Encephalocraniocutaneous lipomatosis

Summary

Encephalocraniocutaneous lipomatosis (MONDO:0013074) is a disease caused by FGFR1 (GenCC Definitive), with 2 cohort genes.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Causal gene: FGFR1 (GenCC Definitive)
• Cohort genes: 2
• ClinVar variants: 154
• Phenotypes (HPO): 55

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		77	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

55 HPO clinical features (Orphanet curated; top 50 by frequency):

HPO ID	Term	Frequency
HP:0000488	Retinopathy	Very frequent (80-99%)
HP:0000991	Xanthomatosis	Very frequent (80-99%)
HP:0001012	Multiple lipomas	Very frequent (80-99%)
HP:0001249	Intellectual disability	Very frequent (80-99%)
HP:0001250	Seizure	Very frequent (80-99%)
HP:0001263	Global developmental delay	Very frequent (80-99%)
HP:0001482	Subcutaneous nodule	Very frequent (80-99%)
HP:0001596	Alopecia	Very frequent (80-99%)
HP:0009125	Lipodystrophy	Very frequent (80-99%)
HP:0012759	Neurodevelopmental abnormality	Very frequent (80-99%)
HP:0001276	Hypertonia	Frequent (30-79%)
HP:0001331	Absent septum pellucidum	Frequent (30-79%)
HP:0001704	Tricuspid valve prolapse	Frequent (30-79%)
HP:0002059	Cerebral atrophy	Frequent (30-79%)
HP:0002063	Rigidity	Frequent (30-79%)
HP:0002092	Pulmonary arterial hypertension	Frequent (30-79%)
HP:0002119	Ventriculomegaly	Frequent (30-79%)
HP:0002120	Cerebral cortical atrophy	Frequent (30-79%)
HP:0002167	Abnormality of speech or vocalization	Frequent (30-79%)
HP:0002300	Mutism	Frequent (30-79%)
HP:0002381	Aphasia	Frequent (30-79%)
HP:0002514	Cerebral calcification	Frequent (30-79%)
HP:0002797	Osteolysis	Frequent (30-79%)
HP:0003552	Muscle stiffness	Frequent (30-79%)
HP:0004493	Craniofacial hyperostosis	Frequent (30-79%)
HP:0005306	Capillary hemangioma	Frequent (30-79%)
HP:0007957	Corneal opacity	Frequent (30-79%)
HP:0010529	Echolalia	Frequent (30-79%)
HP:0010622	Neoplasm of the skeletal system	Frequent (30-79%)
HP:0012062	Bone cyst	Frequent (30-79%)
HP:0012157	Subcortical cerebral atrophy	Frequent (30-79%)
HP:0100761	Visceral angiomatosis	Frequent (30-79%)
HP:0000256	Macrocephaly	Frequent (30-79%)
HP:0000271	Abnormality of the face	Frequent (30-79%)
HP:0000492	Abnormal eyelid morphology	Frequent (30-79%)
HP:0000499	Abnormal eyelash morphology	Frequent (30-79%)
HP:0000612	Iris coloboma	Frequent (30-79%)
HP:0000614	Abnormal nasolacrimal system morphology	Frequent (30-79%)
HP:0000708	Atypical behavior	Frequent (30-79%)
HP:0000929	Abnormal skull morphology	Frequent (30-79%)
HP:0001052	Nevus flammeus	Frequent (30-79%)
HP:0001257	Spasticity	Frequent (30-79%)
HP:0001274	Agenesis of corpus callosum	Frequent (30-79%)
HP:0000943	Dysostosis multiplex	Occasional (5-29%)
HP:0001269	Hemiparesis	Occasional (5-29%)
HP:0001650	Aortic valve stenosis	Occasional (5-29%)
HP:0001679	Abnormal aortic morphology	Occasional (5-29%)
HP:0001680	Coarctation of aorta	Occasional (5-29%)
HP:0002301	Hemiplegia	Occasional (5-29%)
HP:0002445	Tetraplegia	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	encephalocraniocutaneous lipomatosis
Mondo ID	MONDO:0013074
MeSH	C535736
OMIM	613001
Orphanet	2396
ICD-11	1084215843
NCIT	C4701
SNOMED CT	238905009
UMLS	C0406612
MedGen	140807
GARD	0002108
Is cancer (heuristic)	no

