Acute lymphoblastic leukemia

Summary

Acute lymphoblastic leukemia (MONDO:0004967) is a cancer (an umbrella term covering 12 Mondo subtypes) with 61 cohort genes (90 GWAS associations across 18 studies; 18 CIViC-evidence somatic drivers; 220 ClinVar predisposition records) and 1,029 clinical trials. The dominant Reactome pathway is Negative regulation of FLT3 (3 cohort genes). Molecularly, BCR::ABL1 Fusion AND ABL1 Mutation confers sensitivity to Dasatinib in Acute Lymphoblastic Leukemia (CIViC Level A); 17 further subtype–drug associations are mapped below. Top therapeutic interventions include mercaptopurine anhydrous, daunorubicin, and pegaspargase.

At a glance

• Classification: Cancer
• Prevalence: 1-5 / 10 000 (Europe) [Orphanet-validated]
• Umbrella term: 12 Mondo subtypes
• Cohort genes: 61
• GWAS associations: 90
• ClinVar variants: 220
• Clinical trials: 1,029
• Precision-medicine evidence (CIViC): 18 subtype–drug associations

Clinical features

Epidemiology

Prevalence records

5 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Point prevalence	1-5 / 10 000	11	Europe	Validated
Annual incidence	1-9 / 100 000	1.3	France	Validated
Annual incidence	1-9 / 100 000	1.6	United States	Validated
Lifetime Prevalence	1-5 / 10 000	22	United States	Validated
Annual incidence	1-9 / 100 000	2.75	Europe	Not yet validated

Identifiers

Disease identifiers

Field	Value
Canonical name	acute lymphoblastic leukemia
Mondo ID	MONDO:0004967
EFO	EFO:0000220
Orphanet	513
DOID	DOID:9952
ICD-10-CM	C91.0
NCIT	C3167
SNOMED CT	91857003
UMLS	C0023449
MedGen	7317
GARD	0000522
Is cancer (heuristic)	yes

Also known as: acute lymphoblastic leukaemia (ALL) · acute lymphoblastic leukaemia (disease) · acute lymphoblastic leukemia · acute lymphoblastic leukemia (ALL) · acute lymphoblastic leukemia (disease) · acute lymphoblastic leukemia/lymphoma · acute lymphocytic leukaemia · acute lymphocytic leukemia · acute lymphocytic leukemias · acute lymphogenous leukaemia · acute lymphogenous leukemia · acute lymphoid leukaemia · acute lymphoid leukemia · ALL · ALL - acute lymphocytic leukaemia · ALL - acute lymphocytic leukemia · leukemia, lymphoblastic, malignant · lymphoblastic leukaemia · lymphoblastic leukemia · lymphoblastic leukemia, acute (+6 more)

Data availability: 220 ClinVar variants · 90 GWAS associations (18 studies) · 1 GenCC gene-disease record · 1 HPO phenotype · 31 cell lines · 30 intOGen driver records.

Disease family

An umbrella term covering 12 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 › precursor lymphoblastic lymphoma/leukemia › acute lymphoblastic leukemia

Related subtypes (3): lymphoblastic lymphoma, T lymphoblastic leukemia/lymphoma, B-lymphoblastic leukemia/lymphoma with recurrent genetic abnormality

Subtypes (12): childhood acute lymphoblastic leukemia, prolymphocytic leukemia, adult acute lymphoblastic leukemia, null-cell leukemia, B-cell acute lymphoblastic leukemia, B-cell chronic lymphocytic leukemia, T-cell acute lymphoblastic leukemia, lymphoblastic leukemia, acute, with lymphomatous features, plasma cell leukemia, acute biphenotypic leukemia, precursor B-cell acute lymphoblastic leukemia, precursor T-cell acute lymphoblastic leukemia

Genetics & variants

GWAS landscape

90 GWAS associations across 18 studies. Top hits map to 32 distinct genes (as reported by GWAS).

Top associations by p-value

rsID	p-value	Gene	Risk allele	Odds ratio
rs7089424	2e-62	ARID5B	T	1.64
rs10821936	6e-46	ARID5B	C	1.86
rs6964969	2e-29	IKZF1 - RNU6-1091P	C	1.67
rs11978267	2e-29	IKZF1	A	1.43
rs4748813	3e-20	PIP4K2A	T	1.35
rs4132601	1e-19	IKZF1	C	1.69
rs2239633	7e-13	CEBPE	T	1.27
rs4617118	2e-12	CCDC26	G	1.28
rs4982731	9e-12	CIROP - CEBPE	C	1.36
rs1945213	9e-11	OR5AL2P - OR5AL1	C
rs3824662	3e-10	GATA3	A	1.77
rs2290400	1e-09	GSDMB	T	1.17
rs4245595	2e-09	ARID5B	C	1.63
rs2069426	4e-09	CDKN2B-AS1, CDKN2B	A	1.35
rs920590	6e-09	CSGALNACT1 - INTS10	C
rs7142143	7e-09	PYGL	C	3.61
rs1110701	7e-09	IKZF1 - RNU6-1091P	G	1.69
rs17505102	9e-09	TP63	G	1.59
rs2167364	2e-08	DDC	G	1.32
rs2390536	2e-08	SP4	A	1.18
rs2089222	8e-08	MAP1LC3B2	A	2.26
rs359312	9e-08	ST8SIA6	T	3.91
rs17079534	2e-07	NFU1P1 - MYRIP	A	4.07
rs11155133	3e-07	RPS3AP24 - RN7SKP106	G	3.62
rs11638062	3e-07	AGBL1	?	1.8
rs2191566	4e-07	ZNF230	G	1.52
rs3942852	5e-07	PTPRJ	C
rs17007695	9e-07	IL15 - INPP4B	C	2.67
rs1569175	9e-07	MAIP1 - SPATS2L	T	2.73
rs936094	1e-06	RXFP1	C

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST90056175	Kachuri L	2021	2,666	60,272	Genetic determinants of blood-cell traits influence susceptibility to childhood acute lymphoblastic leukemia.
GCST005315	Wiemels JL	2018	1,949	8,584	GWAS in childhood acute lymphoblastic leukemia reveals novel genetic associations at chromosomes 17q12 and 8q24.21.
GCST001912	Xu H	2013	972	1,386	Novel susceptibility variants at 10p12.31-12.2 for childhood acute lymphoblastic leukemia in ethnically diverse populations.
GCST007276	Qian M	2018	940	0	Novel susceptibility variants at the ERG locus for childhood acute lymphoblastic leukemia in Hispanics.
GCST000463	Papaemmanuil E	2009	907	2,398	Loci on 7p12.2, 10q21.2 and 14q11.2 are associated with risk of childhood acute lymphoblastic leukemia.
GCST012357	Hao Q	2021	466	1,466	Age-related differences of genetic susceptibility to patients with acute lymphoblastic leukemia.
GCST001320	Ellinghaus E	2011	419	0	Identification of germline susceptibility loci in ETV6-RUNX1-rearranged childhood acute lymphoblastic leukemia.
GCST002657	Evans TJ	2014	358	1,192	Confirmation of childhood acute lymphoblastic leukemia variants, ARID5B and IKZF1, and interaction with parental environmental exposures.
GCST000323	Yang JJ	2009	356	0	Genome-wide interrogation of germline genetic variation associated with treatment response in childhood acute lymphoblastic leukemia.
GCST000464	Trevino LR	2009	317	17,958	Germline genomic variants associated with childhood acute lymphoblastic leukemia.

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	47

MAF distribution

Bucket	Variants
common (>=0.05)	45
low_freq (0.01-0.05)	4
rare (<0.01)	1
unknown	0

Functional consequences

Consequence	Count
intron_variant	39
intergenic_variant	6
non_coding_transcript_exon_variant	2
regulatory_region_variant	1
3_prime_UTR_variant	1
missense_variant	1

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
rs7089424	10	61992400	T>G	0.05	intron_variant	ARID5B	2e-62	Tier 4: intronic/intergenic
rs10821936	10	61963818	C>A,T	0.33	intron_variant	ARID5B	6e-46	Tier 4: intronic/intergenic
rs6964969	7	50405553	A>G	0.28	regulatory_region_variant	IKZF1 - RNU6-1091P	2e-29	Tier 3: regulatory
rs11978267	7	50398606	A>C,G	0.05	intron_variant	IKZF1	2e-29	Tier 4: intronic/intergenic
rs4748813	10	22557806	T>A,C	0.05	intron_variant	PIP4K2A	3e-20	Tier 4: intronic/intergenic
rs4132601	7	50402906	T>G	0.28	3_prime_UTR_variant	IKZF1	1e-19	Tier 2: splice/UTR
rs2239633	14	23119848	G>A,C,T	0.05	intron_variant	CEBPE	7e-13	Tier 4: intronic/intergenic
rs4617118	8	129143897	A>C,G	0.05	intron_variant	CCDC26	2e-12	Tier 4: intronic/intergenic
rs4982731	14	23116124	C>G,T	0.28	intron_variant	CIROP - CEBPE	9e-12	Tier 4: intronic/intergenic
rs1945213	11	56408195	C>G,T	0.31	intergenic_variant	OR5AL2P - OR5AL1	9e-11	Tier 4: intronic/intergenic
rs3824662	10	8062245	C>A,G,T	0.2	intron_variant	GATA3	3e-10	Tier 4: intronic/intergenic
rs2290400	17	39909987	T>A,C,G	0.05	intron_variant	GSDMB	1e-09	Tier 4: intronic/intergenic
rs4245595	10	61963136	C>T	0.34	intron_variant	ARID5B	2e-09	Tier 4: intronic/intergenic
rs2069426	9	22006274	G>A,C,T	0.05	intron_variant	CDKN2B-AS1, CDKN2B	4e-09	Tier 4: intronic/intergenic
rs920590	8	19793650	T>A,C	0.31	intron_variant	CSGALNACT1 - INTS10	6e-09	Tier 4: intronic/intergenic
rs7142143	14	50936813	T>C	0.01	intron_variant	PYGL	7e-09	Tier 4: intronic/intergenic
rs1110701	7	50410929	A>C,G,T	0.28	intergenic_variant	IKZF1 - RNU6-1091P	7e-09	Tier 4: intronic/intergenic
rs17505102	3	189683987	G>C,T	0.15	intron_variant	TP63	9e-09	Tier 4: intronic/intergenic
rs2167364	7	50498129	T>A,C,G	0.31	intron_variant	DDC	2e-08	Tier 4: intronic/intergenic
rs2390536	7	21445779	G>A,T	0.05	intron_variant	SP4	2e-08	Tier 4: intronic/intergenic
rs2089222	12	116564853	G>A,C,T	0.03	intron_variant	MAP1LC3B2	8e-08	Tier 4: intronic/intergenic
rs359312	10	17346144	C>A,G,T	0.05	intron_variant	ST8SIA6	9e-08	Tier 4: intronic/intergenic
rs17079534	3	39805581	G>A,C	0.005	non_coding_transcript_exon_variant	NFU1P1 - MYRIP	2e-07	Tier 4: intronic/intergenic
rs11155133	6	140848688	A>G	0.01	intron_variant	RPS3AP24 - RN7SKP106	3e-07	Tier 4: intronic/intergenic
rs11638062	15	86620033	A>G	0.05	intron_variant	AGBL1	3e-07	Tier 4: intronic/intergenic
rs2191566	19	44007237	G>A,C,T	0.28	intron_variant	ZNF230	4e-07	Tier 4: intronic/intergenic
rs3942852	11	48093537	C>T	0.22	intron_variant	PTPRJ	5e-07	Tier 4: intronic/intergenic
rs17007695	4	141788570	T>A,C	0.05	intergenic_variant	IL15 - INPP4B	9e-07	Tier 4: intronic/intergenic
rs1569175	2	200157231	T>A,C,G	0.05	intron_variant	MAIP1 - SPATS2L	9e-07	Tier 4: intronic/intergenic
rs936094	4	158523162	T>A,C,G	0.17	intron_variant	RXFP1	1e-06	Tier 4: intronic/intergenic

