IFNGR2

Summary

IFNGR2 (interferon gamma receptor 2, HGNC:5440) is a protein-coding gene on chromosome 21q22.11, encoding Interferon gamma receptor 2 (P38484). Associates with IFNGR1 to form a receptor for the cytokine interferon gamma (IFNG).

This gene (IFNGR2) encodes the non-ligand-binding beta chain of the gamma interferon receptor. Human interferon-gamma receptor is a heterodimer of IFNGR1 and IFNGR2. Defects in IFNGR2 are a cause of mendelian susceptibility to mycobacterial disease (MSMD), also known as familial disseminated atypical mycobacterial infection. MSMD is a genetically heterogeneous disease with autosomal recessive, autosomal dominant or X-linked inheritance.

Source: NCBI Gene 3460 — RefSeq curated summary.

At a glance

• Gene–disease (curated): immunodeficiency 28 (Strong, GenCC) — +3 more curated relationships
• GWAS associations: 16
• Clinical variants (ClinVar): 275 total — 7 pathogenic, 3 likely-pathogenic
• Phenotypes (HPO): 3
• Druggable target: yes
• MANE Select transcript: NM_005534

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:5440
Approved symbol	IFNGR2
Name	interferon gamma receptor 2
Location	21q22.11
Locus type	gene with protein product
Status	Approved
Aliases	AF-1
Ensembl gene	ENSG00000159128
Ensembl biotype	protein_coding
OMIM	147569
Entrez	3460

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 8 protein_coding, 2 nonsense_mediated_decay

ENST00000290219, ENST00000381995, ENST00000405436, ENST00000421802, ENST00000439213, ENST00000545369, ENST00000696724, ENST00000897490, ENST00000964419, ENST00000964420

RefSeq mRNA: 2 — MANE Select: NM_005534 NM_001329128, NM_005534

CCDS: CCDS33544, CCDS82660

Canonical transcript exons

ENST00000290219 — 7 exons

Exon	Start	End
ENSE00001338849	33403413	33403616
ENSE00003495624	33426884	33427032
ENSE00003514417	33432177	33432336
ENSE00003547942	33414888	33415020
ENSE00003612383	33421480	33421685
ENSE00003640768	33432714	33432871
ENSE00003901258	33436828	33437516

Expression profiles

Bgee: expression breadth ubiquitous, 144 present calls, max score 98.77.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 91.1807 / max 927.4479, expressed in 1825 samples.

FANTOM5 promoters (9 alternative TSS)

Promoter ID	TPM avg	Samples expressed
188862	85.5675	1821
188863	2.0944	926
188860	0.9313	512
188861	0.8222	465
188865	0.5755	276
188864	0.3756	184
188859	0.3423	132
188869	0.3330	157
188858	0.1389	71

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
monocyte	CL:0000576	98.77	gold quality
leukocyte	CL:0000738	98.71	gold quality
blood	UBERON:0000178	98.15	gold quality
granulocyte	CL:0000094	97.67	gold quality
placenta	UBERON:0001987	97.18	gold quality
nerve	UBERON:0001021	96.70	gold quality
tibial nerve	UBERON:0001323	96.70	gold quality
vermiform appendix	UBERON:0001154	96.46	gold quality
rectum	UBERON:0001052	96.34	gold quality
spleen	UBERON:0002106	96.33	gold quality
gall bladder	UBERON:0002110	96.33	gold quality
subcutaneous adipose tissue	UBERON:0002190	96.14	gold quality
adipose tissue	UBERON:0001013	96.11	gold quality
omental fat pad	UBERON:0010414	96.11	gold quality
duodenum	UBERON:0002114	96.03	gold quality
minor salivary gland	UBERON:0001830	95.92	gold quality
stromal cell of endometrium	CL:0002255	95.82	gold quality
saliva-secreting gland	UBERON:0001044	95.79	gold quality
lymph node	UBERON:0000029	95.73	gold quality
lower esophagus mucosa	UBERON:0035834	95.68	gold quality
esophagus mucosa	UBERON:0002469	95.54	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	95.53	gold quality
bone marrow	UBERON:0002371	95.39	gold quality
bone element	UBERON:0001474	95.38	gold quality
islet of Langerhans	UBERON:0000006	95.33	gold quality
smooth muscle tissue	UBERON:0001135	95.22	gold quality
bone marrow cell	CL:0002092	95.15	gold quality
thoracic mammary gland	UBERON:0005200	95.09	gold quality
right lung	UBERON:0002167	95.03	gold quality
vagina	UBERON:0000996	94.97	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-MTAB-9221	yes	26.35
E-ANND-3	yes	12.27
E-MTAB-10042	yes	4.59

