Lymphoma

Summary

Lymphoma (MONDO:0005062) is a cancer (an umbrella term covering 27 Mondo subtypes) with 27 cohort genes (22 GWAS associations across 14 studies; 15 CIViC-evidence somatic drivers; 9 ClinVar predisposition records) and 2,229 clinical trials. The dominant Reactome pathway is Co-inhibition by PD-1 (7 cohort genes). Molecularly, ZMYM2::FGFR1 Fusion OR BCR::FGFR1 Fusion OR CEP43::FGFR1 Fusion OR TRIM24::FGFR1 Fusion OR FGFR1 Translocation confers sensitivity to Pemigatinib in Lymphoma (CIViC Level A); 6 further subtype–drug associations are mapped below. Top therapeutic interventions include cyclophosphamide anhydrous, procarbazine, and vincristine sulfate.

At a glance

• Classification: Cancer
• Umbrella term: 27 Mondo subtypes
• Cohort genes: 27
• GWAS associations: 22
• ClinVar variants: 9
• Clinical trials: 2,229
• Precision-medicine evidence (CIViC): 7 subtype–drug associations

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	lymphoma
Mondo ID	MONDO:0005062
EFO	EFO:0000574
MeSH	D008223
Orphanet	223735
DOID	DOID:0060058
NCIT	C3208
SNOMED CT	118600007
UMLS	C0024299
MedGen	44223
MedDRA	10025310
Is cancer (heuristic)	yes

Also known as: lymphoma · lymphoma (Hodgkin and non-Hodgkin) · lymphoma (Hodgkin’s and non-Hodgkin’s) · lymphoma, malignant · lymphomatous · malignant lymphoma · MLYM

Data availability: 9 ClinVar variants · 22 GWAS associations (14 studies) · 49 cell lines · 58 intOGen driver records.

Disease family

An umbrella term covering 27 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 › lymphoid neoplasm › lymphoma

Related subtypes (5): precursor lymphoblastic lymphoma/leukemia, neoplasm of immature B and T cells, lymphoid leukemia, malignant lymphatic vessel tumor, T-cell and NK-cell neoplasm

Subtypes (27): prostate lymphoma, nasal cavity lymphoma, bladder lymphoma, tracheal lymphoma, retroperitoneal lymphoma, ureteral lymphoma, ovarian lymphoma, B-cell lymphoma, unclassifiable, with features intermediate between diffuse large b-cell lymphoma and classical Hodgkin lymphoma, pediatric lymphoma, adult lymphoma, breast lymphoma, heart lymphoma, chest wall lymphoma, lung lymphoma, mediastinal malignant lymphoma, eye lymphoma, B-cell neoplasm, gastrointestinal lymphoma, Hodgkins lymphoma, peripheral T-cell lymphoma, not otherwise specified, composite lymphoma, AIDS-related primary central nervous system lymphoma, primary organ-specific lymphoma, non-Hodgkin lymphoma, extranodal nasal NK/T cell lymphoma, methotrexate-associated lymphoproliferative disorders, progressive transformation of germinal centers

Genetics & variants

GWAS landscape

22 GWAS associations across 14 studies. Top hits map to 9 distinct genes (as reported by GWAS).

Top associations by p-value

rsID	p-value	Gene	Risk allele	Odds ratio
rs4713570	1e-16	HLA-DQA1 - HLA-DQB1	T	0.23
rs6773854	3e-13	BCL6-AS1 - LINC01991	C	1.44
rs4530903	3e-12	HLA-DRB1 - HLA-DQA1	T	1.93
rs9268853	2e-10	HLA-DRB9	C	1.56
rs2647045	4e-10	HLA-DQB1 - MTCO3P1	?	1.69
rs13255292	5e-10	PVT1	T	0.15
rs7945144	1e-09	RNU6-376P - DDX6	G	0.17
rs2621416	2e-09	HLA-DQB2 - HLA-DOB	G	1.57
rs115957064	8e-09	EXOC2	T	1.68
rs143700307	3e-08	QRSL1P1 - XCL2	A	0.49
rs117972357	3e-08	LINC02318	A	1.44
rs12289961	4e-08	OR10Q2P	T	1.29
rs915103621	5e-08	AUTS2	G	14.36
rs948562	3e-07	ZFP91-CNTF, ZFP91	G	1.32
rs707824	6e-07	LINC01108 - RNU6-793P	T	1.33
rs2647046	2e-06	HLA-DQB1 - MTCO3P1	?	1.25
rs7453920	5e-06	HLA-DQB2	?	1.19

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST90018878	Sakaue S	2021	3,546	487,257	A cross-population atlas of genetic associations for 220 human phenotypes.
GCST90079120	Backman JD	2021	965	73,265	Exome sequencing and analysis of 454,787 UK Biobank participants.
GCST90083106	Backman JD	2021	965	73,265	Exome sequencing and analysis of 454,787 UK Biobank participants.
GCST90042740	Jiang L	2021	603	455,745	A generalized linear mixed model association tool for biobank-scale data.
GCST90435646	Zhou W	2018	573	404,466	Efficiently controlling for case-control imbalance and sample relatedness in large-scale genetic association studies.
GCST90079636	Backman JD	2021	521	387,409	Exome sequencing and analysis of 454,787 UK Biobank participants.
GCST90083622	Backman JD	2021	521	387,409	Exome sequencing and analysis of 454,787 UK Biobank participants.
GCST90018658	Sakaue S	2021	335	177,342	A cross-population atlas of genetic associations for 220 human phenotypes.
GCST001826	Vijai J	2013	275	4,044	Susceptibility loci associated with specific and shared subtypes of lymphoid malignancies.
GCST90481541	Verma A	2024	265	451,051	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

Tier	Variants
Tier 1: coding	0
Tier 2: splice/UTR	1
Tier 3: regulatory	1
Tier 4: intronic/intergenic	15

MAF distribution

Bucket	Variants
common (>=0.05)	14
low_freq (0.01-0.05)	0
rare (<0.01)	1
unknown	2

Functional consequences

Consequence	Count
intron_variant	8
intergenic_variant	6
3_prime_UTR_variant	1
non_coding_transcript_exon_variant	1
regulatory_region_variant	1

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
rs4713570	6	32658263	C>G,T	0.05	intergenic_variant	HLA-DQA1 - HLA-DQB1	1e-16	Tier 4: intronic/intergenic
rs6773854	3	187931631	T>A,C,G	0.21	intergenic_variant	BCL6-AS1 - LINC01991	3e-13	Tier 4: intronic/intergenic
rs4530903	6	32614112	C>T	0.05	intergenic_variant	HLA-DRB1 - HLA-DQA1	3e-12	Tier 4: intronic/intergenic
rs9268853	6	32461866	T>A,C	0.05	intron_variant	HLA-DRB9	2e-10	Tier 4: intronic/intergenic
rs2647045	6	32700323	G>A	0.05	intergenic_variant	HLA-DQB1 - MTCO3P1	4e-10	Tier 4: intronic/intergenic
rs13255292	8	128064327	C>T	0.05	intron_variant	PVT1	5e-10	Tier 4: intronic/intergenic
rs7945144	11	118738007	A>G	0.05	intron_variant	RNU6-376P - DDX6	1e-09	Tier 4: intronic/intergenic
rs2621416	6	32774091	T>A,C,G	0.05	intergenic_variant	HLA-DQB2 - HLA-DOB	2e-09	Tier 4: intronic/intergenic
rs115957064	6	485991	C>T		3_prime_UTR_variant	EXOC2	8e-09	Tier 2: splice/UTR
rs143700307	1	168480046	G>A	0.05	intron_variant	QRSL1P1 - XCL2	3e-08	Tier 4: intronic/intergenic
rs117972357	14	95577209	G>A		intron_variant	LINC02318	3e-08	Tier 4: intronic/intergenic
rs12289961	11	58292720	C>G,T	0.05	non_coding_transcript_exon_variant	OR10Q2P	4e-08	Tier 4: intronic/intergenic
rs915103621	7	70449704	A>G	0.001	intron_variant	AUTS2	5e-08	Tier 4: intronic/intergenic
rs948562	11	58580292	A>C,G,T	0.05	intron_variant	ZFP91-CNTF, ZFP91	3e-07	Tier 4: intronic/intergenic
rs707824	6	14636732	T>A,C,G	0.05	intergenic_variant	LINC01108 - RNU6-793P	6e-07	Tier 4: intronic/intergenic
rs2647046	6	32700559	A>C,G,T	0.05	regulatory_region_variant	HLA-DQB1 - MTCO3P1	2e-06	Tier 3: regulatory
rs7453920	6	32762235	A>G,T	0.05	intron_variant	HLA-DQB2	5e-06	Tier 4: intronic/intergenic

