Intestinal obstruction

Summary

Intestinal obstruction (MONDO:0004565) is a disease (an umbrella term covering 6 Mondo subtypes) with 2 cohort genes (2 GWAS associations across 20 studies) and 66 clinical trials. Top therapeutic interventions include loperamide, methylnaltrexone, and sulfasalazine.

At a glance

• Umbrella term: 6 Mondo subtypes
• Cohort genes: 2
• GWAS associations: 2
• ClinVar variants: 3
• Clinical trials: 66

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	intestinal obstruction
Mondo ID	MONDO:0004565
MeSH	D007415
DOID	DOID:8437
NCIT	C9175
SNOMED CT	81060008
UMLS	C0021843
MedGen	43933
Is cancer (heuristic)	no

Also known as: bowel obstruction

Data availability: 3 ClinVar variants · 2 GWAS associations (20 studies).

Disease family

An umbrella term covering 6 Mondo subtypes.

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

Related subtypes (57): intestinal atresia, steatorrhea, angiodysplasia of intestine, endometriosis of intestine, hypertrophic pyloric stenosis, mucocele of appendix, gastroenteritis, diverticulitis, postgastrectomy syndrome, chronic intestinal vascular insufficiency, bowel dysfunction, irritable bowel syndrome, Whipple disease, inflammatory bowel disease, intestinal polyp, necrotizing enterocolitis, intestinal perforation, neurogenic bowel, pneumatosis cystoides intestinalis, volvulus of midgut, abetalipoproteinemia, aplasia cutis congenita-intestinal lymphangiectasia syndrome, trichohepatoenteric syndrome, protein-losing enteropathy, chronic diarrhea with villous atrophy, Satoyoshi syndrome, glucose-galactose malabsorption, congenital diarrhea 7 with exudative enteropathy, chronic atrial and intestinal dysrhythmia, congenital enterocyte heparan sulfate deficiency, short bowel syndrome, intractable diarrhea-choanal atresia-eye anomalies syndrome, solitary rectal ulcer syndrome, NK-cell enteropathy, chronic intestinal failure, intestinal lymphangiectasia, refractory celiac disease, eosinophilic gastrointestinal disease, cryptogenic multifocal ulcerous stenosing enteritis, chronic enteropathy associated with SLCO2A1 gene, cytosolic phospholipase-A2 alpha deficiency associated bleeding disorder, malakoplakia, malabsorption syndrome, ischemic bowel disorder, intestinal neoplasm, intestinal motility disease, 4-hydroxyphenylacetic aciduria, parasitic intestinal disorder, Aeromonas hydrophila intestinal disease, large intestine disorder, small intestine disorder, primary desmosis coli, isolated mesenteric vein thrombosis, collagenous sprue, visceral leiomyopathy, African degenerative, intestinal dysmotility syndrome, intestinal fistula

Subtypes (6): duodenal obstruction, ileus, intestinal volvulus, intestinal impaction, intussusception, encapsulating peritoneal sclerosis

Genetics & variants

GWAS landscape

2 GWAS associations across 20 studies. Top hits map to 0 distinct genes (as reported by GWAS).

Top associations by p-value

rsID	p-value	Gene	Risk allele	Odds ratio
rs180887182	2e-07	TDRKH-AS1 - LINGO4	?
rs140525799	2e-07	VSTM5 - HPRT1P3	?

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST90478404	Verma A	2024	10,138	429,558	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90476751	Verma A	2024	7,406	308,262	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90478411	Verma A	2024	6,438	439,666	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90436345	Zhou W	2018	3,994	334,783	Efficiently controlling for case-control imbalance and sample relatedness in large-scale genetic association studies.
GCST90436349	Zhou W	2018	3,346	334,783	Efficiently controlling for case-control imbalance and sample relatedness in large-scale genetic association studies.
GCST90478403	Verma A	2024	3,065	115,440	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90480863	Verma A	2024	3,065	115,440	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90476753	Verma A	2024	2,992	312,676	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90651948	Liu TY	2025	2,544	188,622	Diversity and longitudinal records: Genetic architecture of disease associations and polygenic risk in the Taiwanese Han population.
GCST90476750	Verma A	2024	1,803	53,702	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