ClinVar germline variants

220 retrieved; paginated sample, class counts are floors:

74 uncertain significance, 40 likely pathogenic, 35 pathogenic/likely pathogenic, 23 conflicting classifications of pathogenicity, 19 benign/likely benign, 14 pathogenic, 11 benign, 4 likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
190240	NM_001987.4(ETV6):c.1153-5_1153-1del	ETV6	Pathogenic	criteria provided, single submitter
16272	NM_004119.3(FLT3):c.2504A>T (p.Asp835Val)	FLT3	Pathogenic	no assertion criteria provided
16276	NM_004119.3(FLT3):c.2503G>T (p.Asp835Tyr)	FLT3	Pathogenic	no assertion criteria provided
16278	NM_004119.3(FLT3):c.1777_1779del (p.Asp593del)	FLT3	Pathogenic	no assertion criteria provided
208722	NM_002074.5(GNB1):c.239T>C (p.Ile80Thr)	GNB1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
224711	NM_002074.5(GNB1):c.227A>G (p.Asp76Gly)	GNB1	Pathogenic	criteria provided, multiple submitters, no conflicts
224715	NM_002074.5(GNB1):c.239T>A (p.Ile80Asn)	GNB1	Pathogenic	criteria provided, multiple submitters, no conflicts
1342126	NM_006060.6(IKZF1):c.247C>T (p.Arg83Ter)	IKZF1	Pathogenic	criteria provided, multiple submitters, no conflicts
142559	NM_002485.5(NBN):c.1903A>T (p.Lys635Ter)	LOC126860438	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
492103	NM_002485.5(NBN):c.1882_1885del (p.Glu628fs)	LOC126860438	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1073756	NM_002485.5(NBN):c.1106C>G (p.Ser369Ter)	NBN	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1075847	NM_002485.5(NBN):c.4del (p.Trp2fs)	NBN	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
127878	NM_002485.5(NBN):c.698_701del (p.Lys233fs)	NBN	Pathogenic	criteria provided, multiple submitters, no conflicts
141731	NM_002485.5(NBN):c.1142del (p.Pro381fs)	NBN	Pathogenic	criteria provided, multiple submitters, no conflicts
1454384	NM_002485.5(NBN):c.1168G>T (p.Glu390Ter)	NBN	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1769001	NM_002485.5(NBN):c.1287T>A (p.Tyr429Ter)	NBN	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
182737	NM_002485.5(NBN):c.2140C>T (p.Arg714Ter)	NBN	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
184862	NM_002485.5(NBN):c.1723G>T (p.Glu575Ter)	NBN	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
185838	NM_002485.5(NBN):c.210_211del (p.Asp70fs)	NBN	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
186314	NM_002485.5(NBN):c.37+1G>A	NBN	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
186736	NM_002485.5(NBN):c.1483_1484delinsA (p.Pro495fs)	NBN	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
190228	NM_002485.5(NBN):c.842T>G (p.Leu281Ter)	NBN	Pathogenic	criteria provided, multiple submitters, no conflicts
190229	NM_002485.5(NBN):c.1030C>T (p.Gln344Ter)	NBN	Pathogenic	criteria provided, multiple submitters, no conflicts
2122405	NM_002485.5(NBN):c.247dup (p.Met83fs)	NBN	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
216086	NM_002485.5(NBN):c.211_212insGA (p.Asn71fs)	NBN	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
219533	NM_002485.5(NBN):c.1747C>T (p.Gln583Ter)	NBN	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
233424	NM_002485.5(NBN):c.2184+1G>T	NBN	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
234246	NM_002485.5(NBN):c.1651dup (p.Arg551fs)	NBN	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
370213	NM_002485.5(NBN):c.265C>T (p.Arg89Ter)	NBN	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
370898	NM_002485.5(NBN):c.317dup (p.Arg107fs)	NBN	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 7 · Orphanet: 85 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 5

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

Gene	HGNC	Evidence routes
IKZF1	IKZF1	GWAS, Orphanet
CDKN2A	CDKN2A	GWAS, Orphanet
IKZF3	IKZF3	GWAS, Orphanet
GATA3	GATA3	GWAS, Orphanet
PIP4K2A	PIP4K2A	GWAS, Orphanet

Somatic driver evidence (intOGen + CIViC, cohort fanout)

Gene	intOGen role	Cancer types	CIViC
IKZF1	Act	AML,ANSC,SKCM	CIViC #73
CDKN2A	LoF	ACYC,BLCA,BRCA,CHOL,COAD,COADREAD,CSCC,EGC,ESCA,ESCC,GBM,HCC,HNSC,LGGNOS,LUAD,LUSC,MEL,MLYM,NPC,NSCLC,OS,PAAD,PANCREAS,RCC,SKCM,SKIN,STAD,STOMACH,WDTC	CIViC #14
RUNX1	LoF	ACYC,ALL,AML,BRCA,GBM	CIViC #43
SH2B3	Act	MDS	CIViC #7954
ABL1	LoF	UCEC	CIViC #4
NT5C2			CIViC #9189
BCR	Act	BL,CLLSLL,DLBCLNOS,LUSC,NHL,WDTC
IKZF3	Act	CHOL,CLLSLL,DLBCLNOS
TP63	LoF	BLCA,CESC,HNSC,MEL,NBL
MAML2	ambiguous	AML,LUSC,VULVA
RSPO2	Act	COADREAD
ERG	Act	ANGS	CIViC #71
ETV6	Act	ALL,BLCA,DLBCLNOS	CIViC #1769
FLT3	Act	ALL,AML	CIViC #24
GATA3	Act	ALL,BRCA	CIViC #2189
NCOA3			CIViC #74
NUP214	Act	PRCC,SIC
PAX5	Act	DLBCLNOS,PRAD	CIViC #4111

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
SH2B3	Moderate	Autosomal recessive	acute lymphoblastic leukemia	7