ClinVar germline variants

9 retrieved; paginated sample, class counts are floors:

4 pathogenic, 2 likely pathogenic, 1 pathogenic/likely pathogenic, 1 uncertain significance, 1 conflicting classifications of pathogenicity

ClinVar	Variant (HGVS)	Gene	Classification	Review
638279	NM_003482.4(KMT2D):c.10624_10625del (p.Leu3542fs)	KMT2D	Pathogenic	criteria provided, single submitter
219789	NM_002485.5(NBN):c.93_94del (p.Ala32fs)	NBN	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
91366	NM_000535.7(PMS2):c.736_741delinsTGTGTGTGAAG (p.Pro246_Pro247delinsCysValTer)	PMS2	Pathogenic	reviewed by expert panel
13333	NM_002834.5(PTPN11):c.188A>G (p.Tyr63Cys)	PTPN11	Pathogenic	reviewed by expert panel
12356	NM_000546.6(TP53):c.743G>A (p.Arg248Gln)	TP53	Pathogenic	reviewed by expert panel
638280	NM_003482.4(KMT2D):c.11897_11911del (p.Phe3966_Gln3971delinsTer)	KMT2D	Likely pathogenic	no assertion criteria provided
638281	NM_015559.3(SETBP1):c.1703G>T (p.Ser568Ile)	SETBP1	Likely pathogenic	no assertion criteria provided
638278	NM_001042424.3(NSD2):c.3295G>A (p.Glu1099Lys)	NSD2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
638277	NM_005896.4(IDH1):c.784G>A (p.Glu262Lys)	IDH1	Uncertain significance	no assertion criteria provided

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 107 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 2

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

Gene	HGNC	Evidence routes
BCL6	BCL6	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
CCND3	Act	BL,DLBCLNOS,MLYM,NHL	CIViC #10
FGFR1	Act	BLCA,GBM,OVT,PANCREAS,PAST,PGNG,WDTC	CIViC #1885
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
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
BCL2	Act	DLBCLNOS,MLYM,NHL	CIViC #59
BCL6	Act	DLBCLNOS,MLYM	CIViC #566
NSD2	Act	ALL,BL,PCM,UTUC	CIViC #6107
SETBP1	Act	ACC	CIViC #10024
HLA-DQA1	Act	PLMESO
HLA-DRA			CIViC #2622
IDH1	Act	AML,CHOL,GB,GBM,HCC,HGGNOS,LGGNOS,MBL,MEL,MT,OS,PAST,PCM,PRAD,SKCM	CIViC #26
KMT2D	LoF	ACYC,ALL,ANSC,BCC,BL,BLADDER,BLCA,BRCA,CCRCC,CEAD,CESC,CHOL,CHRCC,CLLSLL,CSCC,DLBCLNOS,ESCA,GBM,HCC,HGGNOS,HNSC,LNM,LUSC,MBL,MLYM,NBL,NETNOS,NHL,NPC,NSCLC,OVT,PAAD,PANCREAS,PAST,PLMESO,PRAD,PRCC,PROSTATE,RCC,SACA,SCLC,SKCM,STAD,STOMACH,UCEC,UCS	CIViC #64
PMS2	ambiguous	HCC	CIViC #4371
PTPN11	Act	ALL,AML,CLLSLL,COADREAD,GBM,LGGNOS,NBL,PAST,PCM	CIViC #4685

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
FGFR1	Orphanet:168953	Myeloid/lymphoid neoplasm associated with FGFR1 rearrangement
FGFR1	Orphanet:2117	Hartsfield syndrome
FGFR1	Orphanet:220386	Semilobar holoprosencephaly
FGFR1	Orphanet:2396	Encephalocraniocutaneous lipomatosis
FGFR1	Orphanet:251576	Gliosarcoma
FGFR1	Orphanet:251579	Giant cell glioblastoma
FGFR1	Orphanet:251615	Pilomyxoid astrocytoma
FGFR1	Orphanet:2645	Osteoglosphonic dysplasia
FGFR1	Orphanet:280200	Microform holoprosencephaly
FGFR1	Orphanet:314950	Primary hypereosinophilic syndrome
FGFR1	Orphanet:3157	Septo-optic dysplasia spectrum
FGFR1	Orphanet:3366	Non-syndromic metopic craniosynostosis
FGFR1	Orphanet:432	Normosmic congenital hypogonadotropic hypogonadism
FGFR1	Orphanet:478	Kallmann syndrome
FGFR1	Orphanet:93258	Pfeiffer syndrome type 1
FGFR1	Orphanet:93924	Lobar holoprosencephaly
FGFR1	Orphanet:99798	Oligodontia
KRAS	Orphanet:1333	Familial pancreatic carcinoma
KRAS	Orphanet:1340	Cardiofaciocutaneous syndrome
KRAS	Orphanet:144	Lynch syndrome
KRAS	Orphanet:146	Differentiated thyroid carcinoma
KRAS	Orphanet:2396	Encephalocraniocutaneous lipomatosis
KRAS	Orphanet:251615	Pilomyxoid astrocytoma
KRAS	Orphanet:2612	Linear nevus sebaceus syndrome
KRAS	Orphanet:268114	RAS-associated autoimmune leukoproliferative disease
KRAS	Orphanet:3339	Oculoectodermal syndrome
KRAS	Orphanet:648	Noonan syndrome
KRAS	Orphanet:86834	Juvenile myelomonocytic leukemia
ATM	Orphanet:100	Ataxia-telangiectasia
ATM	Orphanet:1331	Familial prostate cancer

Cohort genes → proteins

27 cohort genes, 26 distinct canonical proteins.

