IFIH1-related type 1 interferonopathy

Summary

IFIH1-related type 1 interferonopathy (MONDO:0700262) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 4

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	IFIH1-related type 1 interferonopathy
Mondo ID	MONDO:0700262
GARD	0026405
Is cancer (heuristic)	no

Data availability: 4 ClinVar variants.

Disease family

An umbrella term covering 2 Mondo subtypes.

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › hereditary disorder of connective tissue › IFIH1-related type 1 interferonopathy

Related subtypes (86): Ewing sarcoma of bone, hereditary multiple osteochondromas, acroosteolysis dominant type, diaphyseal medullary stenosis-bone malignancy syndrome, cherubism, chondrocalcinosis 2, desmoid tumor, familial ossifying fibroma, hyperparathyroidism 1, hyperparathyroidism 2 with jaw tumors, uterine corpus leiomyoma, multiple symmetric lipomatosis, systemic lupus erythematosus, Ollier disease, Peyronie disease, Singleton-Merten dysplasia, Blau syndrome, inherited torticollis, arterial tortuosity syndrome, camptodactyly-arthropathy-coxa vara-pericarditis syndrome, chondrosarcoma, trichohepatoenteric syndrome, brittle cornea syndrome, neonatal severe primary hyperparathyroidism, proteosome-associated autoinflammatory syndrome, chronic recurrent multifocal osteomyelitis, Pelger-Huet-like anomaly and episodic fever with abdominal pain, acquired polycythemia vera, autosomal recessive inherited pseudoxanthoma elasticum, X-linked reticulate pigmentary disorder, CHILD syndrome, ossification of the posterior longitudinal ligament of the spine, MASS syndrome, pyogenic arthritis-pyoderma gangrenosum-acne syndrome, Spondyloenchondrodysplasia with immune dysregulation, sweet syndrome, chronic myeloid leukemia, hyperparathyroidism 3, bone fragility with contractures, arterial rupture, and deafness, encephalocraniocutaneous lipomatosis, psoriasis 14, pustular, Maffucci syndrome, autoinflammation-PLCG2-associated antibody deficiency-immune dysregulation, deficiency of adenosine deaminase 2, STING-associated vasculopathy with onset in infancy, autoimmune interstitial lung disease-arthritis syndrome, progeroid and marfanoid aspect-lipodystrophy syndrome, thrombocytopenia 6, multiple epiphyseal dysplasia due to collagen 9 anomaly, Ehlers-Danlos syndrome, kyphoscoliotic type 1, juvenile hyaline fibromatosis, IL10-related early-onset inflammatory bowel disease, infantile myofibromatosis, Marfan and Marfan-related disorder, neonatal inflammatory skin and bowel disease, familial isolated pituitary adenoma, inherited acute myeloid leukemia, hereditary periodic fever syndrome, autoinflammatory syndrome with pyogenic bacterial infection and amylopectinosis, aneurysmal bone cyst, familial chilblain lupus, pseudo-TORCH syndrome 2, Aicardi-Goutieres syndrome, jugulotympanic paraganglioma, type 2 collagenopathy, hyperparathyroidism 4, VEXAS syndrome, autoinflammatory syndrome, familial, Behcet-like, congenital progressive bone marrow failure-B-cell immunodeficiency-skeletal dysplasia syndrome, LAMA5-related multisystemic syndrome, EMILIN-1-related connective tissue disease, TREX1-related type 1 interferonopathy, RNASEH2B-related type 1 interferonopathy, RNASEH2C-related type 1 interferonopathy, RNASEH2A-related type 1 interferonopathy, SAMHD1-related type 1 interferonopathy, ADAR-related type 1 interferonopathy, RNU7-1-related type 1 interferonopathy, autoinflammatory disease, X-linked, autoinflammatory syndrome with immunodeficiency, autoinflammatory disease, systemic, with vasculitis, autoinflammatory disease, multisystem, with immune dysregulation, X-linked, arterial tortuosity-bone fragility syndrome, linkeropathy, hypermobility spectrum disorder, Sharpin-related autoinflammatory syndrome

Subtypes (2): Aicardi-Goutieres syndrome 7, Singleton-Merten syndrome 1

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

4 retrieved; paginated sample, class counts are floors:

2 uncertain significance, 1 likely pathogenic, 1 conflicting classifications of pathogenicity

