Vascular disorder

disease

On this page

Also known as disease of vasculaturedisease or disorder of vasculaturedisorder of vasculaturevasculature diseasevasculature disease or disordervasculopathy

Summary

Vascular disorder (MONDO:0005385) is a disease (an umbrella term covering 60 Mondo subtypes) with 12 cohort genes (13 GWAS associations across 17 studies) and 10 clinical trials. Top therapeutic interventions include alirocumab.

At a glance

Umbrella term: 60 Mondo subtypes
Cohort genes: 12
GWAS associations: 13
ClinVar variants: 12
Clinical trials: 10

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	vascular disorder
Mondo ID	MONDO:0005385
EFO	EFO:0004264
MeSH	D014652
DOID	DOID:178
ICD-10-CM	I00-I99, I70-I79
NCIT	C35117
SNOMED CT	27550009
UMLS	C0042373
MedGen	22621
Anatomy (UBERON)	UBERON:0002049, UBERON:0007798
Is cancer (heuristic)	no

Also known as: disease of vasculature · disease or disorder of vasculature · disorder of vasculature · vascular disorder · vasculature disease · vasculature disease or disorder · vasculopathy

Data availability: 12 ClinVar variants · 13 GWAS associations (17 studies).

Disease family

An umbrella term covering 60 Mondo subtypes.

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

Subtypes (60): 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, arterial tortuosity 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

13 GWAS associations across 17 studies. Top hits map to 8 distinct genes (as reported by GWAS).

Top associations by p-value

rsID	p-value	Gene	Risk allele	Odds ratio
rs186886479	3e-14	UGGT2	T	3.06
rs200401136	5e-14	OARD1	C	3.07
rs529485874	6e-14	MIR4455 - LINC02437	G	3.1
rs73885319	1e-13	APOL1	A	0.34
rs554840714	2e-13	LINC02719 - GUCY1A2	C	3.06
rs143732408	4e-12	FRMD4A	G	3.21
rs537826069	8e-12	CHD1-DT - LINC02113	T	3.23
rs186687949	9e-12	ZFHX3, LOHAN2	C	3.04
rs540246290	1e-11	CYCSP42 - RNU6-1326P	C	3.38
rs576948131	3e-11	DOK5	A	3.22
rs558392723	3e-11	UBE2FP2 - RPS15AP34	T	3.31
rs185086631	4e-11	COBL	G	3.83

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST90478029	Verma A	2024	3,991	437,343	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90473833	UK Biobank Whole-Genome Sequencing Consortium	2025	3,567	454,873	Whole-genome sequencing of 490,640 UK Biobank participants.
GCST90474051	UK Biobank Whole-Genome Sequencing Consortium	2025	2,055	456,385	Whole-genome sequencing of 490,640 UK Biobank participants.
GCST90080239	Backman JD	2021	1,491	386,337	Exome sequencing and analysis of 454,787 UK Biobank participants.
GCST90084225	Backman JD	2021	1,491	386,337	Exome sequencing and analysis of 454,787 UK Biobank participants.
GCST90436170	Zhou W	2018	1,333	400,595	Efficiently controlling for case-control imbalance and sample relatedness in large-scale genetic association studies.
GCST90476001	Verma A	2024	1,243	118,279	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90480216	Verma A	2024	1,243	118,279	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90080467	Backman JD	2021	855	386,913	Exome sequencing and analysis of 454,787 UK Biobank participants.
GCST90084453	Backman JD	2021	855	386,913	Exome sequencing and analysis of 454,787 UK Biobank participants.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

Tier	Variants
Tier 1: coding	1
Tier 2: splice/UTR	0
Tier 3: regulatory	0
Tier 4: intronic/intergenic	11

MAF distribution

Bucket	Variants
common (>=0.05)	1
low_freq (0.01-0.05)	0
rare (<0.01)	11
unknown	0

