Intestinal polyposis syndrome

Summary

Intestinal polyposis syndrome (MONDO:0015185) is a disease (an umbrella term covering 8 Mondo subtypes) with 2 cohort genes and 2 clinical trials.

At a glance

• Umbrella term: 8 Mondo subtypes
• Cohort genes: 2
• ClinVar variants: 2
• Clinical trials: 2

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	intestinal polyposis syndrome
Mondo ID	MONDO:0015185
Orphanet	104010
NCIT	C155954
SNOMED CT	254589009
UMLS	C0345891
MedGen	577190
GARD	0019847
MedDRA	10057018
Is cancer (heuristic)	no

Data availability: 2 ClinVar variants.

Disease family

An umbrella term covering 8 Mondo subtypes.

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › hereditary neoplastic syndrome › intestinal polyposis syndrome

Related subtypes (116): mosaic variegated aneuploidy syndrome, tuberous sclerosis, hereditary breast ovarian cancer syndrome, hereditary multiple osteochondromas, nevoid basal cell carcinoma syndrome, leukemia, chronic lymphocytic, susceptibility to, 2, blue rubber bleb nevus, cherubism, Beckwith-Wiedemann syndrome, multiple self-healing squamous epithelioma, erythroleukemia, familial, susceptibility to, goiter, multinodular 1, with or without Sertoli-Leydig cell tumors, hyperparathyroidism 2 with jaw tumors, Kaposi sarcoma, susceptibility to, hereditary leiomyomatosis and renal cell cancer, susceptibility to uveal melanoma, melanoma and neural system tumor syndrome, nasopharyngeal carcinoma, susceptibility to, 2, WAGR syndrome, neuroblastoma, susceptibility to, 1, Rothmund-Thomson syndrome, mismatch repair cancer syndrome 1, Wiskott-Aldrich syndrome, N syndrome, hereditary thrombocytopenia and hematologic cancer predisposition syndrome, prostate cancer/brain cancer susceptibility, Brooke-Spiegler syndrome, pancreatic cancer, susceptibility to, 1, Carney-Stratakis syndrome, nasopharyngeal carcinoma, susceptibility to, 1, ovarian cancer, susceptibility to, 1, colorectal cancer, susceptibility to, 1, lung cancer susceptibility 1, leukemia, chronic lymphocytic, susceptibility to, 1, Kostmann syndrome, colorectal cancer, susceptibility to, 2, colorectal cancer, susceptibility to, 3, colorectal cancer, susceptibility to, 5, colorectal cancer, susceptibility to, 6, colorectal cancer, susceptibility to, 7, leukemia, chronic lymphocytic, susceptibility to, 3, leukemia, chronic lymphocytic, susceptibility to, 4, leukemia, chronic lymphocytic, susceptibility to, 5, lung cancer susceptibility 3, colorectal cancer, susceptibility to, 8, colorectal cancer, susceptibility to, 9, colorectal cancer, susceptibility to, 10, colorectal cancer, susceptibility to, 11, lung cancer susceptibility 4, neuroblastoma, susceptibility to, 3, neuroblastoma, susceptibility to, 4, neuroblastoma, susceptibility to, 5, neuroblastoma, susceptibility to, 6, leukemia, acute lymphocytic, susceptibility to, 1, leukemia, acute lymphocytic, susceptibility to, 2, lung cancer susceptibility 5, BAP1-related tumor predisposition syndrome, familial cutaneous telangiectasia and oropharyngeal predisposition cancer syndrome, Maffucci syndrome, basal cell carcinoma, susceptibility to, 7, colorectal cancer, susceptibility to, 12, leukemia, acute lymphoblastic, susceptibility to, 3, cholangiocarcinoma, susceptibility to, progeroid features-hepatocellular carcinoma predisposition syndrome, neuroblastoma, susceptibility to, 7, DDX41-related hematologic malignancy predisposition syndrome, nasopharyngeal carcinoma, susceptibility to, 3, familial isolated hyperparathyroidism, dyskeratosis congenita, familial rhabdoid tumor, multiple endocrine neoplasia, hereditary pheochromocytoma-paraganglioma, PTEN hamartoma tumor syndrome, familial multiple fibrofolliculoma, hereditary retinoblastoma, familial atypical multiple mole melanoma syndrome, hereditary nonpolyposis colon cancer, Li-Fraumeni syndrome, Cobb syndrome, neurofibromatosis, susceptibility to familial cutaneous melanoma, pancreatic cancer, susceptibility to, 5, leukemia, acute myeloid, susceptibility to, diffuse gastric and lobular breast cancer syndrome with or without cleft lip and/or palate, glioma susceptibility, hemangioma, capillary infantile, susceptibility to, CDH1-related diffuse gastric and lobular breast cancer syndrome, NTHL1-deficiency tumor predisposition syndrome, SAMD9-related spectrum and myeloid neoplasm risk, neuroblastoma, susceptibility to, 2, BARD1-related cancer predisposition, BRCA1-related cancer predisposition, BRCA2-related cancer predisposition, ATM-related cancer predisposition, CHEK2-related cancer predisposition, PALB2-related cancer predisposition, RAD51C-related cancer predisposition, RAD51D-related cancer predisposition, Li-fraumeni-like syndrome, breast cancer, familial, susceptibility to, 1, breast cancer, familial, susceptibility to, 2, breast cancer, familial, susceptibility to, 3, colorectal cancer, susceptibility to, 4, colorectal cancer, susceptibility to, on chromosome 15, ovarian cancer, familial, susceptibility to, 1, ovarian cancer, familial, susceptibility to, 2, ovarian cancer, familial, susceptibility to, 3, inherited hematologic cancer-predisposing syndrome, mosaic neurofibromatosis/schwannomatosis, tumor predisposition syndrome 2, prostate cancer, hereditary, X-linked 3, follicular lymphoma, susceptibility to, GPR161-related medulloblastoma predisposition, SAMD9L-related spectrum and myeloid neoplasm risk, HAVCR2-related cancer predisposition, EGLN1-related erythrocytosis and pheochromocytoma/paraganglioma predisposition

