Hypogonadotropic hypogonadism 2 with or without anosmia

Summary

Hypogonadotropic hypogonadism 2 with or without anosmia (MONDO:0007844) is a disease caused by FGFR1 (GenCC Definitive), with 5 cohort genes.

At a glance

• Causal gene: FGFR1 (GenCC Definitive)
• Cohort genes: 5
• ClinVar variants: 964

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	hypogonadotropic hypogonadism 2 with or without anosmia
Mondo ID	MONDO:0007844
OMIM	147950
DOID	DOID:0090083
UMLS	C1563720
MedGen	289648
GARD	0003070
Is cancer (heuristic)	no

Also known as: FGFR1 hypogonadotropic hypogonadism · HH2 · hypogonadotropic hypogonadism 2 with or without anosmia · hypogonadotropic hypogonadism caused by mutation in FGFR1 · KAL2

Data availability: 964 ClinVar variants · 4 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › syndromic disease › Kallmann syndrome › hypogonadotropic hypogonadism 2 with or without anosmia

Related subtypes (17): hypogonadotropic hypogonadism 3 with or without anosmia, hypogonadotropic hypogonadism 1 with or without anosmia, hypogonadotropic hypogonadism 4 with or without anosmia, hypogonadotropic hypogonadism 5 with or without anosmia, hypogonadotropic hypogonadism 6 with or without anosmia, hypogonadotropic hypogonadism 8 with or without anosmia, hypogonadotropic hypogonadism 9 with or without anosmia, hypogonadotropic hypogonadism 11 with or without anosmia, hypogonadotropic hypogonadism 14 with or without anosmia, hypogonadotropic hypogonadism 15 with or without anosmia, hypogonadotropic hypogonadism 16 with or without anosmia, hypogonadotropic hypogonadism 17 with or without anosmia, hypogonadotropic hypogonadism 18 with or without anosmia, hypogonadotropic hypogonadism 19 with or without anosmia, hypogonadotropic hypogonadism 20 with or without anosmia, hypogonadotropic hypogonadism 21 with or without anosmia, hypogonadotropic hypogonadism 22 with or without anosmia

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:

228 uncertain significance, 192 likely benign, 71 pathogenic, 43 conflicting classifications of pathogenicity, 36 likely pathogenic, 15 pathogenic/likely pathogenic, 9 benign/likely benign, 5 benign, 1 risk factor

