Hereditary thrombocytopenia and hematologic cancer predisposition syndrome

Summary

Hereditary thrombocytopenia and hematologic cancer predisposition syndrome (MONDO:0011071) is a cancer caused by RUNX1 (GenCC Definitive), with 5 cohort genes (2 CIViC-evidence somatic drivers; 1,535 ClinVar predisposition records).

At a glance

• Classification: Cancer
• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Causal gene: RUNX1 (GenCC Definitive)
• Cohort genes: 5
• ClinVar variants: 1,535

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		259	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Identifiers

Disease identifiers

Field	Value
Canonical name	hereditary thrombocytopenia and hematologic cancer predisposition syndrome
Mondo ID	MONDO:0011071
MeSH	C563324
Orphanet	71290
NCIT	C162696
SNOMED CT	725034002
GARD	0010352
Is cancer (heuristic)	yes

Also known as: familial platelet syndrome with predisposition to acute myelogenous leukaemia · familial thrombocytopenia with propensity to acute myelogenous leukaemia · hereditary thrombocytopenia and hematologic cancer predisposition syndrome · thrombocytopenia, familial, with propensity to acute myelogenous leukaemia

Data availability: 1,535 ClinVar variants · 1,593 ClinGen variant curations · 4 GenCC gene-disease records.

Disease family

An umbrella term covering 2 Mondo subtypes.

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › hereditary neoplastic syndrome › hereditary thrombocytopenia and hematologic cancer predisposition syndrome