Functional consequences

Consequence	Count
intron_variant	8
intergenic_variant	3
missense_variant	1

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
rs186886479	13	95852736	T>A	0	intron_variant	UGGT2	3e-14	Tier 4: intronic/intergenic
rs200401136	6	41046824	C>G	0.001	intergenic_variant	OARD1	5e-14	Tier 4: intronic/intergenic
rs529485874	4	184941798	G>A	0.001	intron_variant	MIR4455 - LINC02437	6e-14	Tier 4: intronic/intergenic
rs73885319	22	36265860	A>G	0.224	missense_variant	APOL1	1e-13	Tier 1: coding
rs554840714	11	106491059	C>T	0.001	intergenic_variant	LINC02719 - GUCY1A2	2e-13	Tier 4: intronic/intergenic
rs143732408	10	14254020	G>A,T	0.001	intron_variant	FRMD4A	4e-12	Tier 4: intronic/intergenic
rs537826069	5	99246596	T>C	0	intergenic_variant	CHD1-DT - LINC02113	8e-12	Tier 4: intronic/intergenic
rs186687949	16	73428380	C>T	0.001	intron_variant	ZFHX3, LOHAN2	9e-12	Tier 4: intronic/intergenic
rs540246290	21	15521971	C>T	0.001	intron_variant	CYCSP42 - RNU6-1326P	1e-11	Tier 4: intronic/intergenic
rs576948131	20	54556737	A>G	0	intron_variant	DOK5	3e-11	Tier 4: intronic/intergenic
rs558392723	16	63182531	T>A,C,G	0.001	intron_variant	UBE2FP2 - RPS15AP34	3e-11	Tier 4: intronic/intergenic
rs185086631	7	51076360	G>A,T	0	intron_variant	COBL	4e-11	Tier 4: intronic/intergenic

ClinVar germline variants

12 retrieved; paginated sample, class counts are floors:

5 conflicting classifications of pathogenicity, 4 uncertain significance, 1 pathogenic, 1 likely benign, 1 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
13334	NM_002834.5(PTPN11):c.218C>T (p.Thr73Ile)	PTPN11	Pathogenic	criteria provided, multiple submitters, no conflicts
1899906	NM_032119.4(ADGRV1):c.2834G>A (p.Gly945Glu)	ADGRV1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2061798	NM_001690.4(ATP6V1A):c.1655G>A (p.Arg552His)	ATP6V1A	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
3136362	NM_018896.5(CACNA1G):c.3620G>T (p.Arg1207Leu)	CACNA1G	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1431399	NM_022168.4(IFIH1):c.1943del (p.Gly648fs)	IFIH1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1315439	NM_030665.4(RAI1):c.2120C>G (p.Ser707Cys)	RAI1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2637050	NM_018263.6(ASXL2):c.1775A>G (p.Gln592Arg)	ASXL2	Uncertain significance	criteria provided, multiple submitters, no conflicts
4074950	NM_182641.4(BPTF):c.6956A>C (p.Gln2319Pro)	BPTF	Uncertain significance	criteria provided, single submitter
4074935	NM_001958.5(EEF1A2):c.1336G>T (p.Gly446Cys)	EEF1A2	Uncertain significance	criteria provided, single submitter
4075119	NM_006734.4(HIVEP2):c.1381C>T (p.His461Tyr)	HIVEP2	Uncertain significance	criteria provided, single submitter
588698	NM_013275.6(ANKRD11):c.5578C>T (p.Pro1860Ser)	ANKRD11	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
3440505	NM_030632.3(ASXL3):c.5396C>T (p.Pro1799Leu)	ASXL3	Likely benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 24 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
CACNA1G	Orphanet:458803	Spinocerebellar ataxia type 42
ADGRV1	Orphanet:231178	Usher syndrome type 2
ADGRV1	Orphanet:36387	Genetic epilepsy with febrile seizure plus
IFIH1	Orphanet:51	Aicardi-Goutières syndrome
IFIH1	Orphanet:689231	IFIH1-related hereditary spastic paraplegia
IFIH1	Orphanet:85191	Singleton-Merten dysplasia
ANKRD11	Orphanet:2332	KBG syndrome
ANKRD11	Orphanet:261250	16q24.3 microdeletion syndrome
ASXL2	Orphanet:689408	Shashi-Pena syndrome
ASXL3	Orphanet:352577	Bainbridge-Ropers syndrome
EEF1A2	Orphanet:178469	Autosomal dominant non-syndromic intellectual disability
EEF1A2	Orphanet:442835	Non-specific early-onset epileptic encephalopathy
BPTF	Orphanet:529962	17q24.2 microdeletion syndrome
BPTF	Orphanet:686482	BPTF-related intellectual disability-facial dysmorphism-skeletal anomalies syndrome
HIVEP2	Orphanet:178469	Autosomal dominant non-syndromic intellectual disability
ATP6V1A	Orphanet:357074	Autosomal recessive cutis laxa type 2, classic type
ATP6V1A	Orphanet:442835	Non-specific early-onset epileptic encephalopathy
PTPN11	Orphanet:2499	Metachondromatosis
PTPN11	Orphanet:500	Noonan syndrome with multiple lentigines
PTPN11	Orphanet:648	Noonan syndrome
PTPN11	Orphanet:86834	Juvenile myelomonocytic leukemia
RAI1	Orphanet:1713	17p11.2 microduplication syndrome
RAI1	Orphanet:477817	PMP22-RAI1 contiguous gene duplication syndrome
RAI1	Orphanet:819	Smith-Magenis syndrome

