Neurofibromatosis type 1

Summary

Neurofibromatosis type 1 (MONDO:0018975) is a disease caused by NF1 (GenCC Definitive), with 26 cohort genes and 181 clinical trials. Top therapeutic interventions include selumetinib, deoxycholic acid, and lovastatin.

At a glance

• Prevalence: 1-5 / 10 000 (Europe) [Orphanet-validated]
• Causal gene: NF1 (GenCC Definitive)
• Cohort genes: 26
• ClinVar variants: 13,855
• Phenotypes (HPO): 77
• Clinical trials: 181

Clinical features

Epidemiology

Prevalence records

10 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Prevalence at birth	1-5 / 10 000	33.3	Worldwide	Validated
Point prevalence	1-5 / 10 000	21.3	Europe	Validated
Point prevalence	1-5 / 10 000	21	United Kingdom	Validated
Point prevalence	1-5 / 10 000	24.46	Finland	Validated
Point prevalence	1-5 / 10 000	47.5	New Zealand	Validated
Point prevalence	1-9 / 100 000	6.7	Canada	Validated
Point prevalence	1-5 / 10 000	20	Sweden	Validated
Prevalence at birth	1-5 / 10 000	36.65	United States	Validated
Prevalence at birth	1-5 / 10 000	36.9	United Kingdom	Validated
Prevalence at birth	1-5 / 10 000	50	Finland	Validated

Signs & symptoms

Clinical features (HPO)

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

HPO ID	Term	Frequency
HP:0000707	Abnormality of the nervous system	Very frequent (80-99%)
HP:0000823	Delayed puberty	Very frequent (80-99%)
HP:0000995	Melanocytic nevus	Very frequent (80-99%)
HP:0001012	Multiple lipomas	Very frequent (80-99%)
HP:0001256	Intellectual disability, mild	Very frequent (80-99%)
HP:0001328	Specific learning disability	Very frequent (80-99%)
HP:0001482	Subcutaneous nodule	Very frequent (80-99%)
HP:0002858	Meningioma	Very frequent (80-99%)
HP:0007440	Generalized hyperpigmentation	Very frequent (80-99%)
HP:0007565	Multiple cafe-au-lait spots	Very frequent (80-99%)
HP:0008069	Neoplasm of the skin	Very frequent (80-99%)
HP:0009592	Astrocytoma	Very frequent (80-99%)
HP:0009732	Plexiform neurofibroma	Very frequent (80-99%)
HP:0009737	Lisch nodules	Very frequent (80-99%)
HP:0012733	Macule	Very frequent (80-99%)
HP:0000028	Cryptorchidism	Frequent (30-79%)
HP:0000098	Tall stature	Frequent (30-79%)
HP:0000364	Hearing abnormality	Frequent (30-79%)
HP:0000365	Hearing impairment	Frequent (30-79%)
HP:0000478	Abnormality of the eye	Frequent (30-79%)
HP:0000504	Abnormality of vision	Frequent (30-79%)
HP:0000520	Proptosis	Frequent (30-79%)
HP:0000997	Axillary freckling	Frequent (30-79%)
HP:0001100	Heterochromia iridis	Frequent (30-79%)
HP:0001251	Ataxia	Frequent (30-79%)
HP:0002167	Abnormality of speech or vocalization	Frequent (30-79%)
HP:0002315	Headache	Frequent (30-79%)
HP:0002354	Memory impairment	Frequent (30-79%)
HP:0002652	Skeletal dysplasia	Frequent (30-79%)
HP:0002757	Recurrent fractures	Frequent (30-79%)
HP:0002857	Genu valgum	Frequent (30-79%)
HP:0003100	Slender long bone	Frequent (30-79%)
HP:0003401	Paresthesia	Frequent (30-79%)
HP:0007018	Attention deficit hyperactivity disorder	Frequent (30-79%)
HP:0030052	Inguinal freckling	Frequent (30-79%)
HP:0000238	Hydrocephalus	Occasional (5-29%)
HP:0000256	Macrocephaly	Occasional (5-29%)
HP:0000492	Abnormal eyelid morphology	Occasional (5-29%)
HP:0000501	Glaucoma	Occasional (5-29%)
HP:0000505	Visual impairment	Occasional (5-29%)
HP:0000512	Abnormal electroretinogram	Occasional (5-29%)
HP:0000518	Cataract	Occasional (5-29%)
HP:0000545	Myopia	Occasional (5-29%)
HP:0000567	Chorioretinal coloboma	Occasional (5-29%)
HP:0000729	Autistic behavior	Occasional (5-29%)
HP:0000818	Abnormality of the endocrine system	Occasional (5-29%)
HP:0000822	Hypertension	Occasional (5-29%)
HP:0000826	Precocious puberty	Occasional (5-29%)
HP:0000924	Abnormality of the skeletal system	Occasional (5-29%)
HP:0000938	Osteopenia	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	neurofibromatosis type 1
Mondo ID	MONDO:0018975
MeSH	C538607, D009456
OMIM	162200
Orphanet	636
DOID	DOID:0111253
ICD-10-CM	Q85.01
ICD-11	337970533
NCIT	C3273
SNOMED CT	92824003
UMLS	C0027831
MedGen	18013
GARD	0007866
MedDRA	10047712
NORD	1502
Is cancer (heuristic)	no

Also known as: neurofibromatosis · Neurofibromatosis 1 · neurofibromatosis 1 · neurofibromatosis type 1 · neurofibromatosis type i · neurofibromatosis, type 1 · NF1 · Nf1-Microdeletion syndrome · nonmosaic neurofibromatosis type 1 · nonmosaic NF1 · peripheral neurofibromatosis · Recklinghausen’s disease · type 1 neurofibromatosis

Data availability: 13,855 ClinVar variants · 4 GenCC gene-disease records · 149 cell lines.

Disease family

An umbrella term covering 3 Mondo subtypes.

