Aortic aneurysm

disease

On this page

Also known as abdominal aortic aneurysm, rupturedaortic aneurysm (disease)aortic aneurysm of unspecified site, rupturedruptured abdominal aortic aneurysmruptured thoracic aneurysmruptured thoracic aortic aneurysmruptured thoracoabdominal aortic aneurysmthoracic aortic aneurysm which HAS rupturedthoracic aortic aneurysm, rupturedthoracoabdominal aortic aneurysm, ruptured

Summary

Aortic aneurysm (MONDO:0005160) is a disease with 7 cohort genes (67 GWAS associations across 17 studies) and 149 clinical trials. The dominant Reactome pathway is TGF-beta receptor signaling activates SMADs (3 cohort genes). Top therapeutic interventions include ferric carboxymaltose, melatonin, and modimelanotide.

At a glance

Cohort genes: 7
GWAS associations: 67
ClinVar variants: 11
Clinical trials: 149

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	aortic aneurysm
Mondo ID	MONDO:0005160
EFO	EFO:0001666
MeSH	D001014
DOID	DOID:3627
SNOMED CT	73067008
UMLS	C0003486
MedGen	362
Is cancer (heuristic)	no

Also known as: abdominal aortic aneurysm, ruptured · aortic aneurysm · aortic aneurysm (disease) · aortic aneurysm of unspecified site, ruptured · ruptured abdominal aortic aneurysm · ruptured thoracic aneurysm · ruptured thoracic aortic aneurysm · ruptured thoracoabdominal aortic aneurysm · thoracic aortic aneurysm which HAS ruptured · thoracic aortic aneurysm, ruptured · thoracoabdominal aortic aneurysm, ruptured

Data availability: 11 ClinVar variants · 67 GWAS associations (17 studies) · 1 HPO phenotype.

Disease family

An umbrella term covering 2 Mondo subtypes.

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

Subtypes (2): abdominal aortic aneurysm, thoracic aortic aneurysm

Genetics & variants

GWAS landscape

67 GWAS associations across 17 studies. Top hits map to 21 distinct genes (as reported by GWAS).

Top associations by p-value

rsID	p-value	Gene	Risk allele	Odds ratio
rs1333047	5e-40	CDKN2B-AS1	A	0.13
rs12857403	2e-37	LINC00540 - FTH1P7	A	0.15
rs10757279	4e-36	CDKN2B-AS1	A	0.13
rs12875918	5e-35	LINC00540 - FTH1P7	G	0.16
rs4936098	4e-29	ADAMTS8, ZBTB44-DT	A	0.11
chr12:57525756	1e-21		G	0.09
chr20:44570683	2e-21		C	0.12
rs11172113	4e-20	LRP1	T	0.09
rs429358	2e-19	APOE	T	0.12
rs964184	3e-18	ZPR1	G	0.12
chr18:20194159	4e-18		G	0.08
rs10455872	7e-18	LPA	A	0.15
rs3827066	2e-17	ZNF335	C	0.12
chr10:96071212	4e-17		T	0.1
rs1106370	1e-16	SPSB1 - LINC02606	G	0.08
rs9510086	3e-16	LINC00540 - FTH1P7	C	0.21
rs10736085	5e-16	PLCE1	T	0.08
chr10:91004916	9e-16		C	0.08
rs6857	1e-15	LNCOB1, NECTIN2	C	0.12
chr15:48914926	6e-15		A	0.12
rs6507224	6e-15	RBBP8-AS1	A	0.08
rs3176336	1e-14	CDKN1A	A	0.07
rs4970836	3e-14	CELSR2 - PSRC1	G	0.09
rs7255	3e-14	GDF7	T	0.07
rs7528419	9e-14	CELSR2	A	0.09
chr15:78899003	1e-13		C	0.07
rs12054709	1e-13	CAST	G	0.07
rs1892971	2e-13	RNU7-159P - MMP13	G	0.08
rs111704647	2e-13	CHRNA3	C	0.08
rs12730935	1e-12	IL6R	G	0.07

