Intestinal pseudo-obstruction

Summary

Intestinal pseudo-obstruction (MONDO:0002803) is a disease with 3 cohort genes and 5 clinical trials.

At a glance

• Cohort genes: 3
• ClinVar variants: 5
• Clinical trials: 5

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	intestinal pseudo-obstruction
Mondo ID	MONDO:0002803
MeSH	D007418
DOID	DOID:3878
NCIT	C34733
SNOMED CT	235825006
UMLS	C0021847
MedGen	5864
GARD	0006789
Is cancer (heuristic)	no

Also known as: Chronic intestinal pseudo-obstruction. · hollow visceral myopathy · intestinal pseudo-obstruction · intestinal pseudoobstruction · intestine pseudoobstruction · pseudo-obstruction of intestine

Data availability: 5 ClinVar variants.

Disease family

An umbrella term covering 2 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › digestive system disorder › intestinal disorder › intestinal obstruction › ileus › intestinal pseudo-obstruction

Related subtypes (2): paralytic ileus, meconium ileus

Subtypes (2): colonic pseudo-obstruction, chronic intestinal pseudoobstruction

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

5 retrieved; paginated sample, class counts are floors:

2 pathogenic, 1 uncertain significance, 1 pathogenic/likely pathogenic, 1 conflicting classifications of pathogenicity

ClinVar	Variant (HGVS)	Gene	Classification	Review
427825	NM_024769.3(CLMP):c.[29-2A>G];[410G>A]		Pathogenic	criteria provided, single submitter
50385	NM_024769.5(CLMP):c.664C>T (p.Arg222Ter)	CLMP	Pathogenic	criteria provided, multiple submitters, no conflicts
224071	NM_024769.5(CLMP):c.508C>T (p.Arg170Ter)	LOC112042785	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3185244	NM_001953.5(TYMP):c.410G>T (p.Gly137Val)	TYMP	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1339480	NM_001615.4(ACTG2):c.981G>T (p.Lys327Asn)	ACTG2	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 5 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
ACTG2	Orphanet:104077	Myopathic intestinal pseudoobstruction
ACTG2	Orphanet:2241	Megacystis-microcolon-intestinal hypoperistalsis syndrome
ACTG2	Orphanet:2604	Familial visceral myopathy
CLMP	Orphanet:2301	Congenital short bowel syndrome
TYMP	Orphanet:298	Mitochondrial neurogastrointestinal encephalomyopathy

Cohort genes → proteins

3 cohort genes, 3 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	3

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
ACTG2	HGNC:145	ENSG00000163017	P63267	Actin, gamma-enteric smooth muscle	clinvar
CLMP	HGNC:24039	ENSG00000166250	Q9H6B4	CXADR-like membrane protein	clinvar
TYMP	HGNC:3148	ENSG00000025708	P19971	Thymidine phosphorylase	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
ACTG2	Actin, gamma-enteric smooth muscle	Actins are highly conserved proteins that are involved in various types of cell motility and are ubiquitously expressed in all eukaryotic cells.
CLMP	CXADR-like membrane protein	May be involved in the cell-cell adhesion.
TYMP	Thymidine phosphorylase	May have a role in maintaining the integrity of the blood vessels.

Protein-family classification

Druggable: 2 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.67

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
Antibody/Immunoglobulin	1	9.7×	0.298
Enzyme (other)	1	4.0×	0.345
Other/Unknown	1	0.6×	0.914

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
ACTG2	Other/Unknown	no		Actin, Actin_CS, Actin/actin-like_CS
CLMP	Antibody/Immunoglobulin	yes		Ig_sub2, Ig_sub, Ig-like_dom
TYMP	Enzyme (other)	yes	2.4.2.4	Thymidine/pyrmidine_PPase, Glycosyl_Trfase_fam3, PYNP_C

Expression context

Cohort genes with no expression data: 0.

