Intracranial berry aneurysm

Summary

Intracranial berry aneurysm (MONDO:0016483) is a disease (an umbrella term covering 12 Mondo subtypes) with 2 cohort genes.

At a glance

• Prevalence: Unknown (Worldwide) [Orphanet-validated]
• Umbrella term: 12 Mondo subtypes
• Cohort genes: 2
• Phenotypes (HPO): 15

Clinical features

Signs & symptoms

Clinical features (HPO)

15 HPO clinical features (Orphanet curated; top 15 by frequency):

HPO ID	Term	Frequency
HP:0007029	Cerebral berry aneurysm	Obligate (100%)
HP:0000822	Hypertension	Frequent (30-79%)
HP:0001123	Visual field defect	Frequent (30-79%)
HP:0001250	Seizure	Frequent (30-79%)
HP:0001269	Hemiparesis	Frequent (30-79%)
HP:0002326	Transient ischemic attack	Frequent (30-79%)
HP:0002363	Abnormal brainstem morphology	Frequent (30-79%)
HP:0002621	Atherosclerosis	Frequent (30-79%)
HP:0012518	Abnormality of circle of Willis	Frequent (30-79%)
HP:0002138	Subarachnoid hemorrhage	Occasional (5-29%)
HP:0002170	Intracranial hemorrhage	Occasional (5-29%)
HP:0002616	Aortic root aneurysm	Occasional (5-29%)
HP:0002647	Aortic dissection	Occasional (5-29%)
HP:0012246	Oculomotor nerve palsy	Occasional (5-29%)
HP:0040197	Encephalomalacia	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	intracranial berry aneurysm
Mondo ID	MONDO:0016483
OMIM	105800
Orphanet	231160
DOID	DOID:0060228
ICD-11	59881644
SNOMED CT	703226008
UMLS	C3839866
MedGen	825711
GARD	0017161
Is cancer (heuristic)	no

Also known as: aneurysm, intracranial berry · familial aneurysmal subarachnoid haemorrhage · familial berry aneurysm · familial intracranial saccular aneurysm

Data availability: 2 GenCC gene-disease records · 1 HPO phenotype.

Disease family

An umbrella term covering 12 Mondo subtypes.

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 › brain aneurysm › intracranial berry aneurysm

Subtypes (12): aneurysm, intracranial berry type 1, aneurysm, intracranial berry, 5, aneurysm, intracranial berry, 2, aneurysm, intracranial berry, 3, aneurysm, intracranial berry, 4, aneurysm, intracranial berry, 6, aneurysm, intracranial berry, 7, aneurysm, intracranial berry, 8, aneurysm, intracranial berry, 9, aneurysm, intracranial berry, 10, aneurysm, intracranial berry, 11, aneurysm, intracranial berry, 12

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: 10 · Orphanet: 3 · 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
ANGPTL6	Strong	Autosomal dominant	brain aneurysm	2
THSD1	Strong	Autosomal dominant	aneurysm, intracranial berry, 12	8

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
THSD1	Orphanet:231160	Familial cerebral saccular aneurysm
THSD1	Orphanet:363999	Non-immune hydrops fetalis
ANGPTL6	Orphanet:231160	Familial cerebral saccular aneurysm

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
THSD1	HGNC:17754	ENSG00000136114	Q9NS62	Thrombospondin type-1 domain-containing protein 1	gencc
ANGPTL6	HGNC:23140	ENSG00000130812	Q8NI99	Angiopoietin-related protein 6	gencc

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
THSD1	Thrombospondin type-1 domain-containing protein 1	Is a positive regulator of nascent focal adhesion assembly, involved in the modulation of endothelial cell attachment to the extracellular matrix.
ANGPTL6	Angiopoietin-related protein 6	May play a role in the wound healing process.

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)
THSD1	Other/Unknown	no		TSP1_rpt, TSP1_rpt_sf, THSD1
ANGPTL6	Other/Unknown	no		Fibrinogen_a/b/g_C_dom, Fibrinogen_a/b/g_C_1, Fibrinogen_CS

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
apex of heart	1
right lung	1
ventricular zone	1
male germ line stem cell (sensu Vertebrata) in testis	1
primordial germ cell in gonad	1
right lobe of liver	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
THSD1	138	broad	marker	ventricular zone, right lung, apex of heart
ANGPTL6	153	tissue_specific	yes	right lobe of liver, primordial germ cell in gonad, male germ line stem cell (sensu Vertebrata) in testis

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
THSD1	473
ANGPTL6	397

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
ANGPTL6	Q8NI99	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
THSD1	Q9NS62	59.46

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 9. 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
Defective B3GALTL causes PpS	1	308.6×	0.014	THSD1
O-glycosylation of TSR domain-containing proteins	1	300.5×	0.014	THSD1
Diseases associated with O-glycosylation of proteins	1	215.5×	0.014	THSD1
O-linked glycosylation	1	144.6×	0.014	THSD1
Diseases of glycosylation	1	131.3×	0.014	THSD1
Diseases of metabolism	1	80.4×	0.019	THSD1
Post-translational protein modification	1	19.2×	0.067	THSD1
Disease	1	13.1×	0.081	THSD1
Metabolism of proteins	1	12.4×	0.081	THSD1

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
focal adhesion assembly	1	263.3×	0.015	THSD1
blood coagulation	1	86.9×	0.023	ANGPTL6
angiogenesis	1	31.2×	0.042	ANGPTL6
cell differentiation	1	14.6×	0.068	ANGPTL6

Therapeutics

Drug target analysis

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

Druggability breadth: 0 of 2 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
THSD1	0	0
ANGPTL6	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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	THSD1, ANGPTL6

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)
THSD1	0	—
ANGPTL6	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.