Cohort genes → proteins

12 cohort genes, 12 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	12

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
CACNA1G	HGNC:1394	ENSG00000006283	O43497	Voltage-dependent T-type calcium channel subunit alpha-1G	clinvar
ADGRV1	HGNC:17416	ENSG00000164199	Q8WXG9	Adhesion G-protein coupled receptor V1	clinvar
IFIH1	HGNC:18873	ENSG00000115267	Q9BYX4	Interferon-induced helicase C domain-containing protein 1	clinvar
ANKRD11	HGNC:21316	ENSG00000167522	Q6UB99	Ankyrin repeat domain-containing protein 11	clinvar
ASXL2	HGNC:23805	ENSG00000143970	Q76L83	Putative Polycomb group protein ASXL2	clinvar
ASXL3	HGNC:29357	ENSG00000141431	Q9C0F0	Putative Polycomb group protein ASXL3	clinvar
EEF1A2	HGNC:3192	ENSG00000101210	Q05639	Elongation factor 1-alpha 2	clinvar
BPTF	HGNC:3581	ENSG00000171634	Q12830	Nucleosome-remodeling factor subunit BPTF	clinvar
HIVEP2	HGNC:4921	ENSG00000010818	P31629	Transcription factor HIVEP2	clinvar
ATP6V1A	HGNC:851	ENSG00000114573	P38606	V-type proton ATPase catalytic subunit A	clinvar
PTPN11	HGNC:9644	ENSG00000179295	Q06124	Tyrosine-protein phosphatase non-receptor type 11	clinvar
RAI1	HGNC:9834	ENSG00000108557	Q7Z5J4	Retinoic acid-induced protein 1	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
CACNA1G	Voltage-dependent T-type calcium channel subunit alpha-1G	Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hormone or neurotransmitter release, gene exp…
ADGRV1	Adhesion G-protein coupled receptor V1	G-protein coupled receptor which has an essential role in the development of hearing and vision.
IFIH1	Interferon-induced helicase C domain-containing protein 1	Innate immune receptor which acts as a cytoplasmic sensor of viral nucleic acids and plays a major role in sensing viral infection and in the activation of a cascade of antiviral responses including the induction of type I interferons and…
ANKRD11	Ankyrin repeat domain-containing protein 11	Chromatin regulator which modulates histone acetylation and gene expression in neural precursor cells.
ASXL2	Putative Polycomb group protein ASXL2	Putative Polycomb group (PcG) protein.
ASXL3	Putative Polycomb group protein ASXL3	Putative Polycomb group (PcG) protein.
EEF1A2	Elongation factor 1-alpha 2	Translation elongation factor that catalyzes the GTP-dependent binding of aminoacyl-tRNA (aa-tRNA) to the A-site of ribosomes during the elongation phase of protein synthesis.
BPTF	Nucleosome-remodeling factor subunit BPTF	Regulatory subunit of the ATP-dependent NURF-1 and NURF-5 ISWI chromatin remodeling complexes, which form ordered nucleosome arrays on chromatin and facilitate access to DNA during DNA-templated processes such as DNA replication, transcrip…
HIVEP2	Transcription factor HIVEP2	This protein specifically binds to the DNA sequence 5’-GGGACTTTCC-3’ which is found in the enhancer elements of numerous viral promoters such as those of SV40, CMV, or HIV1.
ATP6V1A	V-type proton ATPase catalytic subunit A	Catalytic subunit of the V1 complex of vacuolar(H+)-ATPase (V-ATPase), a multisubunit enzyme composed of a peripheral complex (V1) that hydrolyzes ATP and a membrane integral complex (V0) that translocates protons.
PTPN11	Tyrosine-protein phosphatase non-receptor type 11	Acts downstream of various receptor and cytoplasmic protein tyrosine kinases to participate in the signal transduction from the cell surface to the nucleus.
RAI1	Retinoic acid-induced protein 1	Transcriptional regulator of the circadian clock components: CLOCK, BMAL1, BMAL2, PER1/3, CRY1/2, NR1D1/2 and RORA/C.