Classification path: disease › human disease › disease by developmental or physiological process › disorder of development or morphogenesis › developmental defect during embryogenesis › neurofibromatosis type 1

Related subtypes (51): disorder of sexual differentiation, hereditary neurocutaneous angioma, nevoid basal cell carcinoma syndrome, angioosteohypertrophic syndrome, Larsen syndrome, schwannomatosis, linear nevus sebaceous syndrome, lethal Larsen-like syndrome, pseudodiastrophic dysplasia, focal dermal hypoplasia, microtia, neurofibromatosis-Noonan syndrome, Becker nevus syndrome, Legius syndrome, bone fragility with contractures, arterial rupture, and deafness, blindness - scoliosis - arachnodactyly syndrome, cutis laxa - Marfanoid syndrome, Maffucci syndrome, hydrops fetalis, ankyloblepharon filiforme-imperforate anus syndrome, developmental anomaly of metabolic origin, progeroid syndrome, facial cleft, Desbuquois dysplasia, cysts and fistulae of the face and oral cavity, macroglossia, middle ear anomaly, cleft palate, cutis laxa, infectious embryofetopathy, toxic or drug-related embryofetopathy, hemihyperplasia-multiple lipomatosis syndrome, phakomatosis pigmentokeratotica, phakomatosis pigmentovascularis, PTEN hamartoma tumor syndrome, marfanoid habitus-inguinal hernia-advanced bone age syndrome, multiple congenital anomalies/dysmorphic syndrome, congenital limb malformation, hereditary hemorrhagic telangiectasia, urogenital tract malformation, congenital anomaly of kidney and urinary tract, anotia, central nervous system malformation, Ehlers-Danlos syndrome, X-linked external auditory canal atresia-dilated internal auditory canal-facial dysmorphism syndrome, joint laxity, short stature, and myopia, diaphragmatic malformation, abdominal wall malformation, port-wine nevi-mega cisterna magna-hydrocephalus syndrome, conjoined twins, TP63-related ectodermal dysplasia spectrum with limb and orofacial malformations

Subtypes (3): neurofibromatosis, familial spinal, chromosome 17q11.2 deletion syndrome, 1.4Mb, neurofibromatosis type 1 due to NF1 mutation or intragenic deletion

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:

309 uncertain significance, 212 pathogenic, 30 conflicting classifications of pathogenicity, 21 likely pathogenic, 18 pathogenic/likely pathogenic, 10 likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1070145	NC_000017.10:g.(?29559081)(29701173_?)del	EVI2A	Pathogenic	criteria provided, single submitter
1070146	NC_000017.10:g.(?29586040)(29701173_?)del	EVI2A	Pathogenic	criteria provided, single submitter
1070147	NC_000017.10:g.(?29587381)(29662055_?)del	EVI2A	Pathogenic	criteria provided, single submitter
1070266	NC_000017.10:g.(?29527428)(29657848_?)del	EVI2A	Pathogenic	criteria provided, single submitter
1071967	NC_000017.10:g.(?29422055)(29701173_?)del	EVI2A	Pathogenic	criteria provided, single submitter
1072078	NC_000017.10:g.(?29422322)(29664606_?)del	EVI2A	Pathogenic	criteria provided, single submitter
1072079	NC_000017.10:g.(?29422322)(29665163_?)del	EVI2A	Pathogenic	criteria provided, single submitter
1072219	NC_000017.10:g.(?29587625)(29669475_?)del	EVI2A	Pathogenic	criteria provided, single submitter
1072220	NC_000017.10:g.(?29588709)(29701193_?)del	EVI2A	Pathogenic	criteria provided, single submitter
1072221	NC_000017.10:g.(?29592237)(29653280_?)del	EVI2A	Pathogenic	criteria provided, single submitter
1068537	NM_001042492.3(NF1):c.6del (p.Ala3fs)	LOC111811965	Pathogenic	criteria provided, single submitter
1069238	NM_001042492.3(NF1):c.60+2T>C	LOC111811965	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1072626	NM_001042492.3(NF1):c.9del (p.His4fs)	LOC111811965	Pathogenic	criteria provided, multiple submitters, no conflicts
1002110	NM_001042492.3(NF1):c.4931A>G (p.Asp1644Gly)	NF1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1003143	NM_001042492.3(NF1):c.6886_6903del (p.Ile2296_Leu2301del)	NF1	Pathogenic	criteria provided, single submitter
1004008	NM_001042492.3(NF1):c.3539T>G (p.Met1180Arg)	NF1	Pathogenic	criteria provided, single submitter
1012199	NM_001042492.3(NF1):c.598A>T (p.Lys200Ter)	NF1	Pathogenic	criteria provided, single submitter
1016082	NM_001042492.3(NF1):c.1393-592A>G	NF1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1036158	NM_001042492.3(NF1):c.3586C>T (p.Leu1196Phe)	NF1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1037719	NM_001042492.3(NF1):c.2324A>C (p.Glu775Ala)	NF1	Pathogenic	criteria provided, multiple submitters, no conflicts
1042357	NM_001042492.3(NF1):c.3496G>T (p.Gly1166Cys)	NF1	Pathogenic	criteria provided, single submitter
1042977	NM_001042492.3(NF1):c.725T>G (p.Met242Arg)	NF1	Pathogenic	criteria provided, single submitter
1044895	NM_001042492.3(NF1):c.4931A>C (p.Asp1644Ala)	NF1	Pathogenic	criteria provided, single submitter
1048673	NM_001042492.3(NF1):c.7171del (p.Val2391fs)	NF1	Pathogenic	criteria provided, single submitter
1048674	NM_001042492.3(NF1):c.7739-3_7743delCAGAAACT	NF1	Pathogenic	no assertion criteria provided
1048676	NM_001042492.3(NF1):c.6488del (p.Leu2163fs)	NF1	Pathogenic	criteria provided, single submitter
1048677	NM_001042492.3(NF1):c.1714dup (p.Glu572fs)	NF1	Pathogenic	criteria provided, single submitter
1048679	NM_001042492.3(NF1):c.1702_1703dup (p.Thr569fs)	NF1	Pathogenic	no assertion criteria provided
1048680	NM_001042492.3(NF1):c.3114-1G>C	NF1	Pathogenic	no assertion criteria provided
1048682	NM_001042492.3(NF1):c.2034_2035insC (p.Ile679fs)	NF1	Pathogenic	no assertion criteria provided

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 9 · Orphanet: 41 · 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
NF1	Definitive	Autosomal dominant	neurofibromatosis type 1	9