Related subtypes (116): mosaic variegated aneuploidy syndrome, tuberous sclerosis, hereditary breast ovarian cancer syndrome, hereditary multiple osteochondromas, nevoid basal cell carcinoma syndrome, leukemia, chronic lymphocytic, susceptibility to, 2, blue rubber bleb nevus, cherubism, Beckwith-Wiedemann syndrome, multiple self-healing squamous epithelioma, erythroleukemia, familial, susceptibility to, goiter, multinodular 1, with or without Sertoli-Leydig cell tumors, hyperparathyroidism 2 with jaw tumors, Kaposi sarcoma, susceptibility to, hereditary leiomyomatosis and renal cell cancer, susceptibility to uveal melanoma, melanoma and neural system tumor syndrome, nasopharyngeal carcinoma, susceptibility to, 2, WAGR syndrome, neuroblastoma, susceptibility to, 1, Rothmund-Thomson syndrome, mismatch repair cancer syndrome 1, Wiskott-Aldrich syndrome, N syndrome, prostate cancer/brain cancer susceptibility, Brooke-Spiegler syndrome, pancreatic cancer, susceptibility to, 1, Carney-Stratakis syndrome, nasopharyngeal carcinoma, susceptibility to, 1, ovarian cancer, susceptibility to, 1, colorectal cancer, susceptibility to, 1, lung cancer susceptibility 1, leukemia, chronic lymphocytic, susceptibility to, 1, Kostmann syndrome, colorectal cancer, susceptibility to, 2, colorectal cancer, susceptibility to, 3, colorectal cancer, susceptibility to, 5, colorectal cancer, susceptibility to, 6, colorectal cancer, susceptibility to, 7, leukemia, chronic lymphocytic, susceptibility to, 3, leukemia, chronic lymphocytic, susceptibility to, 4, leukemia, chronic lymphocytic, susceptibility to, 5, lung cancer susceptibility 3, colorectal cancer, susceptibility to, 8, colorectal cancer, susceptibility to, 9, colorectal cancer, susceptibility to, 10, colorectal cancer, susceptibility to, 11, lung cancer susceptibility 4, neuroblastoma, susceptibility to, 3, neuroblastoma, susceptibility to, 4, neuroblastoma, susceptibility to, 5, neuroblastoma, susceptibility to, 6, leukemia, acute lymphocytic, susceptibility to, 1, leukemia, acute lymphocytic, susceptibility to, 2, lung cancer susceptibility 5, BAP1-related tumor predisposition syndrome, familial cutaneous telangiectasia and oropharyngeal predisposition cancer syndrome, Maffucci syndrome, basal cell carcinoma, susceptibility to, 7, colorectal cancer, susceptibility to, 12, leukemia, acute lymphoblastic, susceptibility to, 3, cholangiocarcinoma, susceptibility to, progeroid features-hepatocellular carcinoma predisposition syndrome, neuroblastoma, susceptibility to, 7, DDX41-related hematologic malignancy predisposition syndrome, nasopharyngeal carcinoma, susceptibility to, 3, familial isolated hyperparathyroidism, intestinal polyposis syndrome, dyskeratosis congenita, familial rhabdoid tumor, multiple endocrine neoplasia, hereditary pheochromocytoma-paraganglioma, PTEN hamartoma tumor syndrome, familial multiple fibrofolliculoma, hereditary retinoblastoma, familial atypical multiple mole melanoma syndrome, hereditary nonpolyposis colon cancer, Li-Fraumeni syndrome, Cobb syndrome, neurofibromatosis, susceptibility to familial cutaneous melanoma, pancreatic cancer, susceptibility to, 5, leukemia, acute myeloid, susceptibility to, diffuse gastric and lobular breast cancer syndrome with or without cleft lip and/or palate, glioma susceptibility, hemangioma, capillary infantile, susceptibility to, CDH1-related diffuse gastric and lobular breast cancer syndrome, NTHL1-deficiency tumor predisposition syndrome, SAMD9-related spectrum and myeloid neoplasm risk, neuroblastoma, susceptibility to, 2, BARD1-related cancer predisposition, BRCA1-related cancer predisposition, BRCA2-related cancer predisposition, ATM-related cancer predisposition, CHEK2-related cancer predisposition, PALB2-related cancer predisposition, RAD51C-related cancer predisposition, RAD51D-related cancer predisposition, Li-fraumeni-like syndrome, breast cancer, familial, susceptibility to, 1, breast cancer, familial, susceptibility to, 2, breast cancer, familial, susceptibility to, 3, colorectal cancer, susceptibility to, 4, colorectal cancer, susceptibility to, on chromosome 15, ovarian cancer, familial, susceptibility to, 1, ovarian cancer, familial, susceptibility to, 2, ovarian cancer, familial, susceptibility to, 3, inherited hematologic cancer-predisposing syndrome, mosaic neurofibromatosis/schwannomatosis, tumor predisposition syndrome 2, prostate cancer, hereditary, X-linked 3, follicular lymphoma, susceptibility to, GPR161-related medulloblastoma predisposition, SAMD9L-related spectrum and myeloid neoplasm risk, HAVCR2-related cancer predisposition, EGLN1-related erythrocytosis and pheochromocytoma/paraganglioma predisposition

Subtypes (2): thrombocytopenia 5, hereditary thrombocytopenia and hematological cancer predisposition syndrome associated with RUNX1

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

ClinVar germline variants

600 retrieved; paginated sample, class counts are floors:

326 uncertain significance, 181 likely benign, 37 pathogenic, 30 likely pathogenic, 26 benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1013619	NM_001754.5(RUNX1):c.165dup (p.Leu56fs)	RUNX1	Pathogenic	reviewed by expert panel
1013620	NM_001754.5(RUNX1):c.588del (p.Val197fs)	RUNX1	Pathogenic	reviewed by expert panel
1068986	NM_001754.5(RUNX1):c.713_726del (p.Val238fs)	RUNX1	Pathogenic	reviewed by expert panel
1069299	NM_001754.5(RUNX1):c.140_150del (p.Leu47fs)	RUNX1	Pathogenic	reviewed by expert panel
1071785	NM_001754.5(RUNX1):c.777dup (p.Asn260Ter)	RUNX1	Pathogenic	reviewed by expert panel
1073884	NM_001754.5(RUNX1):c.601dup (p.Arg201fs)	RUNX1	Pathogenic	reviewed by expert panel
1073907	NM_001754.5(RUNX1):c.247dup (p.Ala83fs)	RUNX1	Pathogenic	reviewed by expert panel
1074352	NM_001754.5(RUNX1):c.664dup (p.Ser222fs)	RUNX1	Pathogenic	reviewed by expert panel
1074523	NM_001754.5(RUNX1):c.528_531dup (p.Thr178fs)	RUNX1	Pathogenic	reviewed by expert panel
1076589	NM_001754.5(RUNX1):c.149_158dup (p.Ser53fs)	RUNX1	Pathogenic	reviewed by expert panel
1194557	NM_001754.5(RUNX1):c.1242C>G (p.Tyr414Ter)	RUNX1	Pathogenic	reviewed by expert panel
1338044	NM_001754.5(RUNX1):c.830del (p.Pro277fs)	RUNX1	Pathogenic	reviewed by expert panel
1363605	NM_001754.5(RUNX1):c.503del (p.Gly168fs)	RUNX1	Pathogenic	reviewed by expert panel
1438546	NM_001754.5(RUNX1):c.585del (p.Thr196fs)	RUNX1	Pathogenic	reviewed by expert panel
14465	NM_001754.5(RUNX1):c.328A>G (p.Lys110Glu)	RUNX1	Pathogenic	reviewed by expert panel
14466	NM_001754.5(RUNX1):c.508+3del	RUNX1	Pathogenic	reviewed by expert panel
14467	NM_001754.5(RUNX1):c.861C>A (p.Tyr287Ter)	RUNX1	Pathogenic	reviewed by expert panel
14468	NM_001754.5(RUNX1):c.400G>C (p.Ala134Pro)	RUNX1	Pathogenic	reviewed by expert panel
14470	NM_001754.5(RUNX1):c.442_449del (p.Thr148fs)	RUNX1	Pathogenic	reviewed by expert panel
1459069	NM_001754.5(RUNX1):c.496C>T (p.Arg166Ter)	RUNX1	Pathogenic	reviewed by expert panel
1684407	NM_001754.5(RUNX1):c.802C>T (p.Gln268Ter)	RUNX1	Pathogenic	reviewed by expert panel
1684431	NM_001754.5(RUNX1):c.566_584dup (p.Thr196fs)	RUNX1	Pathogenic	reviewed by expert panel
1691247	NM_001754.5(RUNX1):c.735del (p.Thr246fs)	RUNX1	Pathogenic	reviewed by expert panel
1691248	NM_001754.5(RUNX1):c.847C>T (p.Gln283Ter)	RUNX1	Pathogenic	reviewed by expert panel
1692643	NM_001754.5(RUNX1):c.259_260dup (p.Glu88fs)	RUNX1	Pathogenic	reviewed by expert panel
1695383	NM_001754.5(RUNX1):c.268del (p.Val90fs)	RUNX1	Pathogenic	reviewed by expert panel
1704949	NM_001754.5(RUNX1):c.489dup (p.Val164fs)	RUNX1	Pathogenic	reviewed by expert panel
1706546	NM_001754.5(RUNX1):c.590_597del (p.Val197fs)	RUNX1	Pathogenic	reviewed by expert panel
1897839	NM_001754.5(RUNX1):c.285del (p.Asn96fs)	RUNX1	Pathogenic	reviewed by expert panel
1996224	NM_001754.5(RUNX1):c.505dup (p.Arg169fs)	RUNX1	Pathogenic	reviewed by expert panel

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 23 · Orphanet: 12 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Somatic driver evidence (intOGen + CIViC, cohort fanout)

Gene	intOGen role	Cancer types	CIViC
RUNX1	LoF	ACYC,ALL,AML,BRCA,GBM	CIViC #43
ETV6	Act	ALL,BLCA,DLBCLNOS	CIViC #1769

