Microform holoprosencephaly

Summary

Microform holoprosencephaly (MONDO:0017219) is a disease with 5 cohort genes. The dominant Reactome pathway is Hedgehog ‘off’ state (3 cohort genes).

At a glance

• Prevalence: 1-9 / 100 000 (Europe)
• Cohort genes: 5
• ClinVar variants: 14
• Phenotypes (HPO): 35

Clinical features

Epidemiology

Prevalence records

1 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Point prevalence	1-9 / 100 000		Europe	Not yet validated

Signs & symptoms

Clinical features (HPO)

35 HPO clinical features (Orphanet curated; top 35 by frequency):

HPO ID	Term	Frequency
HP:0000453	Choanal atresia	Very frequent (80-99%)
HP:0006315	Single median maxillary incisor	Very frequent (80-99%)
HP:0010644	Midnasal stenosis	Very frequent (80-99%)
HP:0000252	Microcephaly	Frequent (30-79%)
HP:0000322	Short philtrum	Frequent (30-79%)
HP:0000446	Narrow nasal bridge	Frequent (30-79%)
HP:0000601	Hypotelorism	Frequent (30-79%)
HP:0001249	Intellectual disability	Frequent (30-79%)
HP:0001511	Intrauterine growth retardation	Frequent (30-79%)
HP:0001622	Premature birth	Frequent (30-79%)
HP:0004322	Short stature	Frequent (30-79%)
HP:0010804	Tented upper lip vermilion	Frequent (30-79%)
HP:0000062	Ambiguous genitalia	Occasional (5-29%)
HP:0000104	Renal agenesis	Occasional (5-29%)
HP:0000175	Cleft palate	Occasional (5-29%)
HP:0000202	Orofacial cleft	Occasional (5-29%)
HP:0000463	Anteverted nares	Occasional (5-29%)
HP:0000486	Strabismus	Occasional (5-29%)
HP:0000612	Iris coloboma	Occasional (5-29%)
HP:0000821	Hypothyroidism	Occasional (5-29%)
HP:0000871	Panhypopituitarism	Occasional (5-29%)
HP:0001028	Hemangioma	Occasional (5-29%)
HP:0001250	Seizure	Occasional (5-29%)
HP:0001274	Agenesis of corpus callosum	Occasional (5-29%)
HP:0001360	Holoprosencephaly	Occasional (5-29%)
HP:0001636	Tetralogy of Fallot	Occasional (5-29%)
HP:0002099	Asthma	Occasional (5-29%)
HP:0002247	Duodenal atresia	Occasional (5-29%)
HP:0002650	Scoliosis	Occasional (5-29%)
HP:0003196	Short nose	Occasional (5-29%)
HP:0003458	EMG: myopathic abnormalities	Occasional (5-29%)
HP:0008736	Hypoplasia of penis	Occasional (5-29%)
HP:0009800	Maternal diabetes	Occasional (5-29%)
HP:0009914	Cyclopia	Occasional (5-29%)
HP:0030680	Abnormal cardiovascular system morphology	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	microform holoprosencephaly
Mondo ID	MONDO:0017219
Orphanet	280200
DOID	DOID:0111380
ICD-11	44293173
UMLS	C5393309
MedGen	1711978
GARD	0017290
Is cancer (heuristic)	no

Also known as: HoloprosencC)phalie, minor form · holoprosencephaly-like · Holoprosencéphalie, minor form · HPE, minor form · HPE-L · Microform HPE

Data availability: 14 ClinVar variants.

Disease family

An umbrella term covering 3 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › syndromic disease › holoprosencephaly › microform holoprosencephaly

Related subtypes (16): holoprosencephaly 3, holoprosencephaly 4, holoprosencephaly 2, holoprosencephaly 1, holoprosencephaly 6, holoprosencephaly 8, holoprosencephaly 7, chromosome 1q41-q42 deletion syndrome, holoprosencephaly 11, lobar holoprosencephaly, alobar holoprosencephaly, holoprosencephaly 13, X-linked, holoprosencephaly 14, holoprosencephaly 12 with or without pancreatic agenesis, semilobar holoprosencephaly, holoprosencephaly 10

Subtypes (3): solitary median maxillary central incisor syndrome, holoprosencephaly 5, holoprosencephaly 9

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

14 retrieved; paginated sample, class counts are floors:

5 likely pathogenic, 4 uncertain significance, 4 conflicting classifications of pathogenicity, 1 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
235076	NM_001374353.1(GLI2):c.790C>T (p.Arg264Ter)	GLI2	Pathogenic	criteria provided, multiple submitters, no conflicts
235086	NM_023110.3(FGFR1):c.1928G>A (p.Gly643Asp)	FGFR1	Likely pathogenic	no assertion criteria provided
235075	NM_001374353.1(GLI2):c.596dup (p.Ala200fs)	GLI2	Likely pathogenic	no assertion criteria provided
235077	NM_001374353.1(GLI2):c.2013del (p.Ser673fs)	GLI2	Likely pathogenic	no assertion criteria provided
235078	NM_001374353.1(GLI2):c.2186G>A (p.Trp729Ter)	GLI2	Likely pathogenic	no assertion criteria provided
235079	NM_001374353.1(GLI2):c.4710G>C (p.Ter1570Tyr)	GLI2	Likely pathogenic	no assertion criteria provided
1334043	NM_001377229.1(DISP1):c.566C>T (p.Pro189Leu)	DISP1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
41655	NM_000264.5(PTCH1):c.2485G>A (p.Val829Met)	LOC100507346	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1570319	NM_000264.5(PTCH1):c.585-17_585-13del	PTCH1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
135281	NM_016169.4(SUFU):c.1022C>T (p.Pro341Leu)	SUFU	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1064558	NM_001377229.1(DISP1):c.3413del (p.Gly1138fs)	DISP1	Uncertain significance	criteria provided, multiple submitters, no conflicts
1334044	NM_001377229.1(DISP1):c.664G>A (p.Gly222Ser)	DISP1	Uncertain significance	criteria provided, single submitter
235093	NM_001377229.1(DISP1):c.2898G>A (p.Trp966Ter)	DISP1	Uncertain significance	criteria provided, single submitter
235074	NM_001374353.1(GLI2):c.349G>A (p.Ala117Thr)	GLI2	Uncertain significance	no assertion criteria provided

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 47 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SUFU	Orphanet:2495	Meningioma
SUFU	Orphanet:251858	Medulloblastoma with extensive nodularity
SUFU	Orphanet:251863	Desmoplastic/nodular medulloblastoma
SUFU	Orphanet:263662	Familial multiple meningioma
SUFU	Orphanet:280200	Microform holoprosencephaly
SUFU	Orphanet:377	Gorlin syndrome
SUFU	Orphanet:475	Isolated Joubert syndrome
DISP1	Orphanet:220386	Semilobar holoprosencephaly
DISP1	Orphanet:280195	Septopreoptic holoprosencephaly
DISP1	Orphanet:280200	Microform holoprosencephaly
DISP1	Orphanet:93924	Lobar holoprosencephaly
DISP1	Orphanet:93925	Alobar holoprosencephaly
DISP1	Orphanet:93926	Midline interhemispheric variant of holoprosencephaly
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
GLI2	Orphanet:220386	Semilobar holoprosencephaly
GLI2	Orphanet:280195	Septopreoptic holoprosencephaly
GLI2	Orphanet:280200	Microform holoprosencephaly
GLI2	Orphanet:420584	Postaxial polydactyly-anterior pituitary anomalies-facial dysmorphism syndrome
GLI2	Orphanet:93924	Lobar holoprosencephaly
GLI2	Orphanet:93925	Alobar holoprosencephaly
GLI2	Orphanet:93926	Midline interhemispheric variant of holoprosencephaly
GLI2	Orphanet:95494	Combined pituitary hormone deficiencies, genetic forms
PTCH1	Orphanet:220386	Semilobar holoprosencephaly
PTCH1	Orphanet:2353	Schilbach-Rott syndrome
PTCH1	Orphanet:280195	Septopreoptic holoprosencephaly
PTCH1	Orphanet:280200	Microform holoprosencephaly
PTCH1	Orphanet:377	Gorlin syndrome
PTCH1	Orphanet:77301	Monosomy 9q22.3 syndrome
PTCH1	Orphanet:93924	Lobar holoprosencephaly
PTCH1	Orphanet:93925	Alobar holoprosencephaly
PTCH1	Orphanet:93926	Midline interhemispheric variant of holoprosencephaly

Cohort genes → proteins

5 cohort genes, 5 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	5

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
SUFU	HGNC:16466	ENSG00000107882	Q9UMX1	Suppressor of fused homolog	clinvar
DISP1	HGNC:19711	ENSG00000154309	Q96F81	Protein dispatched homolog 1	clinvar
FGFR1	HGNC:3688	ENSG00000077782	P11362	Fibroblast growth factor receptor 1	clinvar
GLI2	HGNC:4318	ENSG00000074047	P10070	Zinc finger protein GLI2	clinvar
PTCH1	HGNC:9585	ENSG00000185920	Q13635	Protein patched homolog 1	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SUFU	Suppressor of fused homolog	Negative regulator in the hedgehog/smoothened signaling pathway.
DISP1	Protein dispatched homolog 1	Functions in hedgehog (Hh) signaling.
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.
GLI2	Zinc finger protein GLI2	Functions as a transcription regulator in the hedgehog (Hh) pathway.
PTCH1	Protein patched homolog 1	Acts as a receptor for sonic hedgehog (SHH), indian hedgehog (IHH) and desert hedgehog (DHH).