Also known as: ECCL · encephalocraniocutaneous lipomatosis · encephalocraniocutaneous lipomatosis, somatic mosaic · Fishman syndrome · Haberland syndrome

Data availability: 154 ClinVar variants · 2 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › musculoskeletal system disorder › musculoskeletal system benign neoplasm › benign connective and soft tissue neoplasm › benign lipomatous neoplasm › lipomatosis › encephalocraniocutaneous lipomatosis

Related subtypes (8): diffuse lipomatosis, mediastinal lipomatosis, pelvic lipomatosis, steroid lipomatosis, adiposis dolorosa, multiple symmetric lipomatosis, congenital infiltrating lipomatosis of the face, pancreatic lipomatosis duodenal stenosis

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

154 retrieved; paginated sample, class counts are floors:

77 uncertain significance, 30 conflicting classifications of pathogenicity, 19 likely benign, 10 benign/likely benign, 7 pathogenic, 6 pathogenic/likely pathogenic, 4 likely pathogenic, 1 benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
16279	NM_023110.3(FGFR1):c.755C>G (p.Pro252Arg)	FGFR1	Pathogenic	criteria provided, multiple submitters, no conflicts
224896	NM_023110.3(FGFR1):c.1638C>A (p.Asn546Lys)	FGFR1	Pathogenic	criteria provided, multiple submitters, no conflicts
224897	NM_023110.3(FGFR1):c.1966A>G (p.Lys656Glu)	FGFR1	Pathogenic	criteria provided, single submitter
235087	NM_023110.3(FGFR1):c.1977+1G>A	FGFR1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2505415	NM_023110.3(FGFR1):c.710G>A (p.Gly237Asp)	FGFR1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
502125	NM_023110.3(FGFR1):c.214C>T (p.Gln72Ter)	FGFR1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
931981	NM_023110.3(FGFR1):c.1671del (p.Leu557fs)	FGFR1	Pathogenic	criteria provided, single submitter
12580	NM_004985.5(KRAS):c.38G>A (p.Gly13Asp)	KRAS	Pathogenic	criteria provided, multiple submitters, no conflicts
12582	NM_004985.5(KRAS):c.35G>A (p.Gly12Asp)	KRAS	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
217822	NM_004985.5(KRAS):c.57G>C (p.Leu19Phe)	KRAS	Pathogenic	criteria provided, single submitter
375962	NM_004985.5(KRAS):c.437C>T (p.Ala146Val)	KRAS	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
375963	NM_033360.4(KRAS):c.436G>C (p.Ala146Pro)	KRAS	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
375965	NM_033360.4(KRAS):c.351A>C (p.Lys117Asn)	KRAS	Pathogenic	criteria provided, multiple submitters, no conflicts
1338542	NM_023110.3(FGFR1):c.809G>A (p.Gly270Asp)	FGFR1	Likely pathogenic	criteria provided, multiple submitters, no conflicts
3595591	NM_023110.3(FGFR1):c.1854+2T>C	FGFR1	Likely pathogenic	criteria provided, single submitter
4796553	NM_023110.3(FGFR1):c.2156T>C (p.Met719Thr)	FGFR1	Likely pathogenic	criteria provided, single submitter
654366	NM_023110.3(FGFR1):c.448+1G>A	FGFR1	Likely pathogenic	criteria provided, multiple submitters, no conflicts
1156684	NM_023110.3(FGFR1):c.789C>T (p.Ala263=)	FGFR1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1186398	NM_023110.3(FGFR1):c.266A>G (p.Gln89Arg)	FGFR1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1197448	NM_023110.3(FGFR1):c.448+1G>C	FGFR1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1302903	NM_023110.3(FGFR1):c.2428C>T (p.His810Tyr)	FGFR1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1304409	NM_023110.3(FGFR1):c.2426G>A (p.Arg809Gln)	FGFR1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1352087	NM_023110.3(FGFR1):c.169C>A (p.Leu57Met)	FGFR1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1416171	NM_023110.3(FGFR1):c.2267G>A (p.Arg756His)	FGFR1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1431252	NM_023110.3(FGFR1):c.1179G>A (p.Ser393=)	FGFR1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1496164	NM_023110.3(FGFR1):c.346G>A (p.Val116Ile)	FGFR1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1509706	NM_023110.3(FGFR1):c.1186G>A (p.Val396Ile)	FGFR1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
16289	NM_023110.3(FGFR1):c.899T>C (p.Ile300Thr)	FGFR1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
16299	NM_023110.3(FGFR1):c.1097C>T (p.Pro366Leu)	FGFR1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
180152	NM_023110.3(FGFR1):c.821A>G (p.Glu274Gly)	FGFR1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 36 · Orphanet: 28 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