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): GLI2, HAND1, NFKB, NFKBID, TSC22D3

Literature-anchored findings (GeneRIF, showing 40)

• Phages displaying fusion proteins with full-length PNRC2 (proline-rich nuclear receptor co-regulatory protein 2), already shown to be a cofactor for other nuclear receptors, and with a polypeptide of the bHLH corepressor TLE1 bound to AF-1. (PMID:14651967)
• In pre eclampsia IFN-gamma R2 protein expression mimicked that in early placental development. (PMID:15585559)
• 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)
• Higher frequency of +874T interferon gamma, both in hetero and in homozygosis and mostly whether simultaneous, plays a role in predisposing to gluten intolerance and an increased risk for coeliac disease. (PMID:15979955)
• 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)
• Two IFN-gammaR2 chains interact through species-specific determinants in their extracellular domains. Finally, these determinants also participate in the interaction of IFN-gammaR2 with IFN-gammaR1. (PMID:16467876)
• interferon-gamma (IFN-gamma) receptor (PMID:16467883)
• Single Nucleotide Polymorphisms in IFNGR2 is associated with gastric cancer (PMID:16885196)
• 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)
• 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)
• Therefore, our results suggest that the interaction between Sirt2 and 14-3-3 beta/gamma is a novel mechanism for the negative regulation of p53 beside the well-characterized Mdm2-mediated repression. (PMID:18249187)
• with progression of HIV-1 infection, interferon-gamma production declines whereas expression of interferon-gamma receptors (R1 and R2) increases (PMID:18620489)
• the transcriptional of IFNgRb/IFNgRa in the heart bioptates appeared to be an early and sensitive marker of inflammatory status of patients with myocarditis (PMID:19172849)
• No significant change was demonstrated in the expression of IFN-gamma receptor beta-chain on surfaces of alveolar macrophages acquired from smokers. (PMID:19269302)
• Results show that the discovery of the anti-Bax activity of the cytoplasmic domain of IFNgammaR2 may shed new light on the mechanism of how cell death is controlled by IFNgamma and Bax. (PMID:19657228)
• The existence of abnormalities in the intracellular processing and protein expression of the IFN-gamma R2 in response to specific stimuli such as IFN-gamma and M. leprae membrane proteins in adherent cells of LL patients. (PMID:20039824)
• These results suggesedt that the microglial and oligodendrocytic expression levels of IFN-gamma-R2 are much lower than the astrocytic expression levels in the human CNS. (PMID:20554027)
• between the two IFNg receptors, IFNgR2 expression appears to be the deciding factor that controls the way in which target cells physiologically respond to IFNgamma. (PMID:20587546)
• Data indicate that perturbation of IFN-gammaR2 internalization by mutating the LI(255-256) motif induces a timely coordinated activation of IFN-gamma/STAT1 signaling pathways that leads to the apoptosis of T cells. (PMID:20709103)
• HBV viraemia appears to have substantial heritability and polymorphisms in the IFNGR2 gene appear to be associated with the variability of viraemia. (PMID:20980339)
