nodular sclerosis classical Hodgkin lymphoma

Summary

nodular sclerosis classical Hodgkin lymphoma (MONDO:0004665) is a cancer with 10 cohort genes (11 GWAS associations across 3 studies; 3 CIViC-evidence somatic drivers) and 2 clinical trials. The dominant Reactome pathway is Translocation of ZAP-70 to Immunological synapse (3 cohort genes). Top therapeutic interventions include fludeoxyglucose f 18, ifosfamide, and vinblastine sulfate.

At a glance

• Classification: Cancer
• Prevalence: 1-9 / 100 000 (Europe) [Orphanet-validated]
• Cohort genes: 10
• GWAS associations: 11
• Clinical trials: 2

Clinical features

Epidemiology

Prevalence records

1 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Annual incidence	1-9 / 100 000	1.28	Europe	Validated

Identifiers

Disease identifiers

Field	Value
Canonical name	nodular sclerosis classical Hodgkin lymphoma
Mondo ID	MONDO:0004665
EFO	EFO:0004708
Orphanet	98843
DOID	DOID:8838
ICD-10-CM	C81.1
ICD-11	1995941600
NCIT	C3518
SNOMED CT	118608000
UMLS	C0152268
MedGen	101830
GARD	0019591
Is cancer (heuristic)	yes

Also known as: Hodgkin lymphoma, nodular sclerosis · Hodgkin’s disease nodular sclerosis · Hodgkin’s disease, nodular sclerosis NOS (morphologic abnormality) · Hodgkin’s disease, nodular sclerosis of unspecified site · Hodgkin’s nodular sclerosis · nodular sclerosis Classic Hodgkin lymphoma · nodular sclerosis classical Hodgkin lymphoma · nodular sclerosis Hodgkin lymphoma · nodular sclerosis Hodgkin’s disease · nodular sclerosis Hodgkin’s lymphoma · NSCHL · NSHD · NSHL

Data availability: 11 GWAS associations (3 studies).

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › classic Hodgkin lymphoma › nodular sclerosis classical Hodgkin lymphoma

Related subtypes (3): Hodgkin’s lymphoma, lymphocytic-histiocytic predominance, Hodgkin’s lymphoma, lymphocytic depletion, Hodgkin’s lymphoma, mixed cellularity

Genetics & variants

GWAS landscape

11 GWAS associations across 3 studies. Top hits map to 6 distinct genes (as reported by GWAS).

Top associations by p-value

rsID	p-value	Gene	Risk allele	Odds ratio
rs9269081	2e-39	HLA-DRB9	?	1.82
rs9268528	8e-18	TSBP1-AS1 - HLA-DRA; HLA-DRB1 - HLA-DQA1; HLA-DRB9; FKBPL - PPT2; TSBP1-AS1 - HLA-DRA	A	2.5
DPB1*03:01	3e-17		?	1.89
rs4459895	9e-17	LPP	A	1.39
Val86 HLA-DRB1	4e-13		?	1.43
rs3781093	9e-13	GATA3	T	1.39
rs6928977	5e-11	AHI1	G	1.23
rs34972832	2e-08	CLEC16A	A	1.24
rs112998813	5e-08	UPF3A	C	1.39
rs9482849	4e-06	THEMIS - PTPRK	C	1.21

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST005211	Sud A	2017	1,278	14,325	Genome-wide association study of classical Hodgkin lymphoma identifies key regulators of disease susceptibility.
GCST001323	Cozen W	2011	393	3,315	A genome-wide meta-analysis of nodular sclerosing Hodgkin lymphoma identifies risk loci at 6p21.32.
GCST90043904	Jiang L	2021	126	456,222	A generalized linear mixed model association tool for biobank-scale data.

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	9

MAF distribution

Bucket	Variants
common (>=0.05)	8
low_freq (0.01-0.05)	0
rare (<0.01)	0
unknown	2

Functional consequences

Consequence	Count
intron_variant	5
unknown	2
non_coding_transcript_exon_variant	1
intron_variant; regulatory_region_variant; intron_variant; intergenic_variant; intron_variant	1
intergenic_variant	1

