Hodgkins lymphoma

Summary

Hodgkins lymphoma (MONDO:0004952) is a cancer (an umbrella term covering 5 Mondo subtypes) with 68 cohort genes (138 GWAS associations across 17 studies; 11 CIViC-evidence somatic drivers) and 679 clinical trials. The dominant Reactome pathway is Intrinsic Pathway for Apoptosis (4 cohort genes). Top therapeutic interventions include brentuximab vedotin, bleomycin, and vinblastine.

At a glance

• Classification: Cancer
• Prevalence: 1-9 / 100 000 (Europe) [Orphanet-validated]
• Umbrella term: 5 Mondo subtypes
• Cohort genes: 68
• GWAS associations: 138
• Clinical trials: 679
• Precision-medicine evidence (CIViC): 1 subtype–drug association

Clinical features

Epidemiology

Prevalence records

5 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Annual incidence	1-9 / 100 000	2.4	Europe	Validated
Lifetime Prevalence	1-5 / 10 000	46.9	Europe	Validated
Annual incidence	1-9 / 100 000	2.8	United States	Validated
Annual incidence	1-9 / 1 000 000	0.25	Japan	Not yet validated
Annual incidence	1-9 / 1 000 000	0.25	China	Not yet validated

Identifiers

Disease identifiers

Field	Value
Canonical name	Hodgkins lymphoma
Mondo ID	MONDO:0004952
EFO	EFO:0000183
MeSH	D006689
Orphanet	98293
DOID	DOID:8567
ICD-10-CM	C81
ICD-11	1528863768
NCIT	C9357
GARD	0002714
NORD	1246
Is cancer (heuristic)	yes

Also known as: HL · Hodgkin disease · Hodgkin lymphoma · Hodgkin’s Disease · Hodgkin’s disease · Hodgkin’s lymphoma · Hodgkin’s sarcoma · lymphoma, Hodgkin’s · stage I subdiaphragmatic Hodgkin lymphoma · stage II subdiaphragmatic Hodgkin lymphoma

Data availability: 138 GWAS associations (17 studies) · 45 cell lines.

Disease family

An umbrella term covering 5 Mondo subtypes.

Classification path: disease › human disease › disease by etiologic mechanism › cancer or benign tumor › neoplastic disease or syndrome › neoplasm › hematopoietic and lymphoid system neoplasm › hematopoietic and lymphoid cell neoplasm › lymphoid neoplasm › lymphoma › Hodgkins lymphoma

Related subtypes (26): prostate lymphoma, nasal cavity lymphoma, bladder lymphoma, tracheal lymphoma, retroperitoneal lymphoma, ureteral lymphoma, ovarian lymphoma, B-cell lymphoma, unclassifiable, with features intermediate between diffuse large b-cell lymphoma and classical Hodgkin lymphoma, pediatric lymphoma, adult lymphoma, breast lymphoma, heart lymphoma, chest wall lymphoma, lung lymphoma, mediastinal malignant lymphoma, eye lymphoma, B-cell neoplasm, gastrointestinal lymphoma, peripheral T-cell lymphoma, not otherwise specified, composite lymphoma, AIDS-related primary central nervous system lymphoma, primary organ-specific lymphoma, non-Hodgkin lymphoma, extranodal nasal NK/T cell lymphoma, methotrexate-associated lymphoproliferative disorders, progressive transformation of germinal centers

Subtypes (5): splenic hodgkin lymphoma, classic Hodgkin lymphoma, lymphoma, Hodgkin, X-linked pseudoautosomal, lymphoma, Hodgkin, Y-linked pseudoautosomal, nodular lymphocyte predominant Hodgkin lymphoma

Genetics & variants

GWAS landscape

138 GWAS associations across 17 studies. Top hits map to 40 distinct genes (as reported by GWAS).

Top associations by p-value

rsID	p-value	Gene	Risk allele	Odds ratio
rs6903608	3e-50	HLA-DRB9	G	1.7
rs2395185	4e-31	HLA-DRB9	?	1.82
rs28383311	2e-21	HLA-DRB1 - HLA-DQA1	A	1.8
rs4459895	4e-18	LPP	A	1.3
rs4538746	2e-17	HLA-DQB1	T	1.22
rs2248462	7e-16	HCP5	?	1.64
rs3129198	3e-15	HLA-DPA2 - COL11A2P1	A	1.54
rs12711846	3e-14	ACOXL, MIR4435-2HG, ACOXL-AS1	G
rs4525246	3e-14	GRAMD1B	C
rs2019960	1e-13	PVT1	G	1.33
rs559464313	2e-13	DRD4	A	4.47
rs532391514	3e-13	PACERR - PLA2G4A	G	2.82
rs3806624	5e-13	EOMES - LINC01980	G	1.14
rs75229018	6e-13	LINC02838 - GDI2P1	C	3.37
rs138809598	7e-13	LINC02737	G	1.67
rs35923643	8e-13	GRAMD1B	G	1.19
rs150945752	1e-12	MEGF11	T	0.03
rs58055559	2e-12	CACNA1I	T	0.03
rs146760080	2e-12	DECR2	C	0.04
rs143894786	2e-12	STAB1	C	0.03
rs17676949	2e-12	PHLPP1 - BCL2	A	0.78
rs565643303	2e-12	TTL	G	3.25
rs144433879	3e-12	ZNF526	A	0.01
rs377333979	3e-12	RNF141	T	3.97
rs200612080	4e-12	CPLANE1	T	0.03
rs547573644	4e-12	LPAR1 - RNY4P18	T	3.92
rs3781093	5e-12	GATA3	T	1.28
rs1058009	6e-12	DLK1	A	0.01
rs210143	7e-12	BAK1	C
rs3129890	7e-12	HLA-DRA - HLA-DRB9	T	1.48

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST90267403	Berndt SI	2022	13,763	18,862	Distinct germline genetic susceptibility profiles identified for common non-Hodgkin lymphoma subtypes.
GCST007062	Sud A	2018	5,325	22,425	Genome-wide association study implicates immune dysfunction in the development of Hodgkin lymphoma.
GCST005209	Sud A	2017	3,077	13,680	Genome-wide association study of classical Hodgkin lymphoma identifies key regulators of disease susceptibility.
GCST90624742	Guler M	2025	2,113	1,106,048	Clustering of lymphoid neoplasms by cell of origin, somatic mutation and drug usage profiles: a multi-trait genome-wide association study.
GCST004099	Law PJ	2017	1,842	7,324	Genome-wide association analysis of chronic lymphocytic leukaemia, Hodgkin lymphoma and multiple myeloma identifies pleiotropic risk loci.
GCST002480	Cozen W	2014	1,816	7,877	A meta-analysis of Hodgkin lymphoma reveals 19p13.3 TCF3 as a novel susceptibility locus.
GCST002237	Frampton M	2013	1,465	6,417	Variation at 3p24.1 and 6q23.3 influences the risk of Hodgkin’s lymphoma.
GCST90134660	Chen C	2022	1,286	0	Association of Single-Nucleotide Variants in the Human Leukocyte Antigen and Other Loci With Childhood Hodgkin Lymphoma.
GCST001387	Urayama KY	2012	1,200	6,417	Genome-wide association study of classical Hodgkin lymphoma and Epstein-Barr virus status-defined subgroups.
GCST90477243	Verma A	2024	975	449,793	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

Tier	Variants
Tier 1: coding	18
Tier 2: splice/UTR	1
Tier 3: regulatory	1
Tier 4: intronic/intergenic	30

MAF distribution

Bucket	Variants
common (>=0.05)	40
low_freq (0.01-0.05)	0
rare (<0.01)	10
unknown	0

Functional consequences

Consequence	Count
intron_variant	20
missense_variant	18
intergenic_variant	9
non_coding_transcript_exon_variant	1
regulatory_region_variant	1
3_prime_UTR_variant	1