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
NF1	Orphanet:139474	17q11.2 microduplication syndrome
NF1	Orphanet:29072	Hereditary pheochromocytoma-paraganglioma
NF1	Orphanet:293199	Pleomorphic rhabdomyosarcoma
NF1	Orphanet:363700	Neurofibromatosis type 1 due to NF1 mutation or intragenic deletion
NF1	Orphanet:638	Neurofibromatosis-Noonan syndrome
NF1	Orphanet:86834	Juvenile myelomonocytic leukemia
NF1	Orphanet:97685	17q11 microdeletion syndrome
NF1	Orphanet:99756	Alveolar rhabdomyosarcoma
NF1	Orphanet:99757	Embryonal rhabdomyosarcoma
RORA	Orphanet:528084	Non-specific syndromic intellectual disability
SPG11	Orphanet:2822	Autosomal recessive spastic paraplegia type 11
SPG11	Orphanet:300605	Juvenile amyotrophic lateral sclerosis
SPG11	Orphanet:466775	Autosomal recessive Charcot-Marie-Tooth disease type 2X
HNF1A	Orphanet:319303	Chromophobe renal cell carcinoma
HNF1A	Orphanet:324575	Hyperinsulinism due to HNF1A deficiency
HNF1A	Orphanet:404511	Clear cell papillary renal cell carcinoma
HNF1A	Orphanet:552	MODY
BRPF1	Orphanet:435638	3p25.3 microdeletion syndrome
BRPF1	Orphanet:698090	Ophthalmological abnormalities-facial dysmorphism-intellectual disability syndrome
CDH15	Orphanet:178469	Autosomal dominant non-syndromic intellectual disability
ARID1B	Orphanet:1465	Coffin-Siris syndrome
ARID1B	Orphanet:251056	6q25.2q25.3 microdeletion syndrome
SPRED1	Orphanet:137605	Legius syndrome
WDR26	Orphanet:513456	Intellectual disability-seizures-abnormal gait-facial dysmorphism syndrome
DCAF8	Orphanet:401964	Autosomal dominant Charcot-Marie-Tooth disease type 2 with giant axons
C19orf12	Orphanet:289560	Mitochondrial membrane protein-associated neurodegeneration
C19orf12	Orphanet:320370	Autosomal recessive spastic paraplegia type 43
ABCA1	Orphanet:31150	Tangier disease
ABCA1	Orphanet:425	Apolipoprotein A-I deficiency
ERG	Orphanet:319	Skeletal Ewing sarcoma
ERG	Orphanet:370334	Extraskeletal Ewing sarcoma
EXT1	Orphanet:321	Multiple osteochondromas
EXT1	Orphanet:502	Trichorhinophalangeal syndrome type 2
EXT1	Orphanet:55880	Chondrosarcoma
GABBR1	Orphanet:178469	Autosomal dominant non-syndromic intellectual disability
NF2	Orphanet:2495	Meningioma
NF2	Orphanet:634475	Mosaic NF2-related schwannomatosis
NF2	Orphanet:637	Full NF2-related schwannomatosis
NF2	Orphanet:93921	Full schwannomatosis
NOTCH1	Orphanet:402075	Familial bicuspid aortic valve
NOTCH1	Orphanet:974	Adams-Oliver syndrome

