Chronic intestinal pseudoobstruction

Summary

Chronic intestinal pseudoobstruction (MONDO:0017574) is a disease (an umbrella term covering 5 Mondo subtypes) with 3 cohort genes and 7 clinical trials. Top therapeutic interventions include rifaximin.

At a glance

• Prevalence: Unknown (Worldwide)
• Umbrella term: 5 Mondo subtypes
• Cohort genes: 3
• ClinVar variants: 8
• Phenotypes (HPO): 6
• Clinical trials: 7

Clinical features

Signs & symptoms

Clinical features (HPO)

6 HPO clinical features (Orphanet curated; top 6 by frequency):

HPO ID	Term	Frequency
HP:0002242	Abnormal intestine morphology	Very frequent (80-99%)
HP:0002021	Pyloric stenosis	Frequent (30-79%)
HP:0002566	Intestinal malrotation	Frequent (30-79%)
HP:0012639	Abnormal nervous system morphology	Frequent (30-79%)
HP:0001643	Patent ductus arteriosus	Occasional (5-29%)
HP:0011875	Abnormal platelet morphology	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	chronic intestinal pseudoobstruction
Mondo ID	MONDO:0017574
Orphanet	2978
SNOMED CT	235828008
UMLS	C0238062
MedGen	536759
GARD	0012744
NORD	970
Is cancer (heuristic)	no

Also known as: Chronic Intestinal Pseudo-Obstruction · chronic intestinal pseudo-obstruction · CIPO · cipo · intestinal pseudo-obstruction, chronic

Data availability: 8 ClinVar variants · 1 cell line.

Disease family

An umbrella term covering 5 Mondo subtypes.

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

Related subtypes (1): colonic pseudo-obstruction

Subtypes (5): intestinal pseudoobstruction, neuronal, chronic idiopathic, X-linked, neuronal intestinal dysplasia, type B, visceral neuropathy, familial, 3, autosomal dominant, myopathic intestinal pseudoobstruction, visceral neuropathy, familial, 1, autosomal recessive

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

8 retrieved; paginated sample, class counts are floors:

5 pathogenic, 1 likely pathogenic, 1 pathogenic/likely pathogenic, 1 conflicting classifications of pathogenicity

ClinVar	Variant (HGVS)	Gene	Classification	Review
132797	NM_001615.4(ACTG2):c.442C>A (p.Arg148Ser)	ACTG2	Pathogenic	criteria provided, single submitter
132802	NM_001615.4(ACTG2):c.119G>A (p.Arg40His)	ACTG2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
132803	NM_001615.4(ACTG2):c.769C>T (p.Arg257Cys)	ACTG2	Pathogenic	criteria provided, multiple submitters, no conflicts
208792	NM_001615.4(ACTG2):c.770G>A (p.Arg257His)	ACTG2	Pathogenic	criteria provided, multiple submitters, no conflicts
217521	NM_001615.4(ACTG2):c.113G>A (p.Arg38His)	ACTG2	Pathogenic	no assertion criteria provided
1683496	NM_003221.4(TFAP2B):c.602-5_606del	TFAP2B	Pathogenic	criteria provided, single submitter
1047916	NM_001615.4(ACTG2):c.968C>T (p.Pro323Leu)	ACTG2	Likely pathogenic	criteria provided, single submitter
627645	NM_001040113.2(MYH11):c.5819del (p.Pro1940fs)	MYH11	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 9 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
TFAP2B	Orphanet:46627	Char syndrome
TFAP2B	Orphanet:466729	Familial patent arterial duct
ACTG2	Orphanet:104077	Myopathic intestinal pseudoobstruction
ACTG2	Orphanet:2241	Megacystis-microcolon-intestinal hypoperistalsis syndrome
ACTG2	Orphanet:2604	Familial visceral myopathy
MYH11	Orphanet:2241	Megacystis-microcolon-intestinal hypoperistalsis syndrome
MYH11	Orphanet:229	Familial aortic dissection
MYH11	Orphanet:91387	Familial thoracic aortic aneurysm and aortic dissection
MYH11	Orphanet:98829	Acute myeloid leukemia with abnormal bone marrow eosinophils inv(16)(p13q22) or t(16;16)(p13;q22)

