B-cell chronic lymphocytic leukemia

Summary

B-cell chronic lymphocytic leukemia (MONDO:0004948) is a cancer with 75 cohort genes (225 GWAS associations across 22 studies; 22 CIViC-evidence somatic drivers; 2 ClinVar predisposition records) and 1,182 clinical trials. The dominant Reactome pathway is Interferon gamma signaling (9 cohort genes). Molecularly, TP53 Mutation confers sensitivity to Alemtuzumab in Chronic Lymphocytic Leukemia (CIViC Level B); 38 further subtype–drug associations are mapped below. Top therapeutic interventions include cyclophosphamide anhydrous, bendamustine, and ofatumumab.

At a glance

• Classification: Cancer
• Prevalence: 1-5 / 10 000 (Europe) [Orphanet-validated]
• Cohort genes: 75
• GWAS associations: 225
• ClinVar variants: 2
• Clinical trials: 1,182
• Precision-medicine evidence (CIViC): 39 subtype–drug associations

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Point prevalence	1-5 / 10 000	48	Europe	Validated
Annual incidence	1-9 / 100 000	7.05	France	Validated

Identifiers

Disease identifiers

Field	Value
Canonical name	B-cell chronic lymphocytic leukemia
Mondo ID	MONDO:0004948
EFO	EFO:0000095
MeSH	D015451
OMIM	151400
Orphanet	67038
DOID	DOID:1040
ICD-10-CM	C91.1
NCIT	C3163
UMLS	C0023434
MedGen	44120
GARD	0006104
MedDRA	10008958
NORD	971
Is cancer (heuristic)	yes

Also known as: B cell chronic lymphocytic leukaemia · B cell chronic lymphocytic leukemia · B cell CLL · B cell lymphocytic leukaemia · B cell lymphocytic leukemia · B-cell chronic lymphocytic leukemia · B-cell chronic lymphogenous leukaemia · B-cell chronic lymphogenous leukemia · B-cell chronic lymphoid leukaemia · B-cell chronic lymphoid leukemia · B-cell CLL · B-cell lymphocytic leukaemia · B-cell lymphocytic leukemia · B-CLL · BCLL · chronic B-cell lymphocytic leukaemia · chronic B-cell lymphocytic leukemia · chronic lymphatic leukemia · chronic lymphocytic leukaemia (CLL) · Chronic Lymphocytic Leukemia (+10 more)

Data availability: 2 ClinVar variants · 225 GWAS associations (22 studies) · 27 cell lines.

Disease family

An umbrella term covering 2 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 › leukemia › chronic leukemia › B-cell chronic lymphocytic leukemia

Related subtypes (7): prolymphocytic leukemia, chronic monocytic leukemia, chronic eosinophilic leukemia, chronic neutrophilic leukemia, T-cell large granular lymphocyte leukemia, aggressive NK-cell leukemia, chronic myelomonocytic leukemia

Subtypes (2): chronic lymphocytic leukemia/small lymphocytic lymphoma, hairy cell leukemia

Genetics & variants

GWAS landscape

225 GWAS associations across 22 studies. Top hits map to 24 distinct genes (as reported by GWAS).

Top associations by p-value

rsID	p-value	Gene	Risk allele	Odds ratio
rs35923643	4e-58	GRAMD1B	G	1.63
rs4776471	5e-40	DRAIC	?	0.75
rs735665	4e-39	GRAMD1B	A	1.62
rs34004493	4e-32	SP140	G	1.39
rs11637565	2e-31	DRAIC	G	1.35
chr9:136496196	9e-30		C	868.28
rs6708784	1e-29	MIR4435-2HG	?	1.28
rs391855	1e-28	RPL10AP12 - IRF8	A	1.34
rs9392504	1e-28	IRF4 - EXOC2	A	1.33
rs58055674	2e-27	MIR4435-2HG, ACOXL	C	1.41
rs1324551	1e-26	FAS	?	0.79
rs13397985	1e-22	SP140	G	1.45
rs4975538	4e-22	TERT	?	1.25
rs539846	6e-22	BMF	?	1.25
rs9391997	9e-22	IRF4	G	1.35
rs872071	2e-20	IRF4	G	1.54
rs9271176	3e-20	HLA-DRB1 - HLA-DQA1	G	1.29
rs142239370	3e-19	PALD1	C	1.53
rs8024033	7e-19	BMF - BUB1B	C	1.26
rs13401811	2e-18	ACOXL	G	1.41
rs142215530	2e-18	MNS1 - ZNF280D	G	1.39
rs11187157	2e-18	Y_RNA - EXOC6	C	1.2
rs2052702	4e-18	DRAIC	A	1.32
rs2521269	4e-18	C11orf21	?	0.82
rs7176508	8e-18	DRAIC	A	1.42
rs17483466	4e-17	MIR4435-2HG, ACOXL	G	1.37
rs391023	5e-17	RPL10AP12 - IRF8	G	1.33
rs2953196	5e-16	GRAMD1B	G	1.3
rs9270750	6e-16	HLA-DRB1 - HLA-DQA1	A	1.32
rs210143	6e-16	BAK1	C	1.26

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST004146	Law PJ	2017	4,478	13,213	Genome-wide association analysis implicates dysregulation of immunity genes in chronic lymphocytic leukaemia.
GCST90624738	Guler M	2025	4,442	1,104,335	Clustering of lymphoid neoplasms by cell of origin, somatic mutation and drug usage profiles: a multi-trait genome-wide association study.
GCST90267402	Berndt SI	2022	3,100	9,505	Distinct germline genetic susceptibility profiles identified for common non-Hodgkin lymphoma subtypes.
GCST003468	Berndt SI	2016	3,100	7,667	Meta-analysis of genome-wide association studies discovers multiple loci for chronic lymphocytic leukemia.
GCST008721	Din L	2019	2,492	24,529	Genetic overlap between autoimmune diseases and non-Hodgkin lymphoma subtypes.
GCST008724	Din L	2019	2,492	11,232	Genetic overlap between autoimmune diseases and non-Hodgkin lymphoma subtypes.
GCST008727	Din L	2019	2,492	23,144	Genetic overlap between autoimmune diseases and non-Hodgkin lymphoma subtypes.
GCST002073	Berndt SI	2013	2,179	6,221	Genome-wide association study identifies multiple risk loci for chronic lymphocytic leukemia.
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.
GCST002299	Speedy HE	2013	1,739	5,199	A genome-wide association study identifies multiple susceptibility loci for chronic lymphocytic leukemia.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

Tier	Variants
Tier 1: coding	0
Tier 2: splice/UTR	3
Tier 3: regulatory	2
Tier 4: intronic/intergenic	45

MAF distribution

Bucket	Variants
common (>=0.05)	48
low_freq (0.01-0.05)	1
rare (<0.01)	0
unknown	1

Functional consequences

Consequence	Count
intron_variant	27
intergenic_variant	14
non_coding_transcript_exon_variant	3
3_prime_UTR_variant	3
regulatory_region_variant	2
unknown	1

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
rs35923643	11	123484683	A>G	0.05	intron_variant	GRAMD1B	4e-58	Tier 4: intronic/intergenic
rs4776471	15	69700119	T>A,C	0.05	intergenic_variant	DRAIC	5e-40	Tier 4: intronic/intergenic
rs735665	11	123490689	G>A	0.19	intron_variant	GRAMD1B	4e-39	Tier 4: intronic/intergenic
rs34004493	2	230289297	A>G	0.05	intron_variant	SP140	4e-32	Tier 4: intronic/intergenic
rs11637565	15	69728186	G>A,C,T	0.05	intergenic_variant	DRAIC	2e-31	Tier 4: intronic/intergenic
chr9:136496196							9e-30	Tier 4: intronic/intergenic
rs6708784	2	111169802	A>G,T	0.05	intron_variant	MIR4435-2HG	1e-29	Tier 4: intronic/intergenic
rs391855	16	85895015	A>G,T	0.05	intergenic_variant	RPL10AP12 - IRF8	1e-28	Tier 4: intronic/intergenic
rs9392504	6	412802	G>A	0.05	intergenic_variant	IRF4 - EXOC2	1e-28	Tier 4: intronic/intergenic
rs58055674	2	111074216	T>C	0.05	intron_variant	MIR4435-2HG, ACOXL	2e-27	Tier 4: intronic/intergenic
rs1324551	10	88991759	C>A,T	0.05	non_coding_transcript_exon_variant	FAS	1e-26	Tier 4: intronic/intergenic
rs13397985	2	230226508	T>C,G	0.18	intron_variant	SP140	1e-22	Tier 4: intronic/intergenic
rs4975538	5	1280715	G>A,C,T	0.05	intron_variant	TERT	4e-22	Tier 4: intronic/intergenic
rs539846	15	40105735	G>A,C,T	0.05	intron_variant	BMF	6e-22	Tier 4: intronic/intergenic
rs9391997	6	409119	A>G	0.494	3_prime_UTR_variant	IRF4	9e-22	Tier 2: splice/UTR
rs872071	6	411064	A>G,T	0.46	3_prime_UTR_variant	IRF4	2e-20	Tier 2: splice/UTR
rs9271176	6	32610350	A>C,G,T	0.05	regulatory_region_variant	HLA-DRB1 - HLA-DQA1	3e-20	Tier 3: regulatory
rs142239370	10	70623113	A>C,G	0.04	intergenic_variant	PALD1	3e-19	Tier 4: intronic/intergenic
rs8024033	15	40111456	C>G	0.05	intergenic_variant	BMF - BUB1B	7e-19	Tier 4: intronic/intergenic
rs13401811	2	110858527	G>A	0.19	intron_variant	ACOXL	2e-18	Tier 4: intronic/intergenic
rs142215530	15	56485493	A>G	0.05	intergenic_variant	MNS1 - ZNF280D	2e-18	Tier 4: intronic/intergenic
rs11187157	10	92742487	T>C	0.44	regulatory_region_variant	Y_RNA - EXOC6	2e-18	Tier 3: regulatory
rs2052702	15	69697166	A>C,G,T	0.386	intergenic_variant	DRAIC	4e-18	Tier 4: intronic/intergenic
rs2521269	11	2299865	C>A,T	0.05	intron_variant	C11orf21	4e-18	Tier 4: intronic/intergenic
rs7176508	15	69726651	A>C,G	0.38	intergenic_variant	DRAIC	8e-18	Tier 4: intronic/intergenic
rs17483466	2	111039881	A>G	0.2	intron_variant	MIR4435-2HG, ACOXL	4e-17	Tier 4: intronic/intergenic
rs391023	16	85894208	C>A,G,T	0.37	intergenic_variant	RPL10AP12 - IRF8	5e-17	Tier 4: intronic/intergenic
rs2953196	11	123497625	A>G,T	0.244	intron_variant	GRAMD1B	5e-16	Tier 4: intronic/intergenic
rs9270750	6	32600569	G>A	0.457	intergenic_variant	HLA-DRB1 - HLA-DQA1	6e-16	Tier 4: intronic/intergenic
rs210143	6	33579153	T>A,C	0.05	intron_variant	BAK1	6e-16	Tier 4: intronic/intergenic