Cohort genes → proteins

26 cohort genes, 25 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	26

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
NF1	HGNC:7765	ENSG00000196712	P21359	Neurofibromin	gencc,clinvar
RORA	HGNC:10258	ENSG00000069667	P35398	Nuclear receptor ROR-alpha	clinvar
SPG11	HGNC:11226	ENSG00000104133	Q96JI7	Spatacsin	clinvar
HNF1A	HGNC:11621	ENSG00000135100	P20823	Hepatocyte nuclear factor 1-alpha	clinvar
TLK2	HGNC:11842	ENSG00000146872	Q86UE8	Serine/threonine-protein kinase tousled-like 2	clinvar
BRPF1	HGNC:14255	ENSG00000156983	P55201	Peregrin	clinvar
ADAP2	HGNC:16487	ENSG00000184060	Q9NPF8	Arf-GAP with dual PH domain-containing protein 2	clinvar
CRLF3	HGNC:17177	ENSG00000176390	Q8IUI8	Cytokine receptor-like factor 3	clinvar
CDH15	HGNC:1754	ENSG00000129910	P55291	Cadherin-15	clinvar
ARID1B	HGNC:18040	ENSG00000049618	Q8NFD5	AT-rich interactive domain-containing protein 1B	clinvar
SPRED1	HGNC:20249	ENSG00000166068	Q7Z699	Sprouty-related, EVH1 domain-containing protein 1	clinvar
WDR26	HGNC:21208	ENSG00000162923	Q9H7D7	WD repeat-containing protein 26	clinvar
DCAF8	HGNC:24891	ENSG00000132716	Q5TAQ9	DDB1- and CUL4-associated factor 8	clinvar
C19orf12	HGNC:25443	ENSG00000131943	Q9NSK7	Protein C19orf12	clinvar
ABHD15	HGNC:26971	ENSG00000168792	Q6UXT9	Protein ABHD15	clinvar
ABCA1	HGNC:29	ENSG00000165029	O95477	Phospholipid-transporting ATPase ABCA1	clinvar
HECW2	HGNC:29853	ENSG00000138411	Q9P2P5	E3 ubiquitin-protein ligase HECW2	clinvar
ERG	HGNC:3446	ENSG00000157554	P11308	Transcriptional regulator ERG	clinvar
EVI2A	HGNC:3499	ENSG00000126860	P22794	Protein EVI2A	clinvar
EVI2B	HGNC:3500	ENSG00000185862	P34910	Protein EVI2B	clinvar
EXT1	HGNC:3512	ENSG00000182197	Q16394	Exostosin-1	clinvar
GABBR1	HGNC:4070	ENSG00000204681	Q9UBS5	Gamma-aminobutyric acid type B receptor subunit 1	clinvar
MIR4733HG	HGNC:55332	ENSG00000264107		MIR4733 host gene	clinvar
NF2	HGNC:7773	ENSG00000186575	P35240	Merlin	clinvar
NOTCH1	HGNC:7881	ENSG00000148400	P46531	Neurogenic locus notch homolog protein 1	clinvar
OMG	HGNC:8135	ENSG00000126861	P23515	Oligodendrocyte-myelin glycoprotein	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
NF1	Neurofibromin	Stimulates the GTPase activity of Ras.
RORA	Nuclear receptor ROR-alpha	Nuclear receptor that binds DNA as a monomer to ROR response elements (RORE) containing a single core motif half-site 5’-AGGTCA-3’ preceded by a short A-T-rich sequence.
SPG11	Spatacsin	May play a role in neurite plasticity by maintaining cytoskeleton stability and regulating synaptic vesicle transport.
HNF1A	Hepatocyte nuclear factor 1-alpha	Transcriptional activator that regulates the tissue specific expression of multiple genes, especially in pancreatic islet cells and in liver.
TLK2	Serine/threonine-protein kinase tousled-like 2	Serine/threonine-protein kinase involved in the process of chromatin assembly and probably also DNA replication, transcription, repair, and chromosome segregation.
BRPF1	Peregrin	Scaffold subunit of various histone acetyltransferase (HAT) complexes, such as the MOZ/MORF and HBO1 complexes, which have a histone H3 acetyltransferase activity.
ADAP2	Arf-GAP with dual PH domain-containing protein 2	GTPase-activating protein for the ADP ribosylation factor family (Potential).
CRLF3	Cytokine receptor-like factor 3	May play a role in the negative regulation of cell cycle progression.
CDH15	Cadherin-15	Cadherins are calcium-dependent cell adhesion proteins.
ARID1B	AT-rich interactive domain-containing protein 1B	Involved in transcriptional activation and repression of select genes by chromatin remodeling (alteration of DNA-nucleosome topology).
SPRED1	Sprouty-related, EVH1 domain-containing protein 1	Tyrosine kinase substrate that inhibits growth-factor-mediated activation of MAP kinase.
WDR26	WD repeat-containing protein 26	G-beta-like protein involved in cell signal transduction.
DCAF8	DDB1- and CUL4-associated factor 8	May function as a substrate receptor for CUL4-DDB1 E3 ubiquitin-protein ligase complex.
ABHD15	Protein ABHD15	May regulate adipocyte lipolysis and liver lipid accumulation.
ABCA1	Phospholipid-transporting ATPase ABCA1	Catalyzes the translocation of specific phospholipids from the cytoplasmic to the extracellular/lumenal leaflet of membrane coupled to the hydrolysis of ATP.
HECW2	E3 ubiquitin-protein ligase HECW2	E3 ubiquitin-protein ligase that mediates ubiquitination of TP73.
ERG	Transcriptional regulator ERG	Transcriptional regulator.
EVI2A	Protein EVI2A	May complex with itself or/and other proteins within the membrane, to function as part of a cell-surface receptor.
EVI2B	Protein EVI2B	Required for granulocyte differentiation and functionality of hematopoietic progenitor cells through the control of cell cycle progression and survival of hematopoietic progenitor cells.
EXT1	Exostosin-1	Glycosyltransferase forming with EXT2 the heterodimeric heparan sulfate polymerase which catalyzes the elongation of the heparan sulfate glycan backbone.
GABBR1	Gamma-aminobutyric acid type B receptor subunit 1	Component of a heterodimeric G-protein coupled receptor for GABA, formed by GABBR1 and GABBR2.
NF2	Merlin	Probable regulator of the Hippo/SWH (Sav/Wts/Hpo) signaling pathway, a signaling pathway that plays a pivotal role in tumor suppression by restricting proliferation and promoting apoptosis.
NOTCH1	Neurogenic locus notch homolog protein 1	Functions as a receptor for membrane-bound ligands Jagged-1 (JAG1), Jagged-2 (JAG2) and Delta-1 (DLL1) to regulate cell-fate determination.
OMG	Oligodendrocyte-myelin glycoprotein	Cell adhesion molecule contributing to the interactive process required for myelination in the central nervous system.

Protein-family classification

Druggable: 6 · Difficult: 7 · Unknown: 13 · Druggable fraction: 0.23

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
Scaffold/PPI	5	3.3×	0.137
Nuclear receptor	1	14.8×	0.294
Transporter	1	3.0×	0.857
Antibody/Immunoglobulin	1	1.1×	0.896
Kinase	1	1.1×	0.896
GPCR	1	0.9×	0.896
Other/Unknown	13	0.9×	0.896
Transcription factor	2	0.6×	0.896
Enzyme (other)	1	0.5×	0.896

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
NF1	Other/Unknown	no		CRAL-TRIO_dom, RasGAP_dom, Rho_GTPase_activation_prot
RORA	Nuclear receptor	yes		Nucl_hrmn_rcpt_lig-bd, Znf_hrmn_rcpt, Nuclear_hrmn_rcpt
SPG11	Other/Unknown	no		Spatacsin, Spatacsin_C_dom
HNF1A	Transcription factor	no		HD, HNF1b_C, HNF1a_C
TLK2	Kinase	yes		Prot_kinase_dom, Ser/Thr_kinase_AS, Kinase-like_dom_sf
BRPF1	Transcription factor	no		PWWP_dom, Bromodomain, Znf_PHD
ADAP2	Scaffold/PPI	no		ArfGAP_dom, PH_domain, PH-like_dom_sf
CRLF3	Antibody/Immunoglobulin	yes		FN3_dom, Ig-like_fold, FN3_sf
CDH15	Other/Unknown	no		Cadherin_Y-type_LIR, Cadherin-like_dom, Cadherin-like_sf
ARID1B	Other/Unknown	no		ARID_dom, BAF250/Osa, BAF250_C
SPRED1	Other/Unknown	no		WH1/EVH1_dom, Sprouty, PH-like_dom_sf
WDR26	Scaffold/PPI	no		WD40_rpt, LisH, CTLH_C
DCAF8	Scaffold/PPI	no		WD40_rpt, WD40/YVTN_repeat-like_dom_sf, WD40_repeat_dom_sf
C19orf12	Other/Unknown	no		C19orf12
ABHD15	Other/Unknown	no		AB_hydrolase_fold, AB_hydrolase_4_sf
ABCA1	Transporter	yes		ABC_transporter-like_ATP-bd, AAA+_ATPase, ABC2_TM
HECW2	Scaffold/PPI	no		C2_dom, HECT_dom, WW_dom
ERG	Other/Unknown	no		Ets_dom, Pointed_dom, SAM/pointed_sf
EVI2A	Other/Unknown	no		Ectropic_vir_integratn_site_2A
EVI2B	Other/Unknown	no		EVI2B
EXT1	Enzyme (other)	yes	2.4.1.224	Exostosin, GT64_dom, Nucleotide-diphossugar_trans
GABBR1	GPCR	yes		Sushi_SCR_CCP_dom, ANF_lig-bd_rcpt, GPCR3_GABA-B
MIR4733HG	Other/Unknown	no
NF2	Other/Unknown	no		FERM_domain, Ez/rad/moesin-like, Moesin_tail_sf
NOTCH1	Scaffold/PPI	no		EGF-type_Asp/Asn_hydroxyl_site, EGF, Notch_dom
OMG	Other/Unknown	no		LRRNT, Leu-rich_rpt, Leu-rich_rpt_typical-subtyp

