Arterial tortuosity syndrome

Summary

Arterial tortuosity syndrome (MONDO:0008818) is a disease caused by SLC2A10 (GenCC Definitive), with 1 cohort gene and 1 clinical trial.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Causal gene: SLC2A10 (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 507
• Phenotypes (HPO): 61
• Clinical trials: 1

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		102	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

61 HPO clinical features (Orphanet curated; top 50 by frequency):

HPO ID	Term	Frequency
HP:0001635	Congestive heart failure	Very frequent (80-99%)
HP:0002616	Aortic root aneurysm	Very frequent (80-99%)
HP:0002617	Dilatation	Very frequent (80-99%)
HP:0004942	Aortic aneurysm	Very frequent (80-99%)
HP:0005344	Abnormality of the carotid arteries	Very frequent (80-99%)
HP:0100545	Arterial stenosis	Very frequent (80-99%)
HP:0100585	Telangiectasia of the skin	Very frequent (80-99%)
HP:0000023	Inguinal hernia	Frequent (30-79%)
HP:0000276	Long face	Frequent (30-79%)
HP:0000316	Hypertelorism	Frequent (30-79%)
HP:0000400	Macrotia	Frequent (30-79%)
HP:0000963	Thin skin	Frequent (30-79%)
HP:0000974	Hyperextensible skin	Frequent (30-79%)
HP:0001363	Craniosynostosis	Frequent (30-79%)
HP:0002647	Aortic dissection	Frequent (30-79%)
HP:0004415	Pulmonary artery stenosis	Frequent (30-79%)
HP:0010668	Abnormal zygomatic bone morphology	Frequent (30-79%)
HP:0012378	Fatigue	Frequent (30-79%)
HP:0100541	Femoral hernia	Frequent (30-79%)
HP:0001382	Joint hypermobility	Frequent (30-79%)
HP:0009099	Median cleft palate	Frequent (30-79%)
HP:0000256	Macrocephaly	Occasional (5-29%)
HP:0000272	Malar flattening	Occasional (5-29%)
HP:0000486	Strabismus	Occasional (5-29%)
HP:0000545	Myopia	Occasional (5-29%)
HP:0000563	Keratoconus	Occasional (5-29%)
HP:0000581	Blepharophimosis	Occasional (5-29%)
HP:0000822	Hypertension	Occasional (5-29%)
HP:0001119	Keratoglobus	Occasional (5-29%)
HP:0001166	Arachnodactyly	Occasional (5-29%)
HP:0001249	Intellectual disability	Occasional (5-29%)
HP:0001252	Hypotonia	Occasional (5-29%)
HP:0001263	Global developmental delay	Occasional (5-29%)
HP:0001328	Specific learning disability	Occasional (5-29%)
HP:0001385	Hip dysplasia	Occasional (5-29%)
HP:0001582	Redundant skin	Occasional (5-29%)
HP:0001637	Abnormal myocardium morphology	Occasional (5-29%)
HP:0001639	Hypertrophic cardiomyopathy	Occasional (5-29%)
HP:0001644	Dilated cardiomyopathy	Occasional (5-29%)
HP:0001658	Myocardial infarction	Occasional (5-29%)
HP:0001695	Cardiac arrest	Occasional (5-29%)
HP:0001838	Rocker bottom foot	Occasional (5-29%)
HP:0002020	Gastroesophageal reflux	Occasional (5-29%)
HP:0002021	Pyloric stenosis	Occasional (5-29%)
HP:0002036	Hiatus hernia	Occasional (5-29%)
HP:0002094	Dyspnea	Occasional (5-29%)
HP:0002098	Respiratory distress	Occasional (5-29%)
HP:0002650	Scoliosis	Occasional (5-29%)
HP:0002673	Coxa valga	Occasional (5-29%)
HP:0002812	Coxa vara	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	arterial tortuosity syndrome
Mondo ID	MONDO:0008818
MeSH	C565942
OMIM	208050
Orphanet	3342
DOID	DOID:0050645
ICD-10-CM	Q87.82
ICD-11	371764699
SNOMED CT	458432002
UMLS	C1859726
MedGen	347942
GARD	0000774
NORD	803
Is cancer (heuristic)	no

Also known as: arterial tortuosity syndrome · ATS

Data availability: 507 ClinVar variants · 7 GenCC gene-disease records.