ClinVar germline variants

2 retrieved; paginated sample, class counts are floors:

2 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1174011	NM_000546.6(TP53):c.-19_*21del (p.Met1fs)	TP53	Pathogenic	no assertion criteria provided
127819	NM_000546.6(TP53):c.659A>G (p.Tyr220Cys)	TP53	Pathogenic	reviewed by expert panel

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 121 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 4

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

Gene	HGNC	Evidence routes
POT1	POT1	GWAS, Orphanet
BCL2	BCL2	GWAS, Orphanet
TERT	TERT	GWAS, Orphanet
HLA-DRB1	HLA-DRB1	GWAS, Orphanet

Somatic driver evidence (intOGen + CIViC, cohort fanout)

Gene	intOGen role	Cancer types	CIViC
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
POT1	Act	ANGS,CLLSLL,LGGNOS,MEL,SOFT_TISSUE	CIViC #9935
BCL2	Act	DLBCLNOS,MLYM,NHL	CIViC #59
SF3B1	Act	AML,BLCA,BRCA,CHOL,CLLSLL,HCC,LUNG,MBL,MEL,PAAD,PCM,PRAD,SKCM,UM	CIViC #44
BTK	Act	NHL	CIViC #65
GNAS	Act	BRCA,COADREAD,ESCA,HCC,LUAD,MBL,PAAD,PANCREAS	CIViC #2319
BIRC3	Act	CLLSLL,LUSC	CIViC #353
MYD88	Act	CLLSLL,DLBCLNOS,MLYM,NHL	CIViC #3742
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
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
PLCG2			CIViC #4327
TERT	Act	PRCC	CIViC #79
ACTA1			CIViC #128
CASP8	LoF	BCC,BLCA,BRCA,CEAD,CESC,CSCC,HNSC,NHL,NPC,STAD,VULVA	CIViC #761
SP140	LoF	PCM	CIViC #8996
PRKD2	Act	PCM
CDKN2B			CIViC #916
RFX7			CIViC #14525
HLA-DQA1	Act	PLMESO
IRF8			CIViC #2836
IRF4	Act	CLLSLL,DLBCLNOS,MLYM,NHL,PCM	CIViC #3043
LEF1	LoF	HCC

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
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
POT1	Orphanet:251627	Oligodendroglioma
POT1	Orphanet:251630	Anaplastic oligodendroglioma
POT1	Orphanet:618	Familial melanoma
POT1	Orphanet:67038	B-cell chronic lymphocytic leukemia
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
SF3B1	Orphanet:39044	Uveal melanoma
SF3B1	Orphanet:75564	Acquired idiopathic sideroblastic anemia
BTK	Orphanet:47	X-linked agammaglobulinemia
BTK	Orphanet:632	Short stature due to isolated growth hormone deficiency with X-linked hypogammaglobulinemia
GNAS	Orphanet:189427	Cushing syndrome due to bilateral macronodular adrenocortical disease
GNAS	Orphanet:2762	Progressive osseous heteroplasia
GNAS	Orphanet:562	McCune-Albright syndrome
GNAS	Orphanet:57782	Mazabraud syndrome
GNAS	Orphanet:79443	Pseudohypoparathyroidism type 1A
GNAS	Orphanet:79444	Pseudohypoparathyroidism type 1C
GNAS	Orphanet:79445	Pseudopseudohypoparathyroidism
GNAS	Orphanet:93276	Polyostotic fibrous dysplasia
GNAS	Orphanet:93277	Monostotic fibrous dysplasia
GNAS	Orphanet:94089	Pseudohypoparathyroidism type 1B
BIRC3	Orphanet:52417	MALT lymphoma
MYD88	Orphanet:33226	Waldenström macroglobulinemia
MYD88	Orphanet:70592	Transient predisposition to invasive pyogenic bacterial infection
MYD88	Orphanet:714046	Primary choroidal lymphoma
NOTCH1	Orphanet:402075	Familial bicuspid aortic valve
NOTCH1	Orphanet:974	Adams-Oliver syndrome
ATM	Orphanet:100	Ataxia-telangiectasia
ATM	Orphanet:1331	Familial prostate cancer
ATM	Orphanet:145	Hereditary breast and/or ovarian cancer syndrome

Cohort genes → proteins

75 cohort genes, 71 distinct canonical proteins.

Evidence partition

Subset	Genes
gwas_only	64
civic_only	8
multi_evidence	3

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
TP53	HGNC:11998	ENSG00000141510	P04637	Cellular tumor antigen p53	clinvar,civic_evidence
POT1	HGNC:17284	ENSG00000128513	Q9NUX5	Protection of telomeres protein 1	gwas,civic_evidence
BCL2	HGNC:990	ENSG00000171791	P10415	Apoptosis regulator Bcl-2	gwas,civic_evidence
SF3B1	HGNC:10768	ENSG00000115524	O75533	Splicing factor 3B subunit 1	civic_evidence
BTK	HGNC:1133	ENSG00000010671	Q06187	Tyrosine-protein kinase BTK	civic_evidence
GNAS	HGNC:4392	ENSG00000087460	O95467	Neuroendocrine secretory protein 55	civic_evidence
BIRC3	HGNC:591	ENSG00000023445	Q13489	Baculoviral IAP repeat-containing protein 3	civic_evidence
MYD88	HGNC:7562	ENSG00000172936	Q99836	Myeloid differentiation primary response protein MyD88	civic_evidence
NOTCH1	HGNC:7881	ENSG00000148400	P46531	Neurogenic locus notch homolog protein 1	civic_evidence
ATM	HGNC:795	ENSG00000149311	Q13315	Serine-protein kinase ATM	civic_evidence
PLCG2	HGNC:9066	ENSG00000197943	P16885	1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2	civic_evidence
RPLP1	HGNC:10372	ENSG00000137818	P05386	Large ribosomal subunit protein P1	gwas
RPS6KB1	HGNC:10436	ENSG00000108443	P23443	Ribosomal protein S6 kinase beta-1	gwas
RREB1	HGNC:10449	ENSG00000124782	Q92766	Ras-responsive element-binding protein 1	gwas
SCO2	HGNC:10604	ENSG00000284194	O43819	Cytochrome c oxidase assembly factor SCO2	gwas
BUB1B	HGNC:1149	ENSG00000156970	O60566	Mitotic checkpoint serine/threonine-protein kinase BUB1 beta	gwas
TACC2	HGNC:11523	ENSG00000138162	O95359	Transforming acidic coiled-coil-containing protein 2	gwas
TERC	HGNC:11727	ENSG00000270141		telomerase RNA component	gwas
TERT	HGNC:11730	ENSG00000164362	O14746	Telomerase reverse transcriptase	gwas
KLF10	HGNC:11810	ENSG00000155090	Q13118	Krueppel-like factor 10	gwas
ACTA1	HGNC:129	ENSG00000143632	P68133	Actin, alpha skeletal muscle	gwas
ACTA2	HGNC:130	ENSG00000107796	P62736	Actin, aortic smooth muscle	gwas
C11orf21	HGNC:13231	ENSG00000110665	Q9P2W6	Uncharacterized protein C11orf21	gwas
TSPAN32	HGNC:13410	ENSG00000064201	Q96QS1	Tetraspanin-32	gwas
DMRTA1	HGNC:13826	ENSG00000176399	Q5VZB9	Doublesex- and mab-3-related transcription factor A1	gwas
CSRNP1	HGNC:14300	ENSG00000144655	Q96S65	Cysteine/serine-rich nuclear protein 1	gwas
CAMK2D	HGNC:1462	ENSG00000145349	Q13557	Calcium/calmodulin-dependent protein kinase type II subunit delta	gwas
TMPRSS5	HGNC:14908	ENSG00000166682	Q9H3S3	Transmembrane protease serine 5	gwas
MYNN	HGNC:14955	ENSG00000085274	Q9NPC7	Myoneurin	gwas
CASP10	HGNC:1500	ENSG00000003400	Q92851	Caspase-10	gwas
CASP8	HGNC:1509	ENSG00000064012	Q14790	Caspase-8	gwas
STRN4	HGNC:15721	ENSG00000090372	Q9NRL3	Striatin-4	gwas
ULK4	HGNC:15784	ENSG00000168038	Q96C45	Serine/threonine-protein kinase ULK4	gwas
FARP2	HGNC:16460	ENSG00000006607	O94887	FERM, ARHGEF and pleckstrin domain-containing protein 2	gwas
PIAS4	HGNC:17002	ENSG00000105229	Q8N2W9	E3 SUMO-protein ligase PIAS4	gwas
ELL2	HGNC:17064	ENSG00000118985	O00472	RNA polymerase II elongation factor ELL2	gwas
SP140	HGNC:17133	ENSG00000079263	Q13342	Nuclear body protein SP140	gwas
SPDEF	HGNC:17257	ENSG00000124664	O95238	SAM pointed domain-containing Ets transcription factor	gwas
PRKD2	HGNC:17293	ENSG00000105287	Q9BZL6	Serine/threonine-protein kinase D2	gwas
RHOU	HGNC:17794	ENSG00000116574	Q7L0Q8	Rho-related GTP-binding protein RhoU	gwas
CDKN2B	HGNC:1788	ENSG00000147883	P42772	Cyclin-dependent kinase 4 inhibitor B	gwas
ZBTB7A	HGNC:18078	ENSG00000178951	O95365	Zinc finger and BTB domain-containing protein 7A	gwas
BANK1	HGNC:18233	ENSG00000153064	Q8NDB2	B-cell scaffold protein with ankyrin repeats	gwas
SCN3B	HGNC:20665	ENSG00000166257	Q9NY72	Sodium channel regulatory subunit beta-3	gwas
IPCEF1	HGNC:21204	ENSG00000074706	Q8WWN9	Interactor protein for cytohesin exchange factors 1	gwas
ILRUN	HGNC:21215	ENSG00000196821	Q9H6K1	Protein ILRUN	gwas
CREBRF	HGNC:24050	ENSG00000164463	Q8IUR6	CREB3 regulatory factor	gwas
BMF	HGNC:24132	ENSG00000104081	Q96LC9	Bcl-2-modifying factor	gwas
CLPTM1L	HGNC:24308	ENSG00000049656	Q96KA5	Lipid scramblase CLPTM1L	gwas
CXXC1	HGNC:24343	ENSG00000154832	Q9P0U4	CXXC-type zinc finger protein 1	gwas

