Proteus-like syndrome

Summary

Proteus-like syndrome (MONDO:0017571) is a disease with 1 cohort gene.

At a glance

• Prevalence: Unknown (Worldwide)
• Cohort genes: 1
• ClinVar variants: 3
• Phenotypes (HPO): 31

Clinical features

Signs & symptoms

Clinical features (HPO)

31 HPO clinical features (Orphanet curated; top 31 by frequency):

HPO ID	Term	Frequency
HP:0000545	Myopia	Very frequent (80-99%)
HP:0000615	Abnormal pupil morphology	Very frequent (80-99%)
HP:0001028	Hemangioma	Very frequent (80-99%)
HP:0001031	Subcutaneous lipoma	Very frequent (80-99%)
HP:0001140	Limbal dermoid	Very frequent (80-99%)
HP:0001249	Intellectual disability	Very frequent (80-99%)
HP:0002816	Genu recurvatum	Very frequent (80-99%)
HP:0007400	Irregular hyperpigmentation	Very frequent (80-99%)
HP:0010807	Open bite	Very frequent (80-99%)
HP:0010816	Epidermal nevus	Very frequent (80-99%)
HP:0100559	Lower limb asymmetry	Very frequent (80-99%)
HP:0100774	Hyperostosis	Very frequent (80-99%)
HP:0000238	Hydrocephalus	Frequent (30-79%)
HP:0000256	Macrocephaly	Frequent (30-79%)
HP:0000303	Mandibular prognathia	Frequent (30-79%)
HP:0000518	Cataract	Frequent (30-79%)
HP:0000541	Retinal detachment	Frequent (30-79%)
HP:0000828	Abnormality of the parathyroid gland	Frequent (30-79%)
HP:0001100	Heterochromia iridis	Frequent (30-79%)
HP:0001334	Communicating hydrocephalus	Frequent (30-79%)
HP:0005293	Venous insufficiency	Frequent (30-79%)
HP:0009721	Shagreen patch	Frequent (30-79%)
HP:0100777	Exostoses	Frequent (30-79%)
HP:0000147	Polycystic ovaries	Occasional (5-29%)
HP:0000268	Dolichocephaly	Occasional (5-29%)
HP:0000463	Anteverted nares	Occasional (5-29%)
HP:0000494	Downslanted palpebral fissures	Occasional (5-29%)
HP:0001744	Splenomegaly	Occasional (5-29%)
HP:0002652	Skeletal dysplasia	Occasional (5-29%)
HP:0010516	Thymus hyperplasia	Occasional (5-29%)
HP:0100730	Bronchogenic cyst	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	Proteus-like syndrome
Mondo ID	MONDO:0017571
Orphanet	2969
NCIT	C179930
SNOMED CT	716862002
UMLS	C1866398
MedGen	356222
GARD	0012801
Is cancer (heuristic)	no

Also known as: Cohen-Hayden syndrome · Proteus like syndrome intellectual disability eye defect · Proteus like syndrome mental retardation eye defect

Data availability: 3 ClinVar variants · 1 GenCC gene-disease record.

Disease family

Classification path: disease › human disease › disease by body system or component › integumentary system disorder › Proteus-like syndrome

Related subtypes (35): Neu-Laxova syndrome, cutaneous mycosis, integumentary system benign neoplasm, integumentary system cancer, nipple neoplasm, nail disorder, disorder of pilosebaceous unit, Bartholin duct cyst, benign mammary dysplasia, skin disorder, breast fibrosis, breast mucosa-associated lymphoid tissue lymphoma, panniculitis, alopecia-epilepsy-pyorrhea-intellectual disability syndrome, autosomal dominant deafness - onychodystrophy syndrome, keratoderma hereditarium mutilans, Rombo syndrome, Sjogren-Larsson syndrome, mucosulfatidosis, ichthyosis prematurity syndrome, ANE syndrome, frontonasal dysplasia with alopecia and genital anomaly, peeling skin-leukonuchia-acral punctate keratoses-cheilitis-knuckle pads syndrome, mandibulofacial dysostosis with alopecia, cutis laxa, X-linked ichthyosis syndrome, demodicidosis, familial atypical multiple mole melanoma syndrome, familial tumoral calcinosis, subcutaneous tissue disorder, Bartholin gland neoplasm, pseudoxanthoma elasticum (inherited or acquired), skin appendage disorder, keratinization disease, paraneoplastic cutaneous 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

3 retrieved; paginated sample, class counts are floors:

2 pathogenic, 1 not provided

ClinVar	Variant (HGVS)	Gene	Classification	Review
7833	NM_000314.8(PTEN):c.1003C>T (p.Arg335Ter)	PTEN	Pathogenic	criteria provided, multiple submitters, no conflicts
7843	NM_000314.8(PTEN):c.507del (p.Ser170fs)	PTEN	Pathogenic	reviewed by expert panel
2578336	NM_000314.8(PTEN):c.634+3_634+7delinsTCTCATCCTTGAATTT	PTEN	not provided	no classification provided

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 17 · Orphanet: 14 · 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
PTEN	Supportive	Autosomal dominant	Proteus-like syndrome	17