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
rs6903608	6	32460508	C>G,T	0.27	intron_variant	HLA-DRB9	3e-50	Tier 4: intronic/intergenic
rs2395185	6	32465390	G>T	0.05	intron_variant	HLA-DRB9	4e-31	Tier 4: intronic/intergenic
rs28383311	6	32619234	A>T	0.05	intergenic_variant	HLA-DRB1 - HLA-DQA1	2e-21	Tier 4: intronic/intergenic
rs4459895	3	188236626	A>C,G,T	0.19	intron_variant	LPP	4e-18	Tier 4: intronic/intergenic
rs4538746	6	32664336	C>A,G,T	0.05	intron_variant	HLA-DQB1	2e-17	Tier 4: intronic/intergenic
rs2248462	6	31479019	G>A	0.05	intron_variant	HCP5	7e-16	Tier 4: intronic/intergenic
rs3129198	6	33103045	G>A	0.05	intergenic_variant	HLA-DPA2 - COL11A2P1	3e-15	Tier 4: intronic/intergenic
rs12711846	2	111098716	A>G	0.05	non_coding_transcript_exon_variant	ACOXL, MIR4435-2HG, ACOXL-AS1	3e-14	Tier 4: intronic/intergenic
rs4525246	11	123524538	G>A,C,T	0.05	intron_variant	GRAMD1B	3e-14	Tier 4: intronic/intergenic
rs2019960	8	128180025	T>C	0.23	intergenic_variant	PVT1	1e-13	Tier 4: intronic/intergenic
rs559464313	11	638633	A>G	0.001	intron_variant	DRD4	2e-13	Tier 4: intronic/intergenic
rs532391514	1	186784767	G>T	0.001	intergenic_variant	PACERR - PLA2G4A	3e-13	Tier 4: intronic/intergenic
rs3806624	3	27723132	A>C,G,T	0.05	regulatory_region_variant	EOMES - LINC01980	5e-13	Tier 3: regulatory
rs75229018	7	48742622	C>T	0	intergenic_variant	LINC02838 - GDI2P1	6e-13	Tier 4: intronic/intergenic
rs138809598	11	96959474	G>A	0.003	intron_variant	LINC02737	7e-13	Tier 4: intronic/intergenic
rs35923643	11	123484683	A>G	0.05	intron_variant	GRAMD1B	8e-13	Tier 4: intronic/intergenic
rs150945752	15	65913823	C>T	0.318	missense_variant	MEGF11	1e-12	Tier 1: coding
rs58055559	22	39682566	C>T	0.291	missense_variant	CACNA1I	2e-12	Tier 1: coding
rs146760080	16	411483	G>C,T	0.373	missense_variant	DECR2	2e-12	Tier 1: coding
rs143894786	3	52519535	G>A,C	0.433	missense_variant	STAB1	2e-12	Tier 1: coding
rs17676949	18	63118405	G>A,C	0.05	intergenic_variant	PHLPP1 - BCL2	2e-12	Tier 4: intronic/intergenic
rs565643303	2	112540783	G>T	0	3_prime_UTR_variant	TTL	2e-12	Tier 2: splice/UTR
rs144433879	19	42225458	G>A	0.306	missense_variant	ZNF526	3e-12	Tier 1: coding
rs377333979	11	10528754	T>C	0	intron_variant	RNF141	3e-12	Tier 4: intronic/intergenic
rs200612080	5	37153826	C>T	0.377	missense_variant	CPLANE1	4e-12	Tier 1: coding
rs547573644	9	111065405	T>G	0.001	intergenic_variant	LPAR1 - RNY4P18	4e-12	Tier 4: intronic/intergenic
rs3781093	10	8059964	T>C	0.14	intron_variant	GATA3	5e-12	Tier 4: intronic/intergenic
rs1058009	14	100734523	G>A	0.447	missense_variant	DLK1	6e-12	Tier 1: coding
rs210143	6	33579153	T>A,C	0.05	intron_variant	BAK1	7e-12	Tier 4: intronic/intergenic
rs3129890	6	32446496	T>A,C	0.05	intron_variant	HLA-DRA - HLA-DRB9	7e-12	Tier 4: intronic/intergenic

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 55 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 1

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

Gene	HGNC	Evidence routes
GATA3	GATA3	GWAS, Orphanet

Somatic driver evidence (intOGen + CIViC, cohort fanout)

Gene	intOGen role	Cancer types	CIViC
TNFAIP3	LoF	DLBCLNOS	CIViC #5828
GATA3	Act	ALL,BRCA	CIViC #2189
HLA-DRA			CIViC #2622
IRF8			CIViC #2836
IRF4	Act	CLLSLL,DLBCLNOS,MLYM,NHL,PCM	CIViC #3043
MYB			CIViC #3730
MYOD1			CIViC #3777
POU2AF1			CIViC #4409
PTPRK	LoF	BLCA,CCRCC,NSCLC
BCL2L11			CIViC #7953
REL			CIViC #57

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SH3BP2	Orphanet:184	Cherubism
TERC	Orphanet:1775	Dyskeratosis congenita
TERC	Orphanet:2032	Idiopathic pulmonary fibrosis
TERC	Orphanet:88	Idiopathic aplastic anemia
TNFAIP3	Orphanet:536	Systemic lupus erythematosus
TNFAIP3	Orphanet:674762	Early-onset autoinflammatory syndrome due to A20 haploinsufficiency
CD40	Orphanet:101090	Hyper-IgM syndrome type 3
CACNA1I	Orphanet:178469	Autosomal dominant non-syndromic intellectual disability
PGRMC1	Orphanet:98994	Total early-onset cataract
ERAP1	Orphanet:117	Behçet disease
LGI4	Orphanet:2680	Hypomyelination neuropathy-arthrogryposis syndrome
UQCC2	Orphanet:1460	Isolated complex III deficiency
AHI1	Orphanet:220493	Joubert syndrome with ocular defect
AHI1	Orphanet:475	Isolated Joubert syndrome
AHI1	Orphanet:791	Retinitis pigmentosa
CORO1A	Orphanet:228003	Severe combined immunodeficiency due to CORO1A deficiency
CPLANE1	Orphanet:2754	Orofaciodigital syndrome type 6
CPLANE1	Orphanet:475	Isolated Joubert syndrome
CPLANE1	Orphanet:65684	Monomelic amyotrophy
ACE	Orphanet:97369	Renal tubular dysgenesis of genetic origin
DLK1	Orphanet:254525	Temple syndrome due to paternal 14q32.2 microdeletion
DLK1	Orphanet:254528	Kagami-Ogata syndrome due to maternal 14q32.2 microdeletion
DLK1	Orphanet:254531	Temple syndrome due to paternal 14q32.2 hypomethylation
DLK1	Orphanet:254534	Kagami-Ogata syndrome due to maternal 14q32.2 hypermethylation
DLK1	Orphanet:650077	Genetic central precocious puberty in female
DLK1	Orphanet:650097	Genetic central precocious puberty in male
DLK1	Orphanet:96184	Temple syndrome due to maternal uniparental disomy of chromosome 14
DLK1	Orphanet:96334	Kagami-Ogata syndrome due to paternal uniparental disomy of chromosome 14
PRR12	Orphanet:659904	Multiple congenital anomalies-neurodevelopmental delay-ocular abnormalities syndrome
ZNF526	Orphanet:528084	Non-specific syndromic intellectual disability
EOMES	Orphanet:171703	Microcephaly-polymicrogyria-corpus callosum agenesis syndrome
GATA3	Orphanet:2237	Hypoparathyroidism-sensorineural deafness-renal disease syndrome
GATA3	Orphanet:585936	B-lymphoblastic leukemia/lymphoma with hyperdiploidy
HLA-DRA	Orphanet:505	Graham Little-Piccardi-Lassueur syndrome
IRF8	Orphanet:319600	Mendelian susceptibility to mycobacterial diseases due to partial IRF8 deficiency
IRF4	Orphanet:3452	Whipple disease
MYB	Orphanet:251671	Angiocentric glioma
MYB	Orphanet:86849	Acute basophilic leukemia
MYB	Orphanet:99861	Precursor T-cell acute lymphoblastic leukemia
MYOD1	Orphanet:994	Fetal akinesia deformation sequence
SERPINF2	Orphanet:79	Congenital alpha2-antiplasmin deficiency
PMP22	Orphanet:101081	Charcot-Marie-Tooth disease type 1A
PMP22	Orphanet:3115	Roussy-Lévy syndrome
PMP22	Orphanet:640	Hereditary neuropathy with liability to pressure palsies
PMP22	Orphanet:64748	Dejerine-Sottas syndrome
PMP22	Orphanet:90658	Charcot-Marie-Tooth disease type 1E
PMP22	Orphanet:98916	Acute inflammatory demyelinating polyradiculoneuropathy
POU2AF1	Orphanet:186	Primary biliary cholangitis
PTPN22	Orphanet:3437	Vogt-Koyanagi-Harada disease
PTPN22	Orphanet:397	Giant cell arteritis

Cohort genes → proteins

68 cohort genes, 66 distinct canonical proteins.

