Gastrointestinal hamartoma

Summary

Gastrointestinal hamartoma (MONDO:0006231) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 1

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	gastrointestinal hamartoma
Mondo ID	MONDO:0006231
EFO	EFO:1000280
NCIT	C96475
UMLS	C3272802
MedGen	474435
Is cancer (heuristic)	no

Also known as: gastrointestinal hamartoma

Data availability: 1 ClinVar variant.

Disease family

An umbrella term covering 4 Mondo subtypes.

Classification path: disease › human disease › disease by etiologic mechanism › cancer or benign tumor › neoplastic disease or syndrome › neoplasm › hamartoma › gastrointestinal hamartoma

Related subtypes (12): chondroid hamartoma, linear nevus sebaceous syndrome, linear and whorled nevoid hypermelanosis, congenital epulis, congenital smooth muscle hamartoma, hamartoma of skin appendage, hamartoma of lung, basaloid follicular hamartoma, angiomyomatous hamartoma, giant mammary hamartoma, mesenchymal hamartoma, odontoma

Subtypes (4): colorectal hamartoma, gastric hamartomatous polyp, juvenile polyp, Peutz-Jeghers polyp

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
1264324	NM_000314.8(PTEN):c.-136G>C	PTEN	Pathogenic	no assertion criteria provided

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.