COL4A1-related disorder

Summary

COL4A1-related disorder (MONDO:0800461) is a disease (an umbrella term covering 5 Mondo subtypes) with 1 cohort gene.

At a glance

• Umbrella term: 5 Mondo subtypes
• Cohort genes: 1
• ClinVar variants: 168

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	COL4A1-related disorder
Mondo ID	MONDO:0800461
GARD	0028064
Is cancer (heuristic)	no

Also known as: COL4A1-related disorders

Data availability: 168 ClinVar variants.

Disease family

An umbrella term covering 5 Mondo subtypes.

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › COL4A1/A2-related disorder › COL4A1-related disorder

Related subtypes (2): brain small vessel disease 2A, autosomal dominant, hemorrhage, intracerebral, susceptibility to

Subtypes (5): brain small vessel disease 1 with or without ocular anomalies, retinal arterial tortuosity, autosomal dominant familial hematuria-retinal arteriolar tortuosity-contractures syndrome, familial schizencephaly, microangiopathy and leukoencephalopathy, pontine, autosomal dominant

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

168 retrieved; paginated sample, class counts are floors:

52 likely benign, 42 uncertain significance, 26 conflicting classifications of pathogenicity, 16 benign/likely benign, 16 likely pathogenic, 6 pathogenic/likely pathogenic, 5 benign, 5 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1333877	NM_001845.6(COL4A1):c.2788G>A (p.Gly930Ser)	COL4A1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1417465	NM_001845.6(COL4A1):c.3187C>T (p.Arg1063Ter)	COL4A1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
17421	NM_001845.6(COL4A1):c.2159G>A (p.Gly720Asp)	COL4A1	Pathogenic	criteria provided, single submitter
208663	NM_001845.6(COL4A1):c.2494G>A (p.Gly832Arg)	COL4A1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
209141	NM_001845.6(COL4A1):c.2662G>A (p.Gly888Arg)	COL4A1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3069147	NM_001845.6(COL4A1):c.3294del (p.Ser1101fs)	COL4A1	Pathogenic	criteria provided, single submitter
3377389	NM_001845.6(COL4A1):c.2707G>C (p.Gly903Arg)	COL4A1	Pathogenic	criteria provided, single submitter
379845	NM_001845.6(COL4A1):c.2317G>A (p.Gly773Arg)	COL4A1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
4531446	NM_001845.6(COL4A1):c.1675G>A (p.Gly559Ser)	COL4A1	Pathogenic	criteria provided, single submitter
870803	NM_001845.6(COL4A1):c.2008G>A (p.Gly670Arg)	COL4A1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
982405	NM_001845.6(COL4A1):c.4843G>A (p.Glu1615Lys)	COL4A1	Pathogenic	criteria provided, single submitter
1324115	NM_001845.6(COL4A1):c.3850G>A (p.Gly1284Arg)	COL4A1	Likely pathogenic	criteria provided, multiple submitters, no conflicts
1922707	NM_001845.6(COL4A1):c.1022G>C (p.Gly341Ala)	COL4A1	Likely pathogenic	criteria provided, multiple submitters, no conflicts
2584470	NM_001845.6(COL4A1):c.2411dup (p.Gly805fs)	COL4A1	Likely pathogenic	criteria provided, single submitter
2631473	NM_001845.6(COL4A1):c.3851G>A (p.Gly1284Glu)	COL4A1	Likely pathogenic	criteria provided, single submitter
2633221	NM_001845.6(COL4A1):c.2486G>T (p.Gly829Val)	COL4A1	Likely pathogenic	criteria provided, single submitter
3061119	NM_001845.6(COL4A1):c.1536+1G>A	COL4A1	Likely pathogenic	no assertion criteria provided
3061221	NM_001845.6(COL4A1):c.2869G>T (p.Gly957Ter)	COL4A1	Likely pathogenic	no assertion criteria provided
3345064	NM_001845.6(COL4A1):c.2096-2del	COL4A1	Likely pathogenic	no assertion criteria provided
3719562	NM_001845.6(COL4A1):c.3958G>A (p.Gly1320Ser)	COL4A1	Likely pathogenic	criteria provided, multiple submitters, no conflicts
3765642	NM_001845.6(COL4A1):c.1784G>A (p.Gly595Asp)	COL4A1	Likely pathogenic	criteria provided, single submitter
4279688	NM_001845.6(COL4A1):c.1973G>A (p.Gly658Asp)	COL4A1	Likely pathogenic	criteria provided, single submitter
4293600	NM_001845.6(COL4A1):c.3505+2T>C	COL4A1	Likely pathogenic	criteria provided, single submitter
4531444	NM_001845.6(COL4A1):c.3506G>T (p.Gly1169Val)	COL4A1	Likely pathogenic	criteria provided, single submitter
4819072	NM_001845.6(COL4A1):c.1121-1G>C	COL4A1	Likely pathogenic	criteria provided, single submitter
4845462	NM_001845.6(COL4A1):c.2324del (p.Pro775fs)	COL4A1	Likely pathogenic	criteria provided, single submitter
489189	NM_001845.6(COL4A1):c.1085-2A>G	COL4A1	Likely pathogenic	criteria provided, multiple submitters, no conflicts
1010870	NM_001845.6(COL4A1):c.3019C>T (p.Pro1007Ser)	COL4A1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1206038	NM_001845.6(COL4A1):c.1754G>A (p.Arg585His)	COL4A1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1546348	NM_001845.6(COL4A1):c.4706C>T (p.Pro1569Leu)	COL4A1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 7 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

