Mantle cell lymphoma

Summary

Mantle cell lymphoma (MONDO:0018876) is a cancer with 5 cohort genes (5 CIViC-evidence somatic drivers; 3 ClinVar predisposition records) and 689 clinical trials. Molecularly, CCND1 Overexpression confers sensitivity to Palbociclib in Mantle Cell Lymphoma (CIViC Level B); 5 further subtype–drug associations are mapped below. Top therapeutic interventions include ibrutinib, acalabrutinib, and zanubrutinib.

At a glance

• Classification: Cancer
• Prevalence: 1-9 / 100 000 (Europe) [Orphanet-validated]
• Cohort genes: 5
• ClinVar variants: 3
• Phenotypes (HPO): 9
• Clinical trials: 689
• Precision-medicine evidence (CIViC): 6 subtype–drug associations

Clinical features

Epidemiology

Prevalence records

3 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Point prevalence	1-9 / 100 000	3.5	Europe	Validated
Annual incidence	1-9 / 1 000 000	0.8	United States	Validated
Annual incidence	1-9 / 100 000	1.05	France	Validated

Signs & symptoms

Clinical features (HPO)

9 HPO clinical features (Orphanet curated; top 9 by frequency):

HPO ID	Term	Frequency
HP:0002716	Lymphadenopathy	Very frequent (80-99%)
HP:0012191	B-cell lymphoma	Very frequent (80-99%)
HP:0001744	Splenomegaly	Frequent (30-79%)
HP:0001824	Weight loss	Frequent (30-79%)
HP:0002039	Anorexia	Frequent (30-79%)
HP:0005561	Abnormality of bone marrow cell morphology	Frequent (30-79%)
HP:0012378	Fatigue	Frequent (30-79%)
HP:0001945	Fever	Frequent (30-79%)
HP:0011024	Abnormality of the gastrointestinal tract	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	mantle cell lymphoma
Mondo ID	MONDO:0018876
EFO	EFO:1001469
MeSH	D020522
Orphanet	52416
DOID	DOID:0050746
ICD-10-CM	C83.1
ICD-11	1804127841
NCIT	C4337
SNOMED CT	443487006
UMLS	C4721414
MedGen	1668377
GARD	0006969
MedDRA	10061275
NORD	1399
Is cancer (heuristic)	yes

Also known as: classical mantle cell lymphoma · LCM · lymphoma, mantle cell · mantle cell lymphoma · mantle zone lymphoma · MCL

Data availability: 3 ClinVar variants · 34 cell lines.

Disease family

An umbrella term covering 2 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › immune system disorder › leukocyte disorder › B-cell neoplasm › B-cell non-Hodgkin lymphoma › aggressive B-cell non-Hodgkin lymphoma › mantle cell lymphoma

Related subtypes (5): Burkitt lymphoma, high grade B-cell lymphoma with MYC and/ or BCL2 and/or BCL6 rearrangement, diffuse large B-cell lymphoma, B-cell prolymphocytic leukemia, precursor B-cell acute lymphoblastic leukemia

Subtypes (2): gastric mantle cell lymphoma, splenic mantle cell lymphoma

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

3 retrieved; paginated sample, class counts are floors:

2 pathogenic, 1 uncertain significance

ClinVar	Variant (HGVS)	Gene	Classification	Review
3040	NM_000051.4(ATM):c.7251_7253dup (p.Lys2418_Arg2419insLys)	ATM	Pathogenic	no assertion criteria provided
3041	NM_000051.4(ATM):c.4081C>T (p.Gln1361Ter)	ATM	Pathogenic	criteria provided, multiple submitters, no conflicts
3039	NM_000051.4(ATM):c.7268A>G (p.Glu2423Gly)	ATM	Uncertain significance	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 36 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Somatic driver evidence (intOGen + CIViC, cohort fanout)

