Congenital hemangioma

Summary

Congenital hemangioma (MONDO:0018715) is a disease caused by variants in GNA11 and GNAQ, with 2 cohort genes and 1 clinical trial.

At a glance

• Causal genes: GNA11 (GenCC Strong), GNAQ (GenCC Strong)
• Cohort genes: 2
• Clinical trials: 1

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	congenital hemangioma
Mondo ID	MONDO:0018715
Orphanet	458775
NCIT	C3841
SNOMED CT	32361000119104
UMLS	C0235753
MedGen	65912
GARD	0021910
Is cancer (heuristic)	no

Also known as: congenital hemangioma

Data availability: 2 GenCC gene-disease records.

Disease family

An umbrella term covering 3 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 › congenital hemangioma

Related subtypes (27): malignant hemangioma, arteriovenous hemangioma/malformation, hemangioma of orbit, intra-abdominal hemangioma, capillary 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, epithelioid hemangioma, hemangioma of retina, hemangioma of choroid, hemangioma of gingiva, diffuse cavernous hemangioma of the rectum

Subtypes (3): non-involuting congenital hemangioma, rapidly involuting congenital hemangioma, partially involuting congenital 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

No tiered GWAS variants or ClinVar records for this disease.

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 15 · Orphanet: 13 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
GNA11	Strong	Autosomal dominant	congenital hemangioma	11
GNAQ	Strong	Autosomal dominant	congenital hemangioma	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
GNA11	Orphanet:101049	Familial hypocalciuric hypercalcemia type 2
GNA11	Orphanet:1556	Cutis marmorata telangiectatica congenita
GNA11	Orphanet:39044	Uveal melanoma
GNA11	Orphanet:428	Autosomal dominant hypocalcemia
GNA11	Orphanet:675359	Anastomosing haemangioma
GNA11	Orphanet:714737	Diffuse capillary malformation with overgrowth
GNA11	Orphanet:79483	Phakomatosis cesioflammea
GNA11	Orphanet:79484	Phakomatosis cesiomarmorata
GNAQ	Orphanet:3205	Sturge-Weber syndrome
GNAQ	Orphanet:39044	Uveal melanoma
GNAQ	Orphanet:624	Familial multiple nevi flammei
GNAQ	Orphanet:675359	Anastomosing haemangioma
GNAQ	Orphanet:79483	Phakomatosis cesioflammea

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
GNA11	HGNC:4379	ENSG00000088256	P29992	Guanine nucleotide-binding protein subunit alpha-11	gencc
GNAQ	HGNC:4390	ENSG00000156052	P50148	Guanine nucleotide-binding protein G(q) subunit alpha	gencc

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
GNA11	Guanine nucleotide-binding protein subunit alpha-11	Guanine nucleotide-binding proteins (G proteins) function as transducers downstream of G protein-coupled receptors (GPCRs) in numerous signaling cascades.
GNAQ	Guanine nucleotide-binding protein G(q) subunit alpha	Guanine nucleotide-binding proteins (G proteins) function as transducers downstream of G protein-coupled receptors (GPCRs) in numerous signaling cascades.

Protein-family classification

Druggable: 0 · Difficult: 0 · 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
Other/Unknown	2	1.8×	0.312

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
GNA11	Other/Unknown	no		Gprotein_alpha_Q, Gprotein_alpha_su, GproteinA_insert
GNAQ	Other/Unknown	no		Gprotein_alpha_Q, Gprotein_alpha_su, GproteinA_insert

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
ileal mucosa	1
jejunal mucosa	1
pancreatic ductal cell	1
CA1 field of hippocampus	1
dorsal motor nucleus of vagus nerve	1
postcentral gyrus	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
GNA11	299	ubiquitous	marker	ileal mucosa, jejunal mucosa, pancreatic ductal cell
GNAQ	302	ubiquitous	marker	CA1 field of hippocampus, dorsal motor nucleus of vagus nerve, postcentral gyrus

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
GNAQ	3,480
GNA11	1,873

Intra-cohort edges

A	B	Sources
GNA11	GNAQ	string_interaction

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
GNAQ	P50148	37
GNA11	P29992	13