Evidence partition

Subset	Genes
gwas_only	14
civic_only	5
multi_evidence	8

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
TP53	HGNC:11998	ENSG00000141510	P04637	Cellular tumor antigen p53	clinvar,civic_evidence
CCND3	HGNC:1585	ENSG00000112576	P30281	G1/S-specific cyclin-D3	civic_evidence
FGFR1	HGNC:3688	ENSG00000077782	P11362	Fibroblast growth factor receptor 1	civic_evidence
KRAS	HGNC:6407	ENSG00000133703	P01116	GTPase KRas	civic_evidence
ATM	HGNC:795	ENSG00000149311	Q13315	Serine-protein kinase ATM	civic_evidence
BCL2	HGNC:990	ENSG00000171791	P10415	Apoptosis regulator Bcl-2	civic_evidence
BCL6	HGNC:1001	ENSG00000113916	P41182	B-cell lymphoma 6 protein	gwas
NSD2	HGNC:12766	ENSG00000109685	O96028	Histone-lysine N-methyltransferase NSD2	clinvar
LPXN	HGNC:14061	ENSG00000110031	O60711	Leupaxin	gwas
SETBP1	HGNC:15573	ENSG00000152217	Q9Y6X0	SET-binding protein	clinvar
RNF182	HGNC:28522	ENSG00000180537	Q8N6D2	E3 ubiquitin-protein ligase RNF182	gwas
ZFP91-CNTF	HGNC:33441	ENSG00000255073		ZFP91-CNTF readthrough (NMD candidate)	gwas
TAP2	HGNC:44	ENSG00000204267	Q03519	Antigen peptide transporter 2	gwas
HLA-DQA1	HGNC:4942	ENSG00000196735	P01909	HLA class II histocompatibility antigen, DQ alpha 1 chain	gwas
HLA-DQA2	HGNC:4943	ENSG00000237541	P01906	HLA class II histocompatibility antigen, DQ alpha 2 chain	gwas
HLA-DQB1	HGNC:4944	ENSG00000179344	P01920	HLA class II histocompatibility antigen, DQ beta 1 chain	gwas
HLA-DQB2	HGNC:4945	ENSG00000232629	P05538	HLA class II histocompatibility antigen, DQ beta 2 chain	gwas
HLA-DRA	HGNC:4947	ENSG00000204287	P01903	HLA class II histocompatibility antigen, DR alpha chain	gwas
HLA-DRB1	HGNC:4948	ENSG00000196126	P01911	HLA class II histocompatibility antigen, DRB1 beta chain	gwas
HLA-DRB5	HGNC:4953	ENSG00000198502	Q30154	HLA class II histocompatibility antigen, DR beta 5 chain	gwas
IDH1	HGNC:5382	ENSG00000138413	O75874	Isocitrate dehydrogenase [NADP] cytoplasmic	clinvar
JARID2	HGNC:6196	ENSG00000008083	Q92833	Protein Jumonji	gwas
LPP	HGNC:6679	ENSG00000145012	Q93052	Lipoma-preferred partner	gwas
KMT2D	HGNC:7133	ENSG00000167548	O14686	Histone-lysine N-methyltransferase 2D	clinvar
NBN	HGNC:7652	ENSG00000104320	O60934	Nibrin	clinvar
PMS2	HGNC:9122	ENSG00000122512	P54278	Mismatch repair endonuclease PMS2	clinvar
PTPN11	HGNC:9644	ENSG00000179295	Q06124	Tyrosine-protein phosphatase non-receptor type 11	clinvar

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.
CCND3	G1/S-specific cyclin-D3	Regulatory component of the cyclin D3-CDK4 (DC) complex that phosphorylates and inhibits members of the retinoblastoma (RB) protein family including RB1 and regulates the cell-cycle during G(1)/S transition.
FGFR1	Fibroblast growth factor receptor 1	Tyrosine-protein kinase that acts as a cell-surface receptor for fibroblast growth factors and plays an essential role in the regulation of embryonic development, cell proliferation, differentiation and migration.
KRAS	GTPase KRas	Ras proteins bind GDP/GTP and possess intrinsic GTPase activity.
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.
BCL2	Apoptosis regulator Bcl-2	Suppresses apoptosis in a variety of cell systems including factor-dependent lymphohematopoietic and neural cells.
BCL6	B-cell lymphoma 6 protein	Transcriptional repressor mainly required for germinal center (GC) formation and antibody affinity maturation which has different mechanisms of action specific to the lineage and biological functions.
NSD2	Histone-lysine N-methyltransferase NSD2	Histone methyltransferase which specifically dimethylates nucleosomal histone H3 at ‘Lys-36’ (H3K36me2).
LPXN	Leupaxin	Transcriptional coactivator for androgen receptor (AR) and serum response factor (SRF).
RNF182	E3 ubiquitin-protein ligase RNF182	E3 ubiquitin-protein ligase that mediates the ubiquitination of ATP6V0C and targets it to degradation via the ubiquitin-proteasome pathway.
TAP2	Antigen peptide transporter 2	ABC transporter associated with antigen processing.
HLA-DQA1	HLA class II histocompatibility antigen, DQ alpha 1 chain	Binds peptides derived from antigens that access the endocytic route of antigen presenting cells (APC) and presents them on the cell surface for recognition by the CD4 T-cells.
HLA-DQA2	HLA class II histocompatibility antigen, DQ alpha 2 chain	Binds peptides derived from antigens that access the endocytic route of antigen presenting cells (APC) and presents them on the cell surface for recognition by the CD4 T-cells.
HLA-DQB1	HLA class II histocompatibility antigen, DQ beta 1 chain	Binds peptides derived from antigens that access the endocytic route of antigen presenting cells (APC) and presents them on the cell surface for recognition by the CD4 T-cells.
HLA-DQB2	HLA class II histocompatibility antigen, DQ beta 2 chain	Binds peptides derived from antigens that access the endocytic route of antigen presenting cells (APC) and presents them on the cell surface for recognition by the CD4 T-cells.
HLA-DRA	HLA class II histocompatibility antigen, DR alpha chain	An alpha chain of antigen-presenting major histocompatibility complex class II (MHCII) molecule.
HLA-DRB1	HLA class II histocompatibility antigen, DRB1 beta chain	A beta chain of antigen-presenting major histocompatibility complex class II (MHCII) molecule.
HLA-DRB5	HLA class II histocompatibility antigen, DR beta 5 chain	Binds peptides derived from antigens that access the endocytic route of antigen presenting cells (APC) and presents them on the cell surface for recognition by the CD4 T-cells.
IDH1	Isocitrate dehydrogenase [NADP] cytoplasmic	Catalyzes the NADP(+)-dependent oxidative decarboxylation of isocitrate (D-threo-isocitrate) to 2-ketoglutarate (2-oxoglutarate), which is required by other enzymes such as the phytanoyl-CoA dioxygenase.
JARID2	Protein Jumonji	Regulator of histone methyltransferase complexes that plays an essential role in embryonic development, including heart and liver development, neural tube fusion process and hematopoiesis.
LPP	Lipoma-preferred partner	May play a structural role at sites of cell adhesion in maintaining cell shape and motility.
KMT2D	Histone-lysine N-methyltransferase 2D	Histone methyltransferase that catalyzes methyl group transfer from S-adenosyl-L-methionine to the epsilon-amino group of ‘Lys-4’ of histone H3 (H3K4).
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.
PMS2	Mismatch repair endonuclease PMS2	Component of the post-replicative DNA mismatch repair system (MMR).
PTPN11	Tyrosine-protein phosphatase non-receptor type 11	Acts downstream of various receptor and cytoplasmic protein tyrosine kinases to participate in the signal transduction from the cell surface to the nucleus.

