IFNGR1

interferon gamma receptor 1, the group of Interferon receptors|CD molecules

Basic information

Region (hg38): 6:137197482-137219449

Previous symbols: [ "IFNGR" ]

Links

ENSG00000027697 ∙ NCBI:3459 ∙ OMIM:107470 ∙ HGNC:5439 ∙ Uniprot:P15260 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Mendelian susceptibility to mycobacterial diseases due to complete IFNgammaR1 deficiency (Supportive), mode of inheritance: AR
• autosomal recessive Mendelian susceptibility to mycobacterial diseases due to partial IFNgammaR1 deficiency (Supportive), mode of inheritance: AR
• autosomal dominant mendelian susceptibility to mycobacterial diseases due to partial IFNgammaR1 deficiency (Supportive), mode of inheritance: AD
• immunodeficiency 27A (Strong), mode of inheritance: AR
• autosomal dominant mendelian susceptibility to mycobacterial diseases due to partial IFNgammaR1 deficiency (Strong), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Immunodeficiency 27B; Immunodeficiency 27A	AD/AR	Allergy/Immunology/Infectious	Individuals may be susceptible to frequent and severe mycobacterial infections, and awareness and early and aggressive treatment of infections may be beneficial; Consideration of potential adverse effects of BCG vaccination in some individuals may be beneficial	Allergy/Immunology/Infectious	8960475; 8960473; 9389728; 10192386

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the IFNGR1 gene.

• Disseminated atypical mycobacterial infection (236 variants)
• Immunodeficiency 27A (66 variants)
• not provided (36 variants)
• not specified (18 variants)
• Inborn genetic diseases (10 variants)
• Interferon gamma receptor deficiency (4 variants)
• Autosomal dominant mendelian susceptibility to mycobacterial diseases due to partial IFNgammaR1 deficiency (3 variants)
• Immunodeficiency 27A;Helicobacter pylori infection, susceptibility to;Hepatitis B virus, susceptibility to;Autosomal dominant mendelian susceptibility to mycobacterial diseases due to partial IFNgammaR1 deficiency;Mycobacterium tuberculosis, susceptibility to (2 variants)
• IFNGR1-related condition (2 variants)
• Immunodeficiency 27A;Autosomal dominant mendelian susceptibility to mycobacterial diseases due to partial IFNgammaR1 deficiency (1 variants)
• Helicobacter pylori infection, susceptibility to (1 variants)
• Mycobacterium tuberculosis, susceptibility to (1 variants)
• IFN-gamma receptor 1 deficiency (1 variants)
• Inherited Immunodeficiency Diseases (1 variants)
• Immunodeficiency 27A;Mycobacterium tuberculosis, susceptibility to;Helicobacter pylori infection, susceptibility to;Hepatitis B virus, susceptibility to;Autosomal dominant mendelian susceptibility to mycobacterial diseases due to partial IFNgammaR1 deficiency (1 variants)
• Hepatitis B virus, susceptibility to;Autosomal dominant mendelian susceptibility to mycobacterial diseases due to partial IFNgammaR1 deficiency;Helicobacter pylori infection, susceptibility to;Mycobacterium tuberculosis, susceptibility to;Immunodeficiency 27A (1 variants)
• Mycobacterium tuberculosis, protection against (1 variants)
• Immunodeficiency 27A;Hepatitis B virus, susceptibility to;Helicobacter pylori infection, susceptibility to;Autosomal dominant mendelian susceptibility to mycobacterial diseases due to partial IFNgammaR1 deficiency;Mycobacterium tuberculosis, susceptibility to (1 variants)
• Hepatitis B virus, susceptibility to (1 variants)
• Autosomal dominant mendelian susceptibility to mycobacterial diseases due to partial IFNgammaR1 deficiency;Immunodeficiency 27A (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the IFNGR1 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			4	43	4	51
missense		2	151	4	1	158
nonsense	1	1				2
start loss			1			1
frameshift	6		3			9
inframe indel			2	1		3
splice donor/acceptor (+/-2bp)	3	4				7
splice region			4	4	1	9
non coding		1	12	17	12	42
Total	10	8	173	65	17

Highest pathogenic variant AF is 0.0000394

Variants in IFNGR1

This is a list of pathogenic ClinVar variants found in the IFNGR1 region.

