Bullous pemphigoid

Summary

Bullous pemphigoid (MONDO:0019082) is a disease with 14 cohort genes (27 GWAS associations across 7 studies) and 49 clinical trials. Top therapeutic interventions include clobetasol propionate, efgartigimod alfa, and human immunoglobulin g.

At a glance

• Prevalence: 1-5 / 10 000 (Europe) [Orphanet-validated]
• Cohort genes: 14
• GWAS associations: 27
• Phenotypes (HPO): 15
• Clinical trials: 49

Clinical features

Epidemiology

Prevalence records

6 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Point prevalence	1-5 / 10 000	25	Europe	Validated
Annual incidence	1-9 / 100 000	2.17	France	Validated
Annual incidence	1-9 / 100 000	1.34	Germany	Validated
Annual incidence	1-9 / 100 000	4.3	United Kingdom	Validated
Annual incidence	1-9 / 100 000	1.21	Switzerland	Validated
Point prevalence	1-5 / 10 000	25.93	Germany	Validated

Signs & symptoms

Clinical features (HPO)

15 HPO clinical features (Orphanet curated; top 15 by frequency):

HPO ID	Term	Frequency
HP:0000819	Diabetes mellitus	Very frequent (80-99%)
HP:0000964	Eczematoid dermatitis	Very frequent (80-99%)
HP:0001025	Urticaria	Very frequent (80-99%)
HP:0001824	Weight loss	Very frequent (80-99%)
HP:0002719	Recurrent infections	Very frequent (80-99%)
HP:0002960	Autoimmunity	Very frequent (80-99%)
HP:0008066	Abnormal blistering of the skin	Very frequent (80-99%)
HP:0010783	Erythema	Very frequent (80-99%)
HP:0012733	Macule	Very frequent (80-99%)
HP:0000989	Pruritus	Frequent (30-79%)
HP:0003765	Psoriasiform dermatitis	Frequent (30-79%)
HP:0033106	Elevated circulating D-dimer concentration	Frequent (30-79%)
HP:4000019	Anti-BP230 antibody positivity	Frequent (30-79%)
HP:4000020	Anti-BP180 antibody positivity	Frequent (30-79%)
HP:0200097	Oral mucosal blisters	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	bullous pemphigoid
Mondo ID	MONDO:0019082
EFO	EFO:0007187
MeSH	D010391
Orphanet	703
DOID	DOID:8506
ICD-10-CM	L12.0
ICD-11	233308710
NCIT	C84389
SNOMED CT	77090002
UMLS	C0030805
MedGen	10620
GARD	0005972
Is cancer (heuristic)	no

Also known as: benign pemphigus · bullous pemphigoid · Old Age pemphigus · Parapemphigus · senile dermatitis herpetiformis

Data availability: 27 GWAS associations (7 studies).

Disease family

Classification path: disease › human disease › disease by body system or component › integumentary system disorder › skin disorder › dermatitis › autoimmune bullous skin disease › bullous pemphigoid

Related subtypes (10): pemphigus, subcorneal pustular dermatosis, dermatitis herpetiformis, anti-p200 pemphigoid, mucous membrane pemphigoid, acquired epidermolysis bullosa, linear IgA Dermatosis, paraneoplastic pemphigus, IgA pemphigus, pemphigoid

Genetics & variants

GWAS landscape

27 GWAS associations across 7 studies. Top hits map to 20 distinct genes (as reported by GWAS).

Top associations by p-value

rsID	p-value	Gene	Risk allele	Odds ratio
rs3129763	5e-111	HLA-DRB1 - HLA-DQA1	T	3.7
rs1140343	4e-101	HLA-DQB1	T	0.3
rs200132752	4e-38	MAST4	?	2.82
rs193922608	9e-38	VHL	?	2.82
rs80338857	4e-29	DHCR7	?	2.7
rs41264352	4e-10	HLA-DQB1	?	0.8
rs187163584	2e-09	CLN3	?	1.54
rs1957693	4e-08	SLC35F4	A	179.2
rs112621731	6e-08	HLA-DRB5 - RNU1-61P	?	0.71
rs9470413	1e-07	CPNE5	C	10.9
rs16943989	1e-07	LPIN2, EMILIN2	A	34.3
rs17017643	2e-07	HNRNPA3P8 - HYDINP1	A	3
rs1061495	2e-07	DELEC1, TNC	G	25.8
rs75702521	3e-07	LINC02712	?	3.05
rs7696323	9e-07	TLR2	A	28
rs10972168	2e-06	DCTN3	C	8.1
rs1891230	3e-06	FMN2	?	0.61
rs9268530	4e-06	TSBP1-AS1 - HLA-DRA	G	5.3
rs12545590	5e-06	CCDC26	?	0.51
rs6941112	7e-06	WHR1	?	0.5
rs62398467	7e-06	HLA-DQB2 - HLA-DOB	?	0.52
rs79859533	8e-06	LINC02064	?	0.86
rs1718459	8e-06	FLNB	G	7.3
rs10510507	8e-06	SGO1-AS1	T	365.6
chr13:80071932-?	9e-06		?	1.13

