Aortic aneurysm, familial thoracic 10

Summary

Aortic aneurysm, familial thoracic 10 (MONDO:0014950) is a disease caused by LOX (GenCC Strong), with 4 cohort genes.

At a glance

• Causal gene: LOX (GenCC Strong)
• Cohort genes: 4
• ClinVar variants: 59

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	aortic aneurysm, familial thoracic 10
Mondo ID	MONDO:0014950
OMIM	617168
UMLS	C4284414
MedGen	924785
GARD	0016207
Is cancer (heuristic)	no

Also known as: AAT10 · aortic aneurysm, familial thoracic 10 · aortic aneurysm, familial thoracic type 10 · familial thoracic aortic aneurysm and aortic dissection caused by mutation in LOX · LOX familial thoracic aortic aneurysm and aortic dissection

Data availability: 59 ClinVar variants · 4 GenCC gene-disease records.

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 10

Related subtypes (8): aortic aneurysm, familial thoracic 4, aortic aneurysm, familial thoracic 2, aortic aneurysm, familial thoracic 6, aortic aneurysm, familial thoracic 7, aortic aneurysm, familial thoracic 8, aortic aneurysm, familial thoracic 9, 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

59 retrieved; paginated sample, class counts are floors:

19 uncertain significance, 10 conflicting classifications of pathogenicity, 6 pathogenic, 6 pathogenic/likely pathogenic, 6 likely benign, 5 likely pathogenic, 4 benign/likely benign, 2 benign, 1 not provided

ClinVar	Variant (HGVS)	Gene	Classification	Review
1098840	NM_002317.7(LOX):c.53_66del (p.Leu18fs)	LOX	Pathogenic	criteria provided, single submitter
1098842	NM_002317.7(LOX):c.445G>T (p.Gly149Ter)	LOX	Pathogenic	criteria provided, single submitter
228806	NM_002317.7(LOX):c.893T>G (p.Met298Arg)	LOX	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2584393	NM_002317.7(LOX):c.681C>G (p.Tyr227Ter)	LOX	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
267291	NM_002317.7(LOX):c.839G>T (p.Ser280Ile)	LOX	Pathogenic	no assertion criteria provided
267293	NM_002317.7(LOX):c.800A>C (p.Gln267Pro)	LOX	Pathogenic	no assertion criteria provided
3899267	NM_002317.7(LOX):c.713dup (p.Cys238fs)	LOX	Pathogenic	criteria provided, single submitter
4056321	NM_002317.7(LOX):c.1106_1109dup (p.Lys370fs)	LOX	Pathogenic	criteria provided, single submitter
489315	NM_002317.7(LOX):c.1035+1G>A	LOX	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1098841	NM_002317.7(LOX):c.351del (p.Arg118fs)	SRFBP1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1804003	NM_002317.7(LOX):c.389C>A (p.Ser130Ter)	SRFBP1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
974875	NM_002317.7(LOX):c.1009C>T (p.Arg337Ter)	SRFBP1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
4845254	NM_000393.5(COL5A2):c.1717G>T (p.Gly573Cys)	COL5A2	Likely pathogenic	no assertion criteria provided
1708066	NM_002317.7(LOX):c.1024_1025dup (p.Gln345fs)	LOX	Likely pathogenic	criteria provided, single submitter
1806188	NM_002317.7(LOX):c.144G>A (p.Trp48Ter)	LOX	Likely pathogenic	criteria provided, single submitter
267292	NM_002317.7(LOX):c.125G>A (p.Trp42Ter)	LOX	Likely pathogenic	criteria provided, single submitter
3336903	NM_002317.7(LOX):c.1222dup (p.Tyr408fs)	LOX	Likely pathogenic	criteria provided, multiple submitters, no conflicts
1188568	NM_002317.7(LOX):c.31G>C (p.Gly11Arg)	LOX	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1330410	NM_002317.7(LOX):c.302C>T (p.Ala101Val)	LOX	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1343849	NM_002317.7(LOX):c.840C>A (p.Ser280Arg)	LOX	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1345289	NM_002317.7(LOX):c.1035G>A (p.Gln345=)	LOX	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1434346	NM_002317.7(LOX):c.1190G>A (p.Arg397His)	LOX	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1450865	NM_002317.7(LOX):c.355C>A (p.Pro119Thr)	LOX	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2446432	NM_002317.7(LOX):c.1132G>C (p.Val378Leu)	LOX	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
521345	NM_002317.7(LOX):c.235G>A (p.Ala79Thr)	LOX	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
617849	NM_002317.7(LOX):c.1044T>A (p.Ser348Arg)	LOX	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1307429	NM_002317.7(LOX):c.493G>C (p.Gly165Arg)	SRFBP1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1098843	NM_002317.7(LOX):c.917T>C (p.Leu306Pro)	LOX	Uncertain significance	criteria provided, single submitter
1215073	NM_002317.7(LOX):c.364C>T (p.Arg122Cys)	LOX	Uncertain significance	criteria provided, multiple submitters, no conflicts
1215447	NM_002317.7(LOX):c.1189C>T (p.Arg397Cys)	LOX	Uncertain significance	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 6 · Orphanet: 4 · 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
LOX	Strong	Unknown	familial thoracic aortic aneurysm and aortic dissection	6

