Aortic aneurysm, familial thoracic 2

Summary

Aortic aneurysm, familial thoracic 2 (MONDO:0011770) is a disease with 6 cohort genes.

At a glance

• Cohort genes: 6
• ClinVar variants: 6

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	aortic aneurysm, familial thoracic 2
Mondo ID	MONDO:0011770
MeSH	C564627
OMIM	607087
UMLS	C1846837
MedGen	335538
GARD	0015409
Is cancer (heuristic)	no

Also known as: AAT2 · aortic aneurysm, familial thoracic 2 · FAA2

Data availability: 6 ClinVar variants.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › familial thoracic aortic aneurysm and aortic dissection › aortic aneurysm, familial thoracic 2

Related subtypes (8): aortic aneurysm, familial thoracic 4, aortic aneurysm, familial thoracic 6, aortic aneurysm, familial thoracic 7, aortic aneurysm, familial thoracic 8, aortic aneurysm, familial thoracic 9, aortic aneurysm, familial thoracic 10, aortic aneurysm, familial thoracic 1, aortic aneurysm, familial thoracic 12

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:

3 uncertain significance, 2 conflicting classifications of pathogenicity, 1 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
18276	NM_001613.4(ACTA2):c.445C>T (p.Arg149Cys)	ACTA2	Pathogenic	criteria provided, multiple submitters, no conflicts
264534	NM_001110556.2(FLNA):c.3995A>G (p.Asp1332Gly)	FLNA	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
213737	NM_030777.4(SLC2A10):c.1370C>T (p.Ala457Val)	SLC2A10	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
492834	NM_000090.4(COL3A1):c.3008T>C (p.Leu1003Pro)	COL3A1	Uncertain significance	no assertion criteria provided
492831	NM_000138.5(FBN1):c.7099G>A (p.Gly2367Arg)	FBN1	Uncertain significance	criteria provided, multiple submitters, no conflicts
492832	NM_001999.4(FBN2):c.2392G>A (p.Gly798Ser)	FBN2	Uncertain significance	no assertion criteria provided

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 32 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
ACTA2	Orphanet:2573	Moyamoya disease
ACTA2	Orphanet:404463	Multisystemic smooth muscle dysfunction syndrome
ACTA2	Orphanet:91387	Familial thoracic aortic aneurysm and aortic dissection
SLC2A10	Orphanet:3342	Arterial tortuosity syndrome
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
FBN2	Orphanet:115	Congenital contractural arachnodactyly
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

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
ACTA2	HGNC:130	ENSG00000107796	P62736	Actin, aortic smooth muscle	clinvar
SLC2A10	HGNC:13444	ENSG00000197496	O95528	Solute carrier family 2, facilitated glucose transporter member 10	clinvar
COL3A1	HGNC:2201	ENSG00000168542	P02461	Collagen alpha-1(III) chain	clinvar
FBN1	HGNC:3603	ENSG00000166147	P35555	Fibrillin-1	clinvar
FBN2	HGNC:3604	ENSG00000138829	P35556	Fibrillin-2	clinvar
FLNA	HGNC:3754	ENSG00000196924	P21333	Filamin-A	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
ACTA2	Actin, aortic smooth muscle	Actins are highly conserved proteins that are involved in various types of cell motility and are ubiquitously expressed in all eukaryotic cells.
SLC2A10	Solute carrier family 2, facilitated glucose transporter member 10	Facilitative glucose transporter required for the development of the cardiovascular system.
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.
FBN2	Fibrillin-2	Fibrillins are structural components of 10-12 nm extracellular calcium-binding microfibrils, which occur either in association with elastin or in elastin-free bundles.
FLNA	Filamin-A	Promotes orthogonal branching of actin filaments and links actin filaments to membrane glycoproteins.