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST90475993	Verma A	2024	22,049	419,651	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90473597	UK Biobank Whole-Genome Sequencing Consortium	2025	5,113	453,327	Whole-genome sequencing of 490,640 UK Biobank participants.
GCST90018783	Sakaue S	2021	3,230	475,964	A cross-population atlas of genetic associations for 220 human phenotypes.
GCST90478017	Verma A	2024	2,825	117,425	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90480203	Verma A	2024	2,825	117,425	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90080048	Backman JD	2021	2,104	385,413	Exome sequencing and analysis of 454,787 UK Biobank participants.
GCST90084034	Backman JD	2021	2,104	385,413	Exome sequencing and analysis of 454,787 UK Biobank participants.
GCST90436154	Zhou W	2018	1,374	400,595	Efficiently controlling for case-control imbalance and sample relatedness in large-scale genetic association studies.
GCST90018563	Sakaue S	2021	1,155	173,601	A cross-population atlas of genetic associations for 220 human phenotypes.
GCST90478016	Verma A	2024	1,071	58,194	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

Tier	Variants
Tier 1: coding	1
Tier 2: splice/UTR	4
Tier 3: regulatory	2
Tier 4: intronic/intergenic	43

MAF distribution

Bucket	Variants
common (>=0.05)	42
low_freq (0.01-0.05)	0
rare (<0.01)	0
unknown	8

Functional consequences

Consequence	Count
unknown	21
intron_variant	15
intergenic_variant	7
3_prime_UTR_variant	4
regulatory_region_variant	2
missense_variant	1

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
rs1333047	9	22124505	A>C,G,T	0.495	intergenic_variant	CDKN2B-AS1	5e-40	Tier 4: intronic/intergenic
rs12857403	13	22291470	A>G,T	0.222	intergenic_variant	LINC00540 - FTH1P7	2e-37	Tier 4: intronic/intergenic
rs10757279	9	22124631	A>G,T	0.422	intergenic_variant	CDKN2B-AS1	4e-36	Tier 4: intronic/intergenic
rs12875918	13	22303324	G>A,C	0.203	intergenic_variant	LINC00540 - FTH1P7	5e-35	Tier 4: intronic/intergenic
rs4936098	11	130410772	A>G,T	0.382	intron_variant	ADAMTS8, ZBTB44-DT	4e-29	Tier 4: intronic/intergenic
chr12:57525756				0.408			1e-21	Tier 4: intronic/intergenic
chr20:44570683				0.154			2e-21	Tier 4: intronic/intergenic
rs11172113	12	57133500	T>C,G	0.416	intron_variant	LRP1	4e-20	Tier 4: intronic/intergenic
rs429358	19	44908684	T>C	0.14	missense_variant	APOE	2e-19	Tier 1: coding
rs964184	11	116778201	G>C	0.14	3_prime_UTR_variant	ZPR1	3e-18	Tier 2: splice/UTR
chr18:20194159				0.489			4e-18	Tier 4: intronic/intergenic
rs10455872	6	160589086	A>G	0.069	intron_variant	LPA	7e-18	Tier 4: intronic/intergenic
rs3827066	20	45957384	C>T	0.129	intron_variant	ZNF335	2e-17	Tier 4: intronic/intergenic
chr10:96071212				0.196			4e-17	Tier 4: intronic/intergenic
rs1106370	1	9383281	G>A,C,T	0.399	intergenic_variant	SPSB1 - LINC02606	1e-16	Tier 4: intronic/intergenic
rs9510086	13	22288301	G>C	0.05	intergenic_variant	LINC00540 - FTH1P7	3e-16	Tier 4: intronic/intergenic
rs10736085	10	94133295	T>A,G	0.494	intron_variant	PLCE1	5e-16	Tier 4: intronic/intergenic
chr10:91004916				0.337			9e-16	Tier 4: intronic/intergenic
rs6857	19	44888997	C>A,G,T	0.132	3_prime_UTR_variant	LNCOB1, NECTIN2	1e-15	Tier 2: splice/UTR
chr15:48914926				0.122			6e-15	Tier 4: intronic/intergenic
rs6507224	18	22611080	A>G,T	0.449	intron_variant	RBBP8-AS1	6e-15	Tier 4: intronic/intergenic
rs3176336	6	36681039	A>G,T	0.396	intron_variant	CDKN1A	1e-14	Tier 4: intronic/intergenic
rs4970836	1	109279175	G>A,C	0.226	intergenic_variant	CELSR2 - PSRC1	3e-14	Tier 4: intronic/intergenic
rs7255	2	20679060	T>A,C	0.471	3_prime_UTR_variant	GDF7	3e-14	Tier 2: splice/UTR
rs7528419	1	109274570	A>G	0.227	3_prime_UTR_variant	CELSR2	9e-14	Tier 2: splice/UTR
chr15:78899003				0.334			1e-13	Tier 4: intronic/intergenic
rs12054709	5	96255876	G>A,T	0.432	intron_variant	CAST	1e-13	Tier 4: intronic/intergenic
rs1892971	11	102924877	G>A	0.219	regulatory_region_variant	RNU7-159P - MMP13	2e-13	Tier 3: regulatory
rs111704647	15	78608308	C>A,G,T	0.294	intron_variant	CHRNA3	2e-13	Tier 4: intronic/intergenic
rs12730935	1	154447416	G>A,C,T	0.397	intron_variant	IL6R	1e-12	Tier 4: intronic/intergenic

