Tufted angioma

Summary

Tufted angioma (MONDO:0011927) is a disease with 2 cohort genes and 3 clinical trials. Top therapeutic interventions include sirolimus.

At a glance

• Prevalence: Unknown (Worldwide) [Orphanet-validated]
• Cohort genes: 2
• ClinVar variants: 4
• Phenotypes (HPO): 16
• Clinical trials: 3

Clinical features

Epidemiology

Prevalence records

1 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		200	Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

16 HPO clinical features (Orphanet curated; top 16 by frequency):

HPO ID	Term	Frequency
HP:0000975	Hyperhidrosis	Frequent (30-79%)
HP:0001903	Anemia	Frequent (30-79%)
HP:0011355	Localized skin lesion	Frequent (30-79%)
HP:0000329	Facial hemangioma	Occasional (5-29%)
HP:0000565	Esotropia	Occasional (5-29%)
HP:0000967	Petechiae	Occasional (5-29%)
HP:0000979	Purpura	Occasional (5-29%)
HP:0000998	Hypertrichosis	Occasional (5-29%)
HP:0001873	Thrombocytopenia	Occasional (5-29%)
HP:0003401	Paresthesia	Occasional (5-29%)
HP:0005548	Megakaryocytopenia	Occasional (5-29%)
HP:0008069	Neoplasm of the skin	Occasional (5-29%)
HP:0010990	Abnormality of the common coagulation pathway	Occasional (5-29%)
HP:0011900	Hypofibrinogenemia	Occasional (5-29%)
HP:0012531	Pain	Occasional (5-29%)
HP:0031490	Hemangioma of the lip	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	tufted angioma
Mondo ID	MONDO:0011927
MeSH	C536924
OMIM	607859
Orphanet	1063
ICD-11	1994573217
NCIT	C4487
SNOMED CT	705155008
UMLS	C0346073
MedGen	83402
GARD	0000425
Is cancer (heuristic)	no

Also known as: angioblastoma of Nakagawa · angioma tufted · Nakagawa angioblastoma · tufted angioma · tufted angioma (disease) · tufted angioma of skin · tufted angioma of the skin · tufted hemangioma · tufted hemangioma of skin · tufted hemangioma of the skin · tufted skin angioma

Data availability: 4 ClinVar variants · 1 HPO phenotype.

Disease family

Classification path: 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 › skin hemangioma › tufted angioma

Related subtypes (9): skin epithelioid hemangioma, cherry hemangioma, angiokeratoma, scrotal hemangioma, verrucous hemangioma, Wyburn-Mason syndrome, Cobb syndrome, angioma serpiginosum, eyelid capillary hemangioma

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

4 retrieved; paginated sample, class counts are floors:

3 uncertain significance, 1 likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
2672184	NM_004297.4(GNA14):c.215C>T (p.Thr72Met)	GNA14	Uncertain significance	criteria provided, single submitter
2672219	NM_004297.4(GNA14):c.356T>C (p.Met119Thr)	GNA14	Uncertain significance	criteria provided, multiple submitters, no conflicts
2672213	NM_002253.4(KDR):c.1136C>T (p.Ala379Val)	KDR	Uncertain significance	criteria provided, multiple submitters, no conflicts
623416	NM_002253.4(KDR):c.2312C>T (p.Thr771Met)	KDR	Likely benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 4 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
GNA14	Orphanet:1063	Tufted angioma
GNA14	Orphanet:2122	Kaposiform hemangioendothelioma
GNA14	Orphanet:675359	Anastomosing haemangioma
KDR	Orphanet:3303	Tetralogy of Fallot

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
GNA14	HGNC:4382	ENSG00000156049	O95837	Guanine nucleotide-binding protein subunit alpha-14	clinvar
KDR	HGNC:6307	ENSG00000128052	P35968	Vascular endothelial growth factor receptor 2	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
GNA14	Guanine nucleotide-binding protein subunit alpha-14	Guanine nucleotide-binding proteins (G proteins) are involved as modulators or transducers in various transmembrane signaling systems.
KDR	Vascular endothelial growth factor receptor 2	Tyrosine-protein kinase that acts as a cell-surface receptor for VEGFA, VEGFC and VEGFD.

