Hodgkin's lymphoma, mixed cellularity

Summary

Hodgkin’s lymphoma, mixed cellularity (MONDO:0004633) is a cancer with 3 cohort genes (3 GWAS associations across 1 studies) and 2 clinical trials. Top therapeutic interventions include fludeoxyglucose f 18, ifosfamide, and vinblastine sulfate.

At a glance

• Classification: Cancer
• Prevalence: 1-9 / 1 000 000 (Europe) [Orphanet-validated]
• Cohort genes: 3
• GWAS associations: 3
• Clinical trials: 2

Clinical features

Epidemiology

Prevalence records

1 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Annual incidence	1-9 / 1 000 000	0.42	Europe	Validated

Identifiers

Disease identifiers

Field	Value
Canonical name	Hodgkin’s lymphoma, mixed cellularity
Mondo ID	MONDO:0004633
EFO	EFO:1002031
Orphanet	98844
DOID	DOID:8654
ICD-10-CM	C81.2
ICD-11	39515681
NCIT	C3517
SNOMED CT	118609008
UMLS	C0152266
MedGen	57521
GARD	0019592
Is cancer (heuristic)	yes

Also known as: classic Hodgkin lymphoma, mixed cellularity type · Hodgkin lymphoma, mixed cellularity · Hodgkin’s disease mixed cellularity · Hodgkin’s disease, mixed cellularity of unspecified site · Hodgkin’s lymphoma mixed cellularity · MCCHL · MCHL · Mixed cellularity Classic Hodgkin lymphoma · mixed cellularity classical Hodgkin lymphoma · mixed cellularity Hodgkin lymphoma · mixed cellularity Hodgkin’s disease · mixed cellularity Hodgkin’s lymphoma

Data availability: 3 GWAS associations (1 study).

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › classic Hodgkin lymphoma › Hodgkin’s lymphoma, mixed cellularity

Related subtypes (3): Hodgkin’s lymphoma, lymphocytic-histiocytic predominance, Hodgkin’s lymphoma, lymphocytic depletion, nodular sclerosis classical Hodgkin lymphoma

Genetics & variants

GWAS landscape

3 GWAS associations across 1 studies. Top hits map to 3 distinct genes (as reported by GWAS).

Top associations by p-value

rsID	p-value	Gene	Risk allele	Odds ratio
rs1633096	3e-23	HLA-F-AS1	?	1.79
rs13196329	3e-14	TSBP1-AS1, TSBP1	?	5.88
Val86 HLA-DRB1	7e-09		?	1.37

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST005210	Sud A	2017	828	14,315	Genome-wide association study of classical Hodgkin lymphoma identifies key regulators of disease susceptibility.

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	3

MAF distribution

Bucket	Variants
common (>=0.05)	2
low_freq (0.01-0.05)	0
rare (<0.01)	0
unknown	1

Functional consequences

Consequence	Count
intron_variant	2
unknown	1

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
rs1633096	6	29739490	G>A,C,T	0.05	intron_variant	HLA-F-AS1	3e-23	Tier 4: intronic/intergenic
rs13196329	6	32357594	A>C	0.05	intron_variant	TSBP1-AS1, TSBP1	3e-14	Tier 4: intronic/intergenic
Val86 HLA-DRB1							7e-09	Tier 4: intronic/intergenic

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 14 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 1

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

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

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
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

3 cohort genes, 3 distinct canonical proteins.

Evidence partition

Subset	Genes
gwas_only	3

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
TSBP1	HGNC:13922	ENSG00000204296	Q5SRN2	Testis-expressed basic protein 1	gwas
HLA-DRB1	HGNC:4948	ENSG00000196126	P01911	HLA class II histocompatibility antigen, DRB1 beta chain	gwas
HLA-F	HGNC:4963	ENSG00000204642	P30511	HLA class I histocompatibility antigen, alpha chain F	gwas

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
HLA-DRB1	HLA class II histocompatibility antigen, DRB1 beta chain	A beta chain of antigen-presenting major histocompatibility complex class II (MHCII) molecule.
HLA-F	HLA class I histocompatibility antigen, alpha chain F	Non-classical major histocompatibility class Ib molecule postulated to play a role in immune surveillance, immune tolerance and inflammation.

Protein-family classification

Druggable: 2 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.67

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	2	19.5×	0.007
Other/Unknown	1	0.6×	0.914

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
TSBP1	Other/Unknown	no		TSBP1
HLA-DRB1	Antibody/Immunoglobulin	yes		MHC_II_b_N, Ig/MHC_CS, Ig_C1-set
HLA-F	Antibody/Immunoglobulin	yes		MHC_I_a_a1/a2, Ig/MHC_CS, Ig_C1-set

Expression context

Cohort genes with no expression data: 0.