ClinVar germline variants

11 retrieved; paginated sample, class counts are floors:

3 uncertain significance, 3 conflicting classifications of pathogenicity, 2 association, 1 pathogenic, 1 pathogenic/likely pathogenic, 1 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
163462	NM_000138.5(FBN1):c.7754T>C (p.Ile2585Thr)	FBN1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1172631	NM_005902.4(SMAD3):c.1A>G (p.Met1Val)	LOC130057352	Pathogenic	criteria provided, multiple submitters, no conflicts
3337667	NM_004612.4(TGFBR1):c.1042T>C (p.Cys348Arg)	TGFBR1	Likely pathogenic	criteria provided, single submitter
161216	NM_000090.4(COL3A1):c.505C>T (p.Leu169Phe)	COL3A1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
568701	NM_000138.5(FBN1):c.1900T>C (p.Ser634Pro)	FBN1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
213840	NM_003238.6(TGFB2):c.356C>T (p.Pro119Leu)	TGFB2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
996563	NM_005744.5(ARIH1):c.43G>C (p.Glu15Gln)	ARIH1	association	no assertion criteria provided
996698	NM_005744.5(ARIH1):c.511C>T (p.Arg171Ter)	ARIH1	association	no assertion criteria provided
996699	NM_005744.5(ARIH1):c.131A>G (p.Glu44Gly)	ARIH1	Uncertain significance	criteria provided, single submitter
161318	NM_002474.3(MYH11):c.4942C>T (p.Arg1648Cys)	MYH11	Uncertain significance	criteria provided, multiple submitters, no conflicts
1297020	NM_018676.4(THSD1):c.1051C>T (p.Gln351Ter)	THSD1	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 28 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
TGFB2	Orphanet:60030	Loeys-Dietz syndrome
TGFB2	Orphanet:91387	Familial thoracic aortic aneurysm and aortic dissection
TGFBR1	Orphanet:284973	Marfan syndrome type 2
TGFBR1	Orphanet:60030	Loeys-Dietz syndrome
TGFBR1	Orphanet:65748	Multiple self-healing squamous epithelioma
TGFBR1	Orphanet:91387	Familial thoracic aortic aneurysm and aortic dissection
THSD1	Orphanet:231160	Familial cerebral saccular aneurysm
THSD1	Orphanet:363999	Non-immune hydrops fetalis
COL3A1	Orphanet:231160	Familial cerebral saccular aneurysm
COL3A1	Orphanet:2500	Acrogeria
COL3A1	Orphanet:286	Vascular Ehlers-Danlos syndrome
COL3A1	Orphanet:636941	Vascular Ehlers-Danlos-polymicrogyria syndrome
COL3A1	Orphanet:86	Familial abdominal aortic aneurysm
FBN1	Orphanet:1885	Isolated ectopia lentis
FBN1	Orphanet:2084	Glaucoma-ectopia lentis-microspherophakia-stiff joints-short stature syndrome
FBN1	Orphanet:2462	Shprintzen-Goldberg syndrome
FBN1	Orphanet:2623	Geleophysic dysplasia
FBN1	Orphanet:2833	Stiff skin syndrome
FBN1	Orphanet:284963	Marfan syndrome type 1
FBN1	Orphanet:284979	Neonatal Marfan syndrome
FBN1	Orphanet:300382	Progeroid and marfanoid aspect-lipodystrophy syndrome
FBN1	Orphanet:3449	Weill-Marchesani syndrome
FBN1	Orphanet:91387	Familial thoracic aortic aneurysm and aortic dissection
FBN1	Orphanet:969	Acromicric dysplasia
MYH11	Orphanet:2241	Megacystis-microcolon-intestinal hypoperistalsis syndrome
MYH11	Orphanet:229	Familial aortic dissection
MYH11	Orphanet:91387	Familial thoracic aortic aneurysm and aortic dissection
MYH11	Orphanet:98829	Acute myeloid leukemia with abnormal bone marrow eosinophils inv(16)(p13q22) or t(16;16)(p13;q22)