• We conclude that the polymorphisms of IFNGR2 may confer resistance to the TB development of newly infected individuals (PMID:22057826)
• JAK2 is a critical factor that stabilizes IFN-gammaR2 surface expression in Th17 cells from AMS patients, making them sensitive to IFN-gamma. (PMID:22219326)
• IFNGR2 haploinsufficiency may underlie clinical tuberculosis in children living in areas of endemic disease. (PMID:23161749)
• IFN-gammaR2-deficient monocytes induce a higher percentage of IL-17(+) cells from both healthy and IFN-gammaR2-deficient CD4(+) T cells. (PMID:23459074)
• We report a molecular study of the two known patients with autosomal recessive, partial interferon-gamma receptor (IFN-gammaR)2 deficiency (PMID:23963039)
• It related to persistence of hepatitis B virus (HBV) infection and viral load in chronic HBV. (PMID:23980639)
• This is the first study that shows an association between SNPs and liver fibrosis in the general population (PMID:25301852)
• Fatal hemophagocytic lymphohistiocytosis has been described in two unrelated pediatric patients with underlying IFNGR2 deficiency. (PMID:25592983)
• The expression of IFNGR2 was significantly higher in patients with RA compared with control subjects and was significantly higher in patients in whom radiographic damage was more severe. (PMID:25708927)
• Statistical analyses revealed that four genetic variants in IFNGR1 were marginally associated with the risk of Tuberculosis (P = 0.02-0.04), while other single nucleotide polymorphisms in IFNGR1 and IFNGR2 did not exhibit any associations (PMID:25815589)
• The variability of potentially important functional polymorphic variants of the IFNG, IFNGR2 and NEIL2 genes was characterized in representatives of four ethnic groups living in the Siberian region. (PMID:26601495)
• IFN-gammaR2 T168N mutant diffusion is confined by distinct actin nanodomains where conformational changes required for JAK/STAT activation by IFN-gamma could not occur. Removing IFN-gammaR2 T168N-bound galectins restored lateral diffusion in lipid nanodomains and JAK/STAT signaling in patient cells, whereas adding galectins impaired these processes in control cells. (PMID:27499022)
• Successful unrelated cord blood transplant for complete IFN-gamma receptor 2 deficiency. (PMID:27522156)
• The IFNGR2Q64R polymorphism is correlated with male sex and paranoid schizophrenia in Tunisians. (PMID:27563937)
• A crystal structure of the extracellular part of human interferon-gamma receptor 2 (IFNGR2) was solved by molecular replacement at 1.8 A resolution. (PMID:27599734)
• Data suggest IFNG plays various roles in dynamics of inflammation in subjects with underlying autoimmunity modeled as “canonical” and “non-canonical” pathways; in canonical pathway, IFNG dimerizes and binds to IFNGR1 in IFNGR1/IFNGR2 hetero-multimer; STAT transcription factors are involved in non-canonical pathway. (IFNG = interferon gamma; IFNGR = IFNG receptor; STAT = signal transducers and activators of transcription) (PMID:28652404)
• A digenic human immunodeficiency characterized by IFNAR1 and IFNGR2 mutations (PMID:29106381)
• The study identified an SNP rs9978223 on IFNGR2 gene, associated with increased risk in acute myocardial infarctionpatient from India. (PMID:29434065)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Ifngr2	ENSMUSG00000022965
rattus_norvegicus	Ifngr2	ENSRNOG00000002032