Gene	intOGen role	Cancer types	CIViC
ATM	LoF	BLCA,BRCA,CCRCC,CHOL,CLLSLL,COAD,COADREAD,ESCA,HCC,LUAD,LUSC,MEL,NSCLC,PAAD,PANCREAS,PANET,PCM,PLMESO,PRAD,PROSTATE,STAD,UCEC,UTUC,WDTC	CIViC #69
ZEB1	Act	GBM,LUAD,LUSC,NPC,PCM,SCLC	CIViC #5649
TP53	LoF	ACC,ALL,AML,ANGS,ANSC,BCC,BL,BLADDER,BLCA,BRCA,CCRCC,CEAD,CESC,CHOL,CHRCC,CLLSLL,COAD,COADREAD,CSCC,DLBCLNOS,EGC,ES,ESCA,ESCC,GB,GBC,GBM,GIST,HCC,HGGNOS,HNSC,LGGNOS,LIPO,LMS,LNM,LUAD,LUSC,MBL,MEL,MLYM,MT,NBL,NETNOS,NHL,NPC,NSCLC,OS,OVT,PAAD,PANCREAS,PAST,PCM,PLMESO,PRAD,PRCC,PROSTATE,RCC,READ,SACA,SARCNOS,SCLC,SIC,SKCM,SKIN,SOFT_TISSUE,STAD,STOMACH,THYM,UCEC,UCS,UTUC,VULVA,WDTC,WT	CIViC #45
CCND1	Act	HNSC,PCM,UCEC	CIViC #8
NOTCH1	LoF	ALL,ANGS,BCC,BLCA,BRCA,CESC,CHOL,CLLSLL,CSCC,DLBCLNOS,ESCA,HNSC,LGGNOS,LUAD,LUSC,MBL,MEL,MGCT,NPC,NSCLC,OVT,READ,SACA,SCLC,SKIN,VULVA	CIViC #50

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
ATM	Orphanet:100	Ataxia-telangiectasia
ATM	Orphanet:1331	Familial prostate cancer
ATM	Orphanet:145	Hereditary breast and/or ovarian cancer syndrome
ATM	Orphanet:227535	Hereditary breast cancer
ATM	Orphanet:370109	Ataxia-telangiectasia variant
ATM	Orphanet:440437	Familial colorectal cancer Type X
ATM	Orphanet:52416	Mantle cell lymphoma
ATM	Orphanet:67038	B-cell chronic lymphocytic leukemia
ZEB1	Orphanet:98973	Posterior polymorphous corneal dystrophy
ZEB1	Orphanet:98974	Fuchs endothelial corneal dystrophy
TP53	Orphanet:1333	Familial pancreatic carcinoma
TP53	Orphanet:145	Hereditary breast and/or ovarian cancer syndrome
TP53	Orphanet:1501	Adrenocortical carcinoma
TP53	Orphanet:210159	Adult hepatocellular carcinoma
TP53	Orphanet:251576	Gliosarcoma
TP53	Orphanet:251579	Giant cell glioblastoma
TP53	Orphanet:251899	Choroid plexus carcinoma
TP53	Orphanet:2807	Papilloma of choroid plexus
TP53	Orphanet:293199	Pleomorphic rhabdomyosarcoma
TP53	Orphanet:3318	Essential thrombocythemia
TP53	Orphanet:524	Li-Fraumeni syndrome
TP53	Orphanet:52688	Myelodysplastic syndrome
TP53	Orphanet:585909	B-lymphoblastic leukemia/lymphoma with t(9;22)(q34.1;q11.2)
TP53	Orphanet:667662	Breast implant-associated anaplastic large cell lymphoma
TP53	Orphanet:668	Osteosarcoma
TP53	Orphanet:67038	B-cell chronic lymphocytic leukemia
TP53	Orphanet:70573	Small cell lung cancer
TP53	Orphanet:96253	Cushing disease
TP53	Orphanet:99756	Alveolar rhabdomyosarcoma
TP53	Orphanet:99757	Embryonal rhabdomyosarcoma
CCND1	Orphanet:29073	Multiple myeloma
CCND1	Orphanet:52416	Mantle cell lymphoma
CCND1	Orphanet:67038	B-cell chronic lymphocytic leukemia
CCND1	Orphanet:892	Von Hippel-Lindau disease
NOTCH1	Orphanet:402075	Familial bicuspid aortic valve
NOTCH1	Orphanet:974	Adams-Oliver syndrome

Cohort genes → proteins

5 cohort genes, 5 distinct canonical proteins.