Cohort genes → proteins

7 cohort genes, 7 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	7

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
TGFB2	HGNC:11768	ENSG00000092969	P61812	Transforming growth factor beta-2 proprotein	clinvar
TGFBR1	HGNC:11772	ENSG00000106799	P36897	TGF-beta receptor type-1	clinvar
THSD1	HGNC:17754	ENSG00000136114	Q9NS62	Thrombospondin type-1 domain-containing protein 1	clinvar
COL3A1	HGNC:2201	ENSG00000168542	P02461	Collagen alpha-1(III) chain	clinvar
FBN1	HGNC:3603	ENSG00000166147	P35555	Fibrillin-1	clinvar
ARIH1	HGNC:689	ENSG00000166233	Q9Y4X5	E3 ubiquitin-protein ligase ARIH1	clinvar
MYH11	HGNC:7569	ENSG00000133392	P35749	Myosin-11	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
TGFB2	Transforming growth factor beta-2 proprotein	Precursor of the Latency-associated peptide (LAP) and Transforming growth factor beta-2 (TGF-beta-2) chains, which constitute the regulatory and active subunit of TGF-beta-2, respectively.
TGFBR1	TGF-beta receptor type-1	Transmembrane serine/threonine kinase forming with the TGF-beta type II serine/threonine kinase receptor, TGFBR2, the non-promiscuous receptor for the TGF-beta cytokines TGFB1, TGFB2 and TGFB3.
THSD1	Thrombospondin type-1 domain-containing protein 1	Is a positive regulator of nascent focal adhesion assembly, involved in the modulation of endothelial cell attachment to the extracellular matrix.
COL3A1	Collagen alpha-1(III) chain	Collagen type III occurs in most soft connective tissues along with type I collagen.
FBN1	Fibrillin-1	Structural component of the 10-12 nm diameter microfibrils of the extracellular matrix, which conveys both structural and regulatory properties to load-bearing connective tissues.
ARIH1	E3 ubiquitin-protein ligase ARIH1	E3 ubiquitin-protein ligase, which catalyzes ubiquitination of target proteins together with ubiquitin-conjugating enzyme E2 UBE2L3.
MYH11	Myosin-11	Muscle contraction.

Protein-family classification

Druggable: 1 · Difficult: 2 · Unknown: 4 · Druggable fraction: 0.14

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	4.0×	0.626
Scaffold/PPI	1	2.5×	0.626
Transcription factor	1	1.2×	0.626
Other/Unknown	4	1.0×	0.626

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
TGFB2	Other/Unknown	no		TGF-b_propeptide, TGF-b_C, TGFb2
TGFBR1	Kinase	yes	2.7.10.2	TGFB_receptor, Activin_recp, Prot_kinase_dom
THSD1	Other/Unknown	no		TSP1_rpt, TSP1_rpt_sf, THSD1
COL3A1	Other/Unknown	no		Fib_collagen_C, VWF_dom, Collagen
FBN1	Other/Unknown	no		EGF-type_Asp/Asn_hydroxyl_site, EGF, EGF-like_Ca-bd_dom
ARIH1	Transcription factor	no	2.3.2.27	Znf_RING, IBR_dom, Znf_RING/FYVE/PHD
MYH11	Scaffold/PPI	no		IQ_motif_EF-hand-BS, Myosin_head_motor_dom-like, Myosin_tail

Expression context

Cohort genes with no expression data: 0.