Protein-family classification

Druggable: 3 · Difficult: 4 · Unknown: 5 · Druggable fraction: 0.25

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
Ion channel	1	9.3×	0.340
Phosphatase	1	7.0×	0.340
Transcription factor	3	2.1×	0.340
GPCR	1	2.0×	0.601
Scaffold/PPI	1	1.4×	0.613
Other/Unknown	5	0.8×	0.899

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
CACNA1G	Ion channel	yes		VDCCAlpha1, VDCC_T_a1, Ion_trans_dom
ADGRV1	GPCR	yes		GPCR_2_secretin-like, Calx_beta, EPTP
IFIH1	Other/Unknown	no		Helicase_C-like, Helicase/UvrB_N, DEATH-like_dom_sf
ANKRD11	Scaffold/PPI	no		Ankyrin_rpt, Ankyrin_rpt-contain_sf, ANKRD11
ASXL2	Other/Unknown	no		Asxl_HARE-HTH, ASX/ASX-like, ASX-like_PHD
ASXL3	Other/Unknown	no		Asxl_HARE-HTH, ASX/ASX-like, ASX-like_PHD
EEF1A2	Other/Unknown	no		T_Tr_GTP-bd_dom, EFTu-like_2, Transl_elong_EF1A_euk/arc
BPTF	Transcription factor	no		Bromodomain, Znf_PHD, Znf_FYVE_PHD
HIVEP2	Transcription factor	no		Znf_C2H2_type, Znf_C2H2_sf,
ATP6V1A	Other/Unknown	no		ATPase_F1/V1/A1_a/bsu_nucl-bd, ATPase_F1/V1/A1_a/bsu_N, ATPase_V1-cplx_asu
PTPN11	Phosphatase	yes	3.1.3.48	PTP_cat, Tyr_Pase_dom, SH2
RAI1	Transcription factor	no		Znf_PHD, Znf_RING/FYVE/PHD, EPHD

Expression context

Cohort genes with no expression data: 0.

11 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)	12
unknown	0

Top tissues across cohort

Tissue	Cohort genes
lateral nuclear group of thalamus	2
palpebral conjunctiva	2
sural nerve	2
tendon of biceps brachii	2
cortical plate	2
right frontal lobe	1
right hemisphere of cerebellum	1
left adrenal gland	1
right adrenal gland	1
right adrenal gland cortex	1
jejunal mucosa	1
parotid gland	1
stromal cell of endometrium	1
caput epididymis	1
cauda epididymis	1
corpus epididymis	1
buccal mucosa cell	1
secondary oocyte	1
apex of heart	1
gastrocnemius	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
CACNA1G	194	broad	yes	lateral nuclear group of thalamus, right hemisphere of cerebellum, right frontal lobe
ADGRV1	196	broad	marker	right adrenal gland cortex, right adrenal gland, left adrenal gland
IFIH1	276	ubiquitous	marker	palpebral conjunctiva, parotid gland, jejunal mucosa
ANKRD11	278	ubiquitous	marker	tendon of biceps brachii, sural nerve, stromal cell of endometrium
ASXL2	288	ubiquitous	marker	caput epididymis, corpus epididymis, cauda epididymis
ASXL3	205	broad	marker	buccal mucosa cell, secondary oocyte, cortical plate
EEF1A2	247	ubiquitous	marker	gastrocnemius, apex of heart, hindlimb stylopod muscle
BPTF	290	ubiquitous	marker	sural nerve, ventricular zone, cortical plate
HIVEP2	296	ubiquitous	marker	tendon of biceps brachii, vena cava, lateral nuclear group of thalamus
ATP6V1A	300	ubiquitous	marker	Brodmann (1909) area 23, middle temporal gyrus, endothelial cell
PTPN11	295	ubiquitous	marker	medial globus pallidus, dorsal motor nucleus of vagus nerve, globus pallidus
RAI1	264	ubiquitous	marker	pigmented layer of retina, nipple, palpebral conjunctiva

