Juvenile polyposis of infancy

Summary

Juvenile polyposis of infancy (MONDO:0019190) is a disease with 1 cohort gene.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Cohort genes: 1
• ClinVar variants: 1
• Phenotypes (HPO): 43

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		11	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

43 HPO clinical features (Orphanet curated; top 43 by frequency):

HPO ID	Term	Frequency
HP:0005227	Adenomatous colonic polyposis	Obligate (100%)
HP:0002239	Gastrointestinal hemorrhage	Very frequent (80-99%)
HP:0002014	Diarrhea	Very frequent (80-99%)
HP:0001903	Anemia	Very frequent (80-99%)
HP:0004326	Cachexia	Frequent (30-79%)
HP:0002243	Protein-losing enteropathy	Frequent (30-79%)
HP:0000256	Macrocephaly	Frequent (30-79%)
HP:0001999	Abnormal facial shape	Frequent (30-79%)
HP:0002003	Large forehead	Frequent (30-79%)
HP:0000316	Hypertelorism	Frequent (30-79%)
HP:0004390	Hamartomatous polyposis	Frequent (30-79%)
HP:0002027	Abdominal pain	Frequent (30-79%)
HP:0002573	Hematochezia	Frequent (30-79%)
HP:0002249	Melena	Frequent (30-79%)
HP:0005505	Refractory anemia	Frequent (30-79%)
HP:0003073	Hypoalbuminemia	Frequent (30-79%)
HP:0001028	Hemangioma	Frequent (30-79%)
HP:0001249	Intellectual disability	Frequent (30-79%)
HP:0001892	Abnormal bleeding	Frequent (30-79%)
HP:0010797	Hemangioblastoma	Occasional (5-29%)
HP:0000494	Downslanted palpebral fissures	Occasional (5-29%)
HP:0005280	Depressed nasal bridge	Occasional (5-29%)
HP:0000369	Low-set ears	Occasional (5-29%)
HP:0000160	Narrow mouth	Occasional (5-29%)
HP:0000331	Short chin	Occasional (5-29%)
HP:0001256	Intellectual disability, mild	Occasional (5-29%)
HP:0002584	Intestinal bleeding	Occasional (5-29%)
HP:0002576	Intussusception	Occasional (5-29%)
HP:0002035	Rectal prolapse	Occasional (5-29%)
HP:0100759	Clubbing of fingers	Occasional (5-29%)
HP:0001627	Abnormal heart morphology	Occasional (5-29%)
HP:0001290	Generalized hypotonia	Occasional (5-29%)
HP:0001270	Motor delay	Occasional (5-29%)
HP:0001631	Atrial septal defect	Occasional (5-29%)
HP:0001643	Patent ductus arteriosus	Occasional (5-29%)
HP:0004322	Short stature	Occasional (5-29%)
HP:0006608	Midclavicular hypoplasia	Occasional (5-29%)
HP:0030257	Freckled genitalia	Occasional (5-29%)
HP:0002007	Frontal bossing	Occasional (5-29%)
HP:0002705	High, narrow palate	Occasional (5-29%)
HP:0011304	Broad thumb	Occasional (5-29%)
HP:0010174	Broad phalanx of the toes	Occasional (5-29%)
HP:0001031	Subcutaneous lipoma	Very rare (<1-4%)

Identifiers

Disease identifiers

Field	Value
Canonical name	juvenile polyposis of infancy
Mondo ID	MONDO:0019190
Orphanet	79076
ICD-11	378686036
UMLS	C5445164
MedGen	1778573
GARD	0016696
Is cancer (heuristic)	no

Also known as: infantile juvenile polyposis syndrome · infantile onset juvenile polyposis syndrome · juvenile polyposis syndrome of infancy

Data availability: 1 ClinVar variant.

Disease family

Classification path: disease › human disease › disease by body system or component › digestive system disorder › juvenile polyposis syndrome › juvenile polyposis of infancy

Related subtypes (2): generalized juvenile polyposis/juvenile polyposis coli, BMPR1A-related juvenile polyposis 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 likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
492346	NM_000314.8(PTEN):c.80-14A>T	PTEN	Likely benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 14 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

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	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.