Tier	Variants
Tier 1: coding	0
Tier 2: splice/UTR	0
Tier 3: regulatory	0
Tier 4: intronic/intergenic	2

MAF distribution

Bucket	Variants
common (>=0.05)	0
low_freq (0.01-0.05)	0
rare (<0.01)	0
unknown	2

Functional consequences

Consequence	Count
intergenic_variant	2

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
rs180887182	1	151794526	T>C		intergenic_variant	TDRKH-AS1 - LINGO4	2e-07	Tier 4: intronic/intergenic
rs140525799	11	93961093	A>G		intergenic_variant	VSTM5 - HPRT1P3	2e-07	Tier 4: intronic/intergenic

ClinVar germline variants

3 retrieved; paginated sample, class counts are floors:

2 pathogenic, 1 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
55994	NM_000111.3(SLC26A3):c.269_270dup (p.Gly91fs)	SLC26A3	Pathogenic	criteria provided, multiple submitters, no conflicts
978618	NM_000111.3(SLC26A3):c.1000G>T (p.Glu334Ter)	SLC26A3	Pathogenic	criteria provided, single submitter
1177291	NM_001615.4(ACTG2):c.442C>T (p.Arg148Cys)	ACTG2	Likely pathogenic	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 4 · 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
SLC26A3	Orphanet:53689	Congenital chloride diarrhea

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
ACTG2	HGNC:145	ENSG00000163017	P63267	Actin, gamma-enteric smooth muscle	clinvar
SLC26A3	HGNC:3018	ENSG00000091138	P40879	Chloride anion exchanger	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.
SLC26A3	Chloride anion exchanger	Mediates chloride-bicarbonate exchange with a chloride bicarbonate stoichiometry of 2:1 in the intestinal epithelia.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.5

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
Transporter	1	38.9×	0.051
Other/Unknown	1	0.9×	0.805

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
ACTG2	Other/Unknown	no		Actin, Actin_CS, Actin/actin-like_CS
SLC26A3	Transporter	yes		SLC26A/SulP_fam, STAS_dom, SLC26A/SulP_dom

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
cauda epididymis	1
saphenous vein	1
seminal vesicle	1
colonic mucosa	1
mucosa of sigmoid colon	1
rectum	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
SLC26A3	159	tissue_specific	marker	colonic mucosa, mucosa of sigmoid colon, rectum

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
SLC26A3	1,831
ACTG2	133

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
SLC26A3	P40879	13
ACTG2	P63267	4

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 15. 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 SLC26A3 causes congenital secretory chloride diarrhea 1 (DIAR1)	1	5710.0×	0.003	SLC26A3
Inorganic anion exchange by SLC26 transporters	1	634.4×	0.011	SLC26A3
Regulation of CDH1 Function	1	475.8×	0.011	ACTG2
Formation of the dystrophin-glycoprotein complex (DGC)	1	154.3×	0.023	ACTG2
Smooth Muscle Contraction	1	132.8×	0.023	ACTG2
SLC transporter disorders	1	102.0×	0.023	SLC26A3
Activation of STAT3 by cadherin engagement	1	81.6×	0.023	ACTG2
Non-integrin membrane-ECM interactions	1	77.2×	0.023	ACTG2
Disorders of transmembrane transporters	1	69.6×	0.023	SLC26A3
R-HSA-425393	1	64.9×	0.023	SLC26A3
Muscle contraction	1	38.6×	0.035	ACTG2
Extracellular matrix organization	1	31.6×	0.039	ACTG2
SLC-mediated transmembrane transport	1	29.6×	0.039	SLC26A3
Transport of small molecules	1	12.6×	0.083	SLC26A3
Disease	1	6.5×	0.147	SLC26A3