Expression context

Cohort genes with no expression data: 0.

23 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)	26
unknown	0

Top tissues across cohort

Tissue	Cohort genes
calcaneal tendon	4
colonic epithelium	4
granulocyte	3
sural nerve	3
leukocyte	3
mononuclear cell	3
adrenal tissue	2
skin of hip	2
bronchial epithelial cell	2
secondary oocyte	2
monocyte	2
cerebellar hemisphere	2
right hemisphere of cerebellum	2
ventricular zone	2
endothelial cell	2
descending thoracic aorta	2
stromal cell of endometrium	2
lateral nuclear group of thalamus	1
upper leg skin	1
liver	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
NF1	283	ubiquitous	marker	colonic epithelium, calcaneal tendon, adrenal tissue
RORA	284	ubiquitous	marker	upper leg skin, lateral nuclear group of thalamus, skin of hip
SPG11	295	ubiquitous	marker	bronchial epithelial cell, granulocyte, calcaneal tendon
HNF1A	81	tissue_specific	yes	right lobe of liver, mucosa of transverse colon, liver
TLK2	185	tissue_specific	marker	calcaneal tendon, sural nerve, colonic epithelium
BRPF1	254	ubiquitous	marker	oocyte, secondary oocyte, granulocyte
ADAP2	253	ubiquitous	marker	monocyte, mononuclear cell, leukocyte
CRLF3	287	ubiquitous	marker	trabecular bone tissue, mononuclear cell, leukocyte
CDH15	139	broad	marker	cerebellar hemisphere, cerebellar cortex, right hemisphere of cerebellum
ARID1B	256	ubiquitous	marker	bone marrow cell, colonic epithelium, sural nerve
SPRED1	248	ubiquitous	marker	ventricular zone, mucosa of sigmoid colon, calcaneal tendon
WDR26	286	ubiquitous	marker	sperm, secondary oocyte, tongue squamous epithelium
DCAF8	160	ubiquitous	marker	right uterine tube, right lobe of thyroid gland, body of pancreas
C19orf12	253	ubiquitous	marker	endothelial cell, kidney epithelium, epithelial cell of pancreas
ABHD15	186	broad	marker	granulocyte, ileal mucosa, islet of Langerhans
ABCA1	272	ubiquitous	marker	adrenal tissue, skin of hip, left adrenal gland
HECW2	227	ubiquitous	marker	left ventricle myocardium, Brodmann (1909) area 23, middle temporal gyrus
ERG	247	broad	marker	tendon of biceps brachii, descending thoracic aorta, thoracic aorta
EVI2A	260	ubiquitous	marker	corpus callosum, inferior vagus X ganglion, endothelial cell
EVI2B	253	broad	marker	monocyte, mononuclear cell, leukocyte
EXT1	285	ubiquitous	marker	stromal cell of endometrium, saphenous vein, descending thoracic aorta
GABBR1	194	ubiquitous	yes	right hemisphere of cerebellum, cerebellar hemisphere, right frontal lobe
MIR4733HG	130		yes	sural nerve, primordial germ cell in gonad, male germ line stem cell (sensu Vertebrata) in testis
NF2	283	ubiquitous	marker	endometrium epithelium, stromal cell of endometrium, dorsal motor nucleus of vagus nerve
NOTCH1	272	ubiquitous	marker	ventricular zone, colonic epithelium, visceral pleura
OMG	215	broad	marker	olfactory segment of nasal mucosa, bronchial epithelial cell, postcentral gyrus

Protein interactions among cohort

Intra-cohort edges: 16.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
NOTCH1	7,411
NF1	5,540
ABCA1	3,551
NF2	3,208
SPRED1	2,744
HNF1A	2,491
WDR26	2,275
ARID1B	2,131
HECW2	2,127
TLK2	2,006

Intra-cohort edges

A	B	Sources
ADAP2	CRLF3	string_interaction
ADAP2	EVI2A	string_interaction
ADAP2	EVI2B	string_interaction
ADAP2	NF1	string_interaction
C19orf12	SPG11	string_interaction
CRLF3	EVI2A	string_interaction
CRLF3	EVI2B	string_interaction
CRLF3	OMG	string_interaction
EVI2A	EVI2B	string_interaction
EVI2A	NF1	biogrid_interaction, intact, string_interaction
EVI2A	OMG	string_interaction
EVI2B	NF1	string_interaction
EVI2B	OMG	string_interaction
NF1	NF2	string_interaction
NF1	OMG	string_interaction
NF1	SPRED1	biogrid_interaction, intact, string_interaction

Structural data

PDB: 17 · AlphaFold-only: 8 · No structure: 1

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
BRPF1	P55201	66
NOTCH1	P46531	29
NF1	P21359	26
GABBR1	Q9UBS5	24
ERG	P11308	8
ABCA1	O95477	7
HNF1A	P20823	6
EXT1	Q16394	6
NF2	P35240	6
WDR26	Q9H7D7	4
RORA	P35398	3
SPG11	Q96JI7	3
SPRED1	Q7Z699	3
TLK2	Q86UE8	2
ARID1B	Q8NFD5	2
DCAF8	Q5TAQ9	2
HECW2	Q9P2P5	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
ADAP2	Q9NPF8	92.49
CRLF3	Q8IUI8	90.15
ABHD15	Q6UXT9	79.70
CDH15	P55291	78.70
OMG	P23515	67.94
C19orf12	Q9NSK7	59.50
EVI2A	P22794	56.81
EVI2B	P34910	51.05