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 11. 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
Fatty Acids bound to GPR40 (FFAR1) regulate insulin secretion	2	1427.5×	4e-06	GNA11, GNAQ
Acetylcholine regulates insulin secretion	2	1142.0×	4e-06	GNA11, GNAQ
G-protein activation	2	475.8×	1e-05	GNA11, GNAQ
Thromboxane signalling through TP receptor	2	475.8×	1e-05	GNA11, GNAQ
ADP signalling through P2Y purinoceptor 1	2	456.8×	1e-05	GNA11, GNAQ
Thrombin signalling through proteinase activated receptors (PARs)	2	356.9×	1e-05	GNA11, GNAQ
Turbulent (oscillatory, disturbed) flow shear stress activates signaling by PIEZO1 and integrins in endothelial cells	2	356.9×	1e-05	GNA11, GNAQ
Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding	2	300.5×	1e-05	GNA11, GNAQ
PLC beta mediated events	2	265.6×	2e-05	GNA11, GNAQ
High laminar flow shear stress activates signaling by PIEZO1 and PECAM1:CDH5:KDR in endothelial cells	2	160.8×	4e-05	GNA11, GNAQ
G alpha (q) signalling events	2	57.4×	3e-04	GNA11, GNAQ

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
entrainment of circadian clock	2	2808.7×	3e-06	GNA11, GNAQ
phototransduction, visible light	2	1296.3×	9e-06	GNA11, GNAQ
G protein-coupled acetylcholine receptor signaling pathway	2	1053.2×	9e-06	GNA11, GNAQ
phospholipase C-activating G protein-coupled receptor signaling pathway	2	131.7×	5e-04	GNA11, GNAQ
regulation of melanocyte differentiation	1	8426.0×	8e-04	GNA11
phospholipase C-activating G protein-coupled glutamate receptor signaling pathway	1	2106.5×	0.003	GNAQ
phospholipase C-activating serotonin receptor signaling pathway	1	1404.3×	0.003	GNAQ
regulation of platelet activation	1	1404.3×	0.003	GNAQ
phospholipase C-activating G protein-coupled acetylcholine receptor signaling pathway	1	1053.2×	0.003	GNA11
developmental pigmentation	1	1053.2×	0.003	GNA11
phospholipase C-activating dopamine receptor signaling pathway	1	1053.2×	0.003	GNA11
cellular response to pH	1	1053.2×	0.003	GNA11
sensory perception of itch	1	936.2×	0.003	GNAQ
ligand-gated ion channel signaling pathway	1	936.2×	0.003	GNA11
endothelin receptor signaling pathway	1	842.6×	0.003	GNA11
response to prostaglandin E	1	702.2×	0.003	GNAQ
glutamate receptor signaling pathway	1	468.1×	0.004	GNAQ
cranial skeletal system development	1	468.1×	0.004	GNA11
cellular response to acidic pH	1	366.4×	0.005	GNAQ
mast cell degranulation	1	312.1×	0.005	GNAQ
regulation of canonical Wnt signaling pathway	1	271.8×	0.006	GNAQ
hormone-mediated signaling pathway	1	200.6×	0.007	GNAQ
action potential	1	179.3×	0.008	GNA11
adenylate cyclase-modulating G protein-coupled receptor signaling pathway	1	168.5×	0.008	GNA11
positive regulation of insulin secretion	1	127.7×	0.010	GNA11
regulation of blood pressure	1	110.9×	0.011	GNA11
blood coagulation	1	86.9×	0.014	GNAQ
neuropeptide signaling pathway	1	86.0×	0.014	GNAQ
skeletal system development	1	62.9×	0.018	GNA11
adenylate cyclase-activating G protein-coupled receptor signaling pathway	1	56.5×	0.019	GNAQ

Therapeutics

Drug target analysis

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

Druggability breadth: 2 of 2 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
GNA11	0	0
GNAQ	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
GNAQ	27	Binding:27
GNA11	18	Binding:18

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

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	2	GNA11, GNAQ

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
GNA11	18	—
GNAQ	27	—

Clinical trials & evidence

Clinical trials

Clinical trials: 1.

Phase distribution (across all retrieved trials)

Phase	Trials
PHASE4	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT02625389	PHASE4	COMPLETED	A Study to Evaluate How Safe and Effective is the Mixture of Lipiodol® Ultra Fluid and Glue When Used for Embolization Procedures