Protein-family classification

Druggable: 1 · Difficult: 1 · Unknown: 3 · Druggable fraction: 0.2

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	5.5×	0.503
Transcription factor	1	1.6×	0.608
Other/Unknown	3	1.1×	0.608

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
SUFU	Other/Unknown	no		Suppressor_of_fused, Suppressor_of_fused_euk, SUFU-like_domain
DISP1	Other/Unknown	no		SSD, MMPL_dom, Dispatched_Hh_regulator
FGFR1	Kinase	yes	2.7.10.1	Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom, Ig_sub2
GLI2	Transcription factor	no		Znf_C2H2_type, Znf_C2H2_sf, GLI-like
PTCH1	Other/Unknown	no		SSD, TM_rcpt_patched, HMGCR/SNAP/NPC1-like_SSD

Expression context

Cohort genes with no expression data: 0.

4 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
tibia	2
kidney epithelium	1
upper arm skin	1
vena cava	1
left testis	1
male germ line stem cell (sensu Vertebrata) in testis	1
right testis	1
buccal mucosa cell	1
calcaneal tendon	1
stromal cell of endometrium	1
germinal epithelium of ovary	1
ventricular zone	1
dorsal root ganglion	1
trigeminal ganglion	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SUFU	226	ubiquitous	yes	upper arm skin, kidney epithelium, vena cava
DISP1	221	ubiquitous	marker	male germ line stem cell (sensu Vertebrata) in testis, right testis, left testis
FGFR1	292	ubiquitous	marker	buccal mucosa cell, stromal cell of endometrium, calcaneal tendon
GLI2	211	ubiquitous	marker	tibia, germinal epithelium of ovary, ventricular zone
PTCH1	275	ubiquitous	marker	tibia, dorsal root ganglion, trigeminal ganglion

Protein interactions among cohort

Intra-cohort edges: 4.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
FGFR1	5,693
PTCH1	3,368
GLI2	3,112
SUFU	2,188
DISP1	621

Intra-cohort edges

A	B	Sources
DISP1	GLI2	string_interaction
GLI2	PTCH1	string_interaction
GLI2	SUFU	string_interaction
PTCH1	SUFU	string_interaction

Structural data

PDB: 4 · AlphaFold-only: 1 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
FGFR1	P11362	83
PTCH1	Q13635	16
SUFU	Q9UMX1	10
DISP1	Q96F81	4

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
GLI2	P10070	42.68

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 34. Enrichment computed across 5 evidence-associated genes (4 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 4 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Hedgehog ‘off’ state	3	133.8×	2e-05	SUFU, GLI2, PTCH1
Hedgehog ‘on’ state	3	119.0×	2e-05	SUFU, GLI2, PTCH1
GLI proteins bind promoters of Hh responsive genes to promote transcription	2	815.7×	2e-05	GLI2, PTCH1
Degradation of GLI2 by the proteasome	2	112.0×	1e-03	SUFU, GLI2
Signaling by FGFR1 amplification mutants	1	1427.5×	0.005	FGFR1
FGFR1c and Klotho ligand binding and activation	1	713.8×	0.007	FGFR1
Signaling by plasma membrane FGFR1 fusions	1	713.8×	0.007	FGFR1
RUNX2 regulates chondrocyte maturation	1	571.0×	0.007	GLI2
Ligand-receptor interactions	1	356.9×	0.010	PTCH1
Epithelial-Mesenchymal Transition (EMT) during gastrulation	1	356.9×	0.010	FGFR1
FGFR1b ligand binding and activation	1	317.2×	0.010	FGFR1
Signaling by activated point mutants of FGFR1	1	237.9×	0.012	FGFR1
FGFR1c ligand binding and activation	1	190.3×	0.014	FGFR1
Phospholipase C-mediated cascade: FGFR1	1	167.9×	0.014	FGFR1
Activation of SMO	1	158.6×	0.014	PTCH1
Downstream signaling of activated FGFR1	1	135.9×	0.014	FGFR1
Signal transduction by L1	1	129.8×	0.014	FGFR1
PI-3K cascade:FGFR1	1	129.8×	0.014	FGFR1
SHC-mediated cascade:FGFR1	1	124.1×	0.014	FGFR1
FRS-mediated FGFR1 signaling	1	114.2×	0.015	FGFR1
Formation of paraxial mesoderm	1	102.0×	0.016	FGFR1
Negative regulation of FGFR1 signaling	1	92.1×	0.017	FGFR1
Signaling by FGFR1 in disease	1	73.2×	0.020	FGFR1
PI3K Cascade	1	68.0×	0.020	FGFR1
NCAM signaling for neurite out-growth	1	68.0×	0.020	FGFR1
Degradation of GLI1 by the proteasome	1	56.0×	0.022	SUFU
GLI3 is processed to GLI3R by the proteasome	1	56.0×	0.022	SUFU
Class B/2 (Secretin family receptors)	1	47.6×	0.025	PTCH1
Signaling by Hedgehog	1	46.0×	0.025	SUFU
Constitutive Signaling by Aberrant PI3K in Cancer	1	31.7×	0.035	FGFR1