Protein-family classification

Druggable: 13 · Difficult: 8 · Unknown: 6 · Druggable fraction: 0.48

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Antibody/Immunoglobulin	7	7.6×	2e-04
Transcription factor	8	2.5×	0.043
Phosphatase	1	3.1×	0.413
Transporter	1	2.9×	0.413
Kinase	2	2.0×	0.413
Enzyme (other)	2	0.9×	0.783
Other/Unknown	6	0.4×	1.000

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
CCND3	Other/Unknown	no		Cyclin_C-dom, Cyclin_N, Cyclin-like_dom
FGFR1	Kinase	yes	2.7.10.1	Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom, Ig_sub2
KRAS	Enzyme (other)	yes	3.6.5.2	Small_GTPase, Small_GTP-bd, Small_GTPase_Ras-type
ATM	Kinase	yes	2.7.11.1	PI3/4_kinase_cat_dom, PIK-rel_kinase_FAT, FATC_dom
BCL2	Other/Unknown	no		Bcl2-like, Bcl2_BH4, Bcl2/BclX
BCL6	Transcription factor	no		BTB/POZ_dom, SKP1/BTB/POZ_sf, Znf_C2H2_type
NSD2	Transcription factor	no	2.1.1.356	PWWP_dom, SET_dom, Znf_RING
LPXN	Transcription factor	no		Znf_LIM, Tgfb1i1/Leupaxin/TGFB1I1
SETBP1	Other/Unknown	no		AT_hook_DNA-bd_motif
RNF182	Transcription factor	no		Znf_RING, Znf_RING/FYVE/PHD, Znf_RING_CS
ZFP91-CNTF	Other/Unknown	no
TAP2	Transporter	yes	7.4.2.14	ABC_transporter-like_ATP-bd, AAA+_ATPase, Tap2/ABCB3
HLA-DQA1	Antibody/Immunoglobulin	yes		MHC_II_a_N, Ig/MHC_CS, Ig_C1-set
HLA-DQA2	Antibody/Immunoglobulin	yes		MHC_II_a_N, Ig/MHC_CS, Ig_C1-set
HLA-DQB1	Antibody/Immunoglobulin	yes		MHC_II_b_N, Ig/MHC_CS, Ig_C1-set
HLA-DQB2	Antibody/Immunoglobulin	yes		MHC_II_b_N, Ig/MHC_CS, Ig_C1-set
HLA-DRA	Antibody/Immunoglobulin	yes		MHC_II_a_N, Ig/MHC_CS, Ig_C1-set
HLA-DRB1	Antibody/Immunoglobulin	yes		MHC_II_b_N, Ig/MHC_CS, Ig_C1-set
HLA-DRB5	Antibody/Immunoglobulin	yes		MHC_II_b_N, Ig/MHC_CS, Ig_C1-set
IDH1	Enzyme (other)	yes	1.1.1.42	Isocitrate_DH_NADP, IsoCit/isopropylmalate_DH_CS, IsoPropMal-DH-like_dom
JARID2	Transcription factor	no		ARID_dom, JmjC_dom, JmjN
LPP	Transcription factor	no		Znf_LIM
KMT2D	Transcription factor	no		SET_dom, Znf_RING, Znf_PHD
NBN	Other/Unknown	no		FHA_dom, BRCT_dom, SMAD_FHA_dom_sf
PMS2	Other/Unknown	no		MutL/Mlh/PMS, DNA_mismatch_S5_2-like, Ribsml_uS5_D2-typ_fold_subgr
PTPN11	Phosphatase	yes	3.1.3.48	PTP_cat, Tyr_Pase_dom, SH2

Expression context

Cohort genes with no expression data: 0.

24 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)	27
unknown	0

Top tissues across cohort

Tissue	Cohort genes
granulocyte	6
vermiform appendix	5
buccal mucosa cell	4
ganglionic eminence	3
ventricular zone	3
calcaneal tendon	3
male germ line stem cell (sensu Vertebrata) in testis	3
lymph node	3
monocyte	3
blood	2
thymus	2
dorsal motor nucleus of vagus nerve	2
cortical plate	2
leukocyte	2
sural nerve	2
right lung	2
medial globus pallidus	2
tendon of biceps brachii	1
stromal cell of endometrium	1
nipple	1

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
CCND3	287	ubiquitous	marker	granulocyte, thymus, blood
FGFR1	292	ubiquitous	marker	buccal mucosa cell, stromal cell of endometrium, calcaneal tendon
KRAS	298	ubiquitous	marker	trigeminal ganglion, pylorus, nipple
ATM	286	ubiquitous	marker	calcaneal tendon, colonic epithelium, corpus callosum
BCL2	275	ubiquitous	marker	dorsal motor nucleus of vagus nerve, superficial temporal artery, calcaneal tendon
BCL6	300	ubiquitous	marker	gastrocnemius, mucosa of stomach, blood
NSD2	281	ubiquitous	marker	ventricular zone, ganglionic eminence, cortical plate
LPXN	242	ubiquitous	marker	granulocyte, leukocyte, mononuclear cell
SETBP1	280	ubiquitous	marker	ventricular zone, buccal mucosa cell, caput epididymis
RNF182	192	broad	yes	endothelial cell, cortical plate, ganglionic eminence
ZFP91-CNTF	89	ubiquitous	yes	sural nerve, primordial germ cell in gonad, male germ line stem cell (sensu Vertebrata) in testis
TAP2	134	ubiquitous	yes	vermiform appendix, lymph node, monocyte
HLA-DQA1	244	broad	marker	gall bladder, rectum, monocyte
HLA-DQA2	127	broad	marker	granulocyte, vermiform appendix, male germ line stem cell (sensu Vertebrata) in testis
HLA-DQB1	268	broad	marker	right lung, spleen, upper lobe of left lung
HLA-DQB2	127	tissue_specific	marker	lymph node, granulocyte, skin of abdomen
HLA-DRA	132	broad	marker	monocyte, leukocyte, vermiform appendix
HLA-DRB1	131	tissue_specific	marker	vermiform appendix, granulocyte, right lung
HLA-DRB5	130	tissue_specific	marker	granulocyte, lymph node, vermiform appendix
IDH1	294	ubiquitous	marker	corpus epididymis, jejunal mucosa, adrenal tissue
JARID2	293	ubiquitous	marker	secondary oocyte, oocyte, buccal mucosa cell
LPP	292	ubiquitous	marker	saphenous vein, urethra, vena cava
KMT2D	272	ubiquitous	marker	buccal mucosa cell, medial globus pallidus, sural nerve
NBN	299	ubiquitous	marker	endometrium epithelium, mammary duct, cauda epididymis
PMS2	143	ubiquitous	marker	thymus, prefrontal cortex, male germ line stem cell (sensu Vertebrata) in testis
PTPN11	295	ubiquitous	marker	medial globus pallidus, dorsal motor nucleus of vagus nerve, globus pallidus

Protein interactions among cohort

Intra-cohort edges: 18.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
TP53	22,736
KRAS	14,509
BCL2	8,343
ATM	7,383
PTPN11	6,009
FGFR1	5,693
IDH1	5,464
BCL6	3,984
JARID2	3,794
NSD2	3,530

Intra-cohort edges

A	B	Sources
ATM	NBN	biogrid_interaction, string_interaction
ATM	TP53	biogrid_interaction, string_interaction
BCL2	BCL6	string_interaction
BCL2	TP53	intact, string_interaction
HLA-DQA1	HLA-DQA2	intact
HLA-DQA1	HLA-DQB1	biogrid_interaction, intact
HLA-DQA1	HLA-DRB5	intact
HLA-DQA2	HLA-DQB2	string_interaction
HLA-DQA2	HLA-DRB1	string_interaction
HLA-DQB2	HLA-DRA	string_interaction
HLA-DRA	HLA-DRB1	biogrid_interaction, intact, string_interaction
HLA-DRA	HLA-DRB5	biogrid_interaction, intact, string_interaction
HLA-DRA	TAP2	string_interaction
HLA-DRB1	HLA-DRB5	biogrid_interaction, intact
IDH1	TP53	string_interaction
KMT2D	TP53	string_interaction
KRAS	TP53	string_interaction
LPP	LPXN	intact

