diffuse large B-cell lymphoma

Summary

diffuse large B-cell lymphoma (MONDO:0018905) is a cancer (an umbrella term covering 30 Mondo subtypes) with 52 cohort genes (32 GWAS associations across 14 studies; 36 CIViC-evidence somatic drivers; 23 ClinVar predisposition records) and 859 clinical trials. The dominant Reactome pathway is Cellular response to chemical stress (6 cohort genes). Molecularly, CDC50A loss-of-function mutation confers sensitivity to R-CHOP Regimen in Diffuse Large B-cell Lymphoma (CIViC Level B); 12 further subtype–drug associations are mapped below. Top therapeutic interventions include cyclophosphamide anhydrous, tafasitamab, and axicabtagene ciloleucel.

At a glance

• Classification: Cancer
• Prevalence: 1-5 / 10 000 (Europe) [Orphanet-validated]
• Umbrella term: 30 Mondo subtypes
• Cohort genes: 52
• GWAS associations: 32
• ClinVar variants: 23
• Clinical trials: 859
• Precision-medicine evidence (CIViC): 13 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	2.79	Europe	Validated
Point prevalence	1-5 / 10 000	43	Europe	Validated
Annual incidence	1-9 / 100 000	6.5	France	Validated
Annual incidence	1-9 / 1 000 000	0.765	Croatia	Validated
Annual incidence	1-9 / 1 000 000	0.298	Latvia	Validated
Annual incidence	1-9 / 100 000	2.227	Austria	Validated
Annual incidence	1-9 / 100 000	5.51	Belgium	Validated
Annual incidence	1-9 / 100 000	1.229	Bulgaria	Validated
Annual incidence	1-9 / 100 000	3.304	Czech Republic	Validated
Annual incidence	1-9 / 100 000	3.815	Estonia	Validated
Annual incidence	1-9 / 100 000	1.244	Finland	Validated
Annual incidence	1-9 / 100 000	4.586	Germany	Validated
Annual incidence	1-9 / 100 000	4.559	Iceland	Validated
Annual incidence	1-9 / 100 000	3.458	Ireland	Validated
Annual incidence	1-9 / 100 000	6.47	Italy	Validated
Annual incidence	1-9 / 100 000	2.984	Lithuania	Validated
Annual incidence	1-9 / 100 000	2.827	Malta	Validated
Annual incidence	1-9 / 100 000	5.115	Norway	Validated
Annual incidence	1-9 / 100 000	1.673	Poland	Validated
Annual incidence	1-9 / 100 000	2.635	Portugal	Validated

Identifiers

Disease identifiers

Field	Value
Canonical name	diffuse large B-cell lymphoma
Mondo ID	MONDO:0018905
EFO	EFO:0000403
MeSH	D016403
Orphanet	544
DOID	DOID:0050745
ICD-10-CM	C83.3
ICD-11	1946973604
NCIT	C8851
UMLS	C0079744
MedGen	86954
GARD	0003178
MedDRA	10012818
Is cancer (heuristic)	yes

Also known as: diffuse large B-cell lymphoma · DLBCL

Data availability: 23 ClinVar variants · 32 GWAS associations (14 studies) · 143 cell lines.

Disease family

An umbrella term covering 30 Mondo subtypes.

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

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

Subtypes (30): relapsed/refractory diffuse large B-cell lymphoma, breast diffuse large B-cell lymphoma, colorectal diffuse large B-cell lymphoma, gastric diffuse large B-cell lymphoma, liver diffuse large B-cell lymphoma, primary cutaneous diffuse large B-cell lymphoma, Leg type, primary pulmonary diffuse large B-cell lymphoma, small intestinal diffuse large B-cell lymphoma, splenic diffuse large B-cell lymphoma, thyroid gland diffuse large B-cell lymphoma, Epstein-Barr virus-positive diffuse large B-cell lymphoma of the elderly, plasmablastic lymphoma, diffuse large B-cell lymphoma of the central nervous system, T-cell/histiocyte rich large B cell lymphoma, diffuse large B-cell lymphoma with chronic inflammation, ALK-positive large B-cell lymphoma, primary effusion lymphoma, lymphomatoid granulomatosis, primary mediastinal large B-cell lymphoma, intravascular large B-cell lymphoma, high grade B-cell lymphoma, diffuse large B-cell lymphoma activated B-cell type, diffuse large B-cell lymphoma germinal center B-cell type, BN2 diffuse large B-cell lymphoma, EZB diffuse large B-cell lymphoma, MCD diffuse large B-cell lymphoma, N1 diffuse large B-cell lymphoma, ST2 diffuse large B-cell lymphoma, A53 diffuse large B-cell lymphoma, primary vitreoretinal large b-cell lymphoma

Genetics & variants

GWAS landscape

32 GWAS associations across 14 studies. Top hits map to 14 distinct genes (as reported by GWAS).

Top associations by p-value

rsID	p-value	Gene	Risk allele	Odds ratio
rs116446171	2e-21	IRF4 - EXOC2	G	2.2
rs4713570	3e-21	HLA-DQA1 - HLA-DQB1	?	1.36
rs112516566	3e-13	LINC02571 - HLA-B	?	1.29
rs13255292	6e-13	PVT1	?	1.25
rs4733601	4e-11	RN7SKP226 - LINC00824	A	1.19
rs2523607	2e-10	HLA-B	A	1.32
rs28589559	7e-10	HLA-DRB1 - HLA-DQA1	G	2.49
rs76106586	1e-09	IRF4 - EXOC2	?	1.84
rs138094736	2e-09	HLA-DRB9	G	3.09
rs11187157	3e-09	Y_RNA - EXOC6	C	1.15
rs3131113	3e-09	UBQLN1P1 - MICC	?	1.2
rs2425752	5e-09	NCOA5	?	1.1
rs1444766	1e-08	KALRN	G	1.14
rs140522	2e-08	CIMAP1B - KLHDC7B-DT	?	1.09
rs3890745	2e-08	MMEL1	?	1.14
rs71557353	3e-08	ZNF322 - GUSBP2	G	1.28
rs79480871	4e-08	ITSN2 - NCOA1	T	1.34
rs1323292	5e-08	RGS2-AS1	?	1.11
rs806321	5e-08	DLEU1	?	1.09
rs79464052	6e-08	ARAP3	C	1.34
rs2681416	8e-08	CD86	A	1.16
rs16978630	9e-08	TNPO2	?	1.33
rs7712513	2e-07	MGC32805 - LINC02201	C	1.39
rs12434407	2e-07	MDGA2	?	0.85
rs751837	3e-07	CDC42BPB	?	3.51
rs40836	6e-07	APOBR - IL27	?	1.16
rs7765004	7e-07	LINC02541 - MARCKS	C	1.38
rs140083693	7e-07	RNU6-376P - DDX6	?	1.21
rs9421684	6e-06	LINC02655 - RPS7P9	A	1.14
rs7097	7e-06	POLR1D	?	1.44

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST002636	Cerhan JR	2014	3,857	7,666	Genome-wide association study identifies multiple susceptibility loci for diffuse large B cell lymphoma.
GCST008722	Din L	2019	3,617	24,813	Genetic overlap between autoimmune diseases and non-Hodgkin lymphoma subtypes.
GCST008725	Din L	2019	3,617	11,516	Genetic overlap between autoimmune diseases and non-Hodgkin lymphoma subtypes.
GCST008728	Din L	2019	3,617	23,428	Genetic overlap between autoimmune diseases and non-Hodgkin lymphoma subtypes.
GCST90267402	Berndt SI	2022	3,100	9,505	Distinct germline genetic susceptibility profiles identified for common non-Hodgkin lymphoma subtypes.
GCST90624739	Guler M	2025	2,280	656,255	Clustering of lymphoid neoplasms by cell of origin, somatic mutation and drug usage profiles: a multi-trait genome-wide association study.
GCST003178	Ghesquieres H	2015	852	0	Genome-Wide Association Study of Event-Free Survival in Diffuse Large B-Cell Lymphoma Treated With Immunochemotherapy.
GCST90079634	Backman JD	2021	768	387,162	Exome sequencing and analysis of 454,787 UK Biobank participants.
GCST90083620	Backman JD	2021	768	387,162	Exome sequencing and analysis of 454,787 UK Biobank participants.
GCST90079119	Backman JD	2021	672	73,558	Exome sequencing and analysis of 454,787 UK Biobank participants.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

Tier	Variants
Tier 1: coding	1
Tier 2: splice/UTR	1
Tier 3: regulatory	1
Tier 4: intronic/intergenic	28

MAF distribution

Bucket	Variants
common (>=0.05)	30
low_freq (0.01-0.05)	1
rare (<0.01)	0
unknown	0

Functional consequences

Consequence	Count
intron_variant	19
intergenic_variant	8
regulatory_region_variant	1
missense_variant	1
non_coding_transcript_exon_variant	1
3_prime_UTR_variant	1