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST011940	Schwarm C	2021	438	0	Identification of two novel bullous pemphigoid- associated alleles, HLA-DQA105:05 and -DRB107:01, in Germans.
GCST90473912	UK Biobank Whole-Genome Sequencing Consortium	2025	263	458,177	Whole-genome sequencing of 490,640 UK Biobank participants.
GCST90296384	Ozeki T	2023	90	0	Association of Genetic Variants of HLA-DQA1 with Bullous Pemphigoid Induced by Dipeptidyl Peptidase-4 Inhibitors.
GCST90296388	Ozeki T	2023	69	0	Association of Genetic Variants of HLA-DQA1 with Bullous Pemphigoid Induced by Dipeptidyl Peptidase-4 Inhibitors.
GCST90296387	Ozeki T	2023	60	0	Association of Genetic Variants of HLA-DQA1 with Bullous Pemphigoid Induced by Dipeptidyl Peptidase-4 Inhibitors.
GCST90296385	Ozeki T	2023	21	0	Association of Genetic Variants of HLA-DQA1 with Bullous Pemphigoid Induced by Dipeptidyl Peptidase-4 Inhibitors.
GCST90296386	Ozeki T	2023	9	0	Association of Genetic Variants of HLA-DQA1 with Bullous Pemphigoid Induced by Dipeptidyl Peptidase-4 Inhibitors.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

Tier	Variants
Tier 1: coding	4
Tier 2: splice/UTR	1
Tier 3: regulatory	1
Tier 4: intronic/intergenic	19

MAF distribution

Bucket	Variants
common (>=0.05)	20
low_freq (0.01-0.05)	0
rare (<0.01)	0
unknown	5

Functional consequences

Consequence	Count
intron_variant	11
intergenic_variant	5
missense_variant	4
synonymous_variant	2
regulatory_region_variant	1
5_prime_UTR_variant	1
unknown	1

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
rs3129763	6	32623148	G>A,T	0.05	regulatory_region_variant	HLA-DRB1 - HLA-DQA1	5e-111	Tier 3: regulatory
rs1140343	6	32661360	T>C,G	0.05	missense_variant	HLA-DQB1	4e-101	Tier 1: coding
rs200132752	5	67164015	C>A,T		missense_variant	MAST4	4e-38	Tier 1: coding
rs193922608	3	10142089	C>A,T		missense_variant	VHL	9e-38	Tier 1: coding
rs80338857	11	71438985	C>A,G,T		missense_variant	DHCR7	4e-29	Tier 1: coding
rs41264352	6	32666059	A>C,T	0.05	intron_variant	HLA-DQB1	4e-10	Tier 4: intronic/intergenic
rs187163584	16	28492207	G>C		5_prime_UTR_variant	CLN3	2e-09	Tier 2: splice/UTR
rs1957693	14	57688561	C>G,T	0.05	intron_variant	SLC35F4	4e-08	Tier 4: intronic/intergenic
rs112621731	6	32533468	A>G	0.05	intergenic_variant	HLA-DRB5 - RNU1-61P	6e-08	Tier 4: intronic/intergenic
rs9470413	6	36828838	A>G	0.05	intron_variant	CPNE5	1e-07	Tier 4: intronic/intergenic
rs16943989	18	2892476	G>A	0.05	synonymous_variant	LPIN2, EMILIN2	1e-07	Tier 4: intronic/intergenic
rs17017643	3	80220227	C>G,T	0.05	intergenic_variant	HNRNPA3P8 - HYDINP1	2e-07	Tier 4: intronic/intergenic
rs1061495	9	115042265	T>A,C	0.05	synonymous_variant	DELEC1, TNC	2e-07	Tier 4: intronic/intergenic
rs75702521	11	127347953	C>T	0.05	intron_variant	LINC02712	3e-07	Tier 4: intronic/intergenic
rs7696323	4	153684593	C>G,T	0.05	intron_variant	TLR2	9e-07	Tier 4: intronic/intergenic
rs10972168	9	34619624	A>G	0.05	intron_variant	DCTN3	2e-06	Tier 4: intronic/intergenic
rs1891230	1	240024333	A>C,G,T	0.05	intergenic_variant	FMN2	3e-06	Tier 4: intronic/intergenic
rs9268530	6	32415446	T>C	0.05	intron_variant	TSBP1-AS1 - HLA-DRA	4e-06	Tier 4: intronic/intergenic
rs12545590	8	129551794	A>C,G,T	0.05	intron_variant	CCDC26	5e-06	Tier 4: intronic/intergenic
rs6941112	6	31978837	G>A	0.05	intron_variant	WHR1	7e-06	Tier 4: intronic/intergenic
rs62398467	6	32796758	C>G,T	0.05	intergenic_variant	HLA-DQB2 - HLA-DOB	7e-06	Tier 4: intronic/intergenic
rs79859533	5	29371235	T>A,C,G	0.05	intron_variant	LINC02064	8e-06	Tier 4: intronic/intergenic
rs1718459	3	58024573	C>G,T	0.05	intron_variant	FLNB	8e-06	Tier 4: intronic/intergenic
rs10510507	3	20903846	C>A	0.05	intergenic_variant	SGO1-AS1	8e-06	Tier 4: intronic/intergenic
chr13:80071932-?							9e-06	Tier 4: intronic/intergenic

