IFNGR2

interferon gamma receptor 2, the group of Fibronectin type III domain containing|Interferon receptors

Basic information

Region (hg38): 21:33403412-33479348

Previous symbols: [ "IFNGT1" ]

Links

ENSG00000159128 ∙ NCBI:3460 ∙ OMIM:147569 ∙ HGNC:5440 ∙ Uniprot:P38484 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• immunodeficiency 28 (Strong), mode of inheritance: AR
• autosomal recessive Mendelian susceptibility to mycobacterial diseases due to complete IFNgammaR2 deficiency (Supportive), mode of inheritance: AR
• autosomal recessive Mendelian susceptibility to mycobacterial diseases due to partial IFNgammaR2 deficiency (Supportive), mode of inheritance: AR
• autosomal dominant mendelian susceptibility to mycobacterial diseases due to partial IFNgammaR2 deficiency (Supportive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Immunodeficiency 28	AR	Allergy/Immunology/Infectious	Individuals may be susceptible to frequent and severe mycobacterial infections, and antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial	Allergy/Immunology/Infectious	15924140; 23161749; 31222290

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the IFNGR2 gene.

• Immunodeficiency 28 (178 variants)
• not provided (58 variants)
• Inborn genetic diseases (12 variants)
• not specified (9 variants)
• Immunodeficiency 27A (2 variants)
• Interferon gamma receptor deficiency (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the IFNGR2 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	43	3	47
missense			81	4	3	88
nonsense						0
start loss		1				1
frameshift	2					2
inframe indel			9			9
splice donor/acceptor (+/-2bp)						0
splice region			2	9	2	13
non coding				14	19	33
Total	2	1	91	61	25

Highest pathogenic variant AF is 0.00000659

Variants in IFNGR2

This is a list of pathogenic ClinVar variants found in the IFNGR2 region.

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

Position	Type	Phenotype	Significance	ClinVar
21-33403415-T-C			Benign (Nov 12, 2018)
21-33403544-A-C		Immunodeficiency 28	Likely pathogenic (Feb 10, 2022)
21-33403544-A-G		Immunodeficiency 28	Pathogenic (Oct 08, 2021)
21-33403546-GC-G		Immunodeficiency 28	Pathogenic (Oct 08, 2021)
21-33403551-C-G		Immunodeficiency 28	Uncertain significance (Jul 26, 2022)
21-33403552-G-A		Immunodeficiency 28	Likely benign (Nov 14, 2022)
21-33403552-G-C		Immunodeficiency 28	Likely benign (May 26, 2021)
21-33403554-C-CGCTGCTGTGGTCGCTGCT		Immunodeficiency 28	Uncertain significance (Feb 20, 2022)
21-33403556-C-T		Immunodeficiency 28	Likely benign (Mar 14, 2023)
21-33403559-C-T		Immunodeficiency 28	Likely benign (Nov 22, 2022)
21-33403562-T-C		Immunodeficiency 28	Uncertain significance (Apr 28, 2022)
21-33403562-T-TGGTCGCTGCTGC		Immunodeficiency 28	Uncertain significance (Aug 26, 2021)
21-33403566-C-CGCT		Immunodeficiency 28	Uncertain significance (Jun 09, 2022)
21-33403580-C-T		Immunodeficiency 28 • Inborn genetic diseases • IFNGR2-related disorder	Conflicting classifications of pathogenicity (Jan 16, 2024)
21-33403588-C-G		Immunodeficiency 28	Likely benign (Aug 28, 2021)
21-33403590-TCGCCGC-T		Immunodeficiency 28	Uncertain significance (Aug 27, 2021)
21-33403590-TCGCCGCCGC-T		Immunodeficiency 28	Uncertain significance (Mar 12, 2022)
21-33403590-TCGCCGCCGCCGC-T		Immunodeficiency 28	Uncertain significance (Sep 01, 2022)
21-33403591-C-T		Immunodeficiency 28	Likely benign (Mar 26, 2022)
21-33403590-T-TCGC		Immunodeficiency 28	Uncertain significance (Aug 28, 2021)
21-33403590-T-TCGCCGC		Immunodeficiency 28	Uncertain significance (Jun 05, 2022)
21-33403594-C-T		Immunodeficiency 28	Likely benign (Jan 02, 2024)
21-33403596-C-T		Immunodeficiency 28	Uncertain significance (Aug 19, 2022)
21-33403599-C-T		Immunodeficiency 28	Uncertain significance (Jul 19, 2022)
21-33403601-G-A		Immunodeficiency 28	Uncertain significance (Aug 23, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
IFNGR2	protein_coding	protein_coding	ENST00000290219	7	76454

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.953	0.0472	125724	0	3	125727	0.0000119

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.828	138	168	0.820	0.00000983	2167
Missense in Polyphen		33	50.461	0.65397		679
Synonymous	0.210	67	69.2	0.968	0.00000484	672
Loss of Function	3.22	1	14.0	0.0714	6.79e-7	168

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000289	0.0000289
Ashkenazi Jewish	0.00	0.00
East Asian	0.000109	0.000109
Finnish	0.00	0.00
European (Non-Finnish)	0.00	0.00
Middle Eastern	0.000109	0.000109
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Associates with IFNGR1 to form a receptor for the cytokine interferon gamma (IFNG) (PubMed:8124716, PubMed:7673114,PubMed:7615558). Ligand binding stimulates activation of the JAK/STAT signaling pathway (PubMed:8124716, PubMed:7673114, PubMed:15356148). Required for signal transduction in contrast to other receptor subunit responsible for ligand binding (PubMed:7673114). {ECO:0000269|PubMed:15356148, ECO:0000269|PubMed:7615558, ECO:0000269|PubMed:7673114, ECO:0000269|PubMed:8124716}.
• Pathway: Salmonella infection - Homo sapiens (human);HIF-1 signaling pathway - Homo sapiens (human);Jak-STAT signaling pathway - Homo sapiens (human);Influenza A - Homo sapiens (human);Inflammatory bowel disease (IBD) - Homo sapiens (human);Chagas disease (American trypanosomiasis) - Homo sapiens (human);Necroptosis - 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);Toxoplasmosis - Homo sapiens (human);Pathways in cancer - Homo sapiens (human);Measles - Homo sapiens (human);Osteoclast differentiation - Homo sapiens (human);Cytokine-cytokine receptor interaction - Homo sapiens (human);Herpes simplex infection - Homo sapiens (human);JAK-STAT-Core;The human immune response to tuberculosis;Type II interferon signaling (IFNG);Cytokine Signaling in Immune system;JAK STAT MolecularVariation 1;Regulation of IFNG signaling;Immune System;IFN gamma signaling;JAK STAT MolecularVariation 2;JAK STAT pathway and regulation;Interferon gamma signaling;Interferon Signaling (Consensus)

Recessive Scores

• pRec: 0.163

Intolerance Scores

• rvis_EVS: 0.66
• rvis_percentile_EVS: 84.55

Haploinsufficiency Scores

• pHI: 0.103
• hipred: Y
• hipred_score: 0.546
• ghis: 0.532

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.883

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Ifngr2
• Phenotype: hematopoietic system phenotype; immune system phenotype

Gene ontology

• Biological process: cell surface receptor signaling pathway;response to virus;cytokine-mediated signaling pathway;interferon-gamma-mediated signaling pathway;regulation of interferon-gamma-mediated signaling pathway
• Cellular component: Golgi membrane;endoplasmic reticulum;endoplasmic reticulum membrane;plasma membrane;integral component of plasma membrane;cytoplasmic vesicle membrane
• Molecular function: cytokine receptor activity;interferon-gamma receptor activity