Evidence partition

Subset	Genes
gwas_only	68

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
SH3BP2	HGNC:10825	ENSG00000087266	P78314	SH3 domain-binding protein 2	gwas
TCF7L1	HGNC:11640	ENSG00000152284	Q9HCS4	Transcription factor 7-like 1	gwas
TERC	HGNC:11727	ENSG00000270141		telomerase RNA component	gwas
TNFAIP3	HGNC:11896	ENSG00000118503	P21580	Tumor necrosis factor alpha-induced protein 3	gwas
CD40	HGNC:11919	ENSG00000101017	P25942	Tumor necrosis factor receptor superfamily member 5	gwas
FCGBP	HGNC:13572	ENSG00000275395	Q9Y6R7	IgGFc-binding protein	gwas
AOPEP	HGNC:1361	ENSG00000148120	Q8N6M6	Aminopeptidase O	gwas
CACNA1I	HGNC:1396	ENSG00000100346	Q9P0X4	Voltage-dependent T-type calcium channel subunit alpha-1I	gwas
SHANK2	HGNC:14295	ENSG00000162105	Q9UPX8	SH3 and multiple ankyrin repeat domains protein 2	gwas
ULK4	HGNC:15784	ENSG00000168038	Q96C45	Serine/threonine-protein kinase ULK4	gwas
KIF16B	HGNC:15869	ENSG00000089177	Q96L93	Kinesin-like protein KIF16B	gwas
NCOA5	HGNC:15909	ENSG00000124160	Q9HCD5	Nuclear receptor coactivator 5	gwas
PGRMC1	HGNC:16090	ENSG00000101856	O00264	Membrane-associated progesterone receptor component 1	gwas
ELL2	HGNC:17064	ENSG00000118985	O00472	RNA polymerase II elongation factor ELL2	gwas
IP6K3	HGNC:17269	ENSG00000161896	Q96PC2	Inositol hexakisphosphate kinase 3	gwas
CLSTN2	HGNC:17448	ENSG00000158258	Q9H4D0	Calsyntenin-2	gwas
OLIG3	HGNC:18003	ENSG00000177468	Q7RTU3	Oligodendrocyte transcription factor 3	gwas
ERAP1	HGNC:18173	ENSG00000164307	Q9NZ08	Endoplasmic reticulum aminopeptidase 1	gwas
STAB1	HGNC:18628	ENSG00000010327	Q9NY15	Stabilin-1	gwas
LGI4	HGNC:18712	ENSG00000153902	Q8N135	Leucine-rich repeat LGI family member 4	gwas
UQCC2	HGNC:21237	ENSG00000137288	Q9BRT2	Ubiquinol-cytochrome c reductase complex assembly factor 2	gwas
AHI1	HGNC:21575	ENSG00000135541	Q8N157	Jouberin	gwas
CORO1A	HGNC:2252	ENSG00000102879	P31146	Coronin-1A	gwas
TM7SF3	HGNC:23049	ENSG00000064115	Q9NS93	Transmembrane 7 superfamily member 3	gwas
RTN4RL2	HGNC:23053	ENSG00000186907	Q86UN3	Reticulon-4 receptor-like 2	gwas
BMF	HGNC:24132	ENSG00000104081	Q96LC9	Bcl-2-modifying factor	gwas
ESYT3	HGNC:24295	ENSG00000158220	A0FGR9	Extended synaptotagmin-3	gwas
NCAPH2	HGNC:25071	ENSG00000025770	Q6IBW4	Condensin-2 complex subunit H2	gwas
TMEM169	HGNC:25130	ENSG00000163449	Q96HH4	Transmembrane protein 169	gwas
CPLANE1	HGNC:25801	ENSG00000197603	Q9H799	Ciliogenesis and planar polarity effector 1	gwas
ACE	HGNC:2707	ENSG00000159640	P12821	Angiotensin-converting enzyme	gwas
CDCP2	HGNC:27297	ENSG00000157211	Q5VXM1	CUB domain-containing protein 2	gwas
DECR2	HGNC:2754	ENSG00000242612	Q9NUI1	Peroxisomal 2,4-dienoyl-CoA reductase [(3E)-enoyl-CoA-producing]	gwas
BRME1	HGNC:28153	ENSG00000132016	Q0VDD7	Break repair meiotic recombinase recruitment factor 1	gwas
CLEC16A	HGNC:29013	ENSG00000038532	Q2KHT3	Protein CLEC16A	gwas
DLK1	HGNC:2907	ENSG00000185559	P80370	Protein delta homolog 1	gwas
GRAMD1B	HGNC:29214	ENSG00000023171	Q3KR37	Protein Aster-B	gwas
PRR12	HGNC:29217	ENSG00000126464	Q9ULL5	Proline-rich protein 12	gwas
ZNF526	HGNC:29415	ENSG00000167625	Q8TF50	Zinc finger protein 526	gwas
MEGF11	HGNC:29635	ENSG00000157890	A6BM72	Multiple epidermal growth factor-like domains protein 11	gwas
ARHGEF28	HGNC:30322	ENSG00000214944	Q8N1W1	Rho guanine nucleotide exchange factor 28	gwas
DTNB	HGNC:3058	ENSG00000138101	O60941	Dystrobrevin beta	gwas
ZNF823	HGNC:30936	ENSG00000197933	P16415	Zinc finger protein 823	gwas
EOMES	HGNC:3372	ENSG00000163508	O95936	Eomesodermin homolog	gwas
GATA3	HGNC:4172	ENSG00000107485	P23771	Trans-acting T-cell-specific transcription factor GATA-3	gwas
HBS1L	HGNC:4834	ENSG00000112339	Q9Y450	HBS1-like protein	gwas
HLA-DRA	HGNC:4947	ENSG00000204287	P01903	HLA class II histocompatibility antigen, DR alpha chain	gwas
IRF8	HGNC:5358	ENSG00000140968	Q02556	Interferon regulatory factor 8	gwas
IL13	HGNC:5973	ENSG00000169194	P35225	Interleukin-13	gwas
IRF4	HGNC:6119	ENSG00000137265	Q15306	Interferon regulatory factor 4	gwas

