GeneBe

IFNGR1

protein-coding

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

Gene summary

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. [provided by RefSeq, Jul 2008]

Previous symbols:
  • IFNGR

MANE transcript

NM_000416.3

Inheritance

AR, AD

ClinVar variants

P:36U:222B:87

Top phenotype

Immunodeficiency 27B; Immunodeficiency 27A

gnomAD constraint

pLI —, LoF o/e 0.35

Max pathogenic AF

—

Genomic locus

chr6:137,197,483-137,219,449

External References & Databases

Ensembl (ENSG00000027697)NCBI Gene (3459)OMIM (107470)HGNC:5439GenCCUniProt (P15260)AlphaFoldClinVar (IFNGR1)gnomADPubMedJAXSFARI

Transcript & Mutation Effects

hg38 • Region Span ~22.0 kb
Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

Mendelian susceptibility to mycobacterial diseases due to complete IFNgammaR1 deficiencySUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0020530

Submitter: Orphanet

autosomal dominant mendelian susceptibility to mycobacterial diseases due to partial IFNgammaR1 deficiencySUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0014429

Submitter: Orphanet

immunodeficiency 27ASTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0008856

Submitter: PanelApp Australia

immunodeficiency 27ASTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0008856

Submitter: Labcorp Genetics (formerly Invitae)

autosomal dominant mendelian susceptibility to mycobacterial diseases due to partial IFNgammaR1 deficiencySTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0014429

Submitter: Labcorp Genetics (formerly Invitae)

autosomal recessive Mendelian susceptibility to mycobacterial diseases due to partial IFNgammaR1 deficiencySUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0017901

Submitter: Orphanet

immunodeficiency 27ADEFINITIVE

Inheritance Pattern: AR

Disease ID:MONDO:0008856

Submitter: Ambry Genetics

autosomal dominant mendelian susceptibility to mycobacterial diseases due to partial IFNgammaR1 deficiencyDEFINITIVE

Inheritance Pattern: AD

Disease ID:MONDO:0014429

Submitter: Ambry Genetics

autosomal dominant mendelian susceptibility to mycobacterial diseases due to partial IFNgammaR1 deficiencySTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0014429

Submitter: PanelApp Australia

Clinical Genomic Database (CGD)

Immunodeficiency 27B; Immunodeficiency 27AAD/AR

Manifestation: Allergy/Immunology/Infectious

Intervention: Allergy/Immunology/Infectious

Rationale: 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

Refs: 8960475; 8960473; 9389728; 10192386Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to IFNGR1 variants in ClinVar

13 Conditions Cataloged
Disseminated atypical mycobacterial infectionTotal: 340
Immunodeficiency 27ATotal: 60
not providedTotal: 58
not specifiedTotal: 39
IFNGR1-related disorderTotal: 21
Inborn genetic diseasesTotal: 21
Autosomal dominant mendelian susceptibility to mycobacterial diseases due to partial IFNgammaR1 deficiencyTotal: 11
Helicobacter pylori infection, susceptibility toTotal: 7

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_000416.3. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

EffectPLPVUSLBBSum
synonymous
4
clinvar
75
clinvar
 79
missense
2
clinvar
2
clinvar
211
clinvar
12
clinvar
 227
nonsense
4
clinvar
2
clinvar
 6
start loss
1
clinvar
1
clinvar
 2
frameshift
14
clinvar
2
clinvar
3
clinvar
 19
splice donor/acceptor (+/-2bp)
4
clinvar
5
clinvar
3
clinvar
 12
Total2511222870345

Highest pathogenic variant AF is 0.000020449594

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 49 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_000416.3RefSeqNP_000407.17MANE Select
ENST00000367739.9EnsemblENSP00000356713.57MANE Select
NM_001363526.1RefSeqNP_001350455.17Standard
NM_001363527.1RefSeqNP_001350456.16Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

  • 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)

Biological Process

  • signal transduction
  • response to virus
  • cytokine-mediated signaling pathway
  • interferon-gamma-mediated signaling pathway
  • regulation of interferon-gamma-mediated signaling pathway

Molecular Function

  • cytokine receptor activity
  • interferon-gamma receptor activity
  • protein binding
  • cytokine binding

Cellular Component

  • plasma membrane
  • integral component of plasma membrane

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000367739
Coding exons
7
Length
21966
Individuals with no LoFs
125736
Homozygous LoFs
0
Heterozygous LoFs
12
Defined
125748
p
0.0000477
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense0.3052462600.9470.00001263194
Missense (PolyPhen)5466.1560.81626906
Synonymous0.954881000.8790.00000572932
Loss of Function2.46616.90.3558.00e-7211

Population LoF Frequency

PopulationCAFp-valueStatus
African0.000370.00037rare
Latino/Admixed American0.0000290.000029rare
Ashkenazi Jewish00.0absent
East Asian0.000110.00011rare
Finnish00.0absent
European (Non-Finnish)0.0000260.000026rare
South Asian00.0absent
Other00.0absent

dbNSFP Gene Annotations

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.;

Recessive Scores

pRec
0.518

Intolerance Scores

LoFtool
0.476
RVIS EVS
-0.2
RVIS percentile EVS
39.11

Essentials

Essential (CRISPR)
N
Essential (CRISPR2)
N
Essential (gene trap)
N
Indispensability pred.
E
Indispensability score
0.981

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium
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