Paralogs (11): IL20RA (ENSG00000016402), IFNGR1 (ENSG00000027697), IL10RA (ENSG00000110324), F3 (ENSG00000117525), IFNAR1 (ENSG00000142166), IL22RA1 (ENSG00000142677), IFNAR2 (ENSG00000159110), IL22RA2 (ENSG00000164485), IL20RB (ENSG00000174564), IFNLR1 (ENSG00000185436), IL10RB (ENSG00000243646)

Protein

Protein identifiers

Interferon gamma receptor 2 — P38484 (reviewed: P38484)

Alternative names: Interferon gamma receptor accessory factor 1, Interferon gamma receptor beta-chain, Interferon gamma transducer 1

All UniProt accessions (8): A0A8Q3SIY7, A8K881, B5MCZ0, E7EUY1, P38484, F8WE34, F8WF11, H7C1V5

UniProt curated annotations — full annotation on UniProt →

Function. Associates with IFNGR1 to form a receptor for the cytokine interferon gamma (IFNG). Ligand binding stimulates activation of the JAK/STAT signaling pathway. Required for signal transduction in contrast to other receptor subunit responsible for ligand binding.

Subunit / interactions. Heterodimer with IFNGR1, to form the IFNG receptor complex. Interacts (via intracellular domain) with JAK2.

Subcellular location. Cell membrane. Cytoplasmic vesicle membrane. Golgi apparatus membrane. Endoplasmic reticulum membrane. Cytoplasm.

Tissue specificity. Expressed in T-cells (at protein level).

Disease relevance. Immunodeficiency 28 (IMD28) [MIM:614889] 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. IMD28 is an autosomal recessive disease that manifests early in life, with severe, often fatal, infection. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the type II cytokine receptor family.

RefSeq proteins (2): NP_001316057, NP_005525* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003961	FN3_dom	Domain
IPR013783	Ig-like_fold	Homologous_superfamily
IPR015373	Interferon/interleukin_rcp_dom	Domain
IPR036116	FN3_sf	Homologous_superfamily
IPR050650

Pfam: PF01108, PF09294

UniProt features (55 total): strand 15, sequence variant 10, mutagenesis site 10, glycosylation site 6, disulfide bond 2, topological domain 2, helix 2, turn 2, domain 2, signal peptide 1, chain 1, transmembrane region 1, short sequence motif 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
5EH1	X-RAY DIFFRACTION	1.8
6E3K	X-RAY DIFFRACTION	3.25
6E3L	X-RAY DIFFRACTION	3.8

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P38484-F1	84.06	0.63

Functional residue map

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

Disulfide bonds (2): 86–94, 209–234

Glycosylation sites (6): 110, 137, 219, 231, 56, 85

Mutagenesis-validated functional residues (10):

Position	Phenotype
110	complete inhibition of transport to the cell membrane.
137	complete inhibition of transport to the cell membrane.
168	does not affect function.
231	complete inhibition of transport to the cell membrane.
274–275	leads to overaccumulation on the cell membrane.
276–277	leads to overaccumulation on the cell membrane. enhances function.
276	leads to small increase in accumulation on the cell membrane.
277	does not affect accumulation on the cell membrane.
278–279	does not affect accumulation on the cell membrane.

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: 288 (showing top): GOBP_CELLULAR_RESPONSE_TO_VIRUS, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, GOBP_INFLAMMATORY_RESPONSE, GOBP_RESPONSE_TO_PEPTIDE, STARK_PREFRONTAL_CORTEX_22Q11_DELETION_DN, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_UP, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, KYNG_DNA_DAMAGE_DN, KYNG_DNA_DAMAGE_BY_4NQO, RASHI_NFKB1_TARGETS, GOBP_DEFENSE_RESPONSE_TO_OTHER_ORGANISM, GOBP_MYELOID_LEUKOCYTE_ACTIVATION, GROSS_HYPOXIA_VIA_ELK3_UP, GROSS_HYPOXIA_VIA_ELK3_AND_HIF1A_DN, GOBP_MACROPHAGE_ACTIVATION

GO Biological Process (9): microglial cell activation (GO:0001774), cell surface receptor signaling pathway (GO:0007166), response to virus (GO:0009615), cytokine-mediated signaling pathway (GO:0019221), type III interferon-mediated signaling pathway (GO:0038196), defense response to virus (GO:0051607), type II interferon-mediated signaling pathway (GO:0060333), cellular response to virus (GO:0098586), positive regulation of glutamate receptor signaling pathway (GO:1900451)

GO Molecular Function (3): cytokine receptor activity (GO:0004896), type II interferon receptor activity (GO:0004906), protein binding (GO:0005515)

GO Cellular Component (9): Golgi membrane (GO:0000139), endoplasmic reticulum (GO:0005783), endoplasmic reticulum membrane (GO:0005789), plasma membrane (GO:0005886), cytoplasmic vesicle membrane (GO:0030659), cytoplasm (GO:0005737), Golgi apparatus (GO:0005794), membrane (GO:0016020), cytoplasmic vesicle (GO:0031410)