Structural data

PDB: 21 · AlphaFold-only: 5 · No structure: 1

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
KRAS	P01116	511
TP53	P04637	313
BCL6	P41182	246
HLA-DRA	P01903	140
PTPN11	Q06124	115
HLA-DRB1	P01911	108
FGFR1	P11362	83
IDH1	O75874	61
BCL2	P10415	55
HLA-DQA1	P01909	28
NSD2	O96028	22
TAP2	Q03519	21
JARID2	Q92833	16
ATM	Q13315	14
KMT2D	O14686	11
HLA-DQB1	P01920	10
PMS2	P54278	9
NBN	O60934	7
LPXN	O60711	4
HLA-DRB5	Q30154	4
CCND3	P30281	2

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
HLA-DQA2	P01906	89.29
HLA-DQB2	P05538	86.87
RNF182	Q8N6D2	70.67
LPP	Q93052	60.99
SETBP1	Q9Y6X0	43.30

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 300. Enrichment computed across 27 evidence-associated genes (23 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 23 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Co-inhibition by PD-1	7	158.0×	2e-12	HLA-DQA1, HLA-DQA2, HLA-DQB2, HLA-DRA, HLA-DRB1, HLA-DRB5, PTPN11
Translocation of ZAP-70 to Immunological synapse	6	165.5×	9e-11	HLA-DQA1, HLA-DQA2, HLA-DQB2, HLA-DRA, HLA-DRB1, HLA-DRB5
Phosphorylation of CD3 and TCR zeta chains	6	141.9×	2e-10	HLA-DQA1, HLA-DQA2, HLA-DQB2, HLA-DRA, HLA-DRB1, HLA-DRB5
Generation of second messenger molecules	6	90.3×	3e-09	HLA-DQA1, HLA-DQA2, HLA-DQB2, HLA-DRA, HLA-DRB1, HLA-DRB5
Interferon gamma signaling	7	38.2×	2e-08	HLA-DQA1, HLA-DQA2, HLA-DQB1, HLA-DQB2, HLA-DRA, HLA-DRB1, HLA-DRB5
Downstream TCR signaling	6	33.5×	9e-07	HLA-DQA1, HLA-DQA2, HLA-DQB2, HLA-DRA, HLA-DRB1, HLA-DRB5
MHC class II antigen presentation	6	23.3×	7e-06	HLA-DQA1, HLA-DQA2, HLA-DQB2, HLA-DRA, HLA-DRB1, HLA-DRB5
FRS-mediated FGFR1 signaling	3	59.6×	5e-04	FGFR1, KRAS, PTPN11
Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks	4	25.5×	5e-04	TP53, NSD2, NBN, ATM
G2/M DNA damage checkpoint	4	20.9×	0.001	TP53, NSD2, NBN, ATM
Sensing of DNA Double Strand Breaks	2	165.5×	0.002	NBN, ATM
TP53 Regulates Transcription of Caspase Activators and Caspases	2	82.8×	0.005	TP53, ATM
Activated NTRK2 signals through FRS2 and FRS3	2	82.8×	0.005	KRAS, PTPN11
Defective homologous recombination repair (HRR) due to PALB2 loss of function	2	82.8×	0.005	NBN, ATM
TP53 Regulates Transcription of DNA Repair Genes	3	23.6×	0.005	TP53, ATM, PMS2
Diseases of DNA Double-Strand Break Repair	2	70.9×	0.005	NBN, ATM
Defective homologous recombination repair (HRR) due to BRCA2 loss of function	2	70.9×	0.005	NBN, ATM
TP53 regulates transcription of several additional cell death genes whose specific roles in p53-dependent apoptosis remain uncertain	2	66.2×	0.005	TP53, BCL6
Stabilization of p53	2	66.2×	0.005	TP53, ATM
Signaling by FLT3 ITD and TKD mutants	2	66.2×	0.005	KRAS, PTPN11
Nonhomologous End-Joining (NHEJ)	3	21.9×	0.005	NSD2, NBN, ATM
DNA Damage/Telomere Stress Induced Senescence	3	21.3×	0.005	TP53, NBN, ATM
Regulation of RUNX1 Expression and Activity	2	58.4×	0.007	CCND3, PTPN11
Resolution of D-Loop Structures	2	55.2×	0.007	NBN, ATM
Tie2 Signaling	2	52.3×	0.007	KRAS, PTPN11
Signaling by CSF3 (G-CSF)	2	49.6×	0.007	KRAS, PTPN11
Diseases of DNA repair	2	49.6×	0.007	NBN, ATM
TP53 Regulates Transcription of Cell Death Genes	2	47.3×	0.007	BCL6, ATM
FRS-mediated FGFR3 signaling	2	47.3×	0.007	KRAS, PTPN11
TP53 Regulates Transcription of Genes Involved in Cytochrome C Release	2	47.3×	0.007	TP53, ATM

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 26 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
peptide antigen assembly with MHC class II protein complex	7	283.6×	5e-14	HLA-DQA1, HLA-DQA2, HLA-DQB1, HLA-DQB2, HLA-DRA, HLA-DRB1, HLA-DRB5
antigen processing and presentation of exogenous peptide antigen via MHC class II	7	146.4×	6e-12	HLA-DQA1, HLA-DQA2, HLA-DQB1, HLA-DQB2, HLA-DRA, HLA-DRB1, HLA-DRB5
positive regulation of immune response	7	129.6×	1e-11	HLA-DQA1, HLA-DQA2, HLA-DQB1, HLA-DQB2, HLA-DRA, HLA-DRB1, HLA-DRB5
positive regulation of T cell activation	7	119.4×	1e-11	HLA-DQA1, HLA-DQA2, HLA-DQB1, HLA-DQB2, HLA-DRA, HLA-DRB1, HLA-DRB5
adaptive immune response	6	19.4×	5e-05	HLA-DQA1, HLA-DQA2, HLA-DQB1, HLA-DQB2, HLA-DRA, HLA-DRB5
antigen processing and presentation of endogenous peptide antigen via MHC class II	2	648.1×	2e-04	HLA-DRA, HLA-DRB1
myeloid dendritic cell antigen processing and presentation	2	432.1×	5e-04	HLA-DRA, HLA-DRB1
double-strand break repair	4	31.2×	5e-04	TP53, NSD2, NBN, ATM
regulation of T-helper cell differentiation	2	324.1×	6e-04	HLA-DRA, HLA-DRB1
positive regulation of CD4-positive, alpha-beta T cell activation	2	324.1×	6e-04	HLA-DRA, HLA-DRB1
cardiac muscle cell proliferation	3	67.0×	6e-04	FGFR1, JARID2, KRAS
neuron apoptotic process	4	28.5×	6e-04	TP53, KRAS, ATM, BCL2
immune response	6	10.9×	6e-04	HLA-DQA1, HLA-DQA2, HLA-DQB1, HLA-DQB2, HLA-DRA, HLA-DRB1
positive regulation of T cell mediated cytotoxicity	3	58.9×	7e-04	TAP2, HLA-DRA, HLA-DRB1
B cell lineage commitment	2	259.3×	7e-04	TP53, BCL2
positive regulation of CD4-positive, CD25-positive, alpha-beta regulatory T cell differentiation	2	259.3×	7e-04	HLA-DRA, HLA-DRB1
negative regulation of telomere capping	2	259.3×	7e-04	NBN, ATM
homeostasis of number of cells within a tissue	3	51.2×	8e-04	KRAS, PTPN11, BCL2
positive regulation of isotype switching to IgA isotypes	2	216.1×	1e-03	NSD2, PMS2
DNA damage checkpoint signaling	3	45.2×	0.001	NBN, ATM, PTPN11
DNA damage response, signal transduction by p53 class mediator	3	41.4×	0.001	TP53, NBN, ATM
thymus development	3	38.9×	0.001	JARID2, ATM, BCL2
positive regulation of memory T cell differentiation	2	144.0×	0.002	HLA-DRA, HLA-DRB1
humoral immune response	3	32.4×	0.002	HLA-DQB1, HLA-DRB1, BCL2
DNA double-strand break processing	2	117.8×	0.003	NBN, ATM
negative regulation of B cell apoptotic process	2	117.8×	0.003	BCL6, BCL2
positive regulation of cellular senescence	2	99.7×	0.004	TP53, KRAS
replicative senescence	2	76.2×	0.006	TP53, ATM
oocyte development	2	72.0×	0.006	ATM, BCL2
glial cell proliferation	2	68.2×	0.007	TP53, KRAS