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
LOX	Orphanet:91387	Familial thoracic aortic aneurysm and aortic dissection
COL5A2	Orphanet:287	Classical Ehlers-Danlos syndrome
MYLK	Orphanet:2241	Megacystis-microcolon-intestinal hypoperistalsis syndrome
MYLK	Orphanet:91387	Familial thoracic aortic aneurysm and aortic dissection

Cohort genes → proteins

4 cohort genes, 4 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	4

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
LOX	HGNC:6664	ENSG00000113083	P28300	Protein-lysine 6-oxidase	gencc,clinvar
COL5A2	HGNC:2210	ENSG00000204262	P05997	Collagen alpha-2(V) chain	clinvar
SRFBP1	HGNC:26333	ENSG00000151304	Q8NEF9	Serum response factor-binding protein 1	clinvar
MYLK	HGNC:7590	ENSG00000065534	Q15746	Myosin light chain kinase, smooth muscle	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
LOX	Protein-lysine 6-oxidase	Responsible for the post-translational oxidative deamination of peptidyl lysine residues in precursors to fibrous collagen and elastin.
COL5A2	Collagen alpha-2(V) chain	Type V collagen is a member of group I collagen (fibrillar forming collagen).
SRFBP1	Serum response factor-binding protein 1	May be involved in regulating transcriptional activation of cardiac genes during the aging process.
MYLK	Myosin light chain kinase, smooth muscle	Calcium/calmodulin-dependent myosin light chain kinase implicated in smooth muscle contraction via phosphorylation of myosin light chains (MLC).

Protein-family classification

Druggable: 2 · Difficult: 0 · Unknown: 2 · 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	6.9×	0.410
Enzyme (other)	1	3.0×	0.441
Other/Unknown	2	0.9×	0.769

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
LOX	Enzyme (other)	yes	1.4.3.13	Lysyl_oxidase, Lysyl_oxidase_CS,
COL5A2	Other/Unknown	no		Fib_collagen_C, VWF_dom, Collagen
SRFBP1	Other/Unknown	no		Bud22_dom, Bud22/SRFB1
MYLK	Kinase	yes	2.7.11.18	Prot_kinase_dom, Ig_sub2, Ig_sub

Expression context

Cohort genes with no expression data: 0.

