Meconium ileus

Summary

Meconium ileus (MONDO:0054868) is a disease with 2 cohort genes and 7 clinical trials. Top therapeutic interventions include cefazolin, citric acid, and neomycin.

At a glance

• Cohort genes: 2
• ClinVar variants: 12
• Clinical trials: 7

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	meconium ileus
Mondo ID	MONDO:0054868
MeSH	D000074270
NCIT	C98979
SNOMED CT	206523001
UMLS	C2939175
MedGen	473705
Is cancer (heuristic)	no

Also known as: meconium ileus

Data availability: 12 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 › meconium ileus

Related subtypes (2): intestinal pseudo-obstruction, paralytic ileus

Subtypes (2): cystic fibrosis associated meconium ileus, intestinal obstruction in the newborn due to guanylate cyclase 2C deficiency

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

12 retrieved; paginated sample, class counts are floors:

4 conflicting classifications of pathogenicity, 3 uncertain significance, 3 pathogenic, 1 likely benign, 1 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
161159	NM_004963.4(GUCY2C):c.2782T>C (p.Cys928Arg)	C12orf60	Pathogenic	no assertion criteria provided
31605	NM_004963.4(GUCY2C):c.2270dup (p.Asn757fs)	C12orf60	Pathogenic	no assertion criteria provided
31604	NM_004963.4(GUCY2C):c.1160A>G (p.Asp387Gly)	GUCY2C	Pathogenic	criteria provided, single submitter
977074	NM_004963.4(GUCY2C):c.1047del (p.Lys350fs)	GUCY2C	Likely pathogenic	criteria provided, single submitter
714778	NM_004963.4(GUCY2C):c.893C>T (p.Thr298Met)	GUCY2C	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
802827	NM_004963.4(GUCY2C):c.2155G>C (p.Glu719Gln)	GUCY2C	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
870487	NM_004963.4(GUCY2C):c.1997A>G (p.Tyr666Cys)	GUCY2C	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
870488	NM_004963.4(GUCY2C):c.1540A>G (p.Ile514Val)	GUCY2C	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1341819	NM_004963.4(GUCY2C):c.1562A>G (p.Asn521Ser)	GUCY2C	Uncertain significance	criteria provided, multiple submitters, no conflicts
1443889	NM_004963.4(GUCY2C):c.932C>T (p.Ser311Phe)	GUCY2C	Uncertain significance	criteria provided, multiple submitters, no conflicts
161158	NM_004963.4(GUCY2C):c.2008G>A (p.Ala670Thr)	GUCY2C	Uncertain significance	criteria provided, multiple submitters, no conflicts
802828	NM_004963.4(GUCY2C):c.949-5T>G	GUCY2C	Likely benign	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 3 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
GUCY2C	Orphanet:103908	Congenital sodium diarrhea
GUCY2C	Orphanet:314373	Chronic infantile diarrhea due to guanylate cyclase 2C overactivity
GUCY2C	Orphanet:314376	Intestinal obstruction in the newborn due to guanylate cyclase 2C deficiency

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
C12orf60	HGNC:28726	ENSG00000182993	Q5U649	Uncharacterized protein C12orf60	clinvar
GUCY2C	HGNC:4688	ENSG00000070019	P25092	Guanylyl cyclase C	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
GUCY2C	Guanylyl cyclase C	Guanylyl cyclase that catalyzes synthesis of cyclic GMP (cGMP) from GTP.

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
Kinase	1	13.9×	0.142
Other/Unknown	1	0.9×	0.805

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
C12orf60	Other/Unknown	no		DUF4533
GUCY2C	Kinase	yes	4.6.1.2	Prot_kinase_dom, A/G_cyclase, Ser-Thr/Tyr_kinase_cat_dom

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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
left testis	1
male germ line stem cell (sensu Vertebrata) in testis	1
sperm	1
colonic mucosa	1
jejunal mucosa	1
mucosa of sigmoid colon	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
C12orf60	198	ubiquitous	yes	sperm, male germ line stem cell (sensu Vertebrata) in testis, left testis
GUCY2C	84	tissue_specific	marker	jejunal mucosa, mucosa of sigmoid colon, colonic mucosa

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
GUCY2C	986
C12orf60	122

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
GUCY2C	P25092	3

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
C12orf60	Q5U649	81.24

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 2. Enrichment computed across 2 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
Intestinal infectious diseases	1	3806.7×	5e-04	GUCY2C
Digestion	1	571.0×	0.002	GUCY2C

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
cGMP biosynthetic process	1	1404.3×	0.002	GUCY2C
receptor guanylyl cyclase signaling pathway	1	1296.3×	0.002	GUCY2C
response to toxic substance	1	210.7×	0.008	GUCY2C
regulation of cell population proliferation	1	115.4×	0.011	GUCY2C
intracellular signal transduction	1	38.1×	0.026	GUCY2C

Therapeutics

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
C12orf60	0	0
GUCY2C	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
GUCY2C	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
GUCY2C	4.6.1.2	guanylate cyclase

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	GUCY2C
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	C12orf60

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)
C12orf60	0	—
GUCY2C	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 7.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	5
PHASE4	2

Top trials by phase / activity

NCT	Phase	Status	Title
NCT01515696	PHASE4	COMPLETED	Impact of Oral Application of Gastrografin on the Meconium Evacuation in Very Low Birth Weight Infants
NCT02140710	PHASE4	COMPLETED	Impact of Visceral Osteopathic Treatment on Meconium Evacuation in Preterm Infants
NCT02710383	Not specified	TERMINATED	Biomarker for Cystic Fibrosis
NCT03593252	Not specified	UNKNOWN	Bowel Preparation in Elective Pediatric Colorectal Surgery
NCT04020939	Not specified	COMPLETED	The Role of Indocyanine Green Angiography Fluorescence on Intestinal Resections in Pediatric Surgery.
NCT04713579	Not specified	COMPLETED	Timing of Stoma Closure in Neonates
NCT05293353	Not specified	UNKNOWN	Neokare Safety and Tolerability Assessment in Neonates With GI Problems

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
CEFAZOLIN	4	1
CITRIC ACID	4	1
NEOMYCIN	4	1
WATER	4	1
FRAMYCETIN	3	1
SENNA	3	1
CHEMBL3754093	0	1
CHEMBL4299247	0	1