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
PTPN11	6,009
ASXL2	4,417
IFIH1	3,706
ATP6V1A	3,301
BPTF	2,682
ANKRD11	2,384
RAI1	1,979
CACNA1G	1,677
ADGRV1	1,658
ASXL3	1,594

Intra-cohort edges

A	B	Sources
ASXL2	ASXL3	string_interaction

Structural data

PDB: 7 · AlphaFold-only: 5 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
PTPN11	Q06124	115
BPTF	Q12830	45
IFIH1	Q9BYX4	9
ATP6V1A	P38606	8
CACNA1G	O43497	2
EEF1A2	Q05639	2
ASXL2	Q76L83	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
ASXL3	Q9C0F0	39.70
RAI1	Q7Z5J4	39.62
ANKRD11	Q6UB99	39.44
HIVEP2	P31629	36.43
ADGRV1	Q8WXG9

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 85. Enrichment computed across 12 evidence-associated genes (8 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 8 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
MET activates PTPN11	1	285.5×	0.036	PTPN11
Co-inhibition by BTLA	1	285.5×	0.036	PTPN11
STAT5 Activation	1	203.9×	0.036	PTPN11
Netrin mediated repulsion signals	1	158.6×	0.036	PTPN11
MAPK1 (ERK2) activation	1	142.8×	0.036	PTPN11
STAT5 activation downstream of FLT3 ITD mutants	1	142.8×	0.036	PTPN11
MAPK3 (ERK1) activation	1	129.8×	0.036	PTPN11
Signaling by Leptin	1	129.8×	0.036	PTPN11
Interleukin-6 signaling	1	119.0×	0.036	PTPN11
Activated NTRK2 signals through FRS2 and FRS3	1	119.0×	0.036	PTPN11
PECAM1 interactions	1	109.8×	0.036	PTPN11
NF-kB activation through FADD/RIP-1 pathway mediated by caspase-8 and -10	1	109.8×	0.036	IFIH1
Regulation of IFNG signaling	1	102.0×	0.036	PTPN11
Prolactin receptor signaling	1	95.2×	0.036	PTPN11
TRAF3-dependent IRF activation pathway	1	95.2×	0.036	IFIH1
Signaling by FLT3 ITD and TKD mutants	1	95.2×	0.036	PTPN11
Spry regulation of FGF signaling	1	89.2×	0.036	PTPN11
Signal regulatory protein family interactions	1	84.0×	0.036	PTPN11
Platelet sensitization by LDL	1	84.0×	0.036	PTPN11
Regulation of RUNX1 Expression and Activity	1	84.0×	0.036	PTPN11
Regulation of MITF-M-dependent genes involved in lysosome biogenesis and autophagy	1	84.0×	0.036	ATP6V1A
GAB1 signalosome	1	79.3×	0.036	PTPN11
PI-3K cascade:FGFR3	1	79.3×	0.036	PTPN11
Tie2 Signaling	1	75.1×	0.036	PTPN11
Activation of IRF3, IRF7 mediated by TBK1, IKKε (IKBKE)	1	75.1×	0.036	PTPN11
Modulation of host responses by IFN-stimulated genes	1	75.1×	0.036	IFIH1
PI-3K cascade:FGFR4	1	71.4×	0.036	PTPN11
Signaling by CSF3 (G-CSF)	1	71.4×	0.036	PTPN11
FRS-mediated FGFR3 signaling	1	68.0×	0.036	PTPN11
Co-inhibition by CTLA4	1	64.9×	0.036	PTPN11

