Diaphragmatic eventration

Summary

Diaphragmatic eventration (MONDO:0006726) is a disease with 2 cohort genes and 4 clinical trials.

At a glance

• Cohort genes: 2
• ClinVar variants: 2
• Clinical trials: 4

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	diaphragmatic eventration
Mondo ID	MONDO:0006726
EFO	EFO:1000898
MeSH	D003965
DOID	DOID:10480
NCIT	C98912
SNOMED CT	34168003
UMLS	C0011981
MedGen	8359
GARD	0024462
Is cancer (heuristic)	no

Also known as: diaphragmatic eventration · diaphragmatic eventration (disease)

Data availability: 2 ClinVar variants · 1 HPO phenotype.

Disease family

Classification path: disease › human disease › disease by body system or component › respiratory system disorder › diaphragm disorder › diaphragmatic eventration

Related subtypes (4): congenital diaphragmatic hernia, diaphragmitis, respiratory paralysis, diaphragmatic malformation

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

2 retrieved; paginated sample, class counts are floors:

1 uncertain significance, 1 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
376498	NM_006218.4(PIK3CA):c.1030G>A (p.Val344Met)	PIK3CA	Pathogenic	criteria provided, multiple submitters, no conflicts
1338823	GRCh38/hg38 17q12(chr17:36719878-37889304)	AATF	Uncertain significance	no assertion criteria provided

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 15 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
PIK3CA	Orphanet:140944	CLOVES syndrome
PIK3CA	Orphanet:144	Lynch syndrome
PIK3CA	Orphanet:168984	CLAPO syndrome
PIK3CA	Orphanet:201	Cowden syndrome
PIK3CA	Orphanet:210159	Adult hepatocellular carcinoma
PIK3CA	Orphanet:221061	Familial cerebral cavernous malformation
PIK3CA	Orphanet:2495	Meningioma
PIK3CA	Orphanet:276280	Hemihyperplasia-multiple lipomatosis syndrome
PIK3CA	Orphanet:295239	Macrodactyly of fingers, unilateral
PIK3CA	Orphanet:295243	Macrodactyly of toes, unilateral
PIK3CA	Orphanet:314662	Segmental progressive overgrowth syndrome with fibroadipose hyperplasia
PIK3CA	Orphanet:60040	Megalencephaly-capillary malformation-polymicrogyria syndrome
PIK3CA	Orphanet:714737	Diffuse capillary malformation with overgrowth
PIK3CA	Orphanet:90308	Capillary-lymphatic-venous malformation with segmental distribution
PIK3CA	Orphanet:99802	Hemimegalencephaly

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
AATF	HGNC:19235	ENSG00000275700	Q9NY61	Protein AATF	clinvar
PIK3CA	HGNC:8975	ENSG00000121879	P42336	Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
AATF	Protein AATF	Part of the small subunit (SSU) processome, first precursor of the small eukaryotic ribosomal subunit.
PIK3CA	Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform	Phosphoinositide-3-kinase (PI3K) phosphorylates phosphatidylinositol (PI) and its phosphorylated derivatives at position 3 of the inositol ring to produce 3-phosphoinositides.

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)
AATF	Other/Unknown	no		AATF_C, AATF, AATF/Bfr2
PIK3CA	Kinase	yes	2.7.1.137	PI3K_Ras-bd_dom, PI3/4_kinase_cat_dom, PI3K_accessory_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
granulocyte	1
leukocyte	1
monocyte	1
adrenal tissue	1
calcaneal tendon	1
tendon	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
AATF	134	ubiquitous	marker	monocyte, leukocyte, granulocyte
PIK3CA	284	ubiquitous	marker	calcaneal tendon, adrenal tissue, tendon

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
PIK3CA	5,157
AATF	3,194

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
PIK3CA	P42336	135
AATF	Q9NY61	3