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 13 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 1

Dual-evidence genes (GWAS + Mendelian — highest-confidence targets)

Gene	HGNC	Evidence routes
HLA-DQB1	HLA-DQB1	GWAS, Orphanet

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
VHL	Orphanet:238557	Chuvash erythrocytosis
VHL	Orphanet:276621	Sporadic pheochromocytoma/secreting paraganglioma
VHL	Orphanet:29072	Hereditary pheochromocytoma-paraganglioma
VHL	Orphanet:892	Von Hippel-Lindau disease
FMN2	Orphanet:88616	Autosomal recessive non-syndromic intellectual disability
CLN3	Orphanet:699780	Juvenile CLN3 disease
CLN3	Orphanet:699796	Protracted juvenile CLN3 disease
DHCR7	Orphanet:818	Smith-Lemli-Opitz syndrome
HLA-DQB1	Orphanet:2073	Narcolepsy type 1
HLA-DQB1	Orphanet:477738	Pediatric multiple sclerosis
HLA-DQB1	Orphanet:703	Bullous pemphigoid
HLA-DQB1	Orphanet:83465	Narcolepsy type 2
HLA-DQB1	Orphanet:930	Idiopathic achalasia

Cohort genes → proteins

14 cohort genes, 11 distinct canonical proteins.

Evidence partition

Subset	Genes
gwas_only	14

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
WHR1	HGNC:11398	ENSG00000204344	P49842	Winged helix repair factor 1	gwas
VHL	HGNC:12687	ENSG00000134086	P40337	von Hippel-Lindau disease tumor suppressor	gwas
FMN2	HGNC:14074	ENSG00000155816	Q9NZ56	Formin-2	gwas
NDFIP2	HGNC:18537	ENSG00000102471	Q9NV92	NEDD4 family-interacting protein 2	gwas
MAST4	HGNC:19037	ENSG00000069020	O15021	Microtubule-associated serine/threonine-protein kinase 4	gwas
CLN3	HGNC:2074	ENSG00000188603	Q13286	Battenin	gwas
CCDC26	HGNC:28416	ENSG00000229140		CCDC26 long non-coding RNA	gwas
DHCR7	HGNC:2860	ENSG00000172893	Q9UBM7	7-dehydrocholesterol reductase	gwas
RPS7P5	HGNC:37037	ENSG00000217327		ribosomal protein S7 pseudogene 5	gwas
HLA-DOB	HGNC:4937	ENSG00000241106	P13765	HLA class II histocompatibility antigen, DO beta chain	gwas
HLA-DQB1	HGNC:4944	ENSG00000179344	P01920	HLA class II histocompatibility antigen, DQ beta 1 chain	gwas
HLA-DQB2	HGNC:4945	ENSG00000232629	P05538	HLA class II histocompatibility antigen, DQ beta 2 chain	gwas
HLA-DRB5	HGNC:4953	ENSG00000198502	Q30154	HLA class II histocompatibility antigen, DR beta 5 chain	gwas
HLA-DRB6	HGNC:4954	ENSG00000229391		major histocompatibility complex, class II, DR beta 6 (pseudogene)	gwas

