Hypersensitivity reaction disease

Summary

Hypersensitivity reaction disease (MONDO:0000605) is a disease (an umbrella term covering 10 Mondo subtypes) with 1 cohort gene (1 GWAS associations across 1 studies) and 158 clinical trials. Top therapeutic interventions include epinephrine, brompheniramine, and histamine.

At a glance

• Umbrella term: 10 Mondo subtypes
• Cohort genes: 1
• GWAS associations: 1
• Clinical trials: 158

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	hypersensitivity reaction disease
Mondo ID	MONDO:0000605
EFO	EFO:1002003
DOID	DOID:0060056
NCIT	C3114
SNOMED CT	473010000
UMLS	C3532523
MedGen	759636
Is cancer (heuristic)	no

Also known as: allergic reaction · hypersensitive · hypersensitivity · hypersensitivity reaction · sensitive · sensitivity

Data availability: 1 GWAS association (1 study).

Disease family

An umbrella term covering 10 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › immune system disorder › hypersensitivity reaction disease

Related subtypes (46): immune system cancer, immune system organ benign neoplasm, bone marrow disorder, thymus gland disorder, inborn error of immunity, leukocyte disorder, psoriasis, spondyloarthropathy, aggressive insulitis, benign insulitis, inflammatory bowel disease, autoimmune disease, TNF receptor 1-associated periodic fever syndrome, epidermodysplasia verruciformis, Vici syndrome, proteosome-associated autoinflammatory syndrome, hyperimmunoglobulinemia D with periodic fever, transcobalamin II deficiency, pyogenic arthritis-pyoderma gangrenosum-acne syndrome, granulomatosis with polyangiitis, autosomal recessive osteopetrosis 7, graft versus host disease, congenital sideroblastic anemia-B-cell immunodeficiency-periodic fever-developmental delay syndrome, Roifman syndrome, cryopyrin-associated periodic syndrome, anti-HLA hyperimmunization, acquired immunodeficiency, erythroderma desquamativum, autoinflammatory syndrome with pyogenic bacterial infection and amylopectinosis, familial Mediterranean fever, 22q11.2 deletion syndrome, T-cell large granular lymphocyte leukemia, twin to twin transfusion syndrome, immunodeficiency disease, immunoproliferative disorder, cytokine receptor deficiency, immunodeficiency-related disorder, phagocytic cell dysfunction, thrombocytopenic purpura, lymphoid system disorder, immune reconstitution inflammatory syndrome, growth hormone insensitivity with immune dysregulation 1, autosomal recessive, cytokine release syndrome, early-onset autoimmunity-autoinflammation-immunodeficiency syndrome, CADINS disease, autoinflammation, panniculitis, and dermatosis syndrome

Subtypes (10): type IV hypersensitivity disease, allergic disease, hypersensitivity vasculitis, type III hypersensitivity disease, IgE responsiveness, atopic, immune dysregulation-polyendocrinopathy-enteropathy-X-linked syndrome, progestogen hypersensitivity, type II hypersensitivity reaction disease, pseudoallergy, anaphylaxis

Genetics & variants

GWAS landscape

1 GWAS associations across 1 studies. Top hits map to 0 distinct genes (as reported by GWAS).

Top associations by p-value

rsID	p-value	Gene	Risk allele	Odds ratio
rs34213790	7e-07	LINC02571 - HLA-B	A	2.06

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST004118	Carr DF	2017	151	0	Genome-wide association study of nevirapine hypersensitivity in a sub-Saharan African HIV-infected population.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

Tier	Variants
Tier 1: coding	0
Tier 2: splice/UTR	0
Tier 3: regulatory	0
Tier 4: intronic/intergenic	1

MAF distribution

Bucket	Variants
common (>=0.05)	1
low_freq (0.01-0.05)	0
rare (<0.01)	0
unknown	0

Functional consequences

Consequence	Count
intron_variant	1

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
rs34213790	6	31350802	G>A	0.37	intron_variant	LINC02571 - HLA-B	7e-07	Tier 4: intronic/intergenic

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 6 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
HLA-B	Orphanet:117	Behçet disease
HLA-B	Orphanet:275798	Pulmonary arterial hypertension associated with connective tissue disease
HLA-B	Orphanet:29207	Reactive arthritis
HLA-B	Orphanet:3287	Takayasu arteritis
HLA-B	Orphanet:36426	Stevens-Johnson syndrome
HLA-B	Orphanet:397	Giant cell arteritis

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
gwas_only	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
HLA-B	HGNC:4932	ENSG00000234745	P01889	HLA class I histocompatibility antigen, B alpha chain	gwas

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
HLA-B	HLA class I histocompatibility antigen, B alpha chain	Antigen-presenting major histocompatibility complex class I (MHCI) 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)
HLA-B	Antibody/Immunoglobulin	yes		MHC_I_a_a1/a2, Ig/MHC_CS, Ig_C1-set