7 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)	7
unknown	0

Top tissues across cohort

Tissue	Cohort genes
visceral pleura	2
skin of hip	2
calcaneal tendon	1
cartilage tissue	1
tendon	1
saphenous vein	1
tibia	1
apex of heart	1
right lung	1
ventricular zone	1
parietal pleura	1
decidua	1
synovial joint	1
cortical plate	1
oocyte	1
secondary oocyte	1
lower esophagus	1
lower esophagus muscularis layer	1
right coronary artery	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
TGFB2	206	ubiquitous	marker	calcaneal tendon, tendon, cartilage tissue
TGFBR1	269	ubiquitous	marker	saphenous vein, tibia, visceral pleura
THSD1	138	broad	marker	ventricular zone, right lung, apex of heart
COL3A1	281	ubiquitous	marker	skin of hip, parietal pleura, visceral pleura
FBN1	275	ubiquitous	marker	synovial joint, skin of hip, decidua
ARIH1	292	ubiquitous	marker	secondary oocyte, oocyte, cortical plate
MYH11	143	broad	marker	right coronary artery, lower esophagus, lower esophagus muscularis layer

Protein interactions among cohort

Intra-cohort edges: 2.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
TGFBR1	4,828
MYH11	3,818
FBN1	3,640
COL3A1	3,629
ARIH1	2,422
THSD1	473
TGFB2	43

Intra-cohort edges

A	B	Sources
COL3A1	FBN1	string_interaction
FBN1	TGFBR1	string_interaction

Structural data

PDB: 6 · AlphaFold-only: 1 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
TGFBR1	P36897	44
TGFB2	P61812	11
COL3A1	P02461	11
FBN1	P35555	11
ARIH1	Q9Y4X5	10
MYH11	P35749	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
THSD1	Q9NS62	59.46

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 83. Enrichment computed across 7 evidence-associated genes (7 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 7 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
TGF-beta receptor signaling activates SMADs	3	139.8×	8e-05	TGFB2, TGFBR1, FBN1
TGFBR3 regulates TGF-beta signaling	2	407.9×	4e-04	TGFB2, TGFBR1
Signaling by TGFBR3	2	105.2×	0.004	TGFB2, TGFBR1
Elastic fibre formation	2	96.0×	0.004	TGFB2, FBN1
Molecules associated with elastic fibres	2	88.2×	0.004	TGFB2, FBN1
Signaling by TGF-beta Receptor Complex	2	57.2×	0.007	TGFB2, TGFBR1
ECM proteoglycans	2	42.9×	0.011	TGFB2, COL3A1
Integrin cell surface interactions	2	38.4×	0.012	COL3A1, FBN1
Loss of Function of TGFBR2 in Cancer	1	543.8×	0.014	TGFBR1
TGFBR2 Kinase Domain Mutants in Cancer	1	543.8×	0.014	TGFBR1
Signaling by TGFB family members	2	33.0×	0.014	TGFB2, TGFBR1
TGFBR1 LBD Mutants in Cancer	1	407.9×	0.017	TGFBR1
Loss of Function of TGFBR1 in Cancer	1	326.3×	0.018	TGFBR1
Loss of Function of SMAD2/3 in Cancer	1	271.9×	0.018	TGFBR1
Signaling by TGF-beta Receptor Complex in Cancer	1	271.9×	0.018	TGFBR1
SMAD2/3 Phosphorylation Motif Mutants in Cancer	1	271.9×	0.018	TGFBR1
TGFBR1 KD Mutants in Cancer	1	271.9×	0.018	TGFBR1
TGF-beta receptor signaling in EMT (epithelial to mesenchymal transition)	1	96.0×	0.038	TGFBR1
Sema4D in semaphorin signaling	1	96.0×	0.038	MYH11
Scavenging by Class A Receptors	1	85.9×	0.038	COL3A1
RHO GTPases activate CIT	1	85.9×	0.038	MYH11
RHO GTPases Activate ROCKs	1	85.9×	0.038	MYH11
Modulation of host responses by IFN-stimulated genes	1	85.9×	0.038	ARIH1
Fibronectin matrix formation	1	81.6×	0.038	COL3A1
Sema4D induced cell migration and growth-cone collapse	1	81.6×	0.038	MYH11
RHO GTPases activate PAKs	1	77.7×	0.038	MYH11
Developmental Lineage of Mammary Gland Myoepithelial Cells	1	77.7×	0.038	MYH11
Disease	3	5.6×	0.038	TGFBR1, THSD1, ARIH1
Syndecan interactions	1	60.4×	0.046	COL3A1
Downregulation of TGF-beta receptor signaling	1	58.3×	0.046	TGFBR1