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
cytoplasm	3
interferon-mediated signaling pathway	2
response to virus	2
endomembrane system	2
intracellular membrane-bounded organelle	2
cellular anatomical structure	2
leukocyte activation involved in inflammatory response	1
macrophage activation	1
glial cell activation	1
signal transduction	1
response to other organism	1
cell surface receptor signaling pathway	1
cellular response to cytokine stimulus	1
cellular response to type III interferon	1
defense response	1
cellular response to type II interferon	1
glutamate receptor signaling pathway	1
positive regulation of signal transduction	1
regulation of glutamate receptor signaling pathway	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
binding	1
Golgi apparatus	1
bounding membrane of organelle	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
membrane	1
cell periphery	1
vesicle membrane	1
cytoplasmic vesicle	1
intracellular anatomical structure	1
intracellular vesicle	1

Protein interactions and networks

STRING

1622 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
IFNGR2	IFNGR1	P15260	999
IFNGR2	IFNG	P01579	998
IFNGR2	JAK1	P23458	996
IFNGR2	JAK2	O60674	995
IFNGR2	IL12RB1	P42701	894
IFNGR2	IFNAR2	P48551	883
IFNGR2	STAT2	P52630	828
IFNGR2	STAT1	P42224	819
IFNGR2	IFNA13	P01562	816
IFNGR2	IFNAR1	P17181	804
IFNGR2	TYK2	P29597	772
IFNGR2	IFNLR1	Q8IU57	713
IFNGR2	IRF9	Q00978	690
IFNGR2	IL12RB2	Q99665	664
IFNGR2	IL18R1	Q13478	660

IntAct

109 interactions, top by confidence:

A	B	Type	Score
SFT2D2	IFNGR2	psi-mi:“MI:0915”(physical association)	0.560
TMEM140	IFNGR2	psi-mi:“MI:0915”(physical association)	0.560
TSPAN2	IFNGR2	psi-mi:“MI:0915”(physical association)	0.560
EMP3	IFNGR2	psi-mi:“MI:0915”(physical association)	0.560
STRIT1	IFNGR2	psi-mi:“MI:0915”(physical association)	0.560
BRICD5	IFNGR2	psi-mi:“MI:0915”(physical association)	0.560
TMEM218	IFNGR2	psi-mi:“MI:0915”(physical association)	0.560
BNIP3	IFNGR2	psi-mi:“MI:0915”(physical association)	0.560
CLDN19	IFNGR2	psi-mi:“MI:0915”(physical association)	0.560
IFNGR2	BNIP3	psi-mi:“MI:0915”(physical association)	0.560
SFTPC	IFNGR2	psi-mi:“MI:0915”(physical association)	0.560
SEC22B	IFNGR2	psi-mi:“MI:0915”(physical association)	0.560
IFNGR2	CXCL9	psi-mi:“MI:0915”(physical association)	0.560
IFNGR2	JAGN1	psi-mi:“MI:0915”(physical association)	0.560
IFNGR2	VMA12	psi-mi:“MI:0915”(physical association)	0.560
ENTPD3	IFNGR2	psi-mi:“MI:0915”(physical association)	0.560
IFNGR2	PMP22	psi-mi:“MI:0915”(physical association)	0.560
IFNGR2	TREX1	psi-mi:“MI:0915”(physical association)	0.560
IFNGR2	TMEM254	psi-mi:“MI:0915”(physical association)	0.560
IFNGR2	TMEM60	psi-mi:“MI:0915”(physical association)	0.560
IFNGR2	CD302	psi-mi:“MI:0915”(physical association)	0.560
IFNGR2	ERMP1	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (63): IFNGR2 (Affinity Capture-RNA), IFNGR2 (Two-hybrid), IFNGR2 (Two-hybrid), IFNGR2 (Two-hybrid), IFNGR2 (Two-hybrid), IFNGR2 (Two-hybrid), IFNGR2 (Two-hybrid), IFNGR2 (Two-hybrid), IFNGR2 (Two-hybrid), IFNGR2 (Two-hybrid), IFNGR2 (Two-hybrid), IFNGR2 (Two-hybrid), IFNGR2 (Two-hybrid), IFNGR2 (Two-hybrid), IFNGR2 (Two-hybrid)