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 116. Enrichment computed across 26 evidence-associated genes (16 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 16 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
RAS signaling downstream of NF1 loss-of-function variants	2	203.9×	0.004	NF1, SPRED1
Defective ABCA1 causes TGD	1	356.9×	0.087	ABCA1
Oncogenic MAPK signaling	2	31.0×	0.087	NF1, SPRED1
Regulation of RAS by GAPs	2	24.2×	0.087	NF1, SPRED1
Loss of Function of FBXW7 in Cancer and NOTCH1 Signaling	1	142.8×	0.089	NOTCH1
Defective LFNG causes SCDO3	1	142.8×	0.089	NOTCH1
Pre-NOTCH Processing in the Endoplasmic Reticulum	1	119.0×	0.089	NOTCH1
Constitutive Signaling by NOTCH1 t(7;9)(NOTCH1:M1580_K2555) Translocation Mutant	1	102.0×	0.089	NOTCH1
HDL assembly	1	89.2×	0.089	ABCA1
Regulation of NFE2L2 gene expression	1	89.2×	0.089	NOTCH1
Axonal growth inhibition (RHOA activation)	1	79.3×	0.089	OMG
NFE2L2 regulating tumorigenic genes	1	59.5×	0.089	NOTCH1
FGFRL1 modulation of FGFR1 signaling	1	54.9×	0.089	SPRED1
Phosphorylation of CLOCK, acetylation of BMAL1 (ARNTL) at target gene promoters	1	54.9×	0.089	RORA
Defective EXT2 causes exostoses 2	1	51.0×	0.089	EXT1
Defective EXT1 causes exostoses 1, TRPS2 and CHDS	1	51.0×	0.089	EXT1
Signaling by FGFR1	1	51.0×	0.089	SPRED1
RUNX3 regulates NOTCH signaling	1	51.0×	0.089	NOTCH1
Constitutive Signaling by NOTCH1 HD Domain Mutants	1	47.6×	0.089	NOTCH1
R-HSA-1368082	1	44.6×	0.089	RORA
Regulation of gene expression in late stage (branching morphogenesis) pancreatic bud precursor cells	1	44.6×	0.089	NOTCH1
Plasma lipoprotein assembly	1	44.6×	0.089	ABCA1
The CRY:PER:kinase complex represses transactivation by the BMAL:CLOCK (ARNTL:CLOCK) complex	1	44.6×	0.089	RORA
Regulation of lipid metabolism by PPARalpha	2	17.6×	0.089	RORA, ABCA1
MAPK1/MAPK3 signaling	2	16.4×	0.089	NF1, SPRED1
MAPK family signaling cascades	2	12.9×	0.089	NF1, SPRED1
PPARA activates gene expression	2	11.8×	0.089	RORA, ABCA1
Chromatin organization	2	10.2×	0.089	BRPF1, ARID1B
Chromatin modifying enzymes	2	9.0×	0.089	BRPF1, ARID1B
Pre-NOTCH Processing in Golgi	1	39.6×	0.091	NOTCH1

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 24 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
Schwann cell proliferation	2	468.1×	0.001	NF1, NF2
vasculogenesis involved in coronary vascular morphogenesis	2	468.1×	0.001	SPRED1, NOTCH1
negative regulation of Schwann cell proliferation	2	200.6×	0.007	NF1, NF2
negative regulation of MAPK cascade	3	37.6×	0.008	NF1, SPRED1, NF2
regulation of stem cell proliferation	2	117.0×	0.010	NF2, NOTCH1
protein catabolic process	3	29.7×	0.010	SPG11, EXT1, NOTCH1
liver development	3	27.7×	0.010	NF1, HNF1A, NOTCH1
positive regulation of DNA-templated transcription	6	7.0×	0.010	RORA, HNF1A, BRPF1, CRLF3, ARID1B, NOTCH1
negative regulation of oligodendrocyte differentiation	2	93.6×	0.011	NF1, NOTCH1
negative regulation of cell migration involved in sprouting angiogenesis	2	82.6×	0.013	SPRED1, NOTCH1
negative regulation of cell-matrix adhesion	2	73.9×	0.015	NF1, NF2
hypersensitivity	1	702.2×	0.020	EXT1
heart field specification	1	702.2×	0.020	EXT1
coronary sinus valve morphogenesis	1	702.2×	0.020	NOTCH1
Notch signaling pathway involved in regulation of secondary heart field cardioblast proliferation	1	702.2×	0.020	NOTCH1
foregut morphogenesis	1	702.2×	0.020	NOTCH1
positive regulation of mast cell apoptotic process	1	702.2×	0.020	NF1
lymphocyte adhesion to endothelial cell of high endothelial venule	1	702.2×	0.020	EXT1
positive regulation of neutrophil differentiation	1	702.2×	0.020	EVI2B
regulation of glial cell differentiation	1	702.2×	0.020	NF1
smoothened signaling pathway involved in lung development	1	702.2×	0.020	EXT1
regulation of epithelial cell proliferation involved in prostate gland development	1	702.2×	0.020	NOTCH1
sweat gland development	1	702.2×	0.020	EXT1
venous endothelial cell differentiation	1	702.2×	0.020	NOTCH1
perichondral bone morphogenesis	1	702.2×	0.020	EXT1
phagosome-lysosome fusion involved in apoptotic cell clearance	1	702.2×	0.020	SPG11
observational learning	1	702.2×	0.020	NF1
endoderm development	2	52.0×	0.020	EXT1, NOTCH1
motor behavior	2	46.8×	0.020	SPG11, EXT1
neural tube development	2	43.9×	0.020	NF1, NOTCH1

Therapeutics

Drugs indicated for this disease

No approved or late-stage (phase ≥3) drug is indicated for this disease; the following are in earlier-phase trials only.