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
intracellular pH elevation	1	2808.7×	0.003	SLC26A3
mesenchyme migration	1	1685.2×	0.003	ACTG2
cellular response to acetaldehyde	1	1685.2×	0.003	ACTG2
membrane hyperpolarization	1	936.2×	0.003	SLC26A3
monoatomic anion transport	1	702.2×	0.004	SLC26A3
sulfate transmembrane transport	1	601.9×	0.004	SLC26A3
cellular response to interleukin-6	1	495.6×	0.004	ACTG2
sperm capacitation	1	337.0×	0.005	SLC26A3
cellular response to cAMP	1	145.3×	0.010	SLC26A3
chloride transmembrane transport	1	118.7×	0.011	SLC26A3
monoatomic ion transport	1	78.0×	0.015	SLC26A3
response to ethanol	1	73.3×	0.015	ACTG2
positive regulation of gene expression	1	19.4×	0.051	ACTG2

Therapeutics

Drugs indicated for this disease

0 approved, 1 in late-stage (phase 3) trials. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

Drug	Development status
Sodium Chloride	Phase 3 (in late-stage trials)

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): Dexamethasone, Lanreotide, Metoclopramide, Octreotide.

Drug target analysis

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

Druggability breadth: 1 of 2 evidence-associated genes (50%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
ACTG2	0	0
SLC26A3	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
SLC26A3	6	Binding:6

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	1	SLC26A3
D	Druggable family + AlphaFold only, no drug	0
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	—
SLC26A3	6	—