ESM2 similar proteins: A0A1B0GW64, A4FUY1, A5D7B2, A6QQ85, A8MVS5, B0FP48, E5RIL1, O18796, O19131, O75022, O75023, P09564, P0C191, P15151, P19438, P24071, P31994, P31995, P32506, P32942, P38484, P49772, P50555, Q01113, Q13477, Q14CZ8, Q28110, Q5DRQ8, Q61190, Q640R3, Q6AZ51, Q6BAA4, Q6GTX8, Q6PGD0, Q6UW56, Q6UX52, Q75VT8, Q7Z692, Q863H2, Q86YD3

SIGNOR signaling

5 interactions.

A	Effect	B	Mechanism
IFNGR2	“form complex”	IFNGR2/INFGR1	binding
JAK2	“up-regulates activity”	IFNGR2	binding
JAK1	“up-regulates activity”	IFNGR2	phosphorylation
IFNGR2	“up-regulates activity”	JAK2	binding
IFNG	up-regulates	IFNGR2	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	7
Likely pathogenic	3
Uncertain significance	93
Likely benign	97
Benign	31

Top pathogenic / likely-pathogenic (10)

Variant ID	HGVS	Classification
1075480	NM_005534.4(IFNGR2):c.709dup (p.Thr237fs)	Pathogenic
14726	NM_005534.4(IFNGR2):c.278_279del (p.Glu93fs)	Pathogenic
14727	NM_005534.4(IFNGR2):c.503C>A (p.Thr168Asn)	Pathogenic
14728	NM_005534.4(IFNGR2):c.663_689del (p.Phe224_Ile232del)	Pathogenic
37286	NM_005534.4(IFNGR2):c.382_387dup (p.Thr128_Met129dup)	Pathogenic
949584	NM_005534.4(IFNGR2):c.503_504del (p.Thr168fs)	Pathogenic
987750	NM_005534.4(IFNGR2):c.4del (p.Arg2fs)	Pathogenic
1066015	NM_005534.4(IFNGR2):c.1A>C (p.Met1Leu)	Likely pathogenic
1299495	NM_005534.4(IFNGR2):c.800del (p.Phe267fs)	Likely pathogenic
987732	NM_005534.4(IFNGR2):c.1A>G (p.Met1Val)	Likely pathogenic

SpliceAI

2683 predictions. Top by Δscore:

Variant	Effect	Δscore
21:33421478:A:AG	acceptor_gain	1.0000
21:33421479:G:GG	acceptor_gain	1.0000
21:33421479:GCACC:G	acceptor_gain	1.0000
21:33432709:TTTAG:T	acceptor_loss	1.0000
21:33432710:TTAGC:T	acceptor_loss	1.0000
21:33432712:A:AG	acceptor_gain	1.0000
21:33432712:AG:A	acceptor_loss	1.0000
21:33432713:G:GA	acceptor_gain	1.0000
21:33436816:A:AG	acceptor_gain	1.0000
21:33436817:A:G	acceptor_gain	1.0000
21:33436826:A:G	acceptor_gain	1.0000
21:33436827:G:GG	acceptor_gain	1.0000
21:33467004:ACTT:A	donor_loss	1.0000
21:33467005:CT:C	donor_loss	1.0000
21:33467008:A:AC	donor_gain	1.0000
21:33467008:ACAT:A	donor_loss	1.0000
21:33467009:C:CA	donor_gain	1.0000
21:33467009:CA:C	donor_gain	1.0000
21:33467009:CATG:C	donor_gain	1.0000
21:33467009:CATGA:C	donor_gain	1.0000
21:33468781:ACTT:A	donor_loss	1.0000
21:33468783:TTACC:T	donor_loss	1.0000
21:33468784:T:TG	donor_loss	1.0000
21:33468785:ACC:A	donor_loss	1.0000
21:33468786:C:G	donor_loss	1.0000
21:33468924:ATCC:A	acceptor_loss	1.0000
21:33468926:CCT:C	acceptor_loss	1.0000
21:33468928:T:C	acceptor_loss	1.0000
21:33403613:CCAGG:C	donor_loss	0.9900
21:33403617:G:GC	donor_loss	0.9900

