recessive X-linked ichthyosis

Summary

recessive X-linked ichthyosis (MONDO:0010622) is a disease caused by STS (GenCC Definitive), with 6 cohort genes and 1 clinical trial.

At a glance

• Prevalence: 1-5 / 10 000 (Europe) [Orphanet-validated]
• Causal gene: STS (GenCC Definitive)
• Cohort genes: 6
• ClinVar variants: 42
• Phenotypes (HPO): 12
• Clinical trials: 1

Clinical features

Epidemiology

Prevalence records

3 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Annual incidence	1-5 / 10 000	15	Europe	Validated
Point prevalence	1-5 / 10 000	16.6	Europe	Validated
Annual incidence	1-9 / 100 000	9.9	Italy	Not yet validated

Signs & symptoms

Clinical features (HPO)

12 HPO clinical features (Orphanet curated; top 12 by frequency):

HPO ID	Term	Frequency
HP:0000958	Dry skin	Very frequent (80-99%)
HP:0000962	Hyperkeratosis	Very frequent (80-99%)
HP:0000966	Hypohidrosis	Very frequent (80-99%)
HP:0008064	Ichthyosis	Very frequent (80-99%)
HP:0007018	Attention deficit hyperactivity disorder	Frequent (30-79%)
HP:0007759	Opacification of the corneal stroma	Frequent (30-79%)
HP:0000028	Cryptorchidism	Occasional (5-29%)
HP:0000717	Autism	Occasional (5-29%)
HP:0001270	Motor delay	Occasional (5-29%)
HP:0002167	Abnormality of speech or vocalization	Occasional (5-29%)
HP:0007549	Desquamation of skin soon after birth	Occasional (5-29%)
HP:0001249	Intellectual disability	Very rare (<1-4%)

Identifiers

Disease identifiers

Field	Value
Canonical name	recessive X-linked ichthyosis
Mondo ID	MONDO:0010622
OMIM	308100
Orphanet	461
DOID	DOID:1700
ICD-10-CM	Q80.1
ICD-11	1466487054
NCIT	C84779
SNOMED CT	3944006
UMLS	C0079588
MedGen	86937
GARD	0007904
MedDRA	10048063
NORD	1293
Is cancer (heuristic)	no

Also known as: ichthyosis (disease), X-linked · ichthyosis , X-linked, X-linked recessive · Ichthyosis, X Linked · ichthyosis, X-linked · recessive X-linked ichthyosis · RXLI · SSDD · steroid sulfatase deficiency · X linked ichthyosis · X-linked ichthyosis · X-linked recessive ichthyosis · XLI

Data availability: 42 ClinVar variants · 6 GenCC gene-disease records · 11 cell lines.

Disease family

An umbrella term covering 1 Mondo subtype.

Classification path: disease › human disease › disease by body system or component › integumentary system disorder › skin disorder › epidermal disease › ichthyosis › inherited ichthyosis › recessive X-linked ichthyosis

Related subtypes (12): congenital cataract-ichthyosis syndrome, Netherton syndrome, ichthyosis-oral and digital anomalies syndrome, neonatal ichthyosis-sclerosing cholangitis syndrome, autosomal recessive congenital ichthyosis, keratinopathic ichthyosis, peeling skin syndrome, ichthyosis vulgaris, ichthyosis linearis circumflexa, IFAP syndrome, ichthyosis hystrix, ichthyosis with erythrokeratoderma

Subtypes (1): ichthyosis, X-linked, without steroid sulfatase deficiency

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

42 retrieved; paginated sample, class counts are floors:

24 pathogenic, 7 uncertain significance, 5 likely pathogenic, 3 conflicting classifications of pathogenicity, 2 benign/likely benign, 1 not provided

