myeloid neoplasm associated with FGFR1 rearrangement

Summary

myeloid neoplasm associated with FGFR1 rearrangement (MONDO:0013296) is a cancer with 1 cohort gene (1 CIViC-evidence somatic driver; 1 ClinVar predisposition record).

At a glance

• Classification: Cancer
• Cohort genes: 1
• ClinVar variants: 1

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	myeloid neoplasm associated with FGFR1 rearrangement
Mondo ID	MONDO:0013296
OMIM	613523
Orphanet	168953
DOID	DOID:0080167
ICD-11	2019647878
NCIT	C84277
UMLS	C3150773
MedGen	462123
GARD	0017043
Is cancer (heuristic)	yes

Also known as: 8p11 myeloproliferative syndrome · 8p11 stem cell leukemia/lymphoma syndrome · 8p11 stem cell syndrome · chromosome 8p11 myeloproliferative syndrome · myeloid and lymphoid neoplasms associated with FGFR1 abnormalities · myeloid and lymphoid neoplasms with FGFR1 rearrangement · myeloid/lymphoid neoplasm associated with FGFR1 rearrangement · myeloid/lymphoid neoplasms with FGFR1 rearrangement · stem cell leukemia/lymphoma

Data availability: 1 ClinVar variant.

Disease family

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 › myeloid/lymphoid neoplasms associated with eosinophilia and abnormality of PDGFRA, PDGFRB, FGFR1 or JAK2 › myeloid neoplasm associated with FGFR1 rearrangement

Related subtypes (3): myeloid neoplasm associated with PDGFRA rearrangement, myeloid neoplasm associated with PDGFRB rearrangement, myeloid/lymphoid neoplasm associated with JAK2 rearrangement

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

1 retrieved; paginated sample, class counts are floors:

1 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
691593	t(8;22)(p11;q11)	BCR	Pathogenic	no assertion criteria provided

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 4 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Somatic driver evidence (intOGen + CIViC, cohort fanout)

Gene	intOGen role	Cancer types	CIViC
BCR	Act	BL,CLLSLL,DLBCLNOS,LUSC,NHL,WDTC

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
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

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
BCR	HGNC:1014	ENSG00000186716	P11274	Breakpoint cluster region protein	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
BCR	Breakpoint cluster region protein	Protein with a unique structure having two opposing regulatory activities toward small GTP-binding proteins.

Protein-family classification

Druggable: 0 · Difficult: 1 · Unknown: 0 · 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	17.3×	0.058

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
BCR	Scaffold/PPI	no		C2_dom, RhoGAP_dom, DH_dom

Expression context

Cohort genes with no expression data: 0.

1 cohort gene 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)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
caudate nucleus	1
nucleus accumbens	1
putamen	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
BCR	275	ubiquitous	marker	nucleus accumbens, caudate nucleus, putamen

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
BCR	1,858

Structural data

PDB: 1 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
BCR	P11274	5

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 17. Enrichment computed across 1 evidence-associated genes (1 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 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
FGFR1 mutant receptor activation	1	1142.0×	0.013	BCR
Signaling by cytosolic FGFR1 fusion mutants	1	634.4×	0.013	BCR
Signaling by FGFR in disease	1	423.0×	0.013	BCR
Signaling by FGFR1 in disease	1	292.8×	0.015	BCR
RHOB GTPase cycle	1	154.3×	0.018	BCR
RHOC GTPase cycle	1	146.4×	0.018	BCR
RAC2 GTPase cycle	1	126.9×	0.018	BCR
RAC3 GTPase cycle	1	119.0×	0.018	BCR
RHOA GTPase cycle	1	74.6×	0.023	BCR
CDC42 GTPase cycle	1	72.3×	0.023	BCR
RAC1 GTPase cycle	1	61.1×	0.023	BCR
RHO GTPase cycle	1	60.1×	0.023	BCR
Diseases of signal transduction by growth factor receptors and second messengers	1	56.8×	0.023	BCR
Signaling by Rho GTPases	1	34.2×	0.034	BCR
Signaling by Rho GTPases, Miro GTPases and RHOBTB3	1	33.5×	0.034	BCR
Disease	1	13.1×	0.081	BCR
Signal Transduction	1	10.2×	0.098	BCR