Therapeutics

Drugs indicated for this disease

12 approved, 82 in late-stage (phase 3) trials. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

Drug	Development status
Allopurinol	Approved (phase 4)
Cortisone Acetate	Approved (phase 4)
Dexamethasone	Approved (phase 4)
Hydrocortisone	Approved (phase 4)
Lorlatinib	Approved (phase 4)
Methylprednisolone Acetate	Approved (phase 4)
Plerixafor	Approved (phase 4)
Prednisolone	Approved (phase 4)
Prednisone	Approved (phase 4)
Rasburicase	Approved (phase 4)
Tafasitamab	Approved (phase 4)
Tagraxofusp	Approved (phase 4)
Aldesleukin	Phase 3 (in late-stage trials)
Alemtuzumab	Phase 3 (in late-stage trials)
Amphotericin B	Phase 3 (in late-stage trials)
Asparaginase	Phase 3 (in late-stage trials)
Azacitidine	Phase 3 (in late-stage trials)
Bendamustine	Phase 3 (in late-stage trials)
Bexarotene	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)
Busulfan	Phase 3 (in late-stage trials)
Calcium	Phase 3 (in late-stage trials)
Calcium Carbonate	Phase 3 (in late-stage trials)
Carboplatin	Phase 3 (in late-stage trials)
Carmustine	Phase 3 (in late-stage trials)
Carvedilol	Phase 3 (in late-stage trials)
Chlorambucil	Phase 3 (in late-stage trials)
Cisplatin	Phase 3 (in late-stage trials)
Cladribine	Phase 3 (in late-stage trials)
Cyclosporine	Phase 3 (in late-stage trials)
Cytarabine	Phase 3 (in late-stage trials)
Dacarbazine	Phase 3 (in late-stage trials)
Dactinomycin	Phase 3 (in late-stage trials)
Denileukin Diftitox	Phase 3 (in late-stage trials)
Doxorubicin	Phase 3 (in late-stage trials)
Enalapril	Phase 3 (in late-stage trials)
Epoetin Beta	Phase 3 (in late-stage trials)
Epratuzumab	Phase 3 (in late-stage trials)
Ergocalciferol	Phase 3 (in late-stage trials)
Etoposide	Phase 3 (in late-stage trials)
Etoposide Phosphate	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)
Galiximab	Phase 3 (in late-stage trials)
Gemcitabine	Phase 3 (in late-stage trials)
Glofitamab	Phase 3 (in late-stage trials)
Hyaluronidase	Phase 3 (in late-stage trials)
INTERFERON ALFA-2A	Phase 3 (in late-stage trials)
INTERFERON GAMMA-1B	Phase 3 (in late-stage trials)
Ibrutinib	Phase 3 (in late-stage trials)
Idarubicin	Phase 3 (in late-stage trials)
Idelalisib	Phase 3 (in late-stage trials)
Ifosfamide	Phase 3 (in late-stage trials)
Insulin Aspart	Phase 3 (in late-stage trials)
Insulin Glargine	Phase 3 (in late-stage trials)
Interferon	Phase 3 (in late-stage trials)
Interferon Alfa	Phase 3 (in late-stage trials)
Keyhole Limpet Hemocyanin	Phase 3 (in late-stage trials)
Lansoprazole	Phase 3 (in late-stage trials)
Lenalidomide	Phase 3 (in late-stage trials)
Lipegfilgrastim	Phase 3 (in late-stage trials)
Mechlorethamine	Phase 3 (in late-stage trials)
Melphalan	Phase 3 (in late-stage trials)
Methotrexate	Phase 3 (in late-stage trials)
Methoxsalen	Phase 3 (in late-stage trials)
Methylprednisolone	Phase 3 (in late-stage trials)
Mitoguazone	Phase 3 (in late-stage trials)
Nivolumab	Phase 3 (in late-stage trials)
Nystatin	Phase 3 (in late-stage trials)
Obinutuzumab	Phase 3 (in late-stage trials)
Oxaliplatin	Phase 3 (in late-stage trials)
Palifermin	Phase 3 (in late-stage trials)
Pegaspargase	Phase 3 (in late-stage trials)
Pegfilgrastim	Phase 3 (in late-stage trials)
Pixantrone	Phase 3 (in late-stage trials)
Pralatrexate	Phase 3 (in late-stage trials)
Procarbazine	Phase 3 (in late-stage trials)
Rituximab	Phase 3 (in late-stage trials)
Romidepsin	Phase 3 (in late-stage trials)
Sargramostim	Phase 3 (in late-stage trials)
TOSITUMOMAB 131I	Phase 3 (in late-stage trials)
Temsirolimus	Phase 3 (in late-stage trials)
Thioguanine	Phase 3 (in late-stage trials)
Tocilizumab	Phase 3 (in late-stage trials)
Toripalimab	Phase 3 (in late-stage trials)
Tositumomab	Phase 3 (in late-stage trials)
Tucidinostat	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)
Vorinostat	Phase 3 (in late-stage trials)

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): ANTINEOPLASTON A10, Acetaminophen, Alvocidib, Amifostine, Amoxicillin, Arsenic Trioxide, Atezolizumab, Atorvastatin, Avelumab, Balstilimab, Bevacizumab, Bismuth Subcitrate, Bismuth Subsalicylate, CPI 613, Camrelizumab, Carfilzomib, Catequentinib, Cemiplimab, Clarithromycin, Clofarabine, Cyanocobalamin, Daratumumab, Darbepoetin Alfa, Dasatinib Anhydrous, Decitabine, Detumomab, Didanosine, Diphenhydramine, Durvalumab, Duvelisib, Eflapegrastim, Eltrombopag, Endostatin, N-Terminal-Mggshhhhh, Entinostat, Entospletinib, Enzastaurin, Everolimus, Folic Acid, Forodesine, Gallium Nitrate, Ganciclovir, Glucarpidase, Glutamine, Granisetron, Human Immunoglobulin G, Hydroxyurea, INDIUM IN 111 IBRITUMOMAB TIUXETAN, Ibritumomab Tiuxetan, Inotuzumab Ozogamicin, Irinotecan, Isatuximab, Isotretinoin, Ivabradine, Ixabepilone, Ixazomib Citrate, Lamivudine, Ledipasvir, Lisocabtagene Maraleucel, Lomustine, Mitoxantrone, Mogamulizumab, Mycophenolate Mofetil, Mycophenolic Acid, Nelarabine, Niraparib, Norethindrone Acetate, Ofatumumab, Omeprazole, Orelabrutinib, Paclitaxel, Pacritinib, Palbociclib, Panobinostat, Parsaclisib, Pembrolizumab, Pentostatin, Perifosine, Pirarubicin, Plitidepsin, Potassium Iodide, Pyridoxine, Regramostim, Ridaforolimus, Ruxolitinib, SGN-30, Selinexor, Sintilimab, Sirolimus, Sodium Chloride, Sofosbuvir, Sugemalimab, Tabelecleucel, Tacrolimus Anhydrous, Tanespimycin, Tazemetostat, Temozolomide, Teniposide, Thalidomide, Thiotepa, Tislelizumab, Tretinoin, Triptorelin, Valganciclovir, Valproic Acid, Venetoclax, Vinorelbine, YTTRIUM Y 90 IBRITUMOMAB TIUXETAN, Zanolimumab, Zanubrutinib, Zidovudine.

