vein of Galen aneurysm

Summary

vein of Galen aneurysm (MONDO:0015196) is a disease with 7 cohort genes. The dominant Reactome pathway is Chromatin organization (3 cohort genes).

At a glance

• Prevalence: Unknown (Worldwide)
• Cohort genes: 7
• ClinVar variants: 13
• Phenotypes (HPO): 3

Clinical features

Signs & symptoms

Clinical features (HPO)

3 HPO clinical features (Orphanet curated; top 3 by frequency):

HPO ID	Term	Frequency
HP:0100659	Abnormality of the cerebral vasculature	Very frequent (80-99%)
HP:0002617	Dilatation	Frequent (30-79%)
HP:0100784	Peripheral arteriovenous fistula	Frequent (30-79%)

Identifiers

Disease identifiers

Field	Value
Canonical name	vein of Galen aneurysm
Mondo ID	MONDO:0015196
MeSH	C536535
Orphanet	1053
ICD-11	1884295064
NCIT	C98642
SNOMED CT	253194008
UMLS	C0431420
MedGen	140912
GARD	0005467
Anatomy (UBERON)	UBERON:0006666
Is cancer (heuristic)	no

Also known as: ectasia or varix of the vein of Galen · Galen vein aneurysm · Galenic arteriovenous malformation · vein of Galen aneurysm malformation · vein of Galen arteriovenous malformations · VGAM

Data availability: 13 ClinVar variants.

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 › arteriovenous hemangioma/malformation › vein of Galen aneurysm

Related subtypes (6): arteriovenous malformations of the brain, cerebrofacial arteriovenous metameric syndrome, facial arteriovenous malformation, Cobb syndrome, Foix-Alajouanine syndrome, dural sinus malformation

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

13 retrieved; paginated sample, class counts are floors:

6 uncertain significance, 5 association, 1 pathogenic, 1 conflicting classifications of pathogenicity

ClinVar	Variant (HGVS)	Gene	Classification	Review
1344637	NM_003482.4(KMT2D):c.15689G>A (p.Cys5230Tyr)	KMT2D	Pathogenic	criteria provided, single submitter
228518	NM_001146079.2(CLDN14):c.185A>G (p.Tyr62Cys)	CLDN14	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1344633	NM_001146079.2(CLDN14):c.337G>C (p.Ala113Pro)	CLDN14	association	no assertion criteria provided
2672099	NM_001146079.2(CLDN14):c.116_118del (p.Asn39del)	CLDN14	Uncertain significance	criteria provided, single submitter
4279806	NM_001146079.2(CLDN14):c.682G>A (p.Ala228Thr)	CLDN14	Uncertain significance	criteria provided, single submitter
4279853	NM_001146079.2(CLDN14):c.292G>T (p.Ala98Ser)	CLDN14	Uncertain significance	criteria provided, single submitter
1344632	NM_001146079.2(CLDN14):c.427G>A (p.Val143Met)	CLDN14-AS1	Uncertain significance	criteria provided, single submitter
1344630	NM_004444.5(EPHB4):c.1295_1296del (p.Glu432fs)	EPHB4	association	no assertion criteria provided
1344631	NM_004444.5(EPHB4):c.1526C>G (p.Ala509Gly)	EPHB4	Uncertain significance	criteria provided, single submitter
432911	NM_006766.5(KAT6A):c.1433C>T (p.Thr478Ile)	KAT6A	Uncertain significance	criteria provided, single submitter
1344634	NM_000420.3(KEL):c.604G>A (p.Gly202Ser)	KEL	association	no assertion criteria provided
1344636	NM_000420.3(KEL):c.961C>T (p.Gln321Ter)	KEL	association	no assertion criteria provided
1344638	NM_003070.5(SMARCA2):c.2564G>T (p.Arg855Leu)	SMARCA2	association	no assertion criteria provided

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 11 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SMARCA2	Orphanet:3051	Nicolaides-Baraitser syndrome
SMARCA2	Orphanet:637013	SMARCA2-related blepharophimosis-intellectual disability syndrome
KAT6A	Orphanet:370026	Acute myeloid leukemia with t(8;16)(p11;p13) translocation
KAT6A	Orphanet:457193	KAT6-related intellectual disability-craniofacial anomalies-cardiac defects syndrome
CLDN14	Orphanet:90636	Rare autosomal recessive non-syndromic sensorineural deafness type DFNB
EPHB4	Orphanet:1053	Vein of Galen malformation
EPHB4	Orphanet:568065	EPHB4-related lymphatic-related hydrops fetalis
EPHB4	Orphanet:693912	EPHB4-related capillary malformation-arteriovenous malformation
EPHB4	Orphanet:90186	Meige disease
KMT2D	Orphanet:2322	Kabuki syndrome
KMT2D	Orphanet:589856	Choanal atresia-athelia-hypothyroidism-delayed puberty-short stature syndrome