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): Acetylcysteine, Aminolevulinic Acid, Celecoxib, Cholecalciferol, Everolimus, Lamotrigine, Lovastatin, Methotrexate, PEGINTERFERON ALFA-2B, Pirfenidone, Selumetinib, Sirolimus, Temozolomide, Vinblastine.

Drug target analysis

Approved (phase 4): 3 · Phase ≥3: 3 · Phased (≥1): 5 · Undrugged: 21

Druggability breadth: 10 of 26 evidence-associated genes (38%) 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
RORA	TRETINOIN
TLK2	FEDRATINIB
GABBR1	BACLOFEN

Top cohort targets by molecule count

Symbol	Molecules	Max phase
TLK2	11	4
GABBR1	4	4
RORA	2	4
WDR26	1	2
NOTCH1	1	2
NF1	0	0
SPG11	0	0
HNF1A	0	0
BRPF1	0	0
ADAP2	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
TRETINOIN	4	RORA
FEDRATINIB	4	TLK2
BOSUTINIB	4	TLK2
SUNITINIB	4	TLK2
BACLOFEN	4	GABBR1
ENZASTAURIN	3	TLK2
DOVITINIB	3	TLK2
LESTAURTINIB	3	TLK2
ARBACLOFEN	3	GABBR1
TOCERANIB	2	TLK2
SU-014813	2	TLK2
R-406	2	TLK2
MOLIBRESIB	2	WDR26
SGS-742	2	GABBR1
VAREGACESTAT	2	NOTCH1
CINTIRORGON	1	RORA
KW-2449	1	TLK2
SU-9516	1	TLK2
GAMMA-AMINOBUTYRIC ACID	1	GABBR1

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
TLK2	185	Binding:185
BRPF1	175	Binding:172, Functional:3
RORA	115	Binding:111, Functional:3, Unclassified:1
GABBR1	94	Binding:71, Functional:22, ADMET:1
NOTCH1	23	Binding:19, ADMET:4
ERG	14	Binding:10, Functional:3, ADMET:1
WDR26	6	Binding:6
ABCA1	2	Binding:2
SPG11	1	Binding:1
HNF1A	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
EXT1	2.4.1.224, 2.4.1.225	glucuronosyl-N-acetylglucosaminyl-proteoglycan 4-alpha-N-acetylglucosaminyltransferase, N-acetylglucosaminyl-proteoglycan 4-beta-glucuronosyltransferase

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
RORA	115
TLK2	185
BRPF1	175

Pharmacogenomics

Cohort genes with a PharmGKB record: 25; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

18 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)
TRETINOIN	4	RORA
FEDRATINIB	4	TLK2
BOSUTINIB	4	TLK2
BACLOFEN	4	GABBR1
ENZASTAURIN	3	TLK2
DOVITINIB	3	TLK2
LESTAURTINIB	3	TLK2
ARBACLOFEN	3	GABBR1
TOCERANIB	2	TLK2
SU-014813	2	TLK2
R-406	2	TLK2
MOLIBRESIB	2	WDR26
SGS-742	2	GABBR1
VAREGACESTAT	2	NOTCH1
CINTIRORGON	1	RORA
KW-2449	1	TLK2
SU-9516	1	TLK2
GAMMA-AMINOBUTYRIC ACID	1	GABBR1

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	3	RORA, TLK2, GABBR1
B	Phased (≥1) drug, not yet approved	2	WDR26, NOTCH1
C	Druggable family + PDB, no drug	2	ABCA1, EXT1
D	Druggable family + AlphaFold only, no drug	1	CRLF3
E	Difficult family or no structure, no drug	18	NF1, SPG11, HNF1A, BRPF1, ADAP2, CDH15, ARID1B, SPRED1, DCAF8, C19orf12 (+8 more)