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
ANKRD26	Definitive	Autosomal dominant	thrombocytopenia 2	8
ETV6	Definitive	Autosomal dominant	thrombocytopenia 5	7
RUNX1	Definitive	Autosomal dominant	hereditary thrombocytopenia and hematological cancer predisposition syndrome associated with RUNX1	8

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
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
ANKRD26	Orphanet:168629	Autosomal thrombocytopenia with normal platelets
ETV6	Orphanet:146	Differentiated thyroid carcinoma
ETV6	Orphanet:168629	Autosomal thrombocytopenia with normal platelets
ETV6	Orphanet:2030	Fibrosarcoma
ETV6	Orphanet:2665	Congenital mesoblastic nephroma
ETV6	Orphanet:314950	Primary hypereosinophilic syndrome
ETV6	Orphanet:585929	B-lymphoblastic leukemia/lymphoma with t(12;21)(p13.2;q22.1)
ETV6	Orphanet:98823	Chronic myelomonocytic leukemia

Cohort genes → proteins

5 cohort genes, 4 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	5

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
RUNX1	HGNC:10471	ENSG00000159216	Q01196	Runt-related transcription factor 1	gencc,clinvar
ANKRD26	HGNC:29186	ENSG00000107890	Q9UPS8	Ankyrin repeat domain-containing protein 26	gencc
ETV6	HGNC:3495	ENSG00000139083	P41212	Transcription factor ETV6	gencc
CLIC6	HGNC:2065	ENSG00000159212	Q96NY7	Chloride intracellular channel protein 6	clinvar
RUNX1-AS1	HGNC:56821	ENSG00000286153		RUNX1 antisense RNA 1	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
RUNX1	Runt-related transcription factor 1	Forms the heterodimeric complex core-binding factor (CBF) with CBFB.
ANKRD26	Ankyrin repeat domain-containing protein 26	Acts as a regulator of adipogenesis.
ETV6	Transcription factor ETV6	Transcriptional repressor; binds to the DNA sequence 5’-CCGGAAGT-3'.
CLIC6	Chloride intracellular channel protein 6	In the soluble state, catalyzes glutaredoxin-like thiol disulfide exchange reactions with reduced glutathione as electron donor.

Protein-family classification

Druggable: 0 · Difficult: 2 · Unknown: 3 · Druggable fraction: 0.0

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
Scaffold/PPI	1	3.5×	0.608
Transcription factor	1	1.6×	0.608
Other/Unknown	3	1.1×	0.608

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
RUNX1	Transcription factor	no		AML1_Runt, p53-like_TF_DNA-bd_sf, p53/RUNT-type_TF_DNA-bd_sf
ANKRD26	Scaffold/PPI	no		Ankyrin_rpt, DUF3496, Ankyrin_rpt-contain_sf
ETV6	Other/Unknown	no		Ets_dom, Pointed_dom, SAM/pointed_sf
CLIC6	Other/Unknown	no		CLIC, Glutathione-S-Trfase_C-like, Thioredoxin-like_sf
RUNX1-AS1	Other/Unknown	no

Expression context

Cohort genes with no expression data: 0.

5 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)	5
unknown	0

Top tissues across cohort

Tissue	Cohort genes
mucosa of paranasal sinus	2
male germ line stem cell (sensu Vertebrata) in testis	2
sural nerve	2
epithelium of bronchus	1
olfactory segment of nasal mucosa	1
calcaneal tendon	1
mammary duct	1
parotid gland	1
bronchial epithelial cell	1
bronchus	1
pigmented layer of retina	1
bone marrow cell	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
RUNX1	253	ubiquitous	marker	olfactory segment of nasal mucosa, epithelium of bronchus, mucosa of paranasal sinus
ANKRD26	206	ubiquitous	marker	male germ line stem cell (sensu Vertebrata) in testis, calcaneal tendon, sural nerve
ETV6	252	ubiquitous	marker	mucosa of paranasal sinus, parotid gland, mammary duct
CLIC6	189	broad	marker	pigmented layer of retina, bronchial epithelial cell, bronchus
RUNX1-AS1	114		marker	male germ line stem cell (sensu Vertebrata) in testis, bone marrow cell, sural nerve

