COL4A1 Gene
<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">COL4A1 Gene</th>
</tr>
<tr>
<td class="label">
Symbol</td>
<td>COL4A1</td>
</tr>
<tr>
<td class="label">
Full Name</td>
<td>Collagen Type IV Alpha 1 Chain</td>
</tr>
<tr>
<td class="label">
Chromosomal Location</td>
<td>13q34</td>
</tr>
<tr>
<td class="label">
NCBI Gene ID</td>
<td>1282</td>
</tr>
<tr>
<td class="label">
OMIM ID</td>
<td>120130</td>
</tr>
<tr>
<td class="label">
Ensembl ID</td>
<td>ENSG00000187498</td>
</tr>
<tr>
<td class="label">
UniProt ID</td>
<td>P02462</td>
</tr>
<tr>
<td class="label">
Protein Length</td>
<td>1,664 amino acids</td>
</tr>
<tr>
<td class="label">
Molecular Weight</td>
<td>~161 kDa</td>
</tr>
<tr>
<td class="label">
Gene Family</td>
<td>Type IV collagen alpha chain family</td>
</tr>
<tr>
<td class="label">
Inheritance</td>
<td>Autosomal dominant</td>
</tr>
<tr>
<td class="label">Associated Diseases</td>
<td><a href="/wiki/alzheimer" style="color:#ef9a9a">ALZHEIMER</a>, <a href="/wiki/aging" style="color:#ef9a9a">Aging</a>, <a href="/wiki/als" style="color:#ef9a9a">Als</a>, <a href="/wiki/alzheimer" style="color:#ef9a9a">Alzheimer</a>, <a href="/wiki/atherosclerosis" style="color:#ef9a9a">Atherosclerosis</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">55 edges</a></td>
</tr>
</table>
Overview
...COL4A1 Gene
<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">COL4A1 Gene</th>
</tr>
<tr>
<td class="label">
Symbol</td>
<td>COL4A1</td>
</tr>
<tr>
<td class="label">
Full Name</td>
<td>Collagen Type IV Alpha 1 Chain</td>
</tr>
<tr>
<td class="label">
Chromosomal Location</td>
<td>13q34</td>
</tr>
<tr>
<td class="label">
NCBI Gene ID</td>
<td>1282</td>
</tr>
<tr>
<td class="label">
OMIM ID</td>
<td>120130</td>
</tr>
<tr>
<td class="label">
Ensembl ID</td>
<td>ENSG00000187498</td>
</tr>
<tr>
<td class="label">
UniProt ID</td>
<td>P02462</td>
</tr>
<tr>
<td class="label">
Protein Length</td>
<td>1,664 amino acids</td>
</tr>
<tr>
<td class="label">
Molecular Weight</td>
<td>~161 kDa</td>
</tr>
<tr>
<td class="label">
Gene Family</td>
<td>Type IV collagen alpha chain family</td>
</tr>
<tr>
<td class="label">
Inheritance</td>
<td>Autosomal dominant</td>
</tr>
<tr>
<td class="label">Associated Diseases</td>
<td><a href="/wiki/alzheimer" style="color:#ef9a9a">ALZHEIMER</a>, <a href="/wiki/aging" style="color:#ef9a9a">Aging</a>, <a href="/wiki/als" style="color:#ef9a9a">Als</a>, <a href="/wiki/alzheimer" style="color:#ef9a9a">Alzheimer</a>, <a href="/wiki/atherosclerosis" style="color:#ef9a9a">Atherosclerosis</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">55 edges</a></td>
</tr>
</table>
Overview
Mermaid diagram (expand to render)
Col4A1 Gene plays an important role in the study of neurodegenerative diseases. This page provides comprehensive information about this topic, including its mechanisms, significance in disease processes, and therapeutic implications.
Introduction
Col4A1 Gene is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.
COL4A1 (Collagen Type IV Alpha 1 Chain) encodes the alpha-1 subunit of type IV collagen, a fundamental component of all basement membranes in the body. This gene is crucial for vascular integrity, blood-brain barrier function, and neural development. Mutations in COL4A1 cause hereditary small vessel diseases including porencephaly, hereditary angiopathy with nephropathy, aneurysms, and muscle cramps (HANAC), and intracerebral hemorrhage.
Gene Overview
Gene Structure
The COL4A1 gene spans approximately 162 kb of genomic DNA on chromosome 13q34 and contains 52 exons. The gene encodes a procollagen protein that undergoes extensive post-translational modification:
- N-terminal 7S domain: Non-collagenous domain for tetramer formation
- Triple-helix domain: Gly-X-Y repeating sequence (~1,400 residues)
- C-terminal NC1 domain: Non-collagenous domain for dimer formation
The protein forms a heterotrimer with COL4A2 (alpha-2 chain), creating the α1(IV)₂α2(IV) protomer.