Subtypes (8): Bannayan-Riley-Ruvalcaba syndrome, juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome, Peutz-Jeghers syndrome, Cronkhite-Canada syndrome, hereditary mixed polyposis syndrome, hyperplastic polyposis syndrome, juvenile polyposis syndrome, classic or attenuated familial adenomatous polyposis

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

2 retrieved; paginated sample, class counts are floors:

2 conflicting classifications of pathogenicity

ClinVar	Variant (HGVS)	Gene	Classification	Review
408450	NM_000251.3(MSH2):c.712T>G (p.Tyr238Asp)	MSH2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
473569	NM_006231.4(POLE):c.2T>A (p.Met1Lys)	POLE	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 6 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
MSH2	Orphanet:144	Lynch syndrome
MSH2	Orphanet:252202	Constitutional mismatch repair deficiency syndrome
POLE	Orphanet:352712	Facial dysmorphism-immunodeficiency-livedo-short stature syndrome
POLE	Orphanet:440437	Familial colorectal cancer Type X
POLE	Orphanet:447877	Polymerase proofreading-related polyposis
POLE	Orphanet:85173	IMAGe syndrome

Cohort genes → proteins

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
MSH2	HGNC:7325	ENSG00000095002	P43246	DNA mismatch repair protein Msh2	clinvar
POLE	HGNC:9177	ENSG00000177084	Q07864	DNA polymerase epsilon catalytic subunit A	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
MSH2	DNA mismatch repair protein Msh2	Component of the post-replicative DNA mismatch repair system (MMR).
POLE	DNA polymerase epsilon catalytic subunit A	Catalytic component of the DNA polymerase epsilon complex.

Protein-family classification

Druggable: 0 · Difficult: 1 · 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
Transcription factor	1	4.1×	0.455
Other/Unknown	1	0.9×	0.805

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
MSH2	Other/Unknown	no		DNA_mismatch_repair_MutS_C, DNA_mismatch_repair_MutS-lik_N, DNA_mismatch_repair_MutS_core
POLE	Transcription factor	no	2.7.7.7	DNA-dir_DNA_pol_B_exonuc, DNA-dir_DNA_pol_B, RNaseH-like_sf

Expression context

Cohort genes with no expression data: 0.

2 cohort genes 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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
oocyte	1
secondary oocyte	1
ventricular zone	1
cerebellar hemisphere	1
right hemisphere of cerebellum	1
right testis	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
MSH2	278	ubiquitous	marker	secondary oocyte, oocyte, ventricular zone
POLE	221	ubiquitous	marker	right hemisphere of cerebellum, right testis, cerebellar hemisphere

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
MSH2	4,537
POLE	3,267

Intra-cohort edges

A	B	Sources
MSH2	POLE	string_interaction

Structural data

PDB: 2 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
MSH2	P43246	30
POLE	Q07864	18