AlphaMissense

2187 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
21:33414961:G:C	W49C	0.996
21:33414961:G:T	W49C	0.996
21:33421651:G:C	W126C	0.992
21:33421651:G:T	W126C	0.992
21:33421667:T:C	F132L	0.992
21:33421669:T:A	F132L	0.992
21:33421669:T:G	F132L	0.992
21:33421614:G:C	R114P	0.989
21:33421668:T:G	F132C	0.989
21:33414959:T:A	W49R	0.984
21:33414959:T:C	W49R	0.984
21:33421553:T:A	C94S	0.984
21:33421554:G:C	C94S	0.984
21:33421587:T:G	F105C	0.980
21:33426958:T:C	F163L	0.979
21:33426960:T:A	F163L	0.979
21:33426960:T:G	F163L	0.979
21:33421668:T:C	F132S	0.978
21:33421495:G:C	W74C	0.977
21:33421495:G:T	W74C	0.977
21:33421560:T:C	F96S	0.974
21:33421649:T:A	W126R	0.974
21:33421649:T:C	W126R	0.974
21:33415001:T:G	Y63D	0.972
21:33421529:T:A	C86S	0.971
21:33421530:G:C	C86S	0.971
21:33421587:T:C	F105S	0.971
21:33421620:G:C	R116P	0.970
21:33421553:T:C	C94R	0.969
21:33421560:T:G	F96C	0.966

dbSNP variants (sampled 300 via entrez): RS1000013165 (21:33437034 G>A,C), RS1000015493 (21:33403717 G>A), RS1000068200 (21:33402783 T>C), RS1000217520 (21:33419262 T>A,C), RS1000279793 (21:33419106 T>G), RS1000288046 (21:33402559 T>C), RS1000288589 (21:33416048 G>T), RS1000340386 (21:33415647 T>G), RS1000746000 (21:33428723 T>C), RS1000791560 (21:33426717 C>T), RS1000855369 (21:33401037 T>C), RS1000857367 (21:33425363 C>T), RS1000959290 (21:33406971 G>A), RS1000960263 (21:33435043 T>C), RS1001066385 (21:33404569 G>A,T)

Disease associations

OMIM: gene MIM:147569 | disease phenotypes: MIM:614889, MIM:209950

GenCC curated gene-disease

Disease	Classification	Inheritance
immunodeficiency 28	Strong	Autosomal recessive
autosomal recessive Mendelian susceptibility to mycobacterial diseases due to complete IFNgammaR2 deficiency	Supportive	Autosomal recessive
autosomal recessive Mendelian susceptibility to mycobacterial diseases due to partial IFNgammaR2 deficiency	Supportive	Autosomal recessive
autosomal dominant mendelian susceptibility to mycobacterial diseases due to partial IFNgammaR2 deficiency	Supportive	Autosomal dominant

Mondo (5): immunodeficiency 28 (MONDO:0013953), immunodeficiency 27A (MONDO:0008856), autosomal recessive Mendelian susceptibility to mycobacterial diseases due to complete IFNgammaR2 deficiency (MONDO:0017900), autosomal recessive Mendelian susceptibility to mycobacterial diseases due to partial IFNgammaR2 deficiency (MONDO:0017902), autosomal dominant mendelian susceptibility to mycobacterial diseases due to partial IFNgammaR2 deficiency (MONDO:0017903)

Orphanet (4): Mendelian susceptibility to mycobacterial diseases due to complete IFNgammaR2 deficiency (Orphanet:319547), Autosomal recessive mendelian susceptibility to mycobacterial diseases due to partial IFNgammaR2 deficiency (Orphanet:319574), 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)

HPO phenotypes

3 total (3 of 3 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0002721	Immunodeficiency
HP:0011274	Recurrent mycobacterial infections

GWAS associations

16 associations (top):

