neoplasm of mature B-cells

Summary

neoplasm of mature B-cells (MONDO:0004949) is a cancer (an umbrella term covering 8 Mondo subtypes) with 11 cohort genes (14 GWAS associations across 4 studies; 3 CIViC-evidence somatic drivers) and 6 clinical trials. Top therapeutic interventions include ibrutinib, nemtabrutinib, and sovleplenib.

At a glance

• Classification: Cancer
• Umbrella term: 8 Mondo subtypes
• Cohort genes: 11
• GWAS associations: 14
• Clinical trials: 6

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	neoplasm of mature B-cells
Mondo ID	MONDO:0004949
EFO	EFO:0000096
DOID	DOID:706
NCIT	C27910
SNOMED CT	269476000
UMLS	C1334633
MedGen	235305
GARD	0024136
Is cancer (heuristic)	yes

Also known as: mature B-cell lymphocytic neoplasm · mature B-cell neoplasm · mature B-cell neoplasms

Data availability: 14 GWAS associations (4 studies).

Disease family

An umbrella term covering 8 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › immune system disorder › leukocyte disorder › B-cell neoplasm › neoplasm of mature B-cells

Related subtypes (4): lymphoplasmacytic lymphoma, B-cell non-Hodgkin lymphoma, high-grade B-cell lymphoma double-hit/triple-hit, large B-cell lymphoma

Subtypes (8): primary central nervous system lymphoma, B-cell chronic lymphocytic leukemia, plasma cell neoplasm, Burkitt lymphoma, MALT lymphoma, diffuse large B-cell lymphoma, follicular lymphoma, B-cell prolymphocytic leukemia

Genetics & variants

GWAS landscape

14 GWAS associations across 4 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
rs12195582	5e-100	HLA-DRB9 - HLA-DRB5	T	1.78
rs10484561	1e-29	HLA-DQB1 - MTCO3P1	G	1.95
rs2647012	2e-21	HLA-DQB1 - MTCO3P1	G	1.56
rs4938573	6e-20	Y_RNA - CXCR5	C	1.34
rs6457327	5e-11	RNU6-1133P - C6orf15	C	1.69
rs4937362	7e-11	ETS1 - FLI1	T	1.19
rs6444305	1e-10	LPP	G	1.21
rs17749561	8e-10	PHLPP1 - BCL2	G	1.34
rs735665	4e-09	GRAMD1B	T	1.81
rs13254990	1e-08	PVT1	T	1.18
rs3751913	2e-07	CYBC1	C	1.23
rs2681416	2e-07	CD86	A	1.16
rs11082438	4e-07	SLC14A2	G	1.33

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST002643	Skibola CF	2014	2,728	7,758	Genome-wide association study identifies five susceptibility loci for follicular lymphoma outside the HLA region.
GCST000734	Conde L	2010	681	0	Genome-wide association study of follicular lymphoma identifies a risk locus at 6p21.32.
GCST001051	Smedby KE	2011	379	0	GWAS of follicular lymphoma reveals allelic heterogeneity at 6p21.32 and suggests shared genetic susceptibility with diffuse large B-cell lymphoma.
GCST000448	Skibola CF	2009	189	0	Genetic variants at 6p21.33 are associated with susceptibility to follicular lymphoma.

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	12

MAF distribution

Bucket	Variants
common (>=0.05)	13
low_freq (0.01-0.05)	0
rare (<0.01)	0
unknown	0

Functional consequences

Consequence	Count
intron_variant	7
intergenic_variant	4
regulatory_region_variant	1
non_coding_transcript_exon_variant	1

