Drug allergy

Summary

Drug allergy (MONDO:0000775) is a disease with 1 cohort gene (46 GWAS associations across 37 studies) and 13 clinical trials. Top therapeutic interventions include cefaclor anhydrous, cephalexin anhydrous, and cefuroxime.

At a glance

• Cohort genes: 1
• GWAS associations: 46
• Clinical trials: 13

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	drug allergy
Mondo ID	MONDO:0000775
EFO	EFO:0009482
MeSH	D004342
DOID	DOID:0060500
UMLS	C0013182
MedGen	41663
Is cancer (heuristic)	no

Also known as: allergy of exposure to drug · exposure to drug allergic disease

Data availability: 46 GWAS associations (37 studies).

Disease family

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

Related subtypes (11): allergic respiratory disease, gastrointestinal allergy, latex allergy, atopic eczema, atopic IgE-mediated allergic disorder, eye allergy, vulvovaginitis, allergic seminal, allergic otitis media, alpha-gal syndrome, venom allergy, food allergy

Genetics & variants

GWAS landscape

46 GWAS associations across 37 studies. Top hits map to 30 distinct genes (as reported by GWAS).

Top associations by p-value

rsID	p-value	Gene	Risk allele	Odds ratio
HLA-B*55:01	1e-77		?	1.33
rs868092811	2e-14	KIT	A	3.88
rs1005568645	1e-12	MIATNB	C	4.25
rs189974384	1e-12	PIGX, NRROS	A	3.05
rs139209786	2e-12	FAR2	T	4.24
rs534117778	4e-12	TRDN	G	3.58
rs534701794	4e-12	ABCA13	A	4.33
rs576050421	6e-12	NCOA2	T	3.52
rs150173757	8e-12	CPS1 - RPS27P10	C	1.95
rs571339021	9e-12	TSC22D2 - SERP1	G	2.67
rs570617307	2e-11	FBLN5	A	4.24
rs536787230	2e-11	PRIMA1 - FAM181A-AS1	C	3.31
rs552516691	3e-11	SNORA72 - EFR3A	C	4.07
rs556411558	3e-11	PAK1	C	4.03
rs186657537	3e-11	STK24	G	1.98
rs575851669	4e-11	PAFAH1B1	G	3.16
rs543384691	4e-11	CNN2P10 - POGK	G	3.75
rs182500148	4e-11	MIR181A1HG - LINC01222	T	3.5
rs560221841	4e-11	LINC01376	G	3.2
rs370722463	4e-11	LINC01163	C	2.95
rs73055403	1e-10	TPRG1	?
rs181829194	2e-07	RN7SL553P - MTARC2P1	G	18.6
rs117007512	1e-06	TCF12	G	9.56
rs532454805	2e-06	GASK1B-AS1	G	7.94
rs192104207	2e-06	GTF3AP6 - LINC02476	T	15.12
rs6811901	4e-06	CAMK2D	C	3.54
rs139623002	5e-06	SMIM17, ZIM2-AS1	A	5.1
rs17084754	5e-06	KIT - LINC02358	T	2.69
rs116850690	5e-06	VGLL4	A	5.14
rs11802311	6e-06	PSEN2	C	5.65

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST90081388	Backman JD	2021	36,339	339,428	Exome sequencing and analysis of 454,787 UK Biobank participants.
GCST90085374	Backman JD	2021	36,339	339,428	Exome sequencing and analysis of 454,787 UK Biobank participants.
GCST011458	Krebs K	2020	29,396	452,094	Genome-wide Study Identifies Association between HLA-B∗55:01 and Self-Reported Penicillin Allergy.
GCST90081381	Backman JD	2021	20,233	365,807	Exome sequencing and analysis of 454,787 UK Biobank participants.
GCST90085367	Backman JD	2021	20,233	365,807	Exome sequencing and analysis of 454,787 UK Biobank participants.
GCST90691988	Karczewski KJ	2025	20,021	383,239	Pan-UK Biobank genome-wide association analyses enhance discovery and resolution of ancestry-enriched effects.
GCST90081386	Backman JD	2021	7,086	380,334	Exome sequencing and analysis of 454,787 UK Biobank participants.
GCST90085372	Backman JD	2021	7,086	380,334	Exome sequencing and analysis of 454,787 UK Biobank participants.
GCST90081385	Backman JD	2021	5,809	381,836	Exome sequencing and analysis of 454,787 UK Biobank participants.
GCST90085371	Backman JD	2021	5,809	381,836	Exome sequencing and analysis of 454,787 UK Biobank participants.

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	1
Tier 4: intronic/intergenic	44

MAF distribution

Bucket	Variants
common (>=0.05)	16
low_freq (0.01-0.05)	0
rare (<0.01)	19
unknown	10

Functional consequences

Consequence	Count
intron_variant	33
intergenic_variant	10
unknown	1
regulatory_region_variant	1