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
blood	1
granulocyte	1
spleen	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
HLA-B	134	ubiquitous	marker	blood, spleen, granulocyte

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
HLA-B	3,209

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
HLA-B	P01889	237

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 9. 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
Endosomal/Vacuolar pathway	1	1038.2×	0.008	HLA-B
DAP12 interactions	1	475.8×	0.008	HLA-B
Antigen Presentation: Folding, assembly and peptide loading of class I MHC	1	393.8×	0.008	HLA-B
Interferon alpha/beta signaling	1	152.3×	0.012	HLA-B
ER-Phagosome pathway	1	129.8×	0.012	HLA-B
Interferon gamma signaling	1	125.5×	0.012	HLA-B
SARS-CoV-2 activates/modulates innate and adaptive immune responses	1	89.2×	0.013	HLA-B
Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell	1	87.2×	0.013	HLA-B
Neutrophil degranulation	1	23.1×	0.043	HLA-B

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 dendritic cell differentiation	1	5617.3×	0.001	HLA-B
regulation of T cell anergy	1	4213.0×	0.001	HLA-B
regulation of interleukin-12 production	1	4213.0×	0.001	HLA-B
protection from natural killer cell mediated cytotoxicity	1	2808.7×	0.001	HLA-B
regulation of interleukin-6 production	1	1685.2×	0.001	HLA-B
detection of bacterium	1	1404.3×	0.001	HLA-B
antigen processing and presentation of endogenous peptide antigen via MHC class Ib	1	1296.3×	0.001	HLA-B
antigen processing and presentation of endogenous peptide antigen via MHC class I via ER pathway, TAP-independent	1	1296.3×	0.001	HLA-B
positive regulation of T cell mediated cytotoxicity	1	510.7×	0.003	HLA-B
defense response	1	216.1×	0.006	HLA-B
adaptive immune response	1	84.3×	0.014	HLA-B
immune response	1	47.1×	0.023	HLA-B
innate immune response	1	33.6×	0.030	HLA-B

Therapeutics

Drugs indicated for this disease

1 approved. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

Drug	Development status
Sodium Fluoride	Approved (phase 4)

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
HLA-B	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
HLA-B	1	Binding:1

Pharmacogenomics

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

Cohort genes with a CPIC/DPWG dosing guideline

Symbol	CPIC guidelines
HLA-B	1

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	HLA-B
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)
HLA-B	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 158.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	106
PHASE2	14
PHASE1	13
PHASE3	11
PHASE4	6
PHASE1/PHASE2	4
PHASE2/PHASE3	2
EARLY_PHASE1	2

