Primary immunodeficiency or monogenic inflammatory bowel disease

Gene: IFNAR1

Green List (high evidence)

Comment on list classification: As there is sufficient evidence available for the association of biallelic IFNAR1 variants with immunodeficiency, this gene can be promoted to green rating in the next GMS update.

Created: 15 Oct 2025, 2:25 p.m. | Last Modified: 15 Oct 2025, 2:25 p.m.

Panel Version: 8.47

Biallelic variants in IFNAR1 have been associated with 'immunodeficiency 106, susceptibility to viral infections' (MONDO:0030970) with a 'definitive' rating by the SCID-CID GCEP expert panel in ClinGen (https://search.clinicalgenome.org/CCID:008811)

This gene is also associated with relevant phenotype in OMIM (MIM #619935, OMIM record accessed on 15 October).

There are at least 10 unrelated families were reported with biallelic IFNAR1 variants and Immunodeficiency-106.

Created: 15 Oct 2025, 2:23 p.m. | Last Modified: 15 Oct 2025, 2:23 p.m.

Panel Version: 8.44

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Immunodeficiency 106, susceptibility to viral infections, OMIM:619935; immunodeficiency 106, susceptibility to viral infections, MONDO:0030970

Publications

• 31270247
• 33252644
• 32960813
• 35442418
• 35091979

I don't know

Comment on list classification: Not associated with phenotype in OMIM or in Gen2Phen. However, the publications listed below give evidence that the three LOF variants in two unrelated cases are associated with an adverse reaction to attenuated virus vaccines, which are rescued by wt IFNAR1 protein in vitro.

Created: 6 Apr 2020, 1:57 p.m. | Last Modified: 6 Apr 2020, 1:57 p.m.

Panel Version: 2.42

Comment on publications: PMID 31270247: reports two cases of healthy children with adverse reactions to live attuated virus vaccines. Each had biallelic loss-of-function IFNAR1 variations and the effects of these was demonstrated by the patient-derived fibroblasts being susceptible to viruses. This effect was recused by the WT IFNAR1.
PMID 26676772: reports the tageted degradation of IFNAR1 protein by
Influenza A virus (IAV), allowing the virus to escape the powerful innate immune system. Thus the loss of function of IFNAR1 would increase the susceptability to viral infection.
PMID 20020050: reports the tageted degradation of IFNAR1 protein by Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV). Confocal microscopic analysis showed increased translocation of IFNAR1 into the lysosomal compartment and flow cytometry showed reduced levels of IFNAR1 in 3a-expressing cells.

Created: 6 Apr 2020, 11:40 a.m. | Last Modified: 6 Apr 2020, 11:40 a.m.

Panel Version: 2.41

Hypothesis from Abdelazeem Elhabyan (Tanta University Hospitals): this gene is involved in the interferon-mediated immune response to viruses of those is SARS Coronavirus (2003) which down-regulates the IFNAR1 receptors through its 3a protein. Additionally, Influenzavirus A suppress immune response by downregulation of this gene. It has been also linked to adverse reactions to measles and yellow fever vaccines in healthy individuals.
Sources: Expert Review, Literature

Created: 6 Apr 2020, 11:03 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
IFNAR1 associated adverse reactions to certain live attenuated viral vaccines

Publications

• 31270247
• 26676772
• 20020050