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
PTEN	Orphanet:109	Bannayan-Riley-Ruvalcaba syndrome
PTEN	Orphanet:137608	Segmental outgrowth-lipomatosis-arteriovenous malformation-epidermal nevus syndrome
PTEN	Orphanet:145	Hereditary breast and/or ovarian cancer syndrome
PTEN	Orphanet:201	Cowden syndrome
PTEN	Orphanet:210548	Macrocephaly-intellectual disability-autism syndrome
PTEN	Orphanet:2969	Proteus-like syndrome
PTEN	Orphanet:494547	Squamous cell carcinoma of the hypopharynx
PTEN	Orphanet:494550	Squamous cell carcinoma of the larynx
PTEN	Orphanet:500464	Squamous cell carcinoma of the nasal cavity and paranasal sinuses
PTEN	Orphanet:500478	Squamous cell carcinoma of the oropharynx
PTEN	Orphanet:502363	Squamous cell carcinoma of the oral cavity
PTEN	Orphanet:502366	Squamous cell carcinoma of the lip
PTEN	Orphanet:65285	Lhermitte-Duclos disease
PTEN	Orphanet:79076	Juvenile polyposis of infancy

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
PTEN	HGNC:9588	ENSG00000171862	P60484	Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
PTEN	Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN	Dual-specificity protein phosphatase, dephosphorylating tyrosine-, serine- and threonine-phosphorylated proteins.

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
Phosphatase	1	83.9×	0.012

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
PTEN	Phosphatase	yes	3.1.3.16	Tyr_Pase_dom, Tyr_Pase_cat, Tensin_C2-dom

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
calcaneal tendon	1
endothelial cell	1
sperm	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
PTEN	256	ubiquitous	marker	sperm, endothelial cell, calcaneal tendon

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
PTEN	11,626

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
PTEN	P60484	12

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 13. 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
PTEN Loss of Function in Cancer	1	5710.0×	0.002	PTEN
Regulation of PTEN mRNA translation	1	1142.0×	0.004	PTEN
Regulation of PTEN localization	1	1038.2×	0.004	PTEN
Synthesis of IP3 and IP4 in the cytosol	1	423.0×	0.007	PTEN
Transcriptional Regulation by MECP2	1	317.2×	0.007	PTEN
Negative regulation of the PI3K/AKT network	1	278.5×	0.007	PTEN
Ovarian tumor domain proteases	1	278.5×	0.007	PTEN
Synthesis of PIPs at the plasma membrane	1	211.5×	0.007	PTEN
Regulation of PTEN stability and activity	1	184.2×	0.007	PTEN
Regulation of PTEN gene transcription	1	178.4×	0.007	PTEN
TP53 Regulates Metabolic Genes	1	129.8×	0.008	PTEN
Downstream TCR signaling	1	128.3×	0.008	PTEN
Ub-specific processing proteases	1	53.1×	0.019	PTEN

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 synaptic vesicle clustering	1	8426.0×	0.002	PTEN
negative regulation of keratinocyte migration	1	5617.3×	0.002	PTEN
rhythmic synaptic transmission	1	4213.0×	0.002	PTEN
central nervous system myelin maintenance	1	2808.7×	0.002	PTEN
negative regulation of cell cycle G1/S phase transition	1	2407.4×	0.002	PTEN
negative regulation of wound healing, spreading of epidermal cells	1	2407.4×	0.002	PTEN
spindle assembly involved in female meiosis	1	1872.4×	0.002	PTEN
central nervous system neuron axonogenesis	1	1872.4×	0.002	PTEN
postsynaptic density assembly	1	1872.4×	0.002	PTEN
neuron-neuron synaptic transmission	1	1685.2×	0.002	PTEN
negative regulation of peptidyl-serine phosphorylation	1	1685.2×	0.002	PTEN
negative regulation of cell size	1	1685.2×	0.002	PTEN
presynaptic membrane assembly	1	1685.2×	0.002	PTEN
negative regulation of organ growth	1	1404.3×	0.002	PTEN
forebrain morphogenesis	1	1404.3×	0.002	PTEN
multicellular organismal response to stress	1	1296.3×	0.002	PTEN
negative regulation of axonogenesis	1	1296.3×	0.002	PTEN
cellular response to electrical stimulus	1	1296.3×	0.002	PTEN
negative regulation of excitatory postsynaptic potential	1	1296.3×	0.002	PTEN
maternal behavior	1	1123.5×	0.002	PTEN
prepulse inhibition	1	1123.5×	0.002	PTEN
locomotor rhythm	1	1053.2×	0.003	PTEN
synapse maturation	1	936.2×	0.003	PTEN
dendritic spine morphogenesis	1	887.0×	0.003	PTEN
negative regulation of focal adhesion assembly	1	766.0×	0.003	PTEN
regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	1	702.2×	0.003	PTEN
negative regulation of vascular associated smooth muscle cell proliferation	1	674.1×	0.003	PTEN
phosphatidylinositol dephosphorylation	1	648.1×	0.003	PTEN
positive regulation of intracellular signal transduction	1	648.1×	0.003	PTEN
negative regulation of cellular senescence	1	648.1×	0.003	PTEN

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
PTEN	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
PTEN	8	Binding:8

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
PTEN	3.1.3.16, 3.1.3.67	protein-serine/threonine phosphatase, phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase

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	1	PTEN
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

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)
PTEN	8	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.