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SH3BP2	SH3 domain-binding protein 2	Binds differentially to the SH3 domains of certain proteins of signal transduction pathways.
TCF7L1	Transcription factor 7-like 1	Participates in the Wnt signaling pathway.
TNFAIP3	Tumor necrosis factor alpha-induced protein 3	Ubiquitin-editing enzyme that contains both ubiquitin ligase and deubiquitinase activities.
CD40	Tumor necrosis factor receptor superfamily member 5	Receptor for TNFSF5/CD40LG.
FCGBP	IgGFc-binding protein	May be involved in the maintenance of the mucosal structure as a gel-like component of the mucosa.
AOPEP	Aminopeptidase O	Aminopeptidase which catalyzes the hydrolysis of amino acid residues from the N-terminus of peptide or protein substrates.
CACNA1I	Voltage-dependent T-type calcium channel subunit alpha-1I	Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hormone or neurotransmitter release, gene exp…
SHANK2	SH3 and multiple ankyrin repeat domains protein 2	Seems to be an adapter protein in the postsynaptic density (PSD) of excitatory synapses that interconnects receptors of the postsynaptic membrane including NMDA-type and metabotropic glutamate receptors, and the actin-based cytoskeleton.
ULK4	Serine/threonine-protein kinase ULK4	May be involved in the remodeling of cytoskeletal components, such as alpha-tubulin, and in this way regulates neurite branching and elongation, as well as cell motility.
KIF16B	Kinesin-like protein KIF16B	Plus end-directed microtubule-dependent motor protein involved in endosome transport and receptor recycling and degradation.
NCOA5	Nuclear receptor coactivator 5	Nuclear receptor coregulator that can have both coactivator and corepressor functions.
PGRMC1	Membrane-associated progesterone receptor component 1	Component of a progesterone-binding protein complex.
ELL2	RNA polymerase II elongation factor ELL2	Elongation factor component of the super elongation complex (SEC), a complex required to increase the catalytic rate of RNA polymerase II transcription by suppressing transient pausing by the polymerase at multiple sites along the DNA.
IP6K3	Inositol hexakisphosphate kinase 3	Converts inositol hexakisphosphate (InsP6) to diphosphoinositol pentakisphosphate (InsP7/PP-InsP5).
CLSTN2	Calsyntenin-2	Postsynaptic adhesion molecule that binds to presynaptic neurexins to mediate synapse formation, and which is involved in learning and memory.
OLIG3	Oligodendrocyte transcription factor 3	May determine the distinct specification program of class A neurons in the dorsal part of the spinal cord and suppress specification of class B neurons.
ERAP1	Endoplasmic reticulum aminopeptidase 1	Aminopeptidase that plays a central role in peptide trimming, a step required for the generation of most HLA class I-binding peptides.
STAB1	Stabilin-1	Acts as a scavenger receptor for acetylated low density lipoprotein.
LGI4	Leucine-rich repeat LGI family member 4	Component of Schwann cell signaling pathway(s) that controls axon segregation and myelin formation.
UQCC2	Ubiquinol-cytochrome c reductase complex assembly factor 2	Required for the assembly of the ubiquinol-cytochrome c reductase complex (mitochondrial respiratory chain complex III or cytochrome b-c1 complex).
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.
CORO1A	Coronin-1A	May be a crucial component of the cytoskeleton of highly motile cells, functioning both in the invagination of large pieces of plasma membrane, as well as in forming protrusions of the plasma membrane involved in cell locomotion.
TM7SF3	Transmembrane 7 superfamily member 3	Involved in the inhibition of cytokine-induced death of pancreatic beta cells.
RTN4RL2	Reticulon-4 receptor-like 2	Cell surface receptor that plays a functionally redundant role in the inhibition of neurite outgrowth mediated by MAG.
BMF	Bcl-2-modifying factor	May play a role in apoptosis.
ESYT3	Extended synaptotagmin-3	Binds glycerophospholipids in a barrel-like domain and may play a role in cellular lipid transport.
NCAPH2	Condensin-2 complex subunit H2	Regulatory subunit of the condensin-2 complex, a complex that seems to provide chromosomes with an additional level of organization and rigidity and in establishing mitotic chromosome architecture.
CPLANE1	Ciliogenesis and planar polarity effector 1	Involved in ciliogenesis.
ACE	Angiotensin-converting enzyme	Dipeptidyl carboxypeptidase that removes dipeptides from the C-terminus of a variety of circulating hormones, such as angiotensin I, bradykinin or enkephalins, thereby playing a key role in the regulation of blood pressure, electrolyte hom…
DECR2	Peroxisomal 2,4-dienoyl-CoA reductase [(3E)-enoyl-CoA-producing]	Auxiliary enzyme of beta-oxidation.
BRME1	Break repair meiotic recombinase recruitment factor 1	Meiotic recombination factor component of recombination bridges involved in meiotic double-strand break repair.
CLEC16A	Protein CLEC16A	Regulator of mitophagy through the upstream regulation of the RNF41/NRDP1-PRKN pathway.
DLK1	Protein delta homolog 1	May have a role in neuroendocrine differentiation.
GRAMD1B	Protein Aster-B	Cholesterol transporter that mediates non-vesicular transport of cholesterol from the plasma membrane (PM) to the endoplasmic reticulum (ER).
PRR12	Proline-rich protein 12	May play a role in the regulation of cohesin complex loading onto chromatin, probably acting in coordination with NIPBL and MAU2.
ZNF526	Zinc finger protein 526	Probable transcription factor.
MEGF11	Multiple epidermal growth factor-like domains protein 11	May regulate the mosaic spacing of specific neuron subtypes in the retina through homotypic retinal neuron repulsion.
ARHGEF28	Rho guanine nucleotide exchange factor 28	Functions as a RHOA-specific guanine nucleotide exchange factor regulating signaling pathways downstream of integrins and growth factor receptors.
DTNB	Dystrobrevin beta	Scaffolding protein that assembles DMD and SNTA1 molecules to the basal membrane of kidney cells and liver sinusoids.
ZNF823	Zinc finger protein 823	May be involved in transcriptional regulation.
EOMES	Eomesodermin homolog	Functions as a transcriptional activator playing a crucial role during development.
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.
HBS1L	HBS1-like protein	GTPase component of the Pelota-HBS1L complex, a complex that recognizes stalled ribosomes and triggers the No-Go Decay (NGD) pathway.
HLA-DRA	HLA class II histocompatibility antigen, DR alpha chain	An alpha chain of antigen-presenting major histocompatibility complex class II (MHCII) molecule.
IRF8	Interferon regulatory factor 8	Transcription factor that specifically binds to the upstream regulatory region of type I interferon (IFN) and IFN-inducible MHC class I genes (the interferon consensus sequence (ICS)).
IL13	Interleukin-13	Cytokine that plays important roles in allergic inflammation and immune response to parasite infection.
IRF4	Interferon regulatory factor 4	Transcriptional activator.
ITPR3	Inositol 1,4,5-trisphosphate-gated calcium channel ITPR3	Inositol 1,4,5-trisphosphate-gated calcium channel that, upon 1D-myo-inositol 1,4,5-trisphosphate binding, transports calcium from the endoplasmic reticulum lumen to cytoplasm, thus releasing the intracellular calcium and therefore partici…
LPP	Lipoma-preferred partner	May play a structural role at sites of cell adhesion in maintaining cell shape and motility.
MAPK3	Mitogen-activated protein kinase 3	Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway.

Protein-family classification

Druggable: 15 · Difficult: 18 · Unknown: 35 · Druggable fraction: 0.22

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
Ion channel	2	3.3×	0.440
Phosphatase	2	2.5×	0.440
Scaffold/PPI	7	1.8×	0.440
Transcription factor	11	1.3×	0.440
Protease	3	1.6×	0.511
Antibody/Immunoglobulin	3	1.3×	0.620
Other/Unknown	35	0.9×	0.902
Kinase	2	0.8×	0.902
Enzyme (other)	3	0.5×	0.930

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
SH3BP2	Scaffold/PPI	no		SH2, PH_domain, PH-like_dom_sf
TCF7L1	Other/Unknown	no		HMG_box_dom, CTNNB1-bd_N, TCF/LEF
TERC	Other/Unknown	no
TNFAIP3	Transcription factor	no		Znf_A20, OTU_dom, OTU_Deubiquitinase
CD40	Other/Unknown	no		TNFR/NGFR_Cys_rich_reg, TNFR_5, TNFRSF5_N
FCGBP	Other/Unknown	no		EGF, VWF_dom, VWF_type-D
AOPEP	Protease	yes		Peptidase_M1_dom, Peptidase_M1_C, ARM-type_fold
CACNA1I	Ion channel	yes		VDCCAlpha1, VDCC_T_a1, Ion_trans_dom
SHANK2	Scaffold/PPI	no		SH3_domain, PDZ, SAM
ULK4	Kinase	yes		Prot_kinase_dom, Kinase-like_dom_sf, ARM-like
KIF16B	Enzyme (other)	yes	5.6.1.3	FHA_dom, PX_dom, Kinesin_motor_dom
NCOA5	Other/Unknown	no		Anticodon-bd_dom_sf, Nuc_rcpt_coact/corep
PGRMC1	Other/Unknown	no		Cyt_B5-like_heme/steroid-bd, Cyt_B5-like_heme/steroid_sf, MAPR/NEUFC/NENF-like
ELL2	Other/Unknown	no		Occludin_ELL, ELL_N, ELL/occludin
IP6K3	Enzyme (other)	yes	2.7.4.21	IPK, IPK_sf
CLSTN2	Other/Unknown	no		Cadherin-like_dom, ConA-like_dom_sf, Cadherin-like_sf
OLIG3	Transcription factor	no		bHLH_dom, Olig3_bHLH, HLH_DNA-bd_sf
ERAP1	Protease	yes	3.4.11.1	Peptidase_M1, Peptidase_M1_dom, ERAP1-like_C_dom
STAB1	Other/Unknown	no		Link_dom, EGF, FAS1_domain
LGI4	Other/Unknown	no		Cys-rich_flank_reg_C, Leu-rich_rpt, Leu-rich_rpt_typical-subtyp
UQCC2	Other/Unknown	no		UQCC2
AHI1	Scaffold/PPI	no		SH3_domain, WD40_rpt, WD40/YVTN_repeat-like_dom_sf
CORO1A	Scaffold/PPI	no		WD40_rpt, DUF1899, Trimer_CC
TM7SF3	Other/Unknown	no		TM7S3/TM198-like_dom, TM7SF3
RTN4RL2	Other/Unknown	no		Cys-rich_flank_reg_C, Leu-rich_rpt, Leu-rich_rpt_typical-subtyp
BMF	Other/Unknown	no		BMF
ESYT3	Other/Unknown	no		C2_dom, SMP_LBD, C2_domain_sf
NCAPH2	Other/Unknown	no		H2_N, H2_M, CNDH2_C
TMEM169	Other/Unknown	no		TMEM169
CPLANE1	Scaffold/PPI	no		CPLANE1, WD40_repeat_dom_sf
ACE	Protease	yes	3.4.15.1	Peptidase_M2
CDCP2	Other/Unknown	no		CUB_dom, Sperma_CUB_dom_sf, ZP-N
DECR2	Enzyme (other)	yes	1.3.1.124	SDR_fam, NAD(P)-bd_dom_sf, DECR2-like
BRME1	Other/Unknown	no		Brme1
CLEC16A	Other/Unknown	no		CLEC16A/TT9_N, CLEC16A/TT9, CLEC16A/TT9_C
DLK1	Other/Unknown	no		EGF-type_Asp/Asn_hydroxyl_site, EGF, EGF-like_Ca-bd_dom
GRAMD1B	Other/Unknown	no		GRAM, PH-like_dom_sf, VASt
PRR12	Other/Unknown	no		DUF4211, DNA_MethProtect_Complex
ZNF526	Transcription factor	no		Znf_C2H2_type, Znf_C2H2_sf
MEGF11	Other/Unknown	no		EGF, LE_dom, EMI_domain
ARHGEF28	Scaffold/PPI	no		DH_dom, PH_domain, PKC_DAG/PE
DTNB	Transcription factor	no		Znf_ZZ, EF-hand-dom_pair, EF-hand_dom_typ1
ZNF823	Transcription factor	no		KRAB, Znf_C2H2_type, KRAB_dom_sf
EOMES	Transcription factor	no		TF_T-box, p53-like_TF_DNA-bd_sf, TF_T-box_CS
GATA3	Transcription factor	no		Znf_GATA, Znf_NHR/GATA, TF_GATA-2/3
HBS1L	Other/Unknown	no		T_Tr_GTP-bd_dom, EFTu-like_2, Transl_B-barrel_sf
HLA-DRA	Antibody/Immunoglobulin	yes		MHC_II_a_N, Ig/MHC_CS, Ig_C1-set
IRF8	Other/Unknown	no		Interferon_reg_fact_DNA-bd_dom, SMAD_FHA_dom_sf, SMAD-like_dom_sf
IL13	Other/Unknown	no		IL-4/IL-13, 4_helix_cytokine-like_core, IL-4/IL-13_CS
IRF4	Other/Unknown	no		Interferon_reg_fact_DNA-bd_dom, SMAD_FHA_dom_sf, SMAD-like_dom_sf

