LADD syndrome 1
diseaseOn this page
Also known as lacrimoauriculodentodigital syndrome 1LADD1
Summary
LADD syndrome 1 (MONDO:0100302) is a disease caused by FGFR2 (GenCC Definitive), with 2 cohort genes.
At a glance
- Causal gene: FGFR2 (GenCC Definitive)
- Cohort genes: 2
- ClinVar variants: 73
Clinical features
No curated clinical features (Orphanet) for this disease.
Identifiers
Disease identifiers
| Field | Value |
|---|---|
| Canonical name | LADD syndrome 1 |
| Mondo ID | MONDO:0100302 |
| OMIM | 149730 |
| UMLS | C5774323 |
| MedGen | 1824096 |
| GARD | 0026132 |
| Is cancer (heuristic) | no |
Also known as: lacrimoauriculodentodigital syndrome 1 · LADD1
Data availability: 73 ClinVar variants · 4 GenCC gene-disease records.
Disease family
Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › autosomal genetic disease › autosomal dominant disease › LADD syndrome › LADD syndrome 1
Related subtypes (2): lacrimoauriculodentodigital syndrome 2, lacrimoauriculodentodigital syndrome 3
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
73 retrieved; paginated sample, class counts are floors:
53 uncertain significance, 14 conflicting classifications of pathogenicity, 3 pathogenic, 2 likely benign, 1 pathogenic/likely pathogenic
| ClinVar | Variant (HGVS) | Gene | Classification | Review |
|---|---|---|---|---|
| 13263 | NM_000141.5(FGFR2):c.1025G>A (p.Cys342Tyr) | FGFR2 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 13296 | NM_000141.5(FGFR2):c.1942G>A (p.Ala648Thr) | FGFR2 | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 13297 | NM_000141.5(FGFR2):c.1947_1949del (p.Arg649_Asp650delinsSer) | FGFR2 | Pathogenic | no assertion criteria provided |
| 13298 | NM_000141.5(FGFR2):c.1882G>A (p.Ala628Thr) | FGFR2 | Pathogenic | criteria provided, single submitter |
| 1052478 | NM_000141.5(FGFR2):c.1348C>T (p.Arg450Cys) | FGFR2 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 134387 | NM_000141.5(FGFR2):c.34G>A (p.Val12Met) | FGFR2 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 1503438 | NM_000141.5(FGFR2):c.287G>T (p.Gly96Val) | FGFR2 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 2891853 | NM_000141.5(FGFR2):c.1029G>A (p.Leu343=) | FGFR2 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 2977031 | NM_000141.5(FGFR2):c.963C>A (p.Asp321Glu) | FGFR2 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 298998 | NM_000141.5(FGFR2):c.1774C>T (p.Arg592Cys) | FGFR2 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 3064171 | NM_000141.5(FGFR2):c.943G>A (p.Ala315Thr) | FGFR2 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 3075688 | NM_000141.5(FGFR2):c.1124A>T (p.Tyr375Phe) | FGFR2 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 3591007 | NM_000141.5(FGFR2):c.556A>G (p.Met186Val) | FGFR2 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 3591089 | NM_000141.5(FGFR2):c.151G>A (p.Val51Met) | FGFR2 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 374814 | NM_000141.5(FGFR2):c.940-2A>G | FGFR2 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 577711 | NM_000141.5(FGFR2):c.989G>A (p.Arg330Gln) | FGFR2 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 877638 | NM_000141.5(FGFR2):c.1213A>G (p.Lys405Glu) | FGFR2 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 579912 | NM_000142.5(FGFR3):c.2005C>G (p.Arg669Gly) | FGFR3 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 1317487 | NM_000141.5(FGFR2):c.67C>A (p.Pro23Thr) | FGFR2 | Uncertain significance | criteria provided, multiple submitters, no conflicts |
| 1372714 | NM_000141.5(FGFR2):c.877C>T (p.His293Tyr) | FGFR2 | Uncertain significance | criteria provided, multiple submitters, no conflicts |