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
rs116446171	6	484453	C>G	0.019	intergenic_variant	IRF4 - EXOC2	2e-21	Tier 4: intronic/intergenic
rs4713570	6	32658263	C>G,T	0.05	intergenic_variant	HLA-DQA1 - HLA-DQB1	3e-21	Tier 4: intronic/intergenic
rs112516566	6	31330599	GA>G,GAA	0.05	intron_variant	LINC02571 - HLA-B	3e-13	Tier 4: intronic/intergenic
rs13255292	8	128064327	C>T	0.05	intron_variant	PVT1	6e-13	Tier 4: intronic/intergenic
rs4733601	8	128257220	A>G	0.477	intergenic_variant	RN7SKP226 - LINC00824	4e-11	Tier 4: intronic/intergenic
rs2523607	6	31355013	T>A,C,G	0.12	intron_variant	HLA-B	2e-10	Tier 4: intronic/intergenic
rs28589559	6	32619939	G>A,C,T	0.1	intron_variant	HLA-DRB1 - HLA-DQA1	7e-10	Tier 4: intronic/intergenic
rs76106586	6	483593	A>G	0.05	intergenic_variant	IRF4 - EXOC2	1e-09	Tier 4: intronic/intergenic
rs138094736	6	32471897	G>A	0.05	intron_variant	HLA-DRB9	2e-09	Tier 4: intronic/intergenic
rs11187157	10	92742487	T>C	0.05	regulatory_region_variant	Y_RNA - EXOC6	3e-09	Tier 3: regulatory
rs3131113	6	30398865	C>T	0.05	intergenic_variant	UBQLN1P1 - MICC	3e-09	Tier 4: intronic/intergenic
rs2425752	20	46073481	T>C,G	0.05	intron_variant	NCOA5	5e-09	Tier 4: intronic/intergenic
rs1444766	3	124206424	A>G,T	0.05	intron_variant	KALRN	1e-08	Tier 4: intronic/intergenic
rs140522	22	50532837	T>A,C,G	0.05	intron_variant	CIMAP1B - KLHDC7B-DT	2e-08	Tier 4: intronic/intergenic
rs3890745	1	2622185	T>A,C,G	0.05	intron_variant	MMEL1	2e-08	Tier 4: intronic/intergenic
rs71557353	6	26873086	T>G	0.15	intron_variant	ZNF322 - GUSBP2	3e-08	Tier 4: intronic/intergenic
rs79480871	2	24471603	C>T	0.062	intron_variant	ITSN2 - NCOA1	4e-08	Tier 4: intronic/intergenic
rs1323292	1	192571891	G>A,C,T	0.05	intron_variant	RGS2-AS1	5e-08	Tier 4: intronic/intergenic
rs806321	13	50267187	C>A,G,T	0.05	intron_variant	DLEU1	5e-08	Tier 4: intronic/intergenic
rs79464052	5	141655607	G>A,C	0.056	intron_variant	ARAP3	6e-08	Tier 4: intronic/intergenic
rs2681416	3	122098766	G>A	0.311	intron_variant	CD86	8e-08	Tier 4: intronic/intergenic
rs16978630	19	12702869	T>C,G	0.05	missense_variant	TNPO2	9e-08	Tier 1: coding
rs7712513	5	122582513	G>A,C,T	0.35	intron_variant	MGC32805 - LINC02201	2e-07	Tier 4: intronic/intergenic
rs12434407	14	47012742	A>G,T	0.05	intron_variant	MDGA2	2e-07	Tier 4: intronic/intergenic
rs751837	14	103018488	T>C	0.05	intron_variant	CDC42BPB	3e-07	Tier 4: intronic/intergenic
rs40836	16	28499216	A>C,G,T	0.05	intergenic_variant	APOBR - IL27	6e-07	Tier 4: intronic/intergenic
rs7765004	6	113750518	A>C	0.33	non_coding_transcript_exon_variant	LINC02541 - MARCKS	7e-07	Tier 4: intronic/intergenic
rs140083693	11	118735970	TA>T,TAA	0.05	intron_variant	RNU6-376P - DDX6	7e-07	Tier 4: intronic/intergenic
rs9421684	10	80702590	G>A	0.05	intergenic_variant	LINC02655 - RPS7P9	6e-06	Tier 4: intronic/intergenic
rs7097	13	27623299	C>A,G,T	0.05	3_prime_UTR_variant	POLR1D	7e-06	Tier 2: splice/UTR

ClinVar germline variants

23 retrieved; paginated sample, class counts are floors:

14 pathogenic, 4 likely pathogenic, 3 conflicting classifications of pathogenicity, 2 uncertain significance

ClinVar	Variant (HGVS)	Gene	Classification	Review
372626	NM_004333.6(BRAF):c.1574T>G (p.Leu525Arg)	BRAF	Pathogenic	criteria provided, single submitter
38208	NM_000059.4(BRCA2):c.9097dup (p.Thr3033fs)	BRCA2	Pathogenic	reviewed by expert panel
2671891	NM_004380.3(CREBBP):c.4268del (p.Pro1423fs)	CREBBP	Pathogenic	no assertion criteria provided
2574035	NM_002015.4(FOXO1):c.482G>A (p.Gly161Asp)	FOXO1	Pathogenic	no assertion criteria provided
557162	NM_002485.5(NBN):c.1396del (p.Arg466fs)	NBN	Pathogenic	criteria provided, multiple submitters, no conflicts
2671889	NM_000535.7(PMS2):c.163+2T>G	PMS2	Pathogenic	no assertion criteria provided
189500	NM_000314.8(PTEN):c.517C>T (p.Arg173Cys)	PTEN	Pathogenic	reviewed by expert panel
653412	NM_000314.8(PTEN):c.968del (p.Asn323fs)	PTEN	Pathogenic	criteria provided, multiple submitters, no conflicts
92828	NM_000314.8(PTEN):c.800del (p.Lys267fs)	PTEN	Pathogenic	criteria provided, multiple submitters, no conflicts
2671887	NM_005877.6(SF3A1):c.1641del (p.Ser548fs)	SF3A1	Pathogenic	no assertion criteria provided
2671890	NM_003745.2(SOCS1):c.462C>A (p.Tyr154Ter)	SOCS1	Pathogenic	no assertion criteria provided
225874	NM_024665.7(TBL1XR1):c.1337A>G (p.Tyr446Cys)	TBL1XR1	Pathogenic	criteria provided, multiple submitters, no conflicts
12347	NM_000546.6(TP53):c.742C>T (p.Arg248Trp)	TP53	Pathogenic	reviewed by expert panel
2671888	NM_000546.6(TP53):c.776A>C (p.Asp259Ala)	TP53	Pathogenic	no assertion criteria provided
2573989	NM_000626.4(CD79B):c.586T>C (p.Tyr196His)	CD79B	Likely pathogenic	no assertion criteria provided
573654	NM_007194.4(CHEK2):c.1095+2T>G	CHEK2	Likely pathogenic	criteria provided, multiple submitters, no conflicts
2574037	NM_001987.5(ETV6):c.33+1G>A	ETV6	Likely pathogenic	no assertion criteria provided
2573649	NM_024665.7(TBL1XR1):c.1192A>T (p.Lys398Ter)	TBL1XR1	Likely pathogenic	no assertion criteria provided
376203	NM_000061.3(BTK):c.1442G>C (p.Cys481Ser)	BTK	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
812892	NM_022552.5(DNMT3A):c.2204A>G (p.Tyr735Cys)	DNMT3A	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
372521	NM_139276.3(STAT3):c.1919A>T (p.Tyr640Phe)	STAT3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
37055	NM_002468.5(MYD88):c.755T>C (p.Leu252Pro)	MYD88	Uncertain significance	criteria provided, single submitter
2574036	NM_001042492.3(NF1):c.7064G>T (p.Ser2355Ile)	NF1	Uncertain significance	no assertion criteria provided

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 168 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 2

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

Gene	HGNC	Evidence routes
HLA-B	HLA-B	GWAS, Orphanet
MYC	MYC	GWAS, Orphanet

Somatic driver evidence (intOGen + CIViC, cohort fanout)

Gene	intOGen role	Cancer types	CIViC
BRAF	Act	BLCA,BRCA,CHOL,CLLSLL,COAD,COADREAD,CSCC,DLBCLNOS,GBM,GIST,HGGNOS,LGGNOS,LUAD,MEL,MLYM,NSCLC,OVT,PAST,PCM,PRAD,PRCC,PROSTATE,READ,SACA,SKCM,STAD,UCEC,WDTC	CIViC #5
BTK	Act	NHL	CIViC #65
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
MYD88	Act	CLLSLL,DLBCLNOS,MLYM,NHL	CIViC #3742
SMARCA4	Act	BL,BLADDER,BLCA,CCRCC,CHOL,COAD,COADREAD,EGC,ESCA,ESCC,HCC,HNSC,LGGNOS,LUAD,MBL,MLYM,NHL,NSCLC,OVT,PAAD,PANCREAS,PAST,PRCC,SACA,STAD,THYM	CIViC #78
KMT2C	LoF	ACC,ACYC,AML,ANSC,BCC,BLCA,BRCA,CCRCC,CEAD,CESC,CHOL,COAD,COADREAD,ES,ESCA,GBC,HCC,HNSC,LUAD,LUSC,MBL,MEL,NPC,OVT,PAAD,PANCREAS,PANET,PAST,PGNG,PRAD,PRCC,PROSTATE,RCC,SACA,SCLC,STAD,STOMACH,UCEC,WDTC	CIViC #14089
TET2	LoF	AML,MDS,MLYM,NHL,PCM,RCC,SOFT_TISSUE	CIViC #55
EZH2	Act	ALL,AML,DLBCLNOS,ES,MLYM,NHL	CIViC #63
FOXP1	LoF	BRCA,PRAD	CIViC #56
KRAS	Act	ALL,AML,ANSC,BLADDER,BLCA,BRCA,CEAD,CESC,CHOL,CLLSLL,COAD,COADREAD,DLBCLNOS,EGC,ESCA,ESCC,HCC,LUAD,LUSC,MEL,MGCT,MT,NSCLC,OVT,PAAD,PANCREAS,PAST,PCM,PRAD,PRCC,READ,STAD,STOMACH,UCEC,UCS,WDTC	CIViC #30
RHOA	Act	BL,BLCA,DLBCLNOS,HNSC,MLYM,NHL,PLMESO,PRAD,SKCM,STAD	CIViC #399
MS4A1			CIViC #827
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
PRDM1	LoF	AML,DLBCLNOS,NHL,PCM,PROSTATE	CIViC #593
RB1	LoF	ACC,BLADDER,BLCA,BRCA,CESC,ESCA,GB,GBM,GIST,HCC,HNSC,LGGNOS,LIPO,LMS,LUAD,LUSC,MEL,MT,NSCLC,OS,OVT,PANCREAS,PCM,PRAD,PROSTATE,RBL,SCLC,SKCM,SOFT_TISSUE,STAD,STOMACH,UCEC,UCS	CIViC #4795
BCL2	Act	DLBCLNOS,MLYM,NHL	CIViC #59
REL			CIViC #57
BRCA2	LoF	BLCA,BRCA,CESC,CHOL,HCC,HNSC,LUSC,MBL,OVT,PAAD,PRAD,PROSTATE,RCC,VULVA	CIViC #7
SNCAIP			CIViC #7608
STAT3	Act	DLBCLNOS,LNM,MLYM,NHL	CIViC #5516
CHEK2	Act	BRCA	CIViC #8950
CD79B	Act	DLBCLNOS,MLYM,NHL	CIViC #868
SOCS1	Act	DLBCLNOS,MLYM,NHL,READ	CIViC #6856
CREBBP	LoF	ALL,BCC,BLADDER,BLCA,BRCA,CCRCC,CLLSLL,DLBCLNOS,ESCA,HCC,HNSC,LUSC,MBL,MLYM,NETNOS,NHL,NSCLC,OVT,PANCREAS,PAST,SACA,SCLC,UTUC,VULVA,WDTC	CIViC #1193
TBL1XR1	Act	ALL,BL,BRCA,DLBCLNOS,MLYM,NHL,PLMESO	CIViC #15004
DNMT3A	LoF	AML,BRCA,CCRCC,HCC,LGGNOS,MDS,PCM,PRCC,WDTC	CIViC #18
ETV6	Act	ALL,BLCA,DLBCLNOS	CIViC #1769
FOXO1	Act	BL,LUSC,MLYM,NHL	CIViC #1925
HDAC2			CIViC #2578

