IgE responsiveness, atopic

Summary

IgE responsiveness, atopic (MONDO:0007817) is a disease with 4 cohort genes and 27 clinical trials.

At a glance

• Cohort genes: 4
• ClinVar variants: 10
• Clinical trials: 27

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	IgE responsiveness, atopic
Mondo ID	MONDO:0007817
MeSH	C564133
OMIM	147050
NCIT	C3116
UMLS	C1840253
MedGen	327063
Is cancer (heuristic)	no

Also known as: IgE responsiveness, atopic · IgE, elevated level of · IGER · immediate hypersensitivity · type 1 hypersensitivity · type 1 hypersensitivity reaction · type I hypersensitivity · type I hypersensitivity reaction · type I immediate hypersensitivity reaction

Data availability: 10 ClinVar variants · 2 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › immune system disorder › hypersensitivity reaction disease › IgE responsiveness, atopic

Related subtypes (9): type IV hypersensitivity disease, allergic disease, hypersensitivity vasculitis, type III hypersensitivity disease, immune dysregulation-polyendocrinopathy-enteropathy-X-linked syndrome, progestogen hypersensitivity, type II hypersensitivity reaction disease, pseudoallergy, anaphylaxis

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

10 retrieved; paginated sample, class counts are floors:

5 uncertain significance, 4 conflicting classifications of pathogenicity, 1 affects

ClinVar	Variant (HGVS)	Gene	Classification	Review
252799	NM_181078.3(IL21R):c.824G>A (p.Arg275Gln)	IL21R	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
626116	NM_181078.3(IL21R):c.-17+563G>A	IL21R	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
626118	NM_000418.4(IL4R):c.1160C>T (p.Ser387Leu)	IL4R	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
225037	NM_181078.3(IL21R):c.1033G>A (p.Gly345Ser)	LOC130058712	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
4270	HAVCR1, 6-AA INS	HAVCR1	Affects	no assertion criteria provided
1478986	NM_181078.3(IL21R):c.995C>T (p.Thr332Met)	IL21R	Uncertain significance	criteria provided, multiple submitters, no conflicts
654227	NM_181078.3(IL21R):c.605C>T (p.Ala202Val)	IL21R	Uncertain significance	criteria provided, multiple submitters, no conflicts
858671	NM_181078.3(IL21R):c.1550G>A (p.Arg517Gln)	IL21R	Uncertain significance	criteria provided, multiple submitters, no conflicts
2442131	NM_000418.4(IL4R):c.134A>G (p.Glu45Gly)	IL4R	Uncertain significance	criteria provided, single submitter
827982	NM_000418.4(IL4R):c.1774G>T (p.Val592Leu)	IL4R	Uncertain significance	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 2 · Orphanet: 1 · 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
IL4R	No Known Disease Relationship	Unknown	IgE responsiveness, atopic
MS4A2	No Known Disease Relationship	Unknown	IgE responsiveness, atopic

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
IL21R	Orphanet:357329	Combined immunodeficiency due to IL21R deficiency

Cohort genes → proteins

4 cohort genes, 4 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	4

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
IL4R	HGNC:6015	ENSG00000077238	P24394	Interleukin-4 receptor subunit alpha	gencc,clinvar
MS4A2	HGNC:7316	ENSG00000149534	Q01362	High affinity immunoglobulin epsilon receptor subunit beta	gencc
HAVCR1	HGNC:17866	ENSG00000113249	Q96D42	Hepatitis A virus cellular receptor 1	clinvar
IL21R	HGNC:6006	ENSG00000103522	Q9HBE5	Interleukin-21 receptor	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
IL4R	Interleukin-4 receptor subunit alpha	Receptor for both interleukin 4 and interleukin 13.
MS4A2	High affinity immunoglobulin epsilon receptor subunit beta	High affinity receptor that binds to the Fc region of immunoglobulins epsilon.
HAVCR1	Hepatitis A virus cellular receptor 1	Phosphatidylserine receptor that plays an important functional role in regulatory B-cell homeostasis including generation, expansion and suppressor functions.
IL21R	Interleukin-21 receptor	This is a receptor for interleukin-21.

Protein-family classification

Druggable: 3 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.75

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	3	21.9×	3e-04
Other/Unknown	1	0.5×	0.962

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
IL4R	Antibody/Immunoglobulin	yes		Hempt_rcpt_S_F1_CS, FN3_dom, Ig-like_fold
MS4A2	Other/Unknown	no		CD20-like_TM, MS4A
HAVCR1	Antibody/Immunoglobulin	yes		Ig/MHC_CS, Ig_sub, Ig-like_dom
IL21R	Antibody/Immunoglobulin	yes		Hempt_rcpt_S_F1_CS, FN3_dom, Ig-like_fold

Expression context

Cohort genes with no expression data: 0.