| 1388509 | NM_000141.5(FGFR2):c.419C>T (p.Ala140Val) | FGFR2 | Uncertain significance | criteria provided, multiple submitters, no conflicts |
| 1412875 | NM_000141.5(FGFR2):c.1985A>G (p.Asn662Ser) | FGFR2 | Uncertain significance | criteria provided, multiple submitters, no conflicts |
| 1506367 | NM_000141.5(FGFR2):c.1085C>T (p.Ala362Val) | FGFR2 | Uncertain significance | criteria provided, multiple submitters, no conflicts |
| 1700436 | NM_000141.5(FGFR2):c.1637A>C (p.Asn546Thr) | FGFR2 | Uncertain significance | criteria provided, multiple submitters, no conflicts |
| 1903593 | NM_000141.5(FGFR2):c.1342A>G (p.Thr448Ala) | FGFR2 | Uncertain significance | criteria provided, multiple submitters, no conflicts |
| 1966091 | NM_000141.5(FGFR2):c.257T>G (p.Val86Gly) | FGFR2 | Uncertain significance | criteria provided, multiple submitters, no conflicts |
| 1971541 | NM_000141.5(FGFR2):c.1486G>A (p.Val496Ile) | FGFR2 | Uncertain significance | criteria provided, multiple submitters, no conflicts |
| 2072601 | NM_000141.5(FGFR2):c.293C>T (p.Thr98Met) | FGFR2 | Uncertain significance | criteria provided, multiple submitters, no conflicts |
| 2076324 | NM_000141.5(FGFR2):c.143A>C (p.Glu48Ala) | FGFR2 | Uncertain significance | criteria provided, multiple submitters, no conflicts |
| 2172927 | NM_000141.5(FGFR2):c.544G>T (p.Gly182Trp) | FGFR2 | Uncertain significance | criteria provided, multiple submitters, no conflicts |
Genes & proteins
Mendelian disease overlap and somatic drivers
GenCC: 90 · Orphanet: 25 · 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 |
|---|---|---|---|---|
| FGFR2 | Definitive | Autosomal dominant | LADD syndrome 1 | 38 |
| FGFR3 | Supportive | Autosomal dominant | LADD syndrome | 52 |
Orphanet rare-disease linkage (cohort genes)
| Gene | Orphanet ID | Rare disease |
|---|---|---|
| FGFR2 | Orphanet:1540 | Jackson-Weiss syndrome |
| FGFR2 | Orphanet:1555 | Cutis gyrata-acanthosis nigricans-craniosynostosis syndrome |
| FGFR2 | Orphanet:168624 | Familial scaphocephaly syndrome, McGillivray type |
| FGFR2 | Orphanet:207 | Crouzon syndrome |
| FGFR2 | Orphanet:2363 | Lacrimoauriculodentodigital syndrome |
| FGFR2 | Orphanet:313855 | FGFR2-related bent bone dysplasia |
| FGFR2 | Orphanet:596008 | Antley-Bixler syndrome without genital anomaly or disorder of steroidogenesis |
| FGFR2 | Orphanet:794 | Saethre-Chotzen syndrome |
| FGFR2 | Orphanet:87 | Apert syndrome |
| FGFR2 | Orphanet:93258 | Pfeiffer syndrome type 1 |
| FGFR2 | Orphanet:93259 | Pfeiffer syndrome type 2 |
| FGFR2 | Orphanet:93260 | Pfeiffer syndrome type 3 |
| FGFR3 | Orphanet:15 | Achondroplasia |
| FGFR3 | Orphanet:1860 | Thanatophoric dysplasia type 1 |
| FGFR3 | Orphanet:2363 | Lacrimoauriculodentodigital syndrome |
| FGFR3 | Orphanet:251576 | Gliosarcoma |
| FGFR3 | Orphanet:251579 | Giant cell glioblastoma |
| FGFR3 | Orphanet:35099 | Non-syndromic bicoronal craniosynostosis |
| FGFR3 | Orphanet:429 | Hypochondroplasia |
| FGFR3 | Orphanet:53271 | Muenke syndrome |
| FGFR3 | Orphanet:794 | Saethre-Chotzen syndrome |
| FGFR3 | Orphanet:85164 | Camptodactyly-tall stature-scoliosis-hearing loss syndrome |
| FGFR3 | Orphanet:85165 | Severe achondroplasia-developmental delay-acanthosis nigricans syndrome |
| FGFR3 | Orphanet:93262 | Crouzon syndrome-acanthosis nigricans syndrome |
| FGFR3 | Orphanet:93274 | Thanatophoric dysplasia type 2 |
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 |
|---|---|---|---|---|---|
| FGFR2 | HGNC:3689 | ENSG00000066468 | P21802 | Fibroblast growth factor receptor 2 | gencc,clinvar |
| FGFR3 | HGNC:3690 | ENSG00000068078 | P22607 | Fibroblast growth factor receptor 3 | gencc,clinvar |
Cohort function summary
Lead sentence per gene, UniProt-curated.