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
BRAF	Orphanet:1340	Cardiofaciocutaneous syndrome
BRAF	Orphanet:146	Differentiated thyroid carcinoma
BRAF	Orphanet:251615	Pilomyxoid astrocytoma
BRAF	Orphanet:389	Langerhans cell histiocytosis
BRAF	Orphanet:500	Noonan syndrome with multiple lentigines
BRAF	Orphanet:54595	Craniopharyngioma
BRAF	Orphanet:58017	Classic hairy cell leukemia
BRAF	Orphanet:626	Large/giant congenital melanocytic nevus
BRAF	Orphanet:648	Noonan syndrome
BRAF	Orphanet:840	Syringocystadenoma papilliferum
BRAF	Orphanet:96253	Cushing disease
BTK	Orphanet:47	X-linked agammaglobulinemia
BTK	Orphanet:632	Short stature due to isolated growth hormone deficiency with X-linked hypogammaglobulinemia
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
MYD88	Orphanet:33226	Waldenström macroglobulinemia
MYD88	Orphanet:70592	Transient predisposition to invasive pyogenic bacterial infection
MYD88	Orphanet:714046	Primary choroidal lymphoma
SMARCA4	Orphanet:1465	Coffin-Siris syndrome
SMARCA4	Orphanet:231108	Rhabdoid tumor predisposition syndrome
SMARCA4	Orphanet:370396	Small cell carcinoma of the ovary
SMARCA4	Orphanet:466962	SMARCA4-deficient sarcoma of thorax
KMT2C	Orphanet:261652	Kleefstra syndrome due to a point mutation
TET2	Orphanet:100019	Myelodysplastic neoplasm with increased blasts type 1
TET2	Orphanet:100020	Myelodysplastic neoplasm with increased blasts type 2
TET2	Orphanet:3318	Essential thrombocythemia
TET2	Orphanet:664729	EBV-induced lymphoproliferative disease due to TET2 deficiency
TET2	Orphanet:75564	Acquired idiopathic sideroblastic anemia
TET2	Orphanet:824	Primary myelofibrosis
TET2	Orphanet:86845	Acute myeloid leukaemia with myelodysplasia-related features
TET2	Orphanet:98826	Myelodysplastic neoplasm with low blasts
TET2	Orphanet:98849	Systemic mastocytosis with associated hematologic neoplasm

Cohort genes → proteins

52 cohort genes, 50 distinct canonical proteins.

Evidence partition

Subset	Genes
gwas_only	19
civic_only	14
multi_evidence	19

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
BRAF	HGNC:1097	ENSG00000157764	P15056	Serine/threonine-protein kinase B-raf	clinvar,civic_evidence
BTK	HGNC:1133	ENSG00000010671	Q06187	Tyrosine-protein kinase BTK	clinvar,civic_evidence
TP53	HGNC:11998	ENSG00000141510	P04637	Cellular tumor antigen p53	clinvar,civic_evidence
MYD88	HGNC:7562	ENSG00000172936	Q99836	Myeloid differentiation primary response protein MyD88	clinvar,civic_evidence
SMARCA4	HGNC:11100	ENSG00000127616	P51532	SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A member 4	civic_evidence
KMT2C	HGNC:13726	ENSG00000055609	Q8NEZ4	Histone-lysine N-methyltransferase 2C	civic_evidence
TET2	HGNC:25941	ENSG00000168769	Q6N021	Methylcytosine dioxygenase TET2	civic_evidence
EZH2	HGNC:3527	ENSG00000106462	Q15910	Histone-lysine N-methyltransferase EZH2	civic_evidence
FOXP1	HGNC:3823	ENSG00000114861	Q9H334	Forkhead box protein P1	civic_evidence
KRAS	HGNC:6407	ENSG00000133703	P01116	GTPase KRas	civic_evidence
RHOA	HGNC:667	ENSG00000067560	P61586	Transforming protein RhoA	civic_evidence
MS4A1	HGNC:7315	ENSG00000156738	P11836	B-lymphocyte antigen CD20	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
PRDM1	HGNC:9346	ENSG00000057657	O75626	PR domain zinc finger protein 1	civic_evidence
RB1	HGNC:9884	ENSG00000139687	P06400	Retinoblastoma-associated protein	civic_evidence
BCL2	HGNC:990	ENSG00000171791	P10415	Apoptosis regulator Bcl-2	civic_evidence
REL	HGNC:9954	ENSG00000162924	Q04864	Proto-oncogene c-Rel	civic_evidence
SF3A1	HGNC:10765	ENSG00000099995	Q15459	Splicing factor 3A subunit 1	clinvar
BRCA2	HGNC:1101	ENSG00000139618	P51587	Breast cancer type 2 susceptibility protein	clinvar
SNCAIP	HGNC:11139	ENSG00000064692	Q9Y6H5	Synphilin-1	gwas
SNX2	HGNC:11173	ENSG00000205302	O60749	Sorting nexin-2	gwas
STAT3	HGNC:11364	ENSG00000168610	P40763	Signal transducer and activator of transcription 3	clinvar
MMEL1	HGNC:14668	ENSG00000142606	Q495T6	Membrane metallo-endopeptidase-like 1	gwas
NCOA5	HGNC:15909	ENSG00000124160	Q9HCD5	Nuclear receptor coactivator 5	gwas
CHEK2	HGNC:16627	ENSG00000183765	O96017	Serine/threonine-protein kinase Chk2	clinvar
CD79B	HGNC:1699	ENSG00000007312	P40259	B-cell antigen receptor complex-associated protein beta chain	clinvar
CD86	HGNC:1705	ENSG00000114013	P42081	T-lymphocyte activation antigen CD86	gwas
ARGFXP1	HGNC:17252	ENSG00000240058		arginine-fifty homeobox pseudogene 1	gwas
CDC42BPB	HGNC:1738	ENSG00000198752	Q9Y5S2	Serine/threonine-protein kinase MRCK beta	gwas
SOCS1	HGNC:19383	ENSG00000185338	O15524	Suppressor of cytokine signaling 1	clinvar
TNPO2	HGNC:19998	ENSG00000105576	O14787	Transportin-2	gwas
LNX2	HGNC:20421	ENSG00000139517	Q8N448	Ligand of Numb protein X 2	gwas
CREBBP	HGNC:2348	ENSG00000005339	Q92793	CREB-binding protein	clinvar
ARAP3	HGNC:24097	ENSG00000120318	Q8WWN8	Arf-GAP with Rho-GAP domain, ANK repeat and PH domain-containing protein 3	gwas
EXOC2	HGNC:24968	ENSG00000112685	Q96KP1	Exocyst complex component 2	gwas
TBL1XR1	HGNC:29529	ENSG00000177565	Q9BZK7	F-box-like/WD repeat-containing protein TBL1XR1	clinvar
DNMT3A	HGNC:2978	ENSG00000119772	Q9Y6K1	DNA (cytosine-5)-methyltransferase 3A	clinvar
ETV6	HGNC:3495	ENSG00000139083	P41212	Transcription factor ETV6	clinvar
FOXO1	HGNC:3819	ENSG00000150907	Q12778	Forkhead box protein O1	clinvar
KALRN	HGNC:4814	ENSG00000160145	O60229	Kalirin	gwas
HDAC2	HGNC:4853	ENSG00000196591	Q92769	Histone deacetylase 2	gwas
HLA-B	HGNC:4932	ENSG00000234745	P01889	HLA class I histocompatibility antigen, B alpha chain	gwas
ITSN2	HGNC:6184	ENSG00000198399	Q9NZM3	Intersectin-2	gwas
MARCKS	HGNC:6759	ENSG00000277443	P29966	Myristoylated alanine-rich C-kinase substrate	gwas
MYC	HGNC:7553	ENSG00000136997	P01106	Myc proto-oncogene protein	gwas
NBN	HGNC:7652	ENSG00000104320	O60934	Nibrin	clinvar
NCOA1	HGNC:7668	ENSG00000084676	Q15788	Nuclear receptor coactivator 1	gwas
NF1	HGNC:7765	ENSG00000196712	P21359	Neurofibromin	clinvar
PMS2	HGNC:9122	ENSG00000122512	P54278	Mismatch repair endonuclease PMS2	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
BRAF	Serine/threonine-protein kinase B-raf	Protein kinase involved in the transduction of mitogenic signals from the cell membrane to the nucleus.
BTK	Tyrosine-protein kinase BTK	Non-receptor tyrosine kinase indispensable for B lymphocyte development, differentiation and signaling.
TP53	Cellular tumor antigen p53	Multifunctional transcription factor that induces cell cycle arrest, DNA repair or apoptosis upon binding to its target DNA sequence.
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.
SMARCA4	SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A member 4	ATPase involved in transcriptional activation and repression of select genes by chromatin remodeling (alteration of DNA-nucleosome topology).
KMT2C	Histone-lysine N-methyltransferase 2C	Histone methyltransferase that catalyzes methyl group transfer from S-adenosyl-L-methionine to the epsilon-amino group of ‘Lys-4’ of histone H3 (H3K4).
TET2	Methylcytosine dioxygenase TET2	Dioxygenase that catalyzes the conversion of the modified genomic base 5-methylcytosine (5mC) into 5-hydroxymethylcytosine (5hmC) and plays a key role in active DNA demethylation.
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.
FOXP1	Forkhead box protein P1	Transcriptional repressor.
KRAS	GTPase KRas	Ras proteins bind GDP/GTP and possess intrinsic GTPase activity.
RHOA	Transforming protein RhoA	Small GTPase which cycles between an active GTP-bound and an inactive GDP-bound state.
MS4A1	B-lymphocyte antigen CD20	B-lymphocyte-specific membrane protein that plays a role in the regulation of cellular calcium influx necessary for the development, differentiation, and activation of B-lymphocytes.
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.
PRDM1	PR domain zinc finger protein 1	Transcription factor that mediates a transcriptional program in various innate and adaptive immune tissue-resident lymphocyte T cell types such as tissue-resident memory T (Trm), natural killer (trNK) and natural killer T (NKT) cells and n…
RB1	Retinoblastoma-associated protein	Tumor suppressor that is a key regulator of the G1/S transition of the cell cycle.
BCL2	Apoptosis regulator Bcl-2	Suppresses apoptosis in a variety of cell systems including factor-dependent lymphohematopoietic and neural cells.
REL	Proto-oncogene c-Rel	Proto-oncogene that may play a role in differentiation and lymphopoiesis.
SF3A1	Splicing factor 3A subunit 1	Component of the 17S U2 SnRNP complex of the spliceosome, a large ribonucleoprotein complex that removes introns from transcribed pre-mRNAs.
BRCA2	Breast cancer type 2 susceptibility protein	Involved in double-strand break repair and/or homologous recombination.
SNCAIP	Synphilin-1	Isoform 2 inhibits the ubiquitin ligase activity of SIAH1 and inhibits proteasomal degradation of target proteins.
SNX2	Sorting nexin-2	Involved in several stages of intracellular trafficking.
STAT3	Signal transducer and activator of transcription 3	Signal transducer and transcription activator that mediates cellular responses to interleukins, KITLG/SCF, LEP and other growth factors.
MMEL1	Membrane metallo-endopeptidase-like 1	Metalloprotease involved in sperm function, possibly by modulating the processes of fertilization and early embryonic development.
NCOA5	Nuclear receptor coactivator 5	Nuclear receptor coregulator that can have both coactivator and corepressor functions.
CHEK2	Serine/threonine-protein kinase Chk2	Serine/threonine-protein kinase which is required for checkpoint-mediated cell cycle arrest, activation of DNA repair and apoptosis in response to the presence of DNA double-strand breaks.
CD79B	B-cell antigen receptor complex-associated protein beta chain	Required in cooperation with CD79A for initiation of the signal transduction cascade activated by the B-cell antigen receptor complex (BCR) which leads to internalization of the complex, trafficking to late endosomes and antigen presentati…
CD86	T-lymphocyte activation antigen CD86	Costimulatory molecule that belongs to the immunoglobulin superfamily that plays an important role in T-lymphocyte activation.
CDC42BPB	Serine/threonine-protein kinase MRCK beta	Serine/threonine-protein kinase which is an important downstream effector of CDC42 and plays a role in the regulation of cytoskeleton reorganization and cell migration.
SOCS1	Suppressor of cytokine signaling 1	Essential negative regulator of type I and type II interferon (IFN) signaling, as well as that of other cytokines, including IL2, IL4, IL6 and leukemia inhibitory factor (LIF).
TNPO2	Transportin-2	Probably functions in nuclear protein import as nuclear transport receptor.
CREBBP	CREB-binding protein	Acetylates histones, giving a specific tag for transcriptional activation.
ARAP3	Arf-GAP with Rho-GAP domain, ANK repeat and PH domain-containing protein 3	Phosphatidylinositol 3,4,5-trisphosphate-dependent GTPase-activating protein that modulates actin cytoskeleton remodeling by regulating ARF and RHO family members.
EXOC2	Exocyst complex component 2	Component of the exocyst complex involved in the docking of exocytic vesicles with fusion sites on the plasma membrane.
TBL1XR1	F-box-like/WD repeat-containing protein TBL1XR1	F-box-like protein involved in the recruitment of the ubiquitin/19S proteasome complex to nuclear receptor-regulated transcription units.
DNMT3A	DNA (cytosine-5)-methyltransferase 3A	Required for genome-wide de novo methylation and is essential for the establishment of DNA methylation patterns during development.
ETV6	Transcription factor ETV6	Transcriptional repressor; binds to the DNA sequence 5’-CCGGAAGT-3’.
FOXO1	Forkhead box protein O1	Transcription factor that is the main target of insulin signaling and regulates metabolic homeostasis in response to oxidative stress.
KALRN	Kalirin	Promotes the exchange of GDP by GTP.
HDAC2	Histone deacetylase 2	Histone deacetylase that catalyzes the deacetylation of lysine residues on the N-terminal part of the core histones (H2A, H2B, H3 and H4).
HLA-B	HLA class I histocompatibility antigen, B alpha chain	Antigen-presenting major histocompatibility complex class I (MHCI) molecule.
ITSN2	Intersectin-2	Adapter protein that may provide indirect link between the endocytic membrane traffic and the actin assembly machinery.
MARCKS	Myristoylated alanine-rich C-kinase substrate	Membrane-associated protein that plays a role in the structural modulation of the actin cytoskeleton, chemotaxis, motility, cell adhesion, phagocytosis, and exocytosis through lipid sequestering and/or protein docking to membranes.
MYC	Myc proto-oncogene protein	Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5’-CAC[GA]TG-3’.
NBN	Nibrin	Component of the MRN complex, which plays a central role in double-strand break (DSB) repair, DNA recombination, maintenance of telomere integrity and meiosis.
NCOA1	Nuclear receptor coactivator 1	Nuclear receptor coactivator that directly binds nuclear receptors and stimulates the transcriptional activities in a hormone-dependent fashion.
NF1	Neurofibromin	Stimulates the GTPase activity of Ras.
PMS2	Mismatch repair endonuclease PMS2	Component of the post-replicative DNA mismatch repair system (MMR).
PTEN	Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN	Dual-specificity protein phosphatase, dephosphorylating tyrosine-, serine- and threonine-phosphorylated proteins.