4 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)	4
unknown	0

Top tissues across cohort

Tissue	Cohort genes
calcaneal tendon	2
stromal cell of endometrium	2
tibia	1
periodontal ligament	1
tendon of biceps brachii	1
colonic epithelium	1
male germ line stem cell (sensu Vertebrata) in testis	1
cauda epididymis	1
saphenous vein	1
seminal vesicle	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
LOX	242	ubiquitous	marker	stromal cell of endometrium, calcaneal tendon, tibia
COL5A2	266	ubiquitous	marker	tendon of biceps brachii, periodontal ligament, stromal cell of endometrium
SRFBP1	235	ubiquitous	marker	calcaneal tendon, male germ line stem cell (sensu Vertebrata) in testis, colonic epithelium
MYLK	289	ubiquitous	marker	cauda epididymis, saphenous vein, seminal vesicle

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
LOX	5,479
MYLK	2,763
SRFBP1	2,607
COL5A2	2,286

Structural data

PDB: 1 · AlphaFold-only: 3 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
MYLK	Q15746	8

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
LOX	P28300	68.06
SRFBP1	Q8NEF9	62.20
COL5A2	P05997	53.15

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 25. Enrichment computed across 4 evidence-associated genes (3 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 3 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Assembly of collagen fibrils and other multimeric structures	2	133.6×	0.002	LOX, COL5A2
Fibronectin matrix formation	1	190.3×	0.023	COL5A2
Crosslinking of collagen fibrils	1	190.3×	0.023	LOX
RHO GTPases activate PAKs	1	181.3×	0.023	MYLK
Attachment of bacteria to epithelial cells	1	165.5×	0.023	COL5A2
Collagen formation	1	152.3×	0.023	LOX
Syndecan interactions	1	141.0×	0.023	COL5A2
MET activates PTK2 signaling	1	126.9×	0.023	COL5A2
Elastic fibre formation	1	112.0×	0.023	LOX
Smooth Muscle Contraction	1	88.5×	0.023	MYLK
Collagen chain trimerization	1	86.5×	0.023	COL5A2
Signaling by PDGF	1	84.6×	0.023	COL5A2
NCAM1 interactions	1	82.8×	0.023	COL5A2
Developmental Lineage of Pancreatic Ductal Cells	1	76.1×	0.023	COL5A2
Collagen degradation	1	58.6×	0.027	COL5A2
Collagen biosynthesis and modifying enzymes	1	56.8×	0.027	COL5A2
Non-integrin membrane-ECM interactions	1	51.4×	0.028	COL5A2
ECM proteoglycans	1	50.1×	0.028	COL5A2
Integrin cell surface interactions	1	44.8×	0.029	COL5A2
Muscle contraction	1	25.7×	0.048	MYLK
RHO GTPase Effectors	1	22.7×	0.052	MYLK
Extracellular matrix organization	1	21.0×	0.053	LOX
Signaling by Rho GTPases	1	11.4×	0.091	MYLK
Signaling by Rho GTPases, Miro GTPases and RHOBTB3	1	11.2×	0.091	MYLK
Signal Transduction	1	3.4×	0.267	MYLK

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 4 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
tonic smooth muscle contraction	1	4213.0×	0.002	MYLK
ascending aorta development	1	4213.0×	0.002	LOX
descending aorta development	1	4213.0×	0.002	LOX
regulation of platelet-derived growth factor receptor-beta signaling pathway	1	4213.0×	0.002	LOX
collagen fibril organization	2	112.3×	0.002	LOX, COL5A2
negative regulation of endodermal cell differentiation	1	2106.5×	0.003	COL5A2
peptidyl-lysine oxidation	1	1404.3×	0.004	LOX
eye morphogenesis	1	1053.2×	0.004	COL5A2
aorta smooth muscle tissue morphogenesis	1	1053.2×	0.004	MYLK
connective tissue development	1	1053.2×	0.004	LOX
platelet-derived growth factor receptor-beta signaling pathway	1	842.6×	0.004	LOX
regulation of bone development	1	842.6×	0.004	LOX
regulation of striated muscle tissue development	1	702.2×	0.005	LOX
regulation of megakaryocyte differentiation	1	468.1×	0.007	LOX
bleb assembly	1	383.0×	0.007	MYLK
elastic fiber assembly	1	383.0×	0.007	LOX
cellular hypotonic response	1	351.1×	0.007	MYLK
cellular response to chemokine	1	247.8×	0.009	LOX
muscle cell development	1	234.1×	0.009	LOX
regulation of synaptic vesicle endocytosis	1	221.7×	0.009	MYLK
response to steroid hormone	1	210.7×	0.009	LOX
smooth muscle contraction	1	200.6×	0.009	MYLK
regulation of transforming growth factor beta receptor signaling pathway	1	200.6×	0.009	LOX
blood vessel morphogenesis	1	200.6×	0.009	LOX
DNA biosynthetic process	1	200.6×	0.009	LOX
maturation of SSU-rRNA	1	191.5×	0.009	SRFBP1
muscle cell cellular homeostasis	1	162.0×	0.010	LOX
positive regulation of calcium ion transport	1	145.3×	0.011	MYLK
positive regulation of wound healing	1	131.7×	0.011	MYLK
skin development	1	110.9×	0.013	COL5A2

