Cryptogenic multifocal ulcerous stenosing enteritis

Summary

Cryptogenic multifocal ulcerous stenosing enteritis (MONDO:0018765) is a disease with 1 cohort gene.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Cohort genes: 1

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		60	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Identifiers

Disease identifiers

Field	Value
Canonical name	cryptogenic multifocal ulcerous stenosing enteritis
Mondo ID	MONDO:0018765
Orphanet	468635
ICD-11	1401898155
SNOMED CT	722849002
UMLS	C4302263
MedGen	927932
GARD	0021945
Is cancer (heuristic)	no

Also known as: CMUSE

Data availability: 1 GenCC gene-disease record.

Disease family

Classification path: disease › human disease › disease by body system or component › digestive system disorder › intestinal disorder › cryptogenic multifocal ulcerous stenosing enteritis

Related subtypes (57): intestinal atresia, steatorrhea, angiodysplasia of intestine, endometriosis of intestine, hypertrophic pyloric stenosis, mucocele of appendix, gastroenteritis, diverticulitis, intestinal obstruction, 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, 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

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

No tiered GWAS variants or ClinVar records for this disease.

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 5 · Orphanet: 2 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
PLA2G4A	Supportive	Autosomal recessive	cryptogenic multifocal ulcerous stenosing enteritis	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
PLA2G4A	Orphanet:468635	Cryptogenic multifocal ulcerous stenosing enteritis
PLA2G4A	Orphanet:477787	Cytosolic phospholipase-A2 alpha deficiency associated bleeding disorder

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
PLA2G4A	HGNC:9035	ENSG00000116711	P47712	Cytosolic phospholipase A2	gencc

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
PLA2G4A	Cytosolic phospholipase A2	Has primarily calcium-dependent phospholipase and lysophospholipase activities, with a major role in membrane lipid remodeling and biosynthesis of lipid mediators of the inflammatory response.

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
Enzyme (other)	1	12.0×	0.083

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
PLA2G4A	Enzyme (other)	yes	3.1.1.4	C2_dom, LysoPLipase_cat_dom, Acyl_Trfase/lysoPLipase

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
cartilage tissue	1
right uterine tube	1
seminal vesicle	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
PLA2G4A	248	ubiquitous	marker	seminal vesicle, cartilage tissue, right uterine tube

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
PLA2G4A	2,535

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
PLA2G4A	P47712	3

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
phospho-PLA2 pathway	1	5710.0×	0.002	PLA2G4A
Acyl chain remodeling of CL	1	1903.3×	0.003	PLA2G4A
Hydrolysis of LPC	1	1268.9×	0.003	PLA2G4A
Acyl chain remodelling of PI	1	671.8×	0.003	PLA2G4A
Platelet sensitization by LDL	1	671.8×	0.003	PLA2G4A
Acyl chain remodelling of PG	1	634.4×	0.003	PLA2G4A
Arachidonate metabolism	1	571.0×	0.003	PLA2G4A
Acyl chain remodelling of PS	1	519.1×	0.003	PLA2G4A
ADP signalling through P2Y purinoceptor 1	1	456.8×	0.003	PLA2G4A
Acyl chain remodelling of PC	1	423.0×	0.003	PLA2G4A
Acyl chain remodelling of PE	1	393.8×	0.003	PLA2G4A
Synthesis of PA	1	292.8×	0.004	PLA2G4A
COPI-independent Golgi-to-ER retrograde traffic	1	207.6×	0.005	PLA2G4A

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
phosphatidylglycerol catabolic process	1	8426.0×	0.001	PLA2G4A
platelet activating factor biosynthetic process	1	4213.0×	0.001	PLA2G4A
cellular response to antibiotic	1	2407.4×	0.001	PLA2G4A
icosanoid metabolic process	1	1872.4×	0.001	PLA2G4A
positive regulation of prostaglandin secretion	1	1872.4×	0.001	PLA2G4A
positive regulation of T-helper 1 type immune response	1	1685.2×	0.001	PLA2G4A
monoacylglycerol biosynthetic process	1	1532.0×	0.001	PLA2G4A
positive regulation of platelet activation	1	1296.3×	0.001	PLA2G4A
leukotriene biosynthetic process	1	1296.3×	0.001	PLA2G4A
phosphatidylcholine catabolic process	1	1296.3×	0.001	PLA2G4A
prostaglandin biosynthetic process	1	1123.5×	0.001	PLA2G4A
glycerol metabolic process	1	1123.5×	0.001	PLA2G4A
phosphatidylcholine acyl-chain remodeling	1	1123.5×	0.001	PLA2G4A
glycerophospholipid catabolic process	1	1053.2×	0.001	PLA2G4A
positive regulation of macrophage activation	1	842.6×	0.002	PLA2G4A
arachidonate secretion	1	702.2×	0.002	PLA2G4A
arachidonate metabolic process	1	481.5×	0.002	PLA2G4A
establishment of localization in cell	1	160.5×	0.007	PLA2G4A
regulation of cell population proliferation	1	115.4×	0.009	PLA2G4A

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 1 evidence-associated genes (100%) 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
PLA2G4A	ZAFIRLUKAST

Top cohort targets by molecule count

Symbol	Molecules	Max phase
PLA2G4A	3	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
ZAFIRLUKAST	4	PLA2G4A
ECOPLADIB	2	PLA2G4A
EFIPLADIB	2	PLA2G4A

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
PLA2G4A	95	Binding:91, Functional:4

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
PLA2G4A	3.1.1.4	phospholipase A2

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

3 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)
ZAFIRLUKAST	4	PLA2G4A
ECOPLADIB	2	PLA2G4A
EFIPLADIB	2	PLA2G4A

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	PLA2G4A
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	0

Undrugged target profiles

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

Clinical trials & evidence

Clinical trials

Clinical trials: 0.