Protein-family classification

Druggable: 17 · Difficult: 18 · Unknown: 17 · Druggable fraction: 0.33

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	6	3.2×	0.096
Scaffold/PPI	7	2.3×	0.132
Transcription factor	11	1.8×	0.133
Antibody/Immunoglobulin	4	2.2×	0.230
Complement	1	5.2×	0.318
Phosphatase	1	1.6×	0.697
Enzyme (other)	4	0.9×	0.823
Protease	1	0.7×	0.859
Other/Unknown	17	0.6×	1.000

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
BRAF	Kinase	yes	2.7.10.2	Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom, PKC_DAG/PE
BTK	Kinase	yes	2.7.10.2	Prot_kinase_dom, SH2, Ser-Thr/Tyr_kinase_cat_dom
TP53	Transcription factor	no		p53_tumour_suppressor, p53-like_TF_DNA-bd_sf, p53_tetrameristn
MYD88	Other/Unknown	no		TIR_dom, Death_dom, DEATH-like_dom_sf
SMARCA4	Other/Unknown	no		SNF2_N, Bromodomain, Helicase_C-like
KMT2C	Transcription factor	no		HMGI/Y_DNA-bd_CS, SET_dom, Znf_RING
TET2	Other/Unknown	no		2OGFeDO_JBP1/TET_oxygenase_dom, TET1/2/3, TET_oxygenase
EZH2	Enzyme (other)	yes	2.1.1.356	SANT/Myb, SET_dom, EZH1/EZH2_N
FOXP1	Transcription factor	no		Fork_head_dom, TF_fork_head_CS_2, FOXP-CC
KRAS	Enzyme (other)	yes	3.6.5.2	Small_GTPase, Small_GTP-bd, Small_GTPase_Ras-type
RHOA	Enzyme (other)	yes	3.6.5.2	Small_GTPase, Small_GTPase_Rho, Small_GTP-bd
MS4A1	Other/Unknown	no		CD20-like_TM, MS4A
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
PRDM1	Transcription factor	no		SET_dom, Znf_C2H2_type, PRDM1
RB1	Other/Unknown	no		RB_B, RB_A, Cyclin-like_dom
BCL2	Other/Unknown	no		Bcl2-like, Bcl2_BH4, Bcl2/BclX
REL	Transcription factor	no		NFkB/Dor, IPT_dom, p53-like_TF_DNA-bd_sf
SF3A1	Other/Unknown	no		Surp, Ubiquitin-like_dom, SF3A1_dom
BRCA2	Other/Unknown	no		BRCA2_repeat, NA-bd_OB-fold, BRCA2_OB_1
SNCAIP	Scaffold/PPI	no		Ankyrin_rpt, SNCAIP_SNCA-bd, Ankyrin_rpt-contain_sf
SNX2	Scaffold/PPI	no		PX_dom, Sorting_nexin_N, Vps5_C
STAT3	Transcription factor	no		SH2, STAT, p53-like_TF_DNA-bd_sf
MMEL1	Protease	yes	3.4.24.B14	Peptidase_M13, Peptidase_M13_N, Peptidase_M13_C
NCOA5	Other/Unknown	no		Anticodon-bd_dom_sf, Nuc_rcpt_coact/corep
CHEK2	Kinase	yes	2.7.11.1	FHA_dom, Prot_kinase_dom, Ser/Thr_kinase_AS
CD79B	Antibody/Immunoglobulin	yes		Phos_immunorcpt_sig_ITAM, Ig_sub, Ig-like_dom
CD86	Antibody/Immunoglobulin	yes		Ig_sub, Ig-like_dom, Ig_V-set
ARGFXP1	Other/Unknown	no
CDC42BPB	Kinase	yes		CRIB_dom, Prot_kinase_dom, AGC-kinase_C
SOCS1	Scaffold/PPI	no		SH2, SOCS_box, SOCS1_SH2
TNPO2	Other/Unknown	no		HEAT, Importin-beta_N, ARM-like
LNX2	Transcription factor	no		PDZ, Znf_RING, Znf_RING/FYVE/PHD
CREBBP	Transcription factor	no	2.3.1.48	Znf_TAZ, Znf_ZZ, Bromodomain
ARAP3	Scaffold/PPI	no		RA_dom, RhoGAP_dom, ArfGAP_dom
EXOC2	Antibody/Immunoglobulin	yes		IPT_dom, Ig-like_fold, Ig_E-set
TBL1XR1	Scaffold/PPI	no		WD40_rpt, LisH, WD40/YVTN_repeat-like_dom_sf
DNMT3A	Complement	yes	2.1.1.37	PWWP_dom, C5_MeTfrase, C5_DNA_meth_AS
ETV6	Other/Unknown	no		Ets_dom, Pointed_dom, SAM/pointed_sf
FOXO1	Transcription factor	no		Fork_head_dom, TF_fork_head_CS_2, FOXO-TAD
KALRN	Kinase	yes		DH_dom, Prot_kinase_dom, CRAL-TRIO_dom
HDAC2	Enzyme (other)	yes	3.5.1.98	HDACs, HDAC_I/II, Ureohydrolase_dom_sf
HLA-B	Antibody/Immunoglobulin	yes		MHC_I_a_a1/a2, Ig/MHC_CS, Ig_C1-set
ITSN2	Scaffold/PPI	no		C2_dom, DH_dom, EH_dom
MARCKS	Other/Unknown	no		MARCKS
MYC	Transcription factor	no		Tscrpt_reg_Myc, Myc-LZ, bHLH_dom
NBN	Other/Unknown	no		FHA_dom, BRCT_dom, SMAD_FHA_dom_sf
NCOA1	Transcription factor	no	2.3.1.48	PAS, Nuc_rcpt_coact, NCO_DUF1518
NF1	Other/Unknown	no		CRAL-TRIO_dom, RasGAP_dom, Rho_GTPase_activation_prot
PMS2	Other/Unknown	no		MutL/Mlh/PMS, DNA_mismatch_S5_2-like, Ribsml_uS5_D2-typ_fold_subgr

Expression context

Cohort genes with no expression data: 0.