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
WHR1	Winged helix repair factor 1	DNA-binding protein which is required for efficient transcription-coupled nucleotide excision repair (TC-NER).
VHL	von Hippel-Lindau disease tumor suppressor	Involved in the ubiquitination and subsequent proteasomal degradation via the von Hippel-Lindau ubiquitination complex.
FMN2	Formin-2	Actin-binding protein that is involved in actin cytoskeleton assembly and reorganization.
NDFIP2	NEDD4 family-interacting protein 2	Activates HECT domain-containing E3 ubiquitin-protein ligases, including ITCH, NEDD4, NEDD4L, SMURF2, WWP1 and WWP2, and consequently modulates the stability of their targets.
CLN3	Battenin	Mediates microtubule-dependent, anterograde transport connecting the Golgi network, endosomes, autophagosomes, lysosomes and plasma membrane, and participates in several cellular processes such as regulation of lysosomal pH, lysosome prote…
DHCR7	7-dehydrocholesterol reductase	Oxidoreductase that catalyzes the last step of the cholesterol synthesis pathway, which transforms cholesta-5,7-dien-3beta-ol (7-dehydrocholesterol,7-DHC) into cholesterol by reducing the C7-C8 double bond of its sterol core.
HLA-DOB	HLA class II histocompatibility antigen, DO beta chain	Important modulator in the HLA class II restricted antigen presentation pathway by interaction with the HLA-DM molecule in B-cells.
HLA-DQB1	HLA class II histocompatibility antigen, DQ beta 1 chain	Binds peptides derived from antigens that access the endocytic route of antigen presenting cells (APC) and presents them on the cell surface for recognition by the CD4 T-cells.
HLA-DQB2	HLA class II histocompatibility antigen, DQ beta 2 chain	Binds peptides derived from antigens that access the endocytic route of antigen presenting cells (APC) and presents them on the cell surface for recognition by the CD4 T-cells.
HLA-DRB5	HLA class II histocompatibility antigen, DR beta 5 chain	Binds peptides derived from antigens that access the endocytic route of antigen presenting cells (APC) and presents them on the cell surface for recognition by the CD4 T-cells.

Protein-family classification

Druggable: 8 · Difficult: 0 · Unknown: 6 · Druggable fraction: 0.57

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	4	8.3×	0.005
Transporter	1	5.6×	0.414
Kinase	1	2.0×	0.503
Enzyme (other)	2	1.7×	0.503
Other/Unknown	6	0.8×	0.893

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
WHR1	Other/Unknown	no		STK19-like
VHL	Enzyme (other)	yes	2.3.2.B13	VHL_tumour_suppress_b/a_dom, VHL_alpha_dom, VHL_beta_dom
FMN2	Other/Unknown	no		DEP_dom, FH2_Formin, FH2_Formin_sf
NDFIP2	Other/Unknown	no		NEDD4/Bsd2
MAST4	Kinase	yes		Prot_kinase_dom, AGC-kinase_C, PDZ
CLN3	Transporter	yes		Battenin_disease_Cln3, Battenin_disease_Cln3_subgr, MFS_trans_sf
CCDC26	Other/Unknown	no
DHCR7	Enzyme (other)	yes	1.3.1.21	ERG24_DHCR-like, Sterol_reductase_CS
RPS7P5	Other/Unknown	no
HLA-DOB	Antibody/Immunoglobulin	yes		MHC_II_b_N, Ig/MHC_CS, Ig_C1-set
HLA-DQB1	Antibody/Immunoglobulin	yes		MHC_II_b_N, Ig/MHC_CS, Ig_C1-set
HLA-DQB2	Antibody/Immunoglobulin	yes		MHC_II_b_N, Ig/MHC_CS, Ig_C1-set
HLA-DRB5	Antibody/Immunoglobulin	yes		MHC_II_b_N, Ig/MHC_CS, Ig_C1-set
HLA-DRB6	Other/Unknown	no

Expression context

Cohort genes with no expression data: 0.