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
IKZF1	Orphanet:317473	Common variable immunodeficiency phenotype due to IKAROS functional haploinsufficiency
IKZF1	Orphanet:36426	Stevens-Johnson syndrome
IKZF1	Orphanet:585909	B-lymphoblastic leukemia/lymphoma with t(9;22)(q34.1;q11.2)
IKZF1	Orphanet:695172	Combined immunodeficiency due to dimerization defective IKAROS mutation
IKZF1	Orphanet:697414	Early-onset combined immunodeficiency with low Ig due to dominant negative IKAROS mutation
CDKN2A	Orphanet:1333	Familial pancreatic carcinoma
CDKN2A	Orphanet:1501	Adrenocortical carcinoma
CDKN2A	Orphanet:252206	Melanoma and neural system tumor syndrome
CDKN2A	Orphanet:404560	Familial atypical multiple mole melanoma syndrome
CDKN2A	Orphanet:524	Li-Fraumeni syndrome
CDKN2A	Orphanet:585909	B-lymphoblastic leukemia/lymphoma with t(9;22)(q34.1;q11.2)
CDKN2A	Orphanet:618	Familial melanoma
CDKN2A	Orphanet:99861	Precursor T-cell acute lymphoblastic leukemia
RUNX1	Orphanet:102724	Acute myeloid leukemia with t(8;21)(q22;q22) translocation
RUNX1	Orphanet:521	Chronic myeloid leukemia
RUNX1	Orphanet:71290	Familial platelet disorder with associated myeloid malignancy
RUNX1	Orphanet:98850	Aggressive systemic mastocytosis
SH2B3	Orphanet:3318	Essential thrombocythemia
SH2B3	Orphanet:391366	Growth retardation-mild developmental delay-chronic hepatitis syndrome
ABL1	Orphanet:521	Chronic myeloid leukemia
ABL1	Orphanet:585909	B-lymphoblastic leukemia/lymphoma with t(9;22)(q34.1;q11.2)
ABL1	Orphanet:643503	Marfanoid habitus-facial dysmorphism-skeletal abnormality-heart defect syndrome
ABL1	Orphanet:99861	Precursor T-cell acute lymphoblastic leukemia
NT5C2	Orphanet:320396	Autosomal recessive spastic paraplegia type 45
BCR	Orphanet:261330	Distal 22q11.2 microdeletion syndrome
BCR	Orphanet:521	Chronic myeloid leukemia
BCR	Orphanet:585909	B-lymphoblastic leukemia/lymphoma with t(9;22)(q34.1;q11.2)
BCR	Orphanet:99861	Precursor T-cell acute lymphoblastic leukemia
RYR2	Orphanet:293888	Inherited isolated arrhythmogenic cardiomyopathy, dominant-left variant
RYR2	Orphanet:293899	Inherited isolated arrhythmogenic ventricular dysplasia, biventricular variant
RYR2	Orphanet:293910	Inherited isolated arrhythmogenic cardiomyopathy, dominant-right variant
RYR2	Orphanet:3286	Catecholaminergic polymorphic ventricular tachycardia
TBXAS1	Orphanet:1802	Ghosal hematodiaphyseal dysplasia
IKZF3	Orphanet:67038	B-cell chronic lymphocytic leukemia
IKZF3	Orphanet:699590	Immune dysregulation with immunodeficiency due to AIOLOS haploinsufficiency
IKZF3	Orphanet:699593	Combined immunodeficiency-lymphopenia-cancer predisposing syndrome due to AIOLOS deficiency
TP63	Orphanet:1072	Ankyloblepharon filiforme adnatum-cleft palate syndrome
TP63	Orphanet:141291	Cleft lip and alveolus
TP63	Orphanet:1896	EEC syndrome
TP63	Orphanet:199302	Isolated cleft lip
TP63	Orphanet:199306	Cleft lip/palate
TP63	Orphanet:2440	Isolated split hand-split foot malformation
TP63	Orphanet:69085	Limb-mammary syndrome
TP63	Orphanet:93930	Classic bladder exstrophy
TP63	Orphanet:978	ADULT syndrome
CEBPE	Orphanet:169142	Recurrent infections due to specific granule deficiency
CEBPE	Orphanet:566067	CEBPE-associated autoinflammation-immunodeficiency-neutrophil dysfunction syndrome
MAGI2	Orphanet:656	Hereditary steroid-resistant nephrotic syndrome
LMBRD2	Orphanet:528084	Non-specific syndromic intellectual disability
AGBL1	Orphanet:98974	Fuchs endothelial corneal dystrophy

Cohort genes → proteins

61 cohort genes, 60 distinct canonical proteins.

Evidence partition

Subset	Genes
gwas_only	46
civic_only	3
multi_evidence	12

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
IKZF1	HGNC:13176	ENSG00000185811	Q13422	DNA-binding protein Ikaros	gwas,clinvar,civic_evidence
CDKN2A	HGNC:1787	ENSG00000147889	P42771	Cyclin-dependent kinase inhibitor 2A	gwas,clinvar,civic_evidence
RUNX1	HGNC:10471	ENSG00000159216	Q01196	Runt-related transcription factor 1	civic_evidence
SH2B3	HGNC:29605	ENSG00000111252	Q9UQQ2	SH2B adapter protein 3	gencc
ABL1	HGNC:76	ENSG00000097007	P00519	Tyrosine-protein kinase ABL1	civic_evidence
NT5C2	HGNC:8022	ENSG00000076685	P49902	Cytosolic purine 5’-nucleotidase	civic_evidence
RIT2	HGNC:10017	ENSG00000152214	Q99578	GTP-binding protein Rit2	gwas
BCR	HGNC:1014	ENSG00000186716	P11274	Breakpoint cluster region protein	clinvar
RYR2	HGNC:10484	ENSG00000198626	Q92736	Ryanodine receptor 2	gwas
SLCO3A1	HGNC:10952	ENSG00000176463	Q9UIG8	Solute carrier organic anion transporter family member 3A1	gwas
SP4	HGNC:11209	ENSG00000105866	Q02446	Transcription factor Sp4	gwas
TBXAS1	HGNC:11609	ENSG00000059377	P24557	Thromboxane-A synthase	gwas
TIGAR	HGNC:1185	ENSG00000078237	Q9NQ88	Fructose-2,6-bisphosphatase TIGAR	gwas
ZNF230	HGNC:13024	ENSG00000159882	Q9UIE0	Zinc finger protein 230	gwas
IKZF3	HGNC:13178	ENSG00000161405	Q9UKT9	Zinc finger protein Aiolos	gwas
OR2C3	HGNC:15005	ENSG00000196242	Q8N628	Olfactory receptor 2C3	gwas
TP63	HGNC:15979	ENSG00000073282	Q9H3D4	Tumor protein 63	gwas
PARD3	HGNC:16051	ENSG00000148498	Q8TEW0	Partitioning defective 3 homolog	gwas
MAML2	HGNC:16259	ENSG00000184384	Q8IZL2	Mastermind-like protein 2	gwas
ELMO1	HGNC:16286	ENSG00000155849	Q92556	Engulfment and cell motility protein 1	gwas
ARID5B	HGNC:17362	ENSG00000150347	Q14865	AT-rich interactive domain-containing protein 5B	gwas
NPFFR1	HGNC:17425	ENSG00000148734	Q9GZQ6	Neuropeptide FF receptor 1	gwas
CEBPE	HGNC:1836	ENSG00000092067	Q15744	CCAAT/enhancer-binding protein epsilon	gwas
MAGI2	HGNC:18957	ENSG00000187391	Q86UL8	Membrane-associated guanylate kinase, WW and PDZ domain-containing protein 2	gwas
MYRIP	HGNC:19156	ENSG00000170011	Q8NFW9	Rab effector MyRIP	gwas
ST6GALNAC3	HGNC:19343	ENSG00000184005	Q8NDV1	Alpha-N-acetylgalactosaminide alpha-2,6-sialyltransferase 3	gwas
RXFP1	HGNC:19718	ENSG00000171509	Q9HBX9	Relaxin receptor 1	gwas
GPATCH2L	HGNC:20210	ENSG00000089916	Q9NWQ4	G patch domain-containing protein 2-like	gwas
AIG1	HGNC:21607	ENSG00000146416	Q9NVV5	Androgen-induced gene 1 protein	gwas
ST8SIA6	HGNC:23317	ENSG00000148488	P61647	Alpha-2,8-sialyltransferase 8F	gwas
LMBRD2	HGNC:25287	ENSG00000164187	Q68DH5	G-protein coupled receptor-associated protein LMBRD2	gwas
INTS10	HGNC:25548	ENSG00000104613	Q9NVR2	Integrator complex subunit 10	gwas
MAIP1	HGNC:26198	ENSG00000162972	Q8WWC4	m-AAA protease-interacting protein 1, mitochondrial	gwas
AGBL1	HGNC:26504	ENSG00000273540	Q96MI9	Cytosolic carboxypeptidase 4	gwas
DDC	HGNC:2719	ENSG00000132437	P20711	Aromatic-L-amino-acid decarboxylase	gwas
OR8U8	HGNC:27538	ENSG00000262315	P0C7N1	Olfactory receptor 8U8	gwas
DGKB	HGNC:2850	ENSG00000136267	Q9Y6T7	Diacylglycerol kinase beta	gwas
RSPO2	HGNC:28583	ENSG00000147655	Q6UXX9	R-spondin-2	gwas
LHPP	HGNC:30042	ENSG00000107902	Q9H008	Phospholysine phosphohistidine inorganic pyrophosphate phosphatase	gwas
ERC2	HGNC:31922	ENSG00000187672	O15083	ERC protein 2	gwas
CDKN2B-AS1	HGNC:34341	ENSG00000240498		CDKN2B and CDKN2A antisense cis and trans regulatory RNA 1	clinvar
ERG	HGNC:3446	ENSG00000157554	P11308	Transcriptional regulator ERG	clinvar
ETV6	HGNC:3495	ENSG00000139083	P41212	Transcription factor ETV6	clinvar
FLT3	HGNC:3765	ENSG00000122025	P36888	Receptor-type tyrosine-protein kinase FLT3	clinvar
GATA3	HGNC:4172	ENSG00000107485	P23771	Trans-acting T-cell-specific transcription factor GATA-3	gwas
GNB1	HGNC:4396	ENSG00000078369	P62873	Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1	clinvar
GRB10	HGNC:4564	ENSG00000106070	Q13322	Growth factor receptor-bound protein 10	gwas
HS6ST1	HGNC:5201	ENSG00000136720	O60243	Heparan-sulfate 6-O-sulfotransferase 1	gwas
IL15	HGNC:5977	ENSG00000164136	P40933	Interleukin-15	gwas
KCNA3	HGNC:6221	ENSG00000177272	P22001	Potassium voltage-gated channel subfamily A member 3	gwas

