IFNAR1

interferon alpha and beta receptor subunit 1, the group of Interferon receptors

Basic information

Region (hg38): 21:33324386-33359864

Previous symbols: [ "IFNAR" ]

Links

ENSG00000142166 ∙ NCBI:3454 ∙ OMIM:107450 ∙ HGNC:5432 ∙ Uniprot:P17181 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• immunodeficiency 106, susceptibility to viral infections (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Immunodeficiency 106, susceptibility to viral infections	AR	Allergy/Immunology/Infectious	The condition involves increased risk of viral infections as well as adverse events related to live virus vaccination, and antiinfectious prophylaxis, early and aggressive treatment of infections, and consideration of vaccination regimens may be beneficial	Allergy/Immunology/Infectious	31270247; 32960813; 33252644; 34713375; 35091979; 35442418

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the IFNAR1 gene.

• not provided (211 variants)
• Inborn genetic diseases (24 variants)
• not specified (5 variants)
• Immunodeficiency 106, susceptibility to viral infections (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the IFNAR1 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	38	7	46
missense			108	3	3	114
nonsense	4		1			5
start loss						0
frameshift	7	1	2			10
inframe indel			2	2		4
splice donor/acceptor (+/-2bp)		6	1			7
splice region			3	4		7
non coding				26	8	34
Total	11	7	115	69	18

Highest pathogenic variant AF is 0.000223

Variants in IFNAR1

This is a list of pathogenic ClinVar variants found in the IFNAR1 region.

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

Position	Type	Phenotype	Significance	ClinVar
21-33325065-G-A			Uncertain significance (Apr 21, 2022)
21-33325069-T-G			Uncertain significance (Sep 08, 2023)
21-33325070-C-A			Likely benign (Jun 11, 2023)
21-33325071-C-T			Likely benign (Aug 12, 2022)
21-33325072-T-C			Uncertain significance (Nov 22, 2022)
21-33325073-G-A			Likely benign (Nov 17, 2023)
21-33325076-C-T			Likely benign (Apr 11, 2022)
21-33325079-G-A			Likely benign (Jun 27, 2022)
21-33325081-CG-C			Pathogenic (Nov 04, 2023)
21-33325083-A-G		not specified	Conflicting classifications of pathogenicity (Feb 13, 2024)
21-33325086-C-G			Uncertain significance (Aug 31, 2021)
21-33325091-G-A			Likely benign (Jul 06, 2022)
21-33325091-G-C			Likely benign (Nov 02, 2021)
21-33325101-G-A			Uncertain significance (Mar 03, 2022)
21-33325105-C-T		not specified	Uncertain significance (Nov 22, 2023)
21-33325110-T-G			Uncertain significance (Sep 12, 2023)
21-33325119-T-G			Uncertain significance (Dec 12, 2023)
21-33325119-TCCGCAG-T			Uncertain significance (Oct 13, 2023)
21-33325124-A-G			Likely benign (Dec 11, 2023)
21-33325127-C-T			Likely benign (Jul 12, 2023)
21-33325138-G-A			Likely benign (Dec 11, 2023)
21-33325140-C-A			Likely benign (Feb 20, 2022)
21-33325141-G-A			Likely benign (Jun 28, 2023)
21-33335502-T-G		not specified	Benign (Jan 24, 2024)
21-33335515-C-T			Likely benign (May 24, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
IFNAR1	protein_coding	protein_coding	ENST00000270139	11	35435

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
3.25e-12	0.155	125705	0	42	125747	0.000167

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.361	270	287	0.940	0.0000140	3690
Missense in Polyphen		65	73.552	0.88372		988
Synonymous	-0.213	108	105	1.03	0.00000560	1006
Loss of Function	0.755	20	24.0	0.834	0.00000101	321