Study	Trait	p-value
GCST001652_2	Crohn’s disease	3.000000e-07
GCST001729_26	Crohn’s disease	2.000000e-16
GCST001762_443	Obesity-related traits	5.000000e-06
GCST002318_116	Rheumatoid arthritis	3.000000e-08
GCST002318_117	Rheumatoid arthritis	1.000000e-06
GCST002598_2	Educational attainment	3.000000e-06
GCST004131_60	Inflammatory bowel disease	7.000000e-09
GCST004132_103	Crohn’s disease	1.000000e-14
GCST005531_99	Multiple sclerosis	1.000000e-07
GCST005537_60	Chronic inflammatory diseases (ankylosing spondylitis, Crohn’s disease, psoriasis, primary sclerosing cholangitis, ulcerative colitis) (pleiotropy)	4.000000e-16
GCST006479_2	Diverticular disease	5.000000e-06
GCST006959_120	Rheumatoid arthritis	8.000000e-07
GCST006959_34	Rheumatoid arthritis	7.000000e-08
GCST008479_13	Psoriasis	3.000000e-08
GCST009597_118	Multiple sclerosis	2.000000e-09
GCST012489_130	Heel bone mineral density x serum urate levels interaction	8.000000e-10

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0004471	insulin sensitivity measurement
EFO:0004784	self reported educational attainment
EFO:0009959	diverticular disease
EFO:0004531	urate measurement
EFO:0009270	heel bone mineral density

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2364171 (PROTEIN COMPLEX)

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

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs8126756	IFNGR2		0.00	0

GtoPdb / IUPHAR curated pharmacology

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

Target class: catalytic receptor — Interferon receptor family

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Air Pollutants	decreases expression, affects cotreatment, increases abundance, increases oxidation, affects expression	3
Valproic Acid	affects expression, decreases expression, increases methylation	3
Ozone	affects cotreatment, increases oxidation, increases abundance, affects expression	2
Tobacco Smoke Pollution	decreases expression, increases expression	2
Particulate Matter	decreases expression, increases abundance	2
GSK-J4	increases expression	1
FR900359	increases phosphorylation	1
ethylbenzene	increases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
bisphenol A	increases methylation, affects cotreatment	1
titanium dioxide	increases expression	1
trichostatin A	affects expression	1
pyrrolidine dithiocarbamic acid	increases expression, affects cotreatment, decreases reaction	1
nickel chloride	increases expression	1
2-xylene	increases expression	1
benzo(e)pyrene	decreases methylation, increases methylation	1
cadmium acetate	decreases expression	1
aflatoxin B2	decreases methylation	1
zinc sulfide	affects cotreatment, increases expression	1
methacrylaldehyde	affects cotreatment, increases oxidation, increases abundance	1
N,N,N’,N’-tetrakis(2-pyridylmethyl)ethylenediamine	decreases expression	1
cadmium selenide	affects cotreatment, increases expression	1
di-n-butylphosphoric acid	affects expression	1
chloropicrin	decreases expression	1
K 7174	increases expression	1
ICG 001	increases expression	1
abrine	increases expression	1
Sunitinib	decreases expression	1
Arsenic Trioxide	increases expression	1

Cellosaurus cell lines

11 cell lines: 10 cancer cell line, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_1D51	2C4 gamma1A/JAK2	Cancer cell line	Male
CVCL_B8HY	Abcam HCT 116 IFNGR2 KO	Cancer cell line	Male
CVCL_B8X4	Abcam MCF-7 IFNGR2 KO	Cancer cell line	Female
CVCL_B9K8	Abcam A-549 IFNGR2 KO	Cancer cell line	Male
CVCL_C0D3	2C4 gamma1A	Cancer cell line	Male
CVCL_D7RS	Ubigene A-549 IFNGR2 KO	Cancer cell line	Male
CVCL_D8MV	Ubigene HCT 116 IFNGR2 KO	Cancer cell line	Male
CVCL_D9GQ	Ubigene HEK293 IFNGR2 KO	Transformed cell line	Female
CVCL_E0EP	Ubigene HeLa IFNGR2 KO	Cancer cell line	Female
CVCL_SS29	HAP1 IFNGR2 (-) 1	Cancer cell line	Male

Clinical trials (associated diseases)

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