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 65. 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
MET activates PI3K/AKT signaling	1	951.7×	0.008	PIK3CA
Activated NTRK3 signals through PI3K	1	951.7×	0.008	PIK3CA
Activated NTRK2 signals through PI3K	1	815.7×	0.008	PIK3CA
Signaling by LTK in cancer	1	815.7×	0.008	PIK3CA
PI3K/AKT activation	1	634.4×	0.008	PIK3CA
IRS-mediated signalling	1	519.1×	0.008	PIK3CA
PI3K events in ERBB4 signaling	1	519.1×	0.008	PIK3CA
Co-stimulation by ICOS	1	519.1×	0.008	PIK3CA
Signaling by FGFR4 in disease	1	475.8×	0.008	PIK3CA
Erythropoietin activates Phosphoinositide-3-kinase (PI3K)	1	475.8×	0.008	PIK3CA
Signaling by PDGFRA transmembrane, juxtamembrane and kinase domain mutants	1	439.2×	0.008	PIK3CA
Signaling by PDGFRA extracellular domain mutants	1	439.2×	0.008	PIK3CA
Signaling by LTK	1	439.2×	0.008	PIK3CA
Signaling by FLT3 ITD and TKD mutants	1	380.7×	0.008	PIK3CA
Constitutive Signaling by EGFRvIII	1	356.9×	0.008	PIK3CA
PI3K events in ERBB2 signaling	1	335.9×	0.008	PIK3CA
Signaling by ERBB2 ECD mutants	1	335.9×	0.008	PIK3CA
GAB1 signalosome	1	317.2×	0.008	PIK3CA
Signaling by cytosolic FGFR1 fusion mutants	1	317.2×	0.008	PIK3CA
PI-3K cascade:FGFR3	1	317.2×	0.008	PIK3CA
Tie2 Signaling	1	300.5×	0.008	PIK3CA
Role of LAT2/NTAL/LAB on calcium mobilization	1	300.5×	0.008	PIK3CA
Constitutive Signaling by Ligand-Responsive EGFR Cancer Variants	1	285.5×	0.008	PIK3CA
Signaling by ALK	1	285.5×	0.008	PIK3CA
PI-3K cascade:FGFR4	1	285.5×	0.008	PIK3CA
Signaling by FLT3 fusion proteins	1	285.5×	0.008	PIK3CA
PI-3K cascade:FGFR1	1	259.6×	0.008	PIK3CA
Signaling by phosphorylated juxtamembrane, extracellular and kinase domain KIT mutants	1	259.6×	0.008	PIK3CA
PI-3K cascade:FGFR2	1	248.3×	0.008	PIK3CA
Signaling by FGFR3 in disease	1	248.3×	0.008	PIK3CA

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
response to muscle inactivity	1	8426.0×	0.003	PIK3CA
response to butyrate	1	8426.0×	0.003	PIK3CA
response to L-leucine	1	2808.7×	0.005	PIK3CA
cellular response to hydrostatic pressure	1	2808.7×	0.005	PIK3CA
negative regulation of actin filament depolymerization	1	1404.3×	0.005	PIK3CA
regulation of cellular respiration	1	1404.3×	0.005	PIK3CA
regulation of actin filament organization	1	1203.7×	0.005	PIK3CA
autosome genomic imprinting	1	1203.7×	0.005	PIK3CA
negative regulation of fibroblast apoptotic process	1	1203.7×	0.005	PIK3CA
negative regulation of amyloid precursor protein biosynthetic process	1	1053.2×	0.005	AATF
embryonic cleavage	1	842.6×	0.005	AATF
cardiac muscle cell contraction	1	842.6×	0.005	PIK3CA
positive regulation of protein localization to membrane	1	842.6×	0.005	PIK3CA
TORC2 signaling	1	766.0×	0.005	PIK3CA
phosphatidylinositol-3-phosphate biosynthetic process	1	648.1×	0.005	PIK3CA
anoikis	1	648.1×	0.005	PIK3CA
relaxation of cardiac muscle	1	648.1×	0.005	PIK3CA
response to dexamethasone	1	601.9×	0.005	PIK3CA
vasculature development	1	561.7×	0.005	PIK3CA
negative regulation of macroautophagy	1	561.7×	0.005	PIK3CA
vascular endothelial growth factor signaling pathway	1	526.6×	0.005	PIK3CA
negative regulation of anoikis	1	443.5×	0.006	PIK3CA
response to muscle stretch	1	383.0×	0.006	PIK3CA
phosphatidylinositol-mediated signaling	1	351.1×	0.007	PIK3CA
regulation of multicellular organism growth	1	324.1×	0.007	PIK3CA
positive regulation of lamellipodium assembly	1	300.9×	0.007	PIK3CA
negative regulation of apoptotic signaling pathway	1	280.9×	0.007	AATF
positive regulation of TOR signaling	1	247.8×	0.008	PIK3CA
insulin-like growth factor receptor signaling pathway	1	247.8×	0.008	PIK3CA
phosphatidylinositol phosphate biosynthetic process	1	240.7×	0.008	PIK3CA