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
rs9269081	6	32473323	A>C,G	0.05	non_coding_transcript_exon_variant	HLA-DRB9	2e-39	Tier 4: intronic/intergenic
rs9268528	6;6;6;6;6	32415331	A>G,T	0.05	intron_variant; regulatory_region_variant; intron_variant; intergenic_variant; intron_variant	TSBP1-AS1 - HLA-DRA; HLA-DRB1 - HLA-DQA1; HLA-DRB9; FKBPL - PPT2; TSBP1-AS1 - HLA-DRA	8e-18	Tier 3: regulatory
DPB1*03:01							3e-17	Tier 4: intronic/intergenic
rs4459895	3	188236626	A>C,G,T	0.19	intron_variant	LPP	9e-17	Tier 4: intronic/intergenic
Val86 HLA-DRB1							4e-13	Tier 4: intronic/intergenic
rs3781093	10	8059964	T>C	0.14	intron_variant	GATA3	9e-13	Tier 4: intronic/intergenic
rs6928977	6	135305210	T>C,G	0.43	intron_variant	AHI1	5e-11	Tier 4: intronic/intergenic
rs34972832	16	11105081	G>A,T	0.19	intron_variant	CLEC16A	2e-08	Tier 4: intronic/intergenic
rs112998813	13	114294254	T>C	0.07	intron_variant	UPF3A	5e-08	Tier 4: intronic/intergenic
rs9482849	6	127967391	T>C	0.15	intergenic_variant	THEMIS - PTPRK	4e-06	Tier 4: intronic/intergenic

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 27 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 3

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

Gene	HGNC	Evidence routes
GATA3	GATA3	GWAS, Orphanet
HLA-DQB1	HLA-DQB1	GWAS, Orphanet
HLA-DRB1	HLA-DRB1	GWAS, Orphanet

Somatic driver evidence (intOGen + CIViC, cohort fanout)

Gene	intOGen role	Cancer types	CIViC
GATA3	Act	ALL,BRCA	CIViC #2189
HLA-DRA			CIViC #2622
PTPRK	LoF	BLCA,CCRCC,NSCLC

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
AHI1	Orphanet:220493	Joubert syndrome with ocular defect
AHI1	Orphanet:475	Isolated Joubert syndrome
AHI1	Orphanet:791	Retinitis pigmentosa
GATA3	Orphanet:2237	Hypoparathyroidism-sensorineural deafness-renal disease syndrome
GATA3	Orphanet:585936	B-lymphoblastic leukemia/lymphoma with hyperdiploidy
HLA-DPB1	Orphanet:133	Chronic beryllium disease
HLA-DPB1	Orphanet:900	Granulomatosis with polyangiitis
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
HLA-DRA	Orphanet:505	Graham Little-Piccardi-Lassueur syndrome
HLA-DRB1	Orphanet:2073	Narcolepsy type 1
HLA-DRB1	Orphanet:220393	Diffuse cutaneous systemic sclerosis
HLA-DRB1	Orphanet:220402	Limited cutaneous systemic sclerosis
HLA-DRB1	Orphanet:220407	Limited systemic sclerosis
HLA-DRB1	Orphanet:3437	Vogt-Koyanagi-Harada disease
HLA-DRB1	Orphanet:397	Giant cell arteritis
HLA-DRB1	Orphanet:477738	Pediatric multiple sclerosis
HLA-DRB1	Orphanet:536	Systemic lupus erythematosus
HLA-DRB1	Orphanet:545	Follicular lymphoma
HLA-DRB1	Orphanet:703	Bullous pemphigoid
HLA-DRB1	Orphanet:747	Autoimmune pulmonary alveolar proteinosis
HLA-DRB1	Orphanet:797	Sarcoidosis
HLA-DRB1	Orphanet:83465	Narcolepsy type 2
HLA-DRB1	Orphanet:85414	Systemic-onset juvenile idiopathic arthritis

Cohort genes → proteins

10 cohort genes, 10 distinct canonical proteins.

Evidence partition

Subset	Genes
gwas_only	10

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
UPF3A	HGNC:20332	ENSG00000169062	Q9H1J1	Regulator of nonsense transcripts 3A	gwas
AHI1	HGNC:21575	ENSG00000135541	Q8N157	Jouberin	gwas
CLEC16A	HGNC:29013	ENSG00000038532	Q2KHT3	Protein CLEC16A	gwas
GATA3	HGNC:4172	ENSG00000107485	P23771	Trans-acting T-cell-specific transcription factor GATA-3	gwas
HLA-DPB1	HGNC:4940	ENSG00000223865	P04440	HLA class II histocompatibility antigen, DP beta 1 chain	gwas
HLA-DQB1	HGNC:4944	ENSG00000179344	P01920	HLA class II histocompatibility antigen, DQ beta 1 chain	gwas
HLA-DRA	HGNC:4947	ENSG00000204287	P01903	HLA class II histocompatibility antigen, DR alpha chain	gwas
HLA-DRB1	HGNC:4948	ENSG00000196126	P01911	HLA class II histocompatibility antigen, DRB1 beta chain	gwas
LPP	HGNC:6679	ENSG00000145012	Q93052	Lipoma-preferred partner	gwas
PTPRK	HGNC:9674	ENSG00000152894	Q15262	Receptor-type tyrosine-protein phosphatase kappa	gwas

