Follicular lymphoma

Summary

Follicular lymphoma (MONDO:0018906) is a cancer with 6 cohort genes (20 GWAS associations across 13 studies; 4 CIViC-evidence somatic drivers; 6 ClinVar predisposition records) and 530 clinical trials. Molecularly, EZH2 Activating Mutation confers sensitivity to Tazemetostat in Follicular Lymphoma (CIViC Level A); 4 further subtype–drug associations are mapped below. Top therapeutic interventions include cyclophosphamide anhydrous, tazemetostat, and bendamustine.

At a glance

• Classification: Cancer
• Prevalence: 1-5 / 10 000 (Europe) [Orphanet-validated]
• Cohort genes: 6
• GWAS associations: 20
• ClinVar variants: 6
• Phenotypes (HPO): 17
• Clinical trials: 530
• Precision-medicine evidence (CIViC): 5 subtype–drug associations

Clinical features

Epidemiology

Prevalence records

26 prevalence record(s), Orphanet, top 20 (validated / broadest geography first):

Type	Class	Value	Geography	Validation
Annual incidence	1-9 / 100 000	2.192	Europe	Validated
Point prevalence	1-5 / 10 000	37	Europe	Validated
Annual incidence	1-9 / 100 000	3.95	France	Validated
Annual incidence	1-9 / 1 000 000	0.348	Bulgaria	Validated
Annual incidence	1-9 / 1 000 000	0.72	Estonia	Validated
Annual incidence	1-9 / 1 000 000	0.579	Finland	Validated
Annual incidence	1-9 / 1 000 000	0.363	Latvia	Validated
Annual incidence	1-9 / 1 000 000	0.277	Lithuania	Validated
Annual incidence	1-9 / 1 000 000	0.368	Poland	Validated
Annual incidence	1-9 / 100 000	1.52	Austria	Validated
Annual incidence	1-9 / 100 000	3.04	Belgium	Validated
Annual incidence	1-9 / 100 000	1.665	Croatia	Validated
Annual incidence	1-9 / 100 000	1.687	Czech Republic	Validated
Annual incidence	1-9 / 100 000	2.456	Germany	Validated
Annual incidence	1-9 / 100 000	2.769	Iceland	Validated
Annual incidence	1-9 / 100 000	2.08	Ireland	Validated
Annual incidence	1-9 / 100 000	2.541	Italy	Validated
Annual incidence	1-9 / 100 000	1.759	Malta	Validated
Annual incidence	1-9 / 100 000	3.298	Norway	Validated
Annual incidence	1-9 / 100 000	1.364	Portugal	Validated

Signs & symptoms

Clinical features (HPO)

17 HPO clinical features (Orphanet curated; top 17 by frequency):

HPO ID	Term	Frequency
HP:0001824	Weight loss	Very frequent (80-99%)
HP:0001945	Fever	Very frequent (80-99%)
HP:0002665	Lymphoma	Very frequent (80-99%)
HP:0002716	Lymphadenopathy	Very frequent (80-99%)
HP:0100721	Mediastinal lymphadenopathy	Very frequent (80-99%)
HP:0001744	Splenomegaly	Frequent (30-79%)
HP:0012378	Fatigue	Frequent (30-79%)
HP:0030166	Night sweats	Frequent (30-79%)
HP:0002202	Pleural effusion	Occasional (5-29%)
HP:0001004	Lymphedema	Occasional (5-29%)
HP:0001287	Meningitis	Occasional (5-29%)
HP:0002585	Abnormality of the peritoneum	Occasional (5-29%)
HP:0003072	Hypercalcemia	Occasional (5-29%)
HP:0025435	Increased circulating lactate dehydrogenase concentration	Occasional (5-29%)
HP:0200036	Skin nodule	Occasional (5-29%)
HP:0001541	Ascites	Occasional (5-29%)
HP:0033823	Mediastinal mass	Very rare (<1-4%)

Identifiers

Disease identifiers

Field	Value
Canonical name	follicular lymphoma
Mondo ID	MONDO:0018906
MeSH	D008224
Orphanet	545
DOID	DOID:0050873
ICD-10-CM	C82
ICD-11	797822185
NCIT	C3209
SNOMED CT	308121000
UMLS	C0024301
MedGen	7417
GARD	0002356
NORD	1983
Is cancer (heuristic)	yes

Also known as: follicle center lymphoma · follicle centre lymphoma · follicular center cell lymphoma · follicular centre cell lymphoma · follicular non-Hodgkin lymphoma · follicular non-Hodgkin’s lymphoma · lymphoma, follicular · lymphoma, follicular center cell · lymphoma, follicular centre cell · lymphoma, follicular, malignant

Data availability: 6 ClinVar variants · 20 GWAS associations (13 studies) · 25 cell lines.