50 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)	1
broad (>20)	51
unknown	0

Top tissues across cohort

Tissue	Cohort genes
ganglionic eminence	7
ventricular zone	7
calcaneal tendon	6
colonic epithelium	6
male germ line stem cell (sensu Vertebrata) in testis	6
leukocyte	5
monocyte	5
mononuclear cell	5
cortical plate	5
buccal mucosa cell	4
sural nerve	4
epithelium of nasopharynx	3
spleen	3
visceral pleura	3
lower esophagus mucosa	3
secondary oocyte	3
sperm	3
cervix squamous epithelium	2
oocyte	2
amniotic fluid	2

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
BRAF	265	ubiquitous	marker	buccal mucosa cell, colonic epithelium, calcaneal tendon
BTK	206	broad	marker	monocyte, mononuclear cell, leukocyte
TP53	223	ubiquitous	marker	ventricular zone, ganglionic eminence, tendon of biceps brachii
MYD88	284	ubiquitous	marker	leukocyte, mononuclear cell, monocyte
SMARCA4	295	ubiquitous	marker	ganglionic eminence, cortical plate, cervix squamous epithelium
KMT2C	261	ubiquitous	marker	oocyte, caput epididymis, upper arm skin
TET2	249	ubiquitous	marker	palpebral conjunctiva, amniotic fluid, epithelium of nasopharynx
EZH2	216	ubiquitous	marker	ganglionic eminence, ventricular zone, embryo
FOXP1	256	ubiquitous	marker	pancreatic ductal cell, oviduct epithelium, cardia of stomach
KRAS	298	ubiquitous	marker	trigeminal ganglion, pylorus, nipple
RHOA	295	ubiquitous	marker	monocyte, leukocyte, mononuclear cell
MS4A1	197	broad	marker	epithelium of nasopharynx, spleen, lymph node
NOTCH1	272	ubiquitous	marker	ventricular zone, colonic epithelium, visceral pleura
ATM	286	ubiquitous	marker	calcaneal tendon, colonic epithelium, corpus callosum
PRDM1	221	ubiquitous	marker	lower esophagus mucosa, esophagus squamous epithelium, colonic epithelium
RB1	287	ubiquitous	marker	epithelium of nasopharynx, choroid plexus epithelium, visceral pleura
BCL2	275	ubiquitous	marker	dorsal motor nucleus of vagus nerve, superficial temporal artery, calcaneal tendon
REL	257	ubiquitous	marker	buccal mucosa cell, bone marrow, secondary oocyte
SF3A1	300	ubiquitous	marker	sperm, male germ cell, sural nerve
BRCA2	184	ubiquitous	marker	male germ line stem cell (sensu Vertebrata) in testis, secondary oocyte, ventricular zone
SNCAIP	240	broad	marker	ventricular zone, ganglionic eminence, germinal epithelium of ovary
SNX2	291	ubiquitous	marker	monocyte, mononuclear cell, leukocyte
STAT3	301	ubiquitous	marker	type B pancreatic cell, pericardium, lower lobe of lung
MMEL1	131	broad	yes	male germ line stem cell (sensu Vertebrata) in testis, primordial germ cell in gonad, left testis
NCOA5	231	ubiquitous	marker	oviduct epithelium, ileal mucosa, cortical plate
CHEK2	183	ubiquitous	marker	primordial germ cell in gonad, lower esophagus mucosa, male germ line stem cell (sensu Vertebrata) in testis
CD79B	210	broad	marker	granulocyte, spleen, lymph node
CD86	218	broad	marker	monocyte, mononuclear cell, leukocyte
ARGFXP1	16		yes	male germ line stem cell (sensu Vertebrata) in testis, right uterine tube, sural nerve
CDC42BPB	268	ubiquitous	marker	stromal cell of endometrium, mucosa of stomach, body of uterus

Protein interactions among cohort

Intra-cohort edges: 52.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
TP53	22,736
MYC	20,608
KRAS	14,509
PTEN	11,626
STAT3	10,108
EZH2	9,646
BCL2	8,343
SMARCA4	8,138
HDAC2	7,586
NOTCH1	7,411

Intra-cohort edges

A	B	Sources
ATM	BRCA2	string_interaction
ATM	CHEK2	string_interaction
ATM	NBN	biogrid_interaction, string_interaction
ATM	NOTCH1	intact
ATM	TP53	biogrid_interaction, string_interaction
BCL2	TP53	intact, string_interaction
BRAF	BRCA2	biogrid_interaction
BRAF	CD79B	intact
BRAF	HDAC2	biogrid_interaction
BRAF	KRAS	biogrid_interaction, intact, string_interaction
BRAF	NF1	string_interaction
BRAF	PMS2	string_interaction
BRAF	PTEN	biogrid_interaction, string_interaction
BRAF	TP53	string_interaction
BRCA2	CHEK2	string_interaction
BRCA2	NBN	string_interaction
BRCA2	PMS2	string_interaction
BRCA2	TP53	string_interaction
BTK	CD79B	string_interaction
CD79B	NF1	biogrid_interaction
CD79B	SMARCA4	intact
CHEK2	NBN	string_interaction
CHEK2	TP53	intact, string_interaction
CREBBP	FOXO1	biogrid_interaction
CREBBP	MYC	biogrid_interaction
CREBBP	NCOA1	biogrid_interaction, intact, string_interaction
CREBBP	TP53	biogrid_interaction, intact, string_interaction
DNMT3A	EZH2	intact, string_interaction
DNMT3A	HDAC2	string_interaction
DNMT3A	MYC	biogrid_interaction, string_interaction
DNMT3A	TET2	string_interaction
ETV6	TET2	string_interaction
EZH2	HDAC2	string_interaction
EZH2	TET2	string_interaction
FOXO1	PTEN	string_interaction
FOXP1	MYC	string_interaction
FOXP1	TP53	biogrid_interaction
HDAC2	TET2	string_interaction
KALRN	MYC	intact
KALRN	SNCAIP	biogrid_interaction, intact
KMT2C	TP53	intact, string_interaction
KRAS	NF1	string_interaction
KRAS	PTEN	string_interaction
KRAS	RHOA	intact
KRAS	TP53	string_interaction
MYC	TP53	string_interaction
NF1	PTEN	biogrid_interaction, string_interaction
NF1	TP53	string_interaction
PRDM1	STAT3	string_interaction
PTEN	TP53	string_interaction

Structural data

PDB: 44 · AlphaFold-only: 6 · No structure: 2

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
KRAS	P01116	511
TP53	P04637	313
NCOA1	Q15788	301
HLA-B	P01889	237
BTK	Q06187	156
CREBBP	Q92793	144
BRAF	P15056	131
RHOA	P61586	131
BCL2	P10415	55
SF3A1	Q15459	51
HDAC2	Q92769	48
ETV6	P41212	44
DNMT3A	Q9Y6K1	43
EZH2	Q15910	38
CHEK2	O96017	38
SMARCA4	P51532	31
NOTCH1	P46531	29
NF1	P21359	26
MYC	P01106	25
RB1	P06400	19
MYD88	Q99836	14
ATM	Q13315	14
BRCA2	P51587	14
KALRN	O60229	13
PTEN	P60484	12
FOXO1	Q12778	11
MS4A1	P11836	10
KMT2C	Q8NEZ4	9
PMS2	P54278	9
ITSN2	Q9NZM3	8

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
TNPO2	O14787	91.28
MMEL1	Q495T6	90.34
SOCS1	O15524	84.20
EXOC2	Q96KP1	80.82
SNX2	O60749	76.87
REL	Q04864	66.46