ClinVar	Variant (HGVS)	Gene	Classification	Review
3363162	Single allele	LOC106029240	Pathogenic	criteria provided, single submitter
2579751	Single allele	LOC113875037	Pathogenic	criteria provided, single submitter
3024126	GRCh38/hg38 Xp22.31(chrX:6989414-7926139)x0	LOC113875037	Pathogenic	criteria provided, single submitter
188048	NC_000023.11:g.(6560264_6560764)_(8187691_8193324)del	LOC126863198	Pathogenic	no assertion criteria provided
3765504	NC_000023.11:g.7050286_7926129del	LOC126863198	Pathogenic	no assertion criteria provided
188050	NC_000023.11:g.(6500268_6517018)_(7739446_7762747)del	LOC130067910	Pathogenic	no assertion criteria provided
188047	NC_000023.11:g.(6499768_6517018)_(8187691_8193324)del	LOC130067915	Pathogenic	no assertion criteria provided
188049	NC_000023.11:g.(6674278_6675309)_(7911900_7922037)del	MIR4767	Pathogenic	no assertion criteria provided
1300212	GRCh37/hg19 Xp22.31(chrX:6575924-8173248)x0	PNPLA4	Pathogenic	criteria provided, single submitter
1300213	GRCh37/hg19 Xp22.31(chrX:6456940-8135053)x0	PNPLA4	Pathogenic	criteria provided, single submitter
1703531	GRCh37/hg19 Xp22.31(chrX:6954111-8058641)	PNPLA4	Pathogenic	no assertion criteria provided
2506547	GRCh37/hg19 Xp22.31(chrX:6968337-8434424)	PNPLA4	Pathogenic	criteria provided, single submitter
4083500	GRCh37/hg19 Xp22.31(chrX:6968337-7894160)x0	PNPLA4	Pathogenic	criteria provided, single submitter
625682	GRCh37/hg19 Xp22.31(chrX:6497085-8135053)	PNPLA4	Pathogenic	criteria provided, single submitter
625683	GRCh37/hg19 Xp22.31(chrX:6497085-7910475)	PNPLA4	Pathogenic	criteria provided, single submitter
4820163	NC_000023.10:g.(6452559_6453559)_(8136659_8137559)del	PUDP	Pathogenic	criteria provided, single submitter
625642	GRCh37/hg19 Xp22.31(chrX:6696168-7396902)	PUDP	Pathogenic	criteria provided, single submitter
10552	NM_001320752.2(STS):c.1099T>A (p.Trp367Arg)	STS	Pathogenic	no assertion criteria provided
10553	NM_001320752.2(STS):c.1322G>A (p.Cys441Tyr)	STS	Pathogenic	no assertion criteria provided
10556	NM_001320752.2(STS):c.1316A>G (p.His439Arg)	STS	Pathogenic	no assertion criteria provided
10557	NM_001320752.2(STS):c.1241+1G>T	STS	Pathogenic	no assertion criteria provided
1677277	NM_000351.4:g.(?6551155)(8032120_?)del	STS	Pathogenic	no assertion criteria provided
3383027	NM_001320752.2(STS):c.806+1G>A	STS	Pathogenic	criteria provided, single submitter
625856	NM_001320752.2(STS):c.272G>A (p.Trp91Ter)	STS	Pathogenic	criteria provided, single submitter
1325152	NM_001320752.2(STS):c.437del (p.Pro146fs)	STS	Likely pathogenic	criteria provided, single submitter
1803158	NM_001320752.2(STS):c.1108G>T (p.Gly370Cys)	STS	Likely pathogenic	criteria provided, single submitter
2737074	NM_001320752.2(STS):c.1060G>A (p.Gly354Arg)	STS	Likely pathogenic	criteria provided, multiple submitters, no conflicts
3256558	NM_001320752.2(STS):c.382G>A (p.Gly128Arg)	STS	Likely pathogenic	criteria provided, single submitter
3382684	NM_001320752.2(STS):c.1241+1G>C	STS	Likely pathogenic	criteria provided, single submitter
10554	NM_001320752.2(STS):c.1007C>T (p.Ser336Leu)	STS	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 47 · Orphanet: 20 · 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	Semidominant	autosomal dominant ichthyosis vulgaris	36
FLG	Definitive	Semidominant	autosomal dominant ichthyosis vulgaris	6
STS	Definitive	X-linked	recessive X-linked ichthyosis	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
STS	Orphanet:281090	Syndromic recessive X-linked ichthyosis
STS	Orphanet:461	Recessive X-linked ichthyosis
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
FLG	Orphanet:461	Recessive X-linked ichthyosis

Cohort genes → proteins

6 cohort genes, 5 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	6

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
STS	HGNC:11425	ENSG00000101846	P08842	Steryl-sulfatase	gencc,clinvar
FGFR1	HGNC:3688	ENSG00000077782	P11362	Fibroblast growth factor receptor 1	gencc
FLG	HGNC:3748	ENSG00000143631	P20930	Filaggrin	gencc
PUDP	HGNC:16818	ENSG00000130021	Q08623	Pseudouridine-5’-phosphatase	clinvar
PNPLA4	HGNC:24887	ENSG00000006757	P41247	Patatin-like phospholipase domain-containing protein 4	clinvar
MIR4767	HGNC:41548	ENSG00000264268		microRNA 4767	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
STS	Steryl-sulfatase	Catalyzes the conversion of sulfated steroid precursors, such as dehydroepiandrosterone sulfate (DHEA-S) and estrone sulfate to the free steroid.
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.
FLG	Filaggrin	Aggregates keratin intermediate filaments and promotes disulfide-bond formation among the intermediate filaments during terminal differentiation of mammalian epidermis.
PUDP	Pseudouridine-5’-phosphatase	Dephosphorylates pseudouridine 5’-phosphate, a potential intermediate in rRNA degradation.
PNPLA4	Patatin-like phospholipase domain-containing protein 4	Has abundant triacylglycerol lipase activity.