Disease family

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

Related subtypes (59): arterial disorder, ischemic colitis, thrombotic disease, capillary disorder, angiodysplasia, hepatic vascular disorder, vascular hemostatic disease, vein disorder, ischemic disease, peripheral vascular disease, venous thromboembolism, ocular vascular disorder, cholesterol embolism, thoracic outlet syndrome, idiopathic spontaneous coronary artery dissection, cerebral arteriopathy with subcortical infarcts and leukoencephalopathy, angioosteohypertrophic syndrome, Bannayan-Riley-Ruvalcaba syndrome, hereditary arterial and articular multiple calcification syndrome, pulmonary venoocclusive disease, multiple cutaneous and mucosal venous malformations, arterial dissection-lentiginosis syndrome, patent ductus arteriosus, multisystemic smooth muscle dysfunction syndrome, STING-associated vasculopathy with onset in infancy, capillary malformation, Ehlers-Danlos syndrome, vascular-like type, calciphylaxis, neonatal Marfan syndrome, Ehlers-Danlos syndrome, vascular type, lethal arteriopathy syndrome due to fibulin-4 deficiency, congenital portosystemic shunt, arterial calcification of infancy, vasculitis, Loeys-Dietz syndrome, skin vascular disease, lymphatic malformation, familial thoracic aortic aneurysm and aortic dissection, congenital anomaly of superior vena cava, congenital anomaly of the inferior vena cava, congenital anomaly of hepatic vein, congenital renal artery stenosis, internal carotid agenesis, coronary sinus stenosis, coronary sinus atresia, vascular occlusion disorder, vascular insufficiency disorder, blood vessel neoplasm, vascular ectasia, vascular disorder of penis, fibrocartilaginous embolism, vascular malformation, lymphatic vessel neoplasm, neurovascular disorder, superior vena cava syndrome, coronary microvascular disorder, segmental arterial mediolysis, bleeding disorder, vascular-type, arterial tortuosity-bone fragility syndrome

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

507 retrieved; paginated sample, class counts are floors:

196 uncertain significance, 167 likely benign, 50 conflicting classifications of pathogenicity, 26 pathogenic, 21 benign, 17 benign/likely benign, 14 pathogenic/likely pathogenic, 12 likely pathogenic, 4 not provided

ClinVar	Variant (HGVS)	Gene	Classification	Review
1323610	NM_030777.4(SLC2A10):c.485G>A (p.Trp162Ter)	SLC2A10	Pathogenic	criteria provided, single submitter
1392857	NM_030777.4(SLC2A10):c.483del (p.Trp162fs)	SLC2A10	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1399156	NM_030777.4(SLC2A10):c.1424T>A (p.Leu475Ter)	SLC2A10	Pathogenic	criteria provided, single submitter
1454308	NM_030777.4(SLC2A10):c.473_476del (p.Ala158fs)	SLC2A10	Pathogenic	criteria provided, multiple submitters, no conflicts
161095	NM_030777.4(SLC2A10):c.417T>A (p.Tyr139Ter)	SLC2A10	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
161096	NM_030777.4(SLC2A10):c.685C>T (p.Arg229Ter)	SLC2A10	Pathogenic	criteria provided, multiple submitters, no conflicts
161097	NM_030777.4(SLC2A10):c.692G>A (p.Arg231Gln)	SLC2A10	Pathogenic	criteria provided, multiple submitters, no conflicts
161098	NM_030777.4(SLC2A10):c.756C>A (p.Cys252Ter)	SLC2A10	Pathogenic	criteria provided, single submitter
161100	NM_030777.4(SLC2A10):c.1309G>A (p.Glu437Lys)	SLC2A10	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
161101	NM_030777.4(SLC2A10):c.1330C>T (p.Arg444Ter)	SLC2A10	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
161104	NM_030777.4(SLC2A10):c.313C>T (p.Arg105Cys)	SLC2A10	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
161106	NM_030777.4(SLC2A10):c.691C>T (p.Arg231Trp)	SLC2A10	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
161107	NM_030777.4(SLC2A10):c.731_734del (p.Leu244fs)	SLC2A10	Pathogenic	criteria provided, multiple submitters, no conflicts
1911562	NM_030777.4(SLC2A10):c.10del (p.Ser4fs)	SLC2A10	Pathogenic	criteria provided, single submitter
213751	NM_030777.4(SLC2A10):c.1411+2T>A	SLC2A10	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2426942	NC_000020.10:g.(?45357972)(45358147_?)del	SLC2A10	Pathogenic	criteria provided, single submitter
2442860	NM_030777.4(SLC2A10):c.761_762del (p.Ala254fs)	SLC2A10	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2501291	NM_030777.4(SLC2A10):c.899T>G (p.Leu300Trp)	SLC2A10	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2761376	NM_030777.4(SLC2A10):c.343_832delinsC (p.Ser115_Ala278delinsPro)	SLC2A10	Pathogenic	criteria provided, single submitter
2983016	NM_030777.4(SLC2A10):c.289del (p.Ser97fs)	SLC2A10	Pathogenic	criteria provided, single submitter
3248277	NC_000020.10:g.(?45353660)(45355645_?)del	SLC2A10	Pathogenic	criteria provided, single submitter
3319431	NM_030777.4(SLC2A10):c.1A>T (p.Met1Leu)	SLC2A10	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3587316	NM_030777.4(SLC2A10):c.484del (p.Trp162fs)	SLC2A10	Pathogenic	criteria provided, single submitter
3617449	NM_030777.4(SLC2A10):c.483dup (p.Trp162fs)	SLC2A10	Pathogenic	criteria provided, single submitter
3679463	NM_030777.4(SLC2A10):c.22del (p.Leu8fs)	SLC2A10	Pathogenic	criteria provided, single submitter
3722256	NM_030777.4(SLC2A10):c.1129del (p.His377fs)	SLC2A10	Pathogenic	criteria provided, single submitter
3725150	NM_030777.4(SLC2A10):c.1446C>A (p.Tyr482Ter)	SLC2A10	Pathogenic	criteria provided, single submitter
3730294	NM_030777.4(SLC2A10):c.1A>C (p.Met1Leu)	SLC2A10	Pathogenic	criteria provided, single submitter
3773763	NM_030777.4(SLC2A10):c.297_301del (p.Trp100fs)	SLC2A10	Pathogenic	criteria provided, single submitter
3776307	NM_030777.4(SLC2A10):c.801del (p.Ser268fs)	SLC2A10	Pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 7 · Orphanet: 1 · 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
SLC2A10	Definitive	Autosomal recessive	arterial tortuosity syndrome	7

