Parkes Weber syndrome

Summary

Parkes Weber syndrome (MONDO:0700325) is a disease with 1 cohort gene and 2 clinical trials.

At a glance

• Prevalence: Unknown (Worldwide) [Orphanet-validated]
• Cohort genes: 1
• ClinVar variants: 1
• Phenotypes (HPO): 44
• Clinical trials: 2

Clinical features

Signs & symptoms

Clinical features (HPO)

44 HPO clinical features (Orphanet curated; top 44 by frequency):

HPO ID	Term	Frequency
HP:0002814	Abnormality of the lower limb	Very frequent (80-99%)
HP:0100026	Arteriovenous malformation	Very frequent (80-99%)
HP:0001722	High-output congestive heart failure	Frequent (30-79%)
HP:0002617	Dilatation	Frequent (30-79%)
HP:0002619	Varicose veins	Frequent (30-79%)
HP:0004947	Arteriovenous fistula	Frequent (30-79%)
HP:0004948	Vascular tortuosity	Frequent (30-79%)
HP:0007394	Prominent superficial blood vessels	Frequent (30-79%)
HP:0008968	Muscle hypertrophy of the lower extremities	Frequent (30-79%)
HP:0012721	Venous malformation	Frequent (30-79%)
HP:0025104	Capillary malformation	Frequent (30-79%)
HP:0025474	Erythematous plaque	Frequent (30-79%)
HP:0032555	Bounding pulse	Frequent (30-79%)
HP:0100553	Hemihypertrophy of lower limb	Frequent (30-79%)
HP:0100784	Peripheral arteriovenous fistula	Frequent (30-79%)
HP:0000016	Urinary retention	Occasional (5-29%)
HP:0000079	Abnormality of the urinary system	Occasional (5-29%)
HP:0000100	Nephrotic syndrome	Occasional (5-29%)
HP:0001892	Abnormal bleeding	Occasional (5-29%)
HP:0002138	Subarachnoid hemorrhage	Occasional (5-29%)
HP:0002196	Myelopathy	Occasional (5-29%)
HP:0002315	Headache	Occasional (5-29%)
HP:0002390	Spinal arteriovenous malformation	Occasional (5-29%)
HP:0002408	Cerebral arteriovenous malformation	Occasional (5-29%)
HP:0002817	Abnormality of the upper limb	Occasional (5-29%)
HP:0002936	Distal sensory impairment	Occasional (5-29%)
HP:0003418	Back pain	Occasional (5-29%)
HP:0003474	Somatic sensory dysfunction	Occasional (5-29%)
HP:0005521	Disseminated intravascular coagulation	Occasional (5-29%)
HP:0006489	Abnormality of the femoral metaphysis	Occasional (5-29%)
HP:0007340	Lower limb muscle weakness	Occasional (5-29%)
HP:0010484	Hypertrophy of the upper limb	Occasional (5-29%)
HP:0012514	Lower limb pain	Occasional (5-29%)
HP:0012531	Pain	Occasional (5-29%)
HP:0030833	Neck pain	Occasional (5-29%)
HP:0031138	Abnormal B-type natriuretic peptide level	Occasional (5-29%)
HP:0031939	Conus terminalis arteriovenous malformation	Occasional (5-29%)
HP:0040189	Scaling skin	Occasional (5-29%)
HP:0100749	Chest pain	Occasional (5-29%)
HP:0100766	Abnormal lymphatic vessel morphology	Occasional (5-29%)
HP:0100775	Dural ectasia	Occasional (5-29%)
HP:0200042	Skin ulcer	Occasional (5-29%)
HP:0007461	Hemangiomatosis	Very rare (<1-4%)
HP:0010550	Paraplegia	Very rare (<1-4%)

Identifiers

Disease identifiers

Field	Value
Canonical name	Parkes Weber syndrome
Mondo ID	MONDO:0700325
Orphanet	90307
Is cancer (heuristic)	no

Also known as: PWS

Data availability: 1 ClinVar variant.

Disease family

Classification path: disease › human disease › disease by body system or component › cardiovascular disorder › vascular disorder › vascular malformation › congenital vascular malformation › Parkes Weber syndrome

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/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1691383	NM_002755.4(MAP2K1):c.173_187del (p.Gln58_Glu62del)	MAP2K1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 2 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
MAP2K1	Orphanet:1340	Cardiofaciocutaneous syndrome
MAP2K1	Orphanet:389	Langerhans cell histiocytosis

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
MAP2K1	HGNC:6840	ENSG00000169032	Q02750	Dual specificity mitogen-activated protein kinase kinase 1	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
MAP2K1	Dual specificity mitogen-activated protein kinase kinase 1	Dual specificity protein kinase which acts as an essential component of the MAP kinase signal transduction pathway.