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
TP53	Cellular tumor antigen p53	Multifunctional transcription factor that induces cell cycle arrest, DNA repair or apoptosis upon binding to its target DNA sequence.
POT1	Protection of telomeres protein 1	Component of the telomerase ribonucleoprotein (RNP) complex that is essential for the replication of chromosome termini.
BCL2	Apoptosis regulator Bcl-2	Suppresses apoptosis in a variety of cell systems including factor-dependent lymphohematopoietic and neural cells.
SF3B1	Splicing factor 3B subunit 1	Component of the 17S U2 SnRNP complex of the spliceosome, a large ribonucleoprotein complex that removes introns from transcribed pre-mRNAs.
BTK	Tyrosine-protein kinase BTK	Non-receptor tyrosine kinase indispensable for B lymphocyte development, differentiation and signaling.
BIRC3	Baculoviral IAP repeat-containing protein 3	Multi-functional protein which regulates not only caspases and apoptosis, but also modulates inflammatory signaling and immunity, mitogenic kinase signaling and cell proliferation, as well as cell invasion and metastasis.
MYD88	Myeloid differentiation primary response protein MyD88	Adapter protein involved in the Toll-like receptor and IL-1 receptor signaling pathway in the innate immune response.
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.
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.
PLCG2	1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2	The production of the second messenger molecules diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3) is mediated by activated phosphatidylinositol-specific phospholipase C enzymes.
RPLP1	Large ribosomal subunit protein P1	Plays an important role in the elongation step of protein synthesis.
RPS6KB1	Ribosomal protein S6 kinase beta-1	Serine/threonine-protein kinase that acts downstream of mTOR signaling in response to growth factors and nutrients to promote cell proliferation, cell growth and cell cycle progression.
RREB1	Ras-responsive element-binding protein 1	Transcription factor that binds specifically to the RAS-responsive elements (RRE) of gene promoters.
SCO2	Cytochrome c oxidase assembly factor SCO2	Copper metallochaperone essential for the synthesis and maturation of cytochrome c oxidase subunit II (MT-CO2/COX2); together with SCO1, facilitates the incorporation of copper into the Cu(A) site of MT-CO2/COX2.
BUB1B	Mitotic checkpoint serine/threonine-protein kinase BUB1 beta	Essential component of the mitotic checkpoint.
TACC2	Transforming acidic coiled-coil-containing protein 2	Plays a role in the microtubule-dependent coupling of the nucleus and the centrosome.
TERT	Telomerase reverse transcriptase	Telomerase is a ribonucleoprotein enzyme essential for the replication of chromosome termini in most eukaryotes.
KLF10	Krueppel-like factor 10	Transcriptional repressor which binds to the consensus sequence 5’-GGTGTG-3'.
ACTA1	Actin, alpha skeletal muscle	Actins are highly conserved proteins that are involved in various types of cell motility and are ubiquitously expressed in all eukaryotic cells.
ACTA2	Actin, aortic smooth muscle	Actins are highly conserved proteins that are involved in various types of cell motility and are ubiquitously expressed in all eukaryotic cells.
CSRNP1	Cysteine/serine-rich nuclear protein 1	Binds to the consensus sequence 5’-AGAGTG-3’ and has transcriptional activator activity.
CAMK2D	Calcium/calmodulin-dependent protein kinase type II subunit delta	Calcium/calmodulin-dependent protein kinase involved in the regulation of Ca(2+) homeostatis and excitation-contraction coupling (ECC) in heart by targeting ion channels, transporters and accessory proteins involved in Ca(2+) influx into t…
TMPRSS5	Transmembrane protease serine 5	May play a role in hearing.
CASP10	Caspase-10	Involved in the activation cascade of caspases responsible for apoptosis execution.
CASP8	Caspase-8	Thiol protease that plays a key role in programmed cell death by acting as a molecular switch for apoptosis, necroptosis and pyroptosis, and is required to prevent tissue damage during embryonic development and adulthood.
STRN4	Striatin-4	Calmodulin-binding scaffolding protein which is the center of the striatin-interacting phosphatase and kinase (STRIPAK) complexes.
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.
FARP2	FERM, ARHGEF and pleckstrin domain-containing protein 2	Functions as a guanine nucleotide exchange factor that activates RAC1.
PIAS4	E3 SUMO-protein ligase PIAS4	Functions as an E3-type small ubiquitin-like modifier (SUMO) ligase, stabilizing the interaction between UBE2I and the substrate, and as a SUMO-tethering factor.
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.
SP140	Nuclear body protein SP140	Component of the nuclear body, also known as nuclear domain 10, PML oncogenic domain, and KR body.
SPDEF	SAM pointed domain-containing Ets transcription factor	May function as an androgen-independent transactivator of the prostate-specific antigen (PSA) promoter.
PRKD2	Serine/threonine-protein kinase D2	Serine/threonine-protein kinase that converts transient diacylglycerol (DAG) signals into prolonged physiological effects downstream of PKC, and is involved in the regulation of cell proliferation via MAPK1/3 (ERK1/2) signaling, oxidative…
RHOU	Rho-related GTP-binding protein RhoU	Binds to and activates protein kinase PAK1.
CDKN2B	Cyclin-dependent kinase 4 inhibitor B	Interacts strongly with CDK4 and CDK6.
ZBTB7A	Zinc finger and BTB domain-containing protein 7A	Transcription factor that represses the transcription of a wide range of genes involved in cell proliferation and differentiation.
BANK1	B-cell scaffold protein with ankyrin repeats	Involved in B-cell receptor (BCR)-induced Ca(2+) mobilization from intracellular stores.
SCN3B	Sodium channel regulatory subunit beta-3	Regulatory subunit of multiple voltage-gated sodium (Nav) channels directly mediating the depolarization of excitable membranes.
IPCEF1	Interactor protein for cytohesin exchange factors 1	Enhances the promotion of guanine-nucleotide exchange by PSCD2 on ARF6 in a concentration-dependent manner.
ILRUN	Protein ILRUN	Negative regulator of innate antiviral response.
CREBRF	CREB3 regulatory factor	Acts as a negative regulator of the endoplasmic reticulum stress response or unfolded protein response (UPR).
BMF	Bcl-2-modifying factor	May play a role in apoptosis.
CLPTM1L	Lipid scramblase CLPTM1L	Scramblase that mediates the translocation of glucosaminylphosphatidylinositol (alpha-D-GlcN-(1-6)-(1,2-diacyl-sn-glycero-3-phospho)-1D-myo-inositol, GlcN-PI) across the endoplasmic reticulum (ER) membrane, from the cytosolic leaflet to th…
CXXC1	CXXC-type zinc finger protein 1	Transcriptional activator that exhibits a unique DNA binding specificity for CpG unmethylated motifs with a preference for CpGG.
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.
RFX7	DNA-binding protein RFX7	Transcription factor.
LRRC34	Leucine-rich repeat-containing protein 34	Highly expressed in stem cells where it may be involved in regulation of pluripotency.
HYCC2	Hyccin 2	Component of a complex required to localize phosphatidylinositol 4-kinase (PI4K) to the plasma membrane.
GRAMD1B	Protein Aster-B	Cholesterol transporter that mediates non-vesicular transport of cholesterol from the plasma membrane (PM) to the endoplasmic reticulum (ER).
VMP1	Vacuole membrane protein 1	Phospholipid scramblase involved in lipid homeostasis and membrane dynamics processes.