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
rs12195582	6	32476767	C>T	0.465	intron_variant	HLA-DRB9 - HLA-DRB5	5e-100	Tier 4: intronic/intergenic
rs10484561	6	32697643	T>G	0.11	intergenic_variant	HLA-DQB1 - MTCO3P1	1e-29	Tier 4: intronic/intergenic
rs2647012	6	32696681	T>A,C,G	0.44	intergenic_variant	HLA-DQB1 - MTCO3P1	2e-21	Tier 4: intronic/intergenic
rs4938573	11	118871133	C>A,G,T	0.204	regulatory_region_variant	Y_RNA - CXCR5	6e-20	Tier 3: regulatory
rs6457327	6	31106253	A>C,T	0.38	intergenic_variant	RNU6-1133P - C6orf15	5e-11	Tier 4: intronic/intergenic
rs4937362	11	128622844	T>A,C,G	0.456	non_coding_transcript_exon_variant	ETS1 - FLI1	7e-11	Tier 4: intronic/intergenic
rs6444305	3	188582114	G>A,C,T	0.276	intron_variant	LPP	1e-10	Tier 4: intronic/intergenic
rs17749561	18	63115978	G>A	0.09	intergenic_variant	PHLPP1 - BCL2	8e-10	Tier 4: intronic/intergenic
rs735665	11	123490689	G>A	0.21	intron_variant	GRAMD1B	4e-09	Tier 4: intronic/intergenic
rs13254990	8	128064205	C>T	0.315	intron_variant	PVT1	1e-08	Tier 4: intronic/intergenic
rs3751913	17	82447676	T>A,C	0.121	intron_variant	CYBC1	2e-07	Tier 4: intronic/intergenic
rs2681416	3	122098766	G>A	0.311	intron_variant	CD86	2e-07	Tier 4: intronic/intergenic
rs11082438	18	45285245	G>T	0.064	intron_variant	SLC14A2	4e-07	Tier 4: intronic/intergenic

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 11 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Somatic driver evidence (intOGen + CIViC, cohort fanout)

Gene	intOGen role	Cancer types	CIViC
ETS1			CIViC #1762
HLA-C	LoF	DLBCLNOS	CIViC #2608
BCL2	Act	DLBCLNOS,MLYM,NHL	CIViC #59

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
CYBC1	Orphanet:379	Chronic granulomatous disease
ETS1	Orphanet:536	Systemic lupus erythematosus
HLA-C	Orphanet:585909	B-lymphoblastic leukemia/lymphoma with t(9;22)(q34.1;q11.2)
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
BCL2	Orphanet:480541	High grade B-cell lymphoma with MYC and/ or BCL2 and/or BCL6 rearrangement
BCL2	Orphanet:545	Follicular lymphoma
BCL2	Orphanet:98839	Intravascular large B-cell lymphoma

Cohort genes → proteins

11 cohort genes, 10 distinct canonical proteins.

Evidence partition

Subset	Genes
gwas_only	11

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
CXCR5	HGNC:1060	ENSG00000160683	P32302	C-X-C chemokine receptor type 5	gwas
SLC14A2	HGNC:10919	ENSG00000132874	Q15849	Urea transporter 2	gwas
C6orf15	HGNC:13927	ENSG00000204542	Q6UXA7	Uncharacterized protein C6orf15	gwas
CD86	HGNC:1705	ENSG00000114013	P42081	T-lymphocyte activation antigen CD86	gwas
CYBC1	HGNC:28672	ENSG00000178927	Q9BQA9	Cytochrome b-245 chaperone 1	gwas
ETS1	HGNC:3488	ENSG00000134954	P14921	Protein C-ets-1	gwas
HLA-C	HGNC:4933	ENSG00000204525	P10321	HLA class I histocompatibility antigen, C alpha chain	gwas
HLA-DQB1	HGNC:4944	ENSG00000179344	P01920	HLA class II histocompatibility antigen, DQ beta 1 chain	gwas
LPP	HGNC:6679	ENSG00000145012	Q93052	Lipoma-preferred partner	gwas
PVT1	HGNC:9709	ENSG00000249859		Pvt1 oncogene	gwas
BCL2	HGNC:990	ENSG00000171791	P10415	Apoptosis regulator Bcl-2	gwas