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
FGFR1	Definitive	Autosomal dominant	encephalocraniocutaneous lipomatosis	36

Orphanet rare-disease linkage (cohort genes)

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

Cohort genes → proteins

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
FGFR1	HGNC:3688	ENSG00000077782	P11362	Fibroblast growth factor receptor 1	gencc,clinvar
KRAS	HGNC:6407	ENSG00000133703	P01116	GTPase KRas	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
FGFR1	Fibroblast growth factor receptor 1	Tyrosine-protein kinase that acts as a cell-surface receptor for fibroblast growth factors and plays an essential role in the regulation of embryonic development, cell proliferation, differentiation and migration.
KRAS	GTPase KRas	Ras proteins bind GDP/GTP and possess intrinsic GTPase activity.

Protein-family classification

Druggable: 2 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

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
Kinase	1	13.9×	0.142
Enzyme (other)	1	6.0×	0.160

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
FGFR1	Kinase	yes	2.7.10.1	Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom, Ig_sub2
KRAS	Enzyme (other)	yes	3.6.5.2	Small_GTPase, Small_GTP-bd, Small_GTPase_Ras-type

Expression context

Cohort genes with no expression data: 0.

2 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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
buccal mucosa cell	1
calcaneal tendon	1
stromal cell of endometrium	1
nipple	1
pylorus	1
trigeminal ganglion	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
FGFR1	292	ubiquitous	marker	buccal mucosa cell, stromal cell of endometrium, calcaneal tendon
KRAS	298	ubiquitous	marker	trigeminal ganglion, pylorus, nipple

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
KRAS	14,509
FGFR1	5,693

Structural data

PDB: 2 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
KRAS	P01116	511
FGFR1	P11362	83