GO biological processes by enrichment

GO term	Cohort genes	Fold	FDR	Sample cohort genes
positive regulation of epithelial to mesenchymal transition involved in endocardial cushion formation	2	1203.7×	9e-05	TGFB2, TGFBR1
heart development	4	45.0×	9e-05	TGFB2, TGFBR1, COL3A1, FBN1
wound healing	3	97.6×	2e-04	TGFB2, TGFBR1, COL3A1
collagen fibril organization	3	96.3×	2e-04	TGFB2, TGFBR1, COL3A1
elastic fiber assembly	2	437.7×	3e-04	COL3A1, MYH11
transforming growth factor beta receptor signaling pathway	3	68.1×	3e-04	TGFB2, TGFBR1, COL3A1
cardiac epithelial to mesenchymal transition	2	343.9×	4e-04	TGFB2, TGFBR1
ventricular trabecula myocardium morphogenesis	2	300.9×	4e-04	TGFB2, TGFBR1
skeletal system development	3	53.9×	4e-04	TGFB2, TGFBR1, FBN1
neuron fate commitment	2	229.3×	6e-04	TGFB2, TGFBR1
ventricular septum morphogenesis	2	123.5×	0.002	TGFB2, TGFBR1
positive regulation of SMAD protein signal transduction	2	109.4×	0.002	TGFB2, TGFBR1
positive regulation of epithelial to mesenchymal transition	2	90.8×	0.003	TGFB2, TGFBR1
epithelial to mesenchymal transition	2	89.2×	0.003	TGFB2, TGFBR1
cellular response to transforming growth factor beta stimulus	2	78.9×	0.004	TGFBR1, FBN1
extracellular structure organization	1	2407.4×	0.004	TGFBR1
regulation of timing of catagen	1	2407.4×	0.004	TGFB2
positive regulation of activation-induced cell death of T cells	1	2407.4×	0.004	TGFB2
regulation of apoptotic process involved in outflow tract morphogenesis	1	2407.4×	0.004	TGFB2
negative regulation of epithelial to mesenchymal transition involved in endocardial cushion formation	1	2407.4×	0.004	TGFB2
positive regulation of cell growth	2	52.3×	0.006	TGFB2, TGFBR1
cardioblast differentiation	1	1203.7×	0.007	TGFB2
PKR/eIFalpha signaling	1	1203.7×	0.007	ARIH1
uterine wall breakdown	1	1203.7×	0.007	TGFB2
substantia propria of cornea development	1	1203.7×	0.007	TGFB2
epicardium morphogenesis	1	1203.7×	0.007	TGFBR1
male gonad development	2	44.6×	0.007	TGFB2, TGFBR1
skeletal muscle myosin thick filament assembly	1	802.5×	0.007	MYH11
transforming growth factor beta1 production	1	802.5×	0.007	COL3A1
limb joint morphogenesis	1	802.5×	0.007	COL3A1

Therapeutics

Drugs indicated for this disease

No approved or late-stage (phase ≥3) drug is indicated for this disease; the following are in earlier-phase trials only.

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): Melatonin, Sodium Chloride.

Drug target analysis

Approved (phase 4): 1 · Phase ≥3: 1 · Phased (≥1): 2 · Undrugged: 5

Druggability breadth: 3 of 7 evidence-associated genes (43%) 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
TGFBR1	MOMELOTINIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
TGFBR1	28	4
TGFB2	1	2
THSD1	0	0
COL3A1	0	0
FBN1	0	0
ARIH1	0	0
MYH11	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
MOMELOTINIB	4	TGFBR1
DABRAFENIB	4	TGFBR1
NINTEDANIB	4	TGFBR1
DASATINIB	4	TGFBR1
CRIZOTINIB	4	TGFBR1
SARACATINIB	3	TGFBR1
CANERTINIB	3	TGFBR1
TESEVATINIB	3	TGFBR1
CEDIRANIB	3	TGFBR1
LESTAURTINIB	3	TGFBR1
GALUNISERTIB	2	TGFB2, TGFBR1
OSI-632	2	TGFBR1
OSI-027	2	TGFBR1
VACTOSERTIB	2	TGFBR1
BMS-690514	2	TGFBR1
DANUSERTIB	2	TGFBR1
R-406	2	TGFBR1
AT-9283	2	TGFBR1
ZILURGISERTIB	2	TGFBR1
TOZASERTIB	2	TGFBR1
KER-047	2	TGFBR1
GSK-1070916	1	TGFBR1
TAK-901	1	TGFBR1
XL-228	1	TGFBR1
MK-5108	1	TGFBR1
LY-3200882	1	TGFBR1
CYC-116	1	TGFBR1
PF-06952229	1	TGFBR1

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 2.