ClinVar	Variant (HGVS)	Gene	Classification	Review
1455925	NC_000008.10:g.(?37595441)(38961219_?)del	EIF4EBP1	Pathogenic	criteria provided, single submitter
1074220	NM_023110.3(FGFR1):c.979_983del (p.His327fs)	FGFR1	Pathogenic	criteria provided, single submitter
1184446	NM_023110.3(FGFR1):c.2122G>T (p.Glu708Ter)	FGFR1	Pathogenic	criteria provided, single submitter
1208776	NM_023110.3(FGFR1):c.962_963del (p.Lys321fs)	FGFR1	Pathogenic	criteria provided, multiple submitters, no conflicts
132646	NM_023110.3(FGFR1):c.790A>C (p.Asn264His)	FGFR1	Pathogenic	no assertion criteria provided
132647	NM_023110.3(FGFR1):c.1460G>A (p.Gly487Asp)	FGFR1	Pathogenic	criteria provided, single submitter
132648	NM_023110.3(FGFR1):c.2084C>T (p.Thr695Ile)	FGFR1	Pathogenic	no assertion criteria provided
1335817	NM_023110.3(FGFR1):c.1981C>T (p.Arg661Ter)	FGFR1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1341671	NM_023110.3(FGFR1):c.748C>T (p.Arg250Trp)	FGFR1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1341672	NM_023110.3(FGFR1):c.1855-1G>A	FGFR1	Pathogenic	no assertion criteria provided
1418780	NM_023110.3(FGFR1):c.1265dup (p.Leu423fs)	FGFR1	Pathogenic	criteria provided, single submitter
16279	NM_023110.3(FGFR1):c.755C>G (p.Pro252Arg)	FGFR1	Pathogenic	criteria provided, multiple submitters, no conflicts
16282	NM_023110.3(FGFR1):c.1864C>T (p.Arg622Ter)	FGFR1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
16290	NM_023110.3(FGFR1):c.1141T>C (p.Cys381Arg)	FGFR1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
16293	NM_023110.3(FGFR1):c.2038C>T (p.Gln680Ter)	FGFR1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
16296	NM_023110.3(FGFR1):c.1825C>T (p.Arg609Ter)	FGFR1	Pathogenic	criteria provided, multiple submitters, no conflicts
16301	NM_023110.3(FGFR1):c.2292G>T (p.Gln764His)	FGFR1	Pathogenic	no assertion criteria provided
16303	NM_023110.3(FGFR1):c.749G>A (p.Arg250Gln)	FGFR1	Pathogenic	criteria provided, multiple submitters, no conflicts
1709350	NM_023110.3(FGFR1):c.1969dup (p.Thr657fs)	FGFR1	Pathogenic	criteria provided, single submitter
1801171	NM_023110.3(FGFR1):c.246_247del (p.Glu84fs)	FGFR1	Pathogenic	criteria provided, multiple submitters, no conflicts
180153	NM_023110.3(FGFR1):c.1916T>C (p.Ile639Thr)	FGFR1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
180154	NM_023110.3(FGFR1):c.1037_1038del (p.Ser346fs)	FGFR1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
180156	NM_023110.3(FGFR1):c.296A>G (p.Tyr99Cys)	FGFR1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
180160	NM_023110.3(FGFR1):c.2059G>A (p.Gly687Arg)	FGFR1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1997422	NM_023110.3(FGFR1):c.111del (p.Val38fs)	FGFR1	Pathogenic	criteria provided, single submitter
2011123	NM_023110.3(FGFR1):c.625del (p.Arg209fs)	FGFR1	Pathogenic	criteria provided, single submitter
2029325	NM_023110.3(FGFR1):c.780del (p.Leu261fs)	FGFR1	Pathogenic	criteria provided, single submitter
2097346	NM_023110.3(FGFR1):c.1568_1569dup (p.Asp524fs)	FGFR1	Pathogenic	criteria provided, single submitter
2105298	NM_023110.3(FGFR1):c.2048T>G (p.Val683Gly)	FGFR1	Pathogenic	criteria provided, single submitter
2136660	NM_023110.3(FGFR1):c.1883A>G (p.Asn628Ser)	FGFR1	Pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 36 · Orphanet: 21 · 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	hypogonadotropic hypogonadism 2 with or without anosmia	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
PROKR2	Orphanet:3157	Septo-optic dysplasia spectrum
PROKR2	Orphanet:432	Normosmic congenital hypogonadotropic hypogonadism
PROKR2	Orphanet:478	Kallmann syndrome
PROKR2	Orphanet:95496	Pituitary stalk interruption syndrome

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
FGFR1	HGNC:3688	ENSG00000077782	P11362	Fibroblast growth factor receptor 1	gencc,clinvar
PROKR2	HGNC:15836	ENSG00000101292	Q8NFJ6	Prokineticin receptor 2	clinvar
ADGRA2	HGNC:17849	ENSG00000020181	Q96PE1	Adhesion G protein-coupled receptor A2	clinvar
GOT1L1	HGNC:28487	ENSG00000169154	Q8NHS2	Putative aspartate aminotransferase, cytoplasmic 2	clinvar
EIF4EBP1	HGNC:3288	ENSG00000187840	Q13541	Eukaryotic translation initiation factor 4E-binding protein 1	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.
PROKR2	Prokineticin receptor 2	Receptor for prokineticin 2.
ADGRA2	Adhesion G protein-coupled receptor A2	Endothelial receptor which functions together with RECK to enable brain endothelial cells to selectively respond to Wnt7 signals (WNT7A or WNT7B).
EIF4EBP1	Eukaryotic translation initiation factor 4E-binding protein 1	Repressor of translation initiation that regulates EIF4E activity by preventing its assembly into the eIF4F complex: hypophosphorylated form competes with EIF4G1/EIF4G3 and strongly binds to EIF4E, leading to repress translation.