Cohort genes → proteins

7 cohort genes, 6 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	7

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
SMARCA2	HGNC:11098	ENSG00000080503	P51531	SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A member 2	clinvar
KAT6A	HGNC:13013	ENSG00000083168	Q92794	Histone acetyltransferase KAT6A	clinvar
CLDN14	HGNC:2035	ENSG00000159261	O95500	Claudin-14	clinvar
EPHB4	HGNC:3395	ENSG00000196411	P54760	Ephrin type-B receptor 4	clinvar
LNCTSI	HGNC:56660	ENSG00000230479		lncRNA TGF-beta/SMAD3 pathway interacting	clinvar
KEL	HGNC:6308	ENSG00000197993	P23276	Kell blood group glycoprotein	clinvar
KMT2D	HGNC:7133	ENSG00000167548	O14686	Histone-lysine N-methyltransferase 2D	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SMARCA2	SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A member 2	ATPase involved in transcriptional activation and repression of select genes by chromatin remodeling (alteration of DNA-nucleosome topology).
KAT6A	Histone acetyltransferase KAT6A	Histone acetyltransferase that acetylates lysine residues in histone H3 and histone H4 (in vitro).
CLDN14	Claudin-14	Plays a major role in tight junction-specific obliteration of the intercellular space, through calcium-independent cell-adhesion activity.
EPHB4	Ephrin type-B receptor 4	Receptor tyrosine kinase which binds promiscuously transmembrane ephrin-B family ligands residing on adjacent cells, leading to contact-dependent bidirectional signaling into neighboring cells.
KEL	Kell blood group glycoprotein	Zinc endopeptidase with endothelin-3-converting enzyme activity.
KMT2D	Histone-lysine N-methyltransferase 2D	Histone methyltransferase that catalyzes methyl group transfer from S-adenosyl-L-methionine to the epsilon-amino group of ‘Lys-4’ of histone H3 (H3K4).

Protein-family classification

Druggable: 2 · Difficult: 2 · Unknown: 3 · Druggable fraction: 0.29

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
Protease	1	5.2×	0.302
Kinase	1	4.0×	0.302
Transcription factor	2	2.4×	0.302
Other/Unknown	3	0.8×	0.858

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
SMARCA2	Other/Unknown	no		SNF2_N, Bromodomain, Helicase_C-like
KAT6A	Transcription factor	no	2.3.1.48	Znf_PHD, HAT_MYST-type, Histone_H1/H5_H15
CLDN14	Other/Unknown	no		PMP22/EMP/MP20/Claudin, Claudin, Claudin_CS
EPHB4	Kinase	yes	2.7.10.1	Prot_kinase_dom, EPH_LBD, Ser-Thr/Tyr_kinase_cat_dom
LNCTSI	Other/Unknown	no
KEL	Protease	yes		Peptidase_M13, Peptidase_M13_N, Peptidase_M13_C
KMT2D	Transcription factor	no		SET_dom, Znf_RING, Znf_PHD

Expression context

Cohort genes with no expression data: 0.

6 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)	7
unknown	0

Top tissues across cohort

Tissue	Cohort genes
medial globus pallidus	2
calcaneal tendon	1
colonic epithelium	1
cortical plate	1
globus pallidus	1
nipple	1
liver	1
male germ line stem cell (sensu Vertebrata) in testis	1
right lobe of liver	1
body of uterus	1
olfactory bulb	1
type B pancreatic cell	1
gastrocnemius	1
muscle of leg	1
skeletal muscle tissue	1
left testis	1
right testis	1
testis	1
buccal mucosa cell	1
sural nerve	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SMARCA2	301	ubiquitous	marker	calcaneal tendon, colonic epithelium, cortical plate
KAT6A	299	ubiquitous	marker	nipple, medial globus pallidus, globus pallidus
CLDN14	84	tissue_specific	marker	right lobe of liver, liver, male germ line stem cell (sensu Vertebrata) in testis
EPHB4	282	ubiquitous	marker	olfactory bulb, type B pancreatic cell, body of uterus
LNCTSI	115		yes	skeletal muscle tissue, muscle of leg, gastrocnemius
KEL	131	broad	marker	right testis, left testis, testis
KMT2D	272	ubiquitous	marker	buccal mucosa cell, medial globus pallidus, sural nerve

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
SMARCA2	4,237
KMT2D	3,223
EPHB4	2,547
KEL	882
CLDN14	772
KAT6A	649
LNCTSI	0