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 5 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
dorsal/ventral neural tube patterning	2	321.0×	0.002	SUFU, PTCH1
negative regulation of smoothened signaling pathway	2	182.2×	0.002	SUFU, PTCH1
dorsal/ventral pattern formation	2	168.5×	0.002	DISP1, PTCH1
embryonic limb morphogenesis	2	160.5×	0.002	FGFR1, PTCH1
negative regulation of transcription by RNA polymerase II	4	14.2×	0.002	SUFU, FGFR1, GLI2, PTCH1
stem cell proliferation	2	124.8×	0.003	FGFR1, PTCH1
negative regulation of osteoblast differentiation	2	118.3×	0.003	SUFU, PTCH1
patched ligand maturation	1	3370.4×	0.005	DISP1
positive regulation of cellular response to drug	1	3370.4×	0.005	SUFU
response to chlorate	1	1685.2×	0.005	PTCH1
smoothened signaling pathway involved in ventral spinal cord interneuron specification	1	1685.2×	0.005	SUFU
smoothened signaling pathway involved in spinal cord motor neuron cell fate specification	1	1685.2×	0.005	SUFU
neural plate axis specification	1	1685.2×	0.005	PTCH1
vitamin D3 metabolic process	1	1685.2×	0.005	FGFR1
cell proliferation involved in metanephros development	1	1685.2×	0.005	PTCH1
maintenance of protein localization in organelle	1	1685.2×	0.005	SUFU
positive regulation of mitotic cell cycle DNA replication	1	1685.2×	0.005	FGFR1
positive regulation of parathyroid hormone secretion	1	1685.2×	0.005	FGFR1
regulation of extrinsic apoptotic signaling pathway in absence of ligand	1	1685.2×	0.005	FGFR1
neural tube closure	2	74.9×	0.005	SUFU, PTCH1
smoothened signaling pathway	2	72.5×	0.005	DISP1, GLI2
spermatid development	2	58.1×	0.005	SUFU, PTCH1
skeletal system development	2	50.3×	0.005	FGFR1, GLI2
ventral midline development	1	1123.5×	0.005	GLI2
regulation of phosphate transport	1	1123.5×	0.005	FGFR1
floor plate formation	1	1123.5×	0.005	GLI2
spinal cord ventral commissure morphogenesis	1	1123.5×	0.005	GLI2
fibroblast growth factor receptor signaling pathway involved in orbitofrontal cortex development	1	1123.5×	0.005	FGFR1
regulation of lateral mesodermal cell fate specification	1	1123.5×	0.005	FGFR1
cell differentiation involved in kidney development	1	1123.5×	0.005	PTCH1

Therapeutics

Drug target analysis

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

Druggability breadth: 4 of 5 evidence-associated genes (80%) 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

Top cohort targets by molecule count

Symbol	Molecules	Max phase
FGFR1	93	4
SUFU	0	0
DISP1	0	0
GLI2	0	0
PTCH1	0	0

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
LINIFANIB	3	FGFR1
SEMAXANIB	3	FGFR1
OLVEREMBATINIB	3	FGFR1
BRIVANIB ALANINATE	3	FGFR1
ORANTINIB	3	FGFR1

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
FGFR1	1,465	Binding:1428, Functional:24, ADMET:13
GLI2	6	Binding:6
PTCH1	4	Binding:4
SUFU	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
FGFR1	2.7.10.1	receptor protein-tyrosine kinase

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

Pharmacogenomics

Cohort genes with a PharmGKB record: 5; 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
LINIFANIB	3	FGFR1
SEMAXANIB	3	FGFR1
OLVEREMBATINIB	3	FGFR1
BRIVANIB ALANINATE	3	FGFR1
ORANTINIB	3	FGFR1

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	FGFR1
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	4	SUFU, DISP1, GLI2, PTCH1

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
SUFU	1	—
DISP1	0	—
GLI2	6	—
PTCH1	4	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.