Cerebrofacial arteriovenous metameric syndrome

Summary

Cerebrofacial arteriovenous metameric syndrome (MONDO:0015405) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 1

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	cerebrofacial arteriovenous metameric syndrome
Mondo ID	MONDO:0015405
Orphanet	141189
ICD-11	1402414905
SNOMED CT	703266007
UMLS	C3839265
MedGen	825110
GARD	0012662
Is cancer (heuristic)	no

Also known as: CAMS

Data availability: 1 ClinVar variant.

Disease family

An umbrella term covering 3 Mondo subtypes.

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 › cerebrofacial arteriovenous metameric syndrome

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

Subtypes (3): cerebrofacial arteriovenous metameric syndrome type 1, cerebrofacial arteriovenous metameric syndrome type 3, Wyburn-Mason syndrome

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 uncertain significance

ClinVar	Variant (HGVS)	Gene	Classification	Review
2446463	NM_004297.4(GNA14):c.817G>C (p.Asp273His)	GNA14	Uncertain significance	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: 0.