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)
GNA14	Other/Unknown	no		Gprotein_alpha_Q, Gprotein_alpha_su, GproteinA_insert
KDR	Kinase	yes	2.7.10.1	Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom, Tyr_kinase_rcpt_3_CS

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
bronchial epithelial cell	1
oocyte	1
secondary oocyte	1
germinal epithelium of ovary	1
lower lobe of lung	1
parietal pleura	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
GNA14	208	broad	marker	secondary oocyte, oocyte, bronchial epithelial cell
KDR	267	broad	marker	germinal epithelium of ovary, lower lobe of lung, parietal pleura

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
KDR	4,960
GNA14	1,081

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
KDR	P35968	54

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
GNA14	O95837	93.68

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 16. 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
Neuropilin interactions with VEGF and VEGFR	1	1427.5×	0.006	KDR
Signaling by membrane-tethered fusions of PDGFRA or PDGFRB	1	1142.0×	0.006	KDR
Fatty Acids bound to GPR40 (FFAR1) regulate insulin secretion	1	713.8×	0.006	GNA14
VEGF binds to VEGFR leading to receptor dimerization	1	634.4×	0.006	KDR
Acetylcholine regulates insulin secretion	1	571.0×	0.006	GNA14
VEGFR2 mediated cell proliferation	1	285.5×	0.008	KDR
G-protein activation	1	237.9×	0.008	GNA14
Thromboxane signalling through TP receptor	1	237.9×	0.008	GNA14
ADP signalling through P2Y purinoceptor 1	1	228.4×	0.008	GNA14
Thrombin signalling through proteinase activated receptors (PARs)	1	178.4×	0.009	GNA14
Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding	1	150.3×	0.010	GNA14
PLC beta mediated events	1	132.8×	0.010	GNA14
High laminar flow shear stress activates signaling by PIEZO1 and PECAM1:CDH5:KDR in endothelial cells	1	80.4×	0.015	KDR
VEGFA-VEGFR2 Pathway	1	69.6×	0.016	KDR
Integrin cell surface interactions	1	67.2×	0.016	KDR
G alpha (q) signalling events	1	28.7×	0.035	GNA14

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
positive regulation of nitric oxide-cGMP mediated signal transduction	1	8426.0×	0.006	KDR
cellular response to hydrogen sulfide	1	2808.7×	0.006	KDR
post-embryonic camera-type eye morphogenesis	1	2106.5×	0.006	KDR
endocardium development	1	1685.2×	0.006	KDR
blood vessel endothelial cell differentiation	1	1685.2×	0.006	KDR
regulation of hematopoietic progenitor cell differentiation	1	1685.2×	0.006	KDR
regulation of bone development	1	1685.2×	0.006	KDR
vascular endothelial growth factor receptor-2 signaling pathway	1	1404.3×	0.006	KDR
phospholipase C-activating dopamine receptor signaling pathway	1	1053.2×	0.006	GNA14
lymph vessel development	1	936.2×	0.006	KDR
vascular wound healing	1	936.2×	0.006	KDR
positive regulation of mitochondrial depolarization	1	842.6×	0.006	KDR
epithelial cell maturation	1	766.0×	0.006	KDR
positive regulation of positive chemotaxis	1	702.2×	0.006	KDR
endothelium development	1	648.1×	0.006	KDR
positive regulation of vasculogenesis	1	648.1×	0.006	KDR
mesenchymal cell proliferation	1	561.7×	0.006	KDR
endothelial cell differentiation	1	561.7×	0.006	KDR
vascular endothelial growth factor signaling pathway	1	526.6×	0.006	KDR
embryonic hemopoiesis	1	495.6×	0.006	KDR
positive regulation of endothelial cell chemotaxis	1	495.6×	0.006	KDR
surfactant homeostasis	1	401.2×	0.007	KDR
positive regulation of mitochondrial fission	1	383.0×	0.007	KDR
positive regulation of cell migration involved in sprouting angiogenesis	1	366.4×	0.008	KDR
positive regulation of focal adhesion assembly	1	324.1×	0.008	KDR
positive regulation of mesenchymal cell proliferation	1	300.9×	0.008	KDR
cellular response to vascular endothelial growth factor stimulus	1	280.9×	0.008	KDR
branching involved in blood vessel morphogenesis	1	263.3×	0.008	KDR
positive regulation of macroautophagy	1	263.3×	0.008	KDR
positive regulation of stem cell proliferation	1	263.3×	0.008	KDR

