Immunodeficiency 94 with autoinflammation and dysmorphic facies

Summary

Immunodeficiency 94 with autoinflammation and dysmorphic facies (MONDO:0030681) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 5

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	immunodeficiency 94 with autoinflammation and dysmorphic facies
Mondo ID	MONDO:0030681
OMIM	619750
DOID	DOID:0061064
UMLS	C5676918
MedGen	1802872
GARD	0025610
Is cancer (heuristic)	no

Also known as: IMD94 · immunodeficiency 94 with autoinflammation and dysmorphic facies

Data availability: 5 ClinVar variants · 1 GenCC gene-disease record.

Disease family

Classification path: disease › human disease › disease by body system or component › immune system disorder › inborn error of immunity › B cell deficiency › hyperimmunoglobulin syndrome › hyper-IgE syndrome › immunodeficiency 94 with autoinflammation and dysmorphic facies

Related subtypes (13): hyper-IgE recurrent infection syndrome 1, autosomal dominant, combined immunodeficiency due to DOCK8 deficiency, Netherton syndrome, hyper-IgE recurrent infection syndrome 5, autosomal recessive, hyper-IgE recurrent infection syndrome 3, autosomal recessive, hyper-IgE recurrent infection syndrome 4, autosomal recessive, hyper-IgE recurrent infection syndrome 4A, autosomal dominant, hyper-IgE syndrome 6, autosomal dominant, with recurrent infections, autosomal recessive combined immunodeficiency due to complete IL6ST deficiency, autosomal recessive combined immunodeficiency due to partial IL6ST deficiency, autosomal dominant combined immunodeficiency due to partial IL6ST deficiency, autosomal recessive combined immunodeficiency due to IL6R deficiency, autosomal dominant combined immunodeficiency due to ERBIN deficiency

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

5 retrieved; paginated sample, class counts are floors:

3 uncertain significance, 1 pathogenic, 1 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1342185	NM_002184.4(IL6ST):c.560_571del (p.Ser187_Tyr190del)	IL6ST	Pathogenic	no assertion criteria provided
3779767	NM_002184.4(IL6ST):c.2254_2258del (p.Asn752fs)	IL6ST	Likely pathogenic	criteria provided, single submitter
1437640	NM_002184.4(IL6ST):c.283G>A (p.Ala95Thr)	IL6ST	Uncertain significance	criteria provided, multiple submitters, no conflicts
2431701	NM_002184.4(IL6ST):c.76G>A (p.Asp26Asn)	IL6ST	Uncertain significance	criteria provided, single submitter
3235008	NM_002184.4(IL6ST):c.769T>C (p.Tyr257His)	IL6ST	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 6 · 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
IL6ST	Moderate	Autosomal dominant	immunodeficiency 94 with autoinflammation and dysmorphic facies	6

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
IL6ST	Orphanet:656283	Autosomal recessive combined immunodeficiency due to complete IL6ST deficiency
IL6ST	Orphanet:656300	Autosomal recessive combined immunodeficiency due to partial IL6ST deficiency
IL6ST	Orphanet:656313	Autosomal dominant combined immunodeficiency due to partial IL6ST deficiency

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
IL6ST	HGNC:6021	ENSG00000134352	P40189	Interleukin-6 receptor subunit beta	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
IL6ST	Interleukin-6 receptor subunit beta	Signal-transducing molecule.

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)
IL6ST	Antibody/Immunoglobulin	yes		Hematopoietin_rcpt_Gp130_CS, FN3_dom, IgC2-like_lig-bd

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
germinal epithelium of ovary	1
parietal pleura	1
pleura	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
IL6ST	295	ubiquitous	marker	parietal pleura, pleura, germinal epithelium of ovary

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
IL6ST	1,530

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
IL6ST	P40189	20

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 7. 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
MAPK1 (ERK2) activation	1	1142.0×	0.001	IL6ST
MAPK3 (ERK1) activation	1	1038.2×	0.001	IL6ST
Interleukin-27 signaling	1	1038.2×	0.001	IL6ST
Interleukin-6 signaling	1	951.7×	0.001	IL6ST
Interleukin-35 Signalling	1	951.7×	0.001	IL6ST
IL-6-type cytokine receptor ligand interactions	1	634.4×	0.002	IL6ST
Activation of STAT3 by cadherin engagement	1	163.1×	0.006	IL6ST

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
negative regulation of interleukin-6-mediated signaling pathway	1	8426.0×	0.001	IL6ST
oncostatin-M-mediated signaling pathway	1	4213.0×	0.001	IL6ST
leukemia inhibitory factor signaling pathway	1	4213.0×	0.001	IL6ST
interleukin-11-mediated signaling pathway	1	3370.4×	0.001	IL6ST
ciliary neurotrophic factor-mediated signaling pathway	1	3370.4×	0.001	IL6ST
interleukin-27-mediated signaling pathway	1	2407.4×	0.002	IL6ST
positive regulation of adaptive immune response	1	2106.5×	0.002	IL6ST
intestinal epithelial cell development	1	1532.0×	0.002	IL6ST
T-helper 17 cell lineage commitment	1	1532.0×	0.002	IL6ST
positive regulation of acute inflammatory response	1	1404.3×	0.002	IL6ST
positive regulation of astrocyte differentiation	1	1404.3×	0.002	IL6ST
positive regulation of platelet aggregation	1	1296.3×	0.002	IL6ST
interleukin-6-mediated signaling pathway	1	1123.5×	0.002	IL6ST
positive regulation of cardiac muscle hypertrophy	1	732.7×	0.002	IL6ST
cell surface receptor signaling pathway via STAT	1	561.7×	0.003	IL6ST
glycogen metabolic process	1	526.6×	0.003	IL6ST
positive regulation of vascular endothelial growth factor production	1	495.6×	0.003	IL6ST
response to cytokine	1	374.5×	0.004	IL6ST
positive regulation of Notch signaling pathway	1	351.1×	0.004	IL6ST
positive regulation of T cell proliferation	1	259.3×	0.005	IL6ST
positive regulation of osteoblast differentiation	1	224.7×	0.005	IL6ST
cytokine-mediated signaling pathway	1	130.6×	0.009	IL6ST
negative regulation of neuron apoptotic process	1	110.9×	0.010	IL6ST
negative regulation of apoptotic process	1	34.8×	0.030	IL6ST
positive regulation of cell population proliferation	1	33.6×	0.030	IL6ST

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
IL6ST	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
IL6ST	21	Binding:21

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	IL6ST
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)
IL6ST	21	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.