4 cohort genes 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)	4
unknown	0

Top tissues across cohort

Tissue	Cohort genes
granulocyte	2
male germ line stem cell (sensu Vertebrata) in testis	2
mucosa of stomach	1
right lung	1
gall bladder	1
primordial germ cell in gonad	1
adult mammalian kidney	1
rectum	1
blood	1
lymph node	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
IL4R	245	ubiquitous	marker	granulocyte, mucosa of stomach, right lung
MS4A2	138	tissue_specific	marker	primordial germ cell in gonad, gall bladder, male germ line stem cell (sensu Vertebrata) in testis
HAVCR1	123	tissue_specific	marker	male germ line stem cell (sensu Vertebrata) in testis, adult mammalian kidney, rectum
IL21R	178	broad	marker	granulocyte, lymph node, blood

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
IL4R	2,970
IL21R	1,596
HAVCR1	1,528
MS4A2	1,421

Structural data

PDB: 4 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
IL4R	P24394	10
IL21R	Q9HBE5	6
MS4A2	Q01362	2
HAVCR1	Q96D42	2

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 10. Enrichment computed across 4 evidence-associated genes (4 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 4 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Interleukin-21 signaling	1	285.5×	0.022	IL21R
Role of LAT2/NTAL/LAB on calcium mobilization	1	150.3×	0.022	MS4A2
Attachment and Entry	1	150.3×	0.022	HAVCR1
FCERI mediated Ca+2 mobilization	1	89.2×	0.022	MS4A2
FCERI mediated MAPK activation	1	86.5×	0.022	MS4A2
Fc epsilon receptor (FCERI) signaling	1	68.0×	0.022	MS4A2
Dengue Virus Attachment and Entry	1	64.9×	0.022	HAVCR1
FCERI mediated NF-kB activation	1	39.1×	0.030	MS4A2
Differentiation of naive CD4+ T cells to T helper 2 cells (Th2 cells)	1	36.6×	0.030	IL4R
Interleukin-4 and Interleukin-13 signaling	1	25.7×	0.038	IL4R

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 4 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 T-helper 1 cell differentiation	1	1053.2×	0.006	IL4R
positive regulation of mast cell activation	1	842.6×	0.006	HAVCR1
production of molecular mediator involved in inflammatory response	1	601.9×	0.006	IL4R
interleukin-4-mediated signaling pathway	1	601.9×	0.006	IL4R
positive regulation of T-helper 2 cell differentiation	1	526.6×	0.006	IL4R
T-helper 2 cell differentiation	1	468.1×	0.006	IL4R
positive regulation of mast cell degranulation	1	383.0×	0.006	IL4R
T-helper 1 cell differentiation	1	383.0×	0.006	IL4R
immune response	2	23.5×	0.006	IL4R, MS4A2
positive regulation of myoblast fusion	1	263.3×	0.008	IL4R
positive regulation of macrophage activation	1	210.7×	0.009	IL4R
immunoglobulin mediated immune response	1	175.5×	0.010	IL4R
phagocytosis, engulfment	1	168.5×	0.010	HAVCR1
defense response to protozoan	1	150.5×	0.010	IL4R
natural killer cell activation	1	145.3×	0.010	IL21R
positive regulation of immunoglobulin production	1	120.4×	0.011	IL4R
positive regulation of chemokine production	1	93.6×	0.013	IL4R
positive regulation of cold-induced thermogenesis	1	40.9×	0.028	IL4R
cytokine-mediated signaling pathway	1	32.7×	0.033	IL21R
cell surface receptor signaling pathway	1	16.0×	0.064	MS4A2
signal transduction	1	4.0×	0.227	IL4R

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 4 evidence-associated genes (25%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
IL4R	0	0
MS4A2	0	0
HAVCR1	0	0
IL21R	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Pharmacogenomics

Cohort genes with a PharmGKB record: 4; 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	3	IL4R, HAVCR1, IL21R
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	MS4A2

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
IL4R	0	—
MS4A2	0	—
HAVCR1	0	—
IL21R	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 27.

