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CUL3 gene
Reviewed by Medicinsk Expert•Last updated: 2026-10-22•Gene

CUL3 gene

The CUL3 gene provides instructions for making the protein cullin-3, a core component of the ubiquitin-proteasome system that regulates protein degradation and blood pressure.

Normal Function

The CUL3 gene provides instructions for making a protein called cullin-3. This protein plays a role in the ubiquitin-proteasome system, which breaks down (degrades) unwanted proteins inside cells. The ubiquitin-proteasome system acts as the cell's quality control system by disposing of damaged, misshapen, and excess proteins.

Cullin-3 is a core piece of a complex known as an E3 ubiquitin ligase. E3 ubiquitin ligases tag proteins with molecules called ubiquitin. Ubiquitin signals specialized cell structures known as proteasomes to attach (bind) to the tagged proteins and degrade them. By regulating the amount of specific proteins, cullin-3 plays a role in critical cell activities, including cell growth, division, and blood pressure control (specifically by regulating WNK1 and WNK4 proteins).

Health Conditions Related to Genetic Changes

CUL3-related neurodevelopmental disorder

CUL3 gene variants can cause a condition called CUL3-related neurodevelopmental disorder, which affects neurological and physical development. These variants can lead to the production of nonfunctional cullin-3 proteins, or in some cases, no protein production at all. Without normal levels of functioning cullin-3, the breakdown of unwanted proteins becomes impaired, leading to a buildup of unnecessary proteins that interfere with cell function, particularly in nerve cells.

Pseudohypoaldosteronism type 2

Specific variants in a particular region of the CUL3 gene can cause pseudohypoaldosteronism type 2 (PHA2), a condition characterized by high blood pressure (hypertension) and high levels of potassium in the blood (hyperkalemia). These variants lead to the production of an abnormally short cullin-3 protein.

  • This change alters the function of the E3 ubiquitin ligase complex, impairing the breakdown of the WNK4 protein.
  • The resulting excess of WNK4 protein disrupts normal control of blood pressure, causing hypertension and other features of PHA2.
  • The features of PHA2 do not overlap with the neurological or physical problems of CUL3-related neurodevelopmental disorder.

Genomic Location

The CUL3 gene is found on chromosome 2.

Frequently Asked Questions

Typical signs include developmental delays, speech difficulties, motor coordination problems, and sometimes distinctive facial features. Children may also exhibit behavioral issues such as hyperactivity or anxiety. If a child shows a combination of these symptoms, a clinician may recommend genetic testing for CUL3 variants. How does a CUL3 mutation lead to high blood pressure and high potassium levels?::Certain CUL3 variants produce a shortened protein that disrupts the degradation of WNK1 and WNK4 proteins. This imbalance affects kidney sodium handling, leading to sodium retention (raising blood pressure) and impaired potassium excretion (causing hyperkalemia). What blood pressure management strategies are recommended for patients with pseudohypoaldosteronism type 2?::Treatment usually involves a combination of diuretics (e.g., thiazide diuretics) to promote sodium loss and potassium-lowering agents such as potassium binders or dietary potassium restriction. Regular monitoring of serum electrolytes and blood pressure is essential, and antihypertensive medications may be added if needed. Is genetic testing for CUL3 variants available for family members who might be carriers?::Yes. A simple blood or saliva test can sequence the CUL3 gene to identify pathogenic variants. Family members who are carriers can benefit from early monitoring for hypertension or developmental concerns, and genetic counseling can guide reproductive decisions.
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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