Summary of COL4A3
This gene encodes part of a complex that helps make collagen. Collagen helps provide structure and strength to the connective tissues that support the body's muscles, joints, organs, and skin (R).
The Function of COL4A3
Tumstatin, a cleavage fragment corresponding to the collagen alpha 3(IV) NC1 domain, possesses both anti-angiogenic and anti-tumor cell activity; these two anti-tumor properties may be regulated via RGD-independent ITGB3-mediated mechanisms.
Protein names
Recommended name:
Collagen alpha-3Short name:
IVAlternative name(s):
Goodpasture antigen- RS10178458 (COL4A3) ??
- RS11677877 (COL4A3) ??
- RS34505188 (COL4A3) ??
- RS35212277 (COL4A3) ??
- RS6436669 (COL4A3) ??
- RS7606754 (COL4A3) ??
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Top Gene-Substance Interactions
Substances That Increase COL4A3
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Substances That Decrease COL4A3
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Advanced Summary
Alport syndrome More than 40 mutations in the COL4A3 gene have been found to cause Alport syndrome. Most of these mutations change single protein building blocks (amino acids) in a region where the alpha3(IV) collagen chain combines with other type IV collagen chains. Other mutations in the COL4A3 gene severely decrease or prevent the production of alpha3(IV) chains. As a result, there is a serious deficiency of the type IV collagen alpha3-4-5 network in the basement membranes of the kidney, inner ear, and eye. In the kidney, other types of collagen accumulate in the basement membranes, eventually leading to scarring of the kidneys and kidney failure. Mutations in this gene can also lead to abnormal function in the inner ear, resulting in hearing loss. other disorders Mutations in the COL4A3 gene have been found to cause thin basement membrane nephropathy. This condition typically causes people to have blood in their urine (hematuria) but no other signs or symptoms of kidney disease. In the past, this condition was often called benign familial hematuria. Thin basement membrane nephropathy rarely progresses to kidney failure. Goodpasture syndrome is a severe disease of the lungs and the kidneys caused by antibodies to the alpha3(IV) collagen chains. Antibodies are immune system proteins that normally attack foreign substances such as bacteria or viruses, but in Goodpasture syndrome, they target alpha3(IV) collagen chains. It remains unclear why some people make antibodies to their own collagen chains. The antibodies cause inflammation when they attach (bind) to the basement membranes of blood vessels in the air sacs (alveoli) of the lungs and filtering units (glomeruli) of the kidneys. As a result, people with Goodpasture syndrome can develop kidney failure and bleeding in the lungs, which causes them to cough up blood. In some people, antibodies attack only the kidneys. These people are said to have anti-glomerular basement membrane nephritis.
The COL4A3 gene provides instructions for making one component of type IV collagen, which is a flexible protein. Specifically, this gene makes the alpha3(IV) chain of type IV collagen. This chain combines with two other types of alpha (IV) chains (the alpha4 and alpha5 chains) to make a complete type IV collagen molecule. Type IV collagen molecules attach to each other to form complex protein networks. These networks make up a large portion of basement membranes, which are thin sheet-like structures that separate and support cells in many tissues. Type IV collagen alpha3-4-5 networks play an especially important role in the basement membranes of the kidney, inner ear, and eye.
Conditions with Increased Gene Activity
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Conditions with Decreased Gene Activity
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Technical
The following transcription factors affect gene expression:
Tissue specificity:
Alpha 3 and alpha 4 type IV collagens are colocalized and present in kidney, eye, basement membranes of lens capsule, cochlea, lung, skeletal muscle, aorta, synaptic fibers, fetal kidney and fetal lung. PubMed:8083201 reports similar levels of expression of alpha 3 and alpha 4 type IV collagens in kidney, but PubMed:7523402 reports that in kidney levels of alpha 3 type IV collagen are significantly lower than those of alpha 4 type IV collagen. According to PubMed:8083201, alpha 3 type IV collagen is not detected in heart, brain, placenta, liver, pancreas, extrasynaptic muscle fibers, endoneurial and perineurial nerves, fetal brain, fetal heart and fetal liver. According to PubMed:7523402, alpha 3 type IV collagen is strongly expressed in pancreas, neuroretina and calvaria and not expressed in adrenal, ileum and skin. Isoform 1 and isoform 3 are strongly expressed in kidney, lung, suprarenal capsule, muscle and spleen, in each of these tissues isoform 1 is more abundant than isoform 3. Isoform 1 and isoform 3 are expressed at low levels in artery, fat, pericardium and peripherical nerve, but not in placenta, mesangium, skin, pleura and cultured umbilical endothelial cells.
Gene Pathways:
Molecular Function:
- Extracellular Matrix Structural Constituent
- Integrin Binding
- Metalloendopeptidase Inhibitor Activity
- Structural Molecule Activity
Biological Processes:
- Activation Of Cysteine-Type Endopeptidase Activity Involved In Apoptotic Process
- Blood Circulation
- Cell Adhesion
- Cell Proliferation
- Cell Surface Receptor Signaling Pathway
- Collagen-Activated Tyrosine Kinase Receptor Signaling Pathway
- Collagen Catabolic Process
- Endothelial Cell Apoptotic Process
- Extracellular Matrix Organization
- Glomerular Basement Membrane Development
- Negative Regulation Of Angiogenesis
- Negative Regulation Of Cell Proliferation
- Sensory Perception Of Sound