13 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)	14
unknown	0

Top tissues across cohort

Tissue	Cohort genes
granulocyte	4
lymph node	3
cortical plate	2
male germ line stem cell (sensu Vertebrata) in testis	2
spleen	2
vermiform appendix	2
left adrenal gland	1
left adrenal gland cortex	1
right adrenal gland	1
monocyte	1
mononuclear cell	1
Brodmann (1909) area 9	1
prefrontal cortex	1
secondary oocyte	1
sperm	1
upper arm skin	1
cartilage tissue	1
cervix squamous epithelium	1
squamous epithelium	1
mucosa of transverse colon	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
WHR1	134	ubiquitous	marker	left adrenal gland, left adrenal gland cortex, right adrenal gland
VHL	186	ubiquitous	marker	cortical plate, monocyte, mononuclear cell
FMN2	187	broad	marker	cortical plate, prefrontal cortex, Brodmann (1909) area 9
NDFIP2	261	ubiquitous	marker	secondary oocyte, upper arm skin, sperm
MAST4	294	ubiquitous	marker	cervix squamous epithelium, cartilage tissue, squamous epithelium
CLN3	134	ubiquitous	marker	mucosa of transverse colon, placenta, granulocyte
CCDC26	160	tissue_specific	marker	male germ line stem cell (sensu Vertebrata) in testis, colonic epithelium, bone marrow cell
DHCR7	257	ubiquitous	marker	adrenal tissue, right lobe of liver, right adrenal gland cortex
RPS7P5	53	tissue_specific	yes	male germ line stem cell (sensu Vertebrata) in testis, primordial germ cell in gonad, left testis
HLA-DOB	128	tissue_specific	marker	lymph node, spleen, vermiform appendix
HLA-DQB1	268	broad	marker	right lung, spleen, upper lobe of left lung
HLA-DQB2	127	tissue_specific	marker	lymph node, granulocyte, skin of abdomen
HLA-DRB5	130	tissue_specific	marker	granulocyte, lymph node, vermiform appendix
HLA-DRB6	234		marker	granulocyte, tendon of biceps brachii, type B pancreatic cell

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
VHL	3,522
DHCR7	2,345
FMN2	1,995
HLA-DRB5	1,897
CLN3	1,613
HLA-DOB	1,583
HLA-DQB2	1,547
NDFIP2	992
MAST4	943
WHR1	535

Structural data

PDB: 7 · AlphaFold-only: 4 · No structure: 3

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
VHL	P40337	142
HLA-DQB1	P01920	10
WHR1	P49842	5
HLA-DRB5	Q30154	4
FMN2	Q9NZ56	2
MAST4	O15021	1
HLA-DOB	P13765	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
DHCR7	Q9UBM7	91.64
HLA-DQB2	P05538	86.87
CLN3	Q13286	81.81
NDFIP2	Q9NV92	57.15

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 18. Enrichment computed across 14 evidence-associated genes (7 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 7 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Translocation of ZAP-70 to Immunological synapse	2	181.3×	3e-04	HLA-DQB2, HLA-DRB5
Phosphorylation of CD3 and TCR zeta chains	2	155.4×	3e-04	HLA-DQB2, HLA-DRB5
Co-inhibition by PD-1	2	148.3×	3e-04	HLA-DQB2, HLA-DRB5
Interferon gamma signaling	3	53.8×	3e-04	HLA-DQB1, HLA-DQB2, HLA-DRB5
MHC class II antigen presentation	3	38.2×	3e-04	HLA-DOB, HLA-DQB2, HLA-DRB5
Generation of second messenger molecules	2	98.9×	5e-04	HLA-DQB2, HLA-DRB5
Downstream TCR signaling	2	36.7×	0.003	HLA-DQB2, HLA-DRB5
Replication of the SARS-CoV-1 genome	1	407.9×	0.004	VHL
Replication of the SARS-CoV-2 genome	1	407.9×	0.004	VHL
Cholesterol biosynthesis from zymosterol (modified Kandutsch-Russell pathway)	1	407.9×	0.004	DHCR7
Glycosphingolipid transport	1	203.9×	0.008	CLN3
Cholesterol biosynthesis via desmosterol (Bloch pathway)	1	163.1×	0.008	DHCR7
RHOBTB3 ATPase cycle	1	163.1×	0.008	VHL
SUMOylation of ubiquitinylation proteins	1	41.8×	0.030	VHL
Activation of gene expression by SREBF (SREBP)	1	37.1×	0.032	DHCR7
Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha	1	28.1×	0.039	VHL
Neddylation	1	6.8×	0.147	VHL
Antigen processing: Ubiquitination & Proteasome degradation	1	5.3×	0.174	VHL

