Neurocutaneous syndrome

Summary

Neurocutaneous syndrome (MONDO:0042983) is a disease (an umbrella term covering 9 Mondo subtypes) with 2 cohort genes and 4 clinical trials.

At a glance

• Umbrella term: 9 Mondo subtypes
• Cohort genes: 2
• ClinVar variants: 1
• Clinical trials: 4

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	neurocutaneous syndrome
Mondo ID	MONDO:0042983
MeSH	D020752
NCIT	C84348
SNOMED CT	78572006
UMLS	C0265316
MedGen	82706
Is cancer (heuristic)	no

Also known as: neurocutaneous disorder · neurocutaneous disorders · neurocutaneous syndrome · neuroectodermal dysplasia syndrome · neuroectodermal dysplasia syndromes · Phacomatoses · Phacomatosis · Phakomatoses · phakomatosis · syndrome, neurocutaneous · syndrome, neuroectodermal dysplasia · syndromes, neurocutaneous · syndromes, neuroectodermal dysplasia

Data availability: 1 ClinVar variant · 1 GenCC gene-disease record.

Disease family

An umbrella term covering 9 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › nervous system disorder › neurocutaneous syndrome

Related subtypes (71): congenital nervous system disorder, central nervous system disorder, autoimmune disorder of the nervous system, cranial nerve neuropathy, peripheral nervous system disorder, neuronitis, diplegia of upper limb, retinal disorder, developmental disability, restless legs syndrome, movement disorder, toxic encephalopathy, Barre-Lieou syndrome, Gerstmann syndrome, drug-induced akathisia, drug-induced dyskinesia, stiff-person syndrome, Worster-Drought syndrome, corneal-cerebellar syndrome, pachygyria-intellectual disability-epilepsy syndrome, porencephaly-cerebellar hypoplasia-internal malformations syndrome, symmetrical thalamic calcifications, neonatal brainstem dysfunction, primary orthostatic hypotension, rippling muscle disease with myasthenia gravis, periodic paralysis, qualitative or quantitative protein defects in neuromuscular diseases, specific learning disability, cerebellar hypoplasia-tapetoretinal degeneration syndrome, locked-in syndrome, dopa-responsive dystonia, idiopathic recurrent stupor, chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids, spontaneous periodic hypothermia, Sydenham chorea, duplication of the pituitary gland, Balint syndrome, paraneoplastic neurologic syndrome, persistent idiopathic facial pain, serotonin syndrome, hypothalamic adipsic hypernatraemia syndrome, exercise-induced malignant hyperthermia, perineural cyst, neuromuscular disease, neuromyelitis optica, AL amyloidosis, AA amyloidosis, neuroleptic malignant syndrome, infectious disorder of the nervous system, central nervous system malformation, synaptopathy, nervous system neoplasm, sensory ganglionopathy, radiculitis, wet beriberi, perceptual disorders, prepubertal anorexia nervosa, neurovascular disorder, Wallerian degeneration, nervous system injury, neurosarcoidosis, neuroendocrine disorder, tubulinopathy, atactic disorder, hereditary neurological disease, meningitis-retention syndrome, KIF1A related neurological disorder, neurological pain disorder, neurodevelopmental disorder, post 5-alpha-reductase inhibitors treatment syndrome, post-selective serotonin reuptake inhibitor sexual dysfunction

Subtypes (9): tuberous sclerosis, nevoid basal cell carcinoma syndrome, Sturge-Weber syndrome, von Hippel-Lindau disease, neurocutaneous melanocytosis, phakomatosis pigmentokeratotica, phakomatosis pigmentovascularis, Wyburn-Mason syndrome, neurofibromatosis

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

1 retrieved; paginated sample, class counts are floors:

1 conflicting classifications of pathogenicity

ClinVar	Variant (HGVS)	Gene	Classification	Review
334	NM_001042492.3(NF1):c.5858T>C (p.Leu1953Pro)	NF1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 3 · Orphanet: 9 · 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
SREBF2	Moderate	Autosomal dominant	neurocutaneous syndrome	3

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

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
SREBF2	HGNC:11290	ENSG00000198911	Q12772	Sterol regulatory element-binding protein 2	gencc
NF1	HGNC:7765	ENSG00000196712	P21359	Neurofibromin	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SREBF2	Sterol regulatory element-binding protein 2	Precursor of the transcription factor form (Processed sterol regulatory element-binding protein 2), which is embedded in the endoplasmic reticulum membrane.
NF1	Neurofibromin	Stimulates the GTPase activity of Ras.