Protein-family classification

Druggable: 18 · Difficult: 18 · Unknown: 39 · Druggable fraction: 0.24

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	7	2.6×	0.129
Antibody/Immunoglobulin	6	2.3×	0.152
Scaffold/PPI	7	1.6×	0.332
Transcription factor	11	1.2×	0.518
Other/Unknown	39	0.9×	0.881
Enzyme (other)	4	0.6×	0.881
Protease	1	0.5×	0.881

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
TP53	Transcription factor	no		p53_tumour_suppressor, p53-like_TF_DNA-bd_sf, p53_tetrameristn
POT1	Other/Unknown	no		Telomer_end-bd_POT1/Cdc13, NA-bd_OB-fold, POT1
BCL2	Other/Unknown	no		Bcl2-like, Bcl2_BH4, Bcl2/BclX
SF3B1	Other/Unknown	no		ARM-like, SF3b_su1, ARM-type_fold
BTK	Kinase	yes	2.7.10.2	Prot_kinase_dom, SH2, Ser-Thr/Tyr_kinase_cat_dom
GNAS	Other/Unknown	no		NESP55, Gprotein_alpha_S, Gprotein_alpha_su
BIRC3	Transcription factor	no	2.3.2.27	CARD, BIR_rpt, Znf_RING
MYD88	Other/Unknown	no		TIR_dom, Death_dom, DEATH-like_dom_sf
NOTCH1	Scaffold/PPI	no		EGF-type_Asp/Asn_hydroxyl_site, EGF, Notch_dom
ATM	Kinase	yes	2.7.11.1	PI3/4_kinase_cat_dom, PIK-rel_kinase_FAT, FATC_dom
PLCG2	Scaffold/PPI	no	3.1.4.11	C2_dom, PLipase_C_PInositol-sp_X_dom, SH2
RPLP1	Other/Unknown	no		Ribosomal_P1/P2, P1/P2_N_sf
RPS6KB1	Kinase	yes	2.7.11.1	Prot_kinase_dom, AGC-kinase_C, Ser/Thr_kinase_AS
RREB1	Transcription factor	no		Znf_C2H2_type, Znf_C2H2_sf, RREB1
SCO2	Other/Unknown	no		SCO1/SenC, Thioredoxin_domain, Synth_of_cyt-c-oxidase_Sco1/2
BUB1B	Kinase	yes	2.7.11.1	Kinase-like_dom_sf, Mad3/Bub1_I, Bub1/Mad3
TACC2	Other/Unknown	no		TACC_C, TACC
TERC	Other/Unknown	no
TERT	Other/Unknown	no		RT_dom, Telomerase_RT, Telomerase_RBD
KLF10	Transcription factor	no		Znf_C2H2_type, Znf_C2H2_sf
ACTA1	Other/Unknown	no		Actin, Actin_CS, Actin/actin-like_CS
ACTA2	Other/Unknown	no		Actin, Actin_CS, Actin/actin-like_CS
C11orf21	Other/Unknown	no		DUF4620
TSPAN32	Other/Unknown	no		Tetraspanin_EC2_sf, Tetraspanin/Peripherin, PHEMX_LEL
DMRTA1	Other/Unknown	no		DM_DNA-bd, DMA, UBA-like_sf
CSRNP1	Other/Unknown	no		Cys/Ser-rich_nuc_prot, CSRNP_N
CAMK2D	Kinase	yes	2.7.11.17	Prot_kinase_dom, Ser/Thr_kinase_AS, Kinase-like_dom_sf
TMPRSS5	Protease	yes		SRCR, Trypsin_dom, Peptidase_S1A
MYNN	Transcription factor	no		BTB/POZ_dom, SKP1/BTB/POZ_sf, Znf_C2H2_type
CASP10	Enzyme (other)	yes	3.4.22.63	Pept_C14_p20, DED_dom, Pept_C14_p10
CASP8	Enzyme (other)	yes	3.4.22.61	Pept_C14_p20, DED_dom, Pept_C14_p10
STRN4	Scaffold/PPI	no		WD40_rpt, Striatin_N, WD40/YVTN_repeat-like_dom_sf
ULK4	Kinase	yes		Prot_kinase_dom, Kinase-like_dom_sf, ARM-like
FARP2	Scaffold/PPI	no		DH_dom, FERM_domain, Ez/rad/moesin-like
PIAS4	Transcription factor	no		SAP_dom, Znf_MIZ, Znf_RING/FYVE/PHD
ELL2	Other/Unknown	no		Occludin_ELL, ELL_N, ELL/occludin
SP140	Transcription factor	no		SAND_dom, Bromodomain, Znf_PHD
SPDEF	Other/Unknown	no		Ets_dom, Pointed_dom, SAM/pointed_sf
PRKD2	Kinase	yes	2.7.11.13	Prot_kinase_dom, PH_domain, PKC_DAG/PE
RHOU	Other/Unknown	no		Small_GTPase, Small_GTPase_Rho, Small_GTP-bd
CDKN2B	Scaffold/PPI	no		Ankyrin_rpt, Ankyrin_rpt-contain_sf, Ank_Repeat/CDKN_Inhibitor
ZBTB7A	Transcription factor	no		BTB/POZ_dom, SKP1/BTB/POZ_sf, Znf_C2H2_type
BANK1	Scaffold/PPI	no		TIR_dom, DBB_domain, Toll_tir_struct_dom_sf
SCN3B	Antibody/Immunoglobulin	yes		Ig_sub, Ig-like_dom, Ig_V-set
IPCEF1	Scaffold/PPI	no		PH_domain, PH-like_dom_sf, CNKSR
ILRUN	Antibody/Immunoglobulin	yes		UBA-like_sf, Ig-like_fold, Nbr1_FW
CREBRF	Other/Unknown	no		bZIP, CREBRF, bZIP_sf
BMF	Other/Unknown	no		BMF
CLPTM1L	Other/Unknown	no		CLPTM1
CXXC1	Transcription factor	no		Znf_PHD, Znf_CXXC, Znf_FYVE_PHD

Expression context

Cohort genes with no expression data: 1.

69 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)	74
unknown	1

Top tissues across cohort

Tissue	Cohort genes
monocyte	12
granulocyte	8
mononuclear cell	7
leukocyte	6
colonic epithelium	6
buccal mucosa cell	6
lymph node	6
ventricular zone	5
calcaneal tendon	5
vermiform appendix	5
male germ line stem cell (sensu Vertebrata) in testis	5
secondary oocyte	4
right uterine tube	4
tendon of biceps brachii	3
superficial temporal artery	3
epithelium of nasopharynx	3
bone marrow cell	3
Brodmann (1909) area 23	3
mucosa of transverse colon	3
C1 segment of cervical spinal cord	3

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
TP53	223	ubiquitous	marker	ventricular zone, ganglionic eminence, tendon of biceps brachii
POT1	279	ubiquitous	marker	secondary oocyte, germinal epithelium of ovary, calcaneal tendon
BCL2	275	ubiquitous	marker	dorsal motor nucleus of vagus nerve, superficial temporal artery, calcaneal tendon
SF3B1	295	ubiquitous	marker	tibia, ventricular zone, epithelium of nasopharynx
BTK	206	broad	marker	monocyte, mononuclear cell, leukocyte
GNAS	312	ubiquitous	marker	type B pancreatic cell, postcentral gyrus, Brodmann (1909) area 46
BIRC3	238	ubiquitous	marker	vermiform appendix, epithelium of nasopharynx, nasopharynx
MYD88	284	ubiquitous	marker	leukocyte, mononuclear cell, monocyte
NOTCH1	272	ubiquitous	marker	ventricular zone, colonic epithelium, visceral pleura
ATM	286	ubiquitous	marker	calcaneal tendon, colonic epithelium, corpus callosum
PLCG2	249	ubiquitous	marker	renal glomerulus, bone marrow cell, blood
RPLP1	156	ubiquitous	marker	epithelium of bronchus, thymus, trachea
RPS6KB1	275	ubiquitous	marker	endothelial cell, Brodmann (1909) area 23, calcaneal tendon
RREB1	278	ubiquitous	marker	buccal mucosa cell, epithelium of nasopharynx, oral cavity
SCO2	260	ubiquitous	yes	right uterine tube, granulocyte, mucosa of transverse colon
BUB1B	210	ubiquitous	marker	secondary oocyte, oocyte, ventricular zone
TACC2	290	ubiquitous	marker	apex of heart, skeletal muscle tissue of biceps brachii, gastrocnemius
TERC	113	ubiquitous	yes	bone marrow cell, colonic epithelium, male germ line stem cell (sensu Vertebrata) in testis
TERT	105	broad	yes	stromal cell of endometrium, type B pancreatic cell, olfactory bulb
KLF10	288	ubiquitous	marker	mucosa of paranasal sinus, skin of hip, upper leg skin
ACTA1	203	broad	marker	gluteal muscle, skeletal muscle tissue of biceps brachii, diaphragm
ACTA2	289	ubiquitous	marker	cauda epididymis, blood vessel layer, saphenous vein
C11orf21	174	broad	marker	granulocyte, monocyte, mononuclear cell
TSPAN32	166	broad	marker	granulocyte, apex of heart, monocyte
DMRTA1	131	broad	marker	male germ line stem cell (sensu Vertebrata) in testis, right lobe of liver, islet of Langerhans
CSRNP1	233	ubiquitous	marker	mucosa of stomach, vena cava, saphenous vein
CAMK2D	260	ubiquitous	marker	left ventricle myocardium, lateral nuclear group of thalamus, cardiac muscle of right atrium
TMPRSS5	166	tissue_specific	yes	tibial nerve, C1 segment of cervical spinal cord, spinal cord
MYNN	274	ubiquitous	marker	buccal mucosa cell, secondary oocyte, male germ line stem cell (sensu Vertebrata) in testis
CASP10	206	ubiquitous	marker	colonic epithelium, granulocyte, monocyte