Top trials by phase / activity

NCT	Phase	Status	Title
NCT06834165	PHASE4	RECRUITING	Study Evaluating the Safety and Efficacy of Neffy or Intramuscular Adrenalin in Patients With Allergic Reactions After Oral Food Challenge or Allergen Immunotherapy
NCT00359138	PHASE4	COMPLETED	The Duration of the Suppressive Effects of Desloratadine on Allergen Prick Tests After Discontinuation (P04441)
NCT01569191	PHASE4	COMPLETED	Non-Pharmaceutical Treatment of Seasonal Allergic Conjunctivitis
NCT03019224	PHASE4	COMPLETED	Effects of Desensitizing Dentifrices on the Reduction of Pain Sensitivity Caused by In-office Dental Whitening
NCT05119751	PHASE4	COMPLETED	Vestibular Versus Sublingual Route of AIT Tablets
NCT06011603	PHASE4	COMPLETED	Prineo Sensitivity Dressing Study
NCT01072188	PHASE3	COMPLETED	Clinical Efficacy of 10% Arginine Bicarbonate Prophylaxis Paste
NCT01731249	PHASE3	COMPLETED	Efficacy and Safety Study of a Sublingual Immunotherapy Solution to Treat Patients Suffering From Birch Pollen Allergic Rhinoconjunctivitis
NCT02349763	PHASE3	COMPLETED	Dexamethasone Regimens for Prophylaxis of Paclitaxel-associated Hypersensitivity Reaction
NCT03157505	PHASE3	COMPLETED	Efficacy and Safety of Birch Pollen Immunotherapy in Local Allergic Rhinitis
NCT03598426	PHASE3	COMPLETED	Conventional Prophylactic Oral Dexamethasone vs Short-course IV Dexamethasone in Paclitaxel Hypersensitivity
NCT03627767	PHASE3	COMPLETED	Study to Investigate Efficacy and Safety of PF-04965842 in Subjects Aged 12 Years and Over With Moderate to Severe Atopic Dermatitis With the Option of Rescue Treatment in Flaring Subjects
NCT03720470	PHASE3	COMPLETED	Study Evaluating Efficacy and Safety of PF-04965842 and Dupilumab in Adult Subjects With Moderate to Severe Atopic Dermatitis on Background Topical Therapy
NCT04485299	PHASE2/PHASE3	UNKNOWN	Clinical Assessment of Bifluorid 10 vs Varnish Fluoride on The Exposed Hypersensitive Cervical Dentin in Adult Patient
NCT04531540	PHASE3	COMPLETED	Study to Determine Skin Irritation and/or Sensitization Potential of an Antifungal Cream Containing Trolamine (Repeated Insult Patch Test)
NCT04531813	PHASE3	COMPLETED	Study to Determine Skin Irritation Potential of an Antifungal Cream Containing Trolamine After Repeated Skin Application (Cumulative Irritation Patch Test)
NCT06348849	PHASE2/PHASE3	COMPLETED	The Desensitising Effect of Nanosilver Fluoride in Molar-Incisor Hypomineralisation
NCT06937697	PHASE3	COMPLETED	Clinical of Hypersensitivity Reduction Efficacy on Two Toothpastes
NCT07257042	PHASE3	COMPLETED	Oothpaste Containing 8% Arginine Compared to Colgate Cavity Protection Toothpaste in Reducing Dentinal Hypersensitivity
NCT07605806	PHASE1/PHASE2	RECRUITING	Novel Biomarkers of Non-IgE Immediate Hypersensitivity Drug Reactions
NCT00001909	PHASE2	COMPLETED	Phase II Efficacy Study of Aerosolized Recombinant Human IL-4 Receptor in Asthma
NCT00078195	PHASE2	COMPLETED	Omalizumab (Xolair) and Allergy Shots For the Treatment of Seasonal Allergies
NCT00293904	PHASE1/PHASE2	COMPLETED	Safety and Efficacy of an Allergen Vaccine in Grass-Pollen Allergy
NCT00461097	PHASE2	COMPLETED	Oral Immunotherapy for Childhood Egg Allergy
NCT00574379	PHASE2	COMPLETED	Efficacy, Safety and PK of Once or Twice Daily Bilastine (10 or 20 mg) Compared With Placebo in the Symptomatic Treatment of SAR
NCT00580606	PHASE1/PHASE2	COMPLETED	A Randomized, Double-Blind Placebo-Controlled Peanut Sublingual Immunotherapy Trial
NCT01350635	PHASE1/PHASE2	COMPLETED	Skin Test Study of BM32
NCT01366846	PHASE2	COMPLETED	Persistence of Oral Tolerance to Peanut
NCT01904604	PHASE2	COMPLETED	Peanut Epicutaneous Phase II Immunotherapy Clinical Trial
NCT02474836	PHASE2	COMPLETED	Determination of Biological Activity of Three Allergen Extracts
NCT02643641	PHASE2	COMPLETED	Effect of Different Pre-seasonal BM32 Dosings on the Induction of a Protective Immune Response
NCT02686827	PHASE2	COMPLETED	DBPC-Dose-finding-trial of Vitamin D3 for SCIT in Birch Pollen Allergic Patients.
NCT03563066	PHASE2	COMPLETED	Effect of Benralizumab in Atopic Dermatitis
NCT03679676	PHASE2	COMPLETED	Clinical Study Using Biologics to Improve Multi OIT Outcomes (COMBINE)
NCT03688074	PHASE2	COMPLETED	Study to Evaluate Tezepelumab on Airway Inflammation in Adults With Uncontrolled Asthma (CASCADE)
NCT04761822	PHASE2	COMPLETED	COVID19 SARS Vaccinations: Systemic Allergic Reactions to SARS-CoV-2 Vaccinations
NCT06527937	PHASE2	COMPLETED	Pharmacokinetics Study of DESF in Adults With Oral Allergy Syndrome
NCT07038746	PHASE1	RECRUITING	Effects of Inhaled Epinephrine on Systemic Allergic Reactions During Allergy Testing, Immunotherapy or Oral Challenges
NCT00837837	PHASE1	COMPLETED	Study Evaluating Chlorpheniramine Maleate Liquid in Children and Adolescents
NCT00839124	PHASE1	COMPLETED	A Study of Inhalation of 20,000 EU CCRE in Normal Volunteers Compared to Allergic Asthmatic Individuals

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
EPINEPHRINE	4	4
BROMPHENIRAMINE	4	3
HISTAMINE	4	3
ABROCITINIB	4	2
BUTENAFINE	4	2
CALCIUM CARBONATE	4	2
BENRALIZUMAB	4	1
BILASTINE	4	1
CHLORPHENIRAMINE	4	1
DESLORATADINE	4	1
DUPILUMAB	4	1
HYDROGEN PEROXIDE	4	1
LEVOCETIRIZINE	4	1
OMALIZUMAB	4	1
PARICALCITOL	4	1
SODIUM FLUORIDE	4	1
TERFENADINE	4	1
TEZEPELUMAB	4	1
ARGININE	3	2
FLUORIDE ION	3	1
SILVER	3	1
GOLD	2	1
MDX-1303	1	1
CHEMBL46909	0	1
FLUORIDE	0	1