Omphalocele

Summary

Omphalocele (MONDO:0019015) is a disease with 6 cohort genes and 10 clinical trials.

At a glance

• Prevalence: 1-5 / 10 000 (Europe) [Orphanet-validated]
• Cohort genes: 6
• ClinVar variants: 6
• Phenotypes (HPO): 5
• Clinical trials: 10

Clinical features

Epidemiology

Prevalence records

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

Type	Class	Value	Geography	Validation
Point prevalence	1-5 / 10 000		Europe	Validated
Prevalence at birth	1-5 / 10 000	11.7	Europe	Validated
Point prevalence	1-5 / 10 000		Austria	Validated
Point prevalence	1-5 / 10 000		Belgium	Validated
Point prevalence	1-5 / 10 000		Croatia	Validated
Point prevalence	1-5 / 10 000		Denmark	Validated
Point prevalence	1-5 / 10 000		France	Validated
Point prevalence	1-5 / 10 000		Germany	Validated
Point prevalence	1-9 / 100 000		Hungary	Validated
Point prevalence	1-5 / 10 000		Ireland	Validated
Point prevalence	1-5 / 10 000		Italy	Validated
Point prevalence	1-5 / 10 000		Malta	Validated
Point prevalence	1-5 / 10 000		Netherlands	Validated
Point prevalence	1-5 / 10 000		Norway	Validated
Point prevalence	1-5 / 10 000		Poland	Validated
Point prevalence	1-9 / 100 000		Spain	Validated
Point prevalence	1-5 / 10 000		Switzerland	Validated
Point prevalence	1-5 / 10 000		United Kingdom	Validated
Point prevalence	1-5 / 10 000		Ukraine	Validated
Point prevalence	1-5 / 10 000		United States	Validated

Signs & symptoms

Clinical features (HPO)

5 HPO clinical features (Orphanet curated; top 5 by frequency):

HPO ID	Term	Frequency
HP:0001539	Omphalocele	Very frequent (80-99%)
HP:0001622	Premature birth	Very frequent (80-99%)
HP:0011425	Fetal ultrasound soft marker	Very frequent (80-99%)
HP:0011432	Elevated maternal circulating alpha-fetoprotein concentration	Very frequent (80-99%)
HP:0002091	Restrictive ventilatory defect	Frequent (30-79%)

Identifiers

Disease identifiers

Field	Value
Canonical name	omphalocele
Mondo ID	MONDO:0019015
Orphanet	660
DOID	DOID:0060327
ICD-11	1168696429
NCIT	C98997
SNOMED CT	18735004
UMLS	C0795690
MedGen	162756
GARD	0016540
MedDRA	10030308
Is cancer (heuristic)	no

Also known as: congenital omphalocele · eventration · exomphalos · omphalocele · omphalocele (disease)

Data availability: 6 ClinVar variants · 1 HPO phenotype.

Disease family

An umbrella term covering 4 Mondo subtypes.

Classification path: disease › human disease › disease by developmental or physiological process › disorder of development or morphogenesis › developmental defect during embryogenesis › abdominal wall malformation › omphalocele

Related subtypes (3): gastroschisis, omphalomesenteric cyst, body-stalk anomaly

Subtypes (4): omphalocele, autosomal, omphalocele, X-linked, giant omphalocele, small omphalocele

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

6 retrieved; paginated sample, class counts are floors:

5 uncertain significance, 1 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
374077	NM_000302.4(PLOD1):c.1562G>A (p.Trp521Ter)	PLOD1	Pathogenic	criteria provided, single submitter
1683530	NM_001110556.2(FLNA):c.571G>T (p.Asp191Tyr)	FLNA	Uncertain significance	criteria provided, single submitter
1704314	GRCh37/hg19 17p13.3(chr17:468095-661692)x1	GEMIN4	Uncertain significance	no assertion criteria provided
986382	NM_005560.6(LAMA5):c.857G>T (p.Arg286Leu)	LAMA5	Uncertain significance	criteria provided, single submitter
1683733	NM_033116.6(NEK9):c.326ACA[1] (p.Asn110del)	NEK9	Uncertain significance	criteria provided, single submitter
816936	NM_014489.4(PGAP2):c.97G>A (p.Ala33Thr)	PGAP2	Uncertain significance	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 17 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
PGAP2	Orphanet:247262	Hyperphosphatasia-intellectual disability syndrome
NEK9	Orphanet:464366	NEK9-related lethal skeletal dysplasia
NEK9	Orphanet:64754	Nevus comedonicus syndrome
FLNA	Orphanet:1826	Frontometaphyseal dysplasia
FLNA	Orphanet:2301	Congenital short bowel syndrome
FLNA	Orphanet:2484	Melnick-Needles syndrome
FLNA	Orphanet:482606	X-linked keloid scarring-reduced joint mobility-increased optic cup-to-disc ratio syndrome
FLNA	Orphanet:555877	FLNA-related X-linked myxomatous valvular dysplasia
FLNA	Orphanet:75497	X-linked Ehlers-Danlos syndrome
FLNA	Orphanet:88630	Terminal osseous dysplasia-pigmentary defects syndrome
FLNA	Orphanet:90650	Otopalatodigital syndrome type 1
FLNA	Orphanet:90652	Otopalatodigital syndrome type 2
FLNA	Orphanet:98892	Periventricular nodular heterotopia
FLNA	Orphanet:99811	Neuronal intestinal pseudoobstruction
LAMA5	Orphanet:521450	LAMA5-related multisystemic syndrome
LAMA5	Orphanet:656	Hereditary steroid-resistant nephrotic syndrome
PLOD1	Orphanet:1900	Kyphoscoliotic Ehlers-Danlos syndrome due to lysyl hydroxylase 1 deficiency

Cohort genes → proteins

6 cohort genes, 6 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	6

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
GEMIN4	HGNC:15717	ENSG00000179409	P57678	Gem-associated protein 4	clinvar
PGAP2	HGNC:17893	ENSG00000148985	Q9UHJ9	Acyltransferase PGAP2	clinvar
NEK9	HGNC:18591	ENSG00000119638	Q8TD19	Serine/threonine-protein kinase Nek9	clinvar
FLNA	HGNC:3754	ENSG00000196924	P21333	Filamin-A	clinvar
LAMA5	HGNC:6485	ENSG00000130702	O15230	Laminin subunit alpha-5	clinvar
PLOD1	HGNC:9081	ENSG00000083444	Q02809	Procollagen-lysine,2-oxoglutarate 5-dioxygenase 1	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
GEMIN4	Gem-associated protein 4	The SMN complex catalyzes the assembly of small nuclear ribonucleoproteins (snRNPs), the building blocks of the spliceosome, and thereby plays an important role in the splicing of cellular pre-mRNAs.
PGAP2	Acyltransferase PGAP2	Involved in the fatty acid remodeling steps of GPI-anchor maturation where the unsaturated acyl chain at sn-2 of inositol phosphate is replaced by a saturated stearoyl chain.
NEK9	Serine/threonine-protein kinase Nek9	Pleiotropic regulator of mitotic progression, participating in the control of spindle dynamics and chromosome separation.
FLNA	Filamin-A	Promotes orthogonal branching of actin filaments and links actin filaments to membrane glycoproteins.
LAMA5	Laminin subunit alpha-5	Binding to cells via a high affinity receptor, laminin is thought to mediate the attachment, migration and organization of cells into tissues during embryonic development by interacting with other extracellular matrix components.
PLOD1	Procollagen-lysine,2-oxoglutarate 5-dioxygenase 1	Part of a complex composed of PLOD1, P3H3 and P3H4 that catalyzes hydroxylation of lysine residues in collagen alpha chains and is required for normal assembly and cross-linkling of collagen fibrils.

