Moyamoya disease 1

Summary

Moyamoya disease 1 (MONDO:0009649) is a disease with 2 cohort genes.

At a glance

• Cohort genes: 2
• ClinVar variants: 4

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	moyamoya disease 1
Mondo ID	MONDO:0009649
MeSH	C536991
OMIM	252350
SNOMED CT	69116000
UMLS	C2931384
MedGen	419790
GARD	0024684
Is cancer (heuristic)	no

Also known as: MYMY1

Data availability: 4 ClinVar variants.

Disease family

Classification path: disease › human disease › disease by body system or component › nervous system disorder › central nervous system disorder › brain disorder › cerebrovascular disorder › intracranial arterial disease › cerebral arterial disease › Moyamoya disease › moyamoya disease 1

Related subtypes (7): moyamoya angiopathy-short stature-facial dysmorphism-hypergonadotropic hypogonadism syndrome, Moyamoya disease 2, moyamoya disease 3, Moyamoya disease 5, Moyamoya disease with early-onset achalasia, moyamoya disease 7, Moyamoya disease 8

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 conflicting classifications of pathogenicity, 2 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
559596	NM_001130682.3(GUCY1A1):c.1258C>T (p.Arg420Ter)	GUCY1A1	Pathogenic	no assertion criteria provided
559597	NM_001130682.3(GUCY1A1):c.1550G>A (p.Cys517Tyr)	GUCY1A1	Pathogenic	no assertion criteria provided
559598	NM_001130682.3(GUCY1A1):c.334_335del (p.Glu112fs)	GUCY1A1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
417851	NM_001256071.3(RNF213):c.12185G>A (p.Arg4062Gln)	RNF213-AS1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 1 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
GUCY1A1	Orphanet:401945	Moyamoya disease with early-onset achalasia

Cohort genes → proteins

2 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
GUCY1A1	HGNC:4685	ENSG00000164116	Q02108	Guanylate cyclase soluble subunit alpha-1	clinvar
RNF213-AS1	HGNC:54402	ENSG00000263069		RNF213 antisense RNA 1	clinvar

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.5

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
Enzyme (other)	1	6.0×	0.320
Other/Unknown	1	0.9×	0.805

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
GUCY1A1	Enzyme (other)	yes	4.6.1.2	A/G_cyclase, HNOB_dom_associated, A/G_cyclase_CS
RNF213-AS1	Other/Unknown	no

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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
saphenous vein	1
urethra	1
vena cava	1
buccal mucosa cell	1
right uterine tube	1
sural nerve	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
GUCY1A1	289	broad	marker	urethra, vena cava, saphenous vein
RNF213-AS1	169	broad	yes	buccal mucosa cell, right uterine tube, sural nerve

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
GUCY1A1	1,383
RNF213-AS1	0

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
GUCY1A1	Q02108	12

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 2. Enrichment computed across 2 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
Nitric oxide stimulates guanylate cyclase	1	815.7×	0.002	GUCY1A1
Smooth Muscle Contraction	1	265.6×	0.004	GUCY1A1

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
retrograde trans-synaptic signaling by nitric oxide, modulating synaptic transmission	1	16852.0×	6e-04	GUCY1A1
obsolete positive regulation of nitric oxide mediated signal transduction	1	4213.0×	8e-04	GUCY1A1
response to oxygen levels	1	4213.0×	8e-04	GUCY1A1
relaxation of vascular associated smooth muscle	1	2808.7×	9e-04	GUCY1A1
nitric oxide-cGMP-mediated signaling	1	1532.0×	0.001	GUCY1A1
cGMP biosynthetic process	1	1404.3×	0.001	GUCY1A1
obsolete nitric oxide mediated signal transduction	1	1296.3×	0.001	GUCY1A1
obsolete cGMP-mediated signaling	1	802.5×	0.002	GUCY1A1
blood circulation	1	510.7×	0.002	GUCY1A1
regulation of blood pressure	1	221.7×	0.005	GUCY1A1

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 2 evidence-associated genes (50%) 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
GUCY1A1	BENZYDAMINE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
GUCY1A1	2	4
RNF213-AS1	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
BENZYDAMINE	4	GUCY1A1
FRESPACIGUAT	2	GUCY1A1

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
GUCY1A1	45	Binding:40, Functional:5

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
GUCY1A1	4.6.1.2	guanylate cyclase

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

2 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)
BENZYDAMINE	4	GUCY1A1
FRESPACIGUAT	2	GUCY1A1

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	GUCY1A1
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	RNF213-AS1

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)
RNF213-AS1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.