2 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)	3
unknown	0

Top tissues across cohort

Tissue	Cohort genes
granulocyte	2
left testis	1
right testis	1
testis	1
right lung	1
vermiform appendix	1
blood	1
spleen	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
TSBP1	58	tissue_specific	yes	left testis, testis, right testis
HLA-DRB1	131	tissue_specific	marker	vermiform appendix, granulocyte, right lung
HLA-F	139	ubiquitous	marker	granulocyte, spleen, blood

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
HLA-DRB1	3,448
HLA-F	1,296
TSBP1	362

Intra-cohort edges

A	B	Sources
HLA-DRB1	TSBP1	string_interaction

Structural data

PDB: 2 · AlphaFold-only: 1 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
HLA-DRB1	P01911	108
HLA-F	P30511	2

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
TSBP1	Q5SRN2	45.58

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 13. Enrichment computed across 3 evidence-associated genes (2 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 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Interferon gamma signaling	2	125.5×	8e-04	HLA-DRB1, HLA-F
Endosomal/Vacuolar pathway	1	519.1×	0.010	HLA-F
Translocation of ZAP-70 to Immunological synapse	1	317.2×	0.010	HLA-DRB1
Phosphorylation of CD3 and TCR zeta chains	1	271.9×	0.010	HLA-DRB1
Co-inhibition by PD-1	1	259.6×	0.010	HLA-DRB1
Antigen Presentation: Folding, assembly and peptide loading of class I MHC	1	196.9×	0.011	HLA-F
Generation of second messenger molecules	1	173.0×	0.011	HLA-DRB1
Interferon alpha/beta signaling	1	76.1×	0.020	HLA-F
ER-Phagosome pathway	1	64.9×	0.020	HLA-F
Downstream TCR signaling	1	64.2×	0.020	HLA-DRB1
MHC class II antigen presentation	1	44.6×	0.023	HLA-DRB1
SARS-CoV-2 activates/modulates innate and adaptive immune responses	1	44.6×	0.023	HLA-F
Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell	1	43.6×	0.023	HLA-F

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
positive regulation of T cell mediated cytotoxicity	2	510.7×	1e-04	HLA-DRB1, HLA-F
regulation of interleukin-4 production	1	8426.0×	0.001	HLA-DRB1
negative regulation of natural killer cell degranulation	1	8426.0×	0.001	HLA-F
antigen processing and presentation of exogenous peptide antigen via MHC class Ib	1	4213.0×	0.001	HLA-F
antigen processing and presentation of endogenous peptide antigen via MHC class II	1	4213.0×	0.001	HLA-DRB1
negative regulation of natural killer cell cytokine production	1	4213.0×	0.001	HLA-F
regulation of interleukin-10 production	1	4213.0×	0.001	HLA-DRB1
myeloid dendritic cell antigen processing and presentation	1	2808.7×	0.002	HLA-DRB1
regulation of T-helper cell differentiation	1	2106.5×	0.002	HLA-DRB1
positive regulation of CD4-positive, alpha-beta T cell activation	1	2106.5×	0.002	HLA-DRB1
immune response	2	47.1×	0.002	HLA-DRB1, HLA-F
positive regulation of CD4-positive, CD25-positive, alpha-beta regulatory T cell differentiation	1	1685.2×	0.002	HLA-DRB1
positive regulation of natural killer cell degranulation	1	1685.2×	0.002	HLA-F
negative regulation of T cell cytokine production	1	1203.7×	0.002	HLA-F
positive regulation of T cell mediated immune response to tumor cell	1	1203.7×	0.002	HLA-DRB1
positive regulation of natural killer cell cytokine production	1	936.2×	0.002	HLA-F
T-helper 1 type immune response	1	936.2×	0.002	HLA-DRB1
positive regulation of memory T cell differentiation	1	936.2×	0.002	HLA-DRB1
positive regulation of monocyte differentiation	1	766.0×	0.003	HLA-DRB1
detection of bacterium	1	702.2×	0.003	HLA-DRB1
antigen processing and presentation of endogenous peptide antigen via MHC class Ib	1	648.1×	0.003	HLA-F
antigen processing and presentation of endogenous peptide antigen via MHC class I via ER pathway, TAP-independent	1	648.1×	0.003	HLA-F
peptide antigen assembly with MHC class II protein complex	1	526.6×	0.003	HLA-DRB1
inflammatory response to antigenic stimulus	1	468.1×	0.003	HLA-DRB1
negative regulation of natural killer cell mediated cytotoxicity	1	443.5×	0.003	HLA-F
protein tetramerization	1	312.1×	0.005	HLA-DRB1
negative regulation of inflammatory response to antigenic stimulus	1	300.9×	0.005	HLA-DRB1
antigen processing and presentation of exogenous peptide antigen via MHC class II	1	271.8×	0.005	HLA-DRB1
positive regulation of immune response	1	240.7×	0.005	HLA-DRB1
macrophage differentiation	1	234.1×	0.005	HLA-DRB1

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 3 evidence-associated genes (33%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
TSBP1	0	0
HLA-DRB1	0	0
HLA-F	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-DRB1	17	Binding:17

Pharmacogenomics

Cohort genes with a PharmGKB record: 3; 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	2	HLA-DRB1, HLA-F
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	TSBP1

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
TSBP1	0	—
HLA-DRB1	17	—
HLA-F	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