GeneBe

IFNGR2

protein-coding

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

Gene summary

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. [provided by RefSeq, Jul 2008]

Previous symbols:
  • IFNGT1

MANE transcript

NM_005534.4

Inheritance

AR, AD

ClinVar variants

P:9U:94B:82

Top phenotype

Immunodeficiency 28

gnomAD constraint

pLI —, LoF o/e 0.07

Max pathogenic AF

—

Genomic locus

chr21:33,403,413-33,479,348

External References & Databases

Ensembl (ENSG00000159128)NCBI Gene (3460)OMIM (147569)HGNC:5440GenCCUniProt (P38484)AlphaFoldClinVar (IFNGR2)gnomADPubMedJAXSFARI

Transcript & Mutation Effects

hg38 • Region Span ~75.9 kb
Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

autosomal recessive Mendelian susceptibility to mycobacterial diseases due to partial IFNgammaR2 deficiencySUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0017902

Submitter: Orphanet

immunodeficiency 28STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0013953

Submitter: Labcorp Genetics (formerly Invitae)

autosomal dominant mendelian susceptibility to mycobacterial diseases due to partial IFNgammaR2 deficiencySUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0017903

Submitter: Orphanet

immunodeficiency 28STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0013953

Submitter: PanelApp Australia

autosomal recessive Mendelian susceptibility to mycobacterial diseases due to complete IFNgammaR2 deficiencySUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0017900

Submitter: Orphanet

Clinical Genomic Database (CGD)

Immunodeficiency 28AR

Manifestation: Allergy/Immunology/Infectious

Intervention: Allergy/Immunology/Infectious

Rationale: Individuals may be susceptible to frequent and severe mycobacterial infections, and antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial

Refs: 15924140; 23161749; 31222290Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to IFNGR2 variants in ClinVar

8 Conditions Cataloged
Immunodeficiency 28Total: 217
not providedTotal: 49
not specifiedTotal: 43
Inborn genetic diseasesTotal: 34
IFNGR2-related disorderTotal: 12
Immunodeficiency 27ATotal: 2
Susceptibility to severe COVID-19Total: 1
Interferon gamma receptor deficiencyTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_005534.4. 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
3
clinvar
65
clinvar
 68
missense
1
clinvar
90
clinvar
17
clinvar
 108
nonsense
1
clinvar
1
clinvar
 2
start loss
2
clinvar
 2
frameshift
4
clinvar
1
clinvar
 5
splice donor/acceptor (+/-2bp)
0
Total5494820185

Highest pathogenic variant AF is 0.000022608314

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 31 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_005534.4RefSeqNP_005525.27MANE Select
ENST00000290219.11EnsemblENSP00000290219.57MANE Select
NM_001329128.2RefSeqNP_001316057.18Standard
ENST00000381995.5EnsemblENSP00000371425.18Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

  • 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)

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

Molecular Function

  • cytokine receptor activity
  • interferon-gamma receptor activity

Cellular Component

  • Golgi membrane
  • endoplasmic reticulum
  • endoplasmic reticulum membrane
  • plasma membrane
  • integral component of plasma membrane

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000290219
Coding exons
7
Length
76454
Individuals with no LoFs
125724
Homozygous LoFs
0
Heterozygous LoFs
3
Defined
125727
p
0.0000119
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense0.8281381680.8200.000009832167
Missense (PolyPhen)3350.4610.65397679
Synonymous0.2106769.20.9680.00000484672
Loss of Function3.22114.00.07146.79e-7168

Population LoF Frequency

PopulationCAFp-valueStatus
African00.0absent
Latino/Admixed American0.0000290.000029rare
Ashkenazi Jewish00.0absent
East Asian0.000110.00011rare
Finnish00.0absent
European (Non-Finnish)00.0absent
South Asian00.0absent
Other00.0absent

dbNSFP Gene Annotations

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}.;

Recessive Scores

pRec
0.163

Intolerance Scores

RVIS EVS
0.66
RVIS percentile EVS
84.55

Essentials

Essential (CRISPR)
N
Essential (CRISPR2)
N
Essential (gene trap)
N
Indispensability pred.
E
Indispensability score
0.883

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium
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