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
IKZF1	DNA-binding protein Ikaros	Transcription regulator of hematopoietic cell differentiation.
CDKN2A	Cyclin-dependent kinase inhibitor 2A	Acts as a negative regulator of the proliferation of normal cells by interacting strongly with CDK4 and CDK6.
RUNX1	Runt-related transcription factor 1	Forms the heterodimeric complex core-binding factor (CBF) with CBFB.
SH2B3	SH2B adapter protein 3	Links T-cell receptor activation signal to phospholipase C-gamma-1, GRB2 and phosphatidylinositol 3-kinase.
ABL1	Tyrosine-protein kinase ABL1	Non-receptor tyrosine-protein kinase that plays a role in many key processes linked to cell growth and survival such as cytoskeleton remodeling in response to extracellular stimuli, cell motility and adhesion, receptor endocytosis, autopha…
NT5C2	Cytosolic purine 5’-nucleotidase	Broad specificity cytosolic 5’-nucleotidase that catalyzes the dephosphorylation of 6-hydroxypurine nucleoside 5’-monophosphates.
RIT2	GTP-binding protein Rit2	Binds and exchanges GTP and GDP.
BCR	Breakpoint cluster region protein	Protein with a unique structure having two opposing regulatory activities toward small GTP-binding proteins.
RYR2	Ryanodine receptor 2	Cytosolic calcium-activated calcium channel that mediates the release of Ca(2+) from the sarcoplasmic reticulum into the cytosol and thereby plays a key role in triggering cardiac muscle contraction.
SLCO3A1	Solute carrier organic anion transporter family member 3A1	Putative organic anion antiporter with apparent broad substrate specificity.
SP4	Transcription factor Sp4	Binds to GT and GC boxes promoters elements.
TBXAS1	Thromboxane-A synthase	Catalyzes the conversion of prostaglandin H2 (PGH2) to thromboxane A2 (TXA2), a potent inducer of blood vessel constriction and platelet aggregation.
TIGAR	Fructose-2,6-bisphosphatase TIGAR	Fructose-bisphosphatase hydrolyzing fructose-2,6-bisphosphate as well as fructose-1,6-bisphosphate.
ZNF230	Zinc finger protein 230	May be involved in transcriptional regulation.
IKZF3	Zinc finger protein Aiolos	Transcription factor that plays an important role in the regulation of lymphocyte differentiation.
OR2C3	Olfactory receptor 2C3	Odorant receptor.
TP63	Tumor protein 63	Acts as a sequence specific DNA binding transcriptional activator or repressor.
PARD3	Partitioning defective 3 homolog	Adapter protein involved in asymmetrical cell division and cell polarization processes.
MAML2	Mastermind-like protein 2	Acts as a transcriptional coactivator for NOTCH proteins.
ELMO1	Engulfment and cell motility protein 1	Involved in cytoskeletal rearrangements required for phagocytosis of apoptotic cells and cell motility.
ARID5B	AT-rich interactive domain-containing protein 5B	Transcription coactivator that binds to the 5’-AATA[CT]-3’ core sequence and plays a key role in adipogenesis and liver development.
NPFFR1	Neuropeptide FF receptor 1	Receptor for NPAF (A-18-F-amide) and NPFF (F-8-F-amide) neuropeptides, also known as morphine-modulating peptides.
CEBPE	CCAAT/enhancer-binding protein epsilon	Transcriptional activator.
MAGI2	Membrane-associated guanylate kinase, WW and PDZ domain-containing protein 2	Seems to act as a scaffold molecule at synaptic junctions by assembling neurotransmitter receptors and cell adhesion proteins.
MYRIP	Rab effector MyRIP	Rab effector protein involved in melanosome transport.
ST6GALNAC3	Alpha-N-acetylgalactosaminide alpha-2,6-sialyltransferase 3	Transfers the sialyl group (N-acetyl-alpha-neuraminyl or NeuAc) from CMP-NeuAc to the GalNAc residue on the NeuAc-alpha-2,3-Gal-beta-1,3-GalNAc sequence of glycoproteins and glycolipids forming an alpha-2,6-linkage.
RXFP1	Relaxin receptor 1	Receptor for relaxins.
AIG1	Androgen-induced gene 1 protein	Hydrolyzes bioactive fatty-acid esters of hydroxy-fatty acids (FAHFAs), but not other major classes of lipids.
ST8SIA6	Alpha-2,8-sialyltransferase 8F	Alpha-2,8-sialyltransferase that prefers O-glycans to N-glycans or glycolipids as acceptor substrates.
LMBRD2	G-protein coupled receptor-associated protein LMBRD2	Recruited to ligand-activated beta-2 adrenergic receptor/ADRB2, it negatively regulates the adrenergic receptor signaling pathway.
INTS10	Integrator complex subunit 10	Component of the integrator complex, a multiprotein complex that terminates RNA polymerase II (Pol II) transcription in the promoter-proximal region of genes.
MAIP1	m-AAA protease-interacting protein 1, mitochondrial	Promotes sorting of SMDT1/EMRE in mitochondria by ensuring its maturation.
AGBL1	Cytosolic carboxypeptidase 4	Metallocarboxypeptidase that mediates deglutamylation of tubulin and non-tubulin target proteins.
DDC	Aromatic-L-amino-acid decarboxylase	Catalyzes the decarboxylation of L-3,4-dihydroxyphenylalanine (DOPA) to dopamine and L-5-hydroxytryptophan to serotonin.
OR8U8	Olfactory receptor 8U8	Odorant receptor.
DGKB	Diacylglycerol kinase beta	Diacylglycerol kinase that converts diacylglycerol/DAG into phosphatidic acid/phosphatidate/PA and regulates the respective levels of these two bioactive lipids.
RSPO2	R-spondin-2	Activator of the canonical Wnt signaling pathway by acting as a ligand for LGR4-6 receptors.
LHPP	Phospholysine phosphohistidine inorganic pyrophosphate phosphatase	Phosphatase that hydrolyzes imidodiphosphate, 3-phosphohistidine and 6-phospholysine.
ERC2	ERC protein 2	Thought to be involved in the organization of the cytomatrix at the nerve terminals active zone (CAZ) which regulates neurotransmitter release.
ERG	Transcriptional regulator ERG	Transcriptional regulator.
ETV6	Transcription factor ETV6	Transcriptional repressor; binds to the DNA sequence 5’-CCGGAAGT-3'.
FLT3	Receptor-type tyrosine-protein kinase FLT3	Tyrosine-protein kinase that acts as a cell-surface receptor for the cytokine FLT3LG and regulates differentiation, proliferation and survival of hematopoietic progenitor cells and of dendritic cells.
GATA3	Trans-acting T-cell-specific transcription factor GATA-3	Transcriptional activator which binds to the enhancer of the T-cell receptor alpha and delta genes.
GNB1	Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1	Guanine nucleotide-binding proteins (G proteins) are involved as a modulator or transducer in various transmembrane signaling systems.
GRB10	Growth factor receptor-bound protein 10	Adapter protein which modulates coupling of a number of cell surface receptor kinases with specific signaling pathways.
HS6ST1	Heparan-sulfate 6-O-sulfotransferase 1	6-O-sulfation enzyme which catalyzes the transfer of sulfate from 3’-phosphoadenosine 5’-phosphosulfate (PAPS) to position 6 of the N-sulfoglucosamine residue (GlcNS) of heparan sulfate.
IL15	Interleukin-15	Cytokine that plays a major role in the development of inflammatory and protective immune responses to microbial invaders and parasites by modulating immune cells of both the innate and adaptive immune systems.
KCNA3	Potassium voltage-gated channel subfamily A member 3	Mediates the voltage-dependent potassium ion permeability of excitable membranes.
KCNE4	Potassium voltage-gated channel subfamily E member 4	Ancillary protein that functions as a regulatory subunit of the voltage-gated potassium (Kv) channel complex composed of pore-forming and potassium-conducting alpha subunits and of regulatory beta subunits.
KCNMB2	Calcium-activated potassium channel subunit beta-2	Regulatory subunit of the calcium activated potassium KCNMA1 (maxiK) channel.

Protein-family classification

Druggable: 23 · Difficult: 19 · Unknown: 19 · Druggable fraction: 0.38

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
Ion channel	4	7.3×	0.022
Scaffold/PPI	8	2.3×	0.118
Kinase	5	2.3×	0.228
GPCR	5	2.0×	0.228
Transcription factor	11	1.5×	0.228
Enzyme (other)	6	1.2×	0.666
Phosphatase	1	1.4×	0.683
Transporter	1	1.3×	0.683
Protease	1	0.6×	0.906
Other/Unknown	19	0.6×	1.000