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
negative regulation of cellular extravasation	1	16852.0×	9e-04	BCR
negative regulation of respiratory burst	1	16852.0×	9e-04	BCR
negative regulation of neutrophil degranulation	1	8426.0×	9e-04	BCR
negative regulation of blood vessel remodeling	1	8426.0×	9e-04	BCR
intracellular protein transmembrane transport	1	5617.3×	0.001	BCR
neutrophil degranulation	1	3370.4×	0.001	BCR
macrophage migration	1	2808.7×	0.001	BCR
negative regulation of macrophage migration	1	2808.7×	0.001	BCR
renal system process	1	1123.5×	0.003	BCR
regulation of vascular permeability	1	1123.5×	0.003	BCR
definitive hemopoiesis	1	936.2×	0.003	BCR
negative regulation of reactive oxygen species metabolic process	1	936.2×	0.003	BCR
activation of GTPase activity	1	732.7×	0.003	BCR
homeostasis of number of cells	1	674.1×	0.003	BCR
focal adhesion assembly	1	526.6×	0.004	BCR
regulation of Rho protein signal transduction	1	510.7×	0.004	BCR
neuromuscular process controlling balance	1	330.4×	0.005	BCR
positive regulation of phagocytosis	1	318.0×	0.005	BCR
inner ear morphogenesis	1	300.9×	0.005	BCR
keratinocyte differentiation	1	247.8×	0.006	BCR
phagocytosis	1	240.7×	0.006	BCR
small GTPase-mediated signal transduction	1	183.2×	0.007	BCR
modulation of chemical synaptic transmission	1	183.2×	0.007	BCR
regulation of small GTPase mediated signal transduction	1	144.0×	0.009	BCR
negative regulation of inflammatory response	1	137.0×	0.009	BCR
cellular response to lipopolysaccharide	1	98.0×	0.012	BCR
brain development	1	79.5×	0.014	BCR
actin cytoskeleton organization	1	79.1×	0.014	BCR
regulation of cell cycle	1	74.6×	0.014	BCR
protein phosphorylation	1	68.0×	0.015	BCR

Therapeutics

Drug target analysis

Approved (phase 4): 1 · Phase ≥3: 1 · Phased (≥1): 1 · Undrugged: 0

Druggability breadth: 1 of 1 evidence-associated genes (100%) 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
BCR	PONATINIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
BCR	64	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
PONATINIB	4	BCR
DASATINIB ANHYDROUS	4	BCR
IMATINIB MESYLATE	4	BCR
INFIGRATINIB	4	BCR
NILOTINIB	4	BCR
BOSUTINIB	4	BCR
ASCIMINIB	4	BCR
DASATINIB	4	BCR
TIRBANIBULIN	4	BCR
IMATINIB	4	BCR
FEDRATINIB	4	BCR
TIVOZANIB	4	BCR
LENVATINIB	4	BCR
AXITINIB	4	BCR
IBRUTINIB	4	BCR
REGORAFENIB	4	BCR
CABOZANTINIB	4	BCR
VANDETANIB	4	BCR
TOVORAFENIB	4	BCR
NINTEDANIB	4	BCR
ERLOTINIB	4	BCR
CRIZOTINIB	4	BCR
TANESPIMYCIN	3	BCR
RESVERATROL	3	BCR
FLUMATINIB	3	BCR
RADOTINIB	3	BCR
MASITINIB	3	BCR
SARACATINIB	3	BCR
CANERTINIB	3	BCR
TESEVATINIB	3	BCR

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
BCR	486	Binding:478, Functional:6, Toxicity:2

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
BCR	486

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

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

Drug repurposing candidates

30 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)
PONATINIB	4	BCR
DASATINIB ANHYDROUS	4	BCR
IMATINIB MESYLATE	4	BCR
INFIGRATINIB	4	BCR
NILOTINIB	4	BCR
BOSUTINIB	4	BCR
ASCIMINIB	4	BCR
DASATINIB	4	BCR
TIRBANIBULIN	4	BCR
IMATINIB	4	BCR
FEDRATINIB	4	BCR
TIVOZANIB	4	BCR
LENVATINIB	4	BCR
AXITINIB	4	BCR
IBRUTINIB	4	BCR
REGORAFENIB	4	BCR
CABOZANTINIB	4	BCR
VANDETANIB	4	BCR
TOVORAFENIB	4	BCR
NINTEDANIB	4	BCR
ERLOTINIB	4	BCR
CRIZOTINIB	4	BCR
TANESPIMYCIN	3	BCR
RESVERATROL	3	BCR
FLUMATINIB	3	BCR
RADOTINIB	3	BCR
MASITINIB	3	BCR
SARACATINIB	3	BCR
CANERTINIB	3	BCR
TESEVATINIB	3	BCR

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	BCR
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	0

Undrugged target profiles

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

Clinical trials & evidence

Clinical trials

Clinical trials: 0.