Structural data

PDB: 4 · AlphaFold-only: 2 · No structure: 1

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
SMARCA2	P51531	32
EPHB4	P54760	23
KAT6A	Q92794	21
KMT2D	O14686	11

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
KEL	P23276	87.46
CLDN14	O95500	80.00

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 47. Enrichment computed across 7 evidence-associated genes (6 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 6 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Chromatin organization	3	40.8×	0.001	SMARCA2, KAT6A, KMT2D
Chromatin modifying enzymes	3	36.1×	0.001	SMARCA2, KAT6A, KMT2D
Transcriptional regulation by RUNX1	2	48.8×	0.011	SMARCA2, KMT2D
RNA Polymerase II Transcription	3	11.3×	0.018	SMARCA2, KAT6A, KMT2D
Loss of Function of KMT2D in MLL4 Complex Formation in Kabuki Syndrome	1	380.7×	0.021	KMT2D
Epigenetic regulation of gene expression	2	23.8×	0.021	SMARCA2, KMT2D
Gene expression (Transcription)	3	8.9×	0.021	SMARCA2, KAT6A, KMT2D
Generic Transcription Pathway	3	7.5×	0.029	SMARCA2, KAT6A, KMT2D
Formation of the non-canonical BAF (ncBAF) complex	1	112.0×	0.040	SMARCA2
Formation of the canonical BAF (cBAF) complex	1	105.7×	0.040	SMARCA2
Formation of the polybromo-BAF (pBAF) complex	1	105.7×	0.040	SMARCA2
Ephrin signaling	1	95.2×	0.041	EPHB4
Regulation of TP53 Activity through Acetylation	1	76.1×	0.043	KAT6A
Formation of neuronal progenitor and neuronal BAF (npBAF and nBAF)	1	76.1×	0.043	SMARCA2
Activation of HOX genes during differentiation	1	73.2×	0.043	KMT2D
Tight junction interactions	1	61.4×	0.045	CLDN14
Regulation of endogenous retroelements	1	61.4×	0.045	SMARCA2
RUNX1 interacts with co-factors whose precise effect on RUNX1 targets is not known	1	50.1×	0.050	SMARCA2
EPHB-mediated forward signaling	1	44.3×	0.050	EPHB4
Formation of WDR5-containing histone-modifying complexes	1	44.3×	0.050	KMT2D
Regulation of MITF-M-dependent genes involved in pigmentation	1	44.3×	0.050	SMARCA2
Deactivation of the beta-catenin transactivating complex	1	38.8×	0.054	KMT2D
EPH-ephrin mediated repulsion of cells	1	36.6×	0.054	EPHB4
Epigenetic regulation of adipogenesis genes by MLL3 and MLL4 complexes	1	35.9×	0.054	KMT2D
Epigenetic regulation of gene expression by MLL3 and MLL4 complexes	1	32.8×	0.057	KMT2D
MITF-M-dependent gene expression	1	30.2×	0.059	SMARCA2
EPH-Ephrin signaling	1	27.6×	0.062	EPHB4
PKMTs methylate histone lysines	1	26.8×	0.062	KMT2D
Epigenetic regulation by WDR5-containing histone modifying complexes	1	25.7×	0.062	KMT2D
RMTs methylate histone arginines	1	24.4×	0.063	SMARCA2

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 6 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
beta-catenin-TCF complex assembly	1	2808.7×	0.010	KMT2D
heterochromatin formation	2	85.1×	0.010	SMARCA2, KMT2D
regulation of DNA-templated transcription	3	15.8×	0.011	SMARCA2, KAT6A, KMT2D
oocyte growth	1	702.2×	0.020	KMT2D
regulation of axon diameter	1	561.7×	0.020	KEL
intracellular magnesium ion homeostasis	1	468.1×	0.020	KEL
regulation of developmental process	1	401.2×	0.020	KAT6A
regulation of hemopoiesis	1	255.3×	0.024	KAT6A
protein acetylation	1	234.1×	0.024	KAT6A
negative regulation of potassium ion transmembrane transport	1	234.1×	0.024	KEL
positive regulation of intracellular estrogen receptor signaling pathway	1	200.6×	0.026	KMT2D
vasoconstriction	1	147.8×	0.029	KEL
calcium-independent cell-cell adhesion	1	133.8×	0.029	CLDN14
regulation of cell size	1	127.7×	0.029	KEL
regulation of G0 to G1 transition	1	112.3×	0.029	SMARCA2
cell migration involved in sprouting angiogenesis	1	108.0×	0.029	EPHB4
myeloid cell differentiation	1	108.0×	0.029	KAT6A
regulation of nucleotide-excision repair	1	100.3×	0.029	SMARCA2
chromosome organization	1	96.8×	0.029	KAT6A
skeletal muscle fiber development	1	90.6×	0.029	KEL
regulation of mitotic metaphase/anaphase transition	1	82.6×	0.029	SMARCA2
positive regulation of T cell differentiation	1	75.9×	0.029	SMARCA2
oogenesis	1	63.8×	0.029	KMT2D
regulation of signal transduction by p53 class mediator	1	63.8×	0.029	KAT6A
heart morphogenesis	1	62.4×	0.029	EPHB4
positive regulation of myoblast differentiation	1	61.1×	0.029	SMARCA2
response to estrogen	1	57.3×	0.029	KMT2D
ephrin receptor signaling pathway	1	57.3×	0.029	EPHB4
positive regulation of stem cell population maintenance	1	57.3×	0.029	SMARCA2
positive regulation of double-strand break repair	1	57.3×	0.029	SMARCA2