Disease family

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

Related subtypes (7): primary central nervous system lymphoma, B-cell chronic lymphocytic leukemia, plasma cell neoplasm, Burkitt lymphoma, MALT lymphoma, diffuse large B-cell lymphoma, B-cell prolymphocytic leukemia

Genetics & variants

GWAS landscape

20 GWAS associations across 13 studies. Top hits map to 11 distinct genes (as reported by GWAS).

Top associations by p-value

rsID	p-value	Gene	Risk allele	Odds ratio
rs142720403	4e-34	C2	?	1.81
rs61410672	1e-21	MICC - TMPOP1	?	1.58
rs12154137	1e-16	CD83P1 - RNU6-471P	?	1.52
rs140083693	4e-14	RNU6-376P - DDX6	?	1.38
rs62405954	2e-12	RN7SL26P - Metazoa_SRP	?	1.35
rs12497690	2e-10	EOMES - LINC01980	C	1.25
rs4459895	3e-10	LPP	?	0.76
rs74488719	8e-10	H2BC9 - H3C8	?	1.44
rs2690093	9e-10	CARMIL1, CMAHP	A	1.29
rs11187157	3e-09	Y_RNA - EXOC6	C	1.15
rs142239370	1e-08	PALD1	C	1.6
rs151193165	2e-08	LARP1BP1 - TECRL	?
rs2765974	3e-08	CELF2	?	1.14
rs7595037	9e-08	PLEK - WDR4P2	?	1.08
rs2425752	1e-07	NCOA5	?	1.09
rs4723859	1e-07	POU6F2	?	1.31
rs58467928	2e-07	PVT1	?	1.2
rs2835507	3e-07	HLCS	?	0.81
rs12675713	4e-07	CSMD1	?	1.48
rs9421684	6e-06	LINC02655 - RPS7P9	A	1.14

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST90267402	Berndt SI	2022	3,100	9,505	Distinct germline genetic susceptibility profiles identified for common non-Hodgkin lymphoma subtypes.
GCST008718	Din L	2019	2,686	25,256	Genetic overlap between autoimmune diseases and non-Hodgkin lymphoma subtypes.
GCST008719	Din L	2019	2,686	11,959	Genetic overlap between autoimmune diseases and non-Hodgkin lymphoma subtypes.
GCST008720	Din L	2019	2,686	23,871	Genetic overlap between autoimmune diseases and non-Hodgkin lymphoma subtypes.
GCST90624741	Guler M	2025	1,727	656,255	Clustering of lymphoid neoplasms by cell of origin, somatic mutation and drug usage profiles: a multi-trait genome-wide association study.
GCST90481538	Verma A	2024	1,155	449,830	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90079633	Backman JD	2021	538	387,366	Exome sequencing and analysis of 454,787 UK Biobank participants.
GCST90083619	Backman JD	2021	538	387,366	Exome sequencing and analysis of 454,787 UK Biobank participants.
GCST90042739	Jiang L	2021	394	455,954	A generalized linear mixed model association tool for biobank-scale data.
GCST90435645	Zhou W	2018	371	404,466	Efficiently controlling for case-control imbalance and sample relatedness in large-scale genetic association studies.

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	19

MAF distribution

Bucket	Variants
common (>=0.05)	18
low_freq (0.01-0.05)	1
rare (<0.01)	0
unknown	1

Functional consequences

Consequence	Count
intron_variant	13
intergenic_variant	6
regulatory_region_variant	1