Evidence partition

Subset	Genes
civic_only	4
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
ATM	HGNC:795	ENSG00000149311	Q13315	Serine-protein kinase ATM	clinvar,civic_evidence
ZEB1	HGNC:11642	ENSG00000148516	P37275	Zinc finger E-box-binding homeobox 1	civic_evidence
TP53	HGNC:11998	ENSG00000141510	P04637	Cellular tumor antigen p53	civic_evidence
CCND1	HGNC:1582	ENSG00000110092	P24385	G1/S-specific cyclin-D1	civic_evidence
NOTCH1	HGNC:7881	ENSG00000148400	P46531	Neurogenic locus notch homolog protein 1	civic_evidence

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
ATM	Serine-protein kinase ATM	Serine/threonine protein kinase which activates checkpoint signaling upon double strand breaks (DSBs), apoptosis and genotoxic stresses such as ionizing ultraviolet A light (UVA), thereby acting as a DNA damage sensor.
ZEB1	Zinc finger E-box-binding homeobox 1	Acts as a transcriptional repressor.
TP53	Cellular tumor antigen p53	Multifunctional transcription factor that induces cell cycle arrest, DNA repair or apoptosis upon binding to its target DNA sequence.
CCND1	G1/S-specific cyclin-D1	Regulatory component of the cyclin D1-CDK4 (DC) complex that phosphorylates and inhibits members of the retinoblastoma (RB) protein family including RB1 and regulates the cell-cycle during G(1)/S transition.
NOTCH1	Neurogenic locus notch homolog protein 1	Functions as a receptor for membrane-bound ligands Jagged-1 (JAG1), Jagged-2 (JAG2) and Delta-1 (DLL1) to regulate cell-fate determination.

Protein-family classification

Druggable: 1 · Difficult: 3 · Unknown: 1 · Druggable fraction: 0.2

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
Kinase	1	5.5×	0.336
Transcription factor	2	3.3×	0.336
Scaffold/PPI	1	3.5×	0.344
Other/Unknown	1	0.4×	0.983

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
ATM	Kinase	yes	2.7.11.1	PI3/4_kinase_cat_dom, PIK-rel_kinase_FAT, FATC_dom
ZEB1	Transcription factor	no		HD, Di19_Zn-bd, Homeodomain-like_sf
TP53	Transcription factor	no		p53_tumour_suppressor, p53-like_TF_DNA-bd_sf, p53_tetrameristn
CCND1	Other/Unknown	no		Cyclin_C-dom, Cyclin_N, Cyclin-like_dom
NOTCH1	Scaffold/PPI	no		EGF-type_Asp/Asn_hydroxyl_site, EGF, Notch_dom

Expression context

Cohort genes with no expression data: 0.

5 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)	5
unknown	0

Top tissues across cohort

Tissue	Cohort genes
colonic epithelium	3
calcaneal tendon	2
ventricular zone	2
corpus callosum	1
tendon	1
ganglionic eminence	1
tendon of biceps brachii	1
endometrium epithelium	1
stromal cell of endometrium	1
upper arm skin	1
visceral pleura	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
ATM	286	ubiquitous	marker	calcaneal tendon, colonic epithelium, corpus callosum
ZEB1	287	ubiquitous	marker	calcaneal tendon, colonic epithelium, tendon
TP53	223	ubiquitous	marker	ventricular zone, ganglionic eminence, tendon of biceps brachii
CCND1	280	ubiquitous	marker	endometrium epithelium, stromal cell of endometrium, upper arm skin
NOTCH1	272	ubiquitous	marker	ventricular zone, colonic epithelium, visceral pleura

Protein interactions among cohort

Intra-cohort edges: 4.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
TP53	22,736
CCND1	8,328
NOTCH1	7,411
ATM	7,383
ZEB1	4,171

Intra-cohort edges

A	B	Sources
ATM	NOTCH1	intact
ATM	TP53	biogrid_interaction, string_interaction
ATM	ZEB1	biogrid_interaction
CCND1	TP53	string_interaction

Structural data

PDB: 5 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
TP53	P04637	313
NOTCH1	P46531	29
ATM	Q13315	14
CCND1	P24385	11
ZEB1	P37275	1