Phase distribution (across all retrieved trials)

Phase	Trials
PHASE2	11
PHASE1	6
Not specified	5
PHASE1/PHASE2	3
PHASE3	2

Top trials by phase / activity

NCT	Phase	Status	Title
NCT00414141	PHASE3	COMPLETED	Efficacy and Safety/Tolerability of Grass MATA MPL
NCT00423787	PHASE3	COMPLETED	Efficacy and Safety/Tolerability of Ragweed MATA MPL
NCT00104377	PHASE2	COMPLETED	Induction of Immunogenicity With Different Doses of Grass MATA in Subjects Allergic to Grass and Rye Pollen
NCT00110786	PHASE2	COMPLETED	Investigation of Efficacy and Safety of Ragweed MATAMPL, Pollinex-R and Placebo in Patients With Ragweed Allergy
NCT00113750	PHASE2	COMPLETED	Induction of Immunogenicity With Different Doses of TreeMATA in Subjects Allergic to Tree Pollen
NCT00118612	PHASE2	COMPLETED	Different Doses of Tyrosine Adsorbed Tree Pollen Allergoid With Monophosphoryl Lipid A (MPL) in Patients Sensitized to Tree Pollen
NCT00118625	PHASE2	COMPLETED	Assessment of the Contribution of Monophosphoryl Lipid A (MPL) to a Tree Pollen Allergy Vaccine
NCT00133146	PHASE2	COMPLETED	Assessment of the Contribution of Monophosphoryl Lipid A (MPL) to a Grass Pollen Allergy Vaccine
NCT00133159	PHASE2	COMPLETED	Different Doses of Tyrosine Adsorbed Grass Pollen Allergoid With Monophosphoryl Lipid A (MPL) in Patients Sensitized to Grass Pollen
NCT00258635	PHASE2	COMPLETED	Investigation of Safety+Efficacy of Different Doses of RagweedMATAMPL;Assessment of Residual Allergenicity Using Skin Prick Test
NCT00325338	PHASE2	COMPLETED	Follow-up Investigation of Efficacy of Ragweed MATAMPL,and Placebo in Patients With Ragweed-induced Seasonal Allergic Rhinitis
NCT00387478	PHASE2	TERMINATED	Investigation of Efficacy and Safety of Tree MATAMPL,Tree MATA, and Placebo in Patients With Birch-Induced Seasonal Allergic Rhinitis
NCT00461097	PHASE2	COMPLETED	Oral Immunotherapy for Childhood Egg Allergy
NCT00580606	PHASE1/PHASE2	COMPLETED	A Randomized, Double-Blind Placebo-Controlled Peanut Sublingual Immunotherapy Trial
NCT01084174	PHASE1/PHASE2	COMPLETED	A Randomized, Double-Blind, Placebo-Controlled Pilot Study of Sublingual/Oral Immunotherapy for the Treatment of Peanut Allergy
NCT05003804	PHASE1/PHASE2	COMPLETED	Allergic Disease Onset Prevention Study
NCT00104390	PHASE1	COMPLETED	Assessment of Residual Allergenicity of Grass/Rye Pollen Allergoid Using Skin Prick Testing
NCT00107705	PHASE1	COMPLETED	Assessment of Residual Allergenicity of Tree (Birch, Hazel, and Alder) Pollen Allergoid Using Skin Prick Testing
NCT00109759	PHASE1	WITHDRAWN	Evaluation of Safety and Tolerability of Tyrosine Adsorbed Ragweed Pollen Allergoid With MPL (Monophosphoryl Lipid A)
NCT00116285	PHASE1	COMPLETED	Assessment of Residual Allergenicity of Ragweed Pollen Allergoid With Monophosphoryl Lipid A (MPL) Using Skin Prick Testing
NCT00241410	PHASE1	COMPLETED	Safety, Immunological Effect and Efficacy of the Combined Application of MPL and Grass Pollen Allergen
NCT00850668	PHASE1	COMPLETED	Peanut Allergy Vaccine Study in Healthy and Peanut-allergic Adults
NCT01407640	Not specified	COMPLETED	Diagnosis and Physiopathology of Insulin Allergy
NCT02561390	Not specified	COMPLETED	Comparison Between spIgE and Skin Prick Test of Local and Imported Aeroallergens
NCT02561429	Not specified	COMPLETED	Comparison of Difference Histamine Concentration (1, 5 and 10 mg/ml) for Skin Prick Test Positive Control
NCT02733926	Not specified	UNKNOWN	Effect of Vegetation in Kindergartens on the Immune Response of Children
NCT06065137	Not specified	COMPLETED	Standardised Drug Provocation Testing in Perioperative Hypersensitivity

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
CHEMBL443232	0	1