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
IKZF1	Transcription factor	no		Znf_C2H2_type, Znf_C2H2_sf, Ikaros_C2H2-ZF
CDKN2A	Scaffold/PPI	no		Ankyrin_rpt-contain_sf, Ank_Repeat/CDKN_Inhibitor, Tumor_suppres_ARF
RUNX1	Transcription factor	no		AML1_Runt, p53-like_TF_DNA-bd_sf, p53/RUNT-type_TF_DNA-bd_sf
SH2B3	Scaffold/PPI	no		SH2, PH_domain, PH-like_dom_sf
ABL1	Kinase	yes	2.7.10.2	Prot_kinase_dom, SH2, Ser-Thr/Tyr_kinase_cat_dom
NT5C2	Enzyme (other)	yes	3.1.3.5	HAD-SF_hydro_IG_5-nucl, Pur_nucleotidase, HAD_sf
RIT2	Other/Unknown	no		Small_GTPase, Small_GTP-bd, Small_GTPase_Ras-type
BCR	Scaffold/PPI	no		C2_dom, RhoGAP_dom, DH_dom
RYR2	Ion channel	yes		RIH_dom, B30.2/SPRY, EF_hand_dom
SLCO3A1	Transporter	yes		Kazal_dom, OATP, Kazal_dom_sf
SP4	Transcription factor	no		Znf_C2H2_type, Znf_C2H2_sf, Sp4-like
TBXAS1	Other/Unknown	no		Cyt_P450, Cyt_P450_E_grp-I, Cyt_P450_CS
TIGAR	Other/Unknown	no		PG/BPGM_mutase_AS, His_Pase_superF_clade-1, His_PPase_superfam
ZNF230	Transcription factor	no		KRAB, Znf_C2H2_type, KRAB_dom_sf
IKZF3	Transcription factor	no		Znf_C2H2_type, Znf_C2H2_sf, Ikaros_C2H2-ZF
OR2C3	GPCR	yes		GPCR_Rhodpsn, Olfact_rcpt, GPCR_Rhodpsn_7TM
TP63	Transcription factor	no		SAM, p53_tumour_suppressor, p53-like_TF_DNA-bd_sf
PARD3	Scaffold/PPI	no		PDZ, Par3/HAL_N, PDZ_sf
MAML2	Other/Unknown	no		Mastermind-like_N, MAML1-3, MAML_N_sf
ELMO1	Scaffold/PPI	no		PH_domain, ELMO_dom, ARM-like
ARID5B	Other/Unknown	no		ARID_dom, ARID5B_ARID/BRIGHT_DNA-bd, ARID_dom_sf
NPFFR1	GPCR	yes		GPCR_Rhodpsn, NPFF_rcpt, NPFF_rcpt_1
CEBPE	Other/Unknown	no		bZIP, C/EBP_chordates, C/EBP
MAGI2	Kinase	yes		WW_dom, PDZ, Guanylate_kin-like_dom
MYRIP	Transcription factor	no		Myrip/Melanophilin, Rab_BD, Znf_FYVE_PHD
ST6GALNAC3	Enzyme (other)	yes	2.4.99.7	Glyco_trans_29, GT29-like_sf
RXFP1	GPCR	yes		GPCR_Rhodpsn, Leu-rich_rpt, LDrepeatLR_classA_rpt
GPATCH2L	Other/Unknown	no		Splicing_assoc_domain
AIG1	Other/Unknown	no		ADTRP_AIG1
ST8SIA6	Enzyme (other)	yes	2.4.99.8	Glyco_trans_29, Sialyl_trans, GT29-like_sf
LMBRD2	GPCR	yes		LMBR1-like_membr_prot, GPCR-associated_LMBR1
INTS10	Other/Unknown	no		Int_cplx_su10
MAIP1	Other/Unknown	no
AGBL1	Protease	yes		Peptidase_M14, ARM-like, ARM-type_fold
DDC	Enzyme (other)	yes	4.1.1.28	PyrdxlP-dep_de-COase, Aromatic_deC, PyrdxlP-dep_Trfase_major
OR8U8	GPCR	yes		GPCR_Rhodpsn, Olfact_rcpt, GPCR_Rhodpsn_7TM
DGKB	Kinase	yes	2.7.1.107	Diacylglycerol_kin_accessory, Diacylglycerol_kinase_cat_dom, EF_hand_dom
RSPO2	Other/Unknown	no		TSP1_rpt, Furin_repeat, Growth_fac_rcpt_cys_sf
LHPP	Enzyme (other)	yes	3.9.1.3	LHPP/HDHD2, HAD-SF_hydro_IIA, HAD_sf
ERC2	Other/Unknown	no		ELKS/CAST
CDKN2B-AS1	Other/Unknown	no
ERG	Other/Unknown	no		Ets_dom, Pointed_dom, SAM/pointed_sf
ETV6	Other/Unknown	no		Ets_dom, Pointed_dom, SAM/pointed_sf
FLT3	Kinase	yes	2.7.10.1	Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom, Tyr_kinase_rcpt_3_CS
GATA3	Transcription factor	no		Znf_GATA, Znf_NHR/GATA, TF_GATA-2/3
GNB1	Scaffold/PPI	no		WD40_G-protein_beta-like, WD40_rpt, WD40/YVTN_repeat-like_dom_sf
GRB10	Scaffold/PPI	no		RA_dom, SH2, PH_domain
HS6ST1	Other/Unknown	no		Sulfotransferase, Heparan_SO4-6-sulfoTrfase, P-loop_NTPase
IL15	Other/Unknown	no		IL-15/IL-21_fam, 4_helix_cytokine-like_core, IL-15
KCNA3	Ion channel	yes		BTB/POZ_dom, T1-type_BTB, K_chnl_volt-dep_Kv

Expression context

Cohort genes with no expression data: 1.

56 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)	60
unknown	1

Top tissues across cohort

Tissue	Cohort genes
monocyte	8
buccal mucosa cell	6
leukocyte	5
mononuclear cell	5
parotid gland	5
male germ line stem cell (sensu Vertebrata) in testis	5
secondary oocyte	5
corpus callosum	4
mucosa of paranasal sinus	3
cerebellar hemisphere	3
C1 segment of cervical spinal cord	3
endothelial cell	3
ganglionic eminence	3
primordial germ cell in gonad	3
mammary duct	3
Brodmann (1909) area 23	3
endometrium epithelium	3
cervix squamous epithelium	2
cerebellar cortex	2
caudate nucleus	2

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
IKZF1	225	broad	marker	leukocyte, monocyte, mononuclear cell
CDKN2A	220	ubiquitous	marker	parotid gland, cervix squamous epithelium, pituitary gland
RUNX1	253	ubiquitous	marker	olfactory segment of nasal mucosa, epithelium of bronchus, mucosa of paranasal sinus
SH2B3	260	ubiquitous	marker	monocyte, mononuclear cell, leukocyte
ABL1	283	ubiquitous	marker	frontal pole, paraflocculus, middle frontal gyrus
NT5C2	294	ubiquitous	marker	parotid gland, buccal mucosa cell, oral cavity
RIT2	128	tissue_specific	marker	cerebellar cortex, cerebellar hemisphere, cerebellum
BCR	275	ubiquitous	marker	nucleus accumbens, caudate nucleus, putamen
RYR2	210	broad	marker	heart right ventricle, left ventricle myocardium, myocardium
SLCO3A1	279	ubiquitous	marker	buccal mucosa cell, endothelial cell, C1 segment of cervical spinal cord
SP4	265	ubiquitous	marker	cerebellar vermis, germinal epithelium of ovary, superficial temporal artery
TBXAS1	180	ubiquitous	marker	monocyte, mononuclear cell, leukocyte
TIGAR	140	ubiquitous	yes	monocyte, stromal cell of endometrium, leukocyte
ZNF230	193	ubiquitous	yes	blood, secondary oocyte, male germ line stem cell (sensu Vertebrata) in testis
IKZF3	155	broad	marker	granulocyte, lymph node, epithelium of nasopharynx
OR2C3	55		marker	primordial germ cell in gonad, ventricular zone, ganglionic eminence
TP63	207	broad	marker	upper leg skin, skin of hip, upper arm skin
PARD3	278	ubiquitous	marker	cervix squamous epithelium, tongue squamous epithelium, secondary oocyte
MAML2	238	ubiquitous	marker	mucosa of paranasal sinus, cartilage tissue, mammary duct
ELMO1	248	ubiquitous	marker	prefrontal cortex, C1 segment of cervical spinal cord, corpus callosum
ARID5B	299	ubiquitous	marker	type B pancreatic cell, saphenous vein, pericardium
NPFFR1	85	tissue_specific	marker	parotid gland, dorsal motor nucleus of vagus nerve, inferior olivary complex
CEBPE	99	tissue_specific	marker	bone marrow, bone element, trabecular bone tissue
MAGI2	267	ubiquitous	marker	calcaneal tendon, corpus callosum, Brodmann (1909) area 23
MYRIP	261	broad	marker	pigmented layer of retina, retina, endothelial cell
ST6GALNAC3	202	broad	marker	corpus callosum, primordial germ cell in gonad, cortical plate
RXFP1	147	broad	marker	decidua, endothelial cell, endometrium
GPATCH2L	259	ubiquitous	marker	buccal mucosa cell, colonic epithelium, adrenal tissue
AIG1	273	ubiquitous	marker	buccal mucosa cell, right lobe of liver, liver
ST8SIA6	130	broad	marker	male germ line stem cell (sensu Vertebrata) in testis, primordial germ cell in gonad, substantia nigra

Protein interactions among cohort

Intra-cohort edges: 32.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CDKN2A	9,311
ABL1	6,937
GATA3	5,990
RUNX1	4,994
IKZF1	4,096
FLT3	3,570
IKZF3	3,285
MAGI2	3,246
RIT2	3,234
IL15	3,126

Intra-cohort edges

A	B	Sources
ABL1	BCR	string_interaction
ABL1	ETV6	string_interaction
ABL1	IKZF1	string_interaction
ABL1	NUP214	string_interaction
ARID5B	CEBPE	string_interaction
ARID5B	IKZF1	string_interaction
ARID5B	OR2C3	string_interaction
ARID5B	PIP4K2A	string_interaction
CDKN2A	TP63	string_interaction
CEBPE	IKZF1	string_interaction
CEBPE	PIP4K2A	string_interaction
CEBPE	RUNX1	string_interaction
ETV6	FLT3	string_interaction
ETV6	IKZF1	string_interaction
ETV6	RUNX1	string_interaction
FLT3	GRB10	intact
FLT3	PTPRJ	string_interaction
FLT3	RUNX1	string_interaction
GATA3	RUNX1	string_interaction
GRB10	KCNA3	biogrid_interaction
IKZF1	PAX5	string_interaction
IKZF1	RUNX1	string_interaction
IKZF3	PAX5	string_interaction
IKZF3	RUNX1	string_interaction
KCNA3	KCNE4	biogrid_interaction
KCNE4	OR2C3	string_interaction
KRT85	OR2C3	string_interaction
LHPP	PIP4K2A	string_interaction
MAIP1	OR2C3	string_interaction
NPFFR1	OR2C3	string_interaction
OR2C3	ST6GALNAC3	string_interaction
ST6GALNAC3	ST8SIA6	string_interaction

Structural data

PDB: 37 · AlphaFold-only: 23 · No structure: 1

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
GNB1	P62873	1,262
ABL1	P00519	85
ETV6	P41212	44
NT5C2	P49902	43
PDE4B	Q07343	43
RYR2	Q92736	26
TP63	Q9H3D4	26
PYGL	P06737	19
ELMO1	Q92556	18
PIP4K2A	P48426	18
KCNA3	P22001	16
FLT3	P36888	11
IKZF1	Q13422	10
INTS10	Q9NVR2	8
DDC	P20711	8
RSPO2	Q6UXX9	8
ERG	P11308	8
NBN	O60934	7
NUP214	P35658	7
NCOA3	Q9Y6Q9	6
CDKN2A	P42771	5
RUNX1	Q01196	5
BCR	P11274	5
MAGI2	Q86UL8	5
PTPRJ	Q12913	5
NPFFR1	Q9GZQ6	4
IL15	P40933	4
RXFP1	Q9HBX9	3
GATA3	P23771	3
ARID5B	Q14865	2