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
HLA-B*55:01							1e-77	Tier 4: intronic/intergenic
rs868092811	4	54716593	A>G	0	intron_variant	KIT	2e-14	Tier 4: intronic/intergenic
rs1005568645	22	26737787	C>T	0	intron_variant	MIATNB	1e-12	Tier 4: intronic/intergenic
rs189974384	3	196646827	A>G	0.001	intron_variant	PIGX, NRROS	1e-12	Tier 4: intronic/intergenic
rs139209786	12	29155295	T>A	0	intron_variant	FAR2	2e-12	Tier 4: intronic/intergenic
rs534117778	6	123269003	G>A,T	0	intron_variant	TRDN	4e-12	Tier 4: intronic/intergenic
rs534701794	7	48247927	A>C,G	0	intron_variant	ABCA13	4e-12	Tier 4: intronic/intergenic
rs576050421	8	70198412	T>C,G	0.001	intron_variant	NCOA2	6e-12	Tier 4: intronic/intergenic
rs150173757	2	210876600	C>T	0.001	intergenic_variant	CPS1 - RPS27P10	8e-12	Tier 4: intronic/intergenic
rs571339021	3	150516356	G>A	0.001	intergenic_variant	TSC22D2 - SERP1	9e-12	Tier 4: intronic/intergenic
rs570617307	14	91926203	A>G	0.001	intron_variant	FBLN5	2e-11	Tier 4: intronic/intergenic
rs536787230	14	93861694	C>T	0	intergenic_variant	PRIMA1 - FAM181A-AS1	2e-11	Tier 4: intronic/intergenic
rs552516691	8	131741082	C>A,T	0.001	intergenic_variant	SNORA72 - EFR3A	3e-11	Tier 4: intronic/intergenic
rs556411558	11	77394715	C>T	0	intron_variant	PAK1	3e-11	Tier 4: intronic/intergenic
rs186657537	13	98535618	G>A	0.002	intron_variant	STK24	3e-11	Tier 4: intronic/intergenic
rs575851669	17	2621240	G>A,T	0	intron_variant	PAFAH1B1	4e-11	Tier 4: intronic/intergenic
rs543384691	1	166814757	G>A	0	regulatory_region_variant	CNN2P10 - POGK	4e-11	Tier 3: regulatory
rs182500148	1	198984491	T>C	0.001	intron_variant	MIR181A1HG - LINC01222	4e-11	Tier 4: intronic/intergenic
rs560221841	2	19055372	G>A	0.001	intron_variant	LINC01376	4e-11	Tier 4: intronic/intergenic
rs370722463	10	128289710	C>G,T	0.002	intron_variant	LINC01163	4e-11	Tier 4: intronic/intergenic
rs73055403	3	189135298	G>A	0.05	intron_variant	TPRG1	1e-10	Tier 4: intronic/intergenic
rs181829194	3	5361050	C>G,T	0.05	intergenic_variant	RN7SL553P - MTARC2P1	2e-07	Tier 4: intronic/intergenic
rs117007512	15	56959573	T>G		intron_variant	TCF12	1e-06	Tier 4: intronic/intergenic
rs532454805	4	158175500	T>G		intron_variant	GASK1B-AS1	2e-06	Tier 4: intronic/intergenic
rs192104207	7	119383049	C>G,T		intergenic_variant	GTF3AP6 - LINC02476	2e-06	Tier 4: intronic/intergenic
rs6811901	4	113445575	T>A,C	0.05	intron_variant	CAMK2D	4e-06	Tier 4: intronic/intergenic
rs139623002	19	56643369	C>A		intron_variant	SMIM17, ZIM2-AS1	5e-06	Tier 4: intronic/intergenic
rs17084754	4	54744026	C>T	0.05	intergenic_variant	KIT - LINC02358	5e-06	Tier 4: intronic/intergenic
rs116850690	3	11599164	T>A,G	0.05	intron_variant	VGLL4	5e-06	Tier 4: intronic/intergenic
rs11802311	1	226900791	A>C,G	0.05	intron_variant	PSEN2	6e-06	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

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: 13.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	10
PHASE4	1
PHASE2	1
PHASE1	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT06414694	PHASE4	ENROLLING_BY_INVITATION	Inpatient Penicillin Delabeling for Low-Risk Patients
NCT06406114	PHASE2	RECRUITING	Optimizing the Diagnostic Approach to Cephalosporin Allergy Testing
NCT02118987	PHASE1	COMPLETED	Study of Omalizumab as Adjuvant Therapy in Chemotherapy Desensitization
NCT05820802	Not specified	RECRUITING	High Dimensional Analysis of Immune Cells in Pediatric Patients
NCT06803758	Not specified	RECRUITING	Teicoplanin Allergy Testing Using Autologous Serum (TATAS)
NCT07011212	Not specified	NOT_YET_RECRUITING	In Search of the Correct Diagnosis of Beta-lactam Allergy: From the Validation of a Risk Stratification Tool to Accurate Endotyping
NCT07127835	Not specified	RECRUITING	Provocation After Nurse-Directed Assessment (PANDA) Study
NCT02094638	Not specified	COMPLETED	Post-Marketing Surveillance of the Tanreqing Injection: a Real World Study
NCT03164044	Not specified	UNKNOWN	Improved Basophil Activation Test (BAT) in the Diagnostics of Drug Allergy
NCT03784482	Not specified	COMPLETED	Multiple Drug Hypersensitivity Syndrome
NCT04920721	Not specified	UNKNOWN	Retrospective Study of Immediate Hypersensitivity (IHS) Reactions to Platinum Salts in the University Hospital of Nancy
NCT05706246	Not specified	COMPLETED	Perioperative Hypersensitivity in Children
NCT06399601	Not specified	UNKNOWN	A Training Program of Drug Allergy for Healthcare Professionals

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
CEFACLOR ANHYDROUS	4	3
CEPHALEXIN ANHYDROUS	4	3
CEFUROXIME	4	2
CEFADROXIL	4	1
CEFDINIR	4	1
CEFEPIME	4	1
CEFIXIME	4	1
CEFPODOXIME	4	1
CEFPODOXIME PROXETIL	4	1
CEFTAZIDIME	4	1
CEFTRIAXONE	4	1
CHEMBL1555813	0	1
CHEMBL388266	0	1
CHEMBL4740200	0	1