Capillary hemangioma

Summary

Capillary hemangioma (MONDO:0002407) is a disease (an umbrella term covering 6 Mondo subtypes) with 2 cohort genes and 22 clinical trials. Top therapeutic interventions include propranolol, timolol, and nadolol.

At a glance

• Umbrella term: 6 Mondo subtypes
• Cohort genes: 2
• ClinVar variants: 3
• Clinical trials: 22

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	capillary hemangioma
Mondo ID	MONDO:0002407
MeSH	D018324
DOID	DOID:2725
NCIT	C7457
SNOMED CT	56975005
UMLS	C0206733
MedGen	64643
Is cancer (heuristic)	no

Also known as: capillary angioma · capillary hemangioma · capillary hemangioma (morphologic abnormality) · cellular hemangioma of infancy · cellular hemangioma of infancy (strawberry nevus) · infantile hemangioma · juvenile hemangioma

Data availability: 3 ClinVar variants · 1 cell line.

Disease family

An umbrella term covering 6 Mondo subtypes.

Classification path: disease › human disease › disease by etiologic mechanism › cancer or benign tumor › neoplastic disease or syndrome › neoplasm › benign neoplasm › cardiovascular organ benign neoplasm › benign blood vessel neoplasm › hemangioma › capillary hemangioma

Related subtypes (27): malignant hemangioma, arteriovenous hemangioma/malformation, hemangioma of orbit, intra-abdominal hemangioma, venous hemangioma, deep hemangioma, skin hemangioma, subglottic hemangioma, breast hemangioma, cavernous hemangioma, glomeruloid hemangioma, hemangioma of lung, acquired hemangioma, central nervous system hemangioma, hobnail hemangioma, synovial angioma, placental hemangioma, hemangioma of subcutaneous tissue, hemangiomas of small intestine, spindle cell hemangioma, infantile hemangioma of rare localization, congenital hemangioma, epithelioid hemangioma, hemangioma of retina, hemangioma of choroid, hemangioma of gingiva, diffuse cavernous hemangioma of the rectum

Subtypes (6): cherry hemangioma, breast capillary hemangioma, capillary infantile hemangioma, hemangioblastoma, eyelid capillary hemangioma, pyogenic granuloma

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

3 retrieved; paginated sample, class counts are floors:

1 pathogenic, 1 pathogenic/likely pathogenic, 1 uncertain significance

ClinVar	Variant (HGVS)	Gene	Classification	Review
267941	46;XY;inv(6)(p22q13)dn		Pathogenic	criteria provided, single submitter
39814	NM_005465.7(AKT3):c.1393C>T (p.Arg465Trp)	AKT3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
816923	NM_000271.5(NPC1):c.1315A>G (p.Ile439Val)	NPC1	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 7 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
AKT3	Orphanet:83473	Megalencephaly-polymicrogyria-postaxial polydactyly-hydrocephalus syndrome
AKT3	Orphanet:99802	Hemimegalencephaly
NPC1	Orphanet:216972	Niemann-Pick disease type C, severe perinatal form
NPC1	Orphanet:216975	Niemann-Pick disease type C, severe early infantile neurologic onset
NPC1	Orphanet:216978	Niemann-Pick disease type C, late infantile neurologic onset
NPC1	Orphanet:216981	Niemann-Pick disease type C, juvenile neurologic onset
NPC1	Orphanet:216986	Niemann-Pick disease type C, adult neurologic onset

Cohort genes → proteins

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
AKT3	HGNC:393	ENSG00000117020	Q9Y243	RAC-gamma serine/threonine-protein kinase	clinvar
NPC1	HGNC:7897	ENSG00000141458	O15118	NPC intracellular cholesterol transporter 1	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
AKT3	RAC-gamma serine/threonine-protein kinase	AKT3 is one of 3 closely related serine/threonine-protein kinases (AKT1, AKT2 and AKT3) called the AKT kinase, and which regulate many processes including metabolism, proliferation, cell survival, growth and angiogenesis.
NPC1	NPC intracellular cholesterol transporter 1	Intracellular cholesterol transporter which acts in concert with NPC2 and plays an important role in the egress of cholesterol from the endosomal/lysosomal compartment.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 1 · 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	13.9×	0.142
Other/Unknown	1	0.9×	0.805

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
AKT3	Kinase	yes	2.7.11.1	Prot_kinase_dom, AGC-kinase_C, PH_domain
NPC1	Other/Unknown	no		SSD, NPC1-like, NPC1_N

Expression context

Cohort genes with no expression data: 0.