Expression context

Cohort genes with no expression data: 0.

56 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)	2
broad (>20)	66
unknown	0

Top tissues across cohort

Tissue	Cohort genes
monocyte	8
calcaneal tendon	6
granulocyte	5
leukocyte	5
right testis	5
sural nerve	4
bone marrow cell	4
right adrenal gland	4
right adrenal gland cortex	4
left testis	4
colonic epithelium	3
male germ line stem cell (sensu Vertebrata) in testis	3
vermiform appendix	3
mucosa of transverse colon	3
Brodmann (1909) area 23	3
buccal mucosa cell	3
ileal mucosa	3
adrenal tissue	3
right hemisphere of cerebellum	3
right frontal lobe	3

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SH3BP2	213	ubiquitous	marker	granulocyte, sural nerve, monocyte
TCF7L1	230	ubiquitous	marker	popliteal artery, tibial artery, aorta
TERC	113	ubiquitous	yes	bone marrow cell, colonic epithelium, male germ line stem cell (sensu Vertebrata) in testis
TNFAIP3	274	ubiquitous	marker	vena cava, mucosa of paranasal sinus, vermiform appendix
CD40	242	ubiquitous	marker	lymph node, right lung, spleen
FCGBP	132	tissue_specific	marker	mucosa of transverse colon, right lobe of thyroid gland, duodenum
AOPEP	224	ubiquitous	marker	apex of heart, right coronary artery, ascending aorta
CACNA1I	145		yes	Brodmann (1909) area 23, primary visual cortex, middle temporal gyrus
SHANK2	240	broad	marker	Brodmann (1909) area 23, bronchial epithelial cell, middle temporal gyrus
ULK4	203	ubiquitous	marker	decidua, secondary oocyte, buccal mucosa cell
KIF16B	261	ubiquitous	marker	sural nerve, jejunal mucosa, colonic mucosa
NCOA5	231	ubiquitous	marker	oviduct epithelium, ileal mucosa, cortical plate
PGRMC1	301	ubiquitous	marker	seminal vesicle, caput epididymis, adrenal tissue
ELL2	265	ubiquitous	marker	parotid gland, mucosa of paranasal sinus, cartilage tissue
IP6K3	193	broad	marker	gastrocnemius, tibialis anterior, muscle of leg
CLSTN2	223	broad	marker	endothelial cell, pons, Brodmann (1909) area 23
OLIG3	15	broad	yes	islet of Langerhans, cerebellar vermis, thymus
ERAP1	286	ubiquitous	marker	jejunal mucosa, rectum, monocyte
STAB1	233	broad	marker	spleen, right adrenal gland cortex, right adrenal gland
LGI4	214	broad	marker	peripheral nervous system, nerve, tibial nerve
UQCC2	251	ubiquitous	marker	apex of heart, right atrium auricular region, heart left ventricle
AHI1	276	ubiquitous	marker	pituitary gland, calcaneal tendon, right hemisphere of cerebellum
CORO1A	252	ubiquitous	marker	granulocyte, monocyte, leukocyte
TM7SF3	278	ubiquitous	marker	body of pancreas, sperm, gall bladder
RTN4RL2	156	ubiquitous	yes	right lobe of liver, left lobe of thyroid gland, right frontal lobe
BMF	174	ubiquitous	marker	monocyte, bone marrow cell, leukocyte
ESYT3	169	broad	marker	right hemisphere of cerebellum, upper lobe of left lung, right lung
NCAPH2	260	ubiquitous	marker	cerebellar hemisphere, right hemisphere of cerebellum, cerebellar cortex
TMEM169	154	broad	yes	cortical plate, buccal mucosa cell, ganglionic eminence
CPLANE1	195	ubiquitous	marker	sural nerve, calcaneal tendon, male germ line stem cell (sensu Vertebrata) in testis

Protein interactions among cohort

Intra-cohort edges: 15.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
MAPK3	10,793
REL	5,998
GATA3	5,990
DECR2	3,849
CD40	3,765
TNFAIP3	3,716
ACE	3,659
MYOD1	3,624
CORO1A	3,620
IRF8	3,554

Intra-cohort edges

A	B	Sources
AHI1	CPLANE1	string_interaction
BAK1	BCL2L11	string_interaction
BAK1	BMF	string_interaction
BCL2L11	BMF	string_interaction
BMF	REL	intact
CD40	REL	string_interaction
CLEC16A	PTPN22	string_interaction
EOMES	GATA3	string_interaction
GATA3	IL13	string_interaction
GATA3	IRF4	string_interaction
GATA3	PRR12	intact
IP6K3	MAPK3	intact
OLIG3	PTPN22	string_interaction
OLIG3	TNFAIP3	string_interaction
PTPN22	TNFAIP3	string_interaction

Structural data

PDB: 34 · AlphaFold-only: 32 · No structure: 2

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
HLA-DRA	P01903	140
ACE	P12821	97
BAK1	Q16611	55
BCL2L11	O43521	45
ITPR3	Q14573	24
ERAP1	Q9NZ08	23
IRF4	Q15306	19
TNFAIP3	P21580	17
NCK1	P16333	15
CD40	P25942	14
PTPN22	Q9Y2R2	14
IL13	P35225	13
HBS1L	Q9Y450	11
MAPK3	P27361	8
BMF	Q96LC9	5
CACNA1I	Q9P0X4	4
NCOA5	Q9HCD5	4
ELL2	O00472	4
GATA3	P23771	3
SH3BP2	P78314	2
SHANK2	Q9UPX8	2
ULK4	Q96C45	2
KIF16B	Q96L93	2
DECR2	Q9NUI1	2
ARHGEF28	Q8N1W1	2
MICB	Q29980	2
PTPRK	Q15262	2
FCGBP	Q9Y6R7	1
PGRMC1	O00264	1
AHI1	Q8N157	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
CORO1A	P31146	93.25
LGI4	Q8N135	92.80
PMP22	Q01453	89.87
UQCC2	Q9BRT2	88.94
TM7SF3	Q9NS93	88.66
AOPEP	Q8N6M6	83.36
CDCP2	Q5VXM1	82.43
ISLR	O14498	80.88
RTN4RL2	Q86UN3	80.27
CLSTN2	Q9H4D0	79.46
SERPINF2	P08697	78.94
IP6K3	Q96PC2	76.40
DTNB	O60941	76.29
IRF8	Q02556	75.54
MEGF11	A6BM72	74.12
ZNF823	P16415	72.77
CLEC16A	Q2KHT3	72.17
ESYT3	A0FGR9	71.92
GRAMD1B	Q3KR37	68.76
STAB1	Q9NY15	68.00
REL	Q04864	66.46
ZNF526	Q8TF50	63.80
OLIG3	Q7RTU3	63.67
MYOD1	P15172	62.04
LPP	Q93052	60.99
MYB	P10242	59.16
EOMES	O95936	56.74
TMEM169	Q96HH4	54.97
TCF7L1	Q9HCS4	52.59
MAGEC1	O60732	49.28