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
rs142720403	6	31904481	ATTTTCGCAT>A	0.05	intron_variant	C2	4e-34	Tier 4: intronic/intergenic
rs61410672	6	30426894	G>A	0.05	intergenic_variant	MICC - TMPOP1	1e-21	Tier 4: intronic/intergenic
rs12154137	6	27577904	G>A,T	0.05	intergenic_variant	CD83P1 - RNU6-471P	1e-16	Tier 4: intronic/intergenic
rs140083693	11	118735970	TA>T,TAA	0.05	intron_variant	RNU6-376P - DDX6	4e-14	Tier 4: intronic/intergenic
rs62405954	6	33557043	T>C	0.05	intron_variant	RN7SL26P - Metazoa_SRP	2e-12	Tier 4: intronic/intergenic
rs12497690	3	27753906	A>C,T	0.372	intergenic_variant	EOMES - LINC01980	2e-10	Tier 4: intronic/intergenic
rs4459895	3	188236626	A>C,G,T	0.05	intron_variant	LPP	3e-10	Tier 4: intronic/intergenic
rs74488719	6	26255921	G>T	0.05	intron_variant	H2BC9 - H3C8	8e-10	Tier 4: intronic/intergenic
rs2690093	6	25344759	G>A,C	0.166	intron_variant	CARMIL1, CMAHP	9e-10	Tier 4: intronic/intergenic
rs11187157	10	92742487	T>C	0.05	regulatory_region_variant	Y_RNA - EXOC6	3e-09	Tier 3: regulatory
rs142239370	10	70623113	A>C,G	0.04	intergenic_variant	PALD1	1e-08	Tier 4: intronic/intergenic
rs151193165	4	63771822	T>A		intron_variant	LARP1BP1 - TECRL	2e-08	Tier 4: intronic/intergenic
rs2765974	10	11246455	C>A,G,T	0.05	intron_variant	CELF2	3e-08	Tier 4: intronic/intergenic
rs7595037	2	68419963	C>A,T	0.05	intergenic_variant	PLEK - WDR4P2	9e-08	Tier 4: intronic/intergenic
rs2425752	20	46073481	T>C,G	0.05	intron_variant	NCOA5	1e-07	Tier 4: intronic/intergenic
rs4723859	7	39327347	G>A	0.05	intron_variant	POU6F2	1e-07	Tier 4: intronic/intergenic
rs58467928	8	128062204	G>A	0.05	intron_variant	PVT1	2e-07	Tier 4: intronic/intergenic
rs2835507	21	36860937	G>A,C	0.05	intron_variant	HLCS	3e-07	Tier 4: intronic/intergenic
rs12675713	8	3977248	A>C,G	0.05	intron_variant	CSMD1	4e-07	Tier 4: intronic/intergenic
rs9421684	10	80702590	G>A	0.05	intergenic_variant	LINC02655 - RPS7P9	6e-06	Tier 4: intronic/intergenic

ClinVar germline variants

6 retrieved; paginated sample, class counts are floors:

6 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
6253	NM_003921.5(BCL10):c.427_428dup (p.Glu145fs)	BCL10	Pathogenic	no assertion criteria provided
6254	NM_003921.5(BCL10):c.231dup (p.Gly78fs)	BCL10	Pathogenic	no assertion criteria provided
6255	NM_003921.5(BCL10):c.525_541del (p.Val176fs)	BCL10	Pathogenic	no assertion criteria provided
6256	NM_003921.5(BCL10):c.410del (p.Asn137fs)	BCL10	Pathogenic	no assertion criteria provided
6257	NM_003921.5(BCL10):c.398dup (p.Ser134fs)	BCL10	Pathogenic	no assertion criteria provided
6258	NM_003921.5(BCL10):c.629AAG[2] (p.Glu212del)	BCL10	Pathogenic	no assertion criteria provided

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 8 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Somatic driver evidence (intOGen + CIViC, cohort fanout)

Gene	intOGen role	Cancer types	CIViC
EZH2	Act	ALL,AML,DLBCLNOS,ES,MLYM,NHL	CIViC #63
KMT2D	LoF	ACYC,ALL,ANSC,BCC,BL,BLADDER,BLCA,BRCA,CCRCC,CEAD,CESC,CHOL,CHRCC,CLLSLL,CSCC,DLBCLNOS,ESCA,GBM,HCC,HGGNOS,HNSC,LNM,LUSC,MBL,MLYM,NBL,NETNOS,NHL,NPC,NSCLC,OVT,PAAD,PANCREAS,PAST,PLMESO,PRAD,PRCC,PROSTATE,RCC,SACA,SCLC,SKCM,STAD,STOMACH,UCEC,UCS	CIViC #64
BCL2	Act	DLBCLNOS,MLYM,NHL	CIViC #59
BCL10	LoF	DLBCLNOS,MLYM	CIViC #7074

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
EZH2	Orphanet:3447	Weaver syndrome
KMT2D	Orphanet:2322	Kabuki syndrome
KMT2D	Orphanet:589856	Choanal atresia-athelia-hypothyroidism-delayed puberty-short stature syndrome
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
CELF2	Orphanet:442835	Non-specific early-onset epileptic encephalopathy
BCL10	Orphanet:52417	MALT lymphoma

Cohort genes → proteins

6 cohort genes, 6 distinct canonical proteins.

