Aortic disorder

Summary

Aortic disorder (MONDO:0005561) is a disease (an umbrella term covering 17 Mondo subtypes) with 2 cohort genes (8 GWAS associations across 4 studies) and 7 clinical trials. Top therapeutic interventions include sugammadex.

At a glance

• Umbrella term: 17 Mondo subtypes
• Cohort genes: 2
• GWAS associations: 8
• Clinical trials: 7

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	aortic disorder
Mondo ID	MONDO:0005561
EFO	EFO:0005775
MeSH	D001018
DOID	DOID:520
NCIT	C101253
SNOMED CT	47040006
UMLS	C0003493
MedGen	1618
Anatomy (UBERON)	UBERON:0000947
Is cancer (heuristic)	no

Also known as: aorta disease · aorta disease or disorder · disease of aorta · disease or disorder of aorta · disorder of aorta

Data availability: 8 GWAS associations (4 studies) · 2 GenCC gene-disease records.

Disease family

An umbrella term covering 17 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › cardiovascular disorder › vascular disorder › arterial disorder › aortic disorder

Related subtypes (29): vertebral artery insufficiency, splenic artery aneurysm, basilar artery insufficiency, arteriosclerosis disorder, subclavian artery aneurysm, pulmonary artery choriocarcinoma, pulmonary artery leiomyosarcoma, coronary artery disorder, hypertensive disorder, carotid artery disorder, pulmonary embolism, peripheral arterial disease, hypotensive disorder, large artery stroke, cervical artery dissection, anterior spinal artery syndrome, fibromuscular dysplasia, retinal arterial tortuosity, Sneddon syndrome, celiac trunk compression syndrome, pediatric arterial ischemic stroke, absence of the pulmonary artery, arterial occlusion, aberrant subclavian artery, anterior spinal artery stroke, arteritis, pulmonary artery disease, fibromuscular dysplasia, multifocal, carotid web

Subtypes (17): aortic atherosclerosis, aorta atresia, renal artery disease, superior mesenteric artery syndrome, aortic valve disorder, aortic malignant tumor, aortic aneurysm, tricuspid valve stenosis, aortitis, tricuspid valve prolapse, aorta coarctation, subaortic stenosis, membranous, aneurysm of sinus of Valsalva, neoplasm of aortic body, Leriche syndrome, X-linked severe syndromic thoracic aortic aneurysm and dissection, fibromuscular dysplasia of the renal arteries

Genetics & variants

GWAS landscape

8 GWAS associations across 4 studies. Top hits map to 5 distinct genes (as reported by GWAS).

Top associations by p-value

rsID	p-value	Gene	Risk allele	Odds ratio
rs184806872	5e-13	CTIF	G	4.07
rs534538229	1e-12	KCTD8 - YIPF7	T	3.88
rs564301985	3e-12	NES - CRABP2	C	3.02
rs574493019	3e-12	ARHGAP24	T	3.12
rs192499149	5e-07	CRAT37	A	1.6
rs78152556	7e-07	RDH13	T	0.95
rs59580441	2e-06	MAIP1 - SPATS2L	G	0.7
rs574027	2e-06	NTM	G	0.57

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST90478031	Verma A	2024	1,155	446,661	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90480215	Verma A	2024	200	121,048	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90482047	Verma A	2024	200	121,048	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90104135	Choe EK	2022	0	0	Leveraging deep phenotyping from health check-up cohort with 10,000 Korean individuals for phenome-wide association study of 136 traits.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

Tier	Variants
Tier 1: coding	0
Tier 2: splice/UTR	0
Tier 3: regulatory	1
Tier 4: intronic/intergenic	7

MAF distribution

Bucket	Variants
common (>=0.05)	2
low_freq (0.01-0.05)	2
rare (<0.01)	4
unknown	0

Functional consequences

Consequence	Count
intron_variant	6
intergenic_variant	1
regulatory_region_variant	1