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 332. Enrichment computed across 68 evidence-associated genes (45 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 45 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Intrinsic Pathway for Apoptosis	4	26.0×	0.005	BMF, MAPK3, BAK1, BCL2L11
Apoptosis	4	14.9×	0.024	BMF, MAPK3, BAK1, BCL2L11
BH3-only proteins associate with and inactivate anti-apoptotic BCL-2 members	2	56.4×	0.026	BMF, BCL2L11
Fcgamma receptor (FCGR) dependent phagocytosis	3	18.6×	0.026	ITPR3, MAPK3, NCK1
Programmed Cell Death	4	13.0×	0.026	BMF, MAPK3, BAK1, BCL2L11
Interferon gamma signaling	4	11.2×	0.026	HLA-DRA, IRF8, IRF4, MAPK3
Interferon Signaling	4	10.7×	0.026	IRF8, IRF4, MAPK3, NCK1
Platelet activation, signaling and aggregation	4	9.4×	0.035	ISLR, ITPR3, MAPK3, SERPINF2
Apoptotic factor-mediated response	2	39.0×	0.042	MAPK3, BAK1
Hemostasis	6	4.8×	0.047	KIF16B, ISLR, ITPR3, MAPK3, MYB, SERPINF2
Translocation of ZAP-70 to Immunological synapse	2	28.2×	0.062	HLA-DRA, PTPN22
Specification of the neural plate border	2	28.2×	0.062	TCF7L1, MYB
Leishmania infection	3	10.9×	0.062	ITPR3, MAPK3, NCK1
Parasitic Infection Pathways	3	10.9×	0.062	ITPR3, MAPK3, NCK1
Phosphorylation of CD3 and TCR zeta chains	2	24.2×	0.067	HLA-DRA, PTPN22
Developmental Biology	9	2.9×	0.067	TCF7L1, CACNA1I, LGI4, ARHGEF28, IRF4, MAPK3, MYB, MYOD1 (+1 more)
Activation of BH3-only proteins	2	22.1×	0.067	BMF, BCL2L11
Differentiation of naive CD4+ T cells to T helper 2 cells (Th2 cells)	3	9.8×	0.067	GATA3, IL13, IRF4
Cytokine Signaling in Immune system	5	4.5×	0.082	IRF8, IRF4, MAPK3, NCK1, BCL2L11
Antigen activates B Cell Receptor (BCR) leading to generation of second messengers	2	15.9×	0.099	ITPR3, NCK1
Generation of second messenger molecules	2	15.4×	0.099	HLA-DRA, NCK1
Parasite infection	2	15.4×	0.099	MAPK3, NCK1
Leishmania phagocytosis	2	15.4×	0.099	MAPK3, NCK1
Signaling by the B Cell Receptor (BCR)	2	15.4×	0.099	ITPR3, NCK1
MITF-M-regulated melanocyte development	3	7.6×	0.099	TCF7L1, IRF4, MAPK3
Activation and oligomerization of BAK protein	1	126.9×	0.100	BAK1
Nuclear events stimulated by ALK signaling in cancer	2	14.5×	0.102	IRF4, MAPK3
RHO GTPases Activate WASPs and WAVEs	2	14.1×	0.104	MAPK3, NCK1
Interleukin-4 and Interleukin-13 signaling	3	6.9×	0.108	GATA3, IL13, IRF4
Activation of BMF and translocation to mitochondria	1	84.6×	0.112	BMF

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 62 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 T-helper cell differentiation	3	203.8×	1e-04	GATA3, HLA-DRA, IRF4
positive regulation of transcription by RNA polymerase II	15	3.6×	0.004	CD40, OLIG3, AHI1, EOMES, GATA3, IRF8, IL13, IRF4 (+7 more)
thymus development	4	21.7×	0.008	GATA3, MAPK3, MYB, BCL2L11
negative regulation of nucleotide-binding oligomerization domain containing 2 signaling pathway	2	135.9×	0.011	TNFAIP3, PTPN22
positive regulation of release of cytochrome c from mitochondria	3	37.1×	0.011	BMF, BAK1, BCL2L11
antigen processing and presentation of peptide antigen via MHC class I	2	108.7×	0.014	ERAP1, ACE
defense response to protozoan	3	29.1×	0.014	CD40, IRF8, IRF4
cellular response to mechanical stimulus	4	13.9×	0.016	CD40, IL13, MAPK3, BAK1
myeloid cell homeostasis	2	68.0×	0.019	BAK1, BCL2L11
positive regulation of transforming growth factor beta production	2	68.0×	0.019	MYB, SERPINF2
positive regulation of IRE1-mediated unfolded protein response	2	68.0×	0.019	BAK1, BCL2L11
negative regulation of endothelial cell apoptotic process	3	24.0×	0.019	TNFAIP3, GATA3, IL13
associative learning	3	23.3×	0.019	SHANK2, PGRMC1, CLSTN2
T-helper 2 cell differentiation	2	60.4×	0.023	GATA3, MYB
germinal center B cell differentiation	2	54.4×	0.025	IRF8, POU2AF1
cellular response to tumor necrosis factor	4	10.6×	0.025	CD40, GATA3, MAPK3, MYOD1
ear development	2	49.4×	0.027	GATA3, BCL2L11
positive regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway	2	49.4×	0.027	NCK1, BCL2L11
thymocyte apoptotic process	2	45.3×	0.028	BAK1, BCL2L11
positive regulation of protein-containing complex assembly	3	16.3×	0.028	BMF, BAK1, BCL2L11
positive regulation of smooth muscle cell proliferation	3	16.0×	0.028	IL13, MYB, SERPINF2
positive regulation of interleukin-13 production	2	36.2×	0.041	GATA3, IRF4
peptide catabolic process	2	34.0×	0.045	ERAP1, ACE
cellular response to unfolded protein	2	32.0×	0.049	TM7SF3, BAK1
type IV hypersensitivity	1	271.8×	0.057	GATA3
CD8-positive, alpha-beta T cell differentiation involved in immune response	1	271.8×	0.057	EOMES
antigen processing and presentation of peptide or polysaccharide antigen via MHC class II	1	271.8×	0.057	HLA-DRA
mononuclear cell proliferation	1	271.8×	0.057	ACE
negative regulation of toll-like receptor 5 signaling pathway	1	271.8×	0.057	TNFAIP3
phosphoanandamide dephosphorylation	1	271.8×	0.057	PTPN22

Therapeutics

Drugs indicated for this disease

8 approved, 35 in late-stage (phase 3) trials. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

Drug	Development status
Brentuximab Vedotin	Approved (phase 4)
Carmustine	Approved (phase 4)
Chlorambucil	Approved (phase 4)
Dacarbazine	Approved (phase 4)
Lomustine	Approved (phase 4)
Nivolumab	Approved (phase 4)
Pembrolizumab	Approved (phase 4)
Thiotepa	Approved (phase 4)
Bendamustine	Phase 3 (in late-stage trials)
Bleomycin	Phase 3 (in late-stage trials)
Camrelizumab	Phase 3 (in late-stage trials)
Carboplatin	Phase 3 (in late-stage trials)
Cisplatin	Phase 3 (in late-stage trials)
Cyclosporine	Phase 3 (in late-stage trials)
Cytarabine	Phase 3 (in late-stage trials)
Dexamethasone	Phase 3 (in late-stage trials)
Doxorubicin	Phase 3 (in late-stage trials)
Etoposide	Phase 3 (in late-stage trials)
Etoposide Phosphate	Phase 3 (in late-stage trials)
Favezelimab	Phase 3 (in late-stage trials)
Filgrastim	Phase 3 (in late-stage trials)
Fludarabine Phosphate	Phase 3 (in late-stage trials)
Gemcitabine	Phase 3 (in late-stage trials)
Ifosfamide	Phase 3 (in late-stage trials)
Methotrexate	Phase 3 (in late-stage trials)
Methylprednisolone	Phase 3 (in late-stage trials)
Mycophenolate Mofetil	Phase 3 (in late-stage trials)
Panobinostat	Phase 3 (in late-stage trials)
Pegfilgrastim	Phase 3 (in late-stage trials)
Penpulimab	Phase 3 (in late-stage trials)
Prednisone	Phase 3 (in late-stage trials)
Procarbazine	Phase 3 (in late-stage trials)
Rituximab	Phase 3 (in late-stage trials)
Sintilimab	Phase 3 (in late-stage trials)
Sirolimus	Phase 3 (in late-stage trials)
Tacrolimus Anhydrous	Phase 3 (in late-stage trials)
Tifcemalimab	Phase 3 (in late-stage trials)
Tislelizumab	Phase 3 (in late-stage trials)
Toripalimab	Phase 3 (in late-stage trials)
Vinblastine	Phase 3 (in late-stage trials)
Vincristine	Phase 3 (in late-stage trials)
Vinorelbine	Phase 3 (in late-stage trials)
Zimberelimab	Phase 3 (in late-stage trials)