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
Transporter	1	13.0×	0.224
Antibody/Immunoglobulin	1	4.9×	0.283
Other/Unknown	4	1.2×	0.458

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
ACTA2	Other/Unknown	no		Actin, Actin_CS, Actin/actin-like_CS
SLC2A10	Transporter	yes		Sugar/inositol_transpt, MFS_sugar_transport-like, Sugar_transporter_CS
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
FBN2	Other/Unknown	no		EGF-type_Asp/Asn_hydroxyl_site, EGF, EGF-like_Ca-bd_dom
FLNA	Antibody/Immunoglobulin	yes		Filamin/ABP280_rpt, Actinin_actin-bd_CS, CH_dom

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
skin of hip	2
blood vessel layer	1
cauda epididymis	1
saphenous vein	1
bronchial epithelial cell	1
epithelium of bronchus	1
tibia	1
parietal pleura	1
visceral pleura	1
decidua	1
synovial joint	1
adrenal tissue	1
cartilage tissue	1
placenta	1
popliteal artery	1
right coronary artery	1
tibial artery	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
ACTA2	289	ubiquitous	marker	cauda epididymis, blood vessel layer, saphenous vein
SLC2A10	235	ubiquitous	marker	tibia, bronchial epithelial cell, epithelium of bronchus
COL3A1	281	ubiquitous	marker	skin of hip, parietal pleura, visceral pleura
FBN1	275	ubiquitous	marker	synovial joint, skin of hip, decidua
FBN2	194	ubiquitous	marker	cartilage tissue, placenta, adrenal tissue
FLNA	285	ubiquitous	marker	right coronary artery, popliteal artery, tibial artery

Protein interactions among cohort

Intra-cohort edges: 6.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
FLNA	5,321
FBN1	3,640
COL3A1	3,629
FBN2	2,570
SLC2A10	2,046
ACTA2	774

Intra-cohort edges

A	B	Sources
COL3A1	FBN1	string_interaction
COL3A1	FBN2	string_interaction
COL3A1	SLC2A10	string_interaction
FBN1	FBN2	intact, string_interaction
FBN1	SLC2A10	string_interaction
FBN2	SLC2A10	string_interaction

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
FLNA	P21333	26
COL3A1	P02461	11
FBN1	P35555	11

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
ACTA2	P62736	95.43
SLC2A10	O95528	74.78
FBN2	P35556

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 39. Enrichment computed across 6 evidence-associated genes (6 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 6 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Elastic fibre formation	2	112.0×	0.003	FBN1, FBN2
Molecules associated with elastic fibres	2	102.9×	0.003	FBN1, FBN2
Defective SLC2A10 causes arterial tortuosity syndrome (ATS)	1	1903.3×	0.006	SLC2A10
Non-integrin membrane-ECM interactions	2	51.4×	0.006	ACTA2, COL3A1
Integrin cell surface interactions	2	44.8×	0.006	COL3A1, FBN1
Degradation of the extracellular matrix	2	39.2×	0.007	FBN1, FBN2
OAS antiviral response	1	211.5×	0.026	FLNA
GP1b-IX-V activation signalling	1	158.6×	0.027	FLNA
Regulation of CDH1 Function	1	158.6×	0.027	ACTA2
Cell-extracellular matrix interactions	1	112.0×	0.027	FLNA
Scavenging by Class A Receptors	1	100.2×	0.027	COL3A1
Fibronectin matrix formation	1	95.2×	0.027	COL3A1
NOTCH4 Intracellular Domain Regulates Transcription	1	95.2×	0.027	ACTA2
Cellular hexose transport	1	90.6×	0.027	SLC2A10
RHO GTPases activate PAKs	1	90.6×	0.027	FLNA
Developmental Lineage of Mammary Gland Myoepithelial Cells	1	90.6×	0.027	ACTA2
Signaling by NOTCH4	1	82.8×	0.028	ACTA2
Syndecan interactions	1	70.5×	0.031	COL3A1
MET activates PTK2 signaling	1	63.4×	0.032	COL3A1
TGF-beta receptor signaling activates SMADs	1	54.4×	0.036	FBN1
Formation of the dystrophin-glycoprotein complex (DGC)	1	51.4×	0.036	ACTA2
Smooth Muscle Contraction	1	44.3×	0.037	ACTA2
Collagen chain trimerization	1	43.3×	0.037	COL3A1
Signaling by PDGF	1	42.3×	0.037	COL3A1
NCAM1 interactions	1	41.4×	0.037	COL3A1
Developmental Lineage of Pancreatic Ductal Cells	1	38.1×	0.039	COL3A1
Assembly of collagen fibrils and other multimeric structures	1	33.4×	0.043	COL3A1
Collagen degradation	1	29.3×	0.045	COL3A1
Signaling by NOTCH	1	29.3×	0.045	ACTA2
Collagen biosynthesis and modifying enzymes	1	28.4×	0.045	COL3A1