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
UPF3A	Regulator of nonsense transcripts 3A	Involved in nonsense-mediated decay (NMD) of mRNAs containing premature stop codons by associating with the nuclear exon junction complex (EJC) and serving as link between the EJC core and NMD machinery.
AHI1	Jouberin	Involved in vesicle trafficking and required for ciliogenesis, formation of primary non-motile cilium, and recruitment of RAB8A to the basal body of primary cilium.
CLEC16A	Protein CLEC16A	Regulator of mitophagy through the upstream regulation of the RNF41/NRDP1-PRKN pathway.
GATA3	Trans-acting T-cell-specific transcription factor GATA-3	Transcriptional activator which binds to the enhancer of the T-cell receptor alpha and delta genes.
HLA-DPB1	HLA class II histocompatibility antigen, DP 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-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-DRA	HLA class II histocompatibility antigen, DR alpha chain	An alpha chain of antigen-presenting major histocompatibility complex class II (MHCII) molecule.
HLA-DRB1	HLA class II histocompatibility antigen, DRB1 beta chain	A beta chain of antigen-presenting major histocompatibility complex class II (MHCII) molecule.
LPP	Lipoma-preferred partner	May play a structural role at sites of cell adhesion in maintaining cell shape and motility.
PTPRK	Receptor-type tyrosine-protein phosphatase kappa	Regulation of processes involving cell contact and adhesion such as growth control, tumor invasion, and metastasis.

Protein-family classification

Druggable: 5 · Difficult: 3 · Unknown: 2 · Druggable fraction: 0.5

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	11.7×	0.001
Phosphatase	1	8.4×	0.283
Scaffold/PPI	1	1.7×	0.561
Transcription factor	2	1.6×	0.561
Other/Unknown	2	0.4×	0.996

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
UPF3A	Other/Unknown	no		UPF3_dom, Nucleotide-bd_a/b_plait_sf, RBD_domain_sf
AHI1	Scaffold/PPI	no		SH3_domain, WD40_rpt, WD40/YVTN_repeat-like_dom_sf
CLEC16A	Other/Unknown	no		CLEC16A/TT9_N, CLEC16A/TT9, CLEC16A/TT9_C
GATA3	Transcription factor	no		Znf_GATA, Znf_NHR/GATA, TF_GATA-2/3
HLA-DPB1	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-DRA	Antibody/Immunoglobulin	yes		MHC_II_a_N, Ig/MHC_CS, Ig_C1-set
HLA-DRB1	Antibody/Immunoglobulin	yes		MHC_II_b_N, Ig/MHC_CS, Ig_C1-set
LPP	Transcription factor	no		Znf_LIM
PTPRK	Phosphatase	yes	3.1.3.48	PTP_cat, Tyr_Pase_dom, MAM_dom

Expression context

Cohort genes with no expression data: 0.

10 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)	10
unknown	0

Top tissues across cohort

Tissue	Cohort genes
vermiform appendix	3
right hemisphere of cerebellum	2
granulocyte	2
right lung	2
cerebellar hemisphere	1
sural nerve	1
calcaneal tendon	1
pituitary gland	1
left testis	1
right testis	1
testis	1
endometrium epithelium	1
skin of hip	1
upper leg skin	1
lymph node	1
spleen	1
upper lobe of left lung	1
leukocyte	1
monocyte	1
saphenous vein	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
UPF3A	191	ubiquitous	marker	right hemisphere of cerebellum, cerebellar hemisphere, sural nerve
AHI1	276	ubiquitous	marker	pituitary gland, calcaneal tendon, right hemisphere of cerebellum
CLEC16A	225	ubiquitous	marker	left testis, right testis, testis
GATA3	220	broad	marker	upper leg skin, skin of hip, endometrium epithelium
HLA-DPB1	135	ubiquitous	marker	granulocyte, lymph node, vermiform appendix
HLA-DQB1	268	broad	marker	right lung, spleen, upper lobe of left lung
HLA-DRA	132	broad	marker	monocyte, leukocyte, vermiform appendix
HLA-DRB1	131	tissue_specific	marker	vermiform appendix, granulocyte, right lung
LPP	292	ubiquitous	marker	saphenous vein, urethra, vena cava
PTPRK	135	ubiquitous	marker	corpus callosum, colonic epithelium, gall bladder