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): Aldesleukin, Alemtuzumab, Amifostine, Ascorbic Acid, Atezolizumab, Avelumab, Axatilimab, Azacitidine, Basiliximab, Bevacizumab, Bortezomib, Busulfan, Cemiplimab, Clofarabine, Decitabine, Entinostat, Epirubicin, Epoetin Beta, Everolimus, Fludarabine, Goserelin, Ibrutinib, Idelalisib, Ipilimumab, Itacitinib, Lenalidomide, Magrolimab, Maraviroc, Mechlorethamine, Melphalan, Motixafortide, Ofatumumab, Oxaliplatin, Pacritinib, Pexidartinib, Plerixafor, Prednisolone, Prolgolimab, Ruxolitinib, Sargramostim, Sugemalimab, Tanespimycin, Temsirolimus, Thalidomide, Thioguanine, Treosulfan, Tucidinostat, Umbralisib, Vorinostat.

Drug target analysis

Approved (phase 4): 6 · Phase ≥3: 7 · Phased (≥1): 10 · Undrugged: 58

Druggability breadth: 24 of 68 evidence-associated genes (35%) 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
CACNA1I	NIMODIPINE
PGRMC1	ENCORAFENIB
ACE	TELMISARTAN
DLK1	FEDRATINIB
MAPK3	CISPLATIN
PMP22	PROGESTERONE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
PMP22	213	4
ACE	31	4
MAPK3	30	4
DLK1	15	4
CACNA1I	7	4
ERAP1	2	2
BCL2L11	2	3
PGRMC1	1	4
PRR12	1	2
BAK1	1	1

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
NIMODIPINE	4	CACNA1I, PMP22
TACRINE	4	CACNA1I
MIBEFRADIL	4	CACNA1I
ENCORAFENIB	4	PGRMC1
TELMISARTAN	4	ACE
MOEXIPRIL	4	ACE
RAMIPRIL	4	ACE
LISINOPRIL ANHYDROUS	4	ACE
SITAGLIPTIN	4	ACE
TRANDOLAPRIL	4	ACE
CAPTOPRIL	4	ACE, PMP22
PERINDOPRIL	4	ACE
QUINAPRIL	4	ACE
LOSARTAN	4	ACE
FOSINOPRIL	4	ACE
IMIDAPRIL	4	ACE
ENALAPRILAT ANHYDROUS	4	ACE
ENALAPRIL	4	ACE
BENAZEPRIL	4	ACE
FEDRATINIB	4	DLK1
AXITINIB	4	DLK1
NERATINIB	4	DLK1
BOSUTINIB	4	DLK1
SUNITINIB	4	DLK1
CRIZOTINIB	4	DLK1
CISPLATIN	4	MAPK3
TIVOZANIB	4	MAPK3
SORAFENIB	4	MAPK3
NALFURAFINE	4	MAPK3
HEXACHLOROPHENE	4	MAPK3

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 8.

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

Symbol	Assays	Type breakdown
MAPK3	964	Binding:950, Functional:9, ADMET:5
ACE	304	Binding:288, Functional:8, ADMET:5, Unclassified:3
PTPN22	137	Binding:122, Functional:10, ADMET:5
ERAP1	88	Binding:85, Functional:2, ADMET:1
CACNA1I	56	Binding:44, Functional:9, ADMET:3
DLK1	51	Binding:51
BCL2L11	38	Binding:36, Functional:2
BAK1	28	Binding:27, Functional:1
CORO1A	12	Binding:12
ITPR3	11	Binding:9, Functional:2
CD40	10	Binding:10
IP6K3	7	Binding:7
MYB	7	Binding:7
PRR12	6	Binding:6
PGRMC1	4	Binding:4
IRF4	3	Binding:3
REL	3	Binding:3
TNFAIP3	1	Binding:1
AOPEP	1	ADMET:1
DECR2	1	Binding:1
HBS1L	1	Binding:1
NCK1	1	Binding:1
PMP22	1	Functional:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
KIF16B	5.6.1.3	plus-end-directed kinesin ATPase
IP6K3	2.7.4.21	inositol-hexakisphosphate 5-kinase
ERAP1	3.4.11.1, 3.4.11.22	leucyl aminopeptidase, aminopeptidase I
ACE	3.4.15.1	peptidyl-dipeptidase A
DECR2	1.3.1.124, 1.3.1.34	2,4-dienoyl-CoA reductase [(3E)-enoyl-CoA-producing], 2,4-dienoyl-CoA reductase [(2E)-enoyl-CoA-producing]
MAPK3	2.7.11.24	mitogen-activated protein kinase
PTPN22	3.1.3.48	protein-tyrosine-phosphatase
PTPRK	3.1.3.48	protein-tyrosine-phosphatase

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
ACE	304
MAPK3	964
PTPN22	137

Pharmacogenomics

Cohort genes with a PharmGKB record: 68; with CPIC/DPWG dosing guidelines: 0.

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

Drug repurposing candidates

30 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.

Compound	Max phase	Cohort target (bioactivity)
NIMODIPINE	4	CACNA1I, PMP22
TACRINE	4	CACNA1I
MIBEFRADIL	4	CACNA1I
ENCORAFENIB	4	PGRMC1
TELMISARTAN	4	ACE
MOEXIPRIL	4	ACE
RAMIPRIL	4	ACE
LISINOPRIL ANHYDROUS	4	ACE
SITAGLIPTIN	4	ACE
TRANDOLAPRIL	4	ACE
CAPTOPRIL	4	ACE, PMP22
PERINDOPRIL	4	ACE
QUINAPRIL	4	ACE
LOSARTAN	4	ACE
FOSINOPRIL	4	ACE
IMIDAPRIL	4	ACE
ENALAPRILAT ANHYDROUS	4	ACE
ENALAPRIL	4	ACE
BENAZEPRIL	4	ACE
FEDRATINIB	4	DLK1
AXITINIB	4	DLK1
NERATINIB	4	DLK1
BOSUTINIB	4	DLK1
SUNITINIB	4	DLK1
CRIZOTINIB	4	DLK1
CISPLATIN	4	MAPK3
TIVOZANIB	4	MAPK3
SORAFENIB	4	MAPK3
NALFURAFINE	4	MAPK3
HEXACHLOROPHENE	4	MAPK3

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	6	CACNA1I, PGRMC1, ACE, DLK1, MAPK3, PMP22
B	Phased (≥1) drug, not yet approved	4	ERAP1, PRR12, BAK1, BCL2L11
C	Druggable family + PDB, no drug	8	ULK4, KIF16B, DECR2, HLA-DRA, ITPR3, MICB, PTPN22, PTPRK
D	Druggable family + AlphaFold only, no drug	3	AOPEP, IP6K3, ISLR
E	Difficult family or no structure, no drug	47	SH3BP2, TCF7L1, TERC, TNFAIP3, CD40, FCGBP, SHANK2, NCOA5, ELL2, CLSTN2 (+37 more)

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
PTPN22	137	—
SH3BP2	0	—
TCF7L1	0	—
TERC	0	—
TNFAIP3	1	—
CD40	10	—
FCGBP	0	—
AOPEP	1	—
SHANK2	0	—
ULK4	0	—
KIF16B	0	—
NCOA5	0	—
ELL2	0	—
IP6K3	7	—
CLSTN2	0	—
OLIG3	0	—
STAB1	0	—
LGI4	0	—
UQCC2	0	—
AHI1	0	—
CORO1A	12	—
TM7SF3	0	—
RTN4RL2	0	—
BMF	0	—
ESYT3	0	—
NCAPH2	0	—
TMEM169	0	—
CPLANE1	0	—
CDCP2	0	—
DECR2	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 679.