Evidence partition

Subset	Genes
gwas_only	2
civic_only	3
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
EZH2	HGNC:3527	ENSG00000106462	Q15910	Histone-lysine N-methyltransferase EZH2	civic_evidence
KMT2D	HGNC:7133	ENSG00000167548	O14686	Histone-lysine N-methyltransferase 2D	civic_evidence
BCL2	HGNC:990	ENSG00000171791	P10415	Apoptosis regulator Bcl-2	civic_evidence
NCOA5	HGNC:15909	ENSG00000124160	Q9HCD5	Nuclear receptor coactivator 5	gwas
CELF2	HGNC:2550	ENSG00000048740	O95319	CUGBP Elav-like family member 2	gwas
BCL10	HGNC:989	ENSG00000142867	O95999	B-cell lymphoma/leukemia 10	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
EZH2	Histone-lysine N-methyltransferase EZH2	Catalytic subunit of the PRC2/EED-EZH2 complex, a Polycomb group (PcG) complex that methylates ‘Lys-9’ (H3K9me) and ‘Lys-27’ (H3K27me) of histone H3, leading to transcriptional repression of the affected target gene.
KMT2D	Histone-lysine N-methyltransferase 2D	Histone methyltransferase that catalyzes methyl group transfer from S-adenosyl-L-methionine to the epsilon-amino group of ‘Lys-4’ of histone H3 (H3K4).
BCL2	Apoptosis regulator Bcl-2	Suppresses apoptosis in a variety of cell systems including factor-dependent lymphohematopoietic and neural cells.
NCOA5	Nuclear receptor coactivator 5	Nuclear receptor coregulator that can have both coactivator and corepressor functions.
CELF2	CUGBP Elav-like family member 2	RNA-binding protein implicated in the regulation of several post-transcriptional events.
BCL10	B-cell lymphoma/leukemia 10	Plays a key role in both adaptive and innate immune signaling by bridging CARD domain-containing proteins to immune activation.

Protein-family classification

Druggable: 1 · Difficult: 1 · Unknown: 4 · Druggable fraction: 0.17

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
Enzyme (other)	1	2.0×	0.539
Transcription factor	1	1.4×	0.539
Other/Unknown	4	1.2×	0.539

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
EZH2	Enzyme (other)	yes	2.1.1.356	SANT/Myb, SET_dom, EZH1/EZH2_N
KMT2D	Transcription factor	no		SET_dom, Znf_RING, Znf_PHD
BCL2	Other/Unknown	no		Bcl2-like, Bcl2_BH4, Bcl2/BclX
NCOA5	Other/Unknown	no		Anticodon-bd_dom_sf, Nuc_rcpt_coact/corep
CELF2	Other/Unknown	no		RRM_dom, Hud_Sxl_RNA, Nucleotide-bd_a/b_plait_sf
BCL10	Other/Unknown	no		CARD, DEATH-like_dom_sf, BCL10/E10

Expression context

Cohort genes with no expression data: 0.

6 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)	6
unknown	0

Top tissues across cohort

Tissue	Cohort genes
embryo	1
ganglionic eminence	1
ventricular zone	1
buccal mucosa cell	1
medial globus pallidus	1
sural nerve	1
calcaneal tendon	1
dorsal motor nucleus of vagus nerve	1
superficial temporal artery	1
cortical plate	1
ileal mucosa	1
oviduct epithelium	1
CA1 field of hippocampus	1
entorhinal cortex	1
orbitofrontal cortex	1
esophagus squamous epithelium	1
mucosa of sigmoid colon	1
squamous epithelium	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
EZH2	216	ubiquitous	marker	ganglionic eminence, ventricular zone, embryo
KMT2D	272	ubiquitous	marker	buccal mucosa cell, medial globus pallidus, sural nerve
BCL2	275	ubiquitous	marker	dorsal motor nucleus of vagus nerve, superficial temporal artery, calcaneal tendon
NCOA5	231	ubiquitous	marker	oviduct epithelium, ileal mucosa, cortical plate
CELF2	289	ubiquitous	marker	CA1 field of hippocampus, orbitofrontal cortex, entorhinal cortex
BCL10	280	ubiquitous	marker	esophagus squamous epithelium, mucosa of sigmoid colon, squamous epithelium

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
EZH2	9,646
BCL2	8,343
KMT2D	3,223
NCOA5	2,462
BCL10	1,873
CELF2	1,428

Structural data

PDB: 6 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
BCL2	P10415	55
EZH2	Q15910	38
KMT2D	O14686	11
CELF2	O95319	7
BCL10	O95999	5
NCOA5	Q9HCD5	4