Protein-family classification

Druggable: 4 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.8

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
GPCR	2	9.6×	0.064
Kinase	1	5.5×	0.336
Enzyme (other)	1	2.4×	0.471
Other/Unknown	1	0.4×	0.983

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
PROKR2	GPCR	yes		GPCR_Rhodpsn, NPY_rcpt, GPCR_Rhodpsn_7TM
ADGRA2	GPCR	yes		GPS, Cys-rich_flank_reg_C, GPCR_2_secretin-like
GOT1L1	Enzyme (other)	yes	2.6.1.1	Asp_trans, Aminotransferase_I/II_large, PyrdxlP-dep_Trfase_major
EIF4EBP1	Other/Unknown	no		EIF4EBP

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
stromal cell of endometrium	2
buccal mucosa cell	1
calcaneal tendon	1
cortical plate	1
ganglionic eminence	1
ventricular zone	1
endocervix	1
seminal vesicle	1
left testis	1
male germ line stem cell (sensu Vertebrata) in testis	1
testis	1
body of pancreas	1
lower esophagus mucosa	1
parotid gland	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
PROKR2	32	tissue_specific	yes	cortical plate, ganglionic eminence, ventricular zone
ADGRA2	226	ubiquitous	marker	stromal cell of endometrium, seminal vesicle, endocervix
GOT1L1	42	tissue_specific	marker	male germ line stem cell (sensu Vertebrata) in testis, left testis, testis
EIF4EBP1	251	ubiquitous	marker	body of pancreas, parotid gland, lower esophagus mucosa

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
FGFR1	5,693
EIF4EBP1	2,189
GOT1L1	1,699
ADGRA2	1,345
PROKR2	844

Intra-cohort edges

A	B	Sources
FGFR1	PROKR2	string_interaction

Structural data

PDB: 2 · AlphaFold-only: 3 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
FGFR1	P11362	83
EIF4EBP1	Q13541	24

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
GOT1L1	Q8NHS2	91.97
PROKR2	Q8NFJ6	78.50
ADGRA2	Q96PE1	70.47

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 32. 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
Signaling by FGFR1 amplification mutants	1	1903.3×	0.011	FGFR1
FGFR1c and Klotho ligand binding and activation	1	951.7×	0.011	FGFR1
Signaling by plasma membrane FGFR1 fusions	1	951.7×	0.011	FGFR1
Epithelial-Mesenchymal Transition (EMT) during gastrulation	1	475.8×	0.015	FGFR1
FGFR1b ligand binding and activation	1	423.0×	0.015	FGFR1
Signaling by activated point mutants of FGFR1	1	317.2×	0.015	FGFR1
FGFR1c ligand binding and activation	1	253.8×	0.015	FGFR1
Phospholipase C-mediated cascade: FGFR1	1	223.9×	0.015	FGFR1
Downstream signaling of activated FGFR1	1	181.3×	0.015	FGFR1
Signal transduction by L1	1	173.0×	0.015	FGFR1
PI-3K cascade:FGFR1	1	173.0×	0.015	FGFR1
SHC-mediated cascade:FGFR1	1	165.5×	0.015	FGFR1
mTORC1-mediated signalling	1	158.6×	0.015	EIF4EBP1
FRS-mediated FGFR1 signaling	1	152.3×	0.015	FGFR1
Formation of paraxial mesoderm	1	135.9×	0.016	FGFR1
Negative regulation of FGFR1 signaling	1	122.8×	0.016	FGFR1
Eukaryotic Translation Initiation	1	102.9×	0.016	EIF4EBP1
Cap-dependent Translation Initiation	1	102.9×	0.016	EIF4EBP1
Signaling by FGFR1 in disease	1	97.6×	0.016	FGFR1
PI3K Cascade	1	90.6×	0.016	FGFR1
NCAM signaling for neurite out-growth	1	90.6×	0.016	FGFR1
Activation of the mRNA upon binding of the cap-binding complex and eIFs, and subsequent binding to 43S	1	90.6×	0.016	EIF4EBP1
MTOR signalling	1	88.5×	0.016	EIF4EBP1
Constitutive Signaling by Aberrant PI3K in Cancer	1	42.3×	0.031	FGFR1
PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling	1	32.3×	0.039	FGFR1
Peptide ligand-binding receptors	1	24.7×	0.049	PROKR2
PIP3 activates AKT signaling	1	22.3×	0.052	FGFR1
Translation	1	20.7×	0.053	EIF4EBP1
RAF/MAP kinase cascade	1	20.4×	0.053	FGFR1
G alpha (q) signalling events	1	19.1×	0.055	PROKR2