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 25. Enrichment computed across 2 evidence-associated genes (2 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 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Defective Mismatch Repair Associated With MSH3	1	2855.0×	0.004	MSH2
Defective Mismatch Repair Associated With MSH6	1	2855.0×	0.004	MSH2
Defective Mismatch Repair Associated With MSH2	1	1903.3×	0.004	MSH2
Mismatch Repair	1	1427.5×	0.004	MSH2
Diseases of Mismatch Repair (MMR)	1	1427.5×	0.004	MSH2
DNA replication initiation	1	713.8×	0.006	POLE
Mismatch repair (MMR) directed by MSH2:MSH6 (MutSalpha)	1	407.9×	0.008	MSH2
Mismatch repair (MMR) directed by MSH2:MSH3 (MutSbeta)	1	407.9×	0.008	MSH2
Diseases of DNA repair	1	285.5×	0.010	MSH2
PCNA-Dependent Long Patch Base Excision Repair	1	259.6×	0.010	POLE
Gap-filling DNA repair synthesis and ligation in GG-NER	1	219.6×	0.010	POLE
Recognition of DNA damage by PCNA-containing replication complex	1	190.3×	0.011	POLE
Termination of translesion DNA synthesis	1	173.0×	0.011	POLE
Activation of the pre-replicative complex	1	163.1×	0.011	POLE
Dual Incision in GG-NER	1	129.8×	0.013	POLE
HDR through Homologous Recombination (HRR)	1	95.2×	0.015	POLE
TP53 Regulates Transcription of DNA Repair Genes	1	90.6×	0.015	MSH2
Gap-filling DNA repair synthesis and ligation in TC-NER	1	89.2×	0.015	POLE
Dual incision in TC-NER	1	86.5×	0.015	POLE
DNA Repair	1	49.2×	0.025	MSH2
Transcriptional Regulation by TP53	1	31.0×	0.038	MSH2
RNA Polymerase II Transcription	1	11.3×	0.099	MSH2
Gene expression (Transcription)	1	8.9×	0.118	MSH2
Generic Transcription Pathway	1	7.5×	0.133	MSH2
Disease	1	6.5×	0.147	MSH2

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
somatic recombination of immunoglobulin genes involved in immune response	1	8426.0×	0.003	MSH2
DNA replication proofreading	1	2808.7×	0.003	POLE
leading strand elongation	1	2106.5×	0.003	POLE
somatic recombination of immunoglobulin gene segments	1	2106.5×	0.003	MSH2
B cell mediated immunity	1	2106.5×	0.003	MSH2
maintenance of DNA repeat elements	1	1685.2×	0.003	MSH2
nucleotide-excision repair, DNA gap filling	1	1404.3×	0.003	POLE
mitotic recombination	1	1404.3×	0.003	MSH2
positive regulation of isotype switching to IgA isotypes	1	1404.3×	0.003	MSH2
response to UV-B	1	936.2×	0.004	MSH2
DNA damage tolerance	1	842.6×	0.004	MSH2
positive regulation of isotype switching to IgG isotypes	1	766.0×	0.004	MSH2
oxidative phosphorylation	1	702.2×	0.004	MSH2
base-excision repair, gap-filling	1	561.7×	0.004	POLE
negative regulation of DNA recombination	1	561.7×	0.004	MSH2
somatic hypermutation of immunoglobulin genes	1	526.6×	0.004	MSH2
DNA synthesis involved in DNA repair	1	468.1×	0.004	POLE
mitotic intra-S DNA damage checkpoint signaling	1	468.1×	0.004	MSH2
response to X-ray	1	443.5×	0.004	MSH2
isotype switching	1	421.3×	0.004	MSH2
mismatch repair	1	324.1×	0.005	MSH2
DNA-templated DNA replication	1	280.9×	0.006	POLE
intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator	1	247.8×	0.006	MSH2
embryonic organ development	1	240.7×	0.006	POLE
germ cell development	1	227.7×	0.006	MSH2
determination of adult lifespan	1	216.1×	0.006	MSH2
B cell differentiation	1	109.4×	0.012	MSH2
double-strand break repair	1	101.5×	0.012	MSH2
G1/S transition of mitotic cell cycle	1	100.3×	0.012	POLE
DNA replication	1	82.6×	0.014	POLE

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 2

Druggability breadth: 2 of 2 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
MSH2	0	0
POLE	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
MSH2	9	Binding:9

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
POLE	2.7.7.7	DNA-directed DNA polymerase

Pharmacogenomics

Cohort genes with a PharmGKB record: 2; 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	2	MSH2, POLE

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
MSH2	9	—
POLE	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 2.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	2

Top trials by phase / activity

NCT	Phase	Status	Title
NCT01656746	Not specified	COMPLETED	Single Incision Laparoscopic Surgery in Treating Patients With Colorectal Disease
NCT02965209	Not specified	COMPLETED	European Novel Motorized Spiral Endoscopy Trial