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 73. Enrichment computed across 6 evidence-associated genes (4 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 4 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
PKMTs methylate histone lysines	2	80.4×	0.017	EZH2, KMT2D
The NLRP1 inflammasome	1	951.7×	0.026	BCL2
Activation of anterior HOX genes in hindbrain development during early embryogenesis	2	45.7×	0.026	EZH2, KMT2D
Loss of Function of KMT2D in MLL4 Complex Formation in Kabuki Syndrome	1	571.0×	0.032	KMT2D
BH3-only proteins associate with and inactivate anti-apoptotic BCL-2 members	1	317.2×	0.038	BCL2
Inflammasomes	1	285.5×	0.038	BCL2
NFE2L2 regulating tumorigenic genes	1	237.9×	0.038	BCL2
Downstream signaling events of B Cell Receptor (BCR)	1	203.9×	0.038	BCL10
Protein ubiquitination	1	203.9×	0.038	BCL10
Activation of BAD and translocation to mitochondria	1	190.3×	0.038	BCL2
Regulation of MITF-M-dependent genes involved in apoptosis	1	158.6×	0.041	BCL2
Activation of BH3-only proteins	1	124.1×	0.041	BCL2
TCR signaling	1	124.1×	0.041	BCL10
Activation of HOX genes during differentiation	1	109.8×	0.041	KMT2D
Estrogen-dependent nuclear events downstream of ESR-membrane signaling	1	109.8×	0.041	BCL2
Innate Immune System	2	12.8×	0.041	BCL10, BCL2
Nucleotide-binding domain, leucine rich repeat containing receptor (NLR) signaling pathways	1	89.2×	0.046	BCL2
Signaling by the B Cell Receptor (BCR)	1	86.5×	0.046	BCL10
Nuclear events mediated by NFE2L2	1	84.0×	0.046	BCL2
Intrinsic Pathway for Apoptosis	1	73.2×	0.047	BCL2
Transcriptional Regulation by E2F6	1	73.2×	0.047	EZH2
Fc epsilon receptor (FCERI) signaling	1	68.0×	0.048	BCL10
Formation of WDR5-containing histone-modifying complexes	1	66.4×	0.048	KMT2D
C-type lectin receptors (CLRs)	1	59.5×	0.048	BCL10
Deactivation of the beta-catenin transactivating complex	1	58.3×	0.048	KMT2D
Epigenetic regulation of adipogenesis genes by MLL3 and MLL4 complexes	1	53.9×	0.048	KMT2D
Activation of NF-kappaB in B cells	1	49.2×	0.048	BCL10
Epigenetic regulation of gene expression by MLL3 and MLL4 complexes	1	49.2×	0.048	KMT2D
E3 ubiquitin ligases ubiquitinate target proteins	1	48.4×	0.048	BCL10
MITF-M-dependent gene expression	1	45.3×	0.048	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 6 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
B cell apoptotic process	2	468.1×	9e-04	BCL10, BCL2
T cell apoptotic process	2	432.1×	9e-04	BCL10, BCL2
negative regulation of G1/S transition of mitotic cell cycle	2	119.5×	0.008	EZH2, BCL2
melanin metabolic process	1	2808.7×	0.008	BCL2
obsolete negative regulation of cellular pH reduction	1	2808.7×	0.008	BCL2
pigment granule organization	1	2808.7×	0.008	BCL2
beta-catenin-TCF complex assembly	1	2808.7×	0.008	KMT2D
heterochromatin formation	2	85.1×	0.008	EZH2, KMT2D
G1/S transition of mitotic cell cycle	2	66.9×	0.008	EZH2, BCL2
methylation	2	56.7×	0.010	EZH2, KMT2D
positive regulation of cell population proliferation	3	16.8×	0.010	EZH2, KMT2D, BCL2
regulation of nitrogen utilization	1	1404.3×	0.010	BCL2
hepatocyte homeostasis	1	1404.3×	0.010	EZH2
CD8-positive, alpha-beta T cell lineage commitment	1	1404.3×	0.010	BCL2
negative regulation of retinal cell programmed cell death	1	1404.3×	0.010	BCL2
regulation of gliogenesis	1	936.2×	0.010	EZH2
positive regulation of neuron maturation	1	936.2×	0.010	BCL2
cochlear nucleus development	1	936.2×	0.010	BCL2
positive regulation of lymphotoxin A production	1	936.2×	0.010	BCL10
cellular response to trichostatin A	1	936.2×	0.010	EZH2
regulation of viral genome replication	1	936.2×	0.010	BCL2
retinal cell programmed cell death	1	936.2×	0.010	BCL2
dendritic cell apoptotic process	1	936.2×	0.010	BCL2
oocyte growth	1	702.2×	0.010	KMT2D
negative regulation of mature B cell apoptotic process	1	702.2×	0.010	BCL10
regulation of glycoprotein biosynthetic process	1	702.2×	0.010	BCL2
negative regulation of striated muscle cell differentiation	1	702.2×	0.010	EZH2
regulation of kidney development	1	702.2×	0.010	EZH2
response to tetrachloromethane	1	702.2×	0.010	EZH2
B cell lineage commitment	1	561.7×	0.011	BCL2