Phase distribution (across all retrieved trials)

Phase	Trials
PHASE2	249
Not specified	176
PHASE1	129
PHASE1/PHASE2	73
PHASE3	34
EARLY_PHASE1	7
PHASE4	6
PHASE2/PHASE3	5

Top trials by phase / activity

NCT	Phase	Status	Title
NCT04726501	PHASE4	ACTIVE_NOT_RECRUITING	CCCG-HD-2018 for Children and Adolescents With Newly Diagnosed Hodgkin Lymphoma
NCT06761911	PHASE4	NOT_YET_RECRUITING	BV in the Treatment of Relapsed/refractory Hodgkin Lymphoma
NCT06831370	PHASE4	RECRUITING	A Study of Brentuximab Vedotin With Doxorubicin, Vinblastine and Dacarbazine in Adults With Hodgkin Lymphoma in India
NCT00188149	PHASE4	UNKNOWN	Optimization of the Primary Therapy for Patients With Hodgkin’s Disease and Evaluation of PET
NCT01990534	PHASE4	COMPLETED	A Study of Brentuximab Vedotin in Participants With Relapsed or Refractory Hodgkin Lymphoma
NCT05490953	PHASE4	UNKNOWN	Enhancing Effect on Tumour Apoptosis With the Use of Pentoxifylline in Patients With Hodgkin Lymphoma
NCT04459416	PHASE3	ACTIVE_NOT_RECRUITING	Managing Pain and Symptom Burden Caused by Chemotherapy in People With Myeloma or Lymphoma
NCT04685616	PHASE3	RECRUITING	Brentuximab Vedotin in Early Stage Hodgkin Lymphoma
NCT05595447	PHASE2/PHASE3	RECRUITING	Treatment Strategy for Relapsed/Refractory Hodgkin Lymphoma
NCT06170489	PHASE3	RECRUITING	A Phase III Clinical Study Comparing JS004 Plus Toripalimab With Investigator-Selected Chemotherapy in Patients With PD-(L)1monoclonal Antibody Refractory Classic Hodgkin Lymphoma (cHL)
NCT07256158	PHASE3	NOT_YET_RECRUITING	PET Guided Dose Reduction for InvOlved Site Radiotherapy In Early sTage Unfavourable Hodgkin Lymphoma
NCT00002561	PHASE3	COMPLETED	Radiation Therapy and Chemotherapy in Treating Patients With Hodgkin’s Disease
NCT00038558	PHASE3	COMPLETED	Prophylactic Use of Filgrastim SD/01 in Patients With Hodgkin’s Disease Receiving ABVD Chemotherapy
NCT00039910	PHASE3	COMPLETED	Safety and Efficacy of (PN-152,243)/PN-196,444 in the Prevention of Thrombocytopenia
NCT00075478	PHASE3	COMPLETED	Total-Body Irradiation With or Without Fludarabine Phosphate Followed By Donor Stem Cell Transplant in Treating Patients With Hematologic Cancer
NCT00261677	PHASE3	COMPLETED	A Study to Evaluate the Effect of Weekly PROCRIT (Epoetin Alfa) or Placebo on Anemia and Quality of Life in Children With Cancer Undergoing Chemotherapy
NCT00398411	PHASE3	COMPLETED	Moxifloxacin in the Prevention of Bacteremia After High-dose Chemotherapy and Transplantation of Peripheral Stem Cells
NCT00443677	PHASE3	COMPLETED	Treatment of Advanced Hodgkin’s Disease (Stages IIB-III-IV)
NCT00469729	PHASE2/PHASE3	COMPLETED	Efficacy and Safety Study of StemEx®, to Treat Subjects With High Risk Hematologic Malignancies, Following Myeloablative Therapy
NCT00515554	PHASE3	COMPLETED	HD18 for Advanced Stages in Hodgkins Lymphoma
NCT00736320	PHASE3	UNKNOWN	HD16 for Early Stage Hodgkin Lymphoma
NCT00784537	PHASE2/PHASE3	COMPLETED	High-dose Chemotherapy and Stem Cell Transplantation, in Patients PET-2 Positive, After 2 Courses of ABVD and Comparison of RT Versus no RT in PET-2 Negative Patients
NCT00816959	PHASE3	UNKNOWN	Study Evaluating the Effect of R-mabHDI in Lymphocytic Predominant Hodgkin’s Lymphoma
NCT00838357	PHASE3	COMPLETED	A Multi-centre, Open Label, Single-arm Study Intended to Further Investigate the Safety and Efficacy of Plerixafor as a Front-line Mobilisation Agent in Combination With G-CSF in Patients With Lymphoma or MM (Multiple Myeloma).
NCT00928018	PHASE3	COMPLETED	Tacrolimus/Sirolimus/Methotrexate vs Tacrolimus/Methotrexate or Cyclosporine/Mycophenolate Mofetil for GVHD Prophylaxis After Reduced Intensity Allogeneic Stem Cell Transplantation for Patients With Lymphoma
NCT00992030	PHASE3	TERMINATED	R-ABVD vs ABVD-RT in Early Stage Hodgkin’s Lymphoma
NCT01034163	PHASE3	COMPLETED	A Phase III Randomized, Double Blind, Placebo Controlled Multi-center Study of Panobinostat for Maintenance of Response in Patients With Hodgkin’s Lymphoma (HL)
NCT01085058	PHASE2/PHASE3	COMPLETED	Predictive Value of the Cytocapacity Test Patients With Lymphoproliferative Diseases and High-dose Therapy
NCT01188798	PHASE3	COMPLETED	Methotrexate or Pentostatin for Graft-versus-host Disease Prophylaxis in Risk-adapted Allogeneic Bone Marrow Transplantation for Hematologic Malignancies
NCT01231412	PHASE3	COMPLETED	Graft-Versus-Host Disease Prophylaxis in Treating Patients With Hematologic Malignancies Undergoing Unrelated Donor Peripheral Blood Stem Cell Transplant
NCT01251107	PHASE3	COMPLETED	Study Comparing ABVD vs BEACOPP in Advanced Hodgkin’s Lymphoma
NCT01356680	PHASE3	COMPLETED	HD17 for Intermediate Stage Hodgkin Lymphoma
NCT01358747	PHASE3	COMPLETED	Study of a Treatment Driven by Early PET Response to a Treatment Not Monitored by Early PET in Patients With AA Stage 3-4 or 2B HL
NCT01597778	PHASE3	COMPLETED	Double Cord Versus Haploidentical (BMT CTN 1101)
NCT01652261	PHASE3	WITHDRAWN	Very Early FDG-PET/CT-response Adapted Therapy for Advanced Hodgkin Lymphoma (H11)
NCT01712490	PHASE3	COMPLETED	A Frontline Therapy Trial in Participants With Advanced Classical Hodgkin Lymphoma
NCT01854567	PHASE3	COMPLETED	P3 Study of Umbilical Cord Blood Cells Expanded With MPCs for Transplantation in Patients With Hematologic Malignancies
NCT02566395	PHASE3	COMPLETED	Stem Cell Transplantation From HLA Partially-Matched Related Donors for Patients With Hematologic Malignancies
NCT02684292	PHASE3	COMPLETED	Study of Pembrolizumab (MK-3475) vs. Brentuximab Vedotin in Participants With Relapsed or Refractory Classical Hodgkin Lymphoma (MK-3475-204/KEYNOTE-204)
NCT02722733	PHASE3	UNKNOWN	Randomized Trial of G-CSF Alone Versus Intermediate-dose Ara-C Plus G-CSF Mobilization in Hodgkin’s Lymphoma or Non-Hodgkin’s Lymphoma

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
BRENTUXIMAB VEDOTIN	4	51
BLEOMYCIN	4	32
VINBLASTINE	4	28
PLERIXAFOR	4	12
DACARBAZINE	4	8
DOXORUBICIN	4	8
CLOFARABINE	4	5
PROCARBAZINE	4	5
ROMIDEPSIN	4	5
2-MERCAPTOETHANESULFONIC ACID	4	4
BASILIXIMAB	4	3
ETOPOSIDE PHOSPHATE	4	3
PENTOSTATIN	4	3
UMBRALISIB TOSYLATE	4	3
VINCRISTINE	4	3
VINORELBINE	4	3
BENDAMUSTINE HYDROCHLORIDE	4	2
CARMUSTINE	4	2
DIPHENHYDRAMINE	4	2
FLUDARABINE PHOSPHATE	4	2
IDELALISIB	4	2
LETERMOVIR	4	2
MELPHALAN HYDROCHLORIDE	4	2
PACRITINIB	4	2
PANOBINOSTAT	4	2
POLATUZUMAB VEDOTIN	4	2
PRALATREXATE	4	2
THIOTEPA	4	2
TIPIRACIL HYDROCHLORIDE	4	2
TREOSULFAN	4	2

Precision-medicine subtype map (CIViC)

Drug × molecular subtype: 1 predictive associations from 1 curated evidence items; also 1 prognostic.

Molecular subtype	Therapy	Effect	Level	CIViC
EP300 G1506V			CIViC B	EID7234