Drug target analysis

Approved (phase 4): 9 · Phase ≥3: 9 · Phased (≥1): 10 · Undrugged: 17

Druggability breadth: 18 of 27 evidence-associated genes (67%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

Symbol	Example approved molecule
TP53	NITROFURANTOIN
CCND3	PALBOCICLIB
FGFR1	PONATINIB
KRAS	VEMURAFENIB
ATM	AMIODARONE HYDROCHLORIDE
BCL2	IXABEPILONE
NSD2	VENETOCLAX
IDH1	ENASIDENIB
PTPN11	ESTRAMUSTINE PHOSPHATE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
TP53	196	4
FGFR1	93	4
ATM	35	4
CCND3	17	4
BCL2	14	4
KRAS	11	4
IDH1	10	4
NSD2	8	4
PTPN11	8	4
BCL6	2	2

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): 7.

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

Symbol	Assays	Type breakdown
FGFR1	1,465	Binding:1428, Functional:24, ADMET:13
TP53	869	Binding:775, ADMET:83, Functional:10, Toxicity:1
KRAS	861	Binding:829, Functional:32
PTPN11	588	Binding:585, Functional:2, ADMET:1
IDH1	488	Binding:475, Functional:12, ADMET:1
BCL2	446	Binding:418, Functional:23, Toxicity:3, ADMET:2
CCND3	425	Binding:422, ADMET:2, Toxicity:1
NSD2	264	Binding:256, Functional:8
ATM	240	Binding:233, Functional:5, ADMET:2
BCL6	209	Binding:202, Functional:7
HLA-DRB1	17	Binding:17
KMT2D	11	Binding:11
TAP2	3	Binding:3
HLA-DQA1	2	Binding:2
NBN	2	Binding:2
LPXN	1	Binding:1
PMS2	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
FGFR1	2.7.10.1	receptor protein-tyrosine kinase
KRAS	3.6.5.2	small monomeric GTPase
ATM	2.7.11.1	non-specific serine/threonine protein kinase
NSD2	2.1.1.356, 2.1.1.357, 2.1.1.359	[histone H3]-lysine27 N-trimethyltransferase, [histone H3]-lysine36 N-dimethyltransferase, [histone H3]-lysine36 N-trimethyltransferase
TAP2	7.4.2.14, 7.4.2.5	ABC-type antigen peptide transporter, bacterial ABC-type protein transporter
IDH1	1.1.1.42	isocitrate dehydrogenase (NADP+)
PTPN11	3.1.3.48	protein-tyrosine-phosphatase

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
TP53	869
CCND3	425
FGFR1	1,465
KRAS	861
ATM	240
BCL2	446
BCL6	209
NSD2	264
IDH1	488
PTPN11	588

Pharmacogenomics

Cohort genes with a PharmGKB record: 27; with CPIC/DPWG dosing guidelines: 0.

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

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)
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
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)	9	TP53, CCND3, FGFR1, KRAS, ATM, BCL2, NSD2, IDH1, PTPN11
B	Phased (≥1) drug, not yet approved	1	BCL6
C	Druggable family + PDB, no drug	6	TAP2, HLA-DQA1, HLA-DQB1, HLA-DRA, HLA-DRB1, HLA-DRB5
D	Druggable family + AlphaFold only, no drug	2	HLA-DQA2, HLA-DQB2
E	Difficult family or no structure, no drug	9	LPXN, SETBP1, RNF182, ZFP91-CNTF, JARID2, LPP, KMT2D, NBN, PMS2

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
NBN	2	ATM
LPXN	1	—
SETBP1	0	—
RNF182	0	—
ZFP91-CNTF	0	—
TAP2	3	—
HLA-DQA1	2	—
HLA-DQA2	0	—
HLA-DQB1	0	—
HLA-DQB2	0	—
HLA-DRA	0	—
HLA-DRB1	17	—
HLA-DRB5	0	—
JARID2	0	—
LPP	0	—
KMT2D	11	—
PMS2	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 2,229.

Phase distribution (across all retrieved trials)