| Symbol | Protein name | Function (lead sentence) |
|---|---|---|
| FGFR2 | Fibroblast growth factor receptor 2 | Tyrosine-protein kinase that acts as a cell-surface receptor for fibroblast growth factors and plays an essential role in the regulation of cell proliferation, differentiation, migration and apoptosis, and in the regulation of embryonic de… |
| FGFR3 | Fibroblast growth factor receptor 3 | Tyrosine-protein kinase that acts as a cell-surface receptor for fibroblast growth factors and plays an essential role in the regulation of cell proliferation, differentiation and apoptosis. |
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 | 2 | 27.7× | 0.001 |
Per-gene assignment
| Symbol | Family | Druggable? | EC | InterPro (top 3) |
|---|---|---|---|---|
| FGFR2 | Kinase | yes | 2.7.10.1 | Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom, Ig_sub2 |
| FGFR3 | Kinase | yes | 2.7.10.1 | Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom, Ig_sub2 |
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 |
|---|---|
| C1 segment of cervical spinal cord | 1 |
| corpus callosum | 1 |
| spinal cord | 1 |
| skin of hip | 1 |
| upper arm skin | 1 |
| upper leg skin | 1 |
Per-gene tissue summary (top 30)
| Symbol | Bgee breadth | FANTOM5 breadth | SCXA | Top tissues |
|---|---|---|---|---|
| FGFR2 | 272 | broad | marker | C1 segment of cervical spinal cord, spinal cord, corpus callosum |
| FGFR3 | 262 | broad | marker | upper leg skin, skin of hip, upper arm skin |
Protein interactions among cohort
Intra-cohort edges: 0.
Hub genes (top 10 by interactor count)
| Symbol | Interactor count |
|---|---|
| FGFR3 | 4,510 |
| FGFR2 | 449 |
Structural data
PDB: 2 · AlphaFold-only: 0 · No structure: 0
Cohort genes with PDB structures (top 30)
| Symbol | UniProt | PDB entries |
|---|---|---|
| FGFR2 | P21802 | 63 |
| FGFR3 | P22607 | 15 |
Function
Pathway analysis
Distinct Reactome pathways touched by cohort: 29. 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 |
|---|---|---|---|---|
| PI3K Cascade | 2 | 271.9× | 4e-04 | FGFR2, FGFR3 |
| Signaling by FGFR2 amplification mutants | 1 | 5710.0× | 7e-04 | FGFR2 |
| t(4;14) translocations of FGFR3 | 1 | 5710.0× | 7e-04 | FGFR3 |
| Signaling by FGFR2 fusions | 1 | 5710.0× | 7e-04 | FGFR2 |
| Signaling by FGFR3 fusions in cancer | 1 | 5710.0× | 7e-04 | FGFR3 |
| Constitutive Signaling by Aberrant PI3K in Cancer | 2 | 126.9× | 7e-04 | FGFR2, FGFR3 |
| PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling | 2 | 96.8× | 7e-04 | FGFR2, FGFR3 |
| PIP3 activates AKT signaling | 2 | 66.8× | 8e-04 | FGFR2, FGFR3 |
| RAF/MAP kinase cascade | 2 | 61.1× | 9e-04 | FGFR2, FGFR3 |
| FGFR3b ligand binding and activation | 1 | 815.7× | 0.004 | FGFR3 |
| FGFR2b ligand binding and activation | 1 | 571.0× | 0.004 | FGFR2 |
| Signaling by activated point mutants of FGFR3 | 1 | 475.8× | 0.004 | FGFR3 |
| FGFR3c ligand binding and activation | 1 | 439.2× | 0.004 | FGFR3 |
| FGFR2c ligand binding and activation | 1 | 439.2× | 0.004 | FGFR2 |
| Phospholipase C-mediated cascade; FGFR3 | 1 | 439.2× | 0.004 | FGFR3 |
| Activated point mutants of FGFR2 | 1 | 335.9× | 0.005 | FGFR2 |
| Phospholipase C-mediated cascade; FGFR2 | 1 | 317.2× | 0.005 | FGFR2 |