2 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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
calcaneal tendon	1
cortical plate	1
embryo	1
adrenal tissue	1
oocyte	1
secondary oocyte	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
AKT3	231	ubiquitous	marker	cortical plate, calcaneal tendon, embryo
NPC1	292	ubiquitous	marker	secondary oocyte, oocyte, adrenal tissue

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
AKT3	3,392
NPC1	2,648

Structural data

PDB: 2 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
NPC1	O15118	20
AKT3	Q9Y243	2

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 84. Enrichment computed across 2 evidence-associated genes (2 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 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
AKT-mediated inactivation of FOXO1A	1	1427.5×	0.016	AKT3
Inhibition of TSC complex formation by AKT (PKB)	1	1142.0×	0.016	AKT3
G-protein beta:gamma signalling	1	951.7×	0.016	AKT3
RUNX2 regulates genes involved in cell migration	1	713.8×	0.016	AKT3
AKT phosphorylates targets in the nucleus	1	571.0×	0.016	AKT3
Regulation of localization of FOXO transcription factors	1	475.8×	0.016	AKT3
SARS-CoV-2 targets host intracellular signalling and regulatory pathways	1	439.2×	0.016	AKT3
Downregulation of ERBB2:ERBB3 signaling	1	407.9×	0.016	AKT3
AKT phosphorylates targets in the cytosol	1	407.9×	0.016	AKT3
Regulation of TP53 Activity through Association with Co-factors	1	407.9×	0.016	AKT3
Activation of BAD and translocation to mitochondria	1	380.7×	0.016	AKT3
Regulation of beta-cell development	1	356.9×	0.016	AKT3
LDL clearance	1	271.9×	0.016	NPC1
Regulation of gene expression in beta cells	1	259.6×	0.016	AKT3
Co-inhibition by CTLA4	1	259.6×	0.016	AKT3
Regulation of TP53 Expression and Degradation	1	259.6×	0.016	AKT3
Activation of BH3-only proteins	1	248.3×	0.016	AKT3
Regulation of TP53 Activity through Acetylation	1	228.4×	0.016	AKT3
G beta:gamma signalling through PI3Kgamma	1	219.6×	0.016	AKT3
Estrogen-dependent nuclear events downstream of ESR-membrane signaling	1	219.6×	0.016	AKT3
Regulation of T cell activation by CD28 family	1	211.5×	0.016	AKT3
Constitutive Signaling by AKT1 E17K in Cancer	1	211.5×	0.016	AKT3
VEGFR2 mediated vascular permeability	1	203.9×	0.016	AKT3
CD28 dependent PI3K/Akt signaling	1	196.9×	0.016	AKT3
Co-stimulation by CD28	1	190.3×	0.016	AKT3
Downregulation of ERBB2 signaling	1	190.3×	0.016	AKT3
PI3K/AKT Signaling in Cancer	1	184.2×	0.016	AKT3
Rab regulation of trafficking	1	184.2×	0.016	AKT3
Signaling by ERBB2	1	173.0×	0.016	AKT3
FLT3 Signaling	1	173.0×	0.016	AKT3