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
TFAP2B	HGNC:11743	ENSG00000008196	Q92481	Transcription factor AP-2-beta	clinvar
ACTG2	HGNC:145	ENSG00000163017	P63267	Actin, gamma-enteric smooth muscle	clinvar
MYH11	HGNC:7569	ENSG00000133392	P35749	Myosin-11	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
TFAP2B	Transcription factor AP-2-beta	Sequence-specific DNA-binding protein that interacts with inducible viral and cellular enhancer elements to regulate transcription of selected genes.
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.
MYH11	Myosin-11	Muscle contraction.

Protein-family classification

Druggable: 0 · Difficult: 2 · 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
Scaffold/PPI	1	5.8×	0.482
Transcription factor	1	2.8×	0.482
Other/Unknown	1	0.6×	0.914

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
TFAP2B	Transcription factor	no		TF_AP2, TF_AP2_beta, TF_AP2_C
ACTG2	Other/Unknown	no		Actin, Actin_CS, Actin/actin-like_CS
MYH11	Scaffold/PPI	no		IQ_motif_EF-hand-BS, Myosin_head_motor_dom-like, Myosin_tail

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	2
corpus epididymis	1
oocyte	1
saphenous vein	1
seminal vesicle	1
lower esophagus	1
lower esophagus muscularis layer	1
right coronary artery	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
TFAP2B	128	broad	marker	corpus epididymis, cauda epididymis, oocyte
ACTG2	241	broad	marker	seminal vesicle, cauda epididymis, saphenous vein
MYH11	143	broad	marker	right coronary artery, lower esophagus, lower esophagus muscularis layer

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
MYH11	3,818
TFAP2B	1,380
ACTG2	133

Structural data

PDB: 3 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
ACTG2	P63267	4
TFAP2B	Q92481	1
MYH11	P35749	1

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 38. Enrichment computed across 3 evidence-associated genes (3 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 3 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Smooth Muscle Contraction	2	177.1×	0.002	ACTG2, MYH11
Muscle contraction	2	51.4×	0.009	ACTG2, MYH11
Negative regulation of activity of TFAP2 (AP-2) family transcription factors	1	380.7×	0.014	TFAP2B
Activation of the TFAP2 (AP-2) family of transcription factors	1	317.2×	0.014	TFAP2B
Regulation of CDH1 Function	1	317.2×	0.014	ACTG2
TFAP2 (AP-2) family regulates transcription of growth factors and their receptors	1	253.8×	0.014	TFAP2B
Sema4D in semaphorin signaling	1	223.9×	0.014	MYH11
Transcriptional regulation by the AP-2 (TFAP2) family of transcription factors	1	211.5×	0.014	TFAP2B
Specification of the neural plate border	1	211.5×	0.014	TFAP2B
RHO GTPases activate CIT	1	200.3×	0.014	MYH11
RHO GTPases Activate ROCKs	1	200.3×	0.014	MYH11
SUMOylation of transcription factors	1	190.3×	0.014	TFAP2B
Sema4D induced cell migration and growth-cone collapse	1	190.3×	0.014	MYH11
RHO GTPases activate PAKs	1	181.3×	0.014	MYH11
Developmental Lineage of Mammary Gland Myoepithelial Cells	1	181.3×	0.014	MYH11
Semaphorin interactions	1	131.3×	0.018	MYH11
EPHA-mediated growth cone collapse	1	126.9×	0.018	MYH11
RHO GTPases activate PKNs	1	105.7×	0.019	MYH11
Formation of the dystrophin-glycoprotein complex (DGC)	1	102.9×	0.019	ACTG2
Gastrulation	1	86.5×	0.022	TFAP2B
Developmental Biology	2	9.6×	0.025	TFAP2B, MYH11
SUMO E3 ligases SUMOylate target proteins	1	59.5×	0.028	TFAP2B
EPH-Ephrin signaling	1	55.2×	0.028	MYH11
SUMOylation	1	54.4×	0.028	TFAP2B
Activation of STAT3 by cadherin engagement	1	54.4×	0.028	ACTG2
Non-integrin membrane-ECM interactions	1	51.4×	0.028	ACTG2
RHO GTPase Effectors	1	22.7×	0.061	MYH11
Extracellular matrix organization	1	21.0×	0.064	ACTG2
Axon guidance	1	15.1×	0.085	MYH11
Nervous system development	1	14.3×	0.086	MYH11