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 162. Enrichment computed across 5 evidence-associated genes (5 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 5 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
TP53 Regulates Transcription of Caspase Activators and Caspases	2	380.7×	5e-04	ATM, TP53
Pre-NOTCH Transcription and Translation	3	73.7×	5e-04	TP53, CCND1, NOTCH1
Interleukin-4 and Interleukin-13 signaling	3	61.7×	5e-04	ZEB1, TP53, CCND1
Stabilization of p53	2	304.5×	7e-04	ATM, TP53
TP53 Regulates Transcription of Genes Involved in Cytochrome C Release	2	217.5×	9e-04	ATM, TP53
Regulation of TP53 Activity through Methylation	2	217.5×	9e-04	ATM, TP53
Regulation of TP53 Degradation	2	117.1×	0.002	ATM, TP53
Autodegradation of the E3 ubiquitin ligase COP1	2	106.2×	0.002	ATM, TP53
Transcriptional Regulation by VENTX	2	106.2×	0.002	TP53, CCND1
TP53 Regulates Transcription of DNA Repair Genes	2	72.5×	0.005	ATM, TP53
DNA Damage/Telomere Stress Induced Senescence	2	65.3×	0.005	ATM, TP53
Loss of function of TP53 in cancer due to loss of tetramerization ability	1	2284.0×	0.006	TP53
Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks	2	58.6×	0.006	ATM, TP53
G2/M Checkpoints	2	53.7×	0.006	ATM, TP53
G2/M DNA damage checkpoint	2	48.1×	0.007	ATM, TP53
Regulation of TP53 Activity through Phosphorylation	2	47.1×	0.007	ATM, TP53
Regulation of TP53 Expression	1	1142.0×	0.008	TP53
Transcriptional activation of cell cycle inhibitor p21	1	571.0×	0.016	TP53
Loss of Function of FBXW7 in Cancer and NOTCH1 Signaling	1	456.8×	0.017	NOTCH1
Defective LFNG causes SCDO3	1	456.8×	0.017	NOTCH1
Drug-mediated inhibition of CDK4/CDK6 activity	1	456.8×	0.017	CCND1
Activation of NOXA and translocation to mitochondria	1	380.7×	0.017	TP53
Pre-NOTCH Processing in the Endoplasmic Reticulum	1	380.7×	0.017	NOTCH1
Sensing of DNA Double Strand Breaks	1	380.7×	0.017	ATM
PTK6 Regulates Cell Cycle	1	380.7×	0.017	CCND1
Constitutive Signaling by NOTCH1 t(7;9)(NOTCH1:M1580_K2555) Translocation Mutant	1	326.3×	0.018	NOTCH1
RUNX3 regulates CDKN1A transcription	1	326.3×	0.018	TP53
Regulation of NFE2L2 gene expression	1	285.5×	0.020	NOTCH1
PI5P Regulates TP53 Acetylation	1	253.8×	0.022	TP53
Activation of PUMA and translocation to mitochondria	1	228.4×	0.022	TP53

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 5 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
negative regulation of glial cell proliferation	2	674.1×	7e-04	TP53, NOTCH1
cardiac septum morphogenesis	2	481.5×	7e-04	TP53, NOTCH1
mitotic G1 DNA damage checkpoint signaling	2	421.3×	7e-04	TP53, CCND1
replicative senescence	2	396.5×	7e-04	ATM, TP53
cellular response to hypoxia	3	72.7×	7e-04	TP53, CCND1, NOTCH1
response to X-ray	2	354.8×	7e-04	TP53, CCND1
cellular response to gamma radiation	2	240.7×	0.001	ATM, TP53
determination of adult lifespan	2	172.8×	0.002	ATM, TP53
negative regulation of transcription by RNA polymerase II	4	14.2×	0.002	ZEB1, TP53, CCND1, NOTCH1
DNA damage response	3	32.1×	0.002	ATM, TP53, CCND1
somitogenesis	2	149.8×	0.002	ATM, TP53
DNA damage response, signal transduction by p53 class mediator	2	143.4×	0.002	ATM, TP53
positive regulation of transcription by RNA polymerase II	4	11.9×	0.003	ATM, ZEB1, TP53, NOTCH1
cellular senescence	2	118.3×	0.003	ATM, TP53
positive regulation of neuron apoptotic process	2	108.7×	0.003	ATM, TP53
positive regulation of gene expression	3	23.2×	0.004	ATM, TP53, NOTCH1
coronary sinus valve morphogenesis	1	3370.4×	0.004	NOTCH1
Notch signaling pathway involved in regulation of secondary heart field cardioblast proliferation	1	3370.4×	0.004	NOTCH1
foregut morphogenesis	1	3370.4×	0.004	NOTCH1
regulation of mesenchymal cell proliferation	1	3370.4×	0.004	ZEB1
negative regulation of helicase activity	1	3370.4×	0.004	TP53
regulation of epithelial cell proliferation involved in prostate gland development	1	3370.4×	0.004	NOTCH1
venous endothelial cell differentiation	1	3370.4×	0.004	NOTCH1
cellular response to actinomycin D	1	3370.4×	0.004	TP53
regulation of intrinsic apoptotic signaling pathway by p53 class mediator	1	3370.4×	0.004	TP53
negative regulation of G1 to G0 transition	1	3370.4×	0.004	TP53
double-strand break repair	2	81.2×	0.004	ATM, TP53
neuron apoptotic process	2	74.1×	0.004	ATM, TP53
negative regulation of DNA-templated transcription	3	18.9×	0.004	ZEB1, TP53, NOTCH1
endocardium morphogenesis	1	1685.2×	0.005	NOTCH1

