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COL4A3 gene
Reviewed by Medicinsk Expert•Last updated: 2026-10-22•Gene

COL4A3 gene

The COL4A3 gene provides instructions for creating a vital component of collagen IV, which forms essential structural networks in the kidneys, inner ears, and eyes.

Normal Function

The COL4A3 gene provides instructions for making one piece of a protein called collagen IV. Specifically, this gene makes the alpha3(IV) chain of collagen IV. This chain combines with two other types of alpha (IV) chains (the alpha4 and alpha5 chains) to make alpha345(IV) collagen molecules. These molecules attach to each other to form complex protein networks that make up a large portion of basement membranes, which are thin, sheet-like structures that separate and support cells in many tissues. Alpha345(IV) collagen networks play an especially important role in the basement membranes of the kidney, inner ear, and eye.

Health Conditions Related to Genetic Changes

Alport syndrome

Many variants (also called mutations) in the COL4A3 gene can cause Alport syndrome, a condition characterized by kidney disease, hearing loss, and eye abnormalities. Most of these variants change single protein building blocks (amino acids) in a region where the alpha3(IV) collagen chain combines with other collagen IV chains. Other variants in the COL4A3 gene severely decrease or prevent the production of alpha3(IV) chains.

These changes in the structure or amount of alpha3(IV) chains severely impair the formation of alpha345(IV) collagen networks in the basement membranes of the kidney, inner ear, and eye. In the kidney, other types of collagen build up in the basement membranes, eventually scarring the kidneys and leading to kidney failure. Variants in this gene can also lead to abnormal function in the inner ear, resulting in hearing loss, and changes in the lens of the eye and the light-sensitive tissue at the back of the eye (retina).

  • Autosomal dominant Alport syndrome: Caused by variants in a single copy of the COL4A3 gene. Individuals typically experience kidney problems including blood in the urine (hematuria), excess amounts of protein in the urine (proteinuria), and a gradual loss of kidney function.
  • Autosomal recessive Alport syndrome: Caused by variants in both copies of the COL4A3 gene. Individuals may experience hearing loss and eye abnormalities in addition to kidney problems.

Keratoconus

MedlinePlus Genetics provides information about Keratoconus.

Other disorders

  • Thin basement membrane nephropathy: A variant in one of the two copies of the COL4A3 gene can cause this condition. People typically have blood in their urine (hematuria) but no other signs or symptoms of kidney disease. This condition rarely progresses to kidney failure.
  • Goodpasture syndrome: A severe disease of the lungs and the kidneys caused by antibodies to the alpha3(IV) collagen chains. These antibodies cause inflammation when they bind to the basement membranes of blood vessels in the air sacs (alveoli) of the lungs and filtering units (glomeruli) of the kidneys. This can lead to kidney failure and bleeding in the lungs.
  • Anti-glomerular basement membrane nephritis: A condition where antibodies attack only the kidneys.

Other Names for This Gene

  • CO4A3_HUMAN
  • collagen IV, alpha-3 polypeptide
  • collagen type IV alpha 3
  • collagen, type IV, alpha 3 (Goodpasture antigen)
  • Goodpasture antigen
  • TUMSTATIN

Frequently Asked Questions

Genetic testing usually starts with a blood sample (or saliva) that is sent to a clinical laboratory for next‑generation sequencing of the COL4A3 gene and sometimes the whole COL4A1‑COL4A6 cluster. The lab reports any changes it finds. A “variant of uncertain significance” means the laboratory has identified a change in the DNA sequence, but current scientific evidence is insufficient to decide whether that change causes disease. Your doctor may recommend family testing, review of your clinical findings (proteinuria, hearing, eye exams), or re‑evaluation of the variant as new data become available.
The first clue is often microscopic blood or protein in the urine (hematuria or proteinuria) that may be detected on a routine urinalysis, sometimes in childhood or adolescence. Early hearing loss (especially high‑frequency) and subtle eye changes (lenticonus, macular flecks) can also appear. If you have persistent hematuria, any proteinuria, or a family history of kidney disease, schedule an appointment with a nephrologist promptly—early referral allows baseline assessment and timely initiation of protective therapy.
Yes. Controlling blood pressure (target <130/80 mm Hg) with an ACE inhibitor or ARB is the most evidence‑based strategy and can reduce proteinuria and delay renal decline. Avoid nephrotoxic drugs (NSAIDs, certain antibiotics), stay well‑hydrated, maintain a low‑salt diet, and keep a healthy weight. Smoking cessation and regular aerobic exercise also help preserve kidney function.
Most COL4A3 pathogenic variants are inherited in an autosomal recessive manner, meaning two defective copies (one from each parent) are needed for classic Alport syndrome. If you have one pathogenic copy (heterozygous), you may have a milder “thin basement membrane nephropathy” but still pass the variant to each child with a 50 % chance. If your partner also carries a COL4A3 variant, there is a 25 % chance their child could inherit two defective copies and develop the full disease. Genetic counseling is recommended to clarify your specific family situation.
Source: MedlinePlus, National Library of Medicine

MedlinePlus brings together authoritative health information from the National Library of Medicine (NLM), the National Institutes of Health (NIH), and other government agencies and health-related organizations.

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