Protein-family classification

Druggable: 1 · 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	1	27.7×	0.036

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
MAP2K1	Kinase	yes	2.7.12.2	Prot_kinase_dom, Ser/Thr_kinase_AS, Kinase-like_dom_sf

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
oocyte	1
orbitofrontal cortex	1
secondary oocyte	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
MAP2K1	298	ubiquitous	marker	secondary oocyte, oocyte, orbitofrontal cortex

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
MAP2K1	5,944

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
MAP2K1	Q02750	94

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 61. 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
Signaling by MAP2K mutants	1	2855.0×	0.009	MAP2K1
Negative feedback regulation of MAPK pathway	1	1903.3×	0.009	MAP2K1
Prolonged ERK activation events	1	1427.5×	0.009	MAP2K1
MAPK3 (ERK1) activation	1	1038.2×	0.009	MAP2K1
Frs2-mediated activation	1	951.7×	0.009	MAP2K1
Uptake and function of anthrax toxins	1	951.7×	0.009	MAP2K1
Uptake and actions of bacterial toxins	1	815.7×	0.009	MAP2K1
MAP3K8 (TPL2)-dependent MAPK1/3 activation	1	713.8×	0.009	MAP2K1
RAF-independent MAPK1/3 activation	1	634.4×	0.009	MAP2K1
Signalling to ERKs	1	601.0×	0.009	MAP2K1
Signal transduction by L1	1	519.1×	0.009	MAP2K1
Signaling by RAS mutants	1	423.0×	0.009	MAP2K1
RAF activation	1	335.9×	0.009	MAP2K1
Bacterial Infection Pathways	1	335.9×	0.009	MAP2K1
Signaling by high-kinase activity BRAF mutants	1	317.2×	0.009	MAP2K1
MAP kinase activation	1	308.6×	0.009	MAP2K1
MAP2K and MAPK activation	1	285.5×	0.009	MAP2K1
Signaling by RAF1 mutants	1	278.5×	0.009	MAP2K1
Interleukin-1 family signaling	1	271.9×	0.009	MAP2K1
Negative regulation of MAPK pathway	1	265.6×	0.009	MAP2K1
Interleukin-17 signaling	1	253.8×	0.009	MAP2K1
Signaling by moderate kinase activity BRAF mutants	1	253.8×	0.009	MAP2K1
Paradoxical activation of RAF signaling by kinase inactive BRAF	1	253.8×	0.009	MAP2K1
Signaling downstream of RAS mutants	1	253.8×	0.009	MAP2K1
Oncogenic MAPK signaling	1	248.3×	0.009	MAP2K1
Toll Like Receptor 10 (TLR10) Cascade	1	215.5×	0.009	MAP2K1
Toll Like Receptor 5 (TLR5) Cascade	1	215.5×	0.009	MAP2K1
MyD88 cascade initiated on plasma membrane	1	203.9×	0.009	MAP2K1
Signaling by NTRK1 (TRKA)	1	196.9×	0.009	MAP2K1
Toll Like Receptor 3 (TLR3) Cascade	1	193.6×	0.009	MAP2K1

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
negative regulation of homotypic cell-cell adhesion	1	8426.0×	0.002	MAP2K1
Golgi inheritance	1	8426.0×	0.002	MAP2K1
cerebellar cortex formation	1	5617.3×	0.002	MAP2K1
positive regulation of endodermal cell differentiation	1	5617.3×	0.002	MAP2K1
regulation of Golgi inheritance	1	4213.0×	0.002	MAP2K1
regulation of vascular associated smooth muscle contraction	1	3370.4×	0.002	MAP2K1
epithelial cell proliferation involved in lung morphogenesis	1	3370.4×	0.002	MAP2K1
positive regulation of muscle contraction	1	2407.4×	0.002	MAP2K1
regulation of axon regeneration	1	2407.4×	0.002	MAP2K1
trachea formation	1	2407.4×	0.002	MAP2K1
labyrinthine layer development	1	2106.5×	0.002	MAP2K1
negative regulation of hypoxia-induced intrinsic apoptotic signaling pathway	1	2106.5×	0.002	MAP2K1
regulation of early endosome to late endosome transport	1	2106.5×	0.002	MAP2K1
regulation of stress-activated MAPK cascade	1	1872.4×	0.002	MAP2K1
ERBB2-ERBB3 signaling pathway	1	1685.2×	0.002	MAP2K1
Bergmann glial cell differentiation	1	1532.0×	0.002	MAP2K1
placenta blood vessel development	1	1404.3×	0.002	MAP2K1
positive regulation of protein serine/threonine kinase activity	1	1296.3×	0.002	MAP2K1
positive regulation of ATP biosynthetic process	1	1203.7×	0.002	MAP2K1
Schwann cell development	1	1053.2×	0.003	MAP2K1
type B pancreatic cell proliferation	1	887.0×	0.003	MAP2K1
positive regulation of Ras protein signal transduction	1	887.0×	0.003	MAP2K1
vesicle transport along microtubule	1	887.0×	0.003	MAP2K1
regulation of neurotransmitter receptor localization to postsynaptic specialization membrane	1	887.0×	0.003	MAP2K1
face development	1	802.5×	0.003	MAP2K1
melanosome transport	1	766.0×	0.003	MAP2K1
central nervous system neuron differentiation	1	601.9×	0.003	MAP2K1
positive regulation of axonogenesis	1	581.1×	0.003	MAP2K1
thyroid gland development	1	543.6×	0.003	MAP2K1
response to axon injury	1	510.7×	0.003	MAP2K1