3 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)	3
unknown	0

Top tissues across cohort

Tissue	Cohort genes
cauda epididymis	1
saphenous vein	1
seminal vesicle	1
cartilage tissue	1
decidua	1
stromal cell of endometrium	1
granulocyte	1
monocyte	1
right uterine tube	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
ACTG2	241	broad	marker	seminal vesicle, cauda epididymis, saphenous vein
CLMP	220	ubiquitous	marker	cartilage tissue, stromal cell of endometrium, decidua
TYMP	251	ubiquitous	marker	right uterine tube, granulocyte, monocyte

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
TYMP	1,972
CLMP	582
ACTG2	133

Structural data

PDB: 2 · AlphaFold-only: 1 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
ACTG2	P63267	4
TYMP	P19971	4

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
CLMP	Q9H6B4	77.52

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 9. Enrichment computed across 3 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
Pyrimidine salvage	1	519.1×	0.007	TYMP
Regulation of CDH1 Function	1	475.8×	0.007	ACTG2
Pyrimidine catabolism	1	439.2×	0.007	TYMP
Formation of the dystrophin-glycoprotein complex (DGC)	1	154.3×	0.014	ACTG2
Smooth Muscle Contraction	1	132.8×	0.014	ACTG2
Activation of STAT3 by cadherin engagement	1	81.6×	0.017	ACTG2
Non-integrin membrane-ECM interactions	1	77.2×	0.017	ACTG2
Muscle contraction	1	38.6×	0.029	ACTG2
Extracellular matrix organization	1	31.6×	0.031	ACTG2

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 3 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
pyrimidine nucleobase metabolic process	1	2808.7×	0.003	TYMP
pyrimidine nucleoside metabolic process	1	1404.3×	0.003	TYMP
mesenchyme migration	1	1123.5×	0.003	ACTG2
cellular response to acetaldehyde	1	1123.5×	0.003	ACTG2
dTMP catabolic process	1	936.2×	0.003	TYMP
cellular response to interleukin-6	1	330.4×	0.007	ACTG2
postsynaptic modulation of chemical synaptic transmission	1	224.7×	0.008	CLMP
digestive tract development	1	175.5×	0.009	CLMP
response to ethanol	1	48.9×	0.028	ACTG2
chemotaxis	1	45.3×	0.028	TYMP
angiogenesis	1	20.8×	0.056	TYMP
positive regulation of gene expression	1	12.9×	0.082	ACTG2
cell differentiation	1	9.7×	0.100	TYMP

Therapeutics

Drugs indicated or in trials for this disease

No drug has an approved disease-direct ChEMBL indication for this disease.

2 drugs in clinical trials for this disease (phase 2–3, investigational): efficacy not established — a trial record, not an indication.

Drug	Highest phase
Prucalopride	Phase 3
Rifaximin	Phase 2

Drug target analysis

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

Druggability breadth: 1 of 3 evidence-associated genes (33%) 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
TYMP	TIPIRACIL

Top cohort targets by molecule count

Symbol	Molecules	Max phase
TYMP	2	4
ACTG2	0	0
CLMP	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
TIPIRACIL	4	TYMP
TIPIRACIL HYDROCHLORIDE	4	TYMP

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
TYMP	94	Binding:91, Functional:3

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
TYMP	2.4.2.4	thymidine phosphorylase

Pharmacogenomics

Cohort genes with a PharmGKB record: 3; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

2 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)
TIPIRACIL	4	TYMP
TIPIRACIL HYDROCHLORIDE	4	TYMP

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	TYMP
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	1	CLMP
E	Difficult family or no structure, no drug	1	ACTG2

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)
ACTG2	0	—
CLMP	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 5.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	5

Top trials by phase / activity

NCT	Phase	Status	Title
NCT01793168	Not specified	RECRUITING	Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford
NCT06711107	Not specified	ACTIVE_NOT_RECRUITING	Predicting NOM Failure in Bowel Obstruction
NCT03662672	Not specified	COMPLETED	Rib Raising for Post-operative Ileus
NCT04981262	Not specified	COMPLETED	Improved Quality of Life in Children With Intestinal Failure
NCT06020365	Not specified	COMPLETED	Investigation of Fecal Microbiota Transplant in Chronic Intestinal Pseudo-obstruction Patients