Protein interactions among cohort

Intra-cohort edges: 3.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
RUNX1	4,994
ETV6	2,225
ANKRD26	1,721
CLIC6	1,246
RUNX1-AS1	0

Intra-cohort edges

A	B	Sources
ANKRD26	ETV6	string_interaction
ANKRD26	RUNX1	string_interaction
ETV6	RUNX1	string_interaction

Structural data

PDB: 2 · AlphaFold-only: 2 · No structure: 1

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
ETV6	P41212	44
RUNX1	Q01196	5

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
ANKRD26	Q9UPS8	62.91
CLIC6	Q96NY7	60.24

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 51. Enrichment computed across 5 evidence-associated genes (3 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 3 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
RUNX3 regulates RUNX1-mediated transcription	1	1268.9×	0.010	RUNX1
RUNX1 regulates expression of components of tight junctions	1	761.3×	0.010	RUNX1
RUNX1 regulates transcription of genes involved in interleukin signaling	1	761.3×	0.010	RUNX1
RUNX2 regulates genes involved in differentiation of myeloid cells	1	761.3×	0.010	RUNX1
Signaling by membrane-tethered fusions of PDGFRA or PDGFRB	1	761.3×	0.010	ETV6
RUNX1 regulates estrogen receptor mediated transcription	1	634.4×	0.010	RUNX1
RUNX1 regulates transcription of genes involved in BCR signaling	1	634.4×	0.010	RUNX1
RUNX1 regulates transcription of genes involved in WNT signaling	1	634.4×	0.010	RUNX1
RUNX1 regulates transcription of genes involved in differentiation of myeloid cells	1	475.8×	0.011	RUNX1
RUNX1 and FOXP3 control the development of regulatory T lymphocytes (Tregs)	1	380.7×	0.011	RUNX1
RUNX1 regulates transcription of genes involved in differentiation of keratinocytes	1	380.7×	0.011	RUNX1
RUNX3 regulates p14-ARF	1	380.7×	0.011	RUNX1
Differentiation of naive CD4+ T cells to T helper 1 cells (Th1 cells)	1	292.8×	0.013	RUNX1
SLC-mediated transport of organic cations	1	253.8×	0.013	RUNX1
R-HSA-549132	1	253.8×	0.013	RUNX1
Regulation of RUNX1 Expression and Activity	1	223.9×	0.014	RUNX1
Signaling by FLT3 fusion proteins	1	190.3×	0.016	ETV6
Pre-NOTCH Expression and Processing	1	122.8×	0.023	RUNX1
RUNX1 interacts with co-factors whose precise effect on RUNX1 targets is not known	1	100.2×	0.024	RUNX1
Transcriptional regulation by RUNX3	1	90.6×	0.024	RUNX1
SARS-CoV-1 activates/modulates innate immune responses	1	90.6×	0.024	RUNX1
RND1 GTPase cycle	1	88.5×	0.024	ANKRD26
RND3 GTPase cycle	1	86.5×	0.024	ANKRD26
RND2 GTPase cycle	1	86.5×	0.024	ANKRD26
Transcriptional regulation by RUNX2	1	84.6×	0.024	RUNX1
R-HSA-425366	1	60.4×	0.031	RUNX1
Signaling by NOTCH	1	58.6×	0.031	RUNX1
SARS-CoV-1-host interactions	1	58.6×	0.031	RUNX1
Transcriptional regulation by RUNX1	1	48.8×	0.035	RUNX1
SARS-CoV-1 Infection	1	47.6×	0.035	RUNX1

