Meyahealth
HomeGeneticsGeneUSP8 gene
Back to Gene
USP8 gene
Reviewed by Medicinsk Expert•Last updated: 2026-10-22•Gene

USP8 gene

The USP8 gene encodes an enzyme that regulates protein metabolism and cell signaling, with pathogenic variants being a primary cause of Cushing disease.

Normal Function

The USP8 gene provides instructions for making an enzyme that removes molecules called ubiquitin from certain proteins. Within cells, damaged or excess proteins are tagged with ubiquitin, which serves as a signal that the protein should be broken down (metabolized). When the USP8 enzyme removes ubiquitin from a protein, it prevents that protein from being metabolized. As a result, USP8 is known as a rescue protein.

The USP8 enzyme is thought to play an important role in normal cell growth and division. The enzyme is especially important for cell structures called endosomes, which help sort and transport molecules within the cell. Within the endosome, the USP8 enzyme plays a key role in regulating the transport of a protein called epidermal growth factor receptor (EGFR) protein. This receptor protein is part of an important signaling pathway involved in processes such as cell growth and division (proliferation) and cell survival.

Health Conditions Related to Genetic Changes

Cushing disease

Pathogenic variants in the USP8 gene have been found in noncancerous (benign) pituitary tumors (also called adenomas) from patients with Cushing disease. This condition is characterized by high levels of the hormone cortisol in the blood. In some people with Cushing disease, pituitary adenomas contain cells with a pathogenic variant in the USP8 gene.

The pathogenic variants that cause Cushing disease are typically somatic, which means that they are acquired during a person's lifetime and are present only in certain cells. Somatic variants in the USP8 gene are the most common genetic cause of Cushing disease. These USP8 variants cause cells in the pituitary adenoma to produce a version of the USP8 enzyme that does not switch off properly. As a result, the EGFR signaling pathway becomes overactive, causing cells within the adenoma to release too much of a hormone called adrenocorticotropic hormone (ACTH). The higher levels of ACTH released by the pituitary adenoma cause the adrenal glands to release too much cortisol, which leads to the signs and symptoms seen in people with Cushing disease.

Other Names for This Gene

  • HumORF8
  • KIAA0055
  • SPG59
  • ubiquitin carboxyl-terminal hydrolase 8
  • ubiquitin isopeptidase Y
  • UBPY

Frequently Asked Questions

Symptoms of Cushing disease, regardless of cause, include weight gain (especially around the midsection and face), a rounded face (moon face), a fatty hump between the shoulders (buffalo hump), thin skin that bruises easily, purple stretch marks, muscle weakness, and high blood pressure. Mood changes and irregular periods in women are also common.
Diagnosis of Cushing disease involves tests to measure cortisol levels (e.g., 24-hour urine cortisol, late-night salivary cortisol, dexamethasone suppression test). If Cushing disease is confirmed and a pituitary tumor is suspected, the tumor tissue obtained during surgery can be tested for the presence of somatic USP8 gene variants to determine if it's the underlying cause.
The primary treatment for Cushing disease caused by a pituitary