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 613. Enrichment computed across 52 evidence-associated genes (45 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 45 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Cellular response to chemical stress	6	19.0×	2e-04	STAT3, CREBBP, TBL1XR1, MYC, NCOA1, BCL2
Signal Transduction	17	3.8×	2e-04	BRAF, BTK, MYD88, SMARCA4, STAT3, CD86, CDC42BPB, SOCS1 (+9 more)
NOTCH1 Intracellular Domain Regulates Transcription	5	26.4×	2e-04	CREBBP, TBL1XR1, HDAC2, MYC, NOTCH1
Regulation of NFE2L2 gene expression	3	95.2×	3e-04	CREBBP, MYC, NOTCH1
Constitutive Signaling by NOTCH1 PEST Domain Mutants	5	21.9×	3e-04	CREBBP, TBL1XR1, HDAC2, MYC, NOTCH1
Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants	5	21.9×	3e-04	CREBBP, TBL1XR1, HDAC2, MYC, NOTCH1
Notch-HLH transcription pathway	4	36.2×	3e-04	CREBBP, TBL1XR1, HDAC2, NOTCH1
Interleukin-4 and Interleukin-13 signaling	6	13.7×	3e-04	TP53, STAT3, SOCS1, FOXO1, MYC, BCL2
Signaling by Interleukins	7	10.0×	4e-04	MYD88, SMARCA4, STAT3, CD86, SOCS1, MYC, BCL2
STAT3 nuclear events downstream of ALK signaling	3	69.2×	6e-04	STAT3, HDAC2, PRDM1
Defective homologous recombination repair (HRR) due to PALB2 loss of function	3	63.4×	6e-04	BRCA2, NBN, ATM
NFE2L2 regulating tumorigenic genes	3	63.4×	6e-04	CREBBP, NOTCH1, BCL2
Differentiation of naive CD4+ T cells to T helper 2 cells (Th2 cells)	5	16.3×	6e-04	SMARCA4, CREBBP, TBL1XR1, HDAC2, NOTCH1
Diseases of signal transduction by growth factor receptors and second messengers	7	8.8×	6e-04	BRAF, STAT3, CD86, CREBBP, TBL1XR1, MYC, NF1
Regulation of TP53 Expression	2	253.8×	6e-04	TP53, PRDM1
Diseases of DNA Double-Strand Break Repair	3	54.4×	7e-04	BRCA2, NBN, ATM
Defective homologous recombination repair (HRR) due to BRCA2 loss of function	3	54.4×	7e-04	BRCA2, NBN, ATM
Disease	13	3.8×	7e-04	BRAF, BTK, MYD88, BRCA2, STAT3, CD79B, CD86, CREBBP (+5 more)
Stabilization of p53	3	50.8×	8e-04	TP53, CHEK2, ATM
Cellular responses to stress	8	6.5×	8e-04	STAT3, CREBBP, TBL1XR1, MYC, NBN, NCOA1, ATM, BCL2
R-HSA-1368082	3	47.6×	9e-04	CREBBP, TBL1XR1, NCOA1
Epigenetic regulation of gene expression	6	9.5×	1e-03	SMARCA4, KMT2C, CREBBP, TET2, TBL1XR1, NCOA1
Resolution of D-Loop Structures	3	42.3×	0.001	BRCA2, NBN, ATM
Epigenetic regulation of adipogenesis genes by MLL3 and MLL4 complexes	4	19.1×	0.001	KMT2C, CREBBP, TBL1XR1, NCOA1
Regulation of PD-L1(CD274) transcription	5	12.1×	0.001	STAT3, KMT2C, CREBBP, EZH2, MYC
Signaling by CSF3 (G-CSF)	3	38.1×	0.001	STAT3, SOCS1, KRAS
Diseases of DNA repair	3	38.1×	0.001	BRCA2, NBN, ATM
TP53 Regulates Transcription of Genes Involved in Cytochrome C Release	3	36.2×	0.001	TP53, CREBBP, ATM
Regulation of TP53 Activity through Methylation	3	36.2×	0.001	TP53, CHEK2, ATM
Epigenetic regulation of gene expression by MLL3 and MLL4 complexes	4	17.5×	0.001	KMT2C, CREBBP, TBL1XR1, NCOA1

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 50 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 DNA-templated transcription	13	7.3×	8e-06	TP53, BRCA2, SMARCA4, STAT3, CHEK2, CD86, CREBBP, TBL1XR1 (+5 more)
positive regulation of transcription by RNA polymerase II	17	5.1×	8e-06	TP53, MYD88, SMARCA4, STAT3, KMT2C, CREBBP, TET2, TBL1XR1 (+9 more)
DNA damage response, signal transduction by p53 class mediator	5	35.9×	8e-05	TP53, BRCA2, CHEK2, NBN, ATM
neuron apoptotic process	6	22.2×	8e-05	TP53, KRAS, NF1, ATM, RB1, BCL2
negative regulation of transcription by RNA polymerase II	14	5.0×	9e-05	TP53, SMARCA4, STAT3, NCOA5, CREBBP, TBL1XR1, DNMT3A, ETV6 (+6 more)
cellular response to xenobiotic stimulus	5	24.1×	4e-04	BRAF, TP53, CHEK2, MYC, RB1
negative regulation of glial cell proliferation	3	101.1×	5e-04	TP53, NOTCH1, RB1
double-strand break repair	5	20.3×	6e-04	TP53, BRCA2, CHEK2, NBN, ATM
positive regulation of gene expression	9	7.0×	6e-04	BRAF, TP53, MYD88, STAT3, KRAS, MYC, NOTCH1, ATM (+1 more)
B cell receptor signaling pathway	4	32.1×	8e-04	BTK, CD79B, MS4A1, BCL2
negative regulation of G1/S transition of mitotic cell cycle	4	28.7×	0.001	EZH2, PTEN, RB1, BCL2
skeletal muscle cell differentiation	4	27.5×	0.001	KRAS, MYC, NOTCH1, RB1
replicative senescence	3	59.5×	0.001	TP53, CHEK2, ATM
intrinsic apoptotic signaling pathway in response to DNA damage	4	25.9×	0.001	CHEK2, MYC, ATM, BCL2
forebrain astrocyte development	2	224.7×	0.001	KRAS, NF1
regulation of chemokine (C-X-C motif) ligand 2 production	2	224.7×	0.001	MYD88, FOXP1
oocyte development	3	56.2×	0.001	DNMT3A, ATM, BCL2
glial cell proliferation	3	53.2×	0.001	TP53, KRAS, RB1
negative regulation of stem cell differentiation	3	50.6×	0.001	STAT3, EZH2, NOTCH1
positive regulation of miRNA transcription	4	23.2×	0.001	TP53, SMARCA4, STAT3, MYC
protein import into nucleus	5	14.4×	0.001	TP53, STAT3, TNPO2, NF1, NOTCH1
negative regulation of DNA-templated transcription	9	5.7×	0.001	TP53, SMARCA4, DNMT3A, EZH2, FOXO1, FOXP1, HDAC2, NOTCH1 (+1 more)
DNA damage response	7	7.5×	0.002	TP53, CHEK2, FOXO1, FOXP1, MYC, ATM, BCL2
heterochromatin formation	4	20.4×	0.002	SMARCA4, EZH2, HDAC2, RB1
regulation of interleukin-12 production	2	168.5×	0.002	FOXP1, HLA-B
cellular response to hypoxia	5	12.1×	0.002	TP53, DNMT3A, MYC, NOTCH1, BCL2
B cell lineage commitment	2	134.8×	0.003	TP53, BCL2
T-helper 17 type immune response	2	134.8×	0.003	STAT3, NOTCH1
cellular response to bisphenol A	2	134.8×	0.003	CHEK2, DNMT3A
negative regulation of telomere capping	2	134.8×	0.003	NBN, ATM

Therapeutics

Drugs indicated for this disease

8 approved, 60 in late-stage (phase 3) trials. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

Drug	Development status
Axicabtagene Ciloleucel	Approved (phase 4)
Epcoritamab	Approved (phase 4)
Glofitamab	Approved (phase 4)
Loncastuximab Tesirine	Approved (phase 4)
Polatuzumab Vedotin	Approved (phase 4)
Selinexor	Approved (phase 4)
Tafasitamab	Approved (phase 4)
Tisagenlecleucel	Approved (phase 4)
Acalabrutinib	Phase 3 (in late-stage trials)
Aldesleukin	Phase 3 (in late-stage trials)
Avelumab	Phase 3 (in late-stage trials)
Azacitidine	Phase 3 (in late-stage trials)
Bendamustine	Phase 3 (in late-stage trials)
Bleomycin	Phase 3 (in late-stage trials)
Bortezomib	Phase 3 (in late-stage trials)
Brentuximab Vedotin	Phase 3 (in late-stage trials)
Carboplatin	Phase 3 (in late-stage trials)
Carmustine	Phase 3 (in late-stage trials)
Cholecalciferol	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)
Darbepoetin Alfa	Phase 3 (in late-stage trials)
Decitabine	Phase 3 (in late-stage trials)
Dexamethasone	Phase 3 (in late-stage trials)
Dexrazoxane	Phase 3 (in late-stage trials)
Doxorubicin	Phase 3 (in late-stage trials)
Epirubicin	Phase 3 (in late-stage trials)
Epoetin Beta	Phase 3 (in late-stage trials)
Etoposide	Phase 3 (in late-stage trials)
Etoposide Phosphate	Phase 3 (in late-stage trials)
Everolimus	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)
Golcadomide	Phase 3 (in late-stage trials)
INDIUM IN 111 IBRITUMOMAB TIUXETAN	Phase 3 (in late-stage trials)
Ibrutinib	Phase 3 (in late-stage trials)
Ifosfamide	Phase 3 (in late-stage trials)
Lenalidomide	Phase 3 (in late-stage trials)
Lenograstim	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)
Mycophenolate Mofetil	Phase 3 (in late-stage trials)
Obinutuzumab	Phase 3 (in late-stage trials)
Odronextamab	Phase 3 (in late-stage trials)
Ofatumumab	Phase 3 (in late-stage trials)
Orelabrutinib	Phase 3 (in late-stage trials)
Oxaliplatin	Phase 3 (in late-stage trials)
Pegfilgrastim	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)
Ripertamab	Phase 3 (in late-stage trials)
Rituximab	Phase 3 (in late-stage trials)
Thalidomide	Phase 3 (in late-stage trials)
Tislelizumab	Phase 3 (in late-stage trials)
Tocilizumab	Phase 3 (in late-stage trials)
Transplatin	Phase 3 (in late-stage trials)
Tucidinostat	Phase 3 (in late-stage trials)
Utomilumab	Phase 3 (in late-stage trials)
Vinblastine	Phase 3 (in late-stage trials)
Vincristine	Phase 3 (in late-stage trials)
Vindesine	Phase 3 (in late-stage trials)
YTTRIUM Y 90 IBRITUMOMAB TIUXETAN	Phase 3 (in late-stage trials)
Zanubrutinib	Phase 3 (in late-stage trials)

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): Abexinostat, Acetaminophen, Alemtuzumab, Ascorbic Acid, Atezolizumab, Belantamab Mafodotin, Belinostat, Bevacizumab, Blinatumomab, Busulfan, Camrelizumab, Catequentinib, Cirmtuzumab, Copanlisib, Daratumumab, Dasatinib Anhydrous, Diphenhydramine, Durvalumab, Entospletinib, Enzastaurin, Fostamatinib, Hyaluronidase, Hydrocortisone, Idelalisib, Inebilizumab, Inotuzumab Ozogamicin, Isosorbide, Itacitinib, Ixabepilone, Lisocabtagene Maraleucel, Magrolimab, Maraviroc, Metformin, Methylprednisolone, Mosunetuzumab, Navitoclax, Nivolumab, Oblimersen Sodium, Panobinostat, Pembrolizumab, Pemetrexed, Penpulimab, Plerixafor, Pomalidomide, Rasburicase, Regramostim, Romidepsin, Selumetinib, Sintilimab, Sirolimus, TOSITUMOMAB 131I, Tacrolimus Anhydrous, Tamoxifen, Temsirolimus, Terfenadine, Thiotepa, Ublituximab, Umbralisib, Vatalanib, Venetoclax, Vinorelbine.