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00129	0.00129
Ashkenazi Jewish	0.00	0.00
East Asian	0.000187	0.000163
Finnish	0.00	0.00
European (Non-Finnish)	0.000108	0.000105
Middle Eastern	0.000187	0.000163
South Asian	0.000136	0.000131
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Component of the receptor for type I interferons, including interferons alpha, IFNB1 and IFNW1 (PubMed:2153461, PubMed:7665574, PubMed:10049744, PubMed:14532120, PubMed:15337770, PubMed:21854986). Functions in general as heterodimer with IFNAR2 (PubMed:7665574, PubMed:10049744, PubMed:21854986). Type I interferon binding activates the JAK-STAT signaling cascade, and triggers tyrosine phosphorylation of a number of proteins including JAKs, TYK2, STAT proteins and the IFNR alpha- and beta- subunits themselves (PubMed:7665574, PubMed:21854986). Can form an active IFNB1 receptor by itself and activate a signaling cascade that does not involve activation of the JAK-STAT pathway (By similarity). {ECO:0000250|UniProtKB:P33896, ECO:0000269|PubMed:10049744, ECO:0000269|PubMed:14532120, ECO:0000269|PubMed:15337770, ECO:0000269|PubMed:19561067, ECO:0000269|PubMed:2153461, ECO:0000269|PubMed:7665574, ECO:0000305|PubMed:21854986}.
• Pathway: PI3K-Akt signaling pathway - Homo sapiens (human);Kaposi,s sarcoma-associated herpesvirus infection - Homo sapiens (human);Jak-STAT signaling pathway - Homo sapiens (human);Influenza A - Homo sapiens (human);Necroptosis - Homo sapiens (human);Toll-like receptor signaling pathway - Homo sapiens (human);NOD-like receptor signaling pathway - Homo sapiens (human);Natural killer cell mediated cytotoxicity - Homo sapiens (human);Pathways in cancer - Homo sapiens (human);Hepatitis C - Homo sapiens (human);Hepatitis B - Homo sapiens (human);Measles - Homo sapiens (human);Osteoclast differentiation - Homo sapiens (human);Cytokine-cytokine receptor interaction - Homo sapiens (human);Human papillomavirus infection - Homo sapiens (human);Herpes simplex infection - Homo sapiens (human);JAK-STAT-Core;Osteoclast Signaling;Regulation of toll-like receptor signaling pathway;Focal Adhesion-PI3K-Akt-mTOR-signaling pathway;PI3K-Akt Signaling Pathway;The human immune response to tuberculosis;Interferon type I signaling pathways;Toll-like Receptor Signaling Pathway;ifn alpha signaling pathway;Cytokine Signaling in Immune system;JAK STAT MolecularVariation 1;Immune System;IFN alpha signaling;JAK STAT MolecularVariation 2;bone remodeling;JAK STAT pathway and regulation;Regulation of IFNA signaling;Interferon alpha/beta signaling;Downstream signaling in naïve CD8+ T cells;Interferon Signaling (Consensus)

Recessive Scores

• pRec: 0.0742

Intolerance Scores

• loftool: 0.696
• rvis_EVS: 0.04
• rvis_percentile_EVS: 57.31

Haploinsufficiency Scores

• pHI: 0.0941
• hipred: Y
• hipred_score: 0.672
• ghis: 0.495

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.967

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Ifnar1
• 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); growth/size/body region phenotype; endocrine/exocrine gland phenotype; cellular phenotype; homeostasis/metabolism phenotype; skeleton phenotype; renal/urinary 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); hematopoietic system phenotype; 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); neoplasm; digestive/alimentary phenotype; vision/eye phenotype; immune system phenotype

Gene ontology

• Biological process: JAK-STAT cascade;response to virus;cytokine-mediated signaling pathway;response to lipopolysaccharide;cellular response to interferon-alpha;type I interferon signaling pathway
• Cellular component: lysosome;late endosome;plasma membrane;integral component of plasma membrane
• Molecular function: cytokine receptor activity;type I interferon receptor activity;protein binding;type I interferon binding