Protein interactions among cohort

Intra-cohort edges: 39.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
TP53	22,736
BCL2	8,343
NOTCH1	7,411
ATM	7,383
FASN	6,551
TERT	5,717
RPS6KB1	5,474
CASP8	5,040
BIRC3	4,766
SF3B1	4,582

Intra-cohort edges

A	B	Sources
ACOXL	C11orf21	string_interaction
ACOXL	FASN	string_interaction
ACOXL	SP140	string_interaction
ACTA2	VMP1	biogrid_interaction
ATM	KLF10	string_interaction
ATM	NOTCH1	intact
ATM	PIAS4	string_interaction
ATM	TP53	biogrid_interaction, string_interaction
BANK1	PLCG2	string_interaction
BCL2	BMF	string_interaction
BCL2	CASP8	biogrid_interaction
BCL2	TP53	intact, string_interaction
BIRC3	CASP10	biogrid_interaction
BIRC3	CASP8	biogrid_interaction
BTK	PLCG2	string_interaction
BTK	RPS6KB1	biogrid_interaction
C11orf21	TSPAN32	string_interaction
CASP10	CASP8	biogrid_interaction, intact, string_interaction
CASP10	TP53	string_interaction
CDKN2B	DMRTA1	string_interaction
CDKN2B	TP53	string_interaction
CIMAP1B	NCAPH2	string_interaction
CIMAP1B	SCO2	string_interaction
CLPTM1L	TERT	string_interaction
CXXC1	TP53	biogrid_interaction, intact
HLA-DQA1	HLA-DQB1	biogrid_interaction, intact
HLA-DQA1	HLA-DRB5	intact
HLA-DRB1	HLA-DRB5	biogrid_interaction, intact
ILRUN	SPDEF	string_interaction
IRF2	IRF8	biogrid_interaction
IRF2	SP140	string_interaction
IRF4	MYD88	biogrid_interaction
LRRC34	MYNN	string_interaction
PIAS4	RREB1	intact
PLCG2	TP53	biogrid_interaction, intact
POT1	RHOU	biogrid_interaction
POT1	TERT	string_interaction
SP140	TP53	string_interaction
TP53	ZBTB7A	biogrid_interaction

Structural data

PDB: 45 · AlphaFold-only: 26 · No structure: 4

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
GNAS	O95467	490
TP53	P04637	313
BTK	Q06187	156
HLA-DRB1	P01911	108
SF3B1	O75533	74
BCL2	P10415	55
CASP8	Q14790	36
FASN	P49327	34
NOTCH1	P46531	29
HLA-DQA1	P01909	28
TERT	O14746	23
RPS6KB1	P23443	22
IRF4	Q15306	19
POT1	Q9NUX5	14
MYD88	Q99836	14
ATM	Q13315	14
ZBTB7A	O95365	11
HLA-DQB1	P01920	10
BUB1B	O60566	9
CAMK2D	Q13557	9
PLCG2	P16885	8
BIRC3	Q13489	6
CXXC1	Q9P0U4	6
ACTA1	P68133	5
SP140	Q13342	5
BMF	Q96LC9	5
ELL2	O00472	4
PRKD2	Q9BZL6	4
TYMP	P19971	4
HLA-DRB5	Q30154	4

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
ACTA2	P62736	95.43
ACOXL	Q9NUZ1	92.00
CDKN2B	P42772	90.12
TMPRSS5	Q9H3S3	79.62
VMP1	Q96GC9	78.64
CLPTM1L	Q96KA5	78.54
PIAS4	Q8N2W9	77.03
FARP2	O94887	76.34
DTNB	O60941	76.29
IRF8	Q02556	75.54
CIMAP1B	A8MYP8	73.82
TSPAN32	Q96QS1	72.74
CASP10	Q92851	69.54
HYCC2	Q8IXS8	69.27
GRAMD1B	Q3KR37	68.76
STRN4	Q9NRL3	68.59
BANK1	Q8NDB2	61.25
CSRNP1	Q96S65	59.38
LEF1	Q9UJU2	57.74
DMRTA1	Q5VZB9	57.14
CREBRF	Q8IUR6	57.02
EOMES	O95936	56.74
C11orf21	Q9P2W6	55.54
RREB1	Q92766	48.28
MDS2	Q8NDY4	37.44
TACC2	O95359

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 537. Enrichment computed across 92 evidence-associated genes (58 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 58 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Interferon gamma signaling	9	19.5×	4e-07	CAMK2D, HLA-DQA1, HLA-DQB1, HLA-DRB1, HLA-DRB5, IRF8, IRF2, IRF4 (+1 more)
Programmed Cell Death	8	20.2×	1e-06	BCL2, CASP8, BMF, BIRC3, IRF2, PMAIP1, BAK1, BCL2L11
Cytokine Signaling in Immune system	12	8.4×	2e-06	BCL2, CAMK2D, CASP8, IRF8, BIRC3, IRF2, IRF4, MYC (+4 more)
Intrinsic Pathway for Apoptosis	6	30.3×	5e-06	BCL2, CASP8, BMF, PMAIP1, BAK1, BCL2L11
BH3-only proteins associate with and inactivate anti-apoptotic BCL-2 members	4	87.5×	8e-06	BCL2, BMF, PMAIP1, BCL2L11
Generation of second messenger molecules	5	29.8×	5e-05	HLA-DQA1, HLA-DRB1, HLA-DRB5, NCK1, PLCG2
Regulated Necrosis	4	49.2×	8e-05	CASP8, BIRC3, IRF2, BAK1
Apoptosis	6	17.4×	8e-05	BCL2, CASP8, BMF, PMAIP1, BAK1, BCL2L11
Activation of BH3-only proteins	4	34.2×	3e-04	BCL2, BMF, PMAIP1, BCL2L11
Interferon Signaling	6	12.4×	4e-04	CAMK2D, IRF8, IRF2, IRF4, NCK1, NEDD4
TP53 Regulates Transcription of Caspase Activators and Caspases	3	49.2×	0.001	TP53, CASP10, ATM
Immune System	15	3.4×	0.001	BCL2, BTK, CAMK2D, CASP10, CASP8, IRF8, BIRC3, IRF2 (+7 more)
Signal Transduction	17	3.0×	0.001	BCL2, RPS6KB1, BTK, BUB1B, TERT, ACTA2, CAMK2D, CASP10 (+9 more)
Death Receptor Signaling	5	12.0×	0.002	CASP10, CASP8, BIRC3, MYD88, BCL2L11
Toll Like Receptor 4 (TLR4) Cascade	5	11.3×	0.003	BTK, CASP8, BIRC3, MYD88, PLCG2
Translocation of ZAP-70 to Immunological synapse	3	32.8×	0.003	HLA-DQA1, HLA-DRB1, HLA-DRB5
Phosphorylation of CD3 and TCR zeta chains	3	28.1×	0.004	HLA-DQA1, HLA-DRB1, HLA-DRB5
TP53 Regulates Transcription of Cell Death Genes	3	28.1×	0.004	CASP10, ATM, PMAIP1
TP53 Regulates Transcription of Genes Involved in Cytochrome C Release	3	28.1×	0.004	TP53, ATM, PMAIP1
Co-inhibition by PD-1	3	26.9×	0.005	HLA-DQA1, HLA-DRB1, HLA-DRB5
FasL/ CD95L signaling	2	78.8×	0.006	CASP10, CASP8
Interleukin-4 and Interleukin-13 signaling	5	8.9×	0.006	TP53, BCL2, RHOU, IRF4, MYC
MITF-M-dependent gene expression	4	12.5×	0.007	BCL2, TERT, IRF4, LEF1
Pyroptosis	3	21.9×	0.007	TP53, IRF2, BAK1
Activation of NOXA and translocation to mitochondria	2	65.6×	0.008	TP53, PMAIP1
Nucleotide-binding domain, leucine rich repeat containing receptor (NLR) signaling pathways	3	18.5×	0.011	BCL2, CASP8, BIRC3
Antigen activates B Cell Receptor (BCR) leading to generation of second messengers	3	18.5×	0.011	BTK, NCK1, PLCG2
Interferon alpha/beta signaling	4	10.5×	0.011	IRF8, IRF2, IRF4, OAS3
TRAIL signaling	2	49.2×	0.012	CASP10, CASP8
Regulation of NFE2L2 gene expression	2	49.2×	0.012	MYC, NOTCH1

