The Genetics of Cystinuria: Understanding Types A, B, and AB

Living with cystinuria means learning a vocabulary most people never need. Cystine. Twenty-four-hour urine collections. And, eventually, the question: “Which type do you have?”

There are three commonly discussed genetic groups: A, B, and AB. But there is also an older classification called types I, II, and III. They are not interchangeable. Before sorting out the letters, it helps to understand what goes wrong in the kidneys.

How a genetic change becomes a kidney stone

Your kidneys filter blood, then reclaim substances your body needs. Much of that reclaiming happens in tiny tubes called the proximal tubules.

In cystinuria, a transport system in those tubes does not work properly. Instead of being reclaimed efficiently, excess amounts of four amino acids remain in the urine: cystine, ornithine, lysine, and arginine, sometimes shortened to COLA.

Cystine is the stone-forming problem because it dissolves poorly in urine. When enough accumulates, crystals can form and grow into stones. Cystine is related to—but different from—cysteine: two cysteine molecules join together to make cystine.

This is an inherited transport problem, not something someone caused by eating the wrong meal. Diet and treatment can influence stone risk, but they do not create the underlying genetic condition. GeneReviews explains the mechanism and genetics.

Two genes involved in one transport system

Two genes provide instructions for the protein partners that make this transport system work:

• SLC3A1 makes a protein called rBAT.
• SLC7A9 makes its partner, b⁰⁺AT.

Disease-causing changes—called pathogenic variants—can interfere with either partner. The modern genetic labels describe which gene or genes are involved.

Type A: SLC3A1

Type A involves pathogenic variants in SLC3A1. Classic disease usually involves changes affecting both copies of that gene, often written AA.

That usually follows autosomal recessive inheritance: someone inherits an affected copy from each parent. The parents may have no history of cystine stones.

Someone with one affected copy usually does not have classic disease, although specific genetic exceptions exist. A genetics professional can interpret the actual variants rather than relying on the letter alone.

Type B: SLC7A9

Type B involves pathogenic variants in SLC7A9. Classic disease commonly involves both copies, often written BB.

One important difference is that people with just one affected SLC7A9 copy can have increased urinary cystine. Whether that leads to stones varies. Being called a “carrier” does not describe everyone's urine findings or stone risk equally well.

Type AB: findings in both genes

Type AB describes findings involving both SLC3A1 and SLC7A9. You may see it called digenic inheritance, meaning two genes are involved.

This is the group that needs the most careful explanation. Evidence that one pathogenic variant in each gene consistently causes classic cystinuria in humans is limited. Some people described as AB have additional variants—patterns sometimes written AAB or ABB.

The practical point is not to decode your own report from a diagram online. The number, identity, and arrangement of the variants matter. GeneReviews and research on the genetic classification discuss these complications.

What happened to types I, II, and III?

The older system classified families using amino-acid excretion in parents carrying the condition. Type I generally described normal excretion in those parents; types II and III described different degrees of increased excretion.

The newer system uses genetic findings. Old type III does not simply mean modern type AB. The classifications measure different things and do not match one-to-one. This clinical overview explains the distinction.

Does knowing your type change treatment?

Genetic testing can clarify a diagnosis and help with family counseling. But the letters alone do not reliably predict how many stones someone will develop or how difficult their disease will be.

Treatment still depends on your stone history, urine testing, kidney function, and response to prevention. Fluids, dietary guidance, prescribed urine alkalinization, and sometimes cystine-binding medicines remain central parts of care. International clinical recommendations discuss individualized management.

The genetics help explain why cystinuria happens. Your care plan still needs to address how it affects you.

This article is educational and does not replace medical advice or interpretation of an individual genetic test.