Protein-family classification

Druggable: 2 · Difficult: 0 · Unknown: 4 · Druggable fraction: 0.33

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
Antibody/Immunoglobulin	1	4.9×	0.297
Kinase	1	4.6×	0.297
Other/Unknown	4	1.2×	0.458

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
GEMIN4	Other/Unknown	no		GEMIN4
PGAP2	Other/Unknown	no		CWH43_N, PGAP2
NEK9	Kinase	yes		Reg_chr_condens, Prot_kinase_dom, Ser/Thr_kinase_AS
FLNA	Antibody/Immunoglobulin	yes		Filamin/ABP280_rpt, Actinin_actin-bd_CS, CH_dom
LAMA5	Other/Unknown	no		Laminin_IV, EGF, TNFR/NGFR_Cys_rich_reg
PLOD1	Other/Unknown	no		Procol_lys_dOase, Oxoglu/Fe-dep_dioxygenase_dom, Pro_4_hyd_alph

Expression context

Cohort genes with no expression data: 0.

6 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)	6
unknown	0

Top tissues across cohort

Tissue	Cohort genes
right uterine tube	2
left testis	1
right testis	1
sperm	1
corpus epididymis	1
lower esophagus mucosa	1
skin of abdomen	1
left ovary	1
tibia	1
popliteal artery	1
right coronary artery	1
tibial artery	1
metanephros cortex	1
right hemisphere of cerebellum	1
apex of heart	1
smooth muscle tissue	1
stromal cell of endometrium	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
GEMIN4	253	ubiquitous	marker	sperm, left testis, right testis
PGAP2	280	ubiquitous	marker	corpus epididymis, lower esophagus mucosa, skin of abdomen
NEK9	296	ubiquitous	marker	tibia, right uterine tube, left ovary
FLNA	285	ubiquitous	marker	right coronary artery, popliteal artery, tibial artery
LAMA5	264	ubiquitous	marker	right uterine tube, right hemisphere of cerebellum, metanephros cortex
PLOD1	279	ubiquitous	marker	stromal cell of endometrium, smooth muscle tissue, apex of heart

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
FLNA	5,321
LAMA5	2,519
NEK9	2,341
GEMIN4	2,136
PLOD1	1,929
PGAP2	887

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
FLNA	P21333	26
NEK9	Q8TD19	2
LAMA5	O15230	2

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
PLOD1	Q02809	93.04
PGAP2	Q9UHJ9	90.00
GEMIN4	P57678	84.54

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 34. Enrichment computed across 6 evidence-associated genes (5 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 5 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Activation of NIMA Kinases NEK9, NEK6, NEK7	1	285.5×	0.039	NEK9
OAS antiviral response	1	253.8×	0.039	FLNA
GP1b-IX-V activation signalling	1	190.3×	0.039	FLNA
Cell-extracellular matrix interactions	1	134.3×	0.039	FLNA
MET promotes cell motility	1	120.2×	0.039	LAMA5
RHO GTPases activate PAKs	1	108.8×	0.039	FLNA
Attachment of bacteria to epithelial cells	1	99.3×	0.039	LAMA5
Nuclear Envelope Breakdown	1	91.4×	0.039	NEK9
Laminin interactions	1	76.1×	0.039	LAMA5
MET activates PTK2 signaling	1	76.1×	0.039	LAMA5
Mitotic Prophase	1	73.7×	0.039	NEK9
Signaling by MET	1	63.4×	0.039	LAMA5
Nuclear Pore Complex (NPC) Disassembly	1	61.7×	0.039	NEK9
Formation of the dystrophin-glycoprotein complex (DGC)	1	61.7×	0.039	LAMA5
Developmental Lineage of Pancreatic Ductal Cells	1	45.7×	0.047	LAMA5
SARS-CoV-2 modulates host translation machinery	1	44.8×	0.047	GEMIN4
snRNP Assembly	1	42.3×	0.047	GEMIN4
Collagen biosynthesis and modifying enzymes	1	34.1×	0.055	PLOD1
Non-integrin membrane-ECM interactions	1	30.9×	0.056	LAMA5
ECM proteoglycans	1	30.1×	0.056	LAMA5
Degradation of the extracellular matrix	1	23.6×	0.068	LAMA5
Interleukin-4 and Interleukin-13 signaling	1	20.6×	0.074	LAMA5
EML4 and NUDC in mitotic spindle formation	1	18.6×	0.078	NEK9
Platelet degranulation	1	17.6×	0.079	FLNA
Mitotic Prometaphase	1	13.8×	0.093	NEK9
M Phase	1	13.2×	0.093	NEK9
Signaling by Interleukins	1	12.8×	0.093	LAMA5
Extracellular matrix organization	1	12.6×	0.093	LAMA5
Signaling by Receptor Tyrosine Kinases	1	10.3×	0.109	LAMA5
Cell Cycle, Mitotic	1	9.6×	0.113	NEK9

