Immunodeficiency 95

Summary

Immunodeficiency 95 (MONDO:0030692) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 55

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	immunodeficiency 95
Mondo ID	MONDO:0030692
OMIM	619773
DOID	DOID:0061065
UMLS	C5676929
MedGen	1802205
Is cancer (heuristic)	no

Also known as: IMD95 · immunodeficiency 95

Data availability: 55 ClinVar variants · 1 GenCC gene-disease record.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › immunodeficiency disease › immunodeficiency 95

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 96, immunodeficiency 97 with autoinflammation, immunodeficiency 99 with hypogammaglobulinemia and autoimmune cytopenias, immunodeficiency 101 (varicella zoster virus-specific), immunodeficiency 75, immunodeficiency 76, immunodeficiency 106, susceptibility to viral infections, 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

55 retrieved; paginated sample, class counts are floors:

23 conflicting classifications of pathogenicity, 21 uncertain significance, 6 benign/likely benign, 2 likely pathogenic, 1 benign, 1 pathogenic/likely pathogenic, 1 likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
137622	NM_022168.4(IFIH1):c.2336G>A (p.Arg779His)	IFIH1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1687394	NM_022168.4(IFIH1):c.317C>A (p.Ser106Ter)	IFIH1	Likely pathogenic	criteria provided, single submitter
3779757	NM_022168.4(IFIH1):c.2067del (p.Arg689fs)	IFIH1	Likely pathogenic	criteria provided, multiple submitters, no conflicts
1034429	NM_022168.4(IFIH1):c.2182C>T (p.Arg728Ter)	IFIH1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1042492	NM_022168.4(IFIH1):c.2305-2A>G	IFIH1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1516067	NM_022168.4(IFIH1):c.453+1G>A	IFIH1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
261563	NM_022168.4(IFIH1):c.1641+1G>C	IFIH1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2937086	NM_022168.4(IFIH1):c.2068del (p.Leu690fs)	IFIH1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
377048	NM_022168.4(IFIH1):c.1879G>T (p.Glu627Ter)	IFIH1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
445430	NM_022168.4(IFIH1):c.1312T>C (p.Ser438Pro)	IFIH1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
474952	NM_022168.4(IFIH1):c.2524G>A (p.Glu842Lys)	IFIH1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
541774	NM_022168.4(IFIH1):c.1243C>A (p.Gln415Lys)	IFIH1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
541779	NM_022168.4(IFIH1):c.2807+1G>A	IFIH1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
541784	NM_022168.4(IFIH1):c.1066C>A (p.Pro356Thr)	IFIH1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
541788	NM_022168.4(IFIH1):c.2362G>A (p.Ala788Thr)	IFIH1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
580488	NM_022168.4(IFIH1):c.2016del (p.Asp673fs)	IFIH1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
582309	NM_022168.4(IFIH1):c.2788A>C (p.Asn930His)	IFIH1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
625959	NM_022168.4(IFIH1):c.478A>G (p.Asn160Asp)	IFIH1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
626112	NM_022168.4(IFIH1):c.1787_1797del (p.Lys596fs)	IFIH1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
626114	NM_022168.4(IFIH1):c.2733T>C (p.Ser911=)	IFIH1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
626115	NM_022168.4(IFIH1):c.1701G>A (p.Met567Ile)	IFIH1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
704305	NM_022168.4(IFIH1):c.2304+3A>G	IFIH1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
705603	NM_022168.4(IFIH1):c.2863C>G (p.Gln955Glu)	IFIH1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
837942	NM_022168.4(IFIH1):c.1589del (p.Asn530fs)	IFIH1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
845631	NM_022168.4(IFIH1):c.556C>T (p.Arg186Cys)	IFIH1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
987915	NM_022168.4(IFIH1):c.1764del (p.Ala589fs)	IFIH1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
3891372	NC_000003.12:g.163410987_163411003del		Uncertain significance	criteria provided, single submitter
1000906	NM_022168.4(IFIH1):c.730T>C (p.Ser244Pro)	IFIH1	Uncertain significance	criteria provided, multiple submitters, no conflicts
1047466	NM_022168.4(IFIH1):c.1432G>A (p.Val478Met)	IFIH1	Uncertain significance	criteria provided, multiple submitters, no conflicts
1201361	NM_022168.4(IFIH1):c.2558T>C (p.Met853Thr)	IFIH1	Uncertain significance	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 9 · Orphanet: 3 · 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
IFIH1	Limited	Autosomal recessive	immunodeficiency 95	9

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	gencc,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.