6:137206131:CT:C	donor_loss	1.0000
6:137206132:TCA:T	donor_loss	1.0000
6:137206133:CA:C	donor_loss	1.0000
6:137206134:A:AC	donor_gain	1.0000
6:137206134:A:C	donor_loss	1.0000
6:137206134:AC:A	donor_gain	1.0000
6:137206135:C:CC	donor_gain	1.0000
6:137206135:C:CG	donor_loss	1.0000
6:137206135:CC:C	donor_gain	1.0000

AlphaMissense

3210 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:137207019:C:A	W48C	0.999
6:137207019:C:G	W48C	0.999
6:137206986:A:C	F59L	0.998
6:137206986:A:T	F59L	0.998
6:137206988:A:G	F59L	0.998
6:137206204:A:T	V102D	0.997
6:137206987:A:G	F59S	0.997
6:137206290:C:A	W73C	0.996
6:137206290:C:G	W73C	0.996
6:137207021:A:G	W48R	0.996
6:137207021:A:T	W48R	0.996
6:137206255:C:G	C85S	0.995
6:137206256:A:T	C85S	0.995
6:137206987:A:C	F59C	0.995
6:137206152:A:C	F119L	0.992
6:137206152:A:T	F119L	0.992
6:137206154:A:G	F119L	0.992
6:137206178:A:G	S111P	0.992
6:137206199:C:G	A104P	0.992
6:137206254:A:C	C85W	0.992
6:137206292:A:G	W73R	0.992
6:137206292:A:T	W73R	0.992
6:137206212:C:A	W99C	0.991
6:137206212:C:G	W99C	0.991
6:137206255:C:T	C85Y	0.991
6:137207020:C:G	W48S	0.991
6:137207068:G:T	P32Q	0.991
6:137206256:A:G	C85R	0.990
6:137206153:A:C	F119C	0.988
6:137206278:G:C	C77W	0.988

dbSNP variants (sampled 300 via entrez): RS1000204323 (6:137206534 C>A), RS1000373220 (6:137199286 A>G), RS1000380710 (6:137199288 ATG>A), RS1000508416 (6:137205678 T>A), RS1000708913 (6:137197923 T>C), RS1000788286 (6:137212986 A>C,G), RS1000993140 (6:137211658 T>C), RS1001377805 (6:137201302 T>A,C), RS1001415157 (6:137218438 C>A,T), RS1001495470 (6:137200819 G>A), RS1001651889 (6:137207817 T>C), RS1001690637 (6:137211912 A>G), RS1001825002 (6:137214584 T>C), RS1001825823 (6:137199107 T>G), RS1002123914 (6:137207585 C>T)

Disease associations

OMIM: gene MIM:107470 | disease phenotypes: MIM:209950, MIM:600263, MIM:615978, MIM:610424

GenCC curated gene-disease

Disease	Classification	Inheritance
immunodeficiency 27A	Definitive	Autosomal recessive
autosomal dominant mendelian susceptibility to mycobacterial diseases due to partial IFNgammaR1 deficiency	Definitive	Autosomal dominant
autosomal recessive Mendelian susceptibility to mycobacterial diseases due to partial IFNgammaR1 deficiency	Supportive	Autosomal recessive
Mendelian susceptibility to mycobacterial diseases due to complete IFNgammaR1 deficiency	Supportive	Autosomal recessive

Mondo (6): immunodeficiency 27A (MONDO:0008856), Helicobacter pylori infection, susceptibility to (MONDO:0010853), autosomal dominant mendelian susceptibility to mycobacterial diseases due to partial IFNgammaR1 deficiency (MONDO:0014429), hepatitis B virus, susceptibility to (MONDO:0012488), autosomal recessive Mendelian susceptibility to mycobacterial diseases due to partial IFNgammaR1 deficiency (MONDO:0017901), Mendelian susceptibility to mycobacterial diseases due to complete IFNgammaR1 deficiency (MONDO:0020530)

Orphanet (3): Autosomal recessive mendelian susceptibility to mycobacterial diseases due to partial IFNgammaR1 deficiency (Orphanet:319569), Mendelian susceptibility to mycobacterial diseases due to complete IFNgammaR1 deficiency (Orphanet:99898), Autosomal dominant mendelian susceptibility to mycobacterial diseases due to partial IFNgammaR1 deficiency (Orphanet:319581)

HPO phenotypes

108 total (30 of 108 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000031	Epididymitis
HP:0000083	Renal insufficiency
HP:0000099	Glomerulonephritis
HP:0000155	Oral ulcer
HP:0000488	Retinopathy
HP:0000518	Cataract
HP:0000613	Photophobia
HP:0000618	Blindness
HP:0000708	Atypical behavior
HP:0000737	Irritability
HP:0001061	Acne
HP:0001097	Keratoconjunctivitis sicca
HP:0001250	Seizure
HP:0001251	Ataxia
HP:0001269	Hemiparesis
HP:0001287	Meningitis
HP:0001288	Gait disturbance
HP:0001289	Confusion
HP:0001347	Hyperreflexia
HP:0001369	Arthritis
HP:0001433	Hepatosplenomegaly
HP:0001482	Subcutaneous nodule
HP:0001637	Abnormal myocardium morphology
HP:0001653	Mitral regurgitation
HP:0001658	Myocardial infarction
HP:0001659	Aortic regurgitation
HP:0001701	Pericarditis
HP:0001733	Pancreatitis

GWAS associations

9 associations (top):