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 11 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
peptide antigen assembly with MHC class II protein complex	4	383.0×	2e-08	HLA-DOB, HLA-DQB1, HLA-DQB2, HLA-DRB5
antigen processing and presentation of exogenous peptide antigen via MHC class II	4	197.7×	2e-07	HLA-DOB, HLA-DQB1, HLA-DQB2, HLA-DRB5
positive regulation of immune response	4	175.1×	2e-07	HLA-DOB, HLA-DQB1, HLA-DQB2, HLA-DRB5
positive regulation of T cell activation	4	161.3×	2e-07	HLA-DOB, HLA-DQB1, HLA-DQB2, HLA-DRB5
adaptive immune response	4	30.6×	1e-04	HLA-DOB, HLA-DQB1, HLA-DQB2, HLA-DRB5
homologous chromosome movement towards spindle pole in meiosis I anaphase	1	1532.0×	0.008	FMN2
obsolete phagosome-lysosome docking	1	1532.0×	0.008	CLN3
regulation of cellular response to osmotic stress	1	1532.0×	0.008	CLN3
regulation of arginine biosynthetic process	1	1532.0×	0.008	CLN3
negative regulation of antigen processing and presentation of peptide antigen via MHC class II	1	766.0×	0.011	HLA-DOB
renal potassium excretion	1	766.0×	0.011	CLN3
positive regulation of single strand break repair	1	766.0×	0.011	WHR1
regulation of phagosome maturation	1	766.0×	0.011	CLN3
regulation of autophagosome size	1	510.7×	0.012	CLN3
glycolipid transport	1	510.7×	0.012	CLN3
formin-nucleated actin cable assembly	1	510.7×	0.012	FMN2
regulation of modification of synaptic structure	1	510.7×	0.012	CLN3
obsolete cholesterol biosynthetic process via desmosterol	1	383.0×	0.014	DHCR7
establishment of meiotic spindle localization	1	383.0×	0.014	FMN2
positive regulation of caveolin-mediated endocytosis	1	383.0×	0.014	CLN3
lysosomal lumen pH elevation	1	306.4×	0.014	CLN3
polar body extrusion after meiotic divisions	1	306.4×	0.014	FMN2
positive regulation of pinocytosis	1	306.4×	0.014	CLN3
vacuolar transport	1	255.3×	0.014	NDFIP2
positive regulation of Golgi to plasma membrane protein transport	1	255.3×	0.014	CLN3
plasma membrane raft organization	1	255.3×	0.014	CLN3
regulation of cellular response to hypoxia	1	255.3×	0.014	VHL
regulation of autophagosome maturation	1	255.3×	0.014	CLN3
cellular response to hypoxia	2	22.0×	0.014	VHL, FMN2
negative regulation of apoptotic process	3	9.5×	0.014	VHL, FMN2, CLN3

Therapeutics

Drugs indicated for this disease

0 approved, 8 in late-stage (phase 3) trials. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

Drug	Development status
Benralizumab	Phase 3 (in late-stage trials)
Clobetasol Propionate	Phase 3 (in late-stage trials)
Efgartigimod Alfa	Phase 3 (in late-stage trials)
Human Immunoglobulin G	Phase 3 (in late-stage trials)
Methotrexate	Phase 3 (in late-stage trials)
Nomacopan	Phase 3 (in late-stage trials)
Prednisone	Phase 3 (in late-stage trials)
Rituximab	Phase 3 (in late-stage trials)

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): Azathioprine, Clobetasol, Diacerein, Dupilumab, Ixekizumab, Ladarixin, Leflunomide, Ligelizumab, Mometasone Furoate, Mycophenolate Mofetil, Omalizumab, Ustekinumab.

Drug target analysis

Approved (phase 4): 2 · Phase ≥3: 2 · Phased (≥1): 2 · Undrugged: 12

Druggability breadth: 5 of 14 evidence-associated genes (36%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

Symbol	Example approved molecule
VHL	OSIMERTINIB
DHCR7	DOXORUBICIN

Top cohort targets by molecule count

Symbol	Molecules	Max phase
VHL	7	4
DHCR7	2	4
WHR1	0	0
FMN2	0	0
NDFIP2	0	0
MAST4	0	0
CLN3	0	0
CCDC26	0	0
RPS7P5	0	0
HLA-DOB	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
OSIMERTINIB	4	VHL
BRIGATINIB	4	VHL
CRIZOTINIB	4	VHL
ADAGRASIB	4	VHL
DOXORUBICIN	4	DHCR7
TAMOXIFEN	4	DHCR7
ZIMLOVISERTIB	2	VHL
FORETINIB	2	VHL
DT-2216	1	VHL

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 2.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
VHL	3,575	Binding:3482, Functional:54, ADMET:39
DHCR7	43	Functional:23, Binding:20
WHR1	36	Binding:36
MAST4	13	Binding:13

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
VHL	2.3.2.B13
DHCR7	1.3.1.21	7-dehydrocholesterol reductase

Cohort genes with high screening signal

≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.

