◎ Sugi Atlas

Atlas / Disease / Childhood myelodysplastic syndrome

Childhood myelodysplastic syndrome

disease
On this page

Also known as childhood MDSmyelodysplastic syndrome

Summary

Childhood myelodysplastic syndrome (MONDO:0044873) is a disease with 13 cohort genes and 790 clinical trials. Molecularly, TP53 Mutation confers sensitivity to Azacitidine + Eprenetapopt in Myelodysplastic Syndrome (CIViC Level B). Top therapeutic interventions include fludarabine phosphate, venetoclax, and decitabine.

At a glance

  • Cohort genes: 13
  • Clinical trials: 790
  • Precision-medicine evidence (CIViC): 1 subtype–drug association

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

FieldValue
Canonical namechildhood myelodysplastic syndrome
Mondo IDMONDO:0044873
NCITC68744
UMLSC2347761
MedGen389541
GARD0025913
Is cancer (heuristic)no

Also known as: childhood MDS · childhood myelodysplastic syndrome · myelodysplastic syndrome

Data availability: 37 cell lines.

Disease family

An umbrella term covering 1 Mondo subtype.

Classification path: disease › human disease › disease by etiologic mechanism › cancer or benign tumor › neoplastic disease or syndrome › neoplasm › hematopoietic and lymphoid system neoplasm › myeloid hemopathy › myelodysplastic syndrome › childhood myelodysplastic syndrome

Related subtypes (7): myelodysplastic syndrome with single lineage dysplasia, myelodysplastic syndrome associated with isolated del(5q), refractory anemia with excess blasts in transformation, myelodysplastic syndrome with ring sideroblasts, myelodysplastic syndrome with multilineage dysplasia, myelodysplastic syndrome with excess blasts, familial monosomy 7 syndrome

Subtypes (1): refractory cytopenia of childhood

Genetics & variants

GWAS landscape

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

Variant details and genetic-evidence tiers

No tiered GWAS variants or ClinVar records for this disease.

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 80 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

GeneOrphanet IDRare disease
RUNX1Orphanet:102724Acute myeloid leukemia with t(8;21)(q22;q22) translocation
RUNX1Orphanet:521Chronic myeloid leukemia
RUNX1Orphanet:71290Familial platelet disorder with associated myeloid malignancy
RUNX1Orphanet:98850Aggressive systemic mastocytosis
SF3B1Orphanet:39044Uveal melanoma
SF3B1Orphanet:75564Acquired idiopathic sideroblastic anemia
SRSF2Orphanet:98823Chronic myelomonocytic leukemia
SRSF2Orphanet:98849Systemic mastocytosis with associated hematologic neoplasm
SRSF2Orphanet:98850Aggressive systemic mastocytosis
TP53Orphanet:1333Familial pancreatic carcinoma
TP53Orphanet:145Hereditary breast and/or ovarian cancer syndrome
TP53Orphanet:1501Adrenocortical carcinoma
TP53Orphanet:210159Adult hepatocellular carcinoma
TP53Orphanet:251576Gliosarcoma
TP53Orphanet:251579Giant cell glioblastoma
TP53Orphanet:251899Choroid plexus carcinoma
TP53Orphanet:2807Papilloma of choroid plexus
TP53Orphanet:293199Pleomorphic rhabdomyosarcoma
TP53Orphanet:3318Essential thrombocythemia
TP53Orphanet:524Li-Fraumeni syndrome
TP53Orphanet:52688Myelodysplastic syndrome
TP53Orphanet:585909B-lymphoblastic leukemia/lymphoma with t(9;22)(q34.1;q11.2)
TP53Orphanet:667662Breast implant-associated anaplastic large cell lymphoma
TP53Orphanet:668Osteosarcoma
TP53Orphanet:67038B-cell chronic lymphocytic leukemia
TP53Orphanet:70573Small cell lung cancer
TP53Orphanet:96253Cushing disease
TP53Orphanet:99756Alveolar rhabdomyosarcoma
TP53Orphanet:99757Embryonal rhabdomyosarcoma
ASXL1Orphanet:86845Acute myeloid leukaemia with myelodysplasia-related features
ASXL1Orphanet:97297Bohring-Opitz syndrome
ASXL1Orphanet:98823Chronic myelomonocytic leukemia
ASXL1Orphanet:98849Systemic mastocytosis with associated hematologic neoplasm
ASXL1Orphanet:98850Aggressive systemic mastocytosis
BCOROrphanet:2712Oculofaciocardiodental syndrome
BCOROrphanet:457246Clear cell sarcoma of kidney
BCOROrphanet:520Acute promyelocytic leukemia
BCOROrphanet:568Microphthalmia, Lenz type
TET2Orphanet:100019Myelodysplastic neoplasm with increased blasts type 1
TET2Orphanet:100020Myelodysplastic neoplasm with increased blasts type 2
TET2Orphanet:3318Essential thrombocythemia
TET2Orphanet:664729EBV-induced lymphoproliferative disease due to TET2 deficiency
TET2Orphanet:75564Acquired idiopathic sideroblastic anemia
TET2Orphanet:824Primary myelofibrosis
TET2Orphanet:86845Acute myeloid leukaemia with myelodysplasia-related features
TET2Orphanet:98826Myelodysplastic neoplasm with low blasts
TET2Orphanet:98849Systemic mastocytosis with associated hematologic neoplasm
TET2Orphanet:98850Aggressive systemic mastocytosis
DNMT3AOrphanet:276621Sporadic pheochromocytoma/secreting paraganglioma
DNMT3AOrphanet:404443Tatton-Brown-Rahman syndrome