Drug target analysis

Approved (phase 4): 16 · Phase ≥3: 17 · Phased (≥1): 20 · Undrugged: 32

Druggability breadth: 40 of 52 evidence-associated genes (77%) 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
BRAF	VEMURAFENIB
BTK	PONATINIB
TP53	NITROFURANTOIN
TET2	VADADUSTAT
EZH2	TAZEMETOSTAT
KRAS	VEMURAFENIB
ATM	AMIODARONE HYDROCHLORIDE
BCL2	IXABEPILONE
STAT3	MOMELOTINIB
CHEK2	NERATINIB
CDC42BPB	AXITINIB
CREBBP	COLCHICINE
ETV6	CERITINIB
FOXO1	PANOBINOSTAT
HDAC2	VALPROIC ACID
NCOA1	ETOPOSIDE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
TP53	196	4
BTK	84	4
BRAF	48	4
HDAC2	41	4
ATM	35	4
CHEK2	30	4
STAT3	18	4
CDC42BPB	15	4
BCL2	14	4
CREBBP	13	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
VEMURAFENIB	4	BRAF, KRAS
PONATINIB	4	BRAF, BTK
FEDRATINIB	4	BRAF, BTK
SORAFENIB	4	BRAF
DASATINIB ANHYDROUS	4	BRAF
RUXOLITINIB	4	BRAF
INFIGRATINIB PHOSPHATE	4	BRAF
INFIGRATINIB	4	BRAF
REGORAFENIB	4	BRAF
DABRAFENIB	4	BRAF, KRAS
COBIMETINIB	4	BRAF
NILOTINIB	4	BRAF, CDC42BPB
ABEMACICLIB	4	BRAF
ENCORAFENIB	4	BRAF
TOVORAFENIB	4	BRAF
PAZOPANIB	4	BRAF
DASATINIB	4	BRAF, BTK, CDC42BPB
ERLOTINIB	4	BRAF
GEFITINIB	4	BRAF, CHEK2
IMATINIB	4	BRAF
NERATINIB	4	BTK, CHEK2
IBRUTINIB	4	BTK
ENTRECTINIB	4	BTK
CERITINIB	4	BTK, ETV6
VANDETANIB	4	BTK, CDC42BPB
BOSUTINIB	4	BTK, CHEK2
OSIMERTINIB	4	BTK
BRIGATINIB	4	BTK, CHEK2
FUTIBATINIB	4	BTK
ACALABRUTINIB	4	BTK

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 13.

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

Symbol	Assays	Type breakdown
HDAC2	2,775	Binding:2743, ADMET:24, Functional:7, Toxicity:1
BTK	1,836	Binding:1810, Functional:23, ADMET:3
BRAF	1,442	Binding:1400, Functional:37, ADMET:5
STAT3	1,319	Binding:1304, Functional:12, Unclassified:2, ADMET:1
TP53	869	Binding:775, ADMET:83, Functional:10, Toxicity:1
KRAS	861	Binding:829, Functional:32
EZH2	839	Binding:833, Functional:6
CHEK2	690	Binding:687, Functional:2, ADMET:1
CREBBP	687	Binding:644, Functional:43
BCL2	446	Binding:418, Functional:23, Toxicity:3, ADMET:2
ATM	240	Binding:233, Functional:5, ADMET:2
SMARCA4	230	Binding:207, ADMET:12, Functional:11
MYC	202	Binding:202
CDC42BPB	192	Binding:192
DNMT3A	120	Binding:118, ADMET:1, Functional:1
RB1	59	Binding:59
RHOA	48	Binding:48
KMT2C	29	Binding:29
FOXO1	27	Binding:27
MYD88	26	Binding:26
TET2	24	Binding:24
NOTCH1	23	Binding:19, ADMET:4
ETV6	11	Binding:11
PTEN	8	Binding:8
SF3A1	7	Binding:7
NCOA1	5	Binding:3, Functional:2
REL	3	Binding:3
MMEL1	2	Binding:2
TBL1XR1	2	Binding:2
NBN	2	Binding:2
PRDM1	1	Binding:1
SNCAIP	1	Binding:1
SNX2	1	Binding:1
CD79B	1	Binding:1
ARAP3	1	Binding:1
HLA-B	1	Binding:1
MARCKS	1	Binding:1
PMS2	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
BRAF	2.7.10.2, 2.7.11.1	non-specific protein-tyrosine kinase, non-specific serine/threonine protein kinase
BTK	2.7.10.2	non-specific protein-tyrosine kinase
EZH2	2.1.1.356	[histone H3]-lysine27 N-trimethyltransferase
KRAS	3.6.5.2	small monomeric GTPase
RHOA	3.6.5.2	small monomeric GTPase
ATM	2.7.11.1	non-specific serine/threonine protein kinase
MMEL1	3.4.24.B14
CHEK2	2.7.11.1	non-specific serine/threonine protein kinase
CREBBP	2.3.1.48	histone acetyltransferase
DNMT3A	2.1.1.37	DNA (cytosine-5-)-methyltransferase
HDAC2	3.5.1.98	histone deacetylase
NCOA1	2.3.1.48	histone acetyltransferase
PTEN	3.1.3.16, 3.1.3.67	protein-serine/threonine phosphatase, phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
BRAF	1,442
BTK	1,836
TP53	869
SMARCA4	230
EZH2	839
KRAS	861
ATM	240
BCL2	446
STAT3	1,319
CHEK2	690
CDC42BPB	192
CREBBP	687
DNMT3A	120
HDAC2	2,775
MYC	202

Pharmacogenomics

Cohort genes with a PharmGKB record: 52; with CPIC/DPWG dosing guidelines: 1.

Cohort genes with a CPIC/DPWG dosing guideline

Symbol	CPIC guidelines
HLA-B	1

Drug repurposing candidates

29 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)
VEMURAFENIB	4	BRAF, KRAS
PONATINIB	4	BRAF, BTK
FEDRATINIB	4	BRAF, BTK
SORAFENIB	4	BRAF
DASATINIB ANHYDROUS	4	BRAF
RUXOLITINIB	4	BRAF
INFIGRATINIB PHOSPHATE	4	BRAF
INFIGRATINIB	4	BRAF
REGORAFENIB	4	BRAF
DABRAFENIB	4	BRAF, KRAS
COBIMETINIB	4	BRAF
NILOTINIB	4	BRAF, CDC42BPB
ABEMACICLIB	4	BRAF
ENCORAFENIB	4	BRAF
TOVORAFENIB	4	BRAF
PAZOPANIB	4	BRAF
DASATINIB	4	BRAF, BTK, CDC42BPB
ERLOTINIB	4	BRAF
GEFITINIB	4	BRAF, CHEK2
IMATINIB	4	BRAF
NERATINIB	4	BTK, CHEK2
ENTRECTINIB	4	BTK
CERITINIB	4	BTK, ETV6
VANDETANIB	4	BTK, CDC42BPB
BOSUTINIB	4	BTK, CHEK2
OSIMERTINIB	4	BTK
BRIGATINIB	4	BTK, CHEK2
FUTIBATINIB	4	BTK
ACALABRUTINIB	4	BTK

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	16	BRAF, BTK, TP53, TET2, EZH2, KRAS, ATM, BCL2, STAT3, CHEK2 (+6 more)
B	Phased (≥1) drug, not yet approved	4	SMARCA4, NOTCH1, RB1, MYC
C	Druggable family + PDB, no drug	7	RHOA, CD79B, CD86, DNMT3A, KALRN, HLA-B, PTEN
D	Druggable family + AlphaFold only, no drug	2	MMEL1, EXOC2
E	Difficult family or no structure, no drug	23	MYD88, KMT2C, FOXP1, MS4A1, PRDM1, REL, SF3A1, BRCA2, SNCAIP, SNX2 (+13 more)

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
DNMT3A	120	EZH2
NBN	2	ATM
NF1	0	KRAS, BRAF
PTEN	8	TP53
MYD88	26	—
KMT2C	29	—
FOXP1	0	—
RHOA	48	—
MS4A1	0	—
PRDM1	1	—
REL	3	—
SF3A1	7	—
BRCA2	0	—
SNCAIP	1	—
SNX2	1	—
MMEL1	2	—
NCOA5	0	—
CD79B	1	—
CD86	0	—
ARGFXP1	0	—
SOCS1	0	—
TNPO2	0	—
LNX2	0	—
ARAP3	1	—
EXOC2	0	—
TBL1XR1	2	—
KALRN	0	—
HLA-B	1	—
ITSN2	0	—
MARCKS	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 859.