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 84 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
positive regulation of release of cytochrome c from mitochondria	5	45.6×	7e-05	TP53, BMF, PMAIP1, BAK1, BCL2L11
peptide antigen assembly with MHC class II protein complex	4	50.1×	6e-04	HLA-DQA1, HLA-DQB1, HLA-DRB1, HLA-DRB5
positive regulation of apoptotic process	10	6.8×	6e-04	TP53, BCL2, CASP8, SPDEF, BMF, IRF8, ATM, PMAIP1 (+2 more)
positive regulation of transcription by RNA polymerase II	19	3.4×	6e-04	TP53, RREB1, SF3B1, KLF10, CSRNP1, SPDEF, PRKD2, CREBRF (+11 more)
release of cytochrome c from mitochondria	4	33.4×	9e-04	TP53, BCL2, PMAIP1, BAK1
intrinsic apoptotic signaling pathway in response to DNA damage	5	19.3×	9e-04	BCL2, MYC, ATM, BAK1, BCL2L11
apoptotic process	13	4.4×	9e-04	BCL2, RPS6KB1, BUB1B, CSRNP1, CASP10, CASP8, CLPTM1L, BIRC3 (+5 more)
regulation of transcription by RNA polymerase II	21	2.9×	9e-04	TP53, RREB1, KLF10, DMRTA1, CSRNP1, CAMK2D, MYNN, PIAS4 (+13 more)
defense response to protozoan	4	28.7×	0.001	TSPAN32, IRF8, IRF4, MYD88
antigen processing and presentation of exogenous peptide antigen via MHC class II	4	25.9×	0.002	HLA-DQA1, HLA-DQB1, HLA-DRB1, HLA-DRB5
positive regulation of neuron apoptotic process	5	16.2×	0.002	TP53, CASP10, CASP8, ATM, BCL2L11
negative regulation of transcription by RNA polymerase II	16	3.4×	0.002	TP53, RREB1, KLF10, PIAS4, SPDEF, ZBTB7A, CREBRF, EOMES (+8 more)
positive regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway	3	54.7×	0.002	NCK1, PMAIP1, BCL2L11
B cell apoptotic process	3	50.1×	0.002	BCL2, MYC, BAK1
regulation of mitochondrial membrane permeability	3	50.1×	0.002	BCL2, PMAIP1, BAK1
thymocyte apoptotic process	3	50.1×	0.002	TP53, BAK1, BCL2L11
positive regulation of immune response	4	22.9×	0.002	HLA-DQA1, HLA-DQB1, HLA-DRB1, HLA-DRB5
B cell activation	4	21.7×	0.002	BTK, CASP8, BANK1, PLCG2
positive regulation of T cell activation	4	21.1×	0.002	HLA-DQA1, HLA-DQB1, HLA-DRB1, HLA-DRB5
B cell receptor signaling pathway	4	19.1×	0.003	BCL2, BTK, BANK1, PLCG2
adaptive immune response	7	7.0×	0.003	BTK, PRKD2, EOMES, HLA-DQA1, HLA-DQB1, HLA-DRB5, NEDD4
cellular response to hypoxia	6	8.7×	0.003	TP53, BCL2, TERT, MYC, NOTCH1, PMAIP1
apoptotic process involved in embryonic digit morphogenesis	2	133.8×	0.004	NOTCH1, BCL2L11
replicative senescence	3	35.4×	0.004	TP53, TERT, ATM
follicular B cell differentiation	2	100.3×	0.005	IRF8, PLCG2
regulation of T-helper cell differentiation	2	100.3×	0.005	HLA-DRB1, IRF4
glomerular mesangial cell development	2	100.3×	0.005	ACTA2, NOTCH1
epithelial cell fate commitment	2	100.3×	0.005	SPDEF, NOTCH1
endoplasmic reticulum calcium ion homeostasis	3	30.1×	0.005	BCL2, CAMK2D, BAK1
positive regulation of execution phase of apoptosis	3	30.1×	0.005	TP53, CASP10, CASP8

Therapeutics

Drugs indicated for this disease

10 approved, 20 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)
Alemtuzumab	Approved (phase 4)
Duvelisib	Approved (phase 4)
Fludarabine Phosphate	Approved (phase 4)
Ibrutinib	Approved (phase 4)
Idelalisib	Approved (phase 4)
Obinutuzumab	Approved (phase 4)
Ofatumumab	Approved (phase 4)
Rituximab	Approved (phase 4)
Venetoclax	Approved (phase 4)
Bendamustine	Phase 3 (in late-stage trials)
Chlorambucil	Phase 3 (in late-stage trials)
Cholecalciferol	Phase 3 (in late-stage trials)
Cladribine	Phase 3 (in late-stage trials)
Darbepoetin Alfa	Phase 3 (in late-stage trials)
Dinaciclib	Phase 3 (in late-stage trials)
Doxorubicin	Phase 3 (in late-stage trials)
Filgrastim	Phase 3 (in late-stage trials)
Fludarabine	Phase 3 (in late-stage trials)
Lenalidomide	Phase 3 (in late-stage trials)
Mitoxantrone	Phase 3 (in late-stage trials)
Nemtabrutinib	Phase 3 (in late-stage trials)
Orelabrutinib	Phase 3 (in late-stage trials)
Pentostatin	Phase 3 (in late-stage trials)
Pirtobrutinib	Phase 3 (in late-stage trials)
Prednisone	Phase 3 (in late-stage trials)
Sonrotoclax	Phase 3 (in late-stage trials)
Ublituximab	Phase 3 (in late-stage trials)
Vincristine	Phase 3 (in late-stage trials)
Zanubrutinib	Phase 3 (in late-stage trials)

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): Aldesleukin, Allopurinol, Alvocidib, Arsenic Trioxide, Atezolizumab, Auranofin, Azacitidine, Belimumab, Bevacizumab, Bortezomib, Brentuximab Vedotin, Buparlisib, Busulfan, Carmustine, Ciprofloxacin, Cirmtuzumab, Clarithromycin, Clofarabine, Copanlisib, Curcumin, Cyclosporine, Cytarabine, Daratumumab, Dasatinib Anhydrous, Denileukin Diftitox, Dexamethasone, Diphtheria Toxoid, Eltrombopag, Entospletinib, Etoposide, Forodesine, Givinostat, Hyaluronidase, Hydroxychloroquine, Imiquimod, Inebilizumab, Influenza Virus Vaccine, Isosorbide, Lansoprazole, Maraviroc, Melphalan, Metformin, Methotrexate, Methylprednisolone, Metronidazole, Motexafin Gadolinium, Mycophenolate Mofetil, Navitoclax, Niacinamide, Nivolumab, OMEGA-3 FATTY ACIDS, Pembrolizumab, Perifosine, Pertussis Vaccine Adsorbed, Romidepsin, Ruxolitinib, Sargramostim, Sirolimus, Sorafenib, TOSITUMOMAB 131I, Tacrolimus Anhydrous, Tafasitamab, Tenofovir Alafenamide, Tetanus Toxoid, Thalidomide, Tipifarnib, Tirabrutinib, Tisagenlecleucel, Tositumomab, Umbralisib, Valacyclovir, Valganciclovir, Valproic Acid, Vitespen, Vorinostat, YTTRIUM Y 90 IBRITUMOMAB TIUXETAN, Zandelisib.

Drug target analysis

Approved (phase 4): 14 · Phase ≥3: 15 · Phased (≥1): 17 · Undrugged: 58

Druggability breadth: 48 of 92 evidence-associated genes (52%) 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
TP53	NITROFURANTOIN
BCL2	IXABEPILONE
BTK	PONATINIB
ATM	AMIODARONE HYDROCHLORIDE
RPLP1	GENTAMICIN SULFATE
RPS6KB1	FEDRATINIB
BUB1B	CERITINIB
TERT	BERBERINE
KLF10	TOLCAPONE
CAMK2D	MOMELOTINIB
CASP8	PRIMAQUINE PHOSPHATE
PRKD2	MOMELOTINIB
TYMP	TIPIRACIL
FASN	RABEPRAZOLE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
TP53	196	4
BTK	84	4
PRKD2	63	4
CAMK2D	40	4
RPS6KB1	39	4
ATM	35	4
BCL2	14	4
TERT	10	4
FASN	8	4
BIRC3	4	3

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
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
AMIODARONE HYDROCHLORIDE	4	ATM, TP53
FURAZOLIDONE	4	ATM, TP53
AMOXAPINE	4	TP53
RALOXIFENE HYDROCHLORIDE	4	TP53
NICARDIPINE HYDROCHLORIDE	4	TP53
SULCONAZOLE NITRATE	4	TP53
PYRITHIONE ZINC	4	TP53
LACTIC ACID	4	TP53
OXYMETHOLONE	4	TP53
CHLOROXINE	4	TP53
PROPIOLACTONE	4	TP53
CLOMIPRAMINE HYDROCHLORIDE	4	TP53
PHENYL AMINOSALICYLATE	4	TP53
THIORIDAZINE HYDROCHLORIDE	4	TP53
AMITRIPTYLINE HYDROCHLORIDE	4	ATM, TP53
ETHOPROPAZINE HYDROCHLORIDE	4	TP53
MECHLORETHAMINE HYDROCHLORIDE	4	TP53
ECONAZOLE NITRATE	4	TP53
TRIFLUPROMAZINE HYDROCHLORIDE	4	TP53
PROCHLORPERAZINE EDISYLATE	4	TP53
DEQUALINIUM CHLORIDE	4	TP53

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 12.