Cohort genes → proteins

13 cohort genes, 13 distinct canonical proteins.

Evidence partition

SubsetGenes
civic_only13

Cohort genes (full)

SymbolHGNCEnsemblUniProtNameEvidence
RUNX1HGNC:10471ENSG00000159216Q01196Runt-related transcription factor 1civic_evidence
SF3B1HGNC:10768ENSG00000115524O75533Splicing factor 3B subunit 1civic_evidence
SRSF2HGNC:10783ENSG00000161547Q01130Serine/arginine-rich splicing factor 2civic_evidence
TP53HGNC:11998ENSG00000141510P04637Cellular tumor antigen p53civic_evidence
U2AF1HGNC:12453ENSG00000160201Q01081Splicing factor U2AF 35 kDa subunitcivic_evidence
ASXL1HGNC:18318ENSG00000171456Q8IXJ9Polycomb group protein ASXL1civic_evidence
BCORHGNC:20893ENSG00000183337Q6W2J9BCL-6 corepressorcivic_evidence
TET2HGNC:25941ENSG00000168769Q6N021Methylcytosine dioxygenase TET2civic_evidence
DNMT3AHGNC:2978ENSG00000119772Q9Y6K1DNA (cytosine-5)-methyltransferase 3Acivic_evidence
EZH2HGNC:3527ENSG00000106462Q15910Histone-lysine N-methyltransferase EZH2civic_evidence
FLT3HGNC:3765ENSG00000122025P36888Receptor-type tyrosine-protein kinase FLT3civic_evidence
IDH1HGNC:5382ENSG00000138413O75874Isocitrate dehydrogenase [NADP] cytoplasmiccivic_evidence
IDH2HGNC:5383ENSG00000182054P48735Isocitrate dehydrogenase [NADP], mitochondrialcivic_evidence

Cohort function summary

Lead sentence per gene, UniProt-curated.

SymbolProtein nameFunction (lead sentence)
RUNX1Runt-related transcription factor 1Forms the heterodimeric complex core-binding factor (CBF) with CBFB.
SF3B1Splicing factor 3B subunit 1Component of the 17S U2 SnRNP complex of the spliceosome, a large ribonucleoprotein complex that removes introns from transcribed pre-mRNAs.
SRSF2Serine/arginine-rich splicing factor 2Necessary for the splicing of pre-mRNA.
TP53Cellular tumor antigen p53Multifunctional transcription factor that induces cell cycle arrest, DNA repair or apoptosis upon binding to its target DNA sequence.
U2AF1Splicing factor U2AF 35 kDa subunitPlays a critical role in both constitutive and enhancer-dependent splicing by mediating protein-protein interactions and protein-RNA interactions required for accurate 3’-splice site selection.
ASXL1Polycomb group protein ASXL1Probable Polycomb group (PcG) protein involved in transcriptional regulation mediated by ligand-bound nuclear hormone receptors, such as retinoic acid receptors (RARs) and peroxisome proliferator-activated receptor gamma (PPARG).
BCORBCL-6 corepressorTranscriptional corepressor.
TET2Methylcytosine dioxygenase TET2Dioxygenase that catalyzes the conversion of the modified genomic base 5-methylcytosine (5mC) into 5-hydroxymethylcytosine (5hmC) and plays a key role in active DNA demethylation.
DNMT3ADNA (cytosine-5)-methyltransferase 3ARequired for genome-wide de novo methylation and is essential for the establishment of DNA methylation patterns during development.
EZH2Histone-lysine N-methyltransferase EZH2Catalytic subunit of the PRC2/EED-EZH2 complex, a Polycomb group (PcG) complex that methylates ‘Lys-9’ (H3K9me) and ‘Lys-27’ (H3K27me) of histone H3, leading to transcriptional repression of the affected target gene.
FLT3Receptor-type tyrosine-protein kinase FLT3Tyrosine-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.
IDH1Isocitrate dehydrogenase [NADP] cytoplasmicCatalyzes 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.
IDH2Isocitrate dehydrogenase [NADP], mitochondrialPlays a role in intermediary metabolism and energy production.

