Familial porencephaly

Summary

Familial porencephaly (MONDO:0020496) is a disease (an umbrella term covering 7 Mondo subtypes) with 2 cohort genes.

At a glance

• Prevalence: <1 / 1 000 000 (Europe)
• Umbrella term: 7 Mondo subtypes
• Cohort genes: 2

Clinical features

Epidemiology

Prevalence records

1 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Point prevalence	<1 / 1 000 000		Europe	Not yet validated

Identifiers

Disease identifiers

Field	Value
Canonical name	familial porencephaly
Mondo ID	MONDO:0020496
OMIM	175780
Orphanet	99810
DOID	DOID:0112313
ICD-11	1833583032
UMLS	C1867983
MedGen	401353
GARD	0002258
Is cancer (heuristic)	no

Also known as: familial porencephalic white matter disease · hereditary porencephaly

Data availability: 2 GenCC gene-disease records.

Disease family

An umbrella term covering 7 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › nervous system disorder › central nervous system disorder › brain disorder › cerebrovascular disorder › familial porencephaly

Related subtypes (23): cerebral arteritis, intracranial thrombosis, occlusion precerebral artery, vascular dementia, stroke disorder, internal carotid artery stenosis, carotid artery disorder, brain ischemia, brain infarction, cerebral amyloid angiopathy, vascular brain injury, basal ganglia cerebrovascular disorder, intracranial arterial disease, intracranial vasospasm, subclavian steal syndrome, pseudotumor cerebri, cerebral sinovenous thrombosis, HTRA1-related autosomal dominant cerebral small vessel disease, microangiopathy and leukoencephalopathy, pontine, autosomal dominant, cathepsin a-related arteriopathy-strokes-leukoencephalopathy, precerebral artery stenosis, cerebral artery stenosis, APP-related brain and vascular amyloidosis

Subtypes (7): brain small vessel disease 1 with or without ocular anomalies, brain small vessel disease 2A, autosomal dominant, brain small vessel disease 3, brain small vessel disease 4, brain small vessel disease 5 with osteoporosis, brain small vessel disease 6 with leukoencephalopathy, brain small vessel disease 2B, autosomal recessive

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: 16 · Orphanet: 9 · 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
COL4A1	Supportive	Autosomal dominant	familial porencephaly	11
COL4A2	Supportive	Autosomal dominant	familial porencephaly	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
COL4A1	Orphanet:36383	COL4A1/2-related familial vascular leukoencephalopathy
COL4A1	Orphanet:477749	Pontine autosomal dominant microangiopathy with leukoencephalopathy
COL4A1	Orphanet:481986	Familial schizencephaly
COL4A1	Orphanet:73229	HANAC syndrome
COL4A1	Orphanet:75326	Familial isolated retinal arteriolar tortuosity
COL4A1	Orphanet:899	Walker-Warburg syndrome
COL4A1	Orphanet:99810	Familial porencephaly
COL4A2	Orphanet:36383	COL4A1/2-related familial vascular leukoencephalopathy
COL4A2	Orphanet:99810	Familial porencephaly

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
COL4A1	HGNC:2202	ENSG00000187498	P02462	Collagen alpha-1(IV) chain	gencc
COL4A2	HGNC:2203	ENSG00000134871	P08572	Collagen alpha-2(IV) chain	gencc

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
COL4A1	Collagen alpha-1(IV) chain	Type IV collagen is the major structural component of glomerular basement membranes (GBM), forming a ‘chicken-wire’ meshwork together with laminins, proteoglycans and entactin/nidogen.
COL4A2	Collagen alpha-2(IV) chain	Type IV collagen is the major structural component of glomerular basement membranes (GBM), forming a ‘chicken-wire’ meshwork together with laminins, proteoglycans and entactin/nidogen.

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)
COL4A1	Other/Unknown	no		Collagen_IV_NC, Collagen, CTDL_fold
COL4A2	Other/Unknown	no		Collagen_IV_NC, Collagen, CTDL_fold

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
placenta	2
right coronary artery	1
visceral pleura	1
decidua	1
saphenous vein	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
COL4A1	283	ubiquitous	marker	visceral pleura, placenta, right coronary artery
COL4A2	284	ubiquitous	marker	saphenous vein, decidua, placenta

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
COL4A1	2,909
COL4A2	2,746

Intra-cohort edges

A	B	Sources
COL4A1	COL4A2	intact, string_interaction

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
COL4A1	P02462	4
COL4A2	P08572	4

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 15. 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
Anchoring fibril formation	2	761.3×	1e-05	COL4A1, COL4A2
Scavenging by Class A Receptors	2	601.0×	1e-05	COL4A1, COL4A2
Fibronectin matrix formation	2	571.0×	1e-05	COL4A1, COL4A2
Crosslinking of collagen fibrils	2	571.0×	1e-05	COL4A1, COL4A2
Attachment of bacteria to epithelial cells	2	496.5×	1e-05	COL4A1, COL4A2
Laminin interactions	2	380.7×	2e-05	COL4A1, COL4A2
Collagen chain trimerization	2	259.6×	3e-05	COL4A1, COL4A2
Signaling by PDGF	2	253.8×	3e-05	COL4A1, COL4A2
NCAM1 interactions	2	248.3×	3e-05	COL4A1, COL4A2
Assembly of collagen fibrils and other multimeric structures	2	200.3×	4e-05	COL4A1, COL4A2
Collagen degradation	2	175.7×	4e-05	COL4A1, COL4A2
Collagen biosynthesis and modifying enzymes	2	170.4×	4e-05	COL4A1, COL4A2
Non-integrin membrane-ECM interactions	2	154.3×	5e-05	COL4A1, COL4A2
ECM proteoglycans	2	150.3×	5e-05	COL4A1, COL4A2
Integrin cell surface interactions	2	134.3×	5e-05	COL4A1, COL4A2

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
collagen-activated tyrosine kinase receptor signaling pathway	2	1296.3×	1e-05	COL4A1, COL4A2
collagen fibril organization	2	224.7×	2e-04	COL4A1, COL4A2
renal tubule morphogenesis	1	2106.5×	0.003	COL4A1
retinal blood vessel morphogenesis	1	1203.7×	0.004	COL4A1
blood vessel morphogenesis	1	401.2×	0.008	COL4A1
branching involved in blood vessel morphogenesis	1	263.3×	0.008	COL4A1
neuromuscular junction development	1	263.3×	0.008	COL4A1
basement membrane organization	1	255.3×	0.008	COL4A1
endodermal cell differentiation	1	247.8×	0.008	COL4A2
response to activity	1	162.0×	0.011	COL4A2
cellular response to amino acid stimulus	1	153.2×	0.011	COL4A1
cellular response to transforming growth factor beta stimulus	1	138.1×	0.011	COL4A2
DNA-templated transcription	1	112.3×	0.012	COL4A2
epithelial cell differentiation	1	87.8×	0.014	COL4A1
negative regulation of angiogenesis	1	84.3×	0.014	COL4A2
extracellular matrix organization	1	61.1×	0.018	COL4A2
brain development	1	39.8×	0.026	COL4A1
angiogenesis	1	31.2×	0.032	COL4A2

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
COL4A1	0	0
COL4A2	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	COL4A1, COL4A2

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)
COL4A1	0	—
COL4A2	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.