Protein interactions among cohort

Intra-cohort edges: 2.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
GATA3	5,990
HLA-DRB1	3,448
HLA-DRA	3,244
PTPRK	2,161
CLEC16A	2,028
AHI1	1,681
LPP	1,113
UPF3A	1,012
HLA-DPB1	160
HLA-DQB1	128

Intra-cohort edges

A	B	Sources
CLEC16A	HLA-DRB1	string_interaction
HLA-DRA	HLA-DRB1	biogrid_interaction, intact, string_interaction

Structural data

PDB: 8 · AlphaFold-only: 2 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
HLA-DRA	P01903	140
HLA-DRB1	P01911	108
HLA-DPB1	P04440	10
HLA-DQB1	P01920	10
GATA3	P23771	3
UPF3A	Q9H1J1	2
PTPRK	Q15262	2
AHI1	Q8N157	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
CLEC16A	Q2KHT3	72.17
LPP	Q93052	60.99

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 21. Enrichment computed across 10 evidence-associated genes (8 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 8 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	3	237.9×	2e-06	HLA-DPB1, HLA-DRA, HLA-DRB1
Phosphorylation of CD3 and TCR zeta chains	3	203.9×	2e-06	HLA-DPB1, HLA-DRA, HLA-DRB1
Co-inhibition by PD-1	3	194.7×	2e-06	HLA-DPB1, HLA-DRA, HLA-DRB1
Interferon gamma signaling	4	62.8×	2e-06	HLA-DPB1, HLA-DQB1, HLA-DRA, HLA-DRB1
Generation of second messenger molecules	3	129.8×	5e-06	HLA-DPB1, HLA-DRA, HLA-DRB1
Downstream TCR signaling	3	48.1×	9e-05	HLA-DPB1, HLA-DRA, HLA-DRB1
MHC class II antigen presentation	3	33.5×	2e-04	HLA-DPB1, HLA-DRA, HLA-DRB1
Developmental Lineage of Mammary Stem Cells	1	95.2×	0.027	GATA3
Formation of the nephric duct	1	79.3×	0.029	GATA3
EGFR downregulation	1	43.3×	0.048	PTPRK
Differentiation of naive CD4+ T cells to T helper 2 cells (Th2 cells)	1	18.3×	0.102	GATA3
Anchoring of the basal body to the plasma membrane	1	14.1×	0.106	AHI1
Cilium Assembly	1	13.6×	0.106	AHI1
Interleukin-4 and Interleukin-13 signaling	1	12.9×	0.106	GATA3
Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC)	1	12.2×	0.106	UPF3A
RUNX1 regulates transcription of genes involved in differentiation of HSCs	1	11.9×	0.106	GATA3
Estrogen-dependent gene expression	1	9.4×	0.121	GATA3
Regulation of expression of SLITs and ROBOs	1	8.7×	0.121	UPF3A
Factors involved in megakaryocyte development and platelet production	1	8.3×	0.121	GATA3
Organelle biogenesis and maintenance	1	8.2×	0.121	AHI1
Ub-specific processing proteases	1	6.6×	0.141	GATA3