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
CXCR5	C-X-C chemokine receptor type 5	Cytokine receptor that binds to B-lymphocyte chemoattractant (BLC).
SLC14A2	Urea transporter 2	Mediates the transport of urea driven by a concentration gradient across the cell membrane of the renal inner medullary collecting duct which is critical to the urinary concentrating mechanism.
CD86	T-lymphocyte activation antigen CD86	Costimulatory molecule that belongs to the immunoglobulin superfamily that plays an important role in T-lymphocyte activation.
CYBC1	Cytochrome b-245 chaperone 1	Functions as a chaperone necessary for a stable expression of the CYBA and CYBB subunits of the cytochrome b-245 heterodimer.
ETS1	Protein C-ets-1	Transcription factor.
HLA-C	HLA class I histocompatibility antigen, C alpha chain	Antigen-presenting major histocompatibility complex class I (MHCI) molecule with an important role in reproduction and antiviral immunity.
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.
LPP	Lipoma-preferred partner	May play a structural role at sites of cell adhesion in maintaining cell shape and motility.
BCL2	Apoptosis regulator Bcl-2	Suppresses apoptosis in a variety of cell systems including factor-dependent lymphohematopoietic and neural cells.

Protein-family classification

Druggable: 5 · Difficult: 1 · Unknown: 5 · Druggable fraction: 0.45

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	3	8.0×	0.027
Transporter	1	7.1×	0.332
GPCR	1	2.2×	0.624
Other/Unknown	5	0.8×	0.840
Transcription factor	1	0.8×	0.840

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
CXCR5	GPCR	yes		GPCR_Rhodpsn, Chemokine_CXCR5, GPCR_Rhodpsn_7TM
SLC14A2	Transporter	yes		Urea_transporter, Ammonium/urea_transptr
C6orf15	Other/Unknown	no		C6orf15
CD86	Antibody/Immunoglobulin	yes		Ig_sub, Ig-like_dom, Ig_V-set
CYBC1	Other/Unknown	no		Cybc1
ETS1	Other/Unknown	no		Ets_dom, Pointed_dom, SAM/pointed_sf
HLA-C	Antibody/Immunoglobulin	yes		MHC_I_a_a1/a2, Ig_C1-set, Ig-like_dom
HLA-DQB1	Antibody/Immunoglobulin	yes		MHC_II_b_N, Ig/MHC_CS, Ig_C1-set
LPP	Transcription factor	no		Znf_LIM
PVT1	Other/Unknown	no
BCL2	Other/Unknown	no		Bcl2-like, Bcl2_BH4, Bcl2/BclX

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)	11
unknown	0

Top tissues across cohort

Tissue	Cohort genes
spleen	4
granulocyte	2
blood	2
right lung	2
lymph node	1
hair follicle	1
primordial germ cell in gonad	1
right adrenal gland	1
skin of abdomen	1
skin of leg	1
zone of skin	1
leukocyte	1
monocyte	1
mononuclear cell	1
parietal pleura	1
tibia	1
visceral pleura	1
upper lobe of left lung	1
saphenous vein	1
urethra	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
CXCR5	172	tissue_specific	marker	granulocyte, spleen, lymph node
SLC14A2	100	tissue_specific	marker	primordial germ cell in gonad, hair follicle, right adrenal gland
C6orf15	31	tissue_specific	yes	skin of leg, zone of skin, skin of abdomen
CD86	218	broad	marker	monocyte, mononuclear cell, leukocyte
CYBC1	267	ubiquitous	marker	granulocyte, spleen, blood
ETS1	263	ubiquitous	marker	visceral pleura, parietal pleura, tibia
HLA-C	134	ubiquitous	marker	blood, right lung, spleen
HLA-DQB1	268	broad	marker	right lung, spleen, upper lobe of left lung
LPP	292	ubiquitous	marker	saphenous vein, urethra, vena cava
PVT1	227	ubiquitous	marker	lower esophagus mucosa, adrenal tissue, colonic epithelium
BCL2	275	ubiquitous	marker	dorsal motor nucleus of vagus nerve, superficial temporal artery, calcaneal tendon

Protein interactions among cohort

Intra-cohort edges: 2.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
BCL2	8,343
ETS1	3,729
CD86	3,672
CXCR5	1,993
C6orf15	1,420
LPP	1,113
SLC14A2	1,103
HLA-C	836
CYBC1	645
HLA-DQB1	128

