Immunodeficiency 106, susceptibility to viral infections

Summary

Immunodeficiency 106, susceptibility to viral infections (MONDO:0030970) is a disease caused by IFNAR1 (GenCC Definitive), with 1 cohort gene.

At a glance

• Causal gene: IFNAR1 (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 15

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	immunodeficiency 106, susceptibility to viral infections
Mondo ID	MONDO:0030970
OMIM	619935
DOID	DOID:0061075
UMLS	C5677009
MedGen	1804672
Is cancer (heuristic)	no

Also known as: IFNAR1 deficiency · IMD106 · immunodeficiency 106, susceptibility to viral infections

Data availability: 15 ClinVar variants · 3 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › immunodeficiency disease › immunodeficiency 106, susceptibility to viral infections

Related subtypes (94): B cell deficiency, T-cell immunodeficiency, complement deficiency, myalgic encephalomeyelitis/chronic fatigue syndrome, hypoproteinemia, hypercatabolic, X-linked lymphoproliferative syndrome, Wiskott-Aldrich syndrome, autosomal dominant form, immunodeficiency due to CD25 deficiency, immunodeficiency 67, primary immunodeficiency with natural-killer cell deficiency and adrenal insufficiency, immunodeficiency 35, pyogenic bacterial infections due to MyD88 deficiency, lymphoproliferative syndrome 1, FADD-related immunodeficiency, immunodeficiency 31B, Wiskott-Aldrich syndrome 2, cryptosporidiosis-chronic cholangitis-liver disease syndrome, idiopathic CD4 lymphocytopenia, immunodeficiency 23, DOCK2 deficiency, immunodeficiency 45, TFRC-related combined immunodeficiency, combined immunodeficiency, autoimmune hemolytic anemia-autoimmune thrombocytopenia-primary immunodeficiency syndrome, immunodeficiency due to selective anti-polysaccharide antibody deficiency, immunodeficiency 57, immunodeficiency 14b, autosomal recessive, immunodeficiency 98 with autoinflammation, X-linked, immunodeficiency 102, immunodeficiency 74, COVID-19-related, X-linked, immunodeficiency 66, immunodeficiency 80 with or without congenital cardiomyopathy, immunodeficiency 81, immunodeficiency 82 with systemic inflammation, immunodeficiency 84, immunodeficiency 85 and autoimmunity, immunodeficiency 86, immunodeficiency 87 and autoimmunity, immunodeficiency 88, immunodeficiency 89 and autoimmunity, immunodeficiency 91 and hyperinflammation, immunodeficiency 92, immunodeficiency 93 and hypertrophic cardiomyopathy, immunodeficiency 95, immunodeficiency 96, immunodeficiency 97 with autoinflammation, immunodeficiency 99 with hypogammaglobulinemia and autoimmune cytopenias, immunodeficiency 101 (varicella zoster virus-specific), immunodeficiency 75, immunodeficiency 76, immunodeficiency 78 with autoimmunity and developmental delay, immunodeficiency 77, immunodeficiency 107, susceptibility to invasive staphylococcus aureus infection, immunodeficiency 15a, immunodeficiency 60, immunodeficiency 62, immunodeficiency 63 with lymphoproliferation and autoimmunity, immunodeficiency 64, immunodeficiency 65, susceptibility to viral infections, immunodeficiency 69, immunodeficiency 70, immunodeficiency 72 with autoinflammation, GATA2 deficiency with susceptibility to MDS/AML, Shwachman-Diamond syndrome 1, immunodeficiency 53, immunodeficiency 11b with atopic dermatitis, IKBKG-related immunodeficiency with or without ectodermal dysplasia, FNIP1-associated syndrome, FASLG-related immunodeficiency, TNFRSF9-related immunodeficiency, DNAJC21-related Shwachman Diamond syndrome, IRF4-related immune disorder, PTEN harmartoma tumor syndrome with immune disorder, primary immunodeficiency due to calcium channel deficiency, chronic mucocutaneous candidiasis and connective tissue disease due to JNK1 haploinsufficiency, immune deficiency due to impaired neutrophil phagocytosis and migration, hatipoglu immunodeficiency syndrome, immunodeficiency 112, immunodeficiency 113 with autoimmunity and autoinflammation, immunodeficiency 114, folate-responsive, immunodeficiency 115 with autoinflammation, immunodeficiency 117, immunodeficiency 118, immunodeficiency 119, immunodeficiency 121 with autoinflammation, immunodeficiency 122, immunodeficiency 123 with HPV-related verrucosis, immunodeficiency 125, immunodeficiency 126, susceptibility to, immunodeficiency 127, immunodeficiency 128, immunodeficiency 132b, immunodeficiency 133 with ectodermal dysplasia with or without peripheral neuropathy, immunodeficiency 134 (Epstein-Barr virus-specific)

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

15 retrieved; paginated sample, class counts are floors:

