IFNGR1 Gene: Interferon Gamma Receptor 1 - Function, Disease Associations, and Clinical Significance
Comprehensive biomedical resource for IFNGR1, covering genomic data, expression profiles, pathogenic variants, and related disorders.
Gene Information Card
| Symbol | IFNGR1 |
|---|---|
| Full Name | Interferon Gamma Receptor 1 |
| Gene Type | protein coding |
| Chromosomal Location | 6q23.3 |
| NCBI Gene ID | 3459 ncbi.nlm.nih.gov/gene/3459 |
| Ensembl ID | ENSG00000027697 |
| UniProt ID | P15260 |
| OMIM ID | 107470 |
| HGNC ID | 5439 |
| Aliases | CD119, IFNGR, IMD27A, IMD27B |
Description
The IFNGR1 gene encodes the ligand-binding chain (alpha chain) of the interferon-gamma (IFN-γ) receptor. This receptor is a heterodimer composed of IFNGR1 and IFNGR2 chains. IFNGR1 is responsible for binding IFN-γ with high affinity and is essential for signal transduction via the JAK-STAT pathway. Upon IFN-γ binding, the receptor complex activates JAK1 and JAK2, leading to STAT1 phosphorylation, dimerization, and nuclear translocation to regulate the expression of genes involved in innate and adaptive immunity, particularly macrophage activation, antigen presentation, and antimicrobial responses. Defects in IFNGR1 are a primary cause of Mendelian Susceptibility to Mycobacterial Disease (MSMD), characterized by severe infections with weakly virulent mycobacteria.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Disease | Mechanism | Evidence |
| Mendelian Susceptibility to Mycobacterial Disease (MSMD) | Loss-of-function mutations in IFNGR1 impair the IFN-γ/IL-12 axis, critical for immunity against intracellular pathogens. This leads to defective macrophage activation and reduced TNF-α production, allowing uncontrolled mycobacterial growth. | ClinVar, OMIM |
| Immunodeficiency 27A (IMD27A) | Autosomal recessive complete IFNGR1 deficiency results in a complete lack of functional IFN-γ receptor, leading to severe, early-onset mycobacterial infections. | OMIM, ClinVar |
| Immunodeficiency 27B (IMD27B) | Autosomal dominant partial IFNGR1 deficiency is caused by dominant-negative mutations, typically in the intracellular domain, leading to impaired but not absent IFN-γ signaling. This results in milder, later-onset mycobacterial infections. | OMIM, ClinVar |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Tissue | nTPM | Level |
| Spleen | 22.3 | Medium |
| Lung | 18.9 | Medium |
| Bone Marrow | 17.5 | Medium |
| Blood | 15.2 | Medium |
| Liver | 10.1 | Low |
| Brain | 5.4 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| Cell Line | nTPM | Notes |
| THP-1 (Monocyte) | 25.3 | High expression in monocytic cell lines, consistent with its role in immune cells. |
| K-562 (Lymphoblast) | 18.7 | Moderate expression in lymphoblastoid cells. |
| HeLa (Cervical) | 8.2 | Lower expression in non-immune epithelial cell lines. |
| A549 (Lung) | 7.9 | Low expression in lung carcinoma cells. |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| Variant | Type | Frequency | Effect |
| c.818del (p.Lys273SerfsTer18) | Frameshift | Rare | Loss-of-function; leads to premature stop codon and truncated protein, causing autosomal recessive complete IFNGR1 deficiency. |
| c.1114T>C (p.Tyr372His) | Missense | Rare | Dominant-negative; disrupts the JAK1 binding site in the intracellular domain, impairing signal transduction. |
| c.200+2T>C | Splice-site | Rare | Loss-of-function; affects splicing, leading to aberrant mRNA and non-functional protein. |
| c.295C>T (p.Arg99Ter) | Nonsense | Rare | Loss-of-function; introduces a premature stop codon, resulting in a truncated, non-functional receptor. |
Mutation functional classification
Loss of Function (LOF)
Complete loss-of-function mutations (e.g., frameshift, nonsense, splice-site) result in the absence of a functional IFNGR1 protein. This leads to autosomal recessive complete IFNGR1 deficiency (IMD27A), characterized by a complete lack of response to IFN-γ and severe, early-onset mycobacterial infections.
Gain of Function (GOF)
No gain-of-function mutations have been clinically characterized for IFNGR1. The receptor's function is primarily dependent on ligand binding and signal transduction, and constitutive activation would be detrimental.
Dominant Negative (DN)
Dominant-negative mutations, typically missense mutations in the intracellular domain (e.g., p.Tyr372His), produce a receptor that can bind IFN-γ but fails to transduce the signal. This mutant receptor interferes with the function of the wild-type receptor in a heterozygous state, leading to autosomal dominant partial IFNGR1 deficiency (IMD27B).
View complete mutation data：
Gene Ontology (GO)
| • interferon-gamma receptor activity | • cytokine receptor activity |
| • protein homodimerization activity | • signal transducer activity |
| • plasma membrane | • integral component of plasma membrane |
| • immune response | • signal transduction |
| • JAK-STAT cascade | • response to interferon-gamma |
Pathways
• Interferon gamma signaling
• JAK-STAT signaling pathway
• Cytokine-cytokine receptor interaction
• Th1 and Th2 cell differentiation
Protein Summary
The IFNGR1 protein is a 90 kDa, type II transmembrane glycoprotein. It consists of a 228-amino acid extracellular domain responsible for IFN-γ binding, a single transmembrane domain, and a 221-amino acid intracellular domain containing binding sites for JAK1 and STAT1. The protein is N-glycosylated and forms a homodimer that, upon binding IFN-γ, associates with two IFNGR2 chains to form the functional receptor complex. The intracellular domain contains a critical LPKS motif required for JAK1 association and a STAT1 docking site. Post-translational modifications include phosphorylation on serine residues, which may modulate receptor signaling.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| IFNGR1 Knockout HEK293 Cell Line | EDJ-KQ476 | Human | 3459 | Details Get a Quote |
| IFNGR1 Knockout A-549 Cell Line | EDJ-KQ18782 | Human | 3459 | Details Get a Quote |
| IFNGR1 Knockout HCT 116 Cell Line | EDJ-KQ18783 | Human | 3459 | Details Get a Quote |
| IFNGR1 Knockout HeLa Cell Line | EDJ-KQ18784 | Human | 3459 | Details Get a Quote |
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