Duodenal atresia

Summary

Duodenal atresia (MONDO:0009126) is a disease with 1 cohort gene and 3 clinical trials.

At a glance

• Prevalence: 1-9 / 100 000 (Europe) [Orphanet-validated]
• Cohort genes: 1
• ClinVar variants: 1
• Phenotypes (HPO): 16
• Clinical trials: 3

Clinical features

Epidemiology

Prevalence records

28 prevalence record(s), Orphanet, top 20 (validated / broadest geography first):

Type	Class	Value	Geography	Validation
Point prevalence	1-9 / 100 000	9	Europe	Validated
Prevalence at birth	1-9 / 100 000	9	Europe	Validated
Point prevalence	1-9 / 100 000		Belgium	Validated
Point prevalence	1-9 / 100 000		Spain	Validated
Point prevalence	1-9 / 100 000		Ireland	Validated
Point prevalence	1-9 / 100 000		Italy	Validated
Point prevalence	1-5 / 10 000		United Kingdom	Validated
Point prevalence	1-9 / 100 000		Malta	Validated
Point prevalence	1-9 / 100 000		Denmark	Validated
Point prevalence	1-5 / 10 000		France	Validated
Point prevalence	1-9 / 100 000		Reunion	Validated
Point prevalence	1-9 / 100 000		Portugal	Validated
Point prevalence	1-9 / 100 000		Germany	Validated
Point prevalence	1-9 / 100 000		Austria	Validated
Point prevalence	1-9 / 100 000		Switzerland	Validated
Prevalence at birth	1-9 / 100 000	9	Belgium	Validated
Prevalence at birth	1-9 / 100 000	4	Spain	Validated
Prevalence at birth	1-9 / 100 000	6	Ireland	Validated
Prevalence at birth	1-9 / 100 000	7	Italy	Validated
Prevalence at birth	1-5 / 10 000	11	United Kingdom	Validated

Signs & symptoms

Clinical features (HPO)

16 HPO clinical features (Orphanet curated; top 16 by frequency):

HPO ID	Term	Frequency
HP:0001561	Polyhydramnios	Very frequent (80-99%)
HP:0002247	Duodenal atresia	Very frequent (80-99%)
HP:0001622	Premature birth	Frequent (30-79%)
HP:0002013	Vomiting	Frequent (30-79%)
HP:0025656	Prenatal double bubble sign	Frequent (30-79%)
HP:0001508	Failure to thrive	Occasional (5-29%)
HP:0001732	Abnormality of the pancreas	Occasional (5-29%)
HP:0001734	Annular pancreas	Occasional (5-29%)
HP:0001824	Weight loss	Occasional (5-29%)
HP:0001944	Dehydration	Occasional (5-29%)
HP:0002587	Projectile vomiting	Occasional (5-29%)
HP:0003270	Abdominal distention	Occasional (5-29%)
HP:0004414	Abnormality of the pulmonary artery	Occasional (5-29%)
HP:0004909	Hypokalemic hypochloremic metabolic alkalosis	Occasional (5-29%)
HP:0030145	Lack of bowel sounds	Occasional (5-29%)
HP:0034754	Bilious emesis	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	duodenal atresia
Mondo ID	MONDO:0009126
MeSH	C535720
OMIM	223400
Orphanet	1203
DOID	DOID:0080216
ICD-11	295550633
NCIT	C101025
SNOMED CT	51118003
UMLS	C0266174
MedGen	75602
GARD	0000054
MedDRA	10013812
NORD	1066
Is cancer (heuristic)	no

Also known as: atresia of duodenum · congenital atresia of duodenum · congenital duodenal atresia · duodenal atresia · duodenal atresia (disease) · Duodenal Atresia or Stenosis · duodenal stenosis

Data availability: 1 ClinVar variant · 1 HPO phenotype.

Disease family

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

Related subtypes (1): multiple intestinal atresia

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

1 retrieved; paginated sample, class counts are floors:

1 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
375380	NM_004963.4(GUCY2C):c.410T>C (p.Leu137Ser)	GUCY2C	Pathogenic	no assertion criteria provided

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

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
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: 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
Kinase	1	27.7×	0.036

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
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)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
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
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

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
GUCY2C	P25092	3

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 2. 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
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: 1

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
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: 1; 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	0

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
GUCY2C	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 3.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	3

Top trials by phase / activity

NCT	Phase	Status	Title
NCT06731855	Not specified	RECRUITING	An Exploratory Physiological Study of Post-operative Recovery in Surgical Neonates and Dimethylarginine:Arginine Levels
NCT04114279	Not specified	UNKNOWN	Validation of a Totally Synthetic High Fidelity Laparoscopic Duodenal Atresia (DA) Surgical Simulator
NCT06115226	Not specified	UNKNOWN	Laparascopic vs. Laparotomy Management of Neonatal Duodenal Atresia