Atrial septal aneurysm

Summary

Atrial septal aneurysm (MONDO:0020438) is a disease with 1 cohort gene and 3 clinical trials. Top therapeutic interventions include aspirin.

At a glance

• Cohort genes: 1
• ClinVar variants: 1
• Clinical trials: 3

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	atrial septal aneurysm
Mondo ID	MONDO:0020438
Orphanet	99107
ICD-11	100700036
SNOMED CT	95440004
UMLS	C4476553
MedGen	1384602
GARD	0019651
Is cancer (heuristic)	no

Data availability: 1 ClinVar variant.

Disease family

Classification path: disease › human disease › disease by body system or component › cardiovascular disorder › congenital anomaly of cardiovascular system › congenital heart malformation › atrial septal aneurysm

Related subtypes (25): transposition of the great arteries, congenital left-sided heart lesions, interventricular septum aneurysm, congenital heart defects, multiple types, 2, coronary artery congenital malformation, criss-cross heart, triatrial heart, familial idiopathic dilatation of the right atrium, cardiac diverticulum, conotruncal heart malformations, congenital mitral malformation, congenital pericardium anomaly, ectopia cordis, visceral heterotaxy, mesocardia, univentricular cardiopathy, congenital anomaly of the great arteries, Laubry-Pezzi syndrome, congenital Gerbode defect, juxtaposition of the atrial appendages, ectasia of the right atrial appendage, ectasia of the left appendage, congenital acardia, congenital right-sided heart lesions, congenital heart defects, multiple types, 1, X-linked

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 uncertain significance

ClinVar	Variant (HGVS)	Gene	Classification	Review
523426	NM_001256071.3(RNF213):c.11659A>G (p.Lys3887Glu)	RNF213	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 1 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
RNF213	Orphanet:2573	Moyamoya disease

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
RNF213	HGNC:14539	ENSG00000173821	Q63HN8	E3 ubiquitin-protein ligase RNF213	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
RNF213	E3 ubiquitin-protein ligase RNF213	Atypical E3 ubiquitin ligase that can catalyze ubiquitination of both proteins and lipids, and which is involved in various processes, such as lipid metabolism, angiogenesis and cell-autonomous immunity.

Protein-family classification

Druggable: 0 · Difficult: 1 · Unknown: 0 · Druggable fraction: 0.0

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
Transcription factor	1	8.3×	0.121

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
RNF213	Transcription factor	no		Znf_RING, AAA+_ATPase, Znf_RING/FYVE/PHD

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
granulocyte	1
metanephros cortex	1
pancreatic ductal cell	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
RNF213	252	ubiquitous	marker	granulocyte, metanephros cortex, pancreatic ductal cell

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
RNF213	2,368

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
RNF213	Q63HN8	4

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
Suppression of apoptosis	1	1631.4×	0.004	RNF213
Response of Mtb to phagocytosis	1	1427.5×	0.004	RNF213
Infection with Mycobacterium tuberculosis	1	1142.0×	0.004	RNF213
Bacterial Infection Pathways	1	335.9×	0.010	RNF213
Signaling by ALK in cancer	1	271.9×	0.010	RNF213
Signaling by ALK fusions and activated point mutants	1	150.3×	0.014	RNF213
Class I MHC mediated antigen processing & presentation	1	70.1×	0.027	RNF213
Diseases of signal transduction by growth factor receptors and second messengers	1	56.8×	0.029	RNF213
Antigen processing: Ubiquitination & Proteasome degradation	1	37.2×	0.039	RNF213
Adaptive Immune System	1	29.8×	0.044	RNF213
Infectious disease	1	24.8×	0.048	RNF213
Disease	1	13.1×	0.077	RNF213
Immune System	1	13.0×	0.077	RNF213

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
lipid ubiquitination	1	16852.0×	8e-04	RNF213
negative regulation of non-canonical Wnt signaling pathway	1	3370.4×	0.002	RNF213
xenophagy	1	2407.4×	0.002	RNF213
lipid droplet formation	1	991.3×	0.003	RNF213
sprouting angiogenesis	1	481.5×	0.005	RNF213
regulation of lipid metabolic process	1	432.1×	0.005	RNF213
immune system process	1	391.9×	0.005	RNF213
protein K63-linked ubiquitination	1	267.5×	0.006	RNF213
protein autoubiquitination	1	234.1×	0.006	RNF213
defense response to bacterium	1	108.0×	0.012	RNF213
ubiquitin-dependent protein catabolic process	1	74.2×	0.016	RNF213
angiogenesis	1	62.4×	0.017	RNF213
protein ubiquitination	1	41.4×	0.024	RNF213

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
RNF213	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
RNF213	1	Binding:1

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	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	RNF213

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)
RNF213	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 3.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	2
PHASE3	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT00562289	PHASE3	COMPLETED	Patent Foramen Ovale Closure or Anticoagulants Versus Antiplatelet Therapy to Prevent Stroke Recurrence
NCT03147014	Not specified	UNKNOWN	Cardiovascular Response to Maternal Hyperoxygenation in Fetal Congenital Heart Disease
NCT04561882	Not specified	UNKNOWN	Transcatheter Exclusion of Atrial-septal-aneurysm (TEA)

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
ASPIRIN	4	1