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

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
COL4A1	HGNC:2202	ENSG00000187498	P02462	Collagen alpha-1(IV) chain	clinvar

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.

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)
COL4A1	Other/Unknown	no		Collagen_IV_NC, Collagen, CTDL_fold

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
placenta	1
right coronary artery	1
visceral pleura	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

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
COL4A1	2,909

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
COL4A1	P02462	4

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 15. 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
Anchoring fibril formation	1	761.3×	0.006	COL4A1
Scavenging by Class A Receptors	1	601.0×	0.006	COL4A1
Fibronectin matrix formation	1	571.0×	0.006	COL4A1
Crosslinking of collagen fibrils	1	571.0×	0.006	COL4A1
Attachment of bacteria to epithelial cells	1	496.5×	0.006	COL4A1
Laminin interactions	1	380.7×	0.007	COL4A1
Collagen chain trimerization	1	259.6×	0.007	COL4A1
Signaling by PDGF	1	253.8×	0.007	COL4A1
NCAM1 interactions	1	248.3×	0.007	COL4A1
Assembly of collagen fibrils and other multimeric structures	1	200.3×	0.007	COL4A1
Collagen degradation	1	175.7×	0.007	COL4A1
Collagen biosynthesis and modifying enzymes	1	170.4×	0.007	COL4A1
Non-integrin membrane-ECM interactions	1	154.3×	0.007	COL4A1
ECM proteoglycans	1	150.3×	0.007	COL4A1
Integrin cell surface interactions	1	134.3×	0.007	COL4A1

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
renal tubule morphogenesis	1	4213.0×	0.002	COL4A1
retinal blood vessel morphogenesis	1	2407.4×	0.002	COL4A1
collagen-activated tyrosine kinase receptor signaling pathway	1	1296.3×	0.003	COL4A1
blood vessel morphogenesis	1	802.5×	0.003	COL4A1
branching involved in blood vessel morphogenesis	1	526.6×	0.003	COL4A1
neuromuscular junction development	1	526.6×	0.003	COL4A1
basement membrane organization	1	510.7×	0.003	COL4A1
cellular response to amino acid stimulus	1	306.4×	0.004	COL4A1
collagen fibril organization	1	224.7×	0.005	COL4A1
epithelial cell differentiation	1	175.5×	0.006	COL4A1
brain development	1	79.5×	0.013	COL4A1

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 1 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

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	COL4A1

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)
COL4A1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.