Phase	Trials
PHASE2	685
PHASE1/PHASE2	213
PHASE3	158
PHASE4	23
PHASE2/PHASE3	15
PHASE1	6

Top trials by phase / activity

NCT	Phase	Status	Title
NCT05170399	PHASE4	RECRUITING	Vaccine Responses in Patients With B Cell Malignancies
NCT06049134	PHASE4	ACTIVE_NOT_RECRUITING	Immunogenicity and Clinical Efficacy of 20-valent Pneumococcal Conjugate Vaccine (PCV20) in Lymphoma Survivors After Treatment With Anti-CD20 Therapy
NCT00003398	PHASE4	COMPLETED	Bone Marrow Transplantation in Treating Patients With Hematologic Cancer
NCT00158041	PHASE4	COMPLETED	Subcutaneous Amifostine Safety Study
NCT00361140	PHASE4	COMPLETED	Busulfan Safety/Efficacy as Conditioning Prior to Hematopoietic Cell Transplantation (HCT)
NCT00415103	PHASE4	COMPLETED	AMENO-2: Aprepitant Plus Palonosetron Versus Granisetron in the Prevention of Nausea and the Emesis Induced by Chemotherapy in Patients Treated With Haematopoietic Progenitors
NCT00854581	PHASE4	TERMINATED	Zidovudine, Interferon Alfa-2b, PEG-Interferon Alfa-2b in Patients With HTLV-I Associated Adult T-Cell Leukemia/Lymphoma
NCT01088750	PHASE4	COMPLETED	Surgery Alone or With CYC VBL and PRED or CVP Alone in Stage IA or IIA Nodular Lymphocyte-Predominant Hodgkin Lymphoma
NCT01658280	PHASE4	COMPLETED	Conventional Versus Ultrasound-guided Transbronchial Needle Aspiration for the Diagnosis of Hilar/Mediastinal Lymphadenopathies
NCT01841814	PHASE4	WITHDRAWN	Evolution of Bone Mineral Density (BMD) in Patients With Lymphoma Undergoing Chemotherapy
NCT01909934	PHASE4	COMPLETED	Study of Brentuximab Vedotin in Participants With Relapsed or Refractory Systemic Anaplastic Large Cell Lymphoma
NCT02095951	PHASE4	COMPLETED	Preemptive Ethanol Lock Therapy in Pediatric Bloodstream Infection
NCT02347878	PHASE4	UNKNOWN	Self-control Trial to Evaluate the Role of Aprepitant in the Prophylaxis of Post-lumbar-punture-headache (PLPH)
NCT02805218	PHASE4	COMPLETED	PEG-rhG-CSF in Patients With Lymphoma Receiving Chemotherapy
NCT02905916	PHASE4	UNKNOWN	The Efficacy and Safety of PEG-rhG-CSF in Neutropenia After Chemotherapy
NCT02905942	PHASE4	UNKNOWN	PEG-rhG-CSF in Lymphoma Patients After Autologous Hematopoietic Stem Cell Transplantation
NCT02929615	PHASE4	UNKNOWN	Study of Standard and Individualized Treatment Model for Relapse and Refractory Lymphatic System Malignant Tumors
NCT02933333	PHASE4	UNKNOWN	G-CSF Alone or Combination With GM-CSF on Prevention and Treatment of Infection in Children With Malignant Tumor
NCT03010579	PHASE4	UNKNOWN	Erythropoietin in the Treatment of Anemia After Autologous Hematopoietic Stem Cell Transplantation
NCT04349306	PHASE4	COMPLETED	Evaluate the Efficacy and Safety of Rasburicase (Fasturtec®) in the Prevention and Treatment of Hyperuricemia in Pediatric Patients With Non-Hodgkin’s Lymphoma and Acute Leukemia
NCT05510544	PHASE4	UNKNOWN	Plerixafor for Poorly Mobilized Lymphoma
NCT05545202	PHASE4	UNKNOWN	A Randomized, Comparative, Double-blind Trial of Pentaisomaltose and Dimethyl Sulphoxide for Cryoprotection of Hematopoietic Stem Cells in Subjects With Multiple Myeloma or Malignant Lymphoma With a Need for Autologous Transplantation
NCT06026995	PHASE4	UNKNOWN	Clinical Study on PEG-rhG-CSF in Mobilizing Autologous Hematopoietic Stem Cells
NCT00002462	PHASE3	ACTIVE_NOT_RECRUITING	RT or No RT Following Chemotherapy in Treating Patients With Stage III/IV Hodgkin’s Disease
NCT00005584	PHASE3	ACTIVE_NOT_RECRUITING	Combination Chemotherapy With or Without Radiation Therapy in Treating Patients With Hodgkin’s Lymphoma
NCT00379041	PHASE3	ACTIVE_NOT_RECRUITING	Radiation Therapy With or Without Combination Chemotherapy in Treating Patients With Previously Untreated Stage I or Stage II Hodgkin’s Lymphoma
NCT00943423	PHASE3	ACTIVE_NOT_RECRUITING	PET Scan in Planning Treatment in Patients Undergoing Combination Chemotherapy For Stage IA or Stage IIA Hodgkin Lymphoma
NCT03057054	PHASE3	ACTIVE_NOT_RECRUITING	Lactobacillus Plantarum in Preventing Acute Graft Versus Host Disease in Children Undergoing Donor Stem Cell Transplant
NCT03480360	PHASE3	ACTIVE_NOT_RECRUITING	Haploidentical Allogeneic Peripheral Blood Transplantation: Examining Checkpoint Immune Regulators’ Expression
NCT03647072	PHASE3	RECRUITING	PPI Versus Histamine Antagnists as Adjuvant to Chemotherapy
NCT03823534	PHASE3	RECRUITING	Post-Op Pain Control for Prophylactic Intramedullary Nailing.
NCT05006482	PHASE3	RECRUITING	Geriatric Evaluation and Management With Survivorship Health Education for Older Survivors of Cancer, GEM-S Trial
NCT05328258	PHASE3	RECRUITING	Use of GnRHa During Chemotherapy for Fertility Protection
NCT05515029	PHASE3	ACTIVE_NOT_RECRUITING	Preventing of GVHD With Post-transplantation Cyclophosphamide, Abatacept, Vedolizumab and Calcineurin Inhibitor at Patients With Hemoblastosis
NCT05770037	PHASE2/PHASE3	RECRUITING	DETERMINE Trial Treatment Arm 01: Alectinib in Adult, Paediatric and Teenage/Young Adult Patients With ALK Positive Cancers
NCT05775705	PHASE3	NOT_YET_RECRUITING	L-DEP Regimen Combined With PD-1 Antibody as Induction Therapy for Epstein-Barr Virus-positive LA-HLH
NCT06084936	PHASE3	RECRUITING	A Study to Evaluate Glofitamab as a Single Agent vs. Investigator’s Choice in Participants With Relapsed/Refractory Mantle Cell Lymphoma
NCT06475820	PHASE2/PHASE3	ACTIVE_NOT_RECRUITING	Preventing of GVHD With Post-transplantation Cyclophosphamide, Abatacept, Vedolizumab and Baricitinib at Children and Young Adults With Hemoblastosis
NCT06522737	PHASE3	RECRUITING	A Study of Duvelisib Versus Gemcitabine or Bendamustine in Participants With Relapsed/Refractory Nodal T Cell Lymphoma With T Follicular Helper (TFH) Phenotype
NCT00002456	PHASE3	COMPLETED	Graft-Versus-Host Disease Prevention in Treating Patients Who Are Undergoing Bone Marrow Transplantation

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
CYCLOPHOSPHAMIDE ANHYDROUS	4	300
PROCARBAZINE	4	69
VINCRISTINE SULFATE	4	37
2-MERCAPTOETHANESULFONIC ACID	4	36
VINBLASTINE	4	35
BLEOMYCIN SULFATE	4	29
ETOPOSIDE	4	25
FILGRASTIM	4	22
CYTARABINE	4	21
MITOXANTRONE HYDROCHLORIDE	4	19
DOXORUBICIN HYDROCHLORIDE	4	18
THIOTEPA	4	15
PLERIXAFOR	4	12
BUSULFAN	4	11
FLUDARABINE PHOSPHATE	4	9
IFOSFAMIDE	4	8
MECHLORETHAMINE HYDROCHLORIDE	4	7
BRENTUXIMAB VEDOTIN	4	6
APREPITANT	4	4
IDARUBICIN	4	4
RASBURICASE	4	4
CISPLATIN	4	2
GRANISETRON	4	2
PALONOSETRON	4	2
VALPROIC ACID	4	2
INTERFERON ALFA-2B	4	1
PEGINTERFERON ALFA-2B	4	1
PREDNISOLONE	4	1
RESPIRATORY SYNCYTIAL VIRUS PRE-FUSION GLYCOPROTEIN F	4	1
VARICELLA ZOSTER VIRUS ENVELOPE GLYCOPROTEIN E	4	1

Precision-medicine subtype map (CIViC)

Drug × molecular subtype: 7 predictive associations from 7 curated evidence items; also 2 predisposing, 1 oncogenic, 1 prognostic.

Molecular subtype	Therapy	Effect	Level	CIViC
ZMYM2::FGFR1 Fusion OR BCR::FGFR1 Fusion OR CEP43::FGFR1 Fusion OR TRIM24::FGFR1 Fusion OR FGFR1 Translocation	Pemigatinib	Sensitivity/Response	CIViC A	EID12242
ATM D2870A or N2875K	Irinotecan	Sensitivity/Response	CIViC D	EID12759
ATM Mutation	Camptothecin	Sensitivity/Response	CIViC D	EID12758
CCND3 Loss	Palbociclib	Sensitivity/Response	CIViC D	EID263
CREBBP R1446C	HDAC Inhibitor OBP-801	Sensitivity/Response	CIViC D	EID12291
BCL2 Overexpression	Venetoclax + Dinaciclib	Resistance	CIViC D	EID9313
KMT2E::ASNS Fusion	Asparaginase	Resistance	CIViC D	EID5926