Study	Trait	p-value
GCST002783_377	Body mass index	4.000000e-08
GCST002783_51	Body mass index	2.000000e-06
GCST002783_535	Body mass index	2.000000e-07
GCST003075_10	Cognitive decline rate in late mild cognitive impairment	2.000000e-10
GCST003075_127	Cognitive decline rate in late mild cognitive impairment	2.000000e-10
GCST004495_113	BMI (adjusted for smoking behaviour)	5.000000e-06
GCST004497_110	Body mass index (joint analysis main effects and smoking interaction)	5.000000e-06
GCST008891_7	Cognitive performance (processing speed)	1.000000e-06
GCST012073_5	Behcet’s disease	2.000000e-09

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index
EFO:0007710	cognitive decline measurement
EFO:0004318	smoking behavior
EFO:0004363	information processing speed

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C535530	Interferon gamma, receptor 1, deficiency (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2364171 (PROTEIN COMPLEX)

Clinical evidence (CIViC)

Drug × variant × indication: 1 predictive associations from 1 curated evidence items.

Variant	Therapy	Indication	Effect	Level	CIViC
IFNGR1 Loss	Ipilimumab	Melanoma	Resistance	CIViC D	EID12142

PharmGKB: 1 entry (VIP=true, CPIC=false)

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs2234711	IFNGR1		0.00	0

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: catalytic receptor — Interferon receptor family

Binding affinities (BindingDB)

2 measured of 2 human assays (2 total across all organisms); most potent 2 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
2-(2-(2-(3-((4-((4-(3-(5-(tert-Butyl)-2-methoxy-3-(methylsulfonamido)phenyl)ureido)-naphthalen-1-yl)oxy)pyrimidin-2-yl)amino)-5-methoxyphenoxy)ethoxy)ethoxy)acetic acid	IC50	23 nM	US-10072034: Kinase inhibitors
2-(2-(2-(3-((4-((4-(3-(5-(tert-Butyl)-2-methoxy)-3-(methylsulfonamido)phenyl)ureido-naphthalen-1-yl)oxy)pyridin-2-yl)amino-5-methoxyphenoxy)ethoxy)ethoxy)acetic acid	IC50	23 nM	US-10072034: Kinase inhibitors

CTD chemical–gene interactions

80 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects expression, decreases expression, affects cotreatment, increases abundance, increases expression	5
bisphenol A	decreases expression, increases methylation	2
Acetaminophen	increases expression, decreases expression	2
Air Pollutants	affects cotreatment, increases abundance, increases oxidation, decreases expression	2
Arsenic	affects cotreatment, increases abundance, increases expression	2
Ozone	affects cotreatment, increases oxidation, increases abundance, increases expression	2
Progesterone	increases expression, decreases expression	2
Tretinoin	increases expression	2
Valproic Acid	decreases expression, decreases methylation	2
Aflatoxin B1	affects expression, increases expression	2
Antirheumatic Agents	increases expression, decreases expression	2
GSK-J4	increases expression	1
dicrotophos	decreases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
deoxynivalenol	decreases reaction, increases expression	1
lead acetate	decreases expression	1
2,2’-methylenebis(4-methyl-6-tert-butylphenol)	affects expression, affects response to substance	1
titanium dioxide	increases expression	1
nickel chloride	increases expression	1
zinc chromate	increases abundance, increases expression	1
cupric chloride	decreases expression	1
zinc sulfide	affects cotreatment, affects expression	1
methacrylaldehyde	affects cotreatment, increases oxidation, increases abundance	1
N,N,N’,N’-tetrakis(2-pyridylmethyl)ethylenediamine	increases expression	1
cadmium selenide	affects cotreatment, affects expression	1
di-n-butylphosphoric acid	affects expression	1
vanadium pentoxide	decreases expression	1
Am 580	increases expression, decreases reaction	1
chromium hexavalent ion	increases abundance, increases expression	1

Cellosaurus cell lines

17 cell lines: 10 cancer cell line, 5 induced pluripotent stem cell, 2 transformed cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_A4UI	iMSMD-cohet.5	Induced pluripotent stem cell	Female
CVCL_A4UJ	iMSMD-cohet.7	Induced pluripotent stem cell	Female
CVCL_A4UK	iMSMD-cohet.17	Induced pluripotent stem cell	Female
CVCL_A4UL	iMSMD-het.4	Induced pluripotent stem cell	Female
CVCL_A4UM	iMSMD-het.9	Induced pluripotent stem cell	Female
CVCL_B1B3	Abcam HEK293 IFNGR1 KO	Transformed cell line	Female
CVCL_B1UA	Abcam HeLa IFNGR1 KO	Cancer cell line	Female
CVCL_B8HX	Abcam HCT 116 IFNGR1 KO	Cancer cell line	Male
CVCL_B8X3	Abcam MCF-7 IFNGR1 KO	Cancer cell line	Female
CVCL_B9K7	Abcam A-549 IFNGR1 KO	Cancer cell line	Male

Clinical trials (associated diseases)

4 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT05863858	PHASE3	COMPLETED	Eradication of H. Pylori Infection With Moxifloxacin
NCT05247112	Not specified	RECRUITING	Prevalence and Trends of Antimicrobial Resistance of Helicobacter Pylori in Korea
NCT05410652	Not specified	COMPLETED	Helicobacter Pylori 23S rRNA/gyrA Gene Mutation Detection Kit (Fluorescence PCR Fusion Curve Method)
NCT07293169	Not specified	NOT_YET_RECRUITING	Helicobacter Pylori Infection Among Women With Recurrent Abortion of Unknown Cause