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 88. Enrichment computed across 2 evidence-associated genes (2 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 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
SHC-mediated cascade:FGFR1	2	496.5×	2e-04	FGFR1, KRAS
FRS-mediated FGFR1 signaling	2	456.8×	2e-04	FGFR1, KRAS
Signaling by FGFR1 in disease	2	292.8×	3e-04	FGFR1, KRAS
NCAM signaling for neurite out-growth	2	271.9×	3e-04	FGFR1, KRAS
RAF/MAP kinase cascade	2	61.1×	0.005	FGFR1, KRAS
Signaling by FGFR1 amplification mutants	1	2855.0×	0.005	FGFR1
Signaling by RAS GAP mutants	1	1903.3×	0.006	KRAS
Signaling by RAS GTPase mutants	1	1903.3×	0.006	KRAS
FGFR1c and Klotho ligand binding and activation	1	1427.5×	0.006	FGFR1
Signaling by plasma membrane FGFR1 fusions	1	1427.5×	0.006	FGFR1
Activation of RAS in B cells	1	1142.0×	0.006	KRAS
RAS signaling downstream of NF1 loss-of-function variants	1	815.7×	0.006	KRAS
Estrogen-stimulated signaling through PRKCZ	1	815.7×	0.006	KRAS
SOS-mediated signalling	1	713.8×	0.006	KRAS
Epithelial-Mesenchymal Transition (EMT) during gastrulation	1	713.8×	0.006	FGFR1
FGFR1b ligand binding and activation	1	634.4×	0.006	FGFR1
Activated NTRK3 signals through RAS	1	634.4×	0.006	KRAS
EGFR Transactivation by Gastrin	1	571.0×	0.006	KRAS
SHC-related events triggered by IGF1R	1	571.0×	0.006	KRAS
RUNX3 regulates p14-ARF	1	571.0×	0.006	KRAS
Activated NTRK2 signals through RAS	1	571.0×	0.006	KRAS
MET activates RAS signaling	1	519.1×	0.006	KRAS
Signaling by activated point mutants of FGFR1	1	475.8×	0.006	FGFR1
Signaling by FGFR4 in disease	1	475.8×	0.006	KRAS
Activated NTRK2 signals through FRS2 and FRS3	1	475.8×	0.006	KRAS
Constitutive Signaling by Overexpressed ERBB2	1	475.8×	0.006	KRAS
p38MAPK events	1	439.2×	0.006	KRAS
Signaling by PDGFRA transmembrane, juxtamembrane and kinase domain mutants	1	439.2×	0.006	KRAS
Signaling by PDGFRA extracellular domain mutants	1	439.2×	0.006	KRAS
PTK6 Regulates RHO GTPases, RAS GTPase and MAP kinases	1	407.9×	0.006	KRAS

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
cardiac muscle cell proliferation	2	581.1×	3e-04	FGFR1, KRAS
MAPK cascade	2	153.2×	0.002	FGFR1, KRAS
response to mineralocorticoid	1	8426.0×	0.003	KRAS
vitamin D3 metabolic process	1	4213.0×	0.003	FGFR1
positive regulation of mitotic cell cycle DNA replication	1	4213.0×	0.003	FGFR1
positive regulation of parathyroid hormone secretion	1	4213.0×	0.003	FGFR1
regulation of extrinsic apoptotic signaling pathway in absence of ligand	1	4213.0×	0.003	FGFR1
regulation of phosphate transport	1	2808.7×	0.003	FGFR1
forebrain astrocyte development	1	2808.7×	0.003	KRAS
fibroblast growth factor receptor signaling pathway involved in orbitofrontal cortex development	1	2808.7×	0.003	FGFR1
regulation of lateral mesodermal cell fate specification	1	2808.7×	0.003	FGFR1
gene expression	2	79.9×	0.003	FGFR1, KRAS
ventricular zone neuroblast division	1	2106.5×	0.003	FGFR1
response to isolation stress	1	2106.5×	0.003	KRAS
negative regulation of fibroblast growth factor production	1	2106.5×	0.003	FGFR1
positive regulation of phospholipase activity	1	1685.2×	0.003	FGFR1
regulation of branching involved in salivary gland morphogenesis by mesenchymal-epithelial signaling	1	1685.2×	0.003	FGFR1
diphosphate metabolic process	1	1685.2×	0.003	FGFR1
response to gravity	1	1404.3×	0.003	KRAS
chordate embryonic development	1	1404.3×	0.003	FGFR1
positive regulation of MAPKKK cascade by fibroblast growth factor receptor signaling pathway	1	1404.3×	0.003	FGFR1
cementum mineralization	1	1203.7×	0.004	FGFR1
auditory receptor cell development	1	936.2×	0.004	FGFR1
paraxial mesoderm development	1	842.6×	0.004	FGFR1
lung-associated mesenchyme development	1	842.6×	0.004	FGFR1
response to sodium phosphate	1	842.6×	0.004	FGFR1
outer ear morphogenesis	1	766.0×	0.004	FGFR1
type I pneumocyte differentiation	1	766.0×	0.004	KRAS
myoblast proliferation	1	702.2×	0.005	KRAS
branching involved in salivary gland morphogenesis	1	702.2×	0.005	FGFR1