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

Symbol	Assays	Type breakdown
BTK	1,836	Binding:1810, Functional:23, ADMET:3
TP53	869	Binding:775, ADMET:83, Functional:10, Toxicity:1
RPS6KB1	585	Binding:582, Functional:2, ADMET:1
BCL2	446	Binding:418, Functional:23, Toxicity:3, ADMET:2
TERT	391	Binding:389, Functional:2
PRKD2	360	Binding:359, Functional:1
CAMK2D	338	Binding:337, Functional:1
ATM	240	Binding:233, Functional:5, ADMET:2
FASN	142	Binding:136, Functional:6
BIRC3	119	Binding:119
CASP8	116	Binding:106, Functional:10
TYMP	94	Binding:91, Functional:3
RPLP1	90	Binding:90
MYD88	26	Binding:26
NOTCH1	23	Binding:19, ADMET:4
SF3B1	22	Binding:22
CASP10	22	Binding:21, Functional:1
HLA-DRB1	17	Binding:17
BUB1B	12	Binding:12
PLCG2	11	Binding:11
KLF10	10	Binding:10
SP140	8	Binding:8
PIAS4	6	Binding:6
IRF4	3	Binding:3
MYNN	2	Binding:2
ZBTB7A	2	Binding:2
HLA-DQA1	2	Binding:2
LEF1	2	Binding:2
POT1	1	Binding:1
SCO2	1	Binding:1
CREBRF	1	Binding:1
CLPTM1L	1	Binding:1
CXXC1	1	Binding:1
VMP1	1	Binding:1
MNS1	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
BTK	2.7.10.2	non-specific protein-tyrosine kinase
BIRC3	2.3.2.27	RING-type E3 ubiquitin transferase
ATM	2.7.11.1	non-specific serine/threonine protein kinase
PLCG2	3.1.4.11	phosphoinositide phospholipase C
RPS6KB1	2.7.11.1	non-specific serine/threonine protein kinase
BUB1B	2.7.11.1	non-specific serine/threonine protein kinase
CAMK2D	2.7.11.17	Ca2+/calmodulin-dependent protein kinase
CASP10	3.4.22.63	caspase-10
CASP8	3.4.22.61	caspase-8
PRKD2	2.7.11.13	protein kinase C
TYMP	2.4.2.4	thymidine phosphorylase
FASN	2.3.1.39, 2.3.1.85	[acyl-carrier-protein] S-malonyltransferase, fatty-acid synthase system

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
TP53	869
BCL2	446
BTK	1,836
BIRC3	119
ATM	240
RPS6KB1	585
TERT	391
CAMK2D	338
CASP8	116
PRKD2	360
FASN	142

Pharmacogenomics

Cohort genes with a PharmGKB record: 73; 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)
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
AMIODARONE HYDROCHLORIDE	4	ATM, TP53
FURAZOLIDONE	4	ATM, TP53
AMOXAPINE	4	TP53
RALOXIFENE HYDROCHLORIDE	4	TP53
NICARDIPINE HYDROCHLORIDE	4	TP53
SULCONAZOLE NITRATE	4	TP53
PYRITHIONE ZINC	4	TP53
LACTIC ACID	4	TP53
OXYMETHOLONE	4	TP53
CHLOROXINE	4	TP53
PROPIOLACTONE	4	TP53
CLOMIPRAMINE HYDROCHLORIDE	4	TP53
PHENYL AMINOSALICYLATE	4	TP53
THIORIDAZINE HYDROCHLORIDE	4	TP53
AMITRIPTYLINE HYDROCHLORIDE	4	ATM, TP53
ETHOPROPAZINE HYDROCHLORIDE	4	TP53
MECHLORETHAMINE HYDROCHLORIDE	4	TP53
ECONAZOLE NITRATE	4	TP53
TRIFLUPROMAZINE HYDROCHLORIDE	4	TP53
PROCHLORPERAZINE EDISYLATE	4	TP53
DEQUALINIUM CHLORIDE	4	TP53

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	14	TP53, BCL2, BTK, ATM, RPLP1, RPS6KB1, BUB1B, TERT, KLF10, CAMK2D (+4 more)
B	Phased (≥1) drug, not yet approved	3	SF3B1, BIRC3, NOTCH1
C	Druggable family + PDB, no drug	7	ULK4, SCN3B, ILRUN, HLA-DQA1, HLA-DQB1, HLA-DRB1, HLA-DRB5
D	Druggable family + AlphaFold only, no drug	2	TMPRSS5, CASP10
E	Difficult family or no structure, no drug	49	POT1, GNAS, MYD88, PLCG2, RREB1, SCO2, TACC2, TERC, ACTA1, ACTA2 (+39 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)
PLCG2	11	BTK
CASP10	22	CASP8
PIAS4	6	ATM
CDKN2B	0	TP53
BMF	0	BCL2
CLPTM1L	1	TERT
POT1	1	—
GNAS	0	—
MYD88	26	—
RREB1	0	—
SCO2	1	—
TACC2	0	—
TERC	0	—
ACTA1	0	—
ACTA2	0	—
C11orf21	0	—
TSPAN32	0	—
DMRTA1	0	—
CSRNP1	0	—
TMPRSS5	0	—
MYNN	2	—
STRN4	0	—
ULK4	0	—
FARP2	0	—
ELL2	0	—
SP140	8	—
SPDEF	0	—
RHOU	0	—
ZBTB7A	2	—
BANK1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 1,182.

Phase distribution (across all retrieved trials)

Phase	Trials
PHASE2	407
PHASE1	289
PHASE1/PHASE2	145
Not specified	139
PHASE3	95
PHASE4	10
EARLY_PHASE1	10
PHASE2/PHASE3	5