Therapeutics

Drugs indicated for this disease

7 approved, 22 in late-stage (phase 3) trials. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

Drug	Development status
Acalabrutinib	Approved (phase 4)
Brexucabtagene Autoleucel	Approved (phase 4)
Ibrutinib	Approved (phase 4)
Lenalidomide	Approved (phase 4)
Pirtobrutinib	Approved (phase 4)
Temsirolimus	Approved (phase 4)
Zanubrutinib	Approved (phase 4)
Bendamustine	Phase 3 (in late-stage trials)
Bortezomib	Phase 3 (in late-stage trials)
Carmustine	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)
Filgrastim	Phase 3 (in late-stage trials)
Fludarabine	Phase 3 (in late-stage trials)
Fludarabine Phosphate	Phase 3 (in late-stage trials)
Interferon Alfa	Phase 3 (in late-stage trials)
Melphalan	Phase 3 (in late-stage trials)
Mycophenolate Mofetil	Phase 3 (in late-stage trials)
Orelabrutinib	Phase 3 (in late-stage trials)
PEGINTERFERON ALFA-2B	Phase 3 (in late-stage trials)
Parsaclisib	Phase 3 (in late-stage trials)
Prednisone	Phase 3 (in late-stage trials)
Rituximab	Phase 3 (in late-stage trials)
Venetoclax	Phase 3 (in late-stage trials)
Vincristine	Phase 3 (in late-stage trials)

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): ANTINEOPLASTON A10, Abemaciclib, Axicabtagene Ciloleucel, Belinostat, Bevacizumab, Buparlisib, Busulfan, Carfilzomib, Chlorambucil, Cladribine, Copanlisib, Daratumumab, Entospletinib, Enzalutamide, Enzastaurin, Eprenetapopt, Etoposide Phosphate, Everolimus, Gemcitabine, Glofitamab, Hyaluronidase, Idelalisib, Ifosfamide, Isosorbide, Ixabepilone, Ixazomib, Ixazomib Citrate, Loncastuximab Tesirine, Methotrexate, Mitoxantrone, Navitoclax, Obinutuzumab, Ofatumumab, Pacritinib, Palbociclib, Pegfilgrastim, Polatuzumab Vedotin, Romidepsin, Sirolimus, Sonrotoclax, TOSITUMOMAB 131I, Tacrolimus Anhydrous, Tafasitamab, Tanespimycin, Thalidomide, Tipifarnib, Tocilizumab, Tositumomab, Ublituximab, Umbralisib, Vorinostat, YTTRIUM Y 90 IBRITUMOMAB TIUXETAN.

Drug target analysis

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

Druggability breadth: 4 of 5 evidence-associated genes (80%) 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
ATM	AMIODARONE HYDROCHLORIDE
TP53	NITROFURANTOIN
CCND1	PALBOCICLIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
TP53	196	4
ATM	35	4
CCND1	35	4
NOTCH1	1	2
ZEB1	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
AMIODARONE HYDROCHLORIDE	4	ATM, TP53
FURAZOLIDONE	4	ATM, TP53
ESTRADIOL ACETATE	4	ATM
NAFTIFINE HYDROCHLORIDE	4	ATM
METHYSERGIDE MALEATE	4	ATM
AMITRIPTYLINE HYDROCHLORIDE	4	ATM, TP53
XYLOMETAZOLINE HYDROCHLORIDE	4	ATM
FLUVOXAMINE MALEATE	4	ATM
ESTRADIOL VALERATE	4	ATM
PERMETHRIN	4	ATM
MITOTANE	4	ATM
TICLOPIDINE HYDROCHLORIDE	4	ATM
ENOXIMONE	4	ATM
METHYLENE BLUE ANHYDROUS	4	ATM
DITHIAZANINE IODIDE	4	ATM
ETHACRYNIC ACID	4	ATM, TP53
SECNIDAZOLE	4	ATM
MENADIONE	4	ATM, TP53
FENOFIBRATE	4	ATM
DIPYRIDAMOLE	4	ATM
NITROFURANTOIN	4	TP53
DIOSMIN	4	TP53
VERTEPORFIN	4	TP53
CANDESARTAN CILEXETIL	4	TP53
DIENESTROL	4	TP53
CLOTRIMAZOLE	4	TP53
COLCHICINE	4	TP53
NABUMETONE	4	TP53
SALMETEROL XINAFOATE	4	TP53
AMOXAPINE	4	TP53