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 2 evidence-associated genes (50%) 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
PIK3CA	IDELALISIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
PIK3CA	67	4
AATF	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
IDELALISIB	4	PIK3CA
ALPELISIB	4	PIK3CA
DUVELISIB	4	PIK3CA
COPANLISIB	4	PIK3CA
FEDRATINIB	4	PIK3CA
ROMIDEPSIN	4	PIK3CA
COPANLISIB HYDROCHLORIDE	4	PIK3CA
LENIOLISIB	4	PIK3CA
BELINOSTAT	4	PIK3CA
INAVOLISIB	4	PIK3CA
SUNITINIB	4	PIK3CA
DASATINIB	4	PIK3CA
CRIZOTINIB	4	PIK3CA
MIDOSTAURIN	4	PIK3CA
DACTOLISIB	3	PIK3CA
BUPARLISIB	3	PIK3CA
RESVERATROL	3	PIK3CA
IPATASERTIB	3	PIK3CA
TASELISIB	3	PIK3CA
EPIGALOCATECHIN GALLATE	3	PIK3CA
GEDATOLISIB	3	PIK3CA
LESTAURTINIB	3	PIK3CA
OMIPALISIB	2	PIK3CA
VISTUSERTIB	2	PIK3CA
FIMEPINOSTAT	2	PIK3CA
EGANELISIB	2	PIK3CA
BERZOSERTIB	2	PIK3CA
BIMIRALISIB	2	PIK3CA
PICTILISIB	2	PIK3CA
ZSTK-474	2	PIK3CA

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
PIK3CA	2,034	Binding:2009, ADMET:19, Toxicity:4, Functional:2

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
PIK3CA	2.7.1.137, 2.7.1.153, 2.7.11.1	phosphatidylinositol 3-kinase, phosphatidylinositol-4,5-bisphosphate 3-kinase, non-specific serine/threonine protein kinase

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
PIK3CA	2,034

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

30 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)
IDELALISIB	4	PIK3CA
ALPELISIB	4	PIK3CA
DUVELISIB	4	PIK3CA
COPANLISIB	4	PIK3CA
FEDRATINIB	4	PIK3CA
ROMIDEPSIN	4	PIK3CA
COPANLISIB HYDROCHLORIDE	4	PIK3CA
LENIOLISIB	4	PIK3CA
BELINOSTAT	4	PIK3CA
INAVOLISIB	4	PIK3CA
SUNITINIB	4	PIK3CA
DASATINIB	4	PIK3CA
CRIZOTINIB	4	PIK3CA
MIDOSTAURIN	4	PIK3CA
DACTOLISIB	3	PIK3CA
BUPARLISIB	3	PIK3CA
RESVERATROL	3	PIK3CA
IPATASERTIB	3	PIK3CA
TASELISIB	3	PIK3CA
EPIGALOCATECHIN GALLATE	3	PIK3CA
GEDATOLISIB	3	PIK3CA
LESTAURTINIB	3	PIK3CA
OMIPALISIB	2	PIK3CA
VISTUSERTIB	2	PIK3CA
FIMEPINOSTAT	2	PIK3CA
EGANELISIB	2	PIK3CA
BERZOSERTIB	2	PIK3CA
BIMIRALISIB	2	PIK3CA
PICTILISIB	2	PIK3CA
ZSTK-474	2	PIK3CA

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	PIK3CA
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	1	AATF

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)
AATF	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 4.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	4

Top trials by phase / activity

NCT	Phase	Status	Title
NCT06919185	Not specified	NOT_YET_RECRUITING	Short- and Long-term Effects of Robot-assisted Plication in Diaphragmatic Paralysis
NCT01243229	Not specified	COMPLETED	Genetic Analysis of Congenital Diaphragmatic Disorders
NCT04862494	Not specified	UNKNOWN	Diaphragmatic Eventration in Children : Evaluation of Care Strategies and Results in the French Cohort.
NCT07035366	Not specified	COMPLETED	Two Procedures for Uniportal Video Assisted Thoracoscopic Surgery to Treat Severe Cases of Diaphragmatic Eventration in Adult