Therapeutics

Drug target analysis

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

Druggability breadth: 3 of 4 evidence-associated genes (75%) 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
LOX	PYRITHIONE
MYLK	PONATINIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
MYLK	28	4
LOX	4	4
COL5A2	0	0
SRFBP1	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
PYRITHIONE	4	LOX
ZILEUTON	4	LOX
DISULFIRAM	4	LOX
PONATINIB	4	MYLK
AFATINIB	4	MYLK
FEDRATINIB	4	MYLK
RUXOLITINIB	4	MYLK
NIFEDIPINE	4	MYLK
BOSUTINIB	4	MYLK
GILTERITINIB	4	MYLK
TOVORAFENIB	4	MYLK
NINTEDANIB	4	MYLK
SUNITINIB	4	MYLK
DASATINIB	4	MYLK
QUIZARTINIB	4	MYLK
MIDOSTAURIN	4	MYLK
FASUDIL	3	MYLK
DOVITINIB	3	MYLK
LESTAURTINIB	3	MYLK
RUBOXISTAURIN	3	MYLK
THIRAM	2	LOX
VX-702	2	MYLK
SU-014813	2	MYLK
REBASTINIB	2	MYLK
TANZISERTIB	2	MYLK
CEP-32496	2	MYLK
BAFETINIB	2	MYLK
PEXMETINIB	2	MYLK
R-406	2	MYLK
BI-2536	2	MYLK

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 2.

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

Symbol	Assays	Type breakdown
MYLK	303	Binding:303
LOX	15	Binding:15

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
LOX	1.4.3.13	protein-lysine 6-oxidase
MYLK	2.7.11.18	myosin-light-chain kinase

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
MYLK	303

Pharmacogenomics

Cohort genes with a PharmGKB record: 4; 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)
PYRITHIONE	4	LOX
ZILEUTON	4	LOX
DISULFIRAM	4	LOX
PONATINIB	4	MYLK
AFATINIB	4	MYLK
FEDRATINIB	4	MYLK
RUXOLITINIB	4	MYLK
NIFEDIPINE	4	MYLK
BOSUTINIB	4	MYLK
GILTERITINIB	4	MYLK
TOVORAFENIB	4	MYLK
NINTEDANIB	4	MYLK
SUNITINIB	4	MYLK
DASATINIB	4	MYLK
QUIZARTINIB	4	MYLK
MIDOSTAURIN	4	MYLK
FASUDIL	3	MYLK
DOVITINIB	3	MYLK
LESTAURTINIB	3	MYLK
RUBOXISTAURIN	3	MYLK
THIRAM	2	LOX
VX-702	2	MYLK
SU-014813	2	MYLK
REBASTINIB	2	MYLK
TANZISERTIB	2	MYLK
CEP-32496	2	MYLK
BAFETINIB	2	MYLK
PEXMETINIB	2	MYLK
R-406	2	MYLK
BI-2536	2	MYLK

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	2	LOX, MYLK
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	COL5A2, SRFBP1

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)
COL5A2	0	—
SRFBP1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.