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 3 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
hematopoietic stem cell proliferation	2	432.1×	2e-04	RUNX1, ETV6
regulation of connective tissue replacement	1	5617.3×	0.003	RUNX1
myeloid leukocyte differentiation	1	1872.4×	0.003	RUNX1
regulation of plasminogen activation	1	1872.4×	0.003	RUNX1
negative regulation of CD4-positive, alpha-beta T cell differentiation	1	1404.3×	0.003	RUNX1
cardiac muscle tissue regeneration	1	1404.3×	0.003	RUNX1
positive regulation of extracellular matrix organization	1	1404.3×	0.003	RUNX1
vitellogenesis	1	1123.5×	0.003	ETV6
positive regulation of CD8-positive, alpha-beta T cell differentiation	1	1123.5×	0.003	RUNX1
regulation of cardiac muscle cell proliferation	1	1123.5×	0.003	RUNX1
positive regulation of granulocyte differentiation	1	936.2×	0.003	RUNX1
negative regulation of granulocyte differentiation	1	702.2×	0.004	RUNX1
peripheral nervous system neuron development	1	510.7×	0.004	RUNX1
mesenchymal cell apoptotic process	1	510.7×	0.004	ETV6
myeloid cell differentiation	1	216.1×	0.009	RUNX1
positive regulation of collagen biosynthetic process	1	216.1×	0.009	RUNX1
positive regulation of interleukin-2 production	1	156.0×	0.011	RUNX1
regulation of cell differentiation	1	144.0×	0.012	RUNX1
negative regulation of fat cell differentiation	1	104.0×	0.014	ANKRD26
chondrocyte differentiation	1	100.3×	0.014	RUNX1
negative regulation of transcription by RNA polymerase II	2	11.8×	0.014	RUNX1, ETV6
hemopoiesis	1	89.2×	0.015	RUNX1
ossification	1	75.9×	0.017	RUNX1
neurogenesis	1	69.3×	0.018	ETV6
regulation of transcription by RNA polymerase II	2	7.8×	0.025	RUNX1, ETV6
positive regulation of angiogenesis	1	38.5×	0.030	RUNX1
neuron differentiation	1	33.4×	0.033	RUNX1
cell differentiation	1	9.7×	0.107	ETV6
positive regulation of DNA-templated transcription	1	9.3×	0.107	RUNX1
positive regulation of transcription by RNA polymerase II	1	5.0×	0.188	RUNX1

Therapeutics

Drug target analysis

Approved (phase 4): 2 · Phase ≥3: 2 · Phased (≥1): 2 · Undrugged: 3

Druggability breadth: 2 of 5 evidence-associated genes (40%) 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
RUNX1	APOMORPHINE HYDROCHLORIDE
ETV6	CERITINIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
ETV6	4	4
RUNX1	2	4
ANKRD26	0	0
CLIC6	0	0
RUNX1-AS1	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
APOMORPHINE HYDROCHLORIDE	4	RUNX1
CERITINIB	4	ETV6
GILTERITINIB	4	ETV6
ERDAFITINIB	4	ETV6
MOLIBRESIB	2	RUNX1
LY-2874455	1	ETV6

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
RUNX1	20	Binding:17, Functional:3
ETV6	11	Binding:11

Pharmacogenomics

Cohort genes with a PharmGKB record: 4; with CPIC/DPWG dosing guidelines: 0.

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

Drug repurposing candidates

6 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)
APOMORPHINE HYDROCHLORIDE	4	RUNX1
CERITINIB	4	ETV6
GILTERITINIB	4	ETV6
ERDAFITINIB	4	ETV6
MOLIBRESIB	2	RUNX1
LY-2874455	1	ETV6

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	2	RUNX1, ETV6
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	3	ANKRD26, CLIC6, RUNX1-AS1

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
ANKRD26	0	ETV6, RUNX1
CLIC6	0	—
RUNX1-AS1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.