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SLC2A10	Orphanet:3342	Arterial tortuosity syndrome

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
SLC2A10	HGNC:13444	ENSG00000197496	O95528	Solute carrier family 2, facilitated glucose transporter member 10	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SLC2A10	Solute carrier family 2, facilitated glucose transporter member 10	Facilitative glucose transporter required for the development of the cardiovascular system.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

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
Transporter	1	77.8×	0.013

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
SLC2A10	Transporter	yes		Sugar/inositol_transpt, MFS_sugar_transport-like, Sugar_transporter_CS

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
bronchial epithelial cell	1
epithelium of bronchus	1
tibia	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SLC2A10	235	ubiquitous	marker	tibia, bronchial epithelial cell, epithelium of bronchus

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
SLC2A10	2,046

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
SLC2A10	O95528	74.78

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 2. 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
Defective SLC2A10 causes arterial tortuosity syndrome (ATS)	1	11420.0×	2e-04	SLC2A10
Cellular hexose transport	1	543.8×	0.002	SLC2A10

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
negative regulation of connective tissue growth factor production	1	16852.0×	1e-03	SLC2A10
negative regulation of proteoglycan biosynthetic process	1	8426.0×	1e-03	SLC2A10
positive regulation of proteoglycan biosynthetic process	1	5617.3×	1e-03	SLC2A10
negative regulation of integrin-mediated signaling pathway	1	4213.0×	1e-03	SLC2A10
galactose transmembrane transport	1	3370.4×	1e-03	SLC2A10
embryonic skeletal joint development	1	3370.4×	1e-03	SLC2A10
D-glucose import across plasma membrane	1	2808.7×	0.001	SLC2A10
regulation of extracellular matrix organization	1	1872.4×	0.001	SLC2A10
hexose transmembrane transport	1	1404.3×	0.001	SLC2A10
artery development	1	1404.3×	0.001	SLC2A10
circulatory system development	1	1404.3×	0.001	SLC2A10
dehydroascorbic acid transport	1	1203.7×	0.001	SLC2A10
D-glucose transmembrane transport	1	936.2×	0.002	SLC2A10
positive regulation of transforming growth factor beta receptor signaling pathway	1	526.6×	0.003	SLC2A10
skin development	1	443.5×	0.003	SLC2A10
cell redox homeostasis	1	343.9×	0.004	SLC2A10
transport across blood-brain barrier	1	179.3×	0.006	SLC2A10
negative regulation of transforming growth factor beta receptor signaling pathway	1	173.7×	0.006	SLC2A10
negative regulation of gene expression	1	69.1×	0.015	SLC2A10
positive regulation of gene expression	1	38.7×	0.026	SLC2A10

Therapeutics

Drug target analysis

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

Druggability breadth: 0 of 1 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
SLC2A10	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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	1	SLC2A10
E	Difficult family or no structure, no drug	0

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)
SLC2A10	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 1.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT03440697	Not specified	ACTIVE_NOT_RECRUITING	Pathogenetic Basis of Aortopathy and Aortic Valve Disease