Therapeutics

Drugs indicated for this disease

7 approved, 39 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)
Duvelisib	Approved (phase 4)
Epcoritamab	Approved (phase 4)
INTERFERON ALFA-2B	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)
Hyaluronidase	Phase 3 (in late-stage trials)
INDIUM IN 111 IBRITUMOMAB TIUXETAN	Phase 3 (in late-stage trials)
Ibritumomab Tiuxetan	Phase 3 (in late-stage trials)
Ibrutinib	Phase 3 (in late-stage trials)
Idelalisib	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)
Mitoxantrone	Phase 3 (in late-stage trials)
Odronextamab	Phase 3 (in late-stage trials)
Ofatumumab	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): Abexinostat, Acalabrutinib, Acetaminophen, Atezolizumab, Azacitidine, Bortezomib, Brentuximab Vedotin, Busulfan, Carfilzomib, Copanlisib, Cyclosporine, Daratumumab, Diphenhydramine, Entospletinib, Enzastaurin, Epigalocatechin Gallate, Garlic, Golcadomide, Icosapent, Interferon Alfa, Isosorbide, Ixabepilone, Ixazomib, Loncastuximab Tesirine, Maraviroc, Metformin, Mycophenolate Mofetil, Nivolumab, Oblimersen Sodium, Orelabrutinib, Oxaliplatin, Pembrolizumab, Polatuzumab Vedotin, Quercetin, Resveratrol, Romidepsin, Sargramostim, Selenomethionine, Tacrolimus Anhydrous, Thalidomide, Tositumomab, Ublituximab, Umbralisib, Venetoclax, Vitespen, Vorinostat.

Drug target analysis

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

Druggability breadth: 4 of 6 evidence-associated genes (67%) 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
EZH2	TAZEMETOSTAT
BCL2	IXABEPILONE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
BCL2	14	4
EZH2	6	4
KMT2D	0	0
NCOA5	0	0
CELF2	0	0
BCL10	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
TAZEMETOSTAT	4	EZH2
IXABEPILONE	4	BCL2
VENETOCLAX	4	BCL2
EPIGALOCATECHIN GALLATE	3	BCL2
OBATOCLAX	3	BCL2
NAVITOCLAX	3	BCL2
GOSSYPOL	3	BCL2
SONROTOCLAX	3	BCL2
MEVROMETOSTAT	2	EZH2
VALEMETOSTAT	2	EZH2
ZEPRUMETOSTAT	2	EZH2
CHLORCYCLIZINE	2	BCL2
FORMONONETIN	2	BCL2
LACUTOCLAX	2	BCL2
GSK2816126	1	EZH2
CPI-1205	1	EZH2
ABT 737	1	BCL2
VOB-560	1	BCL2
AZD-5991	1	BCL2
TAPOTOCLAX	1	BCL2

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
EZH2	839	Binding:833, Functional:6
BCL2	446	Binding:418, Functional:23, Toxicity:3, ADMET:2
KMT2D	11	Binding:11
CELF2	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
EZH2	2.1.1.356	[histone H3]-lysine27 N-trimethyltransferase

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
EZH2	839
BCL2	446

Pharmacogenomics

Cohort genes with a PharmGKB record: 6; with CPIC/DPWG dosing guidelines: 0.

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

Drug repurposing candidates

19 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
MEVROMETOSTAT	2	EZH2
VALEMETOSTAT	2	EZH2
ZEPRUMETOSTAT	2	EZH2
CHLORCYCLIZINE	2	BCL2
FORMONONETIN	2	BCL2
LACUTOCLAX	2	BCL2
GSK2816126	1	EZH2
CPI-1205	1	EZH2
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)	2	EZH2, BCL2
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	4	KMT2D, NCOA5, CELF2, BCL10

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
KMT2D	11	—
NCOA5	0	—
CELF2	1	—
BCL10	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 530.

Phase distribution (across all retrieved trials)

Phase	Trials
PHASE2	166
PHASE1	127
Not specified	86
PHASE1/PHASE2	79
PHASE3	59
EARLY_PHASE1	8
PHASE2/PHASE3	3
PHASE4	2