Protein-family classification

Druggable: 0 · Difficult: 1 · Unknown: 1 · Druggable fraction: 0.0

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
Transcription factor	1	4.1×	0.455
Other/Unknown	1	0.9×	0.805

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
SREBF2	Transcription factor	no		bHLH_dom, HLH_DNA-bd_sf
NF1	Other/Unknown	no		CRAL-TRIO_dom, RasGAP_dom, Rho_GTPase_activation_prot

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
cortical plate	1
ganglionic eminence	1
ventricular zone	1
adrenal tissue	1
calcaneal tendon	1
colonic epithelium	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SREBF2	287	ubiquitous	marker	ganglionic eminence, cortical plate, ventricular zone
NF1	283	ubiquitous	marker	colonic epithelium, calcaneal tendon, adrenal tissue

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
NF1	5,540
SREBF2	3,073

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
NF1	P21359	26
SREBF2	Q12772	1

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 23. 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
RAS signaling downstream of NF1 loss-of-function variants	1	815.7×	0.013	NF1
Zymostenol biosynthesis via lathosterol (Kandutsch-Russell pathway)	1	634.4×	0.013	SREBF2
Cholesterol biosynthesis	1	571.0×	0.013	SREBF2
EGR2 and SOX10-mediated initiation of Schwann cell myelination	1	184.2×	0.026	SREBF2
Regulation of cholesterol biosynthesis by SREBP (SREBF)	1	158.6×	0.026	SREBF2
Activation of gene expression by SREBF (SREBP)	1	129.8×	0.026	SREBF2
Oncogenic MAPK signaling	1	124.1×	0.026	NF1
Regulation of RAS by GAPs	1	96.8×	0.027	NF1
Adipogenesis	1	78.2×	0.027	SREBF2
Regulation of lipid metabolism by PPARalpha	1	70.5×	0.027	SREBF2
Metabolism of steroids	1	68.8×	0.027	SREBF2
MAPK1/MAPK3 signaling	1	65.6×	0.027	NF1
Transcriptional regulation of white adipocyte differentiation	1	64.9×	0.027	SREBF2
MAPK family signaling cascades	1	51.4×	0.032	NF1
PPARA activates gene expression	1	47.2×	0.032	SREBF2
RAF/MAP kinase cascade	1	30.5×	0.047	NF1
Diseases of signal transduction by growth factor receptors and second messengers	1	28.4×	0.047	NF1
Nervous system development	1	21.5×	0.059	SREBF2
Metabolism of lipids	1	15.8×	0.076	SREBF2
Developmental Biology	1	7.2×	0.154	SREBF2
Disease	1	6.5×	0.161	NF1
Metabolism	1	5.8×	0.172	SREBF2
Signal Transduction	1	5.1×	0.187	NF1

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 mast cell apoptotic process	1	8426.0×	0.004	NF1
regulation of glial cell differentiation	1	8426.0×	0.004	NF1
observational learning	1	8426.0×	0.004	NF1
gamma-aminobutyric acid secretion, neurotransmission	1	4213.0×	0.004	NF1
Schwann cell proliferation	1	2808.7×	0.004	NF1
forebrain astrocyte development	1	2808.7×	0.004	NF1
Schwann cell migration	1	2808.7×	0.004	NF1
glutamate secretion, neurotransmission	1	2808.7×	0.004	NF1
negative regulation of mast cell proliferation	1	2808.7×	0.004	NF1
negative regulation of Schwann cell migration	1	2808.7×	0.004	NF1
vascular associated smooth muscle cell migration	1	2808.7×	0.004	NF1
mast cell apoptotic process	1	2106.5×	0.004	NF1
negative regulation of Rac protein signal transduction	1	2106.5×	0.004	NF1
myeloid leukocyte migration	1	2106.5×	0.004	NF1
mast cell proliferation	1	1685.2×	0.004	NF1
amygdala development	1	1404.3×	0.004	NF1
regulation of blood vessel endothelial cell migration	1	1404.3×	0.004	NF1
negative regulation of cholesterol efflux	1	1404.3×	0.004	SREBF2
vascular associated smooth muscle cell proliferation	1	1404.3×	0.004	NF1
negative regulation of Schwann cell proliferation	1	1203.7×	0.004	NF1
positive regulation of cholesterol storage	1	1203.7×	0.004	SREBF2
negative regulation of neurotransmitter secretion	1	1203.7×	0.004	NF1
hair follicle maturation	1	1053.2×	0.004	NF1
cellular response to laminar fluid shear stress	1	1053.2×	0.004	SREBF2
SREBP signaling pathway	1	936.2×	0.005	SREBF2
negative regulation of leukocyte migration	1	842.6×	0.005	NF1
negative regulation of amyloid-beta clearance	1	842.6×	0.005	SREBF2
negative regulation of vascular associated smooth muscle cell migration	1	842.6×	0.005	NF1
regulation of bone resorption	1	766.0×	0.005	NF1
negative regulation of astrocyte differentiation	1	766.0×	0.005	NF1

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 2

Druggability breadth: 1 of 2 evidence-associated genes (50%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
SREBF2	0	0
NF1	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
SREBF2	22	Binding:22

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

0 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.

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
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	2	SREBF2, NF1

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
SREBF2	22	—
NF1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 4.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	4

Top trials by phase / activity

NCT	Phase	Status	Title
NCT06573723	Not specified	RECRUITING	Institutional Registry of Rare Diseases
NCT03840928	Not specified	UNKNOWN	PatientSpot Formerly Known as ArthritisPower
NCT06033768	Not specified	UNKNOWN	Neurological and Psychological Assessment of Neurocutaneous Syndromes in Upper Egypt Children
NCT07327164	Not specified	COMPLETED	Precision Medicine for Neurocutaneous Syndromes in Western China