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

Symbol	Assays	Type breakdown
TGFBR1	541	Binding:516, Functional:13, ADMET:12
TGFB2	3	Binding:3

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
TGFBR1	2.7.10.2, 2.7.11.30	non-specific protein-tyrosine kinase, receptor protein serine/threonine kinase
ARIH1	2.3.2.27, 2.3.2.31	RING-type E3 ubiquitin transferase, RBR-type E3 ubiquitin transferase

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
TGFBR1	541

Pharmacogenomics

Cohort genes with a PharmGKB record: 7; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

28 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	TGFBR1
DABRAFENIB	4	TGFBR1
NINTEDANIB	4	TGFBR1
DASATINIB	4	TGFBR1
CRIZOTINIB	4	TGFBR1
SARACATINIB	3	TGFBR1
CANERTINIB	3	TGFBR1
TESEVATINIB	3	TGFBR1
CEDIRANIB	3	TGFBR1
LESTAURTINIB	3	TGFBR1
GALUNISERTIB	2	TGFB2, TGFBR1
OSI-632	2	TGFBR1
OSI-027	2	TGFBR1
VACTOSERTIB	2	TGFBR1
BMS-690514	2	TGFBR1
DANUSERTIB	2	TGFBR1
R-406	2	TGFBR1
AT-9283	2	TGFBR1
ZILURGISERTIB	2	TGFBR1
TOZASERTIB	2	TGFBR1
KER-047	2	TGFBR1
GSK-1070916	1	TGFBR1
TAK-901	1	TGFBR1
XL-228	1	TGFBR1
MK-5108	1	TGFBR1
LY-3200882	1	TGFBR1
CYC-116	1	TGFBR1
PF-06952229	1	TGFBR1

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	TGFBR1
B	Phased (≥1) drug, not yet approved	1	TGFB2
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	5	THSD1, COL3A1, FBN1, ARIH1, MYH11

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
THSD1	0	—
COL3A1	0	—
FBN1	0	—
ARIH1	0	—
MYH11	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 149.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	134
PHASE4	4
PHASE2	4
PHASE3	3
PHASE2/PHASE3	2
PHASE1	2