Intra-cohort edges

A	B	Sources
CYBC1	ETS1	intact
HLA-C	HLA-DQB1	intact

Structural data

PDB: 7 · AlphaFold-only: 3 · No structure: 1

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
BCL2	P10415	55
ETS1	P14921	21
HLA-C	P10321	13
HLA-DQB1	P01920	10
SLC14A2	Q15849	9
CD86	P42081	7
CYBC1	Q9BQA9	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
CXCR5	P32302	80.85
LPP	Q93052	60.99
C6orf15	Q6UXA7	43.65

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 59. Enrichment computed across 11 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
The NLRP1 inflammasome	1	543.8×	0.051	BCL2
BH3-only proteins associate with and inactivate anti-apoptotic BCL-2 members	1	181.3×	0.051	BCL2
Inflammasomes	1	163.1×	0.051	BCL2
Endosomal/Vacuolar pathway	1	148.3×	0.051	HLA-C
NFE2L2 regulating tumorigenic genes	1	135.9×	0.051	BCL2
CD28 dependent Vav1 pathway	1	125.5×	0.051	CD86
Activation of BAD and translocation to mitochondria	1	108.8×	0.051	BCL2
SLC-mediated transport of organic cations	1	108.8×	0.051	SLC14A2
Regulation of MITF-M-dependent genes involved in apoptosis	1	90.6×	0.051	BCL2
Co-inhibition by CTLA4	1	74.2×	0.051	CD86
Activation of BH3-only proteins	1	70.9×	0.051	BCL2
DAP12 interactions	1	68.0×	0.051	HLA-C
Estrogen-dependent nuclear events downstream of ESR-membrane signaling	1	62.8×	0.051	BCL2
Regulation of T cell activation by CD28 family	1	60.4×	0.051	CD86
CD28 dependent PI3K/Akt signaling	1	56.3×	0.051	CD86
Antigen Presentation: Folding, assembly and peptide loading of class I MHC	1	56.3×	0.051	HLA-C
Co-stimulation by CD28	1	54.4×	0.051	CD86
PI3K/AKT Signaling in Cancer	1	52.6×	0.051	CD86
Nucleotide-binding domain, leucine rich repeat containing receptor (NLR) signaling pathways	1	51.0×	0.051	BCL2
Oncogene Induced Senescence	1	48.0×	0.051	ETS1
Nuclear events mediated by NFE2L2	1	48.0×	0.051	BCL2
Interferon gamma signaling	2	35.9×	0.051	HLA-C, HLA-DQB1
Signaling by Interleukins	2	18.3×	0.051	CD86, BCL2
Cytokine Signaling in Immune system	2	11.7×	0.051	CD86, BCL2
Intrinsic Pathway for Apoptosis	1	41.8×	0.056	BCL2
Negative regulation of the PI3K/AKT network	1	39.8×	0.056	CD86
Interleukin-10 signaling	1	33.3×	0.065	CD86
Chemokine receptors bind chemokines	1	26.7×	0.077	CXCR5
MITF-M-dependent gene expression	1	25.9×	0.077	BCL2
Extra-nuclear estrogen signaling	1	24.4×	0.078	BCL2