Symbol	ChEMBL assays
VHL	3,575

Pharmacogenomics

Cohort genes with a PharmGKB record: 13; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

9 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.

Compound	Max phase	Cohort target (bioactivity)
OSIMERTINIB	4	VHL
BRIGATINIB	4	VHL
CRIZOTINIB	4	VHL
ADAGRASIB	4	VHL
DOXORUBICIN	4	DHCR7
TAMOXIFEN	4	DHCR7
ZIMLOVISERTIB	2	VHL
FORETINIB	2	VHL
DT-2216	1	VHL

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	2	VHL, DHCR7
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	4	MAST4, HLA-DOB, HLA-DQB1, HLA-DRB5
D	Druggable family + AlphaFold only, no drug	2	CLN3, HLA-DQB2
E	Difficult family or no structure, no drug	6	WHR1, FMN2, NDFIP2, CCDC26, RPS7P5, HLA-DRB6

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
WHR1	36	—
FMN2	0	—
NDFIP2	0	—
MAST4	13	—
CLN3	0	—
CCDC26	0	—
RPS7P5	0	—
HLA-DOB	0	—
HLA-DQB1	0	—
HLA-DQB2	0	—
HLA-DRB5	0	—
HLA-DRB6	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 49.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	20
PHASE2	10
PHASE3	9
PHASE4	4
PHASE1	3
PHASE2/PHASE3	2
PHASE1/PHASE2	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT00472030	PHASE4	COMPLETED	Efficacy and Safety of Omalizumab in Bullous Pemphigoid
NCT02360202	PHASE4	COMPLETED	Evaluation of Fluid Retention Due to Superpotent Topical Corticosteroid
NCT03926377	PHASE4	UNKNOWN	Influence of Dermocorticoids on Bone Mineral Density in Patients With Bullous Pemphigoid
NCT05984381	PHASE4	COMPLETED	Efficacy and Safety of add-on Dapsone Versus add-on Methotrexate in Patients With Bullous Pemphigoid
NCT07210554	PHASE3	NOT_YET_RECRUITING	Study of Stapokibart Injection in Subjects With Moderate to Severe Bullous Pemphigoid
NCT00525616	PHASE3	COMPLETED	Efficiency and Tolerance of Rituximab (mabthéra) in Bullous Pemphigoid
NCT01408550	PHASE3	COMPLETED	Phase III Clinical Trial of NPB-01 in Patients With Bullous Pemphigoid Unresponsive to Corticosteroids
NCT02313870	PHASE3	COMPLETED	Topical Steroids Alone or Associated With Methotrexate in Bullous Pemphigoid
NCT04128176	PHASE3	WITHDRAWN	Efficacy and Safety of Rituximab Combined With Omalizumab in Patients With Bullous Pemphigoid
NCT04206553	PHASE2/PHASE3	COMPLETED	A Study to Evaluate the Efficacy and Safety of Dupilumab in Adult Patients With Bullous Pemphigoid
NCT04612790	PHASE3	TERMINATED	A Study to Investigate the Use of Benralizumab in Patients With Bullous Pemphigoid.
NCT05061771	PHASE3	WITHDRAWN	Nomacopan Therapy in Adult Patients With Bullous Pemphigoid Receiving Adjunct Oral Corticosteroid Therapy (ARREST-BP)
NCT05267600	PHASE2/PHASE3	COMPLETED	A Phase 2/3 Study of Efgartigimod PH20 SC in Adult Participants With Bullous Pemphigoid
NCT05594472	PHASE3	UNKNOWN	Ozonated Olive Oil in Treatment of Pemphigus Vulgaris and Bullous Pemphigoid
NCT05681481	PHASE3	TERMINATED	A Phase 3 Study to Evaluate the Long-term Safety, Tolerability and Efficacy of Efgartigimod PH20 SC in Adult Participants With Bullous Pemphigoid
NCT00286325	PHASE1/PHASE2	COMPLETED	Rituximab in the Treatment of Patients With Bullous Pemphigoid
NCT00431119	PHASE2	COMPLETED	Azathioprine or Mycophenolate Mofetil for Bullous Pemphigoid