Protein-family classification

Druggable: 2 · Difficult: 0 · Unknown: 4 · Druggable fraction: 0.33

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
Phosphatase	1	14.0×	0.208
Kinase	1	4.6×	0.297
Other/Unknown	4	1.2×	0.458

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
STS	Phosphatase	yes	3.1.6.2	Sulfatase_N, Alkaline_phosphatase_core_sf, Sulfatase_CS
FGFR1	Kinase	yes	2.7.10.1	Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom, Ig_sub2
FLG	Other/Unknown	no		S100/CaBP7/8-like_CS, EF_hand_dom, Filaggrin
PUDP	Other/Unknown	no		HAD-SF_hydro_IA, PGP-like_dom2, HAD_sf
PNPLA4	Other/Unknown	no		PNPLA_dom, Acyl_Trfase/lysoPLipase, PLPL
MIR4767	Other/Unknown	no

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)	1
broad (>20)	5
unknown	0

Top tissues across cohort

Tissue	Cohort genes
endothelial cell	1
palpebral conjunctiva	1
placenta	1
buccal mucosa cell	1
calcaneal tendon	1
stromal cell of endometrium	1
skin of hip	1
upper arm skin	1
upper leg skin	1
mucosa of sigmoid colon	1
primordial germ cell in gonad	1
skeletal muscle tissue of rectus abdominis	1
diaphragm	1
hindlimb stylopod muscle	1
oocyte	1
caudate nucleus	1
gastrocnemius	1
minor salivary gland	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
STS	259	ubiquitous	marker	placenta, endothelial cell, palpebral conjunctiva
FGFR1	292	ubiquitous	marker	buccal mucosa cell, stromal cell of endometrium, calcaneal tendon
FLG	162	tissue_specific	yes	upper leg skin, upper arm skin, skin of hip
PUDP	273	ubiquitous	marker	skeletal muscle tissue of rectus abdominis, primordial germ cell in gonad, mucosa of sigmoid colon
PNPLA4	276	ubiquitous	marker	oocyte, hindlimb stylopod muscle, diaphragm
MIR4767	16	ubiquitous	yes	gastrocnemius, minor salivary gland, caudate nucleus

Protein interactions among cohort

Intra-cohort edges: 3.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
FGFR1	5,693
PUDP	2,218
FLG	2,165
STS	1,253
PNPLA4	758
MIR4767	0

Intra-cohort edges

A	B	Sources
PNPLA4	PUDP	string_interaction
PNPLA4	STS	string_interaction
PUDP	STS	string_interaction

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
FGFR1	P11362	83
PUDP	Q08623	3
STS	P08842	2
FLG	P20930	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
PNPLA4	P41247	94.38