Top trials by phase / activity

NCT	Phase	Status	Title
NCT04790045	PHASE4	NOT_YET_RECRUITING	Lymph Node Microenvironment Modifications in Patients With CLL Treated With Venetoclax-based Regimens
NCT06651970	PHASE4	RECRUITING	Acalabrutinib Monotherapy vs Investigator’s Choice of Treatment in Patients With CL Leukaemia and Heart Failure
NCT06876649	PHASE4	RECRUITING	A Master Protocol to Evaluate the Long-Term Safety of (LY3527727) Pirtobrutinib
NCT06876662	PHASE4	RECRUITING	A Study of (LY3527727) Pirtobrutinib in Participants With Previously Treated Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma or Non-Hodgkin Lymphoma
NCT07218341	PHASE4	RECRUITING	A Study of Pirtobrutinib (LY3527727) in Participants With Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
NCT00131313	PHASE4	UNKNOWN	Efficacy and Safety of Nipent, Cytoxan and Rituxan in the Treatment of Chronic Lymphocytic Leukemia.
NCT00802737	PHASE4	COMPLETED	Efficacy and Safety of Ofatumumab Retreatment and Maintenance Treatment in Patients With B-cell Chronic Lymphocytic Leukemia (CLL)
NCT00919321	PHASE4	COMPLETED	The Duration of Humoral Immunity and the Memory Cell Function After Vaccination With 7-valent Pneumococcal Conjugate Vaccine in CLL
NCT01255644	PHASE4	COMPLETED	Antiviral Treatment of Chronic Lymphocytic Leukemia
NCT05316831	PHASE4	COMPLETED	Immune Response After Pneumococcal Vaccination in Patient With Chronic Lymphocytic Leukemia
NCT01804686	PHASE3	RECRUITING	A Long-term Extension Study of PCI-32765 (Ibrutinib)
NCT01886872	PHASE3	ACTIVE_NOT_RECRUITING	Rituximab and Bendamustine Hydrochloride, Rituximab and Ibrutinib, or Ibrutinib Alone in Treating Older Patients With Previously Untreated Chronic Lymphocytic Leukemia
NCT02048813	PHASE3	ACTIVE_NOT_RECRUITING	Ibrutinib and Rituximab Compared With Fludarabine Phosphate, Cyclophosphamide, and Rituximab in Treating Patients With Untreated Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma
NCT02475681	PHASE3	ACTIVE_NOT_RECRUITING	Acalabrutinib, Obinutuzumab and Chlorambucil in Treatment naïve CLL
NCT02477696	PHASE3	ACTIVE_NOT_RECRUITING	Study of Acalabrutinib (ACP-196) Versus Ibrutinib in Previously Treated Participants With High Risk Chronic Lymphocytic Leukemia (CLL)
NCT02970318	PHASE3	ACTIVE_NOT_RECRUITING	A Study of Acalabrutinib vs Investigator’s Choice of Idelalisib Plus Rituximab or Bendamustine Plus Rituximab in R/R CLL
NCT03336333	PHASE3	ACTIVE_NOT_RECRUITING	A Study Comparing Zanubrutinib With Bendamustine Plus Rituximab in Participants With Previously Untreated CLL or SLL
NCT03480360	PHASE3	ACTIVE_NOT_RECRUITING	Haploidentical Allogeneic Peripheral Blood Transplantation: Examining Checkpoint Immune Regulators’ Expression
NCT03701282	PHASE3	ACTIVE_NOT_RECRUITING	Assessing the Ability of Combination Treatment With Venetoclax to Permit Time Limited Therapy in Chronic Lymphocytic Leukemia
NCT03737981	PHASE3	ACTIVE_NOT_RECRUITING	Testing the Addition of a New Anti-cancer Drug, Venetoclax, to the Usual Treatment (Ibrutinib and Obinutuzumab) in Untreated, Older Patients With Chronic Lymphocytic Leukemia
NCT03836261	PHASE3	ACTIVE_NOT_RECRUITING	Study of Acalabrutinib (ACP-196) in Combination With Venetoclax (ABT-199), With and Without Obinutuzumab (GA101) Versus Chemoimmunotherapy for Previously Untreated CLL
NCT03844048	PHASE3	ACTIVE_NOT_RECRUITING	An Extension Study of Venetoclax for Subjects Who Have Completed a Prior Venetoclax Clinical Trial
NCT03868722	PHASE2/PHASE3	RECRUITING	Acalabrutinib and Venetoclax Treatment of Newly Diagnosed Patients With CLL at High Risk of Infection or Early Treatment
NCT04269902	PHASE3	RECRUITING	Testing Early Treatment for Patients With High-Risk Chronic Lymphocytic Leukemia (CLL) or Small Lymphocytic Leukemia (SLL), EVOLVE CLL/SLL Study
NCT04666038	PHASE3	ACTIVE_NOT_RECRUITING	Study of LOXO-305 (Pirtobrutinib) Versus Investigator’s Choice (Idelalisib Plus Rituximab or Bendamustine Plus Rituximab) in Patients With Previously Treated Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma (SLL)
NCT04965493	PHASE3	ACTIVE_NOT_RECRUITING	A Trial of Pirtobrutinib (LOXO-305) Plus Venetoclax and Rituximab (PVR) Versus Venetoclax and Rituximab (VR) in Previously Treated Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL)
NCT05023980	PHASE3	ACTIVE_NOT_RECRUITING	A Study of Pirtobrutinib (LOXO-305) Versus Bendamustine Plus Rituximab (BR) in Untreated Patients With Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma (SLL)
NCT05057494	PHASE3	ACTIVE_NOT_RECRUITING	A Study of Acalabrutinib Plus Venetoclax Versus Venetoclax Plus Obinutuzumab in Previously Untreated Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma
NCT05197192	PHASE3	RECRUITING	A Phase-3-trial of Acalabrutinib, Obinutuzumab & Venetoclax Compared to Obinutuzumab and Venetoclax in Previously Untreated Patients With High Risk CLL
NCT05254743	PHASE3	RECRUITING	A Study of Pirtobrutinib (LOXO-305) Versus Ibrutinib in Participants With Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma (SLL)
NCT05556720	PHASE3	ACTIVE_NOT_RECRUITING	Bringing Optimised COVID-19 Vaccine Schedules To ImmunoCompromised Populations (BOOST-IC): an Adaptive Randomised Controlled Clinical Trial
NCT05624554	PHASE3	ACTIVE_NOT_RECRUITING	A Study of Nemtabrutinib vs Chemoimmunotherapy for Participants With Previously Untreated Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL) Without TP53 Aberrations (MK-1026-008, BELLWAVE-008)
NCT05645107	PHASE3	RECRUITING	A Study to Evaluate Efficacy, Safety, and PK of XEMBIFY®+Standard Medical Treatment (SMT) Compared to Placebo+SMT to Prevent Infections in Participants With HGG and Recurrent or Severe Infections Associated With B-cell Chronic Lymphocytic Leukemia, Multiple Myeloma, and Non-Hodgkin Lymphoma
NCT05947851	PHASE3	RECRUITING	A Study of Nemtabrutinib Plus Venetoclax vs Venetoclax + Rituximab (VR) in Second-line (2L) + Relapsed/Refractory (R/R) Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL) (MK-1026-010/BELLWAVE-010).
NCT06073821	PHASE3	ACTIVE_NOT_RECRUITING	Study of Sonrotoclax (BGB-11417) Plus Zanubrutinib (BGB-3111) Compared With Venetoclax Plus Obinutuzumab in Participants With Chronic Lymphocytic Leukemia (CLL)
NCT06136559	PHASE3	RECRUITING	A Study of Nemtabrutinib (MK-1026) Versus Comparator (Investigator’s Choice of Ibrutinib or Acalabrutinib) in First Line (1L) Chronic Lymphocytic Leukemia (CLL)/ Small Lymphocytic Lymphoma (SLL) (MK-1026-011/BELLWAVE-011)
NCT06428019	PHASE3	RECRUITING	A Study to Evaluate the Risk of Tumor Lysis Syndrome (TLS) in Adult Participants Receiving Oral Venetoclax in Combination With Intravenously Infused Obinutuzumab or Oral Acalabrutinib for Previously Untreated Chronic Lymphocytic Leukemia (CLL)
NCT06846671	PHASE3	RECRUITING	A Study of BGB-16673 Compared to Investigator’s Choice in Participants With Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma Previously Exposed to Both Bruton Tyrosine Kinase (BTK) and B-cell Leukemia/Lymphoma 2 Protein (BCL2) Inhibitors
NCT06943872	PHASE3	RECRUITING	A Study to Investigate Progression-Free Survival With Sonrotoclax Plus Obinutuzumab Or Sonrotoclax Plus Rituximab Compared With Venetoclax Plus Rituximab Treatment In Patients With Relapsed and/or Refractory Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CELESTIAL-RRCLL)
NCT06970743	PHASE3	RECRUITING	A Study of BGB-16673 Compared to Investigator’s Choice in Participants With Relapsed/Refractory Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma Previously Exposed to Covalent Bruton Tyrosine Kinase (BTK) Inhibitors

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
CYCLOPHOSPHAMIDE ANHYDROUS	4	110
BENDAMUSTINE	4	37
OFATUMUMAB	4	36
ACALABRUTINIB	4	34
OBINUTUZUMAB	4	32
VENETOCLAX	4	31
IBRUTINIB	4	30
IDELALISIB	4	29
PIRTOBRUTINIB	4	22
CHLORAMBUCIL	4	20
FLUDARABINE PHOSPHATE	4	18
UBLITUXIMAB	4	16
ALEMTUZUMAB	4	13
DUVELISIB	4	11
PENTOSTATIN	4	9
UMBRALISIB	4	6
LENALIDOMIDE	4	3
VALGANCICLOVIR	4	3
MITOXANTRONE	4	2
RITUXIMAB	4	2
FERRIC OXYHYDROXIDE	4	1
MYCOPHENOLATE MOFETIL	4	1
STREPTOCOCCUS PNEUMONIAE POLYSACCHARIDE CONJUGATED TO CORYNEBACTERIUM DIPHTHERIAE CRM197	4	1
FLUDARABINE	3	15
DINACICLIB	3	3
CHEMBL4747506	0	34
CHEMBL5187554	0	34
CHEMBL5276925	0	34
CHEMBL3970001	0	33
CHEMBL3647964	0	28

Precision-medicine subtype map (CIViC)

Drug × molecular subtype: 39 predictive associations from 47 curated evidence items; also 25 prognostic, 1 predisposing.

Molecular subtype	Therapy	Effect	Level	CIViC
TP53 Mutation	Alemtuzumab	Sensitivity/Response	CIViC B	EID1481
BCL2 G101V	Venetoclax	Resistance	CIViC B	EID8174 +5
BCL2 D103Y	Venetoclax	Resistance	CIViC B	EID8312 +1
BTK C481S	Ibrutinib	Resistance	CIViC B	EID1770 +1
BCL2 R107_R110dup	Venetoclax	Resistance	CIViC B	EID8309
BCL2 V156D	Venetoclax	Resistance	CIViC B	EID8306
BCL2 D103E	Venetoclax	Resistance	CIViC C	EID8311 +1
BCL2 A113G	Venetoclax	Resistance	CIViC C	EID8308
BCL2 D103V	Venetoclax	Resistance	CIViC C	EID8310
BCL2 R129L	Venetoclax	Resistance	CIViC C	EID8307
BTK C481R	Venetoclax	Resistance	CIViC C	EID10374
BTK C481Y	Venetoclax	Resistance	CIViC C	EID10373
BTK T316A	Ibrutinib	Resistance	CIViC C	EID1985
PLCG2 D1140E	Venetoclax	Resistance	CIViC C	EID10372
PLCG2 N571S	Venetoclax	Resistance	CIViC C	EID10371
ATM A2062V	Doxorubicin	Resistance	CIViC D	EID2846
ATM A2274T	Doxorubicin	Resistance	CIViC D	EID2848
ATM C2488Y	Doxorubicin	Resistance	CIViC D	EID2849
ATM D1682H	Doxorubicin	Resistance	CIViC D	EID2845
ATM D1930V	Doxorubicin	Resistance	CIViC D	EID2837
ATM E2187*	Doxorubicin	Resistance	CIViC D	EID2839
ATM F1025L	Doxorubicin	Resistance	CIViC D	EID2835
ATM F2732V	Doxorubicin	Resistance	CIViC D	EID2841
ATM K293*	Doxorubicin	Resistance	CIViC D	EID2832
ATM K468FS	Doxorubicin	Resistance	CIViC D	EID2843
ATM L2427P	Doxorubicin	Resistance	CIViC D	EID2840
ATM Mutation	Doxorubicin	Resistance	CIViC D	EID2222
ATM Q1084*	Doxorubicin	Resistance	CIViC D	EID2836
ATM Q984E	Doxorubicin	Resistance	CIViC D	EID2834
ATM R1575H	Doxorubicin	Resistance	CIViC D	EID2847

+9 more predictive associations (showing top 30 by evidence level).