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 10 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	421.3×	2e-08	HLA-DPB1, HLA-DQB1, HLA-DRA, HLA-DRB1
regulation of T-helper cell differentiation	3	1263.9×	5e-08	GATA3, HLA-DRA, HLA-DRB1
antigen processing and presentation of exogenous peptide antigen via MHC class II	4	217.4×	1e-07	HLA-DPB1, HLA-DQB1, HLA-DRA, HLA-DRB1
positive regulation of immune response	4	192.6×	1e-07	HLA-DPB1, HLA-DQB1, HLA-DRA, HLA-DRB1
positive regulation of T cell activation	4	177.4×	2e-07	HLA-DPB1, HLA-DQB1, HLA-DRA, HLA-DRB1
antigen processing and presentation of endogenous peptide antigen via MHC class II	2	1685.2×	9e-06	HLA-DRA, HLA-DRB1
T cell receptor signaling pathway	4	60.7×	9e-06	GATA3, HLA-DPB1, HLA-DQB1, HLA-DRB1
myeloid dendritic cell antigen processing and presentation	2	1123.5×	2e-05	HLA-DRA, HLA-DRB1
positive regulation of CD4-positive, alpha-beta T cell activation	2	842.6×	4e-05	HLA-DRA, HLA-DRB1
positive regulation of CD4-positive, CD25-positive, alpha-beta regulatory T cell differentiation	2	674.1×	5e-05	HLA-DRA, HLA-DRB1
humoral immune response	3	84.3×	8e-05	GATA3, HLA-DQB1, HLA-DRB1
positive regulation of memory T cell differentiation	2	374.5×	2e-04	HLA-DRA, HLA-DRB1
positive regulation of T cell mediated cytotoxicity	2	102.1×	0.002	HLA-DRA, HLA-DRB1
macrophage differentiation	2	93.6×	0.002	GATA3, HLA-DRB1
adaptive immune response	3	25.3×	0.002	HLA-DPB1, HLA-DQB1, HLA-DRA
negative regulation of type II interferon production	2	76.6×	0.003	GATA3, HLA-DRB1
type IV hypersensitivity	1	1685.2×	0.004	GATA3
antigen processing and presentation of peptide or polysaccharide antigen via MHC class II	1	1685.2×	0.004	HLA-DRA
regulation of interleukin-4 production	1	1685.2×	0.004	HLA-DRB1
obsolete negative regulation of cell proliferation involved in mesonephros development	1	1685.2×	0.004	GATA3
regulation of cellular response to X-ray	1	1685.2×	0.004	GATA3
obsolete negative regulation of fibroblast growth factor receptor signaling pathway involved in ureteric bud formation	1	1685.2×	0.004	GATA3
obsolete negative regulation of glial cell-derived neurotrophic factor receptor signaling pathway involved in ureteric bud formation	1	1685.2×	0.004	GATA3
negative regulation of cell cycle	2	58.1×	0.004	GATA3, PTPRK
immune response	3	14.1×	0.007	HLA-DQB1, HLA-DRA, HLA-DRB1
pro-T cell differentiation	1	842.6×	0.007	GATA3
regulation of interleukin-10 production	1	842.6×	0.007	HLA-DRB1
parathyroid hormone secretion	1	842.6×	0.007	GATA3
regulation of nephron tubule epithelial cell differentiation	1	842.6×	0.007	GATA3
thymic T cell selection	1	561.7×	0.010	GATA3

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 10

Druggability breadth: 1 of 10 evidence-associated genes (10%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
UPF3A	0	0
AHI1	0	0
CLEC16A	0	0
GATA3	0	0
HLA-DPB1	0	0
HLA-DQB1	0	0
HLA-DRA	0	0
HLA-DRB1	0	0
LPP	0	0
PTPRK	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
HLA-DRB1	17	Binding:17

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
PTPRK	3.1.3.48	protein-tyrosine-phosphatase

Pharmacogenomics

Cohort genes with a PharmGKB record: 10; with CPIC/DPWG dosing guidelines: 0.

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

Drug repurposing candidates

0 approved/phased drugs hit cohort targets but don’t yet appear in disease-level clinical trials. Target-inhibition rationale is strongest for cancer driver genes; a bioactivity hit is a screening signal, not a treatment claim.

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	5	HLA-DPB1, HLA-DQB1, HLA-DRA, HLA-DRB1, PTPRK
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	5	UPF3A, AHI1, CLEC16A, GATA3, LPP

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
UPF3A	0	—
AHI1	0	—
CLEC16A	0	—
GATA3	0	—
HLA-DPB1	0	—
HLA-DQB1	0	—
HLA-DRA	0	—
HLA-DRB1	17	—
LPP	0	—
PTPRK	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 2.

Phase distribution (across all retrieved trials)

Phase	Trials
PHASE2	2

Top trials by phase / activity

NCT	Phase	Status	Title
NCT03077828	PHASE2	UNKNOWN	Pembrolizumab and Combination Chemotherapy in Treating Patients With Relapsed or Refractory Hodgkin Lymphoma
NCT03226249	PHASE2	UNKNOWN	PET-Directed Therapy With Pembrolizumab and Combination Chemotherapy in Treating Patients With Previously Untreated Classical Hodgkin Lymphoma

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
FLUDEOXYGLUCOSE F 18	4	1
IFOSFAMIDE	4	1
VINBLASTINE SULFATE	4	1
CHEMBL376464	0	1