Top trials by phase / activity

NCT	Phase	Status	Title
NCT00094575	PHASE4	COMPLETED	Standard Open Surgery Versus Endovascular Repair of Abdominal Aortic Aneurysm (AAA)
NCT01033370	PHASE4	TERMINATED	A Safety and Efficacy Study of Blood Pressure Control in Acute Aortic Emergencies - A Pilot Study (PROMPT)
NCT01107366	PHASE4	WITHDRAWN	ATLANTIS:Extensive Type A Dissections and Thoracic/ Thoraco-Abdominal Aneurysms Repair With LupiAe Hybrid TechNique
NCT01354119	PHASE4	TERMINATED	Long-term Benefit of Aortic Stent-graft in Patients With Distal Aortic Dissection
NCT05744219	PHASE3	RECRUITING	Improved Recovery by Iron Following Surgery With Blood Loss, the IRIS-trial
NCT00315926	PHASE2/PHASE3	COMPLETED	Melatonin and Cardiac Outcome After Major Surgery
NCT00478803	PHASE3	COMPLETED	Conservative Aortic Valve Surgery for Aortic Insufficiency and Aneurysms of the Aortic Root. CAVIAAR
NCT00671203	PHASE3	COMPLETED	Prevention of Colon Ischemia During Aortic Aneurysm (AAA) Repair
NCT00794092	PHASE2/PHASE3	COMPLETED	Magnetic Resonance Imaging of Aortic Aneurysm Instability
NCT00549354	PHASE2	UNKNOWN	Abdominal Aortic/Aorto-Iliac Aneurysm Endoluminal Graft Study
NCT00701142	PHASE2	COMPLETED	Haemocomplettan® P During Aortic Replacement
NCT01256372	PHASE2	COMPLETED	An Trial of Two Dosing Regimens of AP214 for the Prevention of Kidney Injury in Patients Undergoing Cardiac Surgery
NCT05350683	PHASE2	COMPLETED	Effect of Remote Ischemic Preconditioning on the Incidence of Contrast Induced Nephropathy in Patients Undergoing EVAR
NCT01523262	PHASE1	UNKNOWN	Preventing Myocardial Ischemia by Preconditioning in Elective Operation for Abdominal Aortic Aneurysm
NCT02729064	PHASE1	UNKNOWN	Intraoperative Nasal Insulin Effect on Plasma and CSF Insulin Concentration and Blood Glucose
NCT01757730	Not specified	RECRUITING	Magnetic Resonance Elastography as a Method to Estimate Stiffness of Soft Tissues
NCT02306200	Not specified	RECRUITING	Cardiovascular Health Improvement Project
NCT03214601	Not specified	ACTIVE_NOT_RECRUITING	Early Feasibility Study of the RelayBranch Thoracic Stent-Graft System
NCT03233087	Not specified	RECRUITING	Diagnosis and Prognosis for Aortic Aneurysm aNd Dissection in Anzhen(DPANDA) Study
NCT03481075	Not specified	RECRUITING	Patient Specific Biomechanical Modeling of Abdominal Aortic Aneurysm to Improve Aortic Endovascular Repair
NCT04005976	Not specified	RECRUITING	Montalcino Aortic Consortium: Precision Medicine for Heritable Thoracic Aortic Disease
NCT04149600	Not specified	ACTIVE_NOT_RECRUITING	Identification of Genetic Causes of Calcific Aortic Valve Disease
NCT04269447	Not specified	ENROLLING_BY_INVITATION	Prospective Aortic Biobank of POP-STAR
NCT04471909	Not specified	RECRUITING	NEXUS Aortic Arch Clinical Study to Evaluate Safety and Effectiveness
NCT04676672	Not specified	ACTIVE_NOT_RECRUITING	A PMCF Study in Patients With Acute or Chronic Aortic Dissection or Aortic Aneurysm Treated With E-vita OPEN NEO
NCT04966247	Not specified	ACTIVE_NOT_RECRUITING	Cerebral Protection in Aortic Arch Surgery
NCT04986709	Not specified	ACTIVE_NOT_RECRUITING	PMCF Study in Patients With Acute or Chronic Aortic Dissection or Aortic Aneurysm Treated With E-vita OPEN NEO
NCT05479305	Not specified	RECRUITING	Evaluation of the Valiant Captivia Physician Fenestrated Stent Graft System in Aortic Arch and Descending Thoracic Aorta Pathologies
NCT05531084	Not specified	NOT_YET_RECRUITING	Safety and Effectiveness of Surgeon-Modified Stent Grafts forTreatment of Complex Aortic Aneurysms
NCT05603520	Not specified	RECRUITING	Phenotyping Heterogeneity and Regionality of the Aorta
NCT05639400	Not specified	ACTIVE_NOT_RECRUITING	Thoraflex Hybrid and Relay Extension Post-Approval Study
NCT05774938	Not specified	RECRUITING	QoL After Complex Endovascular Aortic Repair
NCT06059053	Not specified	RECRUITING	Outcome of the Semibranch in Pararenal and Thoracoabdominal Aortic Pathologies. A Prospective, Multicentre Registry.
NCT06147024	Not specified	RECRUITING	Utilizing 3D Printed Personalized Aortic Lesion Models in Preoperative Assessment
NCT06286358	Not specified	RECRUITING	Aortopathy Relationship To Imagery and Kinocardiography Features (ARTIK)
NCT06365138	Not specified	RECRUITING	Analysis of Individual Activity at the Time of Aortic Rupture in Patients With Abdominal Aortic Aneurysms
NCT06374355	Not specified	RECRUITING	Semibranch Registry - Retrospective
NCT06411990	Not specified	RECRUITING	Laser In Situ Fenestration Study
NCT06501872	Not specified	RECRUITING	Safety and Effectiveness of Physician-Modified Fenestrated and Branched Aortic Endografting for the Treatment of Thoracoabdominal and Pararenal Aortic Aneurysms
NCT06514170	Not specified	RECRUITING	Gastrointestinal Dysfunction in Aortic Surgery Patients

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
FERRIC CARBOXYMALTOSE	4	1
MELATONIN	4	1
MODIMELANOTIDE	2	1

Cohort genes: TGFB2, TGFBR1, THSD1, COL3A1, FBN1, ARIH1, MYH11
Drugs: Ferric Carboxymaltose, Melatonin