6 risk factor, 4 uncertain significance, 2 pathogenic, 2 likely pathogenic, 1 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1437264	NM_000629.3(IFNAR1):c.1156G>T (p.Glu386Ter)	IFNAR1	Pathogenic	criteria provided, single submitter
2431416	NC_000021.9:g.(33336874_33344911)del	IFNAR1	Pathogenic	criteria provided, single submitter
3000638	NM_000629.3(IFNAR1):c.750T>G (p.Tyr250Ter)	IFNAR1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1498680	NM_000629.3(IFNAR1):c.377-2A>G	IFNAR1	Likely pathogenic	criteria provided, multiple submitters, no conflicts
2581563	NM_000629.3(IFNAR1):c.1356del (p.Phe452fs)	IFNAR1	Likely pathogenic	criteria provided, single submitter
1693254	NM_000629.3(IFNAR1):c.922C>T (p.Gln308Ter)	IFNAR1	risk factor	no assertion criteria provided
1693255	NM_000629.3(IFNAR1):c.1440+331_*239del	IFNAR1	risk factor	no assertion criteria provided
1693257	NM_000629.3(IFNAR1):c.788+1636_1144-1368del	IFNAR1	risk factor	no assertion criteria provided
691594	NM_000629.3(IFNAR1):c.674-2A>G	IFNAR1	risk factor	no assertion criteria provided
691595	NM_000629.3(IFNAR1):c.674-1G>A	IFNAR1	risk factor	no assertion criteria provided
691596	NM_000629.3(IFNAR1):c.783G>A (p.Trp261Ter)	IFNAR1	risk factor	no assertion criteria provided
1299494	NM_000629.3(IFNAR1):c.1672_*3del (p.Ter558del)	IFNAR1	Uncertain significance	criteria provided, single submitter
3064420	NM_000629.3(IFNAR1):c.1671_*1821del (p.Ter558AlaextTer?)	IFNAR1	Uncertain significance	criteria provided, single submitter
3065116	NM_000629.3(IFNAR1):c.*2205_*2213del	IFNAR1	Uncertain significance	criteria provided, single submitter
3065852	NM_000629.3(IFNAR1):c.1672T>C (p.Ter558Arg)	IFNAR1	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 3 · Orphanet: 0 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
IFNAR1	Definitive	Autosomal recessive	immunodeficiency 106, susceptibility to viral infections	3

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
IFNAR1	HGNC:5432	ENSG00000142166	P17181	Interferon alpha/beta receptor 1	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
IFNAR1	Interferon alpha/beta receptor 1	Together with IFNAR2, forms the heterodimeric receptor for type I interferons (including interferons alpha, beta, epsilon, omega and kappa).

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Antibody/Immunoglobulin	1	29.2×	0.034

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
IFNAR1	Antibody/Immunoglobulin	yes		FN3_dom, Ig-like_fold, Interferon/interleukin_rcp_dom

Expression context

Cohort genes with no expression data: 0.

1 cohort gene are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
leukocyte	1
monocyte	1
mononuclear cell	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
IFNAR1	258	ubiquitous	marker	monocyte, mononuclear cell, leukocyte

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
IFNAR1	2,300

Structural data

PDB: 1 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
IFNAR1	P17181	5

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 16. Enrichment computed across 1 evidence-associated genes (1 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Regulation of IFNA/IFNB signaling	1	439.2×	0.018	IFNAR1
Evasion by RSV of host interferon responses	1	326.3×	0.018	IFNAR1
Respiratory Syncytial Virus Infection Pathway	1	196.9×	0.018	IFNAR1
RSV-host interactions	1	156.4×	0.018	IFNAR1
Interferon alpha/beta signaling	1	152.3×	0.018	IFNAR1
Interferon Signaling	1	120.2×	0.018	IFNAR1
SARS-CoV-2-host interactions	1	119.0×	0.018	IFNAR1
Potential therapeutics for SARS	1	114.2×	0.018	IFNAR1
SARS-CoV-2 activates/modulates innate and adaptive immune responses	1	89.2×	0.020	IFNAR1
SARS-CoV-2 Infection	1	80.4×	0.020	IFNAR1
SARS-CoV Infections	1	55.4×	0.026	IFNAR1
Cytokine Signaling in Immune system	1	40.8×	0.033	IFNAR1
Viral Infection Pathways	1	30.8×	0.040	IFNAR1
Infectious disease	1	24.8×	0.046	IFNAR1
Disease	1	13.1×	0.077	IFNAR1
Immune System	1	13.0×	0.077	IFNAR1

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
positive regulation of cellular respiration	1	1872.4×	0.003	IFNAR1
cellular response to interferon-alpha	1	1532.0×	0.003	IFNAR1
cellular response to interferon-beta	1	526.6×	0.005	IFNAR1
type I interferon-mediated signaling pathway	1	343.9×	0.006	IFNAR1
cell surface receptor signaling pathway via JAK-STAT	1	290.6×	0.006	IFNAR1
cellular response to virus	1	200.6×	0.007	IFNAR1
response to virus	1	144.0×	0.008	IFNAR1
response to lipopolysaccharide	1	124.8×	0.008	IFNAR1

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 1

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
IFNAR1	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
IFNAR1	8	Binding:5, Functional:3

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

0 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	1	IFNAR1
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

Undrugged target profiles

1 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
IFNAR1	8	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.