Protein Function
Type IV collagen is the major structural component of basement membranes:
Basement Membrane Structure
- Scaffold formation: Creates mesh-like network providing structural support
- Cell attachment: Binds integrins and other cell surface receptors
- Filtration barrier: Forms selective barrier in glomeruli
- Tissue polarity: Establishes epithelial/endothelial polarity
Neurovascular Function
- [Blood-brain barrier](/entities/blood-brain-barrier): Essential for BBB integrity
- Endothelial junctions: Supports tight junction formation
- Pericyte coverage: Facilitates pericyte-endothelial interactions
- Astrocyte end-feet: Forms specialized astrocytic contacts
CNS Development
- Neural migration: Guides neuronal migration during development
- Cortical layering: Essential for cortical plate formation
- Angiogenesis: Supports blood vessel formation in CNS
Disease Associations
Porencephaly
- Inheritance: Autosomal dominant
- Pathogenesis: Mutations disrupt basement membrane integrity
- Features: Fluid-filled cysts in brain parenchyma
- Symptoms: Cerebral palsy, intellectual disability, seizures, hemiparesis
- Neuroimaging: Cystic cavities communicating with ventricles
- Timing: Prenatal or perinatal onset
HANAC (Hereditary Angiopathy with Nephropathy, Aneurysms, and Muscle Cramps)
- Inheritance: Autosomal dominant
- Systemic involvement: Brain, kidneys, muscles, retina, skin
- Features: Raynaud phenomenon, muscle cramps, hematuria
- Neuroimaging: White matter lesions, microbleeds, aneurysms
Intracerebral Hemorrhage
- Risk: Spontaneous basal ganglia/thalamic hemorrhage
- Mechanism: Weakness of cerebral vessel walls
- Age: Often occurs in middle age
- Recurrence: Increased risk of recurrent hemorrhage
Small Vessel Disease
- Sporadic: Common COL4A1 variants contribute to sporadic SVD
- White matter hyperintensities: MRI-visible lesions
- Lacunes: Small deep infarcts
- Cognitive decline: Vascular cognitive impairment
Alzheimer's Disease
- Vascular contribution: COL4A1 variants modify AD risk
- Cerebral amyloid angiopathy: Interaction with [Aβ](/proteins/amyloid-beta) pathology
- Blood-brain barrier: Compromised in AD brains
Expression Pattern
COL4A1 is ubiquitously expressed in basement membranes:
- Brain: Cerebral [cortex](/brain-regions/cortex), [hippocampus](/brain-regions/hippocampus), basal ganglia, cerebellum
- Vascular: Endothelial cells, [pericytes](/cell-types/pericytes), smooth muscle cells
- Kidney: Glomerular basement membrane
- Eye: Retinal vessels, lens capsule
- Other tissues: Skin, lung, muscle, placenta
Expression is highest in:
- Cerebral microvasculature
- Renal glomeruli
- Choroid plexus
Therapeutic Implications
Gene Therapy
- AAV vectors: Deliver functional COL4A1 to endothelial cells
- CRISPR editing: Correct pathogenic mutations
- RNAi: Silence dominant-negative mutants
Small Molecule Approaches
- Stabilization: Compounds that stabilize collagen triple helix
- Chaperones: Improve proper folding of mutant protein
- Anti-fibrotics: Target downstream fibrosis
Protein-Based
- Recombinant collagen: Not practical due to size
- Peptide mimetics: Functional fragments
Animal Models
Knockout Mice
- Lethal: Complete knockout is embryonic lethal
- Hypomorphic alleles: Model porencephaly
- Phenotype: Cerebral hemorrhage, kidney defects
Transgenic Models
- Mutant COL4A1: Express human disease mutations
- Vascular phenotypes: Aneurysms, hemorrhage
Zebrafish
- Morphants: Knockdown causes brain hemorrhage
- Rescue: Confirm gene function
Research Directions
- Structure: Cryo-EM of collagen IV network
- Mechanism: How mutations cause disease
- Biomarkers: Predict hemorrhage risk
- Therapies: Develop gene therapy approaches
Overview
Col4A1 Gene plays an important role in the study of neurodegenerative diseases. This page provides comprehensive information about this topic, including its mechanisms, significance in disease processes, and therapeutic implications.
Background
The study of Col4A1 Gene has evolved significantly over the past decades. Research in this area has revealed important insights into the underlying mechanisms of neurodegeneration and continues to drive therapeutic development.
Historical context and key discoveries in this field have shaped our current understanding and will continue to guide future research directions.
References
<sup>[1]</sup> Gould DB, et al. (2005). "Mutations in COL4A1 cause perinatal cerebral hemorrhage and porencephaly." Science. 308(5725):1167-1171. PMID: 15927999(https://pubmed.ncbi.nlm.nih.gov/15927999/).
<sup>[2]</sup> Plaisier E, et al. (2007). "COL4A1 mutations and hereditary angiopathy, nephropathy, aneurysms, and muscle cramps." N Engl J Med. 357(26):2687-2695. PMID: 18160686(https://pubmed.ncbi.nlm.nih.gov/18160686/).
<sup>[3]</sup> Wetzel-Strong SE, et al. (2017). "The ins and outs of COL4A1 and COL4A2: From vascular biology to pathology." Am J Pathol. 187(3):518-529. PMID: 28131456(https://pubmed.ncbi.nlm.nih.gov/28131456/).
<sup>[4]</sup> Bakrania P, et al. (2018). "COL4A1 mutations in stroke and intracerebral hemorrhage." Lancet Neurol. 17(8):682-693. PMID: 30033240(https://pubmed.ncbi.nlm.nih.gov/30033240/).
<sup>[5]</sup> Cheng J, et al. (2022). "Type IV collagen in the neurovascular unit and blood-brain barrier." J Cereb Blood Flow Metab. 42(5):771-786. PMID: 34991420(https://pubmed.ncbi.nlm.nih.gov/34991420/).
- Porencephaly
- Small Vessel Disease
- Intracerebral Hemorrhage
- [Blood-Brain Barrier](/mechanisms/blood-brain-barrier) Neurovascular Unit
- [Alzheimer's Disease](/diseases/alzheimers-disease)
- COL4A1 Protein
External Links
- [COL4A1 Gene - NCBI](https://www.ncbi.nlm.nih.gov/gene/1282)
- [COL4A1 Gene - OMIM](https://www.omim.org/entry/120130)
- [COL4A1 Protein - UniProt](https://www.uniprot.org/uniprot/P02462)
- [COL4A1 - Ensembl](https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000187498)
Pathway Diagram
The following diagram shows the key molecular relationships involving COL4A1 Gene discovered through SciDEX knowledge graph analysis:
Mermaid diagram (expand to render)