Therapeutics

Drug target analysis

Approved (phase 4): 2 · Phase ≥3: 2 · Phased (≥1): 2 · Undrugged: 0

Druggability breadth: 2 of 2 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
FGFR1	PONATINIB
KRAS	VEMURAFENIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
FGFR1	93	4
KRAS	11	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
PONATINIB	4	FGFR1
PEMIGATINIB	4	FGFR1
NINTEDANIB	4	FGFR1
FEDRATINIB	4	FGFR1
TIVOZANIB	4	FGFR1
LENVATINIB	4	FGFR1
AXITINIB	4	FGFR1
SORAFENIB	4	FGFR1
NICLOSAMIDE	4	FGFR1
INFIGRATINIB PHOSPHATE	4	FGFR1
INFIGRATINIB	4	FGFR1
REGORAFENIB	4	FGFR1
ENTRECTINIB	4	FGFR1
CABOZANTINIB	4	FGFR1
CAPIVASERTIB	4	FGFR1
VANDETANIB	4	FGFR1
NINTEDANIB ESYLATE	4	FGFR1
BRIGATINIB	4	FGFR1
ERDAFITINIB	4	FGFR1
UPADACITINIB	4	FGFR1
FUTIBATINIB	4	FGFR1
PAZOPANIB	4	FGFR1
SUNITINIB	4	FGFR1
DASATINIB	4	FGFR1
MIDOSTAURIN	4	FGFR1
VEMURAFENIB	4	KRAS
DABRAFENIB	4	KRAS
LONAFARNIB	4	KRAS
SOTORASIB	4	KRAS
ADAGRASIB	4	KRAS

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 2.

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

Symbol	Assays	Type breakdown
FGFR1	1,465	Binding:1428, Functional:24, ADMET:13
KRAS	861	Binding:829, Functional:32

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
FGFR1	2.7.10.1	receptor protein-tyrosine kinase
KRAS	3.6.5.2	small monomeric GTPase

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
FGFR1	1,465
KRAS	861

Pharmacogenomics

Cohort genes with a PharmGKB record: 2; 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.

Compound	Max phase	Cohort target (bioactivity)
PONATINIB	4	FGFR1
PEMIGATINIB	4	FGFR1
NINTEDANIB	4	FGFR1
FEDRATINIB	4	FGFR1
TIVOZANIB	4	FGFR1
LENVATINIB	4	FGFR1
AXITINIB	4	FGFR1
SORAFENIB	4	FGFR1
NICLOSAMIDE	4	FGFR1
INFIGRATINIB PHOSPHATE	4	FGFR1
INFIGRATINIB	4	FGFR1
REGORAFENIB	4	FGFR1
ENTRECTINIB	4	FGFR1
CABOZANTINIB	4	FGFR1
CAPIVASERTIB	4	FGFR1
VANDETANIB	4	FGFR1
NINTEDANIB ESYLATE	4	FGFR1
BRIGATINIB	4	FGFR1
ERDAFITINIB	4	FGFR1
UPADACITINIB	4	FGFR1
FUTIBATINIB	4	FGFR1
PAZOPANIB	4	FGFR1
SUNITINIB	4	FGFR1
DASATINIB	4	FGFR1
MIDOSTAURIN	4	FGFR1
VEMURAFENIB	4	KRAS
DABRAFENIB	4	KRAS
LONAFARNIB	4	KRAS
SOTORASIB	4	KRAS
ADAGRASIB	4	KRAS

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	2	FGFR1, KRAS
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.