ClinVar	Variant (HGVS)	Gene	Classification	Review
3779757	NM_022168.4(IFIH1):c.2067del (p.Arg689fs)	IFIH1	Likely pathogenic	criteria provided, multiple submitters, no conflicts
580488	NM_022168.4(IFIH1):c.2016del (p.Asp673fs)	IFIH1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1363529	NM_022168.4(IFIH1):c.929del (p.Pro310fs)	IFIH1	Uncertain significance	criteria provided, multiple submitters, no conflicts
547992	NM_022168.4(IFIH1):c.454-1G>T	IFIH1	Uncertain significance	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

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

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
IFIH1	Orphanet:51	Aicardi-Goutières syndrome
IFIH1	Orphanet:689231	IFIH1-related hereditary spastic paraplegia
IFIH1	Orphanet:85191	Singleton-Merten dysplasia

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
IFIH1	HGNC:18873	ENSG00000115267	Q9BYX4	Interferon-induced helicase C domain-containing protein 1	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
IFIH1	Interferon-induced helicase C domain-containing protein 1	Innate immune receptor which acts as a cytoplasmic sensor of viral nucleic acids and plays a major role in sensing viral infection and in the activation of a cascade of antiviral responses including the induction of type I interferons and…

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.0

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
Other/Unknown	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
IFIH1	Other/Unknown	no		Helicase_C-like, Helicase/UvrB_N, DEATH-like_dom_sf

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
jejunal mucosa	1
palpebral conjunctiva	1
parotid gland	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
IFIH1	276	ubiquitous	marker	palpebral conjunctiva, parotid gland, jejunal mucosa

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
IFIH1	3,706

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
IFIH1	Q9BYX4	9

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 13. 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
NF-kB activation through FADD/RIP-1 pathway mediated by caspase-8 and -10	1	878.5×	0.005	IFIH1
TRAF3-dependent IRF activation pathway	1	761.3×	0.005	IFIH1
Modulation of host responses by IFN-stimulated genes	1	601.0×	0.005	IFIH1
TRAF6 mediated NF-kB activation	1	456.8×	0.005	IFIH1
TRAF6 mediated IRF7 activation	1	380.7×	0.005	IFIH1
Dengue virus activates/modulates innate and adaptive immune responses	1	335.9×	0.005	IFIH1
Negative regulators of DDX58/IFIH1 signaling	1	326.3×	0.005	IFIH1
Evasion by RSV of host interferon responses	1	326.3×	0.005	IFIH1
Ovarian tumor domain proteases	1	278.5×	0.005	IFIH1
SARS-CoV-1 activates/modulates innate immune responses	1	271.9×	0.005	IFIH1
DDX58/IFIH1-mediated induction of interferon-alpha/beta	1	253.8×	0.005	IFIH1
SARS-CoV-2 activates/modulates innate and adaptive immune responses	1	89.2×	0.012	IFIH1
Ub-specific processing proteases	1	53.1×	0.019	IFIH1

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
regulation of type III interferon production	1	8426.0×	0.002	IFIH1
detection of virus	1	4213.0×	0.002	IFIH1
MDA-5 signaling pathway	1	4213.0×	0.002	IFIH1
positive regulation of response to cytokine stimulus	1	2407.4×	0.002	IFIH1
cellular response to exogenous dsRNA	1	1053.2×	0.004	IFIH1
cytoplasmic pattern recognition receptor signaling pathway	1	887.0×	0.004	IFIH1
protein complex oligomerization	1	674.1×	0.004	IFIH1
positive regulation of interferon-alpha production	1	648.1×	0.004	IFIH1
positive regulation of interferon-beta production	1	391.9×	0.005	IFIH1
negative regulation of viral genome replication	1	374.5×	0.005	IFIH1
type I interferon-mediated signaling pathway	1	343.9×	0.005	IFIH1
protein sumoylation	1	324.1×	0.005	IFIH1
antiviral innate immune response	1	227.7×	0.006	IFIH1
cellular response to virus	1	200.6×	0.007	IFIH1
positive regulation of interleukin-6 production	1	166.8×	0.008	IFIH1
positive regulation of tumor necrosis factor production	1	153.2×	0.008	IFIH1
response to virus	1	144.0×	0.008	IFIH1
defense response to virus	1	69.3×	0.015	IFIH1
innate immune response	1	33.6×	0.030	IFIH1

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
IFIH1	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
IFIH1	1	Binding:1

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	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	IFIH1

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)
IFIH1	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.