| PI-3K cascade:FGFR3 | 1 | 317.2× | 0.005 | FGFR3 |
| SHC-mediated cascade:FGFR3 | 1 | 300.5× | 0.005 | FGFR3 |
| Signaling by FGFR2 IIIa TM | 1 | 300.5× | 0.005 | FGFR2 |
| FRS-mediated FGFR3 signaling | 1 | 271.9× | 0.005 | FGFR3 |
| PI-3K cascade:FGFR2 | 1 | 248.3× | 0.005 | FGFR2 |
| Signaling by FGFR3 in disease | 1 | 248.3× | 0.005 | FGFR3 |
| SHC-mediated cascade:FGFR2 | 1 | 237.9× | 0.005 | FGFR2 |
| FRS-mediated FGFR2 signaling | 1 | 219.6× | 0.005 | FGFR2 |
| Negative regulation of FGFR3 signaling | 1 | 219.6× | 0.005 | FGFR3 |
| FGFR2 alternative splicing | 1 | 211.5× | 0.005 | FGFR2 |
| Negative regulation of FGFR2 signaling | 1 | 184.2× | 0.006 | FGFR2 |
| Signaling by FGFR2 in disease | 1 | 132.8× | 0.008 | FGFR2 |
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 |
|---|---|---|---|---|
| positive regulation of phospholipase activity | 2 | 3370.4× | 7e-06 | FGFR2, FGFR3 |
| endochondral bone growth | 2 | 1685.2× | 2e-05 | FGFR2, FGFR3 |
| bone morphogenesis | 2 | 601.9× | 9e-05 | FGFR2, FGFR3 |
| fibroblast growth factor receptor signaling pathway | 2 | 285.6× | 3e-04 | FGFR2, FGFR3 |
| bone mineralization | 2 | 271.8× | 3e-04 | FGFR2, FGFR3 |
| fibroblast growth factor receptor signaling pathway involved in negative regulation of apoptotic process in bone marrow cell | 1 | 8426.0× | 0.001 | FGFR2 |
| fibroblast growth factor receptor signaling pathway involved in hemopoiesis | 1 | 8426.0× | 0.001 | FGFR2 |
| fibroblast growth factor receptor signaling pathway involved in positive regulation of cell proliferation in bone marrow | 1 | 8426.0× | 0.001 | FGFR2 |
| negative regulation of developmental growth | 1 | 8426.0× | 0.001 | FGFR3 |
| lateral sprouting from an epithelium | 1 | 8426.0× | 0.001 | FGFR2 |
| orbitofrontal cortex development | 1 | 4213.0× | 0.001 | FGFR2 |
| prostate gland morphogenesis | 1 | 4213.0× | 0.001 | FGFR2 |
| squamous basal epithelial stem cell differentiation involved in prostate gland acinus development | 1 | 4213.0× | 0.001 | FGFR2 |
| mammary gland bud formation | 1 | 4213.0× | 0.001 | FGFR2 |
| branch elongation involved in salivary gland morphogenesis | 1 | 4213.0× | 0.001 | FGFR2 |
| mesenchymal cell differentiation involved in lung development | 1 | 4213.0× | 0.001 | FGFR2 |
| fibroblast growth factor receptor apoptotic signaling pathway | 1 | 4213.0× | 0.001 | FGFR3 |
| positive regulation of ERK1 and ERK2 cascade | 2 | 85.1× | 0.001 | FGFR2, FGFR3 |
| positive regulation of MAPK cascade | 2 | 80.6× | 0.001 | FGFR2, FGFR3 |
| cell-cell signaling | 2 | 69.6× | 0.001 | FGFR2, FGFR3 |
| regulation of osteoblast proliferation | 1 | 2808.7× | 0.002 | FGFR2 |
| fibroblast growth factor receptor signaling pathway involved in orbitofrontal cortex development | 1 | 2808.7× | 0.002 | FGFR2 |
| prostate epithelial cord elongation | 1 | 2808.7× | 0.002 | FGFR2 |
| bone maturation | 1 | 2808.7× | 0.002 | FGFR3 |
| ventricular zone neuroblast division | 1 | 2106.5× | 0.002 | FGFR2 |
| embryonic organ morphogenesis | 1 | 2106.5× | 0.002 | FGFR2 |
| reproductive structure development | 1 | 2106.5× | 0.002 | FGFR2 |
| regulation of morphogenesis of a branching structure | 1 | 2106.5× | 0.002 | FGFR2 |
| regulation of smooth muscle cell differentiation | 1 | 1685.2× | 0.002 | FGFR2 |