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
immune response	5	23.5×	2e-04	CXCR5, CD86, ETS1, HLA-C, HLA-DQB1
B cell activation	2	91.1×	0.013	CXCR5, CD86
adaptive immune response	3	25.3×	0.013	CD86, HLA-C, HLA-DQB1
melanin metabolic process	1	1685.2×	0.015	BCL2
obsolete negative regulation of cellular pH reduction	1	1685.2×	0.015	BCL2
pigment granule organization	1	1685.2×	0.015	BCL2
humoral immune response	2	56.2×	0.015	HLA-DQB1, BCL2
regulation of nitrogen utilization	1	842.6×	0.020	BCL2
CD8-positive, alpha-beta T cell lineage commitment	1	842.6×	0.020	BCL2
negative regulation of retinal cell programmed cell death	1	842.6×	0.020	BCL2
positive regulation of neuron maturation	1	561.7×	0.020	BCL2
cochlear nucleus development	1	561.7×	0.020	BCL2
positive regulation of lymphotoxin A production	1	561.7×	0.020	CD86
regulation of viral genome replication	1	561.7×	0.020	BCL2
retinal cell programmed cell death	1	561.7×	0.020	BCL2
dendritic cell apoptotic process	1	561.7×	0.020	BCL2
regulation of glycoprotein biosynthetic process	1	421.3×	0.023	BCL2
urea transport	1	421.3×	0.023	SLC14A2
respiratory burst after phagocytosis	1	421.3×	0.023	CYBC1
B cell lineage commitment	1	337.0×	0.023	BCL2
negative regulation of calcium ion transport into cytosol	1	337.0×	0.023	BCL2
positive regulation of melanocyte differentiation	1	337.0×	0.023	BCL2
urea transmembrane transport	1	337.0×	0.023	SLC14A2
lymphoid progenitor cell differentiation	1	280.9×	0.026	BCL2
PML body organization	1	280.9×	0.026	ETS1
mesenchymal cell development	1	240.7×	0.026	BCL2
gland morphogenesis	1	240.7×	0.026	BCL2
stem cell development	1	240.7×	0.026	BCL2
cell-cell adhesion	2	20.3×	0.026	LPP, BCL2
myeloid cell apoptotic process	1	210.7×	0.026	BCL2

Therapeutics

Drugs indicated for this disease

6 approved, 34 in late-stage (phase 3) trials. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

Drug	Development status
Axicabtagene Ciloleucel	Approved (phase 4)
Epcoritamab	Approved (phase 4)
Idelalisib	Approved (phase 4)
Mosunetuzumab	Approved (phase 4)
Obinutuzumab	Approved (phase 4)
YTTRIUM Y 90 IBRITUMOMAB TIUXETAN	Approved (phase 4)
Aldesleukin	Phase 3 (in late-stage trials)
Bendamustine	Phase 3 (in late-stage trials)
Bevacizumab	Phase 3 (in late-stage trials)
Carboplatin	Phase 3 (in late-stage trials)
Carmustine	Phase 3 (in late-stage trials)
Cisplatin	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)
Filgrastim	Phase 3 (in late-stage trials)
Fludarabine	Phase 3 (in late-stage trials)
Fludarabine Phosphate	Phase 3 (in late-stage trials)
Gemcitabine	Phase 3 (in late-stage trials)
Ibritumomab Tiuxetan	Phase 3 (in late-stage trials)
Ibrutinib	Phase 3 (in late-stage trials)
Ifosfamide	Phase 3 (in late-stage trials)
Inotuzumab Ozogamicin	Phase 3 (in late-stage trials)
Lenalidomide	Phase 3 (in late-stage trials)
Melphalan	Phase 3 (in late-stage trials)
Methotrexate	Phase 3 (in late-stage trials)
Odronextamab	Phase 3 (in late-stage trials)
Parsaclisib	Phase 3 (in late-stage trials)
Pixantrone	Phase 3 (in late-stage trials)
Prednisolone	Phase 3 (in late-stage trials)
Prednisone	Phase 3 (in late-stage trials)
Rituximab	Phase 3 (in late-stage trials)
TOSITUMOMAB 131I	Phase 3 (in late-stage trials)
Tafasitamab	Phase 3 (in late-stage trials)
Tazemetostat	Phase 3 (in late-stage trials)
Tisagenlecleucel	Phase 3 (in late-stage trials)
Vincristine	Phase 3 (in late-stage trials)
Zandelisib	Phase 3 (in late-stage trials)
Zanubrutinib	Phase 3 (in late-stage trials)

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): Acetaminophen, Anakinra, Atezolizumab, Benmelstobart, Bortezomib, Brentuximab Vedotin, Capivasertib, Carfilzomib, Cirmtuzumab, Diphenhydramine, Enzastaurin, Epirubicin, Loncastuximab Tesirine, Nivolumab, Ondansetron, Orelabrutinib, Oxaliplatin, Pembrolizumab, Polatuzumab Vedotin, Ripertamab, Selinexor, Thalidomide, Tositumomab, Tucidinostat, Ublituximab, Umbralisib, Venetoclax, Vindesine, Vorinostat.