Protein-family classification

Druggable: 5 · Difficult: 4 · Unknown: 4 · 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.

FamilyGenesFoldFDR
Complement120.6×0.264
Enzyme (other)32.8×0.264
Transcription factor31.9×0.405
Kinase12.1×0.570
Scaffold/PPI11.3×0.647
Other/Unknown40.6×0.982

Per-gene assignment

SymbolFamilyDruggable?ECInterPro (top 3)
RUNX1Transcription factornoAML1_Runt, p53-like_TF_DNA-bd_sf, p53/RUNT-type_TF_DNA-bd_sf
SF3B1Other/UnknownnoARM-like, SF3b_su1, ARM-type_fold
SRSF2Other/UnknownnoRRM_dom, RRM_euk-type, Nucleotide-bd_a/b_plait_sf
TP53Transcription factornop53_tumour_suppressor, p53-like_TF_DNA-bd_sf, p53_tetrameristn
U2AF1Transcription factornoRRM_dom, Znf_CCCH, RRM_euk-type
ASXL1Other/UnknownnoAsxl_HARE-HTH, ASX/ASX-like, ASX-like_PHD
BCORScaffold/PPInoAnkyrin_rpt, BCOR, PUFD
TET2Other/Unknownno2OGFeDO_JBP1/TET_oxygenase_dom, TET1/2/3, TET_oxygenase
DNMT3AComplementyes2.1.1.37PWWP_dom, C5_MeTfrase, C5_DNA_meth_AS
EZH2Enzyme (other)yes2.1.1.356SANT/Myb, SET_dom, EZH1/EZH2_N
FLT3Kinaseyes2.7.10.1Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom, Tyr_kinase_rcpt_3_CS
IDH1Enzyme (other)yes1.1.1.42Isocitrate_DH_NADP, IsoCit/isopropylmalate_DH_CS, IsoPropMal-DH-like_dom
IDH2Enzyme (other)yes1.1.1.42Isocitrate_DH_NADP, IsoCit/isopropylmalate_DH_CS, IsoPropMal-DH-like_dom

Expression context

Cohort genes with no expression data: 0.

13 cohort genes are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

BucketGenes
narrow (1-5 tissues)0
moderate (6-20)0
broad (>20)13
unknown0

Top tissues across cohort

TissueCohort genes
ventricular zone4
ganglionic eminence4
epithelium of nasopharynx2
tibia2
embryo2
tendon of biceps brachii2
adrenal tissue2
sural nerve2
epithelium of bronchus1
mucosa of paranasal sinus1
olfactory segment of nasal mucosa1
adenohypophysis1
bone marrow1
left uterine tube1
sperm1
buccal mucosa cell1
cortical plate1
amniotic fluid1
palpebral conjunctiva1
cerebellar cortex1

Per-gene tissue summary (top 30)

SymbolBgee breadthFANTOM5 breadthSCXATop tissues
RUNX1253ubiquitousmarkerolfactory segment of nasal mucosa, epithelium of bronchus, mucosa of paranasal sinus
SF3B1295ubiquitousmarkertibia, ventricular zone, epithelium of nasopharynx
SRSF2295ubiquitousmarkertibia, embryo, tendon of biceps brachii
TP53223ubiquitousmarkerventricular zone, ganglionic eminence, tendon of biceps brachii
U2AF1134ubiquitousmarkeradenohypophysis, left uterine tube, bone marrow
ASXL1294ubiquitousmarkersural nerve, sperm, adrenal tissue
BCOR265ubiquitousmarkerbuccal mucosa cell, ganglionic eminence, cortical plate
TET2249ubiquitousmarkerpalpebral conjunctiva, amniotic fluid, epithelium of nasopharynx
DNMT3A223ubiquitousmarkersural nerve, ganglionic eminence, ventricular zone
EZH2216ubiquitousmarkerganglionic eminence, ventricular zone, embryo
FLT3166broadmarkermale germ line stem cell (sensu Vertebrata) in testis, cerebellar hemisphere, cerebellar cortex
IDH1294ubiquitousmarkercorpus epididymis, jejunal mucosa, adrenal tissue
IDH2292ubiquitousmarkerapex of heart, gastrocnemius, hindlimb stylopod muscle

Protein interactions among cohort

Intra-cohort edges: 29.