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
rs184806872	18	48784329	G>A,C,T	0	intron_variant	CTIF	5e-13	Tier 4: intronic/intergenic
rs534538229	4	44574681	T>C	0	intergenic_variant	KCTD8 - YIPF7	1e-12	Tier 4: intronic/intergenic
rs564301985	1	156693291	C>A,T	0	intron_variant	NES - CRABP2	3e-12	Tier 4: intronic/intergenic
rs574493019	4	85626390	T>A	0	intron_variant	ARHGAP24	3e-12	Tier 4: intronic/intergenic
rs192499149	15	91487914	G>A	0.012	intron_variant	CRAT37	5e-07	Tier 4: intronic/intergenic
rs78152556	19	55069794	G>T	0.048	regulatory_region_variant	RDH13	7e-07	Tier 3: regulatory
rs59580441	2	200123912	A>G	0.102	intron_variant	MAIP1 - SPATS2L	2e-06	Tier 4: intronic/intergenic
rs574027	11	131909156	A>C,G,T	0.205	intron_variant	NTM	2e-06	Tier 4: intronic/intergenic

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 14 · Orphanet: 2 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
PRDM5	Limited	Autosomal dominant	aortic disorder	8
ZNF469	Limited	Autosomal dominant	aortic disorder	6

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
ZNF469	Orphanet:90354	Brittle cornea syndrome
PRDM5	Orphanet:90354	Brittle cornea syndrome

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
ZNF469	HGNC:23216	ENSG00000225614	Q96JG9	Zinc finger protein 469	gencc
PRDM5	HGNC:9349	ENSG00000138738	Q9NQX1	PR domain zinc finger protein 5	gencc

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
ZNF469	Zinc finger protein 469	May be involved in transcriptional regulation.
PRDM5	PR domain zinc finger protein 5	Sequence-specific DNA-binding transcription factor.

Protein-family classification

Druggable: 0 · Difficult: 2 · 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	2	8.3×	0.015

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
ZNF469	Transcription factor	no		Znf_C2H2_type, Znf_C2H2_sf, ZNF469
PRDM5	Transcription factor	no		SET_dom, Znf_C2H2_type, Znf_PRDM5-like

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
cartilage tissue	1
tibia	1
upper arm skin	1
calcaneal tendon	1
male germ line stem cell (sensu Vertebrata) in testis	1
sural nerve	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
ZNF469	211	broad	yes	tibia, upper arm skin, cartilage tissue
PRDM5	206	ubiquitous	marker	calcaneal tendon, sural nerve, male germ line stem cell (sensu Vertebrata) in testis

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
PRDM5	1,303
ZNF469	954

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
PRDM5	Q9NQX1	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
ZNF469	Q96JG9

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 0. Enrichment computed across 2 evidence-associated genes (0 with Reactome annotation).

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
regulation of extracellular matrix organization	2	1872.4×	2e-06	ZNF469, PRDM5
negative regulation of transcription by RNA polymerase II	2	17.7×	0.013	ZNF469, PRDM5
methylation	1	85.1×	0.024	PRDM5
cellular response to leukemia inhibitory factor	1	79.5×	0.024	PRDM5
mitotic cell cycle	1	66.9×	0.024	PRDM5
chromatin organization	1	49.6×	0.027	PRDM5
negative regulation of DNA-templated transcription	1	15.8×	0.071	PRDM5
positive regulation of transcription by RNA polymerase II	1	7.4×	0.130	PRDM5

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 2

Druggability breadth: 0 of 2 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
ZNF469	0	0
PRDM5	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	2	ZNF469, PRDM5

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)
ZNF469	0	—
PRDM5	0	—

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
NCT02596048	PHASE4	COMPLETED	A Multicenter Study of Iomeron®-400 Used With Multi-detector Computed Tomography Angiography (MDCTA)
NCT05246397	PHASE4	COMPLETED	Sugammadex Titration in Cardiac Surgery Patients
NCT06022653	Not specified	RECRUITING	Asan Aorta and Peripheral Registry
NCT07064460	Not specified	RECRUITING	Duke Customized Aortic Aneurysm Repair With Endovascular Stent-grafts - Duke CARES Trial
NCT07487961	Not specified	RECRUITING	Assess Abdominal Aortic Diameter in Females
NCT03610529	Not specified	UNKNOWN	CardioSenseSystem Compared Study Regarding Efficacy and Safety in the Monitoring of ECG
NCT04231461	Not specified	COMPLETED	Quality of Life After Cardiac Surgery

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
SUGAMMADEX	4	3
CHEMBL5412674	0	1