Top trials by phase / activity

NCT	Phase	Status	Title
NCT03817853	PHASE4	COMPLETED	An Open-Label, Single Arm Study of Obinutuzumab Short Duration Infusion in Patients With Previously Untreated Advanced Follicular Lymphoma
NCT04842318	PHASE4	UNKNOWN	Rituximab Maintenance Treatment of Newly Diagnosed Follicular Lymphoma After BR or RCHOP or R2: a Multicenter Clinical Study
NCT00877214	PHASE3	ACTIVE_NOT_RECRUITING	Significance of Duration of Maintenance Therapy With Rituximab in Non-Hodgkin Lymphomas
NCT01804686	PHASE3	RECRUITING	A Long-term Extension Study of PCI-32765 (Ibrutinib)
NCT02390869	PHASE3	ACTIVE_NOT_RECRUITING	Rituximab and Lenalidomide vs Rituximab Alone as Maintenance After R-chemoterapy for Relapsed/Refractory FL Patients
NCT04224493	PHASE3	ACTIVE_NOT_RECRUITING	A Study to Assess the Efficacy, Safety, Pharmacodynamics, and Pharmacokinetics of Tazemetostat in Combination With Lenalidomide Plus Rituximab Versus Placebo in Combination With Lenalidomide Plus Rituximab in Adult Patients at Least 18 Years of Age With Relapsed/Refractory Follicular Lymphoma.
NCT04680052	PHASE3	ACTIVE_NOT_RECRUITING	A Phase 3 Study to Assess Efficacy and Safety of Tafasitamab Plus Lenalidomide and Rituximab Compared to Placebo Plus Lenalidomide and Rituximab in Patients With Relapsed/Refractory (R/R) Follicular Lymphoma or Marginal Zone Lymphoma.
NCT05058404	PHASE3	ACTIVE_NOT_RECRUITING	Shortened vs Standard Chemotherapy Combined With Immunotherapy for the Initial Treatment of Patients With High Tumor Burden Follicular Lymphoma
NCT05409066	PHASE3	ACTIVE_NOT_RECRUITING	Study of Subcutaneous Epcoritamab in Combination With Intravenous Rituximab and Oral Lenalidomide (R2) to Assess Adverse Events and Change in Disease Activity in Adult Participants With Follicular Lymphoma
NCT05888493	PHASE3	ACTIVE_NOT_RECRUITING	A Phase III Trial Comparing Tisagenlecleucel to Standard of Care (SoC) in Adult Participants With r/r Follicular Lymphoma
NCT05929222	PHASE3	RECRUITING	Comparison Between Local Radiotherapy Alone or Combined With Obinutuzumab in Early Stage Follicular Lymphoma: the GAZEBO Trial From the Fondazione Italiana Linfomi
NCT06091254	PHASE3	RECRUITING	A Trial to Learn if Odronextamab is Safe and Well-Tolerated and How Well it Works Compared to Rituximab Combined With Different Types of Chemotherapy for Adult Participants With Previously Untreated Follicular Lymphoma
NCT06097364	PHASE3	ACTIVE_NOT_RECRUITING	A Trial to Learn if Odronextamab Combined With Chemotherapy is Safe and Well-Tolerated and How Well it Works Compared to Rituximab Combined With Chemotherapy for Adult Participants With Follicular Lymphoma
NCT06191744	PHASE3	RECRUITING	Study of Subcutaneous Epcoritamab in Combination With Intravenous Rituximab and Oral Lenalidomide (R2) to Assess Adverse Events and Change in Disease Activity in Adult Participants With Previously Untreated Follicular Lymphoma
NCT06284122	PHASE3	RECRUITING	Study of Mosunetuzumab Plus Lenalidomide Compared to Anti-CD20 Anti-body + Chemotherapy in Follicular Lymphoma FLIPI2-5
NCT06911502	PHASE3	RECRUITING	A Study to Compare the Efficacy and Safety of Golcadomide in Combination With Rituximab (Golca + R) vs Investigator’s Choice in Participants With Relapsed/Refractory Follicular Lymphoma Who Have Received at Least 1 Prior Line of Systemic Therapy (GOLSEEK-4)
NCT07029217	PHASE3	RECRUITING	A Study of Reduced Dose Radiation Therapy for People With B-Cell Lymphomas
NCT07187960	PHASE3	NOT_YET_RECRUITING	Evaluation of the Efficacy and Safety of TQB2825 Injection Compared to Immunotherapy in the Treatment of Recurrent/Refractory Follicular Lymphoma
NCT07502118	PHASE2/PHASE3	RECRUITING	NexCAR19 (Talikabtagene Autoleucel) in Relapsed/Refractory B-Cell Malignancies (NexCAR19)
NCT07562022	PHASE3	NOT_YET_RECRUITING	A Study to Evaluate the Safety and Efficacy of SCTB35 in Combination With Lenalidomide in Patients With Relapsed or Refractory Follicular Lymphoma
NCT00060671	PHASE3	TERMINATED	Comparative Trial for Pixantrone in Combination With Rituximab in Indolent Non-Hodgkin’s Lymphoma
NCT00096460	PHASE2/PHASE3	TERMINATED	Autologous or Donor Stem Cell Transplantation in Treating Patients With Recurrent Non-Hodgkin’s Lymphoma (BMT CTN 0202)
NCT00115700	PHASE3	COMPLETED	Radiotherapy Versus Radiotherapy Plus Chemotherapy in Early Stage Follicular Lymphoma
NCT00140569	PHASE3	COMPLETED	Randomized Study for Patients With Follicular Lymphoma Needing Treatment
NCT00140582	PHASE3	COMPLETED	Primary Rituximab and Maintenance
NCT00317096	PHASE3	UNKNOWN	FCM Versus R-FCM Followed by R-Maintenance or Observation Only
NCT00319332	PHASE3	WITHDRAWN	A Comparative Study Of Iodine I 131 Tositumomab Therapeutic Regimen Versus Ibritumomab Tiuxetan Therapeutic Regimen
NCT00384111	PHASE3	TERMINATED	Phase 3 Study of Zevalin Following R-CVP in Previously Untreated Patients With Follicular Non Hodgkin’s Lymphoma (NHL)
NCT00435955	PHASE3	UNKNOWN	Comparison of High-Dose Chemotherapy + Rituximab and CHOP + Rituximab in High-Risk Follicular Lymphoma
NCT00562965	PHASE3	TERMINATED	Study Comparing Inotuzumab Ozogamicin In Combination With Rituximab Versus Defined Investigator’s Choice In Follicular Non-Hodgkin’s Lymphoma (NHL)
NCT00696735	PHASE3	COMPLETED	High-Dose Therapy Treatment in Patients With Follicular Lymphoma
NCT00774826	PHASE3	UNKNOWN	Multicentric Study, Three Randomized Arms (R-CVP vs R-CHOP vs R-FM),for Patients With Stage II-IV Follicular Lymphoma
NCT00801281	PHASE3	COMPLETED	First-line R-CVP vs R-CHOP Induction Immunochemotherapy for Indolent Lymphoma and R Maintenance.
NCT00991211	PHASE3	COMPLETED	Bendamustine Plus Rituximab Versus CHOP Plus Rituximab
NCT01077518	PHASE3	TERMINATED	Ofatumumab Bendamustine Combination Compared With Bendamustine Monotherapy in Indolent B-cell NHL Unresponsive to Rituxtherapy
NCT01303887	PHASE3	COMPLETED	A Trial Looking at Rituximab and Chemotherapy as a Treatment for Follicular Lymphoma in Elderly Patients
NCT01419665	PHASE3	COMPLETED	GP2013 in the Treatment of Patients With Previously Untreated, Advanced Stage Follicular Lymphoma (ASSIST_FL)
NCT01476787	PHASE3	COMPLETED	Combined Rituximab and Lenalidomide Treatment for Untreated Patients With Follicular Lymphoma
NCT01510184	PHASE3	TERMINATED	Study of Zevalin Versus Observation in Participants at Least 60 Years Old With Newly Diagnosed Diffuse Large B-cell Lymphoma in Positron Emission Tomography (PET)-Negative Complete Remission After Rituximab-Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone (R-CHOP) or R-CHOP-like Therapy
NCT01597778	PHASE3	COMPLETED	Double Cord Versus Haploidentical (BMT CTN 1101)