Hub genes (top 10 by interactor count)

SymbolInteractor count
TP5322,736
EZH29,646
IDH15,464
RUNX14,994
IDH24,912
DNMT3A4,771
SF3B14,582
FLT33,570
SRSF23,311
TET22,965

Intra-cohort edges

ABSources
ASXL1DNMT3Astring_interaction
ASXL1EZH2intact, string_interaction
ASXL1FLT3string_interaction
ASXL1IDH1string_interaction
ASXL1IDH2string_interaction
ASXL1RUNX1string_interaction
ASXL1SRSF2string_interaction
ASXL1TET2string_interaction
ASXL1U2AF1string_interaction
DNMT3AEZH2intact, string_interaction
DNMT3AFLT3string_interaction
DNMT3ATET2string_interaction
DNMT3AU2AF1string_interaction
EZH2TET2string_interaction
FLT3IDH1string_interaction
FLT3IDH2string_interaction
FLT3RUNX1string_interaction
FLT3TET2string_interaction
IDH1IDH2biogrid_interaction
IDH1TET2string_interaction
IDH1TP53string_interaction
IDH1U2AF1string_interaction
IDH2TET2string_interaction
RUNX1SRSF2string_interaction
SF3B1SRSF2string_interaction
SF3B1U2AF1string_interaction
SRSF2TET2string_interaction
SRSF2U2AF1intact, string_interaction
TET2U2AF1string_interaction

Structural data

PDB: 13 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

SymbolUniProtPDB entries
TP53P04637313
SF3B1O7553374
IDH1O7587461
DNMT3AQ9Y6K143
EZH2Q1591038
FLT3P3688811
IDH2P4873511
TET2Q6N0216
RUNX1Q011965
BCORQ6W2J95
SRSF2Q011304
ASXL1Q8IXJ94
U2AF1Q010811

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 158. Enrichment computed across 13 evidence-associated genes (12 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 12 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

PathwayCohort genesFoldFDRSample cohort genes
Abnormal conversion of 2-oxoglutarate to 2-hydroxyglutarate1951.7×0.009IDH1
FLT3 mutants bind TKIs1951.7×0.009FLT3
KW2449-resistant FLT3 mutants1951.7×0.009FLT3
semaxanib-resistant FLT3 mutants1951.7×0.009FLT3
crenolanib-resistant FLT3 mutants1951.7×0.009FLT3
gilteritinib-resistant FLT3 mutants1951.7×0.009FLT3
lestaurtinib-resistant FLT3 mutants1951.7×0.009FLT3
midostaurin-resistant FLT3 mutants1951.7×0.009FLT3
pexidartinib-resistant FLT3 mutants1951.7×0.009FLT3
ponatinib-resistant FLT3 mutants1951.7×0.009FLT3
quizartinib-resistant FLT3 mutants1951.7×0.009FLT3
sorafenib-resistant FLT3 mutants1951.7×0.009FLT3
sunitinib-resistant FLT3 mutants1951.7×0.009FLT3
tandutinib-resistant FLT3 mutants1951.7×0.009FLT3
linifanib-resistant FLT3 mutants1951.7×0.009FLT3
tamatinib-resistant FLT3 mutants1951.7×0.009FLT3
Loss of function of TP53 in cancer due to loss of tetramerization ability1951.7×0.009TP53
mRNA Polyadenylation322.0×0.009SF3B1, SRSF2, U2AF1
mRNA Splicing - Major Pathway313.7×0.010SF3B1, SRSF2, U2AF1
mRNA Splicing - Minor Pathway237.3×0.010SF3B1, SRSF2
mRNA 3’-end processing232.8×0.012SRSF2, U2AF1
NADPH regeneration1475.8×0.013IDH1
Regulation of TP53 Expression1475.8×0.013TP53
Regulation of PTEN gene transcription229.7×0.013TP53, EZH2
Dengue Virus-Host Interactions311.4×0.013SF3B1, SRSF2, U2AF1
Defective pyroptosis226.1×0.015DNMT3A, EZH2
Transport of Mature mRNA derived from an Intron-Containing Transcript225.4×0.015SRSF2, U2AF1
PRC2 methylates histones and DNA225.4×0.015DNMT3A, EZH2
RUNX3 regulates RUNX1-mediated transcription1317.2×0.017RUNX1
NFE2L2 regulating TCA cycle genes1317.2×0.017IDH1