Clinical trials & evidence

Clinical trials

Clinical trials: 66.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	50
PHASE4	7
PHASE3	3
PHASE2	3
PHASE1	2
PHASE1/PHASE2	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT01507220	PHASE4	TERMINATED	A Health Economic Trial in Adult Patients Undergoing Open Colectomy MA402S23B301
NCT01507233	PHASE4	TERMINATED	A Health Economic Trial in Adult Patients Undergoing Open Colectomy MA402S23B302
NCT01507246	PHASE4	COMPLETED	Adult Patients Undergoing Open Colectomy MA402S23B303
NCT02058290	PHASE4	TERMINATED	A Health Economic Trial in Adult Patients Undergoing Laparoscopic Colectomy
NCT02812186	PHASE4	COMPLETED	Deep Versus Moderate Neuromuscular Blockade During Laparoscopic Surgery
NCT03334578	PHASE4	WITHDRAWN	The Use of Gastrografin to Help Alleviate Bowel Obstruction in Gastroschisis Patients.
NCT06089551	PHASE4	UNKNOWN	Early vs Postponed Parenteral Nutrition After Emergency Abdominal Surgery
NCT00164879	PHASE3	UNKNOWN	Endolaparoscopic Versus Immediate Surgery for Obstructing Colorectal Cancers
NCT00216372	PHASE3	COMPLETED	Efficacy and Safety of Lanreotide Microparticles as Palliative Treatment in Peritoneal Carcinomatosis
NCT00758186	PHASE3	COMPLETED	Randomized Trial of Colonic Stents as a Bridge to Surgery
NCT00332696	PHASE2	COMPLETED	Octreotide Compared to Placebo in Patients With Inoperable Bowel Obstruction Due to Peritoneal Carcinomatosis
NCT01083537	PHASE1/PHASE2	TERMINATED	Trial of Best Supportive Care and Either Cisplatin or Paclitaxel to Treat Patients With Primary Ovarian Cancer, Primary Peritoneal Cancer or Fallopian Tube Cancer and Inoperable Malignant Bowel Obstruction
NCT02275338	PHASE2	COMPLETED	Study to Assess Efficacy and Safety of Lanreotide Autogel 120 MG in Treatment of Clinical Symptoms Associated With Inoperable Malignant Intestinal Obstruction
NCT02365584	PHASE2	TERMINATED	Quality of Life in Patients With Inoperable Malignant Bowel Obstruction
NCT01596764	PHASE1	COMPLETED	Effects of Methylnaltrexone in Comparison to Naloxone on Loperamide-induced Delay of the Oro-cecal, Whole-gut and Colon Transit Time.
NCT01596777	PHASE1	COMPLETED	Effects of 500 mg Immediate Release and Extended Release Methylnaltrexone on Loperamide-induced Delay of the Oro-cecal and Whole-gut Transit Time in Healthy Subjects
NCT06072976	Not specified	RECRUITING	The Influence of Feeding Source on the Gut Microbiome and Time to Full Feeds in Neonates With Congenital Gastrointestinal Pathologies
NCT06245577	Not specified	ACTIVE_NOT_RECRUITING	Biological Mesh Versus Synthetic Mesh in Interdisciplinary RRP With SCP
NCT06481358	Not specified	ACTIVE_NOT_RECRUITING	Deep Learning-based Artificial Intelligence for the Diagnosis of Small Bowel Obstruction
NCT06610929	Not specified	NOT_YET_RECRUITING	Intestinal Microbiota and Visceral Pain in Chronic Intestinal Pseudo-Obstruction Syndrome (CIPO)
NCT06787014	Not specified	RECRUITING	Resection of the Primary Tumor vs. Systemic Treatment Alone for Patients With Small Intestinal Neuroendocrine Tumors and Unresectable Metastases: a Europe-wide Study
NCT06928545	Not specified	RECRUITING	MagDI U.S. Registry
NCT07078981	Not specified	NOT_YET_RECRUITING	Adhesion Prevention in ASBO Surgery Using 4DryField® PH
NCT07429929	Not specified	NOT_YET_RECRUITING	Saudi Emergency Laparotomy Audit
NCT07432542	Not specified	ACTIVE_NOT_RECRUITING	Pelvic Floor Peritoneal Closure to Prevent Postoperative Ileus in Mid-Low Rectal Cancer Surgery
NCT07434596	Not specified	RECRUITING	Neonatal Intestinal Obstruction: Prenatal Factors and Postnatal Outcomes
NCT00130715	Not specified	COMPLETED	Seprafilm in the Reduction of Incidence of Bowel Obstruction in General Surgery
NCT00536523	Not specified	TERMINATED	Effect of Serotonin Level on Constipation Caused by Chemotherapy in Patients With Ovarian, Fallopian Tube, or Primary Peritoneal Cancer
NCT01040364	Not specified	COMPLETED	Internal Hernias After Laparoscopic Gastric Bypass
NCT01125280	Not specified	UNKNOWN	Prospective Multicenter Validation of a Severity Score of Strangulated Small Bowel Occlusion
NCT01196494	Not specified	TERMINATED	Study of Intraoperative Colonic Irrigation Versus Stent Placement in Obstructive Left-Sided Colonic Cancer
NCT01669044	Not specified	UNKNOWN	Comparison the Hemodynamics Effects Between Dexmedetomidine and Propofol in Major Abdominal Surgical Patients
NCT01899885	Not specified	COMPLETED	Acute High-risk Abdominal Surgery Study - an Optimized Perioperative Course
NCT01911793	Not specified	TERMINATED	Stoma Tube Decompression and Postoperative Ileus After Major Colorectal Surgery
NCT02116881	Not specified	TERMINATED	Incisional Hernia and Adhesion-Related Bowel Obstruction
NCT02639195	Not specified	UNKNOWN	The Impact of Small Bowel Obstruction (SBO) on Quality of Life (QOL)
NCT02928458	Not specified	WITHDRAWN	Clinical and Financial Impact of an Evidenced-Based Adhesive Small Bowel Obstruction Management Protocol
NCT03086304	Not specified	COMPLETED	Effects of Transcutaneous Acupoint Electrical Stimulation on Intestinal Obstruction After Gastrointestinal Surgery
NCT03150992	Not specified	UNKNOWN	EDMONd - Elemental Diet in Bowel Obstruction
NCT03202576	Not specified	COMPLETED	Nasogastric Tube Securement Comparison Study

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
LOPERAMIDE	4	6
METHYLNALTREXONE	4	4
SULFASALAZINE	4	2
BUPIVACAINE	4	1
CEFAZOLIN	4	1
CITRIC ACID	4	1
IOHEXOL	4	1
LANREOTIDE	4	1
MORPHINE SULFATE	4	1
NEOMYCIN	4	1
ROCURONIUM	4	1
FRAMYCETIN	3	1
SENNA	3	1
CHEMBL2096625	0	1
CHEMBL4067090	0	1
CHEMBL3754093	0	1
CHEMBL4299247	0	1