Therapeutics

Drug target analysis

Approved (phase 4): 1 · Phase ≥3: 1 · Phased (≥1): 2 · Undrugged: 5

Druggability breadth: 4 of 7 evidence-associated genes (57%) 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
EPHB4	PONATINIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
EPHB4	46	4
SMARCA2	2	2
KAT6A	0	0
CLDN14	0	0
LNCTSI	0	0
KEL	0	0
KMT2D	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
PONATINIB	4	EPHB4
FEDRATINIB	4	EPHB4
TIVOZANIB	4	EPHB4
SORAFENIB	4	EPHB4
DASATINIB ANHYDROUS	4	EPHB4
VANDETANIB	4	EPHB4
NILOTINIB	4	EPHB4
BOSUTINIB	4	EPHB4
TOVORAFENIB	4	EPHB4
NINTEDANIB	4	EPHB4
SUNITINIB	4	EPHB4
DASATINIB	4	EPHB4
ERLOTINIB	4	EPHB4
CRIZOTINIB	4	EPHB4
GEFITINIB	4	EPHB4
SARACATINIB	3	EPHB4
LINIFANIB	3	EPHB4
CANERTINIB	3	EPHB4
TESEVATINIB	3	EPHB4
POZIOTINIB	3	EPHB4
ALISERTIB	3	EPHB4
CEDIRANIB	3	EPHB4
LESTAURTINIB	3	EPHB4
MOLIBRESIB	2	SMARCA2
CAMIBIRSTAT	2	SMARCA2
DORAMAPIMOD	2	EPHB4
NEFLAMAPIMOD	2	EPHB4
FORETINIB	2	EPHB4
REBASTINIB	2	EPHB4
CEP-32496	2	EPHB4

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 2.

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

Symbol	Assays	Type breakdown
EPHB4	437	Binding:437
SMARCA2	311	Binding:274, Functional:25, ADMET:12
KAT6A	42	Binding:39, Functional:3
KMT2D	11	Binding:11

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
KAT6A	2.3.1.48	histone acetyltransferase
EPHB4	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
SMARCA2	311
EPHB4	437

Pharmacogenomics

Cohort genes with a PharmGKB record: 6; 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)
PONATINIB	4	EPHB4
FEDRATINIB	4	EPHB4
TIVOZANIB	4	EPHB4
SORAFENIB	4	EPHB4
DASATINIB ANHYDROUS	4	EPHB4
VANDETANIB	4	EPHB4
NILOTINIB	4	EPHB4
BOSUTINIB	4	EPHB4
TOVORAFENIB	4	EPHB4
NINTEDANIB	4	EPHB4
SUNITINIB	4	EPHB4
DASATINIB	4	EPHB4
ERLOTINIB	4	EPHB4
CRIZOTINIB	4	EPHB4
GEFITINIB	4	EPHB4
SARACATINIB	3	EPHB4
LINIFANIB	3	EPHB4
CANERTINIB	3	EPHB4
TESEVATINIB	3	EPHB4
POZIOTINIB	3	EPHB4
ALISERTIB	3	EPHB4
CEDIRANIB	3	EPHB4
LESTAURTINIB	3	EPHB4
MOLIBRESIB	2	SMARCA2
CAMIBIRSTAT	2	SMARCA2
DORAMAPIMOD	2	EPHB4
NEFLAMAPIMOD	2	EPHB4
FORETINIB	2	EPHB4
REBASTINIB	2	EPHB4
CEP-32496	2	EPHB4

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	EPHB4
B	Phased (≥1) drug, not yet approved	1	SMARCA2
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	1	KEL
E	Difficult family or no structure, no drug	4	KAT6A, CLDN14, LNCTSI, KMT2D

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
KAT6A	42	—
CLDN14	0	—
LNCTSI	0	—
KEL	0	—
KMT2D	11	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.