Mosaic neurofibromatosis type 1

Summary

Mosaic neurofibromatosis type 1 (MONDO:0859763) is a disease with 1 cohort gene.

At a glance

• Prevalence: Unknown (Worldwide) [Orphanet-validated]
• Cohort genes: 1
• ClinVar variants: 1

Clinical features

Epidemiology

Prevalence records

1 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Point prevalence	1-5 / 10 000	24.4618	Finland	Validated

Identifiers

Disease identifiers

Field	Value
Canonical name	mosaic neurofibromatosis type 1
Mondo ID	MONDO:0859763
Orphanet	634461
UMLS	C5782097
MedGen	1843428
GARD	0026764
Is cancer (heuristic)	no

Data availability: 1 ClinVar variant.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › hereditary neoplastic syndrome › mosaic neurofibromatosis/schwannomatosis › mosaic neurofibromatosis type 1

Related subtypes (2): mosaic NF2-related schwannomatosis, mosaic schwannomatosis

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 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1074271	NM_001042492.3(NF1):c.3301C>T (p.Gln1101Ter)	NF1	Pathogenic	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 9 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

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

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
NF1	HGNC:7765	ENSG00000196712	P21359	Neurofibromin	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
NF1	Neurofibromin	Stimulates the GTPase activity of Ras.

Protein-family classification

Druggable: 0 · Difficult: 0 · 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
Other/Unknown	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
NF1	Other/Unknown	no		CRAL-TRIO_dom, RasGAP_dom, Rho_GTPase_activation_prot

Expression context

Cohort genes with no expression data: 0.

1 cohort gene 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)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
adrenal tissue	1
calcaneal tendon	1
colonic epithelium	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

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
NF1	5,540

Structural data

PDB: 1 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
NF1	P21359	26

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 9. Enrichment computed across 1 evidence-associated genes (1 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 1 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	1631.4×	0.006	NF1
Oncogenic MAPK signaling	1	248.3×	0.015	NF1
Regulation of RAS by GAPs	1	193.6×	0.015	NF1
MAPK1/MAPK3 signaling	1	131.3×	0.017	NF1
MAPK family signaling cascades	1	102.9×	0.017	NF1
RAF/MAP kinase cascade	1	61.1×	0.023	NF1
Diseases of signal transduction by growth factor receptors and second messengers	1	56.8×	0.023	NF1
Disease	1	13.1×	0.086	NF1
Signal Transduction	1	10.2×	0.098	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 1 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	16852.0×	0.002	NF1
regulation of glial cell differentiation	1	16852.0×	0.002	NF1
observational learning	1	16852.0×	0.002	NF1
gamma-aminobutyric acid secretion, neurotransmission	1	8426.0×	0.002	NF1
Schwann cell proliferation	1	5617.3×	0.002	NF1
forebrain astrocyte development	1	5617.3×	0.002	NF1
Schwann cell migration	1	5617.3×	0.002	NF1
glutamate secretion, neurotransmission	1	5617.3×	0.002	NF1
negative regulation of mast cell proliferation	1	5617.3×	0.002	NF1
negative regulation of Schwann cell migration	1	5617.3×	0.002	NF1
vascular associated smooth muscle cell migration	1	5617.3×	0.002	NF1
mast cell apoptotic process	1	4213.0×	0.002	NF1
negative regulation of Rac protein signal transduction	1	4213.0×	0.002	NF1
myeloid leukocyte migration	1	4213.0×	0.002	NF1
mast cell proliferation	1	3370.4×	0.002	NF1
amygdala development	1	2808.7×	0.002	NF1
regulation of blood vessel endothelial cell migration	1	2808.7×	0.002	NF1
vascular associated smooth muscle cell proliferation	1	2808.7×	0.002	NF1
negative regulation of Schwann cell proliferation	1	2407.4×	0.002	NF1
negative regulation of neurotransmitter secretion	1	2407.4×	0.002	NF1
hair follicle maturation	1	2106.5×	0.002	NF1
negative regulation of leukocyte migration	1	1685.2×	0.002	NF1
negative regulation of vascular associated smooth muscle cell migration	1	1685.2×	0.002	NF1
regulation of bone resorption	1	1532.0×	0.002	NF1
negative regulation of astrocyte differentiation	1	1532.0×	0.002	NF1
regulation of long-term synaptic potentiation	1	1532.0×	0.002	NF1
positive regulation of extrinsic apoptotic signaling pathway in absence of ligand	1	1532.0×	0.002	NF1
forebrain morphogenesis	1	1404.3×	0.002	NF1
regulation of cell-matrix adhesion	1	1296.3×	0.003	NF1
negative regulation of neuroblast proliferation	1	1203.7×	0.003	NF1

Therapeutics

Drug target analysis

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

Druggability breadth: 0 of 1 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
NF1	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; 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	1	NF1

Undrugged target profiles

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

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

Clinical trials & evidence

Clinical trials

Clinical trials: 0.