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
AIG1	Q9NVV5	93.92
TBXAS1	P24557	91.50
OR8U8	P0C7N1	89.65
ST6GALNAC3	Q8NDV1	89.19
RIT2	Q99578	88.46
HS6ST1	O60243	87.28
OR2C3	Q8N628	86.84
ST8SIA6	P61647	86.04
AGBL1	Q96MI9	78.53
DGKB	Q9Y6T7	78.02
LMBRD2	Q68DH5	76.95
SLCO3A1	Q9UIG8	75.19
ERC2	O15083	74.26
KRT85	P78386	74.09
MAIP1	Q8WWC4	68.20
SH2B3	Q9UQQ2	63.45
ZNF230	Q9UIE0	58.55
MYRIP	Q8NFW9	58.10
KCNE4	Q8WWG9	57.86
GPATCH2L	Q9NWQ4	51.19
IKZF3	Q9UKT9	48.06
MAML2	Q8IZL2	46.21
SP4	Q02446	39.58

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 413. Enrichment computed across 61 evidence-associated genes (54 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 54 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Negative regulation of FLT3	3	39.6×	0.022	SH2B3, FLT3, PTPRJ
RUNX1 regulates transcription of genes involved in BCR signaling	2	70.5×	0.067	RUNX1, PAX5
FLT3 Signaling	3	19.2×	0.068	SH2B3, FLT3, GRB10
Defective TBXAS1 causes GHDD	1	211.5×	0.081	TBXAS1
Evasion of Oncogene Induced Senescence Due to p14ARF Defects	1	211.5×	0.081	CDKN2A
Evasion of Oxidative Stress Induced Senescence Due to p14ARF Defects	1	211.5×	0.081	CDKN2A
FLT3 mutants bind TKIs	1	211.5×	0.081	FLT3
KW2449-resistant FLT3 mutants	1	211.5×	0.081	FLT3
semaxanib-resistant FLT3 mutants	1	211.5×	0.081	FLT3
crenolanib-resistant FLT3 mutants	1	211.5×	0.081	FLT3
gilteritinib-resistant FLT3 mutants	1	211.5×	0.081	FLT3
lestaurtinib-resistant FLT3 mutants	1	211.5×	0.081	FLT3
midostaurin-resistant FLT3 mutants	1	211.5×	0.081	FLT3
pexidartinib-resistant FLT3 mutants	1	211.5×	0.081	FLT3
ponatinib-resistant FLT3 mutants	1	211.5×	0.081	FLT3
quizartinib-resistant FLT3 mutants	1	211.5×	0.081	FLT3
sorafenib-resistant FLT3 mutants	1	211.5×	0.081	FLT3
sunitinib-resistant FLT3 mutants	1	211.5×	0.081	FLT3
tandutinib-resistant FLT3 mutants	1	211.5×	0.081	FLT3
linifanib-resistant FLT3 mutants	1	211.5×	0.081	FLT3
tamatinib-resistant FLT3 mutants	1	211.5×	0.081	FLT3
RUNX3 regulates p14-ARF	2	42.3×	0.081	CDKN2A, RUNX1
Developmental Lineage of Mammary Stem Cells	2	28.2×	0.081	TP63, GATA3
Transcriptional regulation by RUNX3	3	15.1×	0.081	CDKN2A, RUNX1, MAML2
DNA Double Strand Break Response	2	17.6×	0.094	ABL1, NBN
NOTCH3 Intracellular Domain Regulates Transcription	2	16.3×	0.105	IKZF1, MAML2
Evasion of Oncogene Induced Senescence Due to Defective p16INK4A binding to CDK4	1	105.7×	0.122	CDKN2A
Evasion of Oxidative Stress Induced Senescence Due to Defective p16INK4A binding to CDK4	1	105.7×	0.122	CDKN2A
Defective Intrinsic Pathway for Apoptosis Due to p14ARF Loss of Function	1	105.7×	0.122	CDKN2A
G1 Phase	2	14.6×	0.122	CDKN2A, ABL1

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 57 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 extracellular matrix organization	2	147.8×	0.029	RUNX1, ABL1
negative regulation of mammary gland epithelial cell proliferation	2	118.3×	0.029	CDKN2A, GATA3
mitochondrial depolarization	2	84.5×	0.029	CDKN2A, ABL1
macrophage differentiation	3	24.6×	0.029	CEBPE, GATA3, IL15
positive regulation of interleukin-2 production	3	24.6×	0.029	RUNX1, ABL1, PDE4B
B cell differentiation	4	15.4×	0.029	IKZF3, FLT3, PAX5, PTPRJ
regulation of nucleocytoplasmic transport	2	65.7×	0.041	CDKN2A, NUP214
neutrophil homeostasis	2	53.8×	0.041	SH2B3, PDE4B
regulation of Cdc42 protein signal transduction	2	49.3×	0.041	RIT2, ABL1
cellular response to epinephrine stimulus	2	45.5×	0.041	RYR2, PDE4B
regulation of T cell differentiation	2	42.2×	0.041	IL15, ABL1
ganglioside biosynthetic process	2	39.4×	0.041	ST6GALNAC3, ST8SIA6
detection of calcium ion	2	39.4×	0.041	RYR2, KCNMB2
glycoprotein metabolic process	2	39.4×	0.041	ST6GALNAC3, ST8SIA6
negative regulation of insulin receptor signaling pathway	3	19.7×	0.041	GRB10, PIP4K2A, PTPRJ
neuromuscular process controlling balance	3	17.4×	0.041	BCR, ABL1, NBN
positive regulation of phagocytosis	3	16.7×	0.041	BCR, IL15, PTPRJ
cellular senescence	3	15.6×	0.041	CDKN2A, TP63, ABL1
T cell receptor signaling pathway	4	10.7×	0.041	GATA3, ABL1, PDE4B, PTPRJ
regulation of cell cycle	5	6.5×	0.041	CDKN2A, BCR, ABL1, NBN, NUP214
negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	3	13.9×	0.045	MAGI2, SH2B3, PTPRJ
embryonic hemopoiesis	2	34.8×	0.046	SH2B3, GATA3
ventricular cardiac muscle cell action potential	2	34.8×	0.046	RYR2, KCNE4
sympathetic nervous system development	2	32.9×	0.046	TP63, GATA3
negative regulation of reactive oxygen species metabolic process	2	32.9×	0.046	BCR, TIGAR
keratinocyte differentiation	3	13.0×	0.046	CDKN2A, BCR, TP63
type IV hypersensitivity	1	295.6×	0.048	GATA3
negative regulation of cellular extravasation	1	295.6×	0.048	BCR
obsolete GMP catabolic process to guanine	1	295.6×	0.048	NT5C2
ectoderm and mesoderm interaction	1	295.6×	0.048	TP63

Therapeutics

Drugs indicated for this disease

14 approved, 40 in late-stage (phase 3) trials. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

Drug	Development status
Asparaginase	Approved (phase 4)
Asparaginase Erwinia Chrysanthemi	Approved (phase 4)
Blinatumomab	Approved (phase 4)
Calaspargase Pegol	Approved (phase 4)
Chlorambucil	Approved (phase 4)
Clofarabine	Approved (phase 4)
Crisantaspase	Approved (phase 4)
Cytarabine	Approved (phase 4)
Dasatinib Anhydrous	Approved (phase 4)
Inotuzumab Ozogamicin	Approved (phase 4)
Methotrexate	Approved (phase 4)
Pegaspargase	Approved (phase 4)
Plerixafor	Approved (phase 4)
Rituximab	Approved (phase 4)
Allopurinol	Phase 3 (in late-stage trials)
Apixaban	Phase 3 (in late-stage trials)
Bortezomib	Phase 3 (in late-stage trials)
Busulfan	Phase 3 (in late-stage trials)
Cyclosporine	Phase 3 (in late-stage trials)
Daunorubicin	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)
Epratuzumab	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)
Flumatinib	Phase 3 (in late-stage trials)
Glucarpidase	Phase 3 (in late-stage trials)
Hydrocortisone	Phase 3 (in late-stage trials)
INTERFERON ALFA-2A	Phase 3 (in late-stage trials)
Idarubicin	Phase 3 (in late-stage trials)
Ifosfamide	Phase 3 (in late-stage trials)
Imatinib	Phase 3 (in late-stage trials)
Inotuzumab	Phase 3 (in late-stage trials)
Lestaurtinib	Phase 3 (in late-stage trials)
Methylprednisolone	Phase 3 (in late-stage trials)
Mitoxantrone	Phase 3 (in late-stage trials)
Mycophenolate Mofetil	Phase 3 (in late-stage trials)
Nelarabine	Phase 3 (in late-stage trials)
Olverembatinib	Phase 3 (in late-stage trials)
Ponatinib	Phase 3 (in late-stage trials)
Prednisolone	Phase 3 (in late-stage trials)
Prednisone	Phase 3 (in late-stage trials)
Teniposide	Phase 3 (in late-stage trials)
Thioguanine	Phase 3 (in late-stage trials)
Thiotepa	Phase 3 (in late-stage trials)
Tisagenlecleucel	Phase 3 (in late-stage trials)
Topotecan	Phase 3 (in late-stage trials)
Treosulfan	Phase 3 (in late-stage trials)
Vincristine	Phase 3 (in late-stage trials)
Vindesine	Phase 3 (in late-stage trials)

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): Acetaminophen, Alemtuzumab, Amphotericin B, Azacitidine, Azathioprine, Bendamustine, Brexucabtagene Autoleucel, Cladribine, Curcumin, Daratumumab, Dinaciclib, Diphenhydramine, Gemcitabine, Gemtuzumab Ozogamicin, Hydroxyurea, Isatuximab, Lenalidomide, Melphalan, Motixafortide, Moxetumomab Pasudotox, Nilotinib, OMEGA-3-ACID ETHYL ESTERS, Obinutuzumab, Ofatumumab, Panobinostat, Pegfilgrastim, Pentoxifylline, Pirarubicin, Ruxolitinib, Sargramostim, Sirolimus, Tacrolimus Anhydrous, Tafasitamab, Tucidinostat, Venetoclax, Vinblastine, Vorinostat.