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
cyclodextrin metabolic process	1	8426.0×	0.006	NPC1
intracellular lipid transport	1	2808.7×	0.006	NPC1
membrane raft organization	1	1685.2×	0.006	NPC1
positive regulation of artery morphogenesis	1	1685.2×	0.006	AKT3
sterol transport	1	1404.3×	0.006	NPC1
cholesterol storage	1	1203.7×	0.006	NPC1
establishment of protein localization to membrane	1	936.2×	0.006	NPC1
intestinal cholesterol absorption	1	702.2×	0.006	NPC1
negative regulation of PERK-mediated unfolded protein response	1	702.2×	0.006	AKT3
programmed cell death	1	648.1×	0.006	NPC1
intracellular cholesterol transport	1	648.1×	0.006	NPC1
positive regulation of cell size	1	648.1×	0.006	AKT3
negative regulation of epithelial cell apoptotic process	1	601.9×	0.006	NPC1
negative regulation of macroautophagy	1	561.7×	0.006	NPC1
cellular response to steroid hormone stimulus	1	526.6×	0.006	NPC1
bile acid metabolic process	1	495.6×	0.006	NPC1
cellular response to low-density lipoprotein particle stimulus	1	443.5×	0.006	NPC1
regulation of mitochondrion organization	1	421.3×	0.006	AKT3
positive regulation of vascular endothelial cell proliferation	1	421.3×	0.006	AKT3
cholesterol transport	1	366.4×	0.006	NPC1
response to cadmium ion	1	366.4×	0.006	NPC1
brain morphogenesis	1	366.4×	0.006	AKT3
positive regulation of cell migration involved in sprouting angiogenesis	1	366.4×	0.006	AKT3
lysosomal transport	1	351.1×	0.006	NPC1
negative regulation of cellular senescence	1	324.1×	0.006	AKT3
cholesterol efflux	1	263.3×	0.007	NPC1
adult walking behavior	1	247.8×	0.007	NPC1
positive regulation of TOR signaling	1	247.8×	0.007	AKT3
homeostasis of number of cells within a tissue	1	221.7×	0.007	AKT3
symbiont entry into host cell	1	200.6×	0.008	NPC1

Therapeutics

Drug target analysis

Approved (phase 4): 2 · Phase ≥3: 2 · Phased (≥1): 2 · Undrugged: 0

Druggability breadth: 2 of 2 evidence-associated genes (100%) 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
AKT3	CAPIVASERTIB
NPC1	NABUMETONE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
NPC1	90	4
AKT3	18	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
CAPIVASERTIB	4	AKT3
MIDOSTAURIN	4	AKT3
NABUMETONE	4	NPC1
PHENELZINE	4	NPC1
AMLEXANOX	4	NPC1
IDARUBICIN	4	NPC1
RABEPRAZOLE SODIUM	4	NPC1
NITAZOXANIDE	4	NPC1
NICLOSAMIDE	4	NPC1
NITROXOLINE	4	NPC1
NICARDIPINE	4	NPC1
DAUNORUBICIN HYDROCHLORIDE	4	NPC1
INDOPROFEN	4	NPC1
CYCLOSPORINE	4	NPC1
TERFENADINE	4	NPC1
DIGOXIN	4	NPC1
PRAZOSIN	4	NPC1
MAPROTILINE	4	NPC1
DIGITOXIN	4	NPC1
HYDRALAZINE	4	NPC1
EBASTINE	4	NPC1
DEQUALINIUM	4	NPC1
DOXORUBICIN HYDROCHLORIDE	4	NPC1
VINBLASTINE SULFATE	4	NPC1
FLUOXETINE	4	NPC1
DITHIAZANINE IODIDE	4	NPC1
TRIFLUOPERAZINE	4	NPC1
PACLITAXEL	4	NPC1
NORTRIPTYLINE	4	NPC1
MIBEFRADIL	4	NPC1

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
AKT3	660	Binding:644, Functional:16
NPC1	18	Binding:13, Functional:5

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
AKT3	2.7.11.1	non-specific serine/threonine protein kinase

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
AKT3	660

Pharmacogenomics

Cohort genes with a PharmGKB record: 2; 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)
CAPIVASERTIB	4	AKT3
MIDOSTAURIN	4	AKT3
NABUMETONE	4	NPC1
PHENELZINE	4	NPC1
AMLEXANOX	4	NPC1
IDARUBICIN	4	NPC1
RABEPRAZOLE SODIUM	4	NPC1
NITAZOXANIDE	4	NPC1
NICLOSAMIDE	4	NPC1
NITROXOLINE	4	NPC1
NICARDIPINE	4	NPC1
DAUNORUBICIN HYDROCHLORIDE	4	NPC1
INDOPROFEN	4	NPC1
CYCLOSPORINE	4	NPC1
TERFENADINE	4	NPC1
DIGOXIN	4	NPC1
PRAZOSIN	4	NPC1
MAPROTILINE	4	NPC1
DIGITOXIN	4	NPC1
HYDRALAZINE	4	NPC1
EBASTINE	4	NPC1
DEQUALINIUM	4	NPC1
DOXORUBICIN HYDROCHLORIDE	4	NPC1
VINBLASTINE SULFATE	4	NPC1
FLUOXETINE	4	NPC1
DITHIAZANINE IODIDE	4	NPC1
TRIFLUOPERAZINE	4	NPC1
PACLITAXEL	4	NPC1
NORTRIPTYLINE	4	NPC1
MIBEFRADIL	4	NPC1