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
CYCLOPHOSPHAMIDE ANHYDROUS	4	53
TAZEMETOSTAT	4	15
BENDAMUSTINE	4	12
IDELALISIB	4	12
EPCORITAMAB	4	10
IBRUTINIB	4	9
MOSUNETUZUMAB	4	9
OBINUTUZUMAB	4	8
UMBRALISIB	4	7
VINCRISTINE	4	7
DUVELISIB	4	6
OFATUMUMAB	4	6
UBLITUXIMAB	4	6
DOXORUBICIN	4	5
MITOXANTRONE	4	5
RITUXIMAB	4	4
TAFASITAMAB	4	4
BORTEZOMIB	4	3
FLUDARABINE PHOSPHATE	4	3
TISAGENLECLEUCEL	4	3
YTTRIUM Y 90 IBRITUMOMAB TIUXETAN	4	3
LENALIDOMIDE	4	2
FILGRASTIM	4	1
INOTUZUMAB OZOGAMICIN	4	1
METHYLPREDNISOLONE	4	1
PREDNISOLONE	4	1
PREDNISONE	4	1
GOLCADOMIDE	3	5
ZANDELISIB	3	4
FLUDARABINE	3	3

Precision-medicine subtype map (CIViC)

Drug × molecular subtype: 5 predictive associations from 7 curated evidence items; also 6 oncogenic, 3 diagnostic, 2 prognostic.

Molecular subtype	Therapy	Effect	Level	CIViC
EZH2 Activating Mutation	Tazemetostat	Sensitivity/Response	CIViC A	EID9709 +1
CREBBP HAT mutation	MTOR Inhibitor	Sensitivity/Response	CIViC B	EID12290
EZH2 Y646S OR EZH2 Y646F OR EZH2 Y646H OR EZH2 Y646C OR EZH2 Y646N OR EZH2 A692V OR EZH2 A682G	Tazemetostat	Sensitivity/Response	CIViC B	EID11109
BCL2 F104I	Venetoclax	Resistance	CIViC C	EID8375 +1
EZH2 A682G	Tazemetostat	Sensitivity/Response	CIViC D	EID12877