What is Hepatocyte Nuclear Factor-1 Beta (HNF1B)?
Hepatocyte Nuclear Factor-1 Beta (HNF1B; usually pronounced ‘HNF1 Beta’) is a gene which acts as a switch to turn other genes in the body on and off. It is involved in the development of several organs including the kidneys, pancreas, reproductive tract and liver. Some people have a variation or mutation in the HNF1B gene whereas other people are missing one copy of the gene - both can cause problems with these organs.
It is unknown how many people have HNF1B variations.
What are the signs and symptoms of HNF1B?
HNF1B variations are also known as the renal cysts and diabetes (RCAD) syndrome - these are the two most common feature of the condition. It is also classed as a subtype of a condition called Autosomal dominant tubulointerstitial kidney disease (ADTKD).
Kidneys
The HNF1B gene helps to control the development of the kidneys before birth and the kidneys are the most common organ to be affected by variations in this gene.
Fluid filled swellings called cysts in the kidneys are the most common finding. These are usually seen on an ultrasound scan. The cysts are not cancerous. For some people, the cysts do not cause any problems and there is no effect on the function of the kidneys. For other people, the cysts can cause severe damage, which can eventually lead to kidney failure.
Some people with HNF1B have small kidneys or only one kidney. This may never cause any problems but will require monitoring to make sure that kidney function is not affected.
Abnormalities in the kidneys of a baby with an HNF1B variant may be noticed before the baby is born when the mother is having an antenatal ultrasound scan. This may be described as the appearance of ‘bright kidneys’. The baby will have a follow up scan after birth.
Diabetes
People with variations in the HNF1B gene have an increased risk of developing diabetes. This can occur at any age but is usually first diagnosed in teenagers or young adults. Sometimes it starts during pregnancy. People with HNF1B variations may have a small pancreas so it cannot make enough insulin.
The pancreas also makes enzymes to help break down food. If people do not make enough of these enzymes it can cause abdominal pain, loose stools (poo) and unintentional weight loss.
Other symptoms
Other symptoms of HNF1B include joint pain from gout (a form of arthritis). High levels of uric acid are found in the blood.
Some people have low levels of magnesium on blood tests. This does not usually cause symptoms and only a small number of people need to take magnesium supplements.
People who are missing one copy of the HNF1B gene may have autism spectrum disorder (ASD), attention deficit hyperactivity disorder (ADHD) and/or learning difficulties.
How is HNF1B diagnosed?
HNF1B variations can be hard to diagnose as there is a lot of variation in how the condition presents.
Blood tests can be used to diagnosis diabetes, and a CT or MRI scan may show that the pancreas is small.
An ultrasound scan may show cysts on the kidneys, the presence of a single or small kidneys.
Genetic testing can confirm the diagnosis.
Does HNF1B affect other parts of the body?
Women with HNF1B variations may have abnormalities in their reproductive organs, including a different shaped uterus or a double uterus. This can be seen on an ultrasound or MRI scan and may cause problems with fertility. Many women with HNF1B variants have a successful pregnancy.
Men may develop cysts on the back of the testicles. These are usually painless, do not affect fertility and do not require treatment, although it is recommended to get any growths checked by a doctor. Other abnormalities of the reproductive tract may be present in men with HNF1B variations which may cause problems with fertility.
HNF1B variations can also cause problems with the functioning of the liver. This can be seen on an ultrasound scan or diagnosed by a blood test. However, it rarely causes any symptoms, and severe liver disease is very unlikely to develop.
Does HNF1B run in families?
HNF1B variations can run in families, in around 1 in 2 cases they occur as a de novo (new) variant with no family history. Sometimes other family members may not realise that they also have the condition as its effects can be so mild and variable. For example, a parent may pass on a copy of the affected gene to their child without ever showing any signs of having the condition themselves. The reason for this variability is currently unknown.
HNF1B variations are inherited from one generation to the next in a pattern known as autosomal dominant inheritance.
Everybody has two copies of the HNF1B gene, one from each parent.
One copy of the faulty gene is enough to cause the condition.
There is therefore a 1 in 2 chance that a child born to an affected person will receive an abnormal gene themselves. There is often variety in the type and severity of abnormalities caused by HNF1B variations within the same family.
Genetic counselling may be offered depending on family history.
How is HNF1B treated?
Most people with HNF1B variations do not need any kidney-specific treatment. Kidney function and blood pressure will be checked regularly to make sure that everything remains stable.
Diabetes caused by HNF1B variants is usually treated by insulin injections. It may be possible to initially use tablets.
A lack of pancreatic enzymes can be tested with a stool (poo) sample. If the levels are low, they can be replaced by taking tablets with meals.
Medication such as allopurinol may also be prescribed to reduce the levels of uric acid in the blood to prevent gout.
Genetic counselling may be offered for women with HNF1B who would like to become pregnant.
Where can I get more information or support about HNF1B?
The UK-based HNF1B Facebook group supports people with HNF1B variations as well as their family and friends.
More information about genetic types of diabetes can be found at www.diabetesgenes.org
Publication date: 09/2026
Review date: 09/2029