Kaposiform hemangioendothelioma

Summary

Kaposiform hemangioendothelioma (MONDO:0016236) is a disease with 1 cohort gene and 11 clinical trials. Top therapeutic interventions include sirolimus.

At a glance

• Prevalence: Unknown (Worldwide)
• Cohort genes: 1
• ClinVar variants: 1
• Phenotypes (HPO): 14
• Clinical trials: 11

Clinical features

Signs & symptoms

Clinical features (HPO)

14 HPO clinical features (Orphanet curated; top 14 by frequency):

HPO ID	Term	Frequency
HP:0005520	Chronic disseminated intravascular coagulation	Frequent (30-79%)
HP:0011900	Hypofibrinogenemia	Frequent (30-79%)
HP:0012531	Pain	Frequent (30-79%)
HP:0025474	Erythematous plaque	Frequent (30-79%)
HP:0030350	Erythematous papule	Frequent (30-79%)
HP:0033106	Elevated circulating D-dimer concentration	Frequent (30-79%)
HP:0000967	Petechiae	Frequent (30-79%)
HP:0000969	Edema	Frequent (30-79%)
HP:0000979	Purpura	Frequent (30-79%)
HP:0001004	Lymphedema	Frequent (30-79%)
HP:0001873	Thrombocytopenia	Frequent (30-79%)
HP:0001937	Microangiopathic hemolytic anemia	Frequent (30-79%)
HP:0000975	Hyperhidrosis	Occasional (5-29%)
HP:0000998	Hypertrichosis	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	kaposiform hemangioendothelioma
Mondo ID	MONDO:0016236
MeSH	C537007
Orphanet	2122
NCIT	C27510
SNOMED CT	403983000
UMLS	C1367420
MedGen	234548
GARD	0003077
Is cancer (heuristic)	no

Also known as: congenital cutaneous multifocal kaposiform hemangioendothelioma · Kaposiform hemangio-endothelioma · Kaposiform hemangioendothelioma · KH · KHE

Data availability: 1 ClinVar variant.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › cancer or benign tumor › neoplastic disease or syndrome › neoplasm › connective and soft tissue neoplasm › soft tissue neoplasm › kaposiform hemangioendothelioma

Related subtypes (17): synovium neoplasm, central nervous system mesenchymal non-meningothelial tumor, mediastinal mesenchymal tumor, nodular fasciitis, mixed endometrial stromal and smooth muscle tumor, neoplasm with perivascular epithelioid cell differentiation, desmoid tumor, congenital epulis, inflammatory myofibroblastic tumor, juvenile hyaline fibromatosis, glomus tumor, Mazabraud syndrome, melanoma of soft tissue, malignant soft tissue neoplasm, soft tissue amyloid neoplasm, fibromyxoid tumor, benign soft tissue neoplasm

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

1 retrieved; paginated sample, class counts are floors:

1 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
548667	NM_004297.4(GNA14):c.614A>T (p.Gln205Leu)	GNA14	Pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 3 · 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

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
GNA14	HGNC:4382	ENSG00000156049	O95837	Guanine nucleotide-binding protein subunit alpha-14	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.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.0

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
Other/Unknown	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
GNA14	Other/Unknown	no		Gprotein_alpha_Q, Gprotein_alpha_su, GproteinA_insert

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
oocyte	1
secondary oocyte	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

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
GNA14	1,081

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
GNA14	O95837	93.68

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 9. 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
Fatty Acids bound to GPR40 (FFAR1) regulate insulin secretion	1	1427.5×	0.004	GNA14
Acetylcholine regulates insulin secretion	1	1142.0×	0.004	GNA14
G-protein activation	1	475.8×	0.004	GNA14
Thromboxane signalling through TP receptor	1	475.8×	0.004	GNA14
ADP signalling through P2Y purinoceptor 1	1	456.8×	0.004	GNA14
Thrombin signalling through proteinase activated receptors (PARs)	1	356.9×	0.004	GNA14
Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding	1	300.5×	0.004	GNA14
PLC beta mediated events	1	265.6×	0.004	GNA14
G alpha (q) signalling events	1	57.4×	0.017	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 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
phospholipase C-activating dopamine receptor signaling pathway	1	2106.5×	0.003	GNA14
action potential	1	358.6×	0.007	GNA14
adenylate cyclase-modulating G protein-coupled receptor signaling pathway	1	337.0×	0.007	GNA14
cell chemotaxis	1	185.2×	0.009	GNA14
positive regulation of inflammatory response	1	145.3×	0.009	GNA14
phospholipase C-activating G protein-coupled receptor signaling pathway	1	131.7×	0.009	GNA14
signal transduction	1	16.1×	0.062	GNA14

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
GNA14	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	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: 11.

Phase distribution (across all retrieved trials)

Phase	Trials
PHASE2	5
PHASE4	3
Not specified	3

Top trials by phase / activity

NCT	Phase	Status	Title
NCT04077515	PHASE4	COMPLETED	Safety and Efficacy of Low-dose Sirolimus to Kaposiform Hemangioendothelioma
NCT04448873	PHASE4	COMPLETED	Guided Discontinuation Versus Maintenance Treatment of Sirolimus in Pediatric Patients With Kaposiform Hemangioendothelioma
NCT04921722	PHASE4	UNKNOWN	Percutaneous Administration of Sirolimus in the Treatment of Superficial Complicated Vascular Anomalies
NCT07131644	PHASE2	NOT_YET_RECRUITING	Sirolimus Discontinuation Strategies in Kaposiform Hemangioendothelioma
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
NCT03188068	PHASE2	COMPLETED	Sirolimus Versus Sirolimus Plus Prednisolone for Kaposiform Hemangioendothelioma
NCT04775173	PHASE2	COMPLETED	Efficacy and Safety of Different Concentrations of Sirolimus in the Treatment of Kaposiform Hemangioendothelioma.
NCT02399527	Not specified	RECRUITING	Lymphatic Anomalies Registry for the Assessment of Outcome Data
NCT03001180	Not specified	RECRUITING	Identification of Biomarkers for Patients with Vascular Anomalies
NCT05351216	Not specified	RECRUITING	The Effect of Sirolimus on Immunizations During the Treatment of Kaposiform Hemangioendothelioma

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
SIROLIMUS	4	7