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	2	AKT3, NPC1
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	0

Undrugged target profiles

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

Clinical trials & evidence

Clinical trials

Clinical trials: 22.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	9
PHASE2	5
PHASE2/PHASE3	3
PHASE4	2
PHASE3	2
PHASE1	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT04288700	PHASE4	UNKNOWN	Evaluation of the Efficacy of Captopril Versus Propranolol and Timolol as a Treatment of Infantile Capillary Hemangioma
NCT05479123	PHASE4	TERMINATED	Assessing the Impact of Dosage Frequency of Propranolol on Sleep Patterns in Patients With Infantile Hemangiomas
NCT06798363	PHASE2/PHASE3	RECRUITING	Efficacy and Safety of Different Initial Doses of Oral Propranolol in the Treatment of Ulcerated Infantile Hemangioma
NCT01056341	PHASE2/PHASE3	COMPLETED	Study to Demonstrate the Efficacy and Safety of Propranolol Oral Solution in Infants With Proliferating Infantile Hemangiomas Requiring Systemic Therapy
NCT02505971	PHASE3	COMPLETED	Nadolol Versus Propranolol in Children With Infantile Hemangiomas
NCT03237637	PHASE3	UNKNOWN	Comparative Study to Evaluate the Effectiveness of Atenolol and Propranolol in the Treatment of Infantile Hemangiomas
NCT06677853	PHASE2/PHASE3	COMPLETED	Timolol Maleate Gel for the Treatment of Infantile Hemangioma
NCT01010308	PHASE2	COMPLETED	Nadolol for Proliferating Infantile Hemangiomas
NCT01408056	PHASE2	WITHDRAWN	Timolol Option for Ulcerated Hemangiomas (TOUCH Trial)
NCT01512173	PHASE2	COMPLETED	Study in Infants With Infantile Hemangioma to Compare Propranolol Gel to Placebo
NCT02913612	PHASE2	COMPLETED	Efficacy, Safety and Pharmacokinetics of Topical Timolol in Infants With Infantile Hemangioma (IH)
NCT04684667	PHASE2	UNKNOWN	‘‘Efficacy of Propranolol in the Treatment of Infantile Hemangioma
NCT01434849	PHASE1	TERMINATED	Timolol for the Prevention of Proliferation of Infantile Hemangioma (TiPPIH Trial)
NCT01431326	Not specified	COMPLETED	Pharmacokinetics of Understudied Drugs Administered to Children Per Standard of Care
NCT01673971	Not specified	COMPLETED	Optical Tomographic Imaging of Infantile Hemangiomas
NCT02061735	Not specified	COMPLETED	Ontogeny of Infantile Hemangiomas With Skin Imaging Modalities
NCT03173352	Not specified	UNKNOWN	A Prospective Study on the Incidence and Related Risk Factors of Infantile Hemangioma in China
NCT03842631	Not specified	UNKNOWN	Optimizing Timolol Maleate Treatment of Infantile Hemangioma by Doppler Ultrasound Examination
NCT04105517	Not specified	COMPLETED	Hemangiol, Post Marketing Surveillance Study
NCT05187923	Not specified	UNKNOWN	Computer Aided Tool for Diagnosis of Neck Masses in Children
NCT07104526	Not specified	COMPLETED	Low-Dose Propranolol and Bleomycin for Infantile Hemangioma (IH)
NCT07560332	Not specified	COMPLETED	Oral Propranolol Versus Fractional Carbon Dioxide CO2 Laser Assisted Delivery of Topical Timolol for Treatment of Infantile Hemangioma

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
PROPRANOLOL	4	13
TIMOLOL	4	10
NADOLOL	4	2
ATENOLOL	4	1
BLEOMYCIN	4	1
CAPTOPRIL	4	1
MUPIROCIN	4	1
DEXPROPRANOLOL	2	5
ESATENOLOL	2	1
CHEMBL1744069	0	2
R-NADOLOL	0	2
CHEMBL1230004	0	1
CHEMBL4793658	0	1