COL4A1

COL4A1 (Collagen Type IV Alpha 1 Chain) is a Protein Coding gene. Diseases associated with COL4A1 include Retinal Arteries, Tortuosity Of and Schizencephaly. Among its related pathways are Integrin Pathway and ERK Signaling. Gene Ontology (GO) annotations related to this gene include extracellular matrix structural constituent and extracellular matrix constituent conferring elasticity. An important paralog of this gene is COL4A5.

Collagen Type IV Alpha 1 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.

Arresten, comprising the C-terminal NC1 domain, inhibits angiogenesis and tumor formation. The C-terminal half is found to possess the anti-angiogenic activity. Specifically inhibits endothelial cell proliferation, migration and tube formation.

Basement membrane organization Source: BHF-UCL
Blood vessel morphogenesis Source: BHF-UCL
Brain development Source: BHF-UCL
Branching involved in blood vessel morphogenesis Source: BHF-UCL
Cellular response to amino acid stimulus Source: Ensembl
Collagen-activated tyrosine kinase receptor signaling pathway Source: Ensembl
Collagen fibril organization Source: Reactome
Epithelial cell differentiation Source: Ensembl
Extracellular matrix organization Source: GO_Central
Neuromuscular junction development Source: Ensembl
Renal tubule morphogenesis Source: BHF-UCL
Retinal blood vessel morphogenesis Source: BHF-UCL

Basement membrane

Hereditary angiopathy with nephropathy aneurysms and muscle cramps (HANAC):
The clinical renal manifestations include hematuria and bilateral large cysts. Histologic analysis revealed complex basement membrane defects in kidney and skin. The systemic angiopathy appears to affect both small vessels and large arteries.
Brain small vessel disease 1 with or without ocular anomalies (BSVD1):
An autosomal dominant cerebrovascular disorder with variable manifestations reflecting the location and severity of the vascular defect. BSVD1 features include cerebral hemorrage, unilateral fluid-filled cysts or cavities within the cerebral hemispheres, leukoencephalopathy, hemiplegia, seizures, intellectual disability, and facial paresis. Affected individuals may manifest variable visual defects and ocular anomalies.
Intracerebral hemorrhage (ICH):
A pathological condition characterized by bleeding into one or both cerebral hemispheres including the basal ganglia and the cerebral cortex. It is often associated with hypertension and craniocerebral trauma. Intracerebral bleeding is a common cause of stroke.
Tortuosity of retinal arteries (RATOR):
A disease characterized by marked tortuosity of second- and third-order retinal arteries with normal first-order arteries and venous system. Most patients manifest variable degrees of symptomatic transient vision loss due to retinal hemorrhage following minor stress or trauma.
Schizencephaly (SCHZC):
Extremely rare human congenital disorder characterized by a full-thickness cleft within the cerebral hemispheres. These clefts are lined with gray matter and most commonly involve the parasylvian regions. Large portions of the cerebral hemispheres may be absent and replaced by cerebro-spinal fluid.
Microangiopathy and leukoencephalopathy, pontine, autosomal dominant (PADMAL):
The disease is caused by variants affecting the gene represented in this entry. Causative mutations affect a binding site for miR-29 microRNA located within the 3'UTR of COL4A1 and lead to an up-regulation of this gene. A form of cerebral small vessel disease characterized by the recurrence of ischemic strokes starting in the thirties or forties, and associated with progressive imbalance and cognitive impairment. MRI examination shows ischemic lacunas in the pons and cerebral hemispheres, and diffuse leukoencephalopathy affecting various brain regions.

Lysines at the third position of the tripeptide repeating unit (G-X-Y) are hydroxylated. The modified lysines can be O-glycosylated.
Contains 4-hydroxyproline (Probable). Prolines at the third position of the tripeptide repeating unit (G-X-Y) are hydroxylated in some or all of the chains (By similarity).
Contains 3-hydroxyproline. This modification occurs on the first proline residue in the sequence motif Gly-Pro-Hyp, where Hyp is 4-hydroxyproline.
Type IV collagens contain numerous cysteine residues which are involved in inter- and intramolecular disulfide bonding (PubMed:2844531). 12 of these, located in the NC1 domain, are conserved in all known type IV collagens.
The trimeric structure of the NC1 domains is stabilized by covalent bonds (sulfilimine cross-links) between Lys and Met residues (PubMed:12011424). These cross-links are important for the mechanical stability of the basement membrane (By similarity).
Proteolytic processing produces the C-terminal NC1 peptide, arresten.