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 13 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO termCohort genesFoldFDRSample cohort genes
glyoxylate cycle21296.3×1e-04IDH1, IDH2
isocitrate metabolic process2518.5×7e-04IDH1, IDH2
regulatory ncRNA-mediated heterochromatin formation2288.1×0.001DNMT3A, EZH2
negative regulation of glial cell proliferation2259.3×0.001TP53, IDH2
NADP+ metabolic process2235.7×0.001IDH1, IDH2
bone marrow development2235.7×0.001TP53, ASXL1
hemopoiesis361.7×0.001RUNX1, ASXL1, FLT3
2-oxoglutarate metabolic process2144.0×0.003IDH1, IDH2
myeloid cell differentiation299.7×0.005RUNX1, TET2
positive regulation of MAP kinase activity299.7×0.005EZH2, FLT3
DNA methylation-dependent constitutive heterochromatin formation283.6×0.006DNMT3A, EZH2
tricarboxylic acid cycle278.6×0.006IDH1, IDH2
liver regeneration278.6×0.006EZH2, FLT3
RNA splicing320.4×0.007SF3B1, SRSF2, U2AF1
negative regulation of transcription by RNA polymerase II56.8×0.009RUNX1, TP53, BCOR, DNMT3A, EZH2
negative regulation of helicase activity11296.3×0.009TP53
regulation of phospholipid catabolic process11296.3×0.009IDH1
specification of axis polarity11296.3×0.009BCOR
cellular response to actinomycin D11296.3×0.009TP53
regulation of intrinsic apoptotic signaling pathway by p53 class mediator11296.3×0.009TP53
negative regulation of G1 to G0 transition11296.3×0.009TP53
regulation of connective tissue replacement11296.3×0.009RUNX1
negative regulation of DNA-templated transcription49.7×0.009TP53, BCOR, DNMT3A, EZH2
regulation of kidney size1648.1×0.012ASXL1
positive regulation of mitochondrial membrane permeability1648.1×0.012TP53
hepatocyte homeostasis1648.1×0.012EZH2
negative regulation of tooth mineralization1648.1×0.012BCOR
regulation of phospholipid biosynthetic process1648.1×0.012IDH1
oligodendrocyte apoptotic process1648.1×0.012TP53
negative regulation of glial cell migration1648.1×0.012IDH2

Therapeutics

Drug target analysis

Approved (phase 4): 7 · Phase ≥3: 7 · Phased (≥1): 10 · Undrugged: 3

Druggability breadth: 12 of 13 evidence-associated genes (92%) 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.

SymbolExample approved molecule
RUNX1APOMORPHINE HYDROCHLORIDE
TP53NITROFURANTOIN
TET2VADADUSTAT
EZH2TAZEMETOSTAT
FLT3PONATINIB
IDH1ENASIDENIB
IDH2ENASIDENIB

Top cohort targets by molecule count

SymbolMoleculesMax phase
TP531964
FLT31434
IDH1104
IDH274
EZH264
TET234
RUNX124
SF3B112
SRSF212
U2AF112

Drugs targeting cohort genes (top 30)

MoleculeMax phaseTargets in cohort
APOMORPHINE HYDROCHLORIDE4RUNX1
NITROFURANTOIN4TP53
DIOSMIN4TP53
VERTEPORFIN4TP53
CANDESARTAN CILEXETIL4TP53
DIENESTROL4TP53
CLOTRIMAZOLE4TP53
COLCHICINE4TP53
NABUMETONE4TP53
SALMETEROL XINAFOATE4TP53
AMIODARONE HYDROCHLORIDE4TP53
FURAZOLIDONE4TP53
AMOXAPINE4TP53
RALOXIFENE HYDROCHLORIDE4TP53
NICARDIPINE HYDROCHLORIDE4TP53
SULCONAZOLE NITRATE4TP53
PYRITHIONE ZINC4TP53
LACTIC ACID4TP53
OXYMETHOLONE4TP53
CHLOROXINE4TP53
PROPIOLACTONE4TP53
CLOMIPRAMINE HYDROCHLORIDE4TP53
PHENYL AMINOSALICYLATE4TP53
THIORIDAZINE HYDROCHLORIDE4TP53
AMITRIPTYLINE HYDROCHLORIDE4TP53
ETHOPROPAZINE HYDROCHLORIDE4TP53
MECHLORETHAMINE HYDROCHLORIDE4TP53
ECONAZOLE NITRATE4TP53
TRIFLUPROMAZINE HYDROCHLORIDE4TP53
PROCHLORPERAZINE EDISYLATE4TP53

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 5.