Phase distribution (across all retrieved trials)

Phase	Trials
PHASE2	290
PHASE1	182
Not specified	160
PHASE1/PHASE2	118
PHASE3	73
EARLY_PHASE1	17
PHASE2/PHASE3	11
PHASE4	8

Top trials by phase / activity

NCT	Phase	Status	Title
NCT05518383	PHASE4	RECRUITING	B-cell Mature Non-Hodgkin’s Lymphoma Treatment Protocol in Children and Adolescents 2021
NCT00466258	PHASE4	COMPLETED	LINFOTARGAM: Treatment With Chemotherapy Plus Rituximab and Highly Active Antiretroviral Therapy in Patients With Diffuse Large B Cell Lymphoma and Infection With the Human Immunodeficiency Virus (HIV)
NCT01949818	PHASE4	UNKNOWN	Treatment of Diffuse Large B Cell Lymphoma
NCT02752815	PHASE4	UNKNOWN	Reduced Chemotherapy in Low Risk DLBCL
NCT03376958	PHASE4	COMPLETED	Apatinib for Relapsed and Refractory Diffuse Large B Cell Lymphoma
NCT03513601	PHASE4	UNKNOWN	Treatment of Elderly Patients With Diffuse Large B-cell Lymphoma
NCT03579082	PHASE4	UNKNOWN	A Clinical Trial of Decitabine in Relapse and Refractory Diffuse Large B Cell Lymphoma
NCT05108805	PHASE4	COMPLETED	Chimeric Antigen Receptor (CAR) T Cell Therapy With YESCARTA in the Outpatient Setting
NCT01804686	PHASE3	RECRUITING	A Long-term Extension Study of PCI-32765 (Ibrutinib)
NCT03984448	PHASE2/PHASE3	ACTIVE_NOT_RECRUITING	Testing the Addition of a New Anti-cancer Drug, Venetoclax, to Usual Chemotherapy for High Grade B-cell Lymphomas
NCT04094311	PHASE3	RECRUITING	Study of Out of Specification for Tisagenlecleucel
NCT04332822	PHASE3	RECRUITING	A Randomized, Multicenter, Phase III Trial Comparing Treatment With R-mini-CHOP With R-mini-CHP + Polatuzumab Vedotin in Patients With Diffuse Large Cell B Cell Lymphoma
NCT04384484	PHASE3	ACTIVE_NOT_RECRUITING	Study to Evaluate Loncastuximab Tesirine With Rituximab Versus Immunochemotherapy in Participants With Relapsed or Refractory Diffuse Large B-Cell Lymphoma
NCT04404283	PHASE3	ACTIVE_NOT_RECRUITING	Brentuximab Vedotin Plus Lenalidomide and Rituximab for the Treatment of Relapsed/Refractory DLBCL
NCT04408638	PHASE3	ACTIVE_NOT_RECRUITING	A Phase III Study Evaluating Glofitamab in Combination With Gemcitabine + Oxaliplatin vs Rituximab in Combination With Gemcitabine + Oxaliplatin in Participants With Relapsed/Refractory Diffuse Large B-Cell Lymphoma
NCT04442412	PHASE3	RECRUITING	Prephase Treatment With Prednisone +/- Vitamin D Supplementation Followed by Immunochemotherapy
NCT04529772	PHASE3	ACTIVE_NOT_RECRUITING	A Combination of Acalabrutinib With R-CHOP in Subjects With Previously Untreated Non-GCB DLBCL (ACE-LY-312)
NCT04628494	PHASE3	ACTIVE_NOT_RECRUITING	A Phase 3 Trial of Epcoritamab vs Investigator’s Choice Chemotherapy in Relapsed/Refractory (R/R) Diffuse Large B-cell Lymphoma (DLBCL)
NCT04670029	PHASE3	RECRUITING	Impact of an APA Program on EFS in Patients With Diffuse Large-cell B Lymphoma Treated in 1st Line
NCT04824092	PHASE3	ACTIVE_NOT_RECRUITING	Tafasitamab + Lenalidomide + R-CHOP Versus R-CHOP in Newly Diagnosed High-intermediate and High Risk DLBCL Patients
NCT04833114	PHASE3	ACTIVE_NOT_RECRUITING	Polatuzumab Vedotin Plus Rituximab, Ifosfamide, Carboplatin and Etoposide (Pola-R-ICE) Versus R-ICE Alone in Second Line Treatment of Diffuse Large B-cell Lymphoma (DLBCL)
NCT05018520	PHASE3	RECRUITING	The Safety and Effectiveness of 4R-CHOP+4R vs 6R-CHOP+2R in Newly Diagnosed Patients With DLBCL in Low Risk
NCT05139017	PHASE2/PHASE3	RECRUITING	A Study of Zilovertamab Vedotin (MK-2140) in Combination With Standard of Care in Participants With Relapsed or Refractory Diffuse Large B-Cell Lymphoma (rrDLBCL) (MK-2140-003)
NCT05351346	PHASE3	RECRUITING	Genotype-guided Treatment in DLBCL
NCT05429268	PHASE3	ACTIVE_NOT_RECRUITING	Study to Evaluate the Safety and Efficacy of Tafasitamab Plus Lenalidomide in Participants With Relapsed or Refractory Diffuse Large B-Cell Lymphoma (firmMIND)
NCT05578976	PHASE3	ACTIVE_NOT_RECRUITING	A Study to Evaluate Change in Disease Activity of Subcutaneous (SC) Epcoritamab Combined With Intravenous and Oral Rituximab, Cyclophosphamide, Doxorubicin Hydrochloride, Vincristine, and Prednisone (R-CHOP) or R-CHOP in Adult Participants With Newly Diagnosed Diffuse Large B-Cell Lymphoma (DLBCL)
NCT05820841	PHASE3	RECRUITING	Acalabrutinib in Combination With R-miniCHOP in Older Adults With Untreated Diffuse Large B-Cell Lymphoma
NCT06091865	PHASE3	RECRUITING	A Study to Compare How Well Odronextamab Combined With Chemotherapy Works and How Safe it is Against Rituximab Combined With Chemotherapy, in Adult Patients With Previously Untreated Diffuse Large B-cell Lymphoma
NCT06355401	PHASE2/PHASE3	NOT_YET_RECRUITING	Maintenance Hormonal Therapy and DLBCL
NCT06508658	PHASE3	ACTIVE_NOT_RECRUITING	A Study of Subcutaneously Injected Epcoritamab Plus Oral Lenalidomide Tablets Compared to Intravenously (IV) Infused Rituximab Plus IV Infused Gemcitabine and IV Infused Oxaliplatin in Adult Participants With Relapsed or Refractory Diffuse Large B-Cell Lymphoma
NCT06521255	PHASE3	RECRUITING	Evaluate the Safety and Efficacy of Tafasitamab and Lenalidomide in Combination With Gemcitabine and Oxaliplatin Versus Rituximab in Combination With Gemcitabine and Oxaliplatin in Patients With Relapsed/Refractory Diffuse Large B-Cell Lymphoma
NCT06522555	PHASE3	RECRUITING	The Efficacy and Safety of Pola-ZR2 Versus ZR2 in the Treatment of Old Patients With de Novo Diffuse Large B-cell Lymphoma
NCT06717347	PHASE3	RECRUITING	A Study to Evaluate Zilovertamab Vedotin (MK-2140) Combination With Rituximab Plus Cyclophosphamide, Doxorubicin, and Prednisone (R-CHP) Versus Rituximab Plus Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone (R-CHOP) in Participants With Previously Untreated DLBCL (MK-2140-010)
NCT06929624	PHASE3	RECRUITING	A Phase 3 Clinical Study of SHR-A1912 Combined With R-GemOx Versus R-GemOx in Diffuse Large B-cell Lymphoma
NCT07084662	PHASE2/PHASE3	RECRUITING	Xinlikang Capsule for Chemotherapy-induced Fatigue and Immune Disorders in Diffuse Large B Lymphoma
NCT07188558	PHASE3	RECRUITING	A Study to Investigate Ronde-cel Versus Investigator’s Choice CD19 CAR T-Cell Therapy
NCT07226752	PHASE3	ACTIVE_NOT_RECRUITING	A Sub-study Trial of Epcoritamab vs Investigator’s Choice Chemotherapy in Relapsed/Refractory Diffuse Large B-cell Lymphoma (R/R DLBCL) in China
NCT07493109	PHASE3	RECRUITING	Chidamide for Maintenance Treatment of HBV-infected Diffuse DLBCL in Patients Initially Treated With R-CHOP
NCT07502118	PHASE2/PHASE3	RECRUITING	NexCAR19 (Talikabtagene Autoleucel) in Relapsed/Refractory B-Cell Malignancies (NexCAR19)
NCT00075478	PHASE3	COMPLETED	Total-Body Irradiation With or Without Fludarabine Phosphate Followed By Donor Stem Cell Transplant in Treating Patients With Hematologic Cancer

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
CYCLOPHOSPHAMIDE ANHYDROUS	4	115
TAFASITAMAB	4	18
AXICABTAGENE CILOLEUCEL	4	13
VINCRISTINE	4	7
BENDAMUSTINE	4	5
DOXORUBICIN	4	5
MITOXANTRONE	4	5
OBINUTUZUMAB	4	5
ETOPOSIDE PHOSPHATE	4	4
IBRUTINIB	4	4
YTTRIUM Y 90 IBRITUMOMAB TIUXETAN	4	4
CARMUSTINE	4	3
FLUDARABINE PHOSPHATE	4	3
LENALIDOMIDE	4	3
DECITABINE	4	2
EPIRUBICIN	4	2
GEMCITABINE	4	2
IFOSFAMIDE	4	2
PEGFILGRASTIM	4	2
CYTARABINE	4	1
ETOPOSIDE	4	1
LENOGRASTIM	4	1
MELPHALAN	4	1
MYCOPHENOLATE MOFETIL	4	1
OXALIPLATIN	4	1
PIXANTRONE	4	1
PREDNISONE	4	1
RITUXIMAB	4	1
VINBLASTINE	4	1
RIVOCERANIB	3	2

Precision-medicine subtype map (CIViC)

Drug × molecular subtype: 13 predictive associations from 13 curated evidence items; also 100 oncogenic, 7 prognostic, 5 diagnostic.

Molecular subtype	Therapy	Effect	Level	CIViC
CDC50A loss-of-function mutation	R-CHOP Regimen	Sensitivity/Response	CIViC B	EID11922
EZH2 Y646N	Tazemetostat + Atezolizumab	Sensitivity/Response	CIViC B	EID11112
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	EID11110
MS4A1 Mutation	R-CHOP Regimen	Resistance	CIViC B	EID10367
ALK Fusion	Crizotinib	Sensitivity/Response	CIViC C	EID1264
CLTC::ALK Fusion	Crizotinib	Sensitivity/Response	CIViC C	EID1265
EZH2 Y646H	Tazemetostat	Sensitivity/Response	CIViC C	EID9377
CLTC::ALK Fusion	ALK Inhibitor TAE684	Sensitivity/Response	CIViC D	EID1261
EZH2 Y646F	EPZ011989	Sensitivity/Response	CIViC D	EID11025
EZH2 Y646F	GSK126	Sensitivity/Response	CIViC D	EID11106
EZH2 Y646N	Tazemetostat	Sensitivity/Response	CIViC D	EID11049
EZH2 Y646N	GSK126	Sensitivity/Response	CIViC D	EID11105
BRAF V600E	Venetoclax	Resistance	CIViC D	EID8952