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 29. Enrichment computed across 6 evidence-associated genes (5 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 5 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	1142.0×	0.017	FGFR1
FGFR1c and Klotho ligand binding and activation	1	571.0×	0.017	FGFR1
Signaling by plasma membrane FGFR1 fusions	1	571.0×	0.017	FGFR1
Epithelial-Mesenchymal Transition (EMT) during gastrulation	1	285.5×	0.019	FGFR1
FGFR1b ligand binding and activation	1	253.8×	0.019	FGFR1
Pyrimidine salvage	1	207.6×	0.019	PUDP
Signaling by activated point mutants of FGFR1	1	190.3×	0.019	FGFR1
The activation of arylsulfatases	1	175.7×	0.019	STS
FGFR1c ligand binding and activation	1	152.3×	0.019	FGFR1
Phospholipase C-mediated cascade: FGFR1	1	134.3×	0.019	FGFR1
Downstream signaling of activated FGFR1	1	108.8×	0.019	FGFR1
Metabolism of steroid hormones	1	103.8×	0.019	STS
Signal transduction by L1	1	103.8×	0.019	FGFR1
PI-3K cascade:FGFR1	1	103.8×	0.019	FGFR1
SHC-mediated cascade:FGFR1	1	99.3×	0.019	FGFR1
Triglyceride catabolism	1	95.2×	0.019	PNPLA4
FRS-mediated FGFR1 signaling	1	91.4×	0.019	FGFR1
Formation of paraxial mesoderm	1	81.6×	0.020	FGFR1
Negative regulation of FGFR1 signaling	1	73.7×	0.021	FGFR1
Signaling by FGFR1 in disease	1	58.6×	0.022	FGFR1
Glycosphingolipid catabolism	1	58.6×	0.022	STS
Differentiation of Keratinocytes in Interfollicular Epidermis in Mammalian Skin	1	55.7×	0.022	FLG
PI3K Cascade	1	54.4×	0.022	FGFR1
NCAM signaling for neurite out-growth	1	54.4×	0.022	FGFR1
Constitutive Signaling by Aberrant PI3K in Cancer	1	25.4×	0.045	FGFR1
PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling	1	19.4×	0.056	FGFR1
Formation of the cornified envelope	1	17.6×	0.060	FLG
PIP3 activates AKT signaling	1	13.4×	0.075	FGFR1
RAF/MAP kinase cascade	1	12.2×	0.079	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
vitamin D3 metabolic process	1	1685.2×	0.010	FGFR1
positive regulation of mitotic cell cycle DNA replication	1	1685.2×	0.010	FGFR1
positive regulation of parathyroid hormone secretion	1	1685.2×	0.010	FGFR1
regulation of extrinsic apoptotic signaling pathway in absence of ligand	1	1685.2×	0.010	FGFR1
regulation of phosphate transport	1	1123.5×	0.010	FGFR1
fibroblast growth factor receptor signaling pathway involved in orbitofrontal cortex development	1	1123.5×	0.010	FGFR1
regulation of lateral mesodermal cell fate specification	1	1123.5×	0.010	FGFR1
ventricular zone neuroblast division	1	842.6×	0.010	FGFR1
negative regulation of fibroblast growth factor production	1	842.6×	0.010	FGFR1
positive regulation of phospholipase activity	1	674.1×	0.010	FGFR1
regulation of branching involved in salivary gland morphogenesis by mesenchymal-epithelial signaling	1	674.1×	0.010	FGFR1
diphosphate metabolic process	1	674.1×	0.010	FGFR1
chordate embryonic development	1	561.7×	0.010	FGFR1
positive regulation of MAPKKK cascade by fibroblast growth factor receptor signaling pathway	1	561.7×	0.010	FGFR1
steroid catabolic process	1	481.5×	0.010	STS
cementum mineralization	1	481.5×	0.010	FGFR1
nucleotide metabolic process	1	374.5×	0.011	PUDP
auditory receptor cell development	1	374.5×	0.011	FGFR1
paraxial mesoderm development	1	337.0×	0.011	FGFR1
lung-associated mesenchyme development	1	337.0×	0.011	FGFR1
response to sodium phosphate	1	337.0×	0.011	FGFR1
outer ear morphogenesis	1	306.4×	0.011	FGFR1
branching involved in salivary gland morphogenesis	1	280.9×	0.012	FGFR1
organ induction	1	240.7×	0.013	FGFR1
mesenchymal cell proliferation	1	224.7×	0.014	FGFR1
cornification	1	210.7×	0.014	FLG
positive regulation of endothelial cell chemotaxis	1	198.3×	0.014	FGFR1
cell projection assembly	1	187.2×	0.015	FGFR1
regulation of postsynaptic density assembly	1	177.4×	0.015	FGFR1
positive regulation of vascular endothelial cell proliferation	1	168.5×	0.015	FGFR1

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 6 evidence-associated genes (17%) 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
STS	ESTRADIOL
FGFR1	PONATINIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
FGFR1	93	4
STS	4	4
FLG	0	0
PUDP	0	0
PNPLA4	0	0
MIR4767	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
ESTRADIOL	4	STS
ESTRONE	4	STS
ESTRONE SULFURIC ACID	4	STS
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

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
STS	331	Binding:330, Functional:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
STS	3.1.6.2	steryl-sulfatase
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
STS	331
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)
ESTRADIOL	4	STS
ESTRONE	4	STS
ESTRONE SULFURIC ACID	4	STS
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

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	2	STS, 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	FLG, PUDP, PNPLA4, MIR4767

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)
PUDP	0	STS
FLG	0	—
PNPLA4	0	—
MIR4767	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 1.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT00074685	Not specified	COMPLETED	National Registry for Ichthyosis and Related Disorders