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 1 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
MAP2K1	VEMURAFENIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
MAP2K1	54	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
VEMURAFENIB	4	MAP2K1
SELUMETINIB	4	MAP2K1
TRAMETINIB	4	MAP2K1
COBIMETINIB	4	MAP2K1
BINIMETINIB	4	MAP2K1
DASATINIB	4	MAP2K1
SORAFENIB	4	MAP2K1
FEDRATINIB	4	MAP2K1
AXITINIB	4	MAP2K1
RUXOLITINIB	4	MAP2K1
NERATINIB	4	MAP2K1
TOFACITINIB	4	MAP2K1
VANDETANIB	4	MAP2K1
BOSUTINIB	4	MAP2K1
GILTERITINIB	4	MAP2K1
NINTEDANIB	4	MAP2K1
SUNITINIB	4	MAP2K1
SARACATINIB	3	MAP2K1
AVUTOMETINIB	3	MAP2K1
LINSITINIB	3	MAP2K1
ORANTINIB	3	MAP2K1
CANERTINIB	3	MAP2K1
DOVITINIB	3	MAP2K1
LESTAURTINIB	3	MAP2K1
CI-1040	2	MAP2K1
MIRDAMETINIB	2	MAP2K1
E-6201	2	MAP2K1
FORETINIB	2	MAP2K1
REFAMETINIB	2	MAP2K1
TAK-733	2	MAP2K1

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
MAP2K1	1,200	Binding:1150, Functional:47, ADMET:3

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
MAP2K1	2.7.12.2	mitogen-activated protein kinase kinase

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
MAP2K1	1,200

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

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)
VEMURAFENIB	4	MAP2K1
SELUMETINIB	4	MAP2K1
TRAMETINIB	4	MAP2K1
COBIMETINIB	4	MAP2K1
BINIMETINIB	4	MAP2K1
DASATINIB	4	MAP2K1
SORAFENIB	4	MAP2K1
FEDRATINIB	4	MAP2K1
AXITINIB	4	MAP2K1
RUXOLITINIB	4	MAP2K1
NERATINIB	4	MAP2K1
TOFACITINIB	4	MAP2K1
VANDETANIB	4	MAP2K1
BOSUTINIB	4	MAP2K1
GILTERITINIB	4	MAP2K1
NINTEDANIB	4	MAP2K1
SUNITINIB	4	MAP2K1
SARACATINIB	3	MAP2K1
AVUTOMETINIB	3	MAP2K1
LINSITINIB	3	MAP2K1
ORANTINIB	3	MAP2K1
CANERTINIB	3	MAP2K1
DOVITINIB	3	MAP2K1
LESTAURTINIB	3	MAP2K1
CI-1040	2	MAP2K1
MIRDAMETINIB	2	MAP2K1
E-6201	2	MAP2K1
FORETINIB	2	MAP2K1
REFAMETINIB	2	MAP2K1
TAK-733	2	MAP2K1

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	MAP2K1
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: 2.

Phase distribution (across all retrieved trials)

Phase	Trials
PHASE1/PHASE2	1
Not specified	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT06239116	PHASE1/PHASE2	RECRUITING	A Study of RM-718 in Healthy Subjects and Patients With MC4R Pathway Impairment
NCT01364857	Not specified	COMPLETED	French National Cohort of Children With Port Wine Stain