| branching involved in prostate gland morphogenesis | 1 | 1685.2× | 0.002 | FGFR2 |
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 |
|---|---|
| FGFR2 | PONATINIB |
| FGFR3 | PONATINIB |
Top cohort targets by molecule count
| Symbol | Molecules | Max phase |
|---|---|---|
| FGFR3 | 64 | 4 |
| FGFR2 | 59 | 4 |
Drugs targeting cohort genes (top 30)
| Molecule | Max phase | Targets in cohort |
|---|---|---|
| PONATINIB | 4 | FGFR2, FGFR3 |
| PEMIGATINIB | 4 | FGFR2, FGFR3 |
| NINTEDANIB | 4 | FGFR2, FGFR3 |
| FEDRATINIB | 4 | FGFR2, FGFR3 |
| LENVATINIB | 4 | FGFR2, FGFR3 |
| AXITINIB | 4 | FGFR2, FGFR3 |
| SORAFENIB | 4 | FGFR2, FGFR3 |
| INFIGRATINIB PHOSPHATE | 4 | FGFR2, FGFR3 |
| INFIGRATINIB | 4 | FGFR2, FGFR3 |
| IBRUTINIB | 4 | FGFR2 |
| CERITINIB | 4 | FGFR2, FGFR3 |
| VANDETANIB | 4 | FGFR2, FGFR3 |
| NINTEDANIB ESYLATE | 4 | FGFR2, FGFR3 |
| BRIGATINIB | 4 | FGFR2, FGFR3 |
| ERDAFITINIB | 4 | FGFR2, FGFR3 |
| FUTIBATINIB | 4 | FGFR2, FGFR3 |
| PAZOPANIB | 4 | FGFR2, FGFR3 |
| SUNITINIB | 4 | FGFR2, FGFR3 |
| DASATINIB | 4 | FGFR2, FGFR3 |
| ERLOTINIB | 4 | FGFR2 |
| MIDOSTAURIN | 4 | FGFR2, FGFR3 |
| ENTRECTINIB | 4 | FGFR3 |
| CRIZOTINIB | 4 | FGFR3 |
| LINIFANIB | 3 | FGFR2, FGFR3 |
| SEMAXANIB | 3 | FGFR2, FGFR3 |
| BRIVANIB | 3 | FGFR2, FGFR3 |
| CEDIRANIB | 3 | FGFR2, FGFR3 |
| DOVITINIB | 3 | FGFR2, FGFR3 |
| LESTAURTINIB | 3 | FGFR2, FGFR3 |
| ALISERTIB | 3 | FGFR3 |
Bioactivity and enzyme data
Enzyme cohort genes (≥1 EC): 2.
Cohort genes with ChEMBL bioactivity (full, sorted by assay count)
| Symbol | Assays | Type breakdown |
|---|---|---|
| FGFR3 | 975 | Binding:948, Functional:18, ADMET:9 |
| FGFR2 | 966 | Binding:940, Functional:22, ADMET:4 |
Cohort enzymes (BRENDA EC)
| Symbol | EC numbers | Names |
|---|---|---|
| FGFR2 | 2.7.10.1 | receptor protein-tyrosine kinase |
| FGFR3 | 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 |
|---|---|
| FGFR2 | 966 |
| FGFR3 | 975 |
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 | FGFR2, FGFR3 |
| PEMIGATINIB | 4 | FGFR2, FGFR3 |
| NINTEDANIB | 4 | FGFR2, FGFR3 |
| FEDRATINIB | 4 | FGFR2, FGFR3 |
| LENVATINIB | 4 | FGFR2, FGFR3 |
| AXITINIB | 4 | FGFR2, FGFR3 |
| SORAFENIB | 4 | FGFR2, FGFR3 |
| INFIGRATINIB PHOSPHATE | 4 | FGFR2, FGFR3 |
| INFIGRATINIB | 4 | FGFR2, FGFR3 |
| IBRUTINIB | 4 | FGFR2 |
| CERITINIB | 4 | FGFR2, FGFR3 |
| VANDETANIB | 4 | FGFR2, FGFR3 |
| NINTEDANIB ESYLATE | 4 | FGFR2, FGFR3 |
| BRIGATINIB | 4 | FGFR2, FGFR3 |
| ERDAFITINIB | 4 | FGFR2, FGFR3 |
| FUTIBATINIB | 4 | FGFR2, FGFR3 |
| PAZOPANIB | 4 | FGFR2, FGFR3 |
| SUNITINIB | 4 | FGFR2, FGFR3 |
| DASATINIB | 4 | FGFR2, FGFR3 |
| ERLOTINIB | 4 | FGFR2 |
| MIDOSTAURIN | 4 | FGFR2, FGFR3 |
| ENTRECTINIB | 4 | FGFR3 |
| CRIZOTINIB | 4 | FGFR3 |
| LINIFANIB | 3 | FGFR2, FGFR3 |
| SEMAXANIB | 3 | FGFR2, FGFR3 |
| BRIVANIB | 3 | FGFR2, FGFR3 |
| CEDIRANIB | 3 | FGFR2, FGFR3 |
| DOVITINIB | 3 | FGFR2, FGFR3 |
| LESTAURTINIB | 3 | FGFR2, FGFR3 |
| ALISERTIB | 3 | FGFR3 |
Druggability pyramid
Cohort genes binned by druggability tier (high → low):
| Tier | Definition | Genes | Symbols |
|---|---|---|---|
| A | Approved (phase 4 drug) | 2 | FGFR2, FGFR3 |
| 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.