Cavernous hemangioma

Summary

Cavernous hemangioma (MONDO:0003155) is a disease (an umbrella term covering 7 Mondo subtypes) with 3 cohort genes and 9 clinical trials.

At a glance

• Umbrella term: 7 Mondo subtypes
• Cohort genes: 3
• ClinVar variants: 4
• Clinical trials: 9

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	cavernous hemangioma
Mondo ID	MONDO:0003155
EFO	EFO:1000151
MeSH	D006392
DOID	DOID:483
NCIT	C3086
SNOMED CT	416824008
UMLS	C0018920
MedGen	9184
GARD	0023388
Is cancer (heuristic)	no

Also known as: cavernoma · cavernous angioma · cavernous hemangioma · cavernous hemangioma (morphologic abnormality)

Data availability: 4 ClinVar variants · 1 HPO phenotype.

Disease family

An umbrella term covering 7 Mondo subtypes.

Classification path: disease › human disease › disease by etiologic mechanism › cancer or benign tumor › neoplastic disease or syndrome › neoplasm › hematopoietic and lymphoid system neoplasm › cavernous hemangioma

Related subtypes (8): thymus neoplasm, bone marrow neoplasm, STAT3-related early-onset multisystem autoimmune disease, myeloid hemopathy, lymphoid hemopathy, lymph node neoplasm, spleen neoplasm, hematopoietic and lymphoid cell neoplasm

Subtypes (7): cavernous hemangioma of orbit, intracranial cavernous angioma, dermal unilateral segmental cavernous angioma, giant hemangioma, cavernous hemangioma of colon, cavernous hemangioma of face, liver cavernous 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:

2 pathogenic, 1 pathogenic/likely pathogenic, 1 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
374160	NM_031443.4(CCM2):c.354C>G (p.Tyr118Ter)	CCM2	Pathogenic	criteria provided, single submitter
523476	NM_194454.3(KRIT1):c.902C>G (p.Ser301Ter)	KRIT1	Pathogenic	criteria provided, multiple submitters, no conflicts
468331	NM_007217.4(PDCD10):c.474+5G>A	PDCD10	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
523477	NM_194454.3(KRIT1):c.990-1G>A	KRIT1	Likely 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
KRIT1	Orphanet:221061	Familial cerebral cavernous malformation
CCM2	Orphanet:221061	Familial cerebral cavernous malformation
PDCD10	Orphanet:221061	Familial cerebral cavernous malformation

Cohort genes → proteins

3 cohort genes, 3 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	3

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
KRIT1	HGNC:1573	ENSG00000001631	O00522	Krev interaction trapped protein 1	clinvar
CCM2	HGNC:21708	ENSG00000136280	Q9BSQ5	Cerebral cavernous malformations 2 protein	clinvar
PDCD10	HGNC:8761	ENSG00000114209	Q9BUL8	Programmed cell death protein 10	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
KRIT1	Krev interaction trapped protein 1	Component of the CCM signaling pathway which is a crucial regulator of heart and vessel formation and integrity.
CCM2	Cerebral cavernous malformations 2 protein	Component of the CCM signaling pathway which is a crucial regulator of heart and vessel formation and integrity.
PDCD10	Programmed cell death protein 10	Promotes cell proliferation.

Protein-family classification

Druggable: 0 · Difficult: 1 · Unknown: 2 · 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
Scaffold/PPI	1	5.8×	0.327
Other/Unknown	2	1.2×	0.587

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
KRIT1	Scaffold/PPI	no		FERM_domain, Ankyrin_rpt, PH-like_dom_sf
CCM2	Other/Unknown	no		PTB/PI_dom, PH-like_dom_sf, Malcavernin
PDCD10	Other/Unknown	no		PDCD10, PDC10_dimerisation_sf, PDCD10_N

Expression context

Cohort genes with no expression data: 0.

3 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)	3
unknown	0

Top tissues across cohort

Tissue	Cohort genes
calcaneal tendon	1
colonic epithelium	1
corpus callosum	1
anterior cingulate cortex	1
nucleus accumbens	1
putamen	1
colonic mucosa	1
jejunal mucosa	1
mucosa of sigmoid colon	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
KRIT1	138	ubiquitous	marker	calcaneal tendon, colonic epithelium, corpus callosum
CCM2	243	ubiquitous	marker	putamen, nucleus accumbens, anterior cingulate cortex
PDCD10	295	ubiquitous	marker	jejunal mucosa, mucosa of sigmoid colon, colonic mucosa

Protein interactions among cohort

Intra-cohort edges: 3.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
PDCD10	1,792
CCM2	1,600
KRIT1	1,290

Intra-cohort edges

A	B	Sources
CCM2	KRIT1	biogrid_interaction, intact, string_interaction
CCM2	PDCD10	intact, string_interaction
KRIT1	PDCD10	intact, string_interaction

Structural data

PDB: 3 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
KRIT1	O00522	15
PDCD10	Q9BUL8	10
CCM2	Q9BSQ5	8

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 0. Enrichment computed across 3 evidence-associated genes (0 with Reactome annotation).

