COL4A4 gene
The COL4A4 gene provides instructions for making the alpha4(IV) chain of collagen IV, a protein essential for the structural integrity of basement membranes in the kidneys, ears, and eyes.
Normal Function
The COL4A4 gene provides instructions for making the alpha4(IV) chain of collagen IV. This chain combines with two other types of alpha(IV) chains (the alpha3 and alpha5 chains) to form alpha345(IV) collagen molecules. These molecules form complex protein networks that constitute a large portion of basement membranes—thin, sheet-like structures that support cells in many tissues. These networks are particularly important in the basement membranes of the kidney, inner ear, and eye.
Health Conditions Related to Genetic Changes
Alport syndrome
Many variants in the COL4A4 gene can cause Alport syndrome, a condition characterized by kidney disease, hearing loss, and eye abnormalities. These variants either alter the structure of the alpha4(IV) collagen chain or severely decrease/prevent its production. This impairs the formation of alpha345(IV) collagen networks. In the kidney, this leads to the buildup of other types of collagen, resulting in scarring and eventual kidney failure.
- Autosomal dominant Alport syndrome: Caused by a variant in one copy of the COL4A4 gene. Individuals typically experience kidney problems, including blood in the urine (hematuria), excess protein in the urine (proteinuria), and gradual loss of kidney function.
- Autosomal recessive Alport syndrome: Caused by variants in both copies of the COL4A4 gene. Individuals may experience hearing loss and eye abnormalities in addition to kidney problems.
Other disorders
A variant in one copy of the COL4A4 gene can cause thin basement membrane nephropathy. People with this condition typically have blood in their urine (hematuria) but rarely progress to kidney failure.
Other Names for This Gene
- alpha 4 type IV collagen
- CA44
- CO4A4_HUMAN
- Collagen IV, alpha-4 polypeptide
- collagen of basement membrane, alpha-4 chain
- collagen type IV alpha 4
- collagen, type IV, alpha 4