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
TP53	869	Binding:775, ADMET:83, Functional:10, Toxicity:1
CCND1	576	Binding:574, Functional:1, ADMET:1
ATM	240	Binding:233, Functional:5, ADMET:2
NOTCH1	23	Binding:19, ADMET:4

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
ATM	2.7.11.1	non-specific serine/threonine protein kinase

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
ATM	240
TP53	869
CCND1	576

Pharmacogenomics

Cohort genes with a PharmGKB record: 5; 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)
AMIODARONE HYDROCHLORIDE	4	ATM, TP53
FURAZOLIDONE	4	ATM, TP53
ESTRADIOL ACETATE	4	ATM
NAFTIFINE HYDROCHLORIDE	4	ATM
METHYSERGIDE MALEATE	4	ATM
AMITRIPTYLINE HYDROCHLORIDE	4	ATM, TP53
XYLOMETAZOLINE HYDROCHLORIDE	4	ATM
FLUVOXAMINE MALEATE	4	ATM
ESTRADIOL VALERATE	4	ATM
PERMETHRIN	4	ATM
MITOTANE	4	ATM
TICLOPIDINE HYDROCHLORIDE	4	ATM
ENOXIMONE	4	ATM
METHYLENE BLUE ANHYDROUS	4	ATM
DITHIAZANINE IODIDE	4	ATM
ETHACRYNIC ACID	4	ATM, TP53
SECNIDAZOLE	4	ATM
MENADIONE	4	ATM, TP53
FENOFIBRATE	4	ATM
DIPYRIDAMOLE	4	ATM
NITROFURANTOIN	4	TP53
DIOSMIN	4	TP53
VERTEPORFIN	4	TP53
CANDESARTAN CILEXETIL	4	TP53
DIENESTROL	4	TP53
CLOTRIMAZOLE	4	TP53
COLCHICINE	4	TP53
NABUMETONE	4	TP53
SALMETEROL XINAFOATE	4	TP53
AMOXAPINE	4	TP53

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	3	ATM, TP53, CCND1
B	Phased (≥1) drug, not yet approved	1	NOTCH1
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	ZEB1

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
ZEB1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 689.

Phase distribution (across all retrieved trials)

Phase	Trials
PHASE2	262
PHASE1	182
PHASE1/PHASE2	113
Not specified	79
PHASE3	35
EARLY_PHASE1	13
PHASE4	3
PHASE2/PHASE3	2