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
vitamin D3 metabolic process	1	1685.2×	0.009	FGFR1
regulation of establishment of blood-brain barrier	1	1685.2×	0.009	ADGRA2
positive regulation of mitotic cell cycle DNA replication	1	1685.2×	0.009	FGFR1
positive regulation of parathyroid hormone secretion	1	1685.2×	0.009	FGFR1
regulation of extrinsic apoptotic signaling pathway in absence of ligand	1	1685.2×	0.009	FGFR1
L-aspartate biosynthetic process	1	1123.5×	0.009	GOT1L1
regulation of phosphate transport	1	1123.5×	0.009	FGFR1
fibroblast growth factor receptor signaling pathway involved in orbitofrontal cortex development	1	1123.5×	0.009	FGFR1
regulation of lateral mesodermal cell fate specification	1	1123.5×	0.009	FGFR1
ventricular zone neuroblast division	1	842.6×	0.009	FGFR1
negative regulation of fibroblast growth factor production	1	842.6×	0.009	FGFR1
positive regulation of phospholipase activity	1	674.1×	0.009	FGFR1
regulation of branching involved in salivary gland morphogenesis by mesenchymal-epithelial signaling	1	674.1×	0.009	FGFR1
diphosphate metabolic process	1	674.1×	0.009	FGFR1
chordate embryonic development	1	561.7×	0.009	FGFR1
regulation of chemotaxis	1	561.7×	0.009	ADGRA2
positive regulation of MAPKKK cascade by fibroblast growth factor receptor signaling pathway	1	561.7×	0.009	FGFR1
cementum mineralization	1	481.5×	0.010	FGFR1
auditory receptor cell development	1	374.5×	0.012	FGFR1
paraxial mesoderm development	1	337.0×	0.012	FGFR1
lung-associated mesenchyme development	1	337.0×	0.012	FGFR1
response to sodium phosphate	1	337.0×	0.012	FGFR1
outer ear morphogenesis	1	306.4×	0.012	FGFR1
branching involved in salivary gland morphogenesis	1	280.9×	0.013	FGFR1
negative regulation of vascular endothelial growth factor signaling pathway	1	259.3×	0.014	ADGRA2
organ induction	1	240.7×	0.014	FGFR1
mesenchymal cell proliferation	1	224.7×	0.014	FGFR1
positive regulation of endothelial cell chemotaxis	1	198.3×	0.016	FGFR1
cell projection assembly	1	187.2×	0.016	FGFR1
negative regulation of translational initiation	1	177.4×	0.016	EIF4EBP1

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
PROKR2	0	0
ADGRA2	0	0
GOT1L1	0	0
EIF4EBP1	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): 2.

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

Symbol	Assays	Type breakdown
FGFR1	1,465	Binding:1428, Functional:24, ADMET:13
EIF4EBP1	33	Binding:33
PROKR2	9	Functional:5, Binding:4
ADGRA2	2	Binding:2

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
FGFR1	2.7.10.1	receptor protein-tyrosine kinase
GOT1L1	2.6.1.1	aspartate transaminase

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	3	PROKR2, ADGRA2, GOT1L1
E	Difficult family or no structure, no drug	1	EIF4EBP1

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)
PROKR2	9	—
ADGRA2	2	—
GOT1L1	0	—
EIF4EBP1	33	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.