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

SymbolAssaysType breakdown
FLT33,132Binding:3096, Functional:24, ADMET:8, Toxicity:4
TP53869Binding:775, ADMET:83, Functional:10, Toxicity:1
EZH2839Binding:833, Functional:6
IDH1488Binding:475, Functional:12, ADMET:1
DNMT3A120Binding:118, ADMET:1, Functional:1
IDH284Binding:84
TET224Binding:24
SF3B122Binding:22
RUNX120Binding:17, Functional:3
SRSF28Binding:8
U2AF18Binding:8
BCOR2Binding:2

Cohort enzymes (BRENDA EC)

SymbolEC numbersNames
DNMT3A2.1.1.37DNA (cytosine-5-)-methyltransferase
EZH22.1.1.356[histone H3]-lysine27 N-trimethyltransferase
FLT32.7.10.1receptor protein-tyrosine kinase
IDH11.1.1.42isocitrate dehydrogenase (NADP+)
IDH21.1.1.42isocitrate dehydrogenase (NADP+)

Cohort genes with high screening signal

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

SymbolChEMBL assays
TP53869
DNMT3A120
EZH2839
FLT33,132
IDH1488

Pharmacogenomics

Cohort genes with a PharmGKB record: 13; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

30 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

CompoundMax phaseCohort target (bioactivity)
APOMORPHINE HYDROCHLORIDE4RUNX1
NITROFURANTOIN4TP53
DIOSMIN4TP53
VERTEPORFIN4TP53
CANDESARTAN CILEXETIL4TP53
DIENESTROL4TP53
CLOTRIMAZOLE4TP53
COLCHICINE4TP53
NABUMETONE4TP53
SALMETEROL XINAFOATE4TP53
AMIODARONE HYDROCHLORIDE4TP53
FURAZOLIDONE4TP53
AMOXAPINE4TP53
RALOXIFENE HYDROCHLORIDE4TP53
NICARDIPINE HYDROCHLORIDE4TP53
SULCONAZOLE NITRATE4TP53
PYRITHIONE ZINC4TP53
LACTIC ACID4TP53
OXYMETHOLONE4TP53
CHLOROXINE4TP53
PROPIOLACTONE4TP53
CLOMIPRAMINE HYDROCHLORIDE4TP53
PHENYL AMINOSALICYLATE4TP53
THIORIDAZINE HYDROCHLORIDE4TP53
AMITRIPTYLINE HYDROCHLORIDE4TP53
ETHOPROPAZINE HYDROCHLORIDE4TP53
MECHLORETHAMINE HYDROCHLORIDE4TP53
ECONAZOLE NITRATE4TP53
TRIFLUPROMAZINE HYDROCHLORIDE4TP53
PROCHLORPERAZINE EDISYLATE4TP53

Druggability pyramid

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

TierDefinitionGenesSymbols
AApproved (phase 4 drug)7RUNX1, TP53, TET2, EZH2, FLT3, IDH1, IDH2
BPhased (≥1) drug, not yet approved3SF3B1, SRSF2, U2AF1
CDruggable family + PDB, no drug1DNMT3A
DDruggable family + AlphaFold only, no drug0
EDifficult family or no structure, no drug2ASXL1, BCOR

Undrugged target profiles

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

SymbolChEMBL assaysDrugged partners (top 3)
DNMT3A120EZH2
ASXL10EZH2, TET2
BCOR2—

Clinical trials & evidence

Clinical trials

Clinical trials: 790.

Phase distribution (across all retrieved trials)

PhaseTrials
PHASE2308
PHASE1198
PHASE1/PHASE2112
Not specified103
PHASE345
PHASE2/PHASE311
PHASE49
EARLY_PHASE14