Drug target analysis

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

Druggability breadth: 4 of 11 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
BCL2	IXABEPILONE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
BCL2	14	4
CXCR5	0	0
SLC14A2	0	0
C6orf15	0	0
CD86	0	0
CYBC1	0	0
ETS1	0	0
HLA-C	0	0
HLA-DQB1	0	0
LPP	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
IXABEPILONE	4	BCL2
VENETOCLAX	4	BCL2
EPIGALOCATECHIN GALLATE	3	BCL2
OBATOCLAX	3	BCL2
NAVITOCLAX	3	BCL2
GOSSYPOL	3	BCL2
SONROTOCLAX	3	BCL2
CHLORCYCLIZINE	2	BCL2
FORMONONETIN	2	BCL2
LACUTOCLAX	2	BCL2
ABT 737	1	BCL2
VOB-560	1	BCL2
AZD-5991	1	BCL2
TAPOTOCLAX	1	BCL2

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
BCL2	446	Binding:418, Functional:23, Toxicity:3, ADMET:2
CXCR5	33	Binding:21, Functional:12
HLA-C	1	Binding:1

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
BCL2	446

Pharmacogenomics

Cohort genes with a PharmGKB record: 11; with CPIC/DPWG dosing guidelines: 0.

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

Drug repurposing candidates

14 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)
IXABEPILONE	4	BCL2
VENETOCLAX	4	BCL2
EPIGALOCATECHIN GALLATE	3	BCL2
OBATOCLAX	3	BCL2
NAVITOCLAX	3	BCL2
GOSSYPOL	3	BCL2
SONROTOCLAX	3	BCL2
CHLORCYCLIZINE	2	BCL2
FORMONONETIN	2	BCL2
LACUTOCLAX	2	BCL2
ABT 737	1	BCL2
VOB-560	1	BCL2
AZD-5991	1	BCL2
TAPOTOCLAX	1	BCL2

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	BCL2
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	4	SLC14A2, CD86, HLA-C, HLA-DQB1
D	Druggable family + AlphaFold only, no drug	1	CXCR5
E	Difficult family or no structure, no drug	5	C6orf15, CYBC1, ETS1, LPP, PVT1

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)
CXCR5	33	—
SLC14A2	0	—
C6orf15	0	—
CD86	0	—
CYBC1	0	—
ETS1	0	—
HLA-C	1	—
HLA-DQB1	0	—
LPP	0	—
PVT1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 6.

Phase distribution (across all retrieved trials)

Phase	Trials
PHASE1	5
Not specified	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT05544019	PHASE1	RECRUITING	Study of SGR-1505 in Mature B-Cell Neoplasms
NCT01704963	PHASE1	COMPLETED	A Study to Evaluate the Bruton’s Tyrosine Kinase (Btk) Inhibitor PCI-32765 in Patients With Recurrent Mature B-Cell Neoplasms
NCT02857998	PHASE1	COMPLETED	A Study of Hutchison MediPharma Limited(HMPL)-523 in Patients With Relapsed or Refractory Mature B-cell Neoplasms
NCT03664297	PHASE1	UNKNOWN	Tolerance and Pharmacokinetics of SHR1459 in Patients With Recurrent Replased/Refractory Mature B Cell Neoplasmstumor
NCT05673460	PHASE1	COMPLETED	A Clinical Study of Nemtabrutinib in Japanese Participants With Hematological Malignancies (MK-1026-002)
NCT03280394	Not specified	RECRUITING	Liquid Biopsy in Mature B-cell Tumors

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
IBRUTINIB	4	1
NEMTABRUTINIB	3	1
SOVLEPLENIB	3	1
EDRALBRUTINIB	2	1
SGR-1505	1	1