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 3 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
endothelium development	3	1296.3×	2e-08	KRIT1, CCM2, PDCD10
regulation of angiogenesis	3	421.3×	3e-07	KRIT1, CCM2, PDCD10
intrinsic apoptotic signaling pathway in response to hydrogen peroxide	1	1872.4×	0.006	PDCD10
endothelial cell development	1	1404.3×	0.006	CCM2
blood vessel endothelial cell differentiation	1	1123.5×	0.006	CCM2
Golgi reassembly	1	1123.5×	0.006	PDCD10
angiogenesis	2	41.6×	0.006	KRIT1, PDCD10
venous blood vessel morphogenesis	1	802.5×	0.006	CCM2
negative regulation of blood vessel endothelial cell proliferation involved in sprouting angiogenesis	1	702.2×	0.006	PDCD10
establishment of Golgi localization	1	624.1×	0.006	PDCD10
pericardium development	1	624.1×	0.006	CCM2
endothelial tube morphogenesis	1	624.1×	0.006	CCM2
integrin activation	1	468.1×	0.007	KRIT1
positive regulation of protein serine/threonine kinase activity	1	432.1×	0.007	PDCD10
wound healing, spreading of cells	1	374.5×	0.008	PDCD10
negative regulation of cell migration involved in sprouting angiogenesis	1	330.4×	0.008	PDCD10
regulation of establishment of cell polarity	1	312.1×	0.008	KRIT1
positive regulation of stress-activated MAPK cascade	1	267.5×	0.009	PDCD10
negative regulation of endothelial cell migration	1	255.3×	0.009	KRIT1
positive regulation of peptidyl-serine phosphorylation	1	255.3×	0.009	PDCD10
stress-activated MAPK cascade	1	234.1×	0.009	CCM2
positive regulation of intracellular protein transport	1	224.7×	0.009	PDCD10
positive regulation of MAP kinase activity	1	216.1×	0.009	PDCD10
cell-cell junction organization	1	208.1×	0.009	CCM2
negative regulation of endothelial cell proliferation	1	181.2×	0.010	KRIT1
negative regulation of endothelial cell apoptotic process	1	165.2×	0.010	KRIT1
inner ear development	1	124.8×	0.013	CCM2
positive regulation of Notch signaling pathway	1	117.0×	0.013	PDCD10
cell redox homeostasis	1	114.6×	0.013	KRIT1
vasculogenesis	1	85.1×	0.017	CCM2

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 3 evidence-associated genes (33%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
KRIT1	0	0
CCM2	0	0
PDCD10	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
PDCD10	1	Binding:1

Pharmacogenomics

Cohort genes with a PharmGKB record: 3; 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	3	KRIT1, CCM2, PDCD10

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
KRIT1	0	—
CCM2	0	—
PDCD10	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 9.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	8
PHASE1	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT00783523	PHASE1	COMPLETED	Influence of MMP on Brain AVM Hemorrhage
NCT04076449	Not specified	RECRUITING	Quantitative Susceptibility Biomarker and Brain Structural Property for Cerebral Cavernous Malformation Related Epilepsy
NCT04467489	Not specified	ACTIVE_NOT_RECRUITING	Biomarkers of CASH
NCT05477680	Not specified	RECRUITING	Intraoperative Brain Shift Calculation Study
NCT05484245	Not specified	RECRUITING	Sonography-guided Resection of Brain Mass Lesions
NCT06724029	Not specified	RECRUITING	Neurosurgical Outcome Network
NCT06915649	Not specified	RECRUITING	Exploration and Evaluation of Amygdalo-Hippocampectomy According to Prof. Coubes’ Technique: An Anatomical, Clinical, and Educational Approach
NCT03652181	Not specified	COMPLETED	CASH (Cavernous Angiomas With Symptomatic Hemorrhage) Trial Readiness
NCT05484219	Not specified	SUSPENDED	Functional Navigation in Surgery of Cerebral Tumors and Vascular Malformations