Drug target analysis

Approved (phase 4): 13 · Phase ≥3: 15 · Phased (≥1): 18 · Undrugged: 43

Druggability breadth: 31 of 61 evidence-associated genes (51%) 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
IKZF1	POMALIDOMIDE
RUNX1	APOMORPHINE HYDROCHLORIDE
ABL1	PONATINIB
BCR	PONATINIB
TBXAS1	CLOTRIMAZOLE
IKZF3	POMALIDOMIDE
RXFP1	METHYSERGIDE MALEATE
ETV6	CERITINIB
FLT3	PONATINIB
KCNA3	CLOTRIMAZOLE
NCOA3	METHOTREXATE
PDE4B	INAMRINONE
PIP4K2A	PALBOCICLIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
FLT3	143	4
ABL1	122	4
BCR	64	4
PDE4B	55	4
TBXAS1	46	4
RXFP1	11	4
IKZF3	5	4
ETV6	4	4
KCNA3	4	4
NCOA3	4	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
POMALIDOMIDE	4	IKZF1, IKZF3
LENALIDOMIDE	4	IKZF1, IKZF3
APOMORPHINE HYDROCHLORIDE	4	RUNX1
PONATINIB	4	ABL1, BCR, FLT3
AFATINIB	4	ABL1, FLT3
FEDRATINIB	4	ABL1, BCR, FLT3
TIVOZANIB	4	ABL1, BCR, FLT3
LENVATINIB	4	ABL1, BCR
AXITINIB	4	ABL1, BCR, FLT3
SORAFENIB	4	ABL1, FLT3
DASATINIB ANHYDROUS	4	ABL1, BCR
IMATINIB MESYLATE	4	ABL1, BCR
RUXOLITINIB	4	ABL1
NERATINIB	4	ABL1, FLT3
INFIGRATINIB PHOSPHATE	4	ABL1, FLT3
INFIGRATINIB	4	ABL1, BCR, FLT3
IBRUTINIB	4	ABL1, BCR, FLT3
REGORAFENIB	4	ABL1, BCR, FLT3
ENTRECTINIB	4	ABL1, FLT3
DABRAFENIB	4	ABL1
TOFACITINIB CITRATE	4	ABL1
AFATINIB DIMALEATE	4	ABL1
CABOZANTINIB	4	ABL1, BCR, FLT3
TOFACITINIB	4	ABL1
CERITINIB	4	ABL1, ETV6, FLT3
VANDETANIB	4	ABL1, BCR, FLT3
NILOTINIB	4	ABL1, BCR, FLT3
BOSUTINIB	4	ABL1, BCR, FLT3
FILGOTINIB	4	ABL1, FLT3
TOVORAFENIB	4	ABL1, BCR

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 13.

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

Symbol	Assays	Type breakdown
ABL1	3,282	Binding:3254, ADMET:16, Functional:10, Toxicity:2
FLT3	3,132	Binding:3096, Functional:24, ADMET:8, Toxicity:4
PDE4B	796	Binding:755, Functional:29, ADMET:11, Toxicity:1
BCR	486	Binding:478, Functional:6, Toxicity:2
TBXAS1	210	Binding:138, Functional:72
PIP4K2A	136	Binding:134, Functional:2
NPFFR1	114	Functional:68, Binding:46
IKZF1	106	Binding:105, Functional:1
IKZF3	101	Binding:100, Functional:1
KCNA3	100	Binding:89, Functional:9, Toxicity:1, ADMET:1
RXFP1	82	Functional:75, Binding:7
PYGL	58	Binding:58
NCOA3	42	Binding:39, Functional:3
RUNX1	20	Binding:17, Functional:3
RYR2	15	Binding:15
ERG	14	Binding:10, Functional:3, ADMET:1
GNB1	12	Binding:12
ETV6	11	Binding:11
SLCO3A1	9	Functional:9
GRB10	9	Binding:9
IL15	9	Binding:9
DDC	8	Functional:6, Binding:2
NT5C2	7	Binding:7
ELMO1	6	Binding:6
DGKB	5	Binding:5
PTPRJ	5	Binding:4, ADMET:1
CDKN2A	2	Binding:2
NBN	2	Binding:2
TIGAR	1	Binding:1
LHPP	1	Binding:1
KRT85	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
ABL1	2.7.10.2	non-specific protein-tyrosine kinase
NT5C2	3.1.3.5	5’-nucleotidase
ST6GALNAC3	2.4.99.7	alpha-N-acetylneuraminyl-2,3-beta-galactosyl-1,3-N-acetylgalactosaminide 6-alpha-sialyltransferase
ST8SIA6	2.4.99.8	alpha-N-acetylneuraminate alpha-2,8-sialyltransferase
DDC	4.1.1.28	aromatic-L-amino-acid decarboxylase
DGKB	2.7.1.107	diacylglycerol kinase (ATP)
LHPP	3.9.1.3	phosphohistidine phosphatase
FLT3	2.7.10.1	receptor protein-tyrosine kinase
NCOA3	2.3.1.48	histone acetyltransferase
PDE4B	3.1.4.53	3’,5’-cyclic-AMP phosphodiesterase
PIP4K2A	2.7.1.149	1-phosphatidylinositol-5-phosphate 4-kinase
PTPRJ	3.1.3.48	protein-tyrosine-phosphatase
PYGL	2.4.1.1	glycogen phosphorylase

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
IKZF1	106
ABL1	3,282
BCR	486
TBXAS1	210
IKZF3	101
NPFFR1	114
FLT3	3,132
KCNA3	100
PDE4B	796
PIP4K2A	136

Pharmacogenomics

Cohort genes with a PharmGKB record: 61; with CPIC/DPWG dosing guidelines: 0.

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

Drug repurposing candidates

28 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)
POMALIDOMIDE	4	IKZF1, IKZF3
LENALIDOMIDE	4	IKZF1, IKZF3
APOMORPHINE HYDROCHLORIDE	4	RUNX1
AFATINIB	4	ABL1, FLT3
FEDRATINIB	4	ABL1, BCR, FLT3
TIVOZANIB	4	ABL1, BCR, FLT3
LENVATINIB	4	ABL1, BCR
AXITINIB	4	ABL1, BCR, FLT3
SORAFENIB	4	ABL1, FLT3
IMATINIB MESYLATE	4	ABL1, BCR
RUXOLITINIB	4	ABL1
NERATINIB	4	ABL1, FLT3
INFIGRATINIB PHOSPHATE	4	ABL1, FLT3
INFIGRATINIB	4	ABL1, BCR, FLT3
IBRUTINIB	4	ABL1, BCR, FLT3
REGORAFENIB	4	ABL1, BCR, FLT3
ENTRECTINIB	4	ABL1, FLT3
DABRAFENIB	4	ABL1
TOFACITINIB CITRATE	4	ABL1
AFATINIB DIMALEATE	4	ABL1
CABOZANTINIB	4	ABL1, BCR, FLT3
TOFACITINIB	4	ABL1
CERITINIB	4	ABL1, ETV6, FLT3
VANDETANIB	4	ABL1, BCR, FLT3
NILOTINIB	4	ABL1, BCR, FLT3
BOSUTINIB	4	ABL1, BCR, FLT3
FILGOTINIB	4	ABL1, FLT3
TOVORAFENIB	4	ABL1, BCR

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	13	IKZF1, RUNX1, ABL1, BCR, TBXAS1, IKZF3, RXFP1, ETV6, FLT3, KCNA3 (+3 more)
B	Phased (≥1) drug, not yet approved	5	RYR2, ELMO1, NPFFR1, GNB1, PYGL
C	Druggable family + PDB, no drug	6	NT5C2, MAGI2, DDC, LHPP, KCNMB2, PTPRJ
D	Druggable family + AlphaFold only, no drug	9	SLCO3A1, OR2C3, ST6GALNAC3, ST8SIA6, LMBRD2, AGBL1, OR8U8, DGKB, KCNE4
E	Difficult family or no structure, no drug	28	CDKN2A, SH2B3, RIT2, SP4, TIGAR, ZNF230, TP63, PARD3, MAML2, ARID5B (+18 more)

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
ARID5B	0	PIP4K2A
LHPP	1	PIP4K2A
GATA3	0	RUNX1
PAX5	0	IKZF1
CDKN2A	2	—
SH2B3	0	—
NT5C2	7	—
RIT2	0	—
SLCO3A1	9	—
SP4	0	—
TIGAR	1	—
ZNF230	0	—
OR2C3	0	—
TP63	0	—
PARD3	0	—
MAML2	0	—
CEBPE	0	—
MAGI2	0	—
MYRIP	0	—
ST6GALNAC3	0	—
GPATCH2L	0	—
AIG1	0	—
ST8SIA6	0	—
LMBRD2	0	—
INTS10	0	—
MAIP1	0	—
AGBL1	0	—
DDC	8	—
OR8U8	0	—
DGKB	5	—

Clinical trials & evidence

Clinical trials

Clinical trials: 1,029.