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
BRPF1	175	—
NF1	0	—
SPG11	1	—
HNF1A	1	—
ADAP2	0	—
CRLF3	0	—
CDH15	0	—
ARID1B	0	—
SPRED1	0	—
DCAF8	0	—
C19orf12	0	—
ABHD15	0	—
ABCA1	2	—
HECW2	0	—
ERG	14	—
EVI2A	0	—
EVI2B	0	—
EXT1	0	—
MIR4733HG	0	—
NF2	0	—
OMG	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 181.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	95
PHASE2	44
PHASE1	20
PHASE1/PHASE2	11
PHASE3	5
EARLY_PHASE1	3
PHASE4	2
PHASE2/PHASE3	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT03975829	PHASE4	RECRUITING	Pediatric Long-Term Follow-up and Rollover Study
NCT00169611	PHASE4	COMPLETED	NF1-Attention: Study of Children With Neurofibromatosis Type 1 Treated by Methylphenidate
NCT03871257	PHASE3	ACTIVE_NOT_RECRUITING	A Study of the Drugs Selumetinib Versus Carboplatin/Vincristine in Patients With Neurofibromatosis and Low-Grade Glioma
NCT04924608	PHASE3	ACTIVE_NOT_RECRUITING	Efficacy and Safety of Selumetinib in Adults With NF1 Who Have Symptomatic, Inoperable Plexiform Neurofibromas
NCT05913037	PHASE3	ACTIVE_NOT_RECRUITING	FCN-159 in Adult Patients With Symptomatic, Inoperable Neurofibromatosis Type 1-Related Plexiform Neurofibromas
NCT02256124	PHASE2/PHASE3	TERMINATED	Effect of Lamotrigine on Cognition in NF1
NCT02471339	PHASE3	COMPLETED	Acceptance and Commitment Training for Adolescents and Young Adults With Neurofibromatosis Type 1, Plexiform Neurofibromas, and Chronic Pain
NCT04461886	PHASE3	TERMINATED	A Long-term Study of NPC-12G Gel in Neurofibromatosis Type I
NCT01089101	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Selumetinib in Treating Young Patients With Recurrent or Refractory Low Grade Glioma
NCT01362803	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	AZD6244 Hydrogen Sulfate for Children With Nervous System Tumors
NCT02407405	PHASE2	ACTIVE_NOT_RECRUITING	MEK 1/2 Inhibitor Selumetinib (AZD6244 Hydrogen Sulfate) in Adults With Neurofibromatosis Type 1 (NF1) and Inoperable Plexiform Neurofibromas
NCT02728388	PHASE2	RECRUITING	Photodynamic Therapy for Benign Dermal Neurofibromas- Phase II
NCT02964884	PHASE2	ACTIVE_NOT_RECRUITING	Interventions for Reading Disabilities in NF1
NCT03190915	PHASE2	ACTIVE_NOT_RECRUITING	Trametinib in Treating Patients With Relapsed or Refractory Juvenile Myelomonocytic Leukemia
NCT03962543	PHASE2	ACTIVE_NOT_RECRUITING	MEK Inhibitor Mirdametinib (PD-0325901) in Patients With Neurofibromatosis Type 1 Associated Plexiform Neurofibromas
NCT04481048	PHASE2	ACTIVE_NOT_RECRUITING	Antioxidant Therapy With N-acetylcysteine for Children With Neurofibromatosis Type 1
NCT04750928	PHASE1/PHASE2	RECRUITING	Cyclin-Dependent Kinase (CDK)4/6 Inhibitor Abemaciclib for Neurofibromatosis Type I (NF1) Related Atypical Neurofibromas
NCT04954001	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Study to Evaluate the Safety, Tolerability, PK Characteristics and Anti-tumor Activity of FCN-159 in Adult and Pediatric Participants With Neurofibromatosis Type 1
NCT05253131	PHASE2	NOT_YET_RECRUITING	Trial of Selumetinib and Bromodomain Inhibitor With Durvalumab for Sarcomas
NCT05309668	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Pharmacokinetics, Safety and Efficacy of the Selumetinib Granule Formulation in Children Aged ≥1 to <7 Years With NF1-related Symptomatic, Inoperable PN
NCT05331105	PHASE2	RECRUITING	HL-085 in Adults With Neurofibromatosis Type 1 (NF1) and Inoperable Plexiform Neurofibromas
NCT05735717	PHASE2	RECRUITING	MT2021-08T Cell Receptor Alpha/Beta Depletion PBSC Transplantation for Heme Malignancies
NCT05849662	PHASE1/PHASE2	RECRUITING	A Phase I/II Study of Trametinib and Azacitidine for Patients With Newly Diagnosed Juvenile Myelomonocytic Leukemia
NCT06159166	PHASE1/PHASE2	RECRUITING	Mirdametinib Monotherapy in Adults With Neurofibromatosis 1 (NF1) and Cutaneous Neurofibromas (cNF).
NCT06188741	PHASE2	RECRUITING	Selumetinib for the Prevention of Plexiform Neurofibroma Growth in NF Type 1
NCT06541847	PHASE2	RECRUITING	A Phase 2, Open-Label Study to Evaluate the Safety and Effects of HLX-1502 in Patients With Neurofibromatosis Type 1
NCT06620354	PHASE2	NOT_YET_RECRUITING	Clinical Study on the Treatment of Type I Neurofibromatosis With Smeitinib Hydrosulfate Capsule
NCT06621082	PHASE2	NOT_YET_RECRUITING	The Clinical Study of the Treatment of Patients With Type I Neurofibromatosis With Smetinib Hydrosulfate Capsule
NCT06735820	PHASE1/PHASE2	NOT_YET_RECRUITING	Early Phase Study Evaluating MEK and MDM2 Inhibition in Patients With NF1 and MPNST
NCT07024394	PHASE1/PHASE2	NOT_YET_RECRUITING	Follow-up Study to Evaluate the Safety and Efficacy of FCN-159 in Pediatric Participants With Neurofibromatosis Type 1
NCT07521657	PHASE2	NOT_YET_RECRUITING	Efficacy of Mirdametinib Alone or Combination With Radiotherapy for Germline and Sporadic NF1-Altered High-Grade Glioma
NCT00021541	PHASE2	COMPLETED	R115777 to Treat Children With Neurofibromatosis Type 1 and Progressive Plexiform Neurofibromas
NCT00030264	PHASE2	COMPLETED	Combination Chemotherapy in Treating Patients With Neurofibromatosis and Progressive Plexiform Neurofibromas
NCT00076102	PHASE2	COMPLETED	Pirfenidone in Children and Young Adults With Neurofibromatosis Type I and Progressive Plexiform Neurofibromas
NCT00304083	PHASE2	COMPLETED	Combination Chemotherapy in Treating Patients With Stage III or Stage IV Malignant Peripheral Nerve Sheath Tumors
NCT00326872	PHASE2	TERMINATED	AZD2171 in Treating Patients With Neurofibromatosis Type 1 and Plexiform Neurofibroma and/or Neurofibroma Near the Spine
NCT00589784	PHASE2	COMPLETED	Phase II Trial of Sunitinib (SU011248) in Patients With Recurrent or Inoperable Meningioma
NCT00634270	PHASE2	COMPLETED	A Phase II Study of the mTOR Inhibitor Sirolimus in Neurofibromatosis Type 1 Related Plexiform Neurofibromas
NCT00754780	PHASE2	COMPLETED	Clinical Trial of Pirfenidone in Adult Patients With Neurofibromatosis 1
NCT00846430	PHASE2	COMPLETED	Medical Treatment of High-Risk Neurofibromas

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
SELUMETINIB	4	17
DEOXYCHOLIC ACID	4	3
LOVASTATIN	4	3
PIRFENIDONE	4	3
TRAMETINIB	4	3
POLIDOCANOL	4	2
VINBLASTINE	4	2
ABEMACICLIB	4	1
AMINOLEVULINIC ACID	4	1
BINIMETINIB	4	1
CABOZANTINIB	4	1
DABRAFENIB	4	1
DICLOFENAC SODIUM	4	1
GADOPENTETATE DIMEGLUMINE	4	1
IMIQUIMOD	4	1
LAMOTRIGINE	4	1
METHYLPHENIDATE	4	1
NILOTINIB HYDROCHLORIDE MONOHYDRATE	4	1
SUNITINIB	4	1
TALIMOGENE LAHERPAREPVEC	4	1
AVUTOMETINIB	3	1
CEDIRANIB MALEATE	3	1
TIPIFARNIB	3	1
TUNLAMETINIB	3	1
MIRDAMETINIB	2	4
LUVOMETINIB	2	2
GADOLINIUM	2	1
HILTONOL	2	1
CHEMBL4463209	0	16
CHEMBL5433950	0	3