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
obsolete sequestering of TGFbeta in extracellular matrix	2	1404.3×	8e-05	FBN1, FBN2
embryonic eye morphogenesis	2	510.7×	3e-04	FBN1, FBN2
skin development	2	147.8×	0.003	SLC2A10, COL3A1
camera-type eye development	2	119.5×	0.003	FBN1, FBN2
negative regulation of connective tissue growth factor production	1	2808.7×	0.004	SLC2A10
positive regulation of hepatic stellate cell contraction	1	2808.7×	0.004	ACTA2
regulation of membrane repolarization during atrial cardiac muscle cell action potential	1	2808.7×	0.004	FLNA
regulation of membrane repolarization during cardiac muscle cell action potential	1	2808.7×	0.004	FLNA
cellular response to transforming growth factor beta stimulus	2	92.1×	0.004	ACTA2, FBN1
glucose metabolic process	2	85.1×	0.004	FBN1, FBN2
cerebral cortex development	2	68.5×	0.004	COL3A1, FLNA
positive regulation of hepatic stellate cell migration	1	1404.3×	0.006	ACTA2
negative regulation of proteoglycan biosynthetic process	1	1404.3×	0.006	SLC2A10
transforming growth factor beta1 production	1	936.2×	0.006	COL3A1
limb joint morphogenesis	1	936.2×	0.006	COL3A1
post-embryonic eye morphogenesis	1	936.2×	0.006	FBN1
juxtaglomerular apparatus development	1	936.2×	0.006	ACTA2
tubulin deacetylation	1	936.2×	0.006	FLNA
positive regulation of proteoglycan biosynthetic process	1	936.2×	0.006	SLC2A10
glucose homeostasis	2	43.5×	0.006	FBN1, FBN2
formation of radial glial scaffolds	1	702.2×	0.006	FLNA
obsolete sequestering of BMP in extracellular matrix	1	702.2×	0.006	FBN1
endochondral bone morphogenesis	1	702.2×	0.006	COL3A1
aorta smooth muscle tissue morphogenesis	1	702.2×	0.006	COL3A1
glomerular mesangial cell development	1	702.2×	0.006	ACTA2
negative regulation of integrin-mediated signaling pathway	1	702.2×	0.006	SLC2A10
adenylate cyclase-inhibiting dopamine receptor signaling pathway	1	561.7×	0.006	FLNA
vascular associated smooth muscle contraction	1	561.7×	0.006	ACTA2
galactose transmembrane transport	1	561.7×	0.006	SLC2A10
embryonic skeletal joint development	1	561.7×	0.006	SLC2A10

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 1 · Undrugged: 5

Druggability breadth: 2 of 6 evidence-associated genes (33%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
FLNA	1	2
ACTA2	0	0
SLC2A10	0	0
COL3A1	0	0
FBN1	0	0
FBN2	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
MOLIBRESIB	2	FLNA

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
FLNA	7	Binding:7

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

1 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)
MOLIBRESIB	2	FLNA

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	1	FLNA
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	1	SLC2A10
E	Difficult family or no structure, no drug	4	ACTA2, COL3A1, FBN1, FBN2

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)
ACTA2	0	—
SLC2A10	0	—
COL3A1	0	—
FBN1	0	—
FBN2	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.