Phase distribution (across all retrieved trials)

Phase	Trials
PHASE2	278
Not specified	271
PHASE1	221
PHASE1/PHASE2	124
PHASE3	56
PHASE4	32
PHASE2/PHASE3	24
EARLY_PHASE1	23

Top trials by phase / activity

NCT	Phase	Status	Title
NCT06289673	PHASE4	RECRUITING	Identification of Necessary Information for Treatment Induction in Newly Diagnosed Acute Lymphoblastic Leukemia/Lymphoma
NCT06918054	PHASE4	RECRUITING	Hepatoprotective for Children and Adolescent With Acute Lymphoblastic Leukemia
NCT06918080	PHASE4	ACTIVE_NOT_RECRUITING	Hepatoprotective Measures for Children at High Risk of NAFLD
NCT07016165	PHASE4	RECRUITING	Ciprofloxacin vs Ceftazidime for Empirical Treatment of High-Risk Neutropenic Fever in Children With Hematologic Malignancies
NCT07320534	PHASE4	NOT_YET_RECRUITING	Levofloxacin Prophylaxis to Prevent First Febrile Neutropenia in Pediatric ALL During Induction Phase
NCT00114348	PHASE4	COMPLETED	ALL-REZ BFM 2002: Multi-Center Study for Children With Relapsed Acute Lymphoblastic Leukemia
NCT00192673	PHASE4	UNKNOWN	Poly(Ethylene Glycol)(PEG)-Asparaginase During Two Treatment Courses
NCT00222612	PHASE4	UNKNOWN	Medical Research Council (MRC) Working Party on Leukaemia in Children UK National Acute Lymphoblastic Leukaemia (ALL) Trial: UKALL 2003
NCT00411541	PHASE4	COMPLETED	Pulses of Vincristine and Dexamethasone in BFM Protocols for Children With Acute Lymphoblastic Leukemia
NCT00494897	PHASE4	COMPLETED	PETHEMA LAL-RI/96: Treatment for Patients With Standard Risk Acute Lymphoblastic Leukemia
NCT00526175	PHASE4	COMPLETED	LAL-BR/2001: Study Treatment to Low Risk ALL
NCT00526305	PHASE4	COMPLETED	LAL-Ph-2000: Treatment of Acute Lymphoblastic Leukemia Chromosome Philadelphia Positive
NCT00526409	PHASE4	COMPLETED	LAL-AR-N-2005:Study Treatment for Children High Risk Acute Lymphoblastic Leukemia
NCT00576472	PHASE4	COMPLETED	Learning Impairments Among Survivors of Childhood Cancer
NCT00797810	PHASE4	UNKNOWN	Intensification Therapy of Mature B-ALL, Burkitt and Burkitt Like and Other High Grade Non-Hodgkin’s Lymphoma in Adults
NCT00846703	PHASE4	UNKNOWN	The GD-2008 ALL Protocol for Childhood Acute Lymphoblastic Leukemia
NCT00853008	PHASE4	COMPLETED	Treatment of High Risk Adult Acute Lymphoblastic Leukemia
NCT01358201	PHASE4	UNKNOWN	PETHEMA LAL-07FRAIL: All Treatment In Fragile Patients Ph’ Negative Over 55 Years
NCT01358253	PHASE4	COMPLETED	Rituximab Plus Chemotherapy for CD20+ Adult Acute Lymphoblastic Leukemia
NCT01366898	PHASE4	UNKNOWN	Protocol For the Treatment Acute Lymphoblastic Leukemia With Ph ‘Negative in Elderly Patients (> 55 Years)
NCT01735955	PHASE4	COMPLETED	Study to Allow Access to Nilotinib for Patients Who Are on Nilotinib Treatment in a Novartis-sponsored Study
NCT01873807	PHASE4	UNKNOWN	HD-Idarubicin/Etoposide Intensified Conditioning Regimen Allo-HSCT for Adult ALL
NCT01906671	PHASE4	UNKNOWN	Study on Two Different Formulations of 6-mercaptopurine. Tablet Versus Oral Liquid
NCT02447718	PHASE4	COMPLETED	Vaccinating Children After Chemotherapy
NCT02670564	PHASE4	UNKNOWN	ALL SCTped FORUM - Pharmacogenomic Study (add-on Study)
NCT02894645	PHASE4	UNKNOWN	Malaysia-Singapore Acute Lymphoblastic Leukemia 2010 Study
NCT02933333	PHASE4	UNKNOWN	G-CSF Alone or Combination With GM-CSF on Prevention and Treatment of Infection in Children With Malignant Tumor
NCT02953730	PHASE4	COMPLETED	The Study on the Pharmacokinetics of PEG-rhG-CSF in Children and Adolescents
NCT03677596	PHASE4	COMPLETED	A Study Of Two Inotuzumab Ozogamicin Doses in Relapsed/ Refractory Acute Lymphoblastic Leukemia Transplant Eligible Patients
NCT03920813	PHASE4	UNKNOWN	Determinants of Mercaptopurine Toxicity in Paediatric Acute Lymphoblastic Leukemia Maintenance Therapy
NCT05133310	PHASE4	UNKNOWN	Effect of Simvastatin on Sepsis and Febrile Neutropenia in Patients With Acute Lymphoblastic Leukemia
NCT05687032	PHASE4	COMPLETED	A Study of Inotuzumab Ozogamicin in Chinese Patients With Relapsed or Refractory Acute Lymphoblastic Leukemia
NCT01949129	PHASE2/PHASE3	RECRUITING	Allogeneic Stem Cell Transplantation for Children and Adolescents With Acute Lymphoblastic Leukaemia
NCT02003222	PHASE3	ACTIVE_NOT_RECRUITING	Combination Chemotherapy With or Without Blinatumomab in Treating Patients With Newly Diagnosed BCR-ABL-Negative B Lineage Acute Lymphoblastic Leukemia
NCT02716233	PHASE3	ACTIVE_NOT_RECRUITING	A French Protocol for the Treatment of Acute Lymphoblastic Leukemia (ALL) in Children and Adolescents
NCT03007147	PHASE3	ACTIVE_NOT_RECRUITING	Imatinib Mesylate and Combination Chemotherapy in Treating Patients With Newly Diagnosed Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia
NCT03117751	PHASE2/PHASE3	ACTIVE_NOT_RECRUITING	Total Therapy XVII for Newly Diagnosed Patients With Acute Lymphoblastic Leukemia and Lymphoma
NCT03844048	PHASE3	ACTIVE_NOT_RECRUITING	An Extension Study of Venetoclax for Subjects Who Have Completed a Prior Venetoclax Clinical Trial
NCT04722848	PHASE3	ACTIVE_NOT_RECRUITING	Sequential Treatment With Ponatinib and Blinatumomab vs Chemotherapy and Imatinib in Newly Diagnosed Adult Ph+ ALL
NCT05316701	PHASE3	ACTIVE_NOT_RECRUITING	Precision-T: A Randomized Study of Orca-T in Recipients Undergoing Allogeneic Transplantation for Hematologic Malignancies

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
MERCAPTOPURINE ANHYDROUS	4	72
DAUNORUBICIN	4	61
PEGASPARGASE	4	40
MELPHALAN	4	36
BLINATUMOMAB	4	30
ASPARAGINASE	4	26
CLOFARABINE	4	22
VINCRISTINE	4	21
PONATINIB	4	19
CYCLOPHOSPHAMIDE ANHYDROUS	4	18
INOTUZUMAB OZOGAMICIN	4	18
DASATINIB ANHYDROUS	4	16
DOXORUBICIN	4	16
THIOGUANINE	4	15
MITOXANTRONE	4	12
TISAGENLECLEUCEL	4	12
CYTARABINE	4	11
2-MERCAPTOETHANESULFONIC ACID	4	10
LEUCOVORIN	4	10
PLERIXAFOR	4	10
DEXRAZOXANE	4	9
METHOTREXATE	4	9
CALASPARGASE PEGOL	4	7
ETOPOSIDE PHOSPHATE	4	7
REVUMENIB	4	7
BETAMETHASONE	4	6
DEXAMETHASONE	4	6
FLUDARABINE PHOSPHATE	4	6
IDARUBICIN	4	6
IMATINIB	4	6

Precision-medicine subtype map (CIViC)

Drug × molecular subtype: 18 predictive associations from 22 curated evidence items; also 7 prognostic, 2 oncogenic, 2 diagnostic, 1 predisposing.

Molecular subtype	Therapy	Effect	Level	CIViC
BCR::ABL1 Fusion AND ABL1 Mutation	Dasatinib	Sensitivity/Response	CIViC A	EID11341
ABL1 TKD Mutation OR ABL1 P-Loop Mutation OR ABL1 Non-P-Loop Mutation	Bosutinib	Sensitivity/Response	CIViC B	EID11339
BCR::ABL1 Fusion	Dasatinib	Sensitivity/Response	CIViC C	EID4436
BCR::ABL1 Fusion AND ABL1 T315I	Dasatinib	Resistance	CIViC C	EID4374 +4
BCR::ABL1 Fusion AND ABL1 E255K	Dasatinib	Resistance	CIViC C	EID4718
BCR::ABL1 Fusion AND ABL1 F317I	Dasatinib	Resistance	CIViC C	EID4726
BCR::ABL1 Fusion AND ABL1 M244V	Dasatinib	Resistance	CIViC C	EID4387
BCR::ABL1 Fusion AND ABL1 Y253H	Dasatinib	Resistance	CIViC C	EID7947
BCR::ABL1 Fusion AND ABL1 T315I	Ponatinib	Sensitivity/Response	CIViC D	EID2673
CRLF2 Rearrangement	Sirolimus	Sensitivity/Response	CIViC D	EID11097
FLT3 ITD OR FLT3 TKD MUTATION OR NRAS EXON 2-3 MUTATION OR PTPN11 Mutation OR KRAS Exon 2-3 Mutation	Selumetinib	Sensitivity/Response	CIViC D	EID12553
IGH::CRLF2 Fusion	Ruxolitinib	Sensitivity/Response	CIViC D	EID8540
MEF2D::CSF1R Fusion	GW-2580 + Imatinib	Sensitivity/Response	CIViC D	EID403
WEE1 Overexpression	Adavosertib	Sensitivity/Response	CIViC D	EID9231
BCR::ABL1 Fusion AND ABL1 H396P	Bosutinib	Resistance	CIViC D	EID4379
BCR::ABL1 Fusion AND ABL1 T315I	Ponatinib + Axitinib	Resistance	CIViC D	EID7777
BCR::ABL1 Fusion AND ABL1 T315I	Nilotinib + Imatinib + Dasatinib	Resistance	CIViC D	EID7778
CREBBP Mutation	Therapeutic Glucocorticoid	Resistance	CIViC D	EID8501