Top trials by phase / activity

NCT	Phase	Status	Title
NCT07264894	PHASE4	NOT_YET_RECRUITING	ZSDT for the Treatment of R/R Mantle Cell Lymphoma After BTK Inhibitor Failure: a Multi-center Prospective Clinical Trial
NCT02858804	PHASE4	COMPLETED	EDOCH Alternating With DHAP for New Diagnosed Younger MCL
NCT03190330	PHASE4	COMPLETED	A Study to Assess Safety of ImbruvicaTM in Indian Participants With Chronic Lymphocytic Leukemia or Mantle Cell Lymphoma Who Have Received at Least One Prior Therapy or Chronic Lymphocytic Leukemia With 17p Deletion
NCT01804686	PHASE3	RECRUITING	A Long-term Extension Study of PCI-32765 (Ibrutinib)
NCT02858258	PHASE3	RECRUITING	ASCT After a Rituximab/Ibrutinib/Ara-c Containing iNduction in Generalized Mantle Cell Lymphoma
NCT02972840	PHASE3	ACTIVE_NOT_RECRUITING	A Study of BR Alone Versus in Combination With Acalabrutinib in Subjects With Previously Untreated MCL
NCT03267433	PHASE3	ACTIVE_NOT_RECRUITING	Rituximab With or Without Stem Cell Transplant in Treating Patients With Minimal Residual Disease-Negative Mantle Cell Lymphoma in First Complete Remission
NCT04662255	PHASE3	ACTIVE_NOT_RECRUITING	Study of BTK Inhibitor LOXO-305 Versus Approved BTK Inhibitor Drugs in Patients With Mantle Cell Lymphoma (MCL)
NCT05976763	PHASE3	RECRUITING	Testing Continuous Versus Intermittent Treatment With the Study Drug Zanubrutinib for Older Patients With Previously Untreated Mantle Cell Lymphoma
NCT06363994	PHASE3	RECRUITING	A Global Phase 3 Study of Orelabrutinib+BR Vs.BR in Pts with TN MCL
NCT06496308	PHASE3	RECRUITING	Bendamustine and Rituximab With or Without Orelabrutinib in MCL Treatment
NCT06742996	PHASE3	RECRUITING	A Study to Investigate the Efficacy and Safety of Sonrotoclax Plus Zanubrutinib Compared With Placebo Plus Zanubrutinib in Adults With Relapsed/Refractory Mantle Cell Lymphoma (CELESTIAL-RRMCL)
NCT07377578	PHASE3	RECRUITING	A Study of Rocbrutinib Versus Investigator’s Choice of BTK Inhibitors in Patients With Relapsed or Refractory Mantle Cell Lymphoma
NCT00075478	PHASE3	COMPLETED	Total-Body Irradiation With or Without Fludarabine Phosphate Followed By Donor Stem Cell Transplant in Treating Patients With Hematologic Cancer
NCT00209209	PHASE3	UNKNOWN	Induction Chemotherapy (R-CHOP Vs. R-FC) Followed by Interferon Maintenance Versus Rituximab Maintenance in MCL
NCT00209222	PHASE3	UNKNOWN	Efficacy of R-CHOP vs R-CHOP/R-DHAP in Untreated MCL
NCT00714259	PHASE2/PHASE3	TERMINATED	Non-Myeloablative Allogeneic HSCT From HLA Matched Related or Unrelated Donors for the Treatment of Low Grade B Cell Malignancies
NCT00722137	PHASE3	COMPLETED	Study of the Combination of Rituximab, Cyclophosphamide, Doxorubicin, VELCADE, and Prednisone or Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone in Patients With Newly Diagnosed Mantle Cell Lymphoma
NCT00799461	PHASE3	COMPLETED	Internet-Based Program With or Without Telephone-Based Problem-Solving Training in Helping Long-Term Survivors of Hematopoietic Stem Cell Transplant Cope With Late Complications
NCT00877006	PHASE3	COMPLETED	Study of Bendamustine Hydrochloride and Rituximab (BR) Compared With R-CVP or R-CHOP in the First-Line Treatment of Patients With Advanced Indolent Non-Hodgkin’s Lymphoma (NHL) or Mantle Cell Lymphoma (MCL) - Referred to as the BRIGHT Study
NCT00921414	PHASE3	COMPLETED	Mantel Cell Lymphoma Efficacy of Rituximab Maintenance
NCT01021423	PHASE3	TERMINATED	A Study to Evaluate the Efficacy of Lenalidomide as Maintenance Therapy After Completion of First-line Combination Chemotherapy in Patients With Mantle Cell Lymphoma (MCL).
NCT01073163	PHASE3	COMPLETED	Study to Assess the Effect of Treatment With Bendamustine in Combination With Rituximab on QT Interval in Patients With Advanced Indolent Non-Hodgkin’s Lymphoma (NHL) or Mantle Cell Lymphoma (MCL)
NCT01231412	PHASE3	COMPLETED	Graft-Versus-Host Disease Prophylaxis in Treating Patients With Hematologic Malignancies Undergoing Unrelated Donor Peripheral Blood Stem Cell Transplant
NCT01449344	PHASE3	UNKNOWN	Efficacy and Safety of R-HAD Alone or in Combination With Bortezomib in Patients With Relapsed or Refractory MCL
NCT01456351	PHASE3	COMPLETED	Bendamustine Plus Rituximab Versus Fludarabine Plus Rituximab
NCT01597778	PHASE3	COMPLETED	Double Cord Versus Haploidentical (BMT CTN 1101)
NCT01646021	PHASE3	COMPLETED	Study of Ibrutinib (a Bruton’s Tyrosine Kinase Inhibitor), Versus Temsirolimus in Patients With Relapsed or Refractory Mantle Cell Lymphoma Who Have Received at Least One Prior Therapy
NCT01776840	PHASE3	COMPLETED	A Study of the Bruton’s Tyrosine Kinase Inhibitor Ibrutinib Given in Combination With Bendamustine and Rituximab in Patients With Newly Diagnosed Mantle Cell Lymphoma
NCT01865110	PHASE3	COMPLETED	R-CHOP + R-HAD vs R-CHOP Followed by Maintenance Lenalidomide + Rituximab vs Rituximab for Older Patients With MCL
NCT02354313	PHASE3	UNKNOWN	Phase III, Randomized Trial: Lenalidomide vs Observation After Induction With Rituximab Followed by Cht and ASCT in MCL Adult Patients
NCT02735876	PHASE3	WITHDRAWN	A Study of Acalabrutinib in Combination With Rituximab Versus Ibrutinib Versus Acalabrutinib in Subjects With Relapsed or Refractory Mantle Cell Lymphoma
NCT02793583	PHASE2/PHASE3	TERMINATED	Study to Assess the Efficacy and Safety of Ublituximab + Umbralisib With or Without Bendamustine and Umbralisib Alone in Patients With Previously Treated Non-Hodgkins Lymphoma
NCT02991638	PHASE3	UNKNOWN	Efficacy and Safety of Ibrutinib in Patients With CLL and Other Indolent B-cell Lymphomas Who Are Chronic Hepatitis B Virus Carriers or Occult Hepatitis B Virus Carriers
NCT03112174	PHASE3	COMPLETED	Study of Ibrutinib Combined With Venetoclax in Subjects With Mantle Cell Lymphoma (MCL)
NCT04849715	PHASE3	WITHDRAWN	A Study of Parsaclisib, a PI3Kδ Inhibitor, in Combination With Bendamustine and Rituximab in Patients With Newly Diagnosed Mantle Cell Lymphoma
NCT05020392	PHASE3	UNKNOWN	Autologous Cells Derived Anti-CD19 CAR-Engineered T Cells With Concurrent BTK Inhibitor for B Cell Lymphoma
NCT05097443	PHASE3	UNKNOWN	Orelabrutinib, Rituximab and Combination Chemotherapy in Newly-diagnosed Aggressive B-cell Non-Hodgkin Lymphoma
NCT05164770	PHASE3	UNKNOWN	Study of Zanubrutinib, Rituximab and Combination Chemotherapy in Newly-diagnosed Aggressive B-cell Non-Hodgkin Lymphoma
NCT05431179	PHASE3	WITHDRAWN	A Study of Zilovertamab and Ibrutinib in Patients With Relapsed or Refractory Mantle Cell Lymphoma