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 2 evidence-associated genes (50%) 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
KDR	VANDETANIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
KDR	172	4
GNA14	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
VANDETANIB	4	KDR
ERLOTINIB	4	KDR
INDIGOTINDISULFONATE	4	KDR
PONATINIB	4	KDR
SORAFENIB TOSYLATE	4	KDR
PHENYL AMINOSALICYLATE	4	KDR
VEMURAFENIB	4	KDR
FEDRATINIB	4	KDR
TIVOZANIB	4	KDR
LENVATINIB	4	KDR
AXITINIB	4	KDR
SORAFENIB	4	KDR
PIPERAZINE	4	KDR
NICLOSAMIDE	4	KDR
GLAFENINE	4	KDR
SUNITINIB MALATE	4	KDR
AUROTHIOGLUCOSE	4	KDR
ALECTINIB	4	KDR
ESTRAMUSTINE PHOSPHATE	4	KDR
NERATINIB	4	KDR
INFIGRATINIB PHOSPHATE	4	KDR
INFIGRATINIB	4	KDR
IBRUTINIB	4	KDR
REGORAFENIB	4	KDR
ENTRECTINIB	4	KDR
STIRIPENTOL	4	KDR
CABOZANTINIB S-MALATE	4	KDR
QUIZARTINIB DIHYDROCHLORIDE	4	KDR
CABOZANTINIB	4	KDR
TOFACITINIB	4	KDR

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
KDR	2,687	Binding:2594, Functional:64, ADMET:27, Toxicity:2

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
KDR	2.7.10.1	receptor protein-tyrosine kinase

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
KDR	2,687

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)
VANDETANIB	4	KDR
ERLOTINIB	4	KDR
INDIGOTINDISULFONATE	4	KDR
PONATINIB	4	KDR
SORAFENIB TOSYLATE	4	KDR
PHENYL AMINOSALICYLATE	4	KDR
VEMURAFENIB	4	KDR
FEDRATINIB	4	KDR
TIVOZANIB	4	KDR
LENVATINIB	4	KDR
AXITINIB	4	KDR
SORAFENIB	4	KDR
PIPERAZINE	4	KDR
NICLOSAMIDE	4	KDR
GLAFENINE	4	KDR
SUNITINIB MALATE	4	KDR
AUROTHIOGLUCOSE	4	KDR
ALECTINIB	4	KDR
ESTRAMUSTINE PHOSPHATE	4	KDR
NERATINIB	4	KDR
INFIGRATINIB PHOSPHATE	4	KDR
INFIGRATINIB	4	KDR
IBRUTINIB	4	KDR
REGORAFENIB	4	KDR
ENTRECTINIB	4	KDR
STIRIPENTOL	4	KDR
CABOZANTINIB S-MALATE	4	KDR
QUIZARTINIB DIHYDROCHLORIDE	4	KDR
CABOZANTINIB	4	KDR
TOFACITINIB	4	KDR

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	KDR
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	1	GNA14

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)
GNA14	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 3.

Phase distribution (across all retrieved trials)

Phase	Trials
PHASE2	2
PHASE4	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT04921722	PHASE4	UNKNOWN	Percutaneous Administration of Sirolimus in the Treatment of Superficial Complicated Vascular Anomalies
NCT00975819	PHASE2	COMPLETED	Safety and Efficacy Study of Sirolimus in Complicated Vascular Anomalies
NCT02110069	PHASE2	TERMINATED	A Study to Compare Vincristine to Sirolimus for Treatment of High Risk Vascular Tumors

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
SIROLIMUS	4	3