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 12 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 cortisol secretion	1	1404.3×	0.013	PTPN11
negative regulation of growth hormone secretion	1	1404.3×	0.013	PTPN11
SA node cell to atrial cardiac muscle cell signaling	1	1404.3×	0.013	CACNA1G
AV node cell to bundle of His cell signaling	1	1404.3×	0.013	CACNA1G
positive regulation of lipid kinase activity	1	1404.3×	0.013	EEF1A2
face morphogenesis	2	82.6×	0.013	ANKRD11, PTPN11
positive regulation of interferon-beta production	2	65.3×	0.013	IFIH1, PTPN11
inner ear development	2	62.4×	0.013	ADGRV1, PTPN11
response to nickel cation	1	702.2×	0.017	CACNA1G
microvillus organization	1	702.2×	0.017	PTPN11
regulation of type III interferon production	1	702.2×	0.017	IFIH1
intestinal epithelial cell migration	1	702.2×	0.017	PTPN11
animal organ morphogenesis	2	31.9×	0.019	ASXL2, ASXL3
cerebellar cortex formation	1	468.1×	0.020	PTPN11
detection of virus	1	351.1×	0.020	IFIH1
MDA-5 signaling pathway	1	351.1×	0.020	IFIH1
regulation of type I interferon-mediated signaling pathway	1	351.1×	0.020	PTPN11
AV node cell action potential	1	351.1×	0.020	CACNA1G
ERBB signaling pathway	1	280.9×	0.020	PTPN11
maintenance of animal organ identity	1	280.9×	0.020	ADGRV1
negative regulation of lipid biosynthetic process	1	280.9×	0.020	ASXL3
inner ear receptor cell differentiation	1	280.9×	0.020	ADGRV1
membrane depolarization during AV node cell action potential	1	280.9×	0.020	CACNA1G
membrane depolarization during SA node cell action potential	1	280.9×	0.020	CACNA1G
regulation of chaperone-mediated autophagy	1	280.9×	0.020	EEF1A2
positive regulation of tumor necrosis factor production	2	25.5×	0.020	IFIH1, PTPN11
SA node cell action potential	1	234.1×	0.023	CACNA1G
positive regulation of response to cytokine stimulus	1	200.6×	0.025	IFIH1
negative regulation of neutrophil activation	1	200.6×	0.025	PTPN11
sinoatrial node development	1	175.5×	0.026	CACNA1G

Therapeutics

Drugs indicated for this disease

1 approved, 8 in late-stage (phase 3) trials. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

Drug	Development status
Idecabtagene Vicleucel	Approved (phase 4)
Ambrisentan	Phase 3 (in late-stage trials)
Aspirin	Phase 3 (in late-stage trials)
Atenolol	Phase 3 (in late-stage trials)
Chlorthalidone	Phase 3 (in late-stage trials)
Clopidogrel	Phase 3 (in late-stage trials)
OMEGA-3-ACID ETHYL ESTERS	Phase 3 (in late-stage trials)
Oxygen	Phase 3 (in late-stage trials)
Vitamin E	Phase 3 (in late-stage trials)

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): Acebutolol, Amlodipine, Ascorbic Acid, Atorvastatin, Bevacizumab, Colchicine, Doxazosin, Enalapril, Hydralazine, Metoprolol, Ranolazine, Reserpine, Triamcinolone.

Drug target analysis

Approved (phase 4): 2 · Phase ≥3: 2 · Phased (≥1): 3 · Undrugged: 9

Druggability breadth: 7 of 12 evidence-associated genes (58%) 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
CACNA1G	NIMODIPINE
PTPN11	ESTRAMUSTINE PHOSPHATE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
CACNA1G	8	4
PTPN11	8	4
BPTF	2	2
ADGRV1	0	0
IFIH1	0	0
ANKRD11	0	0
ASXL2	0	0
ASXL3	0	0
EEF1A2	0	0
HIVEP2	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
NIMODIPINE	4	CACNA1G
TACRINE	4	CACNA1G
PIMOZIDE	4	CACNA1G
MIBEFRADIL	4	CACNA1G
ESTRAMUSTINE PHOSPHATE	4	PTPN11
SUVECALTAMIDE	2	CACNA1G
FLUNARIZINE	2	CACNA1G
APINOCALTAMIDE	2	CACNA1G
IPIDACRINE	2	BPTF
BI-2536	2	BPTF
ENOXOLONE	2	PTPN11
CEFSULODIN	2	PTPN11
BATOPROTAFIB	2	PTPN11
VOCIPROTAFIB	2	PTPN11
ULIXACALTAMIDE	1	CACNA1G
JAB-3068	1	PTPN11
PF-07284892	1	PTPN11
BBP-398	1	PTPN11