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
IBRUTINIB	4	21
ACALABRUTINIB	4	20
ZANUBRUTINIB	4	17
PIRTOBRUTINIB	4	14
BENDAMUSTINE	4	13
DOXORUBICIN	4	11
UBLITUXIMAB	4	7
TEMSIROLIMUS	4	6
FLUDARABINE PHOSPHATE	4	5
VINCRISTINE	4	5
BORTEZOMIB	4	4
CISPLATIN	4	4
UMBRALISIB	4	4
VENETOCLAX	4	4
CYCLOPHOSPHAMIDE ANHYDROUS	4	3
LENALIDOMIDE	4	3
CARMUSTINE	4	1
CYTARABINE	4	1
ETOPOSIDE	4	1
FLUDEOXYGLUCOSE F 18	4	1
MELPHALAN	4	1
MYCOPHENOLATE MOFETIL	4	1
PREDNISONE	4	1
RITUXIMAB	4	1
THALIDOMIDE	4	1
ORELABRUTINIB	3	9
CIRMTUZUMAB	3	4
FLUDARABINE	3	3
INTERFERON	3	1
PARSACLISIB	3	1

Precision-medicine subtype map (CIViC)

Drug × molecular subtype: 6 predictive associations from 7 curated evidence items; also 19 oncogenic, 7 prognostic.

Molecular subtype	Therapy	Effect	Level	CIViC
CCND1 Overexpression	Palbociclib	Sensitivity/Response	CIViC B	EID1536 +1
ATM Mutation	Olaparib	Sensitivity/Response	CIViC D	EID1907
ZEB1 Expression	Salinomycin	Sensitivity/Response	CIViC D	EID12500
ZEB1 Expression	Salinomycin + Doxorubicin	Sensitivity/Response	CIViC D	EID900
ZEB1 Expression	Vincristine	Resistance	CIViC D	EID12502
ZEB1 Expression	Doxorubicin + Cytarabine + Gemcitabine	Resistance	CIViC D	EID899