NCT00802243	PHASE2	UNKNOWN	Leflunomide Associated With Topical Corticosteroids for Bullous Pemphigoid
NCT00809822	PHASE2	COMPLETED	Clinical Trial of NPB-01 in Patients With Bullous Pemphigoid Unresponsive to Corticosteroids.
NCT01571895	PHASE2	TERMINATED	Pilot Efficacy and Safety Study of Oral DF2156A in Patients With Active Bullous Pemphigoid
NCT01688882	PHASE2	TERMINATED	Safety, Efficacy and PK/PD of QGE031 vs. Placebo in Patients With Active Bullous Pemphigoid Despite Oral Steroid Treatment
NCT03099538	PHASE2	COMPLETED	Ixekizumab in the Treatment of Bullous Pemphigoid
NCT03286582	PHASE2	TERMINATED	A Proof-of-Concept Study of Topical AC-203 in Patients With Bullous Pemphigoid
NCT04035733	PHASE2	COMPLETED	rVA576 in Adult Mild to Moderate Bullous Pemphigoid Subjects
NCT04117932	PHASE2	COMPLETED	Efficacy and Safety of Ustekinumab in Bullous Pemphigoid
NCT04563923	PHASE2	COMPLETED	Treatment of Bullous Pemphigoid With Avdoralimab (IPH5401), an Anti-C5aR1 Monoclonal Antibody
NCT06371417	PHASE1	RECRUITING	Phase 1b Trial of RAY121 in Immunological Diseases (RAINBOW Trial)
NCT06723106	PHASE1	ENROLLING_BY_INVITATION	Phase 1b Long-term Extension Trial of RAY121 in Immunological Diseases (RAINBOW-LTE Trial)
NCT02502903	PHASE1	COMPLETED	Safety, Tolerability and Activity of BIVV009 in Healthy Volunteers and Patients With Complement Mediated Disorders
NCT02753777	Not specified	RECRUITING	Autoimmune Blistering Diseases Study
NCT05366127	Not specified	NOT_YET_RECRUITING	Validation of a Simplified Severity Score (Investigator Global Assessment: IGA) in Bullous Pemphigoid
NCT06479018	Not specified	RECRUITING	Deciphering IL-17-dependant Inflammatory Response in Bullous Pemphigoid
NCT00213421	Not specified	COMPLETED	Comparison of Two Therapeutic Strategies of Dermoval in Treatment of Bullous Pemphigus
NCT01265082	Not specified	UNKNOWN	Explore the Mechanisms of Pruritus in Bullous Pemphigoid Patients During Remission
NCT02837965	Not specified	COMPLETED	Observational Study Assessing Outcomes, Treatment Patterns and Related Costs in Patients in Bullous Pemphigoid
NCT02874079	Not specified	UNKNOWN	Genetic Susceptibility and Influence of the Microbiomae in Bullous Pemphigoid
NCT02883894	Not specified	COMPLETED	Interest of Dosage of Anti-PB230, Anti-PB180 and Cytokines for Monitoring of Patients Suffering From Bullous Pemphigoid
NCT03272958	Not specified	COMPLETED	Clinical Characteristics of Pruritus and Evaluation of Quality of Life in Patients With Bullous Pemphigoid
NCT03320798	Not specified	COMPLETED	Impact of Neurological Diseases on the Prognosis of Bullous Pemphigoid: A Retrospective Study of 178 Patients
NCT03636763	Not specified	UNKNOWN	Dipeptidyl Peptidase-IV Inhibitors, Risk Factor for Development of Bullous Pemphigoid?

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
CLOBETASOL PROPIONATE	4	3
EFGARTIGIMOD ALFA	4	2
HUMAN IMMUNOGLOBULIN G	4	2
BENRALIZUMAB	4	1
DAPSONE	4	1
DUPILUMAB	4	1
GENTAMICIN SULFATE	4	1
IXEKIZUMAB	4	1
LEFLUNOMIDE	4	1
OMALIZUMAB	4	1
PREDNISONE	4	1
USTEKINUMAB	4	1
CLOBETASOL	3	1
DIACEREIN	3	1
LADARIXIN	3	1
LIGELIZUMAB	3	1
NOMACOPAN	3	1
STAPOKIBART	3	1
CHEMBL15720	0	1