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
metanephric nephron development	1	2808.7×	0.005	TFAP2B
skeletal muscle myosin thick filament assembly	1	1872.4×	0.005	MYH11
distal tubule development	1	1872.4×	0.005	TFAP2B
collecting duct development	1	1404.3×	0.005	TFAP2B
mesenchyme migration	1	1123.5×	0.005	ACTG2
ductus arteriosus closure	1	1123.5×	0.005	TFAP2B
cellular response to acetaldehyde	1	1123.5×	0.005	ACTG2
hindlimb morphogenesis	1	936.2×	0.005	TFAP2B
forelimb morphogenesis	1	702.2×	0.006	TFAP2B
elastic fiber assembly	1	510.7×	0.008	MYH11
regulation of BMP signaling pathway	1	401.2×	0.009	TFAP2B
smooth muscle tissue development	1	351.1×	0.009	TFAP2B
cellular response to interleukin-6	1	330.4×	0.009	ACTG2
sympathetic nervous system development	1	312.1×	0.009	TFAP2B
aorta morphogenesis	1	295.6×	0.009	TFAP2B
smooth muscle contraction	1	267.5×	0.010	MYH11
retina layer formation	1	216.1×	0.011	TFAP2B
cardiac muscle cell development	1	208.1×	0.011	MYH11
actomyosin structure organization	1	187.2×	0.012	MYH11
skin development	1	147.8×	0.014	TFAP2B
regulation of cell differentiation	1	144.0×	0.014	TFAP2B
regulation of insulin secretion	1	130.6×	0.014	TFAP2B
positive regulation of neuron apoptotic process	1	90.6×	0.020	TFAP2B
glucose metabolic process	1	85.1×	0.020	TFAP2B
neuron apoptotic process	1	61.7×	0.026	TFAP2B
fat cell differentiation	1	60.4×	0.026	TFAP2B
response to ethanol	1	48.9×	0.031	ACTG2
kidney development	1	46.8×	0.031	TFAP2B
regulation of cell population proliferation	1	38.5×	0.036	TFAP2B
negative regulation of neuron apoptotic process	1	37.0×	0.037	TFAP2B

Therapeutics

Drug target analysis

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

Druggability breadth: 0 of 3 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
TFAP2B	0	0
ACTG2	0	0
MYH11	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

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	3	TFAP2B, ACTG2, MYH11

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
TFAP2B	0	—
ACTG2	0	—
MYH11	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 7.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	4
PHASE2	3

Top trials by phase / activity

NCT	Phase	Status	Title
NCT00793247	PHASE2	COMPLETED	Efficacy Study of Prucalopride to Treat Chronic Intestinal Pseudo-Obstruction (CIP)
NCT04118699	PHASE2	UNKNOWN	Efficacy and Safety of Rifaximin for Patients With Chronic Intestinal Pseudo-obstruction: a Phase 2 Trial
NCT05724069	PHASE2	COMPLETED	Velusetrag for the Treatment of Chronic Intestinal Pseudo-Obstruction (CIPO).
NCT04506593	Not specified	RECRUITING	Indiana University Gastrointestinal Motility Diagnosis Registry
NCT06943417	Not specified	NOT_YET_RECRUITING	Safety and Efficacy of Endoscopic Full Thickness Biopsy in Patients With Chronic Intestinal Pseudo-obstruction
NCT02731183	Not specified	COMPLETED	Efficacy and Safety of Fecal Microbiota Transplantation for Chronic Intestinal Pseudo-obstruction
NCT04193735	Not specified	UNKNOWN	Pseudo-obstruction Assessment With MRI

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
RIFAXIMIN	4	1