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
PTPN11	588	Binding:585, Functional:2, ADMET:1
BPTF	125	Binding:123, Functional:2
CACNA1G	105	Binding:91, Functional:11, ADMET:2, Toxicity:1
EEF1A2	8	Binding:8
ATP6V1A	2	Binding:2
IFIH1	1	Binding:1
HIVEP2	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
PTPN11	3.1.3.48	protein-tyrosine-phosphatase

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
CACNA1G	105
BPTF	125
PTPN11	588

Pharmacogenomics

Cohort genes with a PharmGKB record: 12; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

18 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)
NIMODIPINE	4	CACNA1G
TACRINE	4	CACNA1G
PIMOZIDE	4	CACNA1G
MIBEFRADIL	4	CACNA1G
ESTRAMUSTINE PHOSPHATE	4	PTPN11
SUVECALTAMIDE	2	CACNA1G
FLUNARIZINE	2	CACNA1G
APINOCALTAMIDE	2	CACNA1G
IPIDACRINE	2	BPTF
BI-2536	2	BPTF
ENOXOLONE	2	PTPN11
CEFSULODIN	2	PTPN11
BATOPROTAFIB	2	PTPN11
VOCIPROTAFIB	2	PTPN11
ULIXACALTAMIDE	1	CACNA1G
JAB-3068	1	PTPN11
PF-07284892	1	PTPN11
BBP-398	1	PTPN11

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	2	CACNA1G, PTPN11
B	Phased (≥1) drug, not yet approved	1	BPTF
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	1	ADGRV1
E	Difficult family or no structure, no drug	8	IFIH1, ANKRD11, ASXL2, ASXL3, EEF1A2, HIVEP2, ATP6V1A, RAI1

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
ADGRV1	0	—
IFIH1	1	—
ANKRD11	0	—
ASXL2	0	—
ASXL3	0	—
EEF1A2	8	—
HIVEP2	1	—
ATP6V1A	2	—
RAI1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 10.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	8
PHASE2	1
PHASE1	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT03537742	PHASE2	COMPLETED	Cardiac Allograft Vasculopathy Inhibition With Alirocumab
NCT07075185	PHASE1	RECRUITING	A Study to Evaluate a Novel Gene Therapy in Patients With Relapsed and Refractory Multiple Myeloma
NCT06392347	Not specified	NOT_YET_RECRUITING	Evaluation of Accelerated Sampling Techniques for Vessel Wall Imaging
NCT06818760	Not specified	RECRUITING	Remote Monitoring in Pregnant Women With Congenital Heart Disease Using Wrist Wearables
NCT00384540	Not specified	COMPLETED	Cardiac Allograft Vasculopathy and Dobutamine Stress Echocardiography / Brain Natriuretic Peptide Coupling
NCT01642680	Not specified	COMPLETED	Optimal Timing of Physical Activity in Cancer Treatment
NCT03882580	Not specified	UNKNOWN	Reporting, Evaluating, Preventing and Treating the Cardiotoxicity Induced by Anticancer Drugs During a Specific Cardio-oncology Consult and Follow up in Routine Care
NCT04051086	Not specified	UNKNOWN	Quantification of Elastin Markers Synthesis in Williams-Beuren Syndrome and 7q11.23 Micro-duplication Syndrome
NCT05251129	Not specified	WITHDRAWN	Statin InTensity to Prevent Coronary Artery Vasculopathy After Heart Transplantation
NCT05485467	Not specified	COMPLETED	The Role of CD34 + Stem Cells and Biomarkers in the Development of CAV in HTX Patients

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
ALIROCUMAB	4	1

Cohort genes: CACNA1G, ADGRV1, IFIH1, ANKRD11, ASXL2, ASXL3, EEF1A2, BPTF, HIVEP2, ATP6V1A, PTPN11, RAI1
Drugs: Alirocumab