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

Position	Type	Phenotype	Significance	ClinVar
6-137197484-C-T		Immunodeficiency 27A	Uncertain significance (Jan 12, 2018)
6-137197544-C-T		Immunodeficiency 27A	Uncertain significance (Apr 27, 2017)
6-137197556-C-T		Immunodeficiency 27A	Uncertain significance (Jan 12, 2018)
6-137197565-T-C		Immunodeficiency 27A	Uncertain significance (Jan 13, 2018)
6-137197569-T-G		Immunodeficiency 27A	Likely benign (Jan 13, 2018)
6-137197581-G-A		Immunodeficiency 27A	Uncertain significance (Jan 13, 2018)
6-137197717-AG-A			not provided (-)
6-137197734-C-T		Immunodeficiency 27A	Uncertain significance (Jan 12, 2018)
6-137197773-G-A		Immunodeficiency 27A	Uncertain significance (Jan 12, 2018)
6-137197787-A-G		Immunodeficiency 27A	Uncertain significance (Jan 13, 2018)
6-137197814-A-T		Immunodeficiency 27A	Benign (Jan 12, 2018)
6-137197825-T-C		Immunodeficiency 27A	Benign (Jan 12, 2018)
6-137197891-C-T			not provided (-)
6-137197903-C-A		Immunodeficiency 27A	Likely benign (Jan 13, 2018)
6-137197960-C-A		Immunodeficiency 27A	Likely benign (Jan 12, 2018)
6-137197990-C-T		Immunodeficiency 27A	Benign (Jan 13, 2018)
6-137198044-T-C		Disseminated atypical mycobacterial infection	Uncertain significance (May 28, 2022)
6-137198047-G-C		Disseminated atypical mycobacterial infection	Uncertain significance (Jul 11, 2022)
6-137198053-T-C		Disseminated atypical mycobacterial infection	Uncertain significance (Oct 03, 2022)
6-137198067-A-G		Disseminated atypical mycobacterial infection	Likely benign (Jun 23, 2023)
6-137198071-A-G		Disseminated atypical mycobacterial infection	Uncertain significance (Oct 19, 2020)
6-137198087-C-T		Disseminated atypical mycobacterial infection	Uncertain significance (Jun 04, 2023)
6-137198088-G-A		Disseminated atypical mycobacterial infection	Likely benign (Jan 11, 2024)
6-137198098-A-C		Disseminated atypical mycobacterial infection	Uncertain significance (Jun 13, 2022)
6-137198101-A-G		Immunodeficiency 27A • Disseminated atypical mycobacterial infection	Benign (Jan 29, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
IFNGR1	protein_coding	protein_coding	ENST00000367739	7	21966

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0155	0.980	125736	0	12	125748	0.0000477

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.305	246	260	0.947	0.0000126	3194
Missense in Polyphen		54	66.156	0.81626		906
Synonymous	0.954	88	100	0.879	0.00000572	932
Loss of Function	2.46	6	16.9	0.355	8.00e-7	211

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000398	0.000398
Ashkenazi Jewish	0.00	0.00
East Asian	0.000111	0.000109
Finnish	0.00	0.00
European (Non-Finnish)	0.0000264	0.0000264
Middle Eastern	0.000111	0.000109
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Associates with IFNGR2 to form a receptor for the cytokine interferon gamma (IFNG) (PubMed:7615558, PubMed:2971451, PubMed:7617032, PubMed:10986460). Ligand binding stimulates activation of the JAK/STAT signaling pathway (PubMed:7673114). Plays an essential role in the IFN-gamma pathway that is required for the cellular response to infectious agents (PubMed:20015550). {ECO:0000269|PubMed:10986460, ECO:0000269|PubMed:20015550, ECO:0000269|PubMed:2971451, ECO:0000269|PubMed:7615558, ECO:0000269|PubMed:7617032, ECO:0000269|PubMed:7673114}.
• Disease: DISEASE: 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. {ECO:0000269|PubMed:10811850, ECO:0000269|PubMed:11139207, ECO:0000269|PubMed:15589309, ECO:0000269|PubMed:16195661, ECO:0000269|PubMed:16715106, ECO:0000269|PubMed:17514500, ECO:0000269|PubMed:20015550, ECO:0000269|PubMed:20186794, ECO:0000269|PubMed:22708048, ECO:0000269|PubMed:25592983, ECO:0000269|PubMed:27868075, ECO:0000269|PubMed:28744922, ECO:0000269|PubMed:9389728}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: 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. {ECO:0000269|PubMed:10192386, ECO:0000269|PubMed:11335768}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Kaposi,s sarcoma-associated herpesvirus infection - Homo sapiens (human);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);chaperones modulate interferon signaling pathway;ifn gamma signaling pathway;Cytokine Signaling in Immune system;JAK STAT MolecularVariation 1;Regulation of IFNG signaling;Immune System;IFN gamma signaling;SHP2 signaling;JAK STAT MolecularVariation 2;JAK STAT pathway and regulation;Interferon gamma signaling;IFN-gamma pathway;Interferon Signaling (Consensus)

Recessive Scores

• pRec: 0.518

Intolerance Scores

• loftool: 0.476
• rvis_EVS: -0.2
• rvis_percentile_EVS: 39.11

Haploinsufficiency Scores

• pHI: 0.501
• hipred: Y
• hipred_score: 0.546
• ghis: 0.547

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.981

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Ifngr1
• Phenotype: nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); digestive/alimentary phenotype; immune system phenotype; skeleton phenotype; renal/urinary system phenotype; embryo phenotype; liver/biliary system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); reproductive system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); hematopoietic system phenotype; neoplasm; endocrine/exocrine gland phenotype; cellular phenotype; homeostasis/metabolism phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan)

Gene ontology

• Biological process: signal transduction;response to virus;cytokine-mediated signaling pathway;interferon-gamma-mediated signaling pathway;regulation of interferon-gamma-mediated signaling pathway
• Cellular component: plasma membrane;integral component of plasma membrane
• Molecular function: cytokine receptor activity;interferon-gamma receptor activity;protein binding;cytokine binding