Top trials by phase / activity

NCTPhaseStatusTitle
NCT00452660PHASE4COMPLETEDEvaluation the Effect of Exjade on Oxidative Stress in Low Risk Myelodysplastic Syndrome Patients With Iron Over Load
NCT00487448PHASE4COMPLETEDSMD_FLAG-IDA_98: FLAG-IDA in Induction Treatment of High Risk Myelodysplastic Syndromes or Secondary Acute Myeloblastic Leukemia
NCT00488436PHASE4COMPLETEDAntithymocyte Globulin and Cyclosporine in Treating Low Risk Patients With Myelodysplastic Syndrome
NCT01200355PHASE4COMPLETEDPosaconazole Versus Micafungin for Prophylaxis Against Invasive Fungal Infections During Neutropenia in Patients Undergoing Chemotherapy for Acute Myelogenous Leukemia, Acute Lymphocytic Leukemia or Myelodysplastic Syndrome
NCT01250951PHASE4COMPLETEDThis Study Will Evaluate Efficacy and Safety of Deferasirox in Patients With Myelodysplastic Syndromes (MDS), Thalassemia and Rare Anemia Types Having Transfusion-induced Iron Overload.
NCT01326845PHASE4TERMINATEDMyelodysplastic Syndrome (MDS) Gastrointestinal (GI) Tolerability Study
NCT01339988PHASE4UNKNOWNBusulfan and Cyclophosphamide Instead of Total Boby Irradiation (TBI) and Cyclophosphamide for Hematological Malignancies Hematocrit (HCT)
NCT02013102PHASE4UNKNOWNA Phase Ⅳ Study of Decitabine in Myelodysplastic Syndrome
NCT03335943PHASE4UNKNOWNMyelodysplastic Syndrome–CDA-2 Hematological Improvement National Affirmation Study
NCT00843882PHASE3ACTIVE_NOT_RECRUITINGLenalidomide With or Without Epoetin Alfa in Treating Patients With Myelodysplastic Syndrome and Anemia
NCT02521493PHASE3ACTIVE_NOT_RECRUITINGResponse-Based Chemotherapy in Treating Newly Diagnosed Acute Myeloid Leukemia or Myelodysplastic Syndrome in Younger Patients With Down Syndrome
NCT04401748PHASE3ACTIVE_NOT_RECRUITINGStudy Of Venetoclax Tablet With Intravenous or Subcutaneous Azacitidine to Assess Change in Disease Activity In Adult Participants With Newly Diagnosed Higher-Risk Myelodysplastic Syndrome
NCT04708054PHASE2/PHASE3RECRUITINGVenetoclax to Improve Outcomes of Fractionated Busulfan Regimen in Patients With High-Risk AML and MDS
NCT05316701PHASE3ACTIVE_NOT_RECRUITINGPrecision-T: A Randomized Study of Orca-T in Recipients Undergoing Allogeneic Transplantation for Hematologic Malignancies
NCT05457556PHASE3ACTIVE_NOT_RECRUITINGMismatched Related Donor Versus Matched Unrelated Donor Stem Cell Transplantation for Children, Adolescents, and Young Adults With Acute Leukemia or Myelodysplastic Syndrome
NCT05674539PHASE3ENROLLING_BY_INVITATIONReduced Intensity Conditioning Regimens for Acute Myeloid Leukemia and Myelodysplastic Syndrome
NCT06756152PHASE2/PHASE3RECRUITINGPreventing of GVHD with Post-transplantation Cyclophosphamide, Abatacept, Vedolizumab and Ruxolitinib At Children and Young Adults with Hemoblastosis
NCT07422480PHASE3RECRUITINGA Study to Compare Elritercept With Epoetin Alfa to Treat Anemia in Adults With Very Low, Low, or Intermediate Risk Myelodysplastic Syndromes (MDS) Who Need Regular Blood Transfusions
NCT00002798PHASE3COMPLETEDCombination Chemotherapy With or Without Bone Marrow Transplantation in Treating Children With Acute Myelogenous Leukemia or Myelodysplastic Syndrome
NCT00006363PHASE3COMPLETEDCombination Chemotherapy With or Without PSC 833, Peripheral Stem Cell Transplantation, and/or Interleukin-2 in Treating Patients With Acute Myeloid Leukemia
NCT00043381PHASE3COMPLETEDDecitabine Versus Supportive Care in Adults With Advanced-stage MDS
NCT00152139PHASE3COMPLETEDStem Cell Transplantation for Patients With Hematologic Malignancies
NCT00186823PHASE3COMPLETEDHaploidentical Stem Cell Transplantation for Patients With Hematologic Malignancies
NCT00226512PHASE3WITHDRAWNTo Determine the Role of Adding Campath-1H or ATG Given In-vivo in Addition to Fludarabine and Low Dose Busulfex on Outcome in Patients Treated With Reduced Intensity Conditioning
NCT00300664PHASE2/PHASE3COMPLETEDA Randomized Trial of Human Growth Hormone (hGH) vs Placebo in Intensively Treated Haemato-Oncology Patients.
NCT00306332PHASE3TERMINATEDT-cell and B-cell Depletion in Allogeneic Peripheral Blood Stem Cell Transplantation
NCT00322101PHASE3COMPLETEDLow-Dose or High-Dose Conditioning Followed by Peripheral Blood Stem Cell Transplant in Treating Patients With Myelodysplastic Syndrome or Acute Myelogenous Leukemia
NCT00369317PHASE3COMPLETEDCombination Chemotherapy in Treating Young Patients With Down Syndrome and Acute Myeloid Leukemia or Myelodysplastic Syndromes
NCT00412360PHASE3COMPLETEDSingle vs Double Umbilical Cord Blood Transplants in Children With High Risk Leukemia and Myelodysplasia (BMT CTN 0501)
NCT00422890PHASE3COMPLETEDTreatment of Imminent Haematological Relapse in Patients With AML and MDS Following Allogeneic Stem Cell Transplantation With 5-azacitidine (Vidaza®)
NCT00450450PHASE3COMPLETEDDonor Bone Marrow Transplant With or Without G-CSF in Treating Young Patients With Hematologic Cancer or Other Diseases
NCT00469144PHASE3COMPLETEDIV Busulfan With Allo-BMT: Study for Patients With Acute Myelogenous Leukemia and Myelodysplastic Syndrome
NCT00656448PHASE3COMPLETEDA Randomized Trial of Procrit vs. No Procrit in AML and High Risk MDS
NCT00774280PHASE3COMPLETEDBusulfan Plus Cyclophosphamide vs Fludarabine as a Conditioning Regimen
NCT00822393PHASE3COMPLETEDClinical Phase III Trial Treosulfan-based Conditioning Versus Reduced-intensity Conditioning (RIC)
NCT00967343PHASE2/PHASE3TERMINATEDEfficacy and Safety of a Donor Lymphocyte Preparation Depleted of Functional Host Alloreactive T-cells (ATIR) in Patients Undergoing a Peripheral Blood Stem Cell Transplant From a Related, Haploidentical Donor
NCT01020175PHASE3COMPLETEDPeripheral Blood (PB) Versus Bone Marrow (BM) in Allogeneic Stem Cell Transplantation
NCT01188798PHASE3COMPLETEDMethotrexate or Pentostatin for Graft-versus-host Disease Prophylaxis in Risk-adapted Allogeneic Bone Marrow Transplantation for Hematologic Malignancies
NCT01196715PHASE3COMPLETEDComparison Study of Standard Care Against Combination of Growth Factors Agents for Low-risk Myelodysplastic Syndromes
NCT01231412PHASE3COMPLETEDGraft-Versus-Host Disease Prophylaxis in Treating Patients With Hematologic Malignancies Undergoing Unrelated Donor Peripheral Blood Stem Cell Transplant

Drugs tested across these trials (top 30)

MoleculeMax phaseTrials referencing
FLUDARABINE PHOSPHATE4140
VENETOCLAX440
DECITABINE421
CLOFARABINE417
BUSULFAN412
GEMTUZUMAB OZOGAMICIN411
MITOXANTRONE411
PLERIXAFOR410
TREOSULFAN410
AZACITIDINE49
CLADRIBINE49
CYCLOPHOSPHAMIDE ANHYDROUS46
DEFERASIROX46
ENASIDENIB45
IDARUBICIN45
QUIZARTINIB45
DAUNORUBICIN HYDROCHLORIDE44
MIDOSTAURIN44
OLUTASIDENIB44
PALIFERMIN44
THIOTEPA44
TRETINOIN44
VORINOSTAT44
ALEMTUZUMAB43
ARSENIC TRIOXIDE43
ASPARAGINASE43
CYTARABINE43
GILTERITINIB43
GLASDEGIB43
IVOSIDENIB43

Precision-medicine subtype map (CIViC)

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

Molecular subtypeTherapyEffectLevelCIViC
TP53 MutationAzacitidine + EprenetapoptSensitivity/ResponseCIViC BEID12029

About this page

Generated deterministically by Sugi Atlas from primary biomedical databases via BioBTree. Every record on this page traces to a primary source.

Generated
Atlas version
v1.1.2
BioBTree
v2.0.2

Sources 69

This page pulls from 69 datasets indexed by BioBTree:

alphafoldantibodybgeebgee_evidencebindingdbbiogrid_interactionbrendabrenda_kineticscellosauruschembl_activitychembl_assaychembl_documentchembl_moleculechembl_targetcivic_evidenceclingen_dosageclinical_trialsclinvarctd_gene_interactiondepmapdiamond_similarityefoensemblentrezesm2_similarityfantom5_genefantom5_promotergardgenccgenerifgogtopdbgtopdb_interactiongwasgwas_studyhgncintactinterpromedgenmeshmimmondomondochildmondoparentncitorphanetpatentpatent_compoundpdbpfampharmgkb_clinicalpharmgkb_genepharmgkb_guidelinepharmgkb_variantpubchempubchem_activitypubchem_assayreactomerefseqrhearnacentralscxa_expressionscxa_gene_experimentsignorstring_interactiontranscriptufeatureumlsuniprot