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 6 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
regulation of membrane repolarization during atrial cardiac muscle cell action potential	1	2808.7×	0.011	FLNA
regulation of membrane repolarization during cardiac muscle cell action potential	1	2808.7×	0.011	FLNA
trunk neural crest cell migration	1	1404.3×	0.011	LAMA5
obsolete hydroxylysine biosynthetic process	1	936.2×	0.011	PLOD1
tubulin deacetylation	1	936.2×	0.011	FLNA
morphogenesis of a polarized epithelium	1	702.2×	0.011	LAMA5
formation of radial glial scaffolds	1	702.2×	0.011	FLNA
regulation of cell migration	2	52.5×	0.011	FLNA, LAMA5
protein localization to plasma membrane	2	36.2×	0.011	FLNA, LAMA5
adenylate cyclase-inhibiting dopamine receptor signaling pathway	1	561.7×	0.011	FLNA
establishment of Sertoli cell barrier	1	561.7×	0.011	FLNA
protein localization to bicellular tight junction	1	468.1×	0.012	FLNA
negative regulation of transcription by RNA polymerase I	1	401.2×	0.012	FLNA
postsynapse organization	1	401.2×	0.012	LAMA5
cilium assembly	2	24.5×	0.012	FLNA, LAMA5
blood coagulation, intrinsic pathway	1	351.1×	0.012	FLNA
morphogenesis of embryonic epithelium	1	255.3×	0.015	LAMA5
branching involved in salivary gland morphogenesis	1	234.1×	0.015	LAMA5
positive regulation of platelet activation	1	216.1×	0.015	FLNA
positive regulation of integrin-mediated signaling pathway	1	216.1×	0.015	FLNA
positive regulation of actin filament bundle assembly	1	200.6×	0.015	FLNA
actin crosslink formation	1	200.6×	0.015	FLNA
wound healing, spreading of cells	1	187.2×	0.016	FLNA
collagen biosynthetic process	1	175.5×	0.016	PLOD1
positive regulation of potassium ion transmembrane transport	1	165.2×	0.016	FLNA
positive regulation of neuron migration	1	165.2×	0.016	FLNA
regulation of epithelial cell proliferation	1	156.0×	0.016	LAMA5
positive regulation of neural precursor cell proliferation	1	127.7×	0.019	FLNA
obsolete negative regulation of DNA-binding transcription factor activity	1	122.1×	0.019	FLNA
megakaryocyte development	1	117.0×	0.019	FLNA

Therapeutics

Drug target analysis

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

Druggability breadth: 5 of 6 evidence-associated genes (83%) 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
NEK9	MOMELOTINIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
NEK9	21	4
FLNA	1	2
GEMIN4	0	0
PGAP2	0	0
LAMA5	0	0
PLOD1	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
MOMELOTINIB	4	NEK9
FEDRATINIB	4	NEK9
DABRAFENIB	4	NEK9
PACRITINIB	4	NEK9
FOSTAMATINIB	4	NEK9
CRIZOTINIB	4	NEK9
DOVITINIB	3	NEK9
LESTAURTINIB	3	NEK9
FORETINIB	2	NEK9
REBASTINIB	2	NEK9
DANUSERTIB	2	NEK9
R-406	2	NEK9
ENMD-2076	2	NEK9
AT-9283	2	NEK9
MILCICLIB	2	NEK9
BMS-754807	2	NEK9
MOLIBRESIB	2	FLNA
GSK-461364	1	NEK9
KW-2449	1	NEK9
XL-019	1	NEK9
CYC-116	1	NEK9
AST-487	1	NEK9

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
NEK9	254	Binding:254
FLNA	7	Binding:7
GEMIN4	2	Binding:2
PLOD1	1	Binding:1

Cohort genes with high screening signal

≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.

Symbol	ChEMBL assays
NEK9	254

Pharmacogenomics

Cohort genes with a PharmGKB record: 6; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

22 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)
MOMELOTINIB	4	NEK9
FEDRATINIB	4	NEK9
DABRAFENIB	4	NEK9
PACRITINIB	4	NEK9
FOSTAMATINIB	4	NEK9
CRIZOTINIB	4	NEK9
DOVITINIB	3	NEK9
LESTAURTINIB	3	NEK9
FORETINIB	2	NEK9
REBASTINIB	2	NEK9
DANUSERTIB	2	NEK9
R-406	2	NEK9
ENMD-2076	2	NEK9
AT-9283	2	NEK9
MILCICLIB	2	NEK9
BMS-754807	2	NEK9
MOLIBRESIB	2	FLNA
GSK-461364	1	NEK9
KW-2449	1	NEK9
XL-019	1	NEK9
CYC-116	1	NEK9
AST-487	1	NEK9

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	NEK9
B	Phased (≥1) drug, not yet approved	1	FLNA
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	4	GEMIN4, PGAP2, LAMA5, PLOD1

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
GEMIN4	2	—
PGAP2	0	—
LAMA5	0	—
PLOD1	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 10.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	10

Top trials by phase / activity

NCT	Phase	Status	Title
NCT06072976	Not specified	RECRUITING	The Influence of Feeding Source on the Gut Microbiome and Time to Full Feeds in Neonates With Congenital Gastrointestinal Pathologies
NCT06731855	Not specified	RECRUITING	An Exploratory Physiological Study of Post-operative Recovery in Surgical Neonates and Dimethylarginine:Arginine Levels
NCT03520465	Not specified	UNKNOWN	Utility of a Supraaponeurotic Mesh as Prophylaxis of the Midline Eventration After an Oncological Colorrectal Resection
NCT03666767	Not specified	COMPLETED	Management and Outcomes of Congenital Anomalies in Low-, Middle- and High-Income Countries
NCT03765060	Not specified	UNKNOWN	The Efficacy and Security of the Small Stitch Technique in Emergency Surgery
NCT03960320	Not specified	COMPLETED	Health Related Quality of Life of Patients With Abdominal Wall Defects
NCT04126863	Not specified	COMPLETED	Omphaloceles and Associated Malformations
NCT04186039	Not specified	WITHDRAWN	Functional Evaluation of the Fetal Lung by Functional Magnetic Resonance Imaging - Blood Oxygenation Level Dependent (MRI-BOLD), in Congenital Diaphragmatic and Parietal Malformations
NCT05293353	Not specified	UNKNOWN	Neokare Safety and Tolerability Assessment in Neonates With GI Problems
NCT06014749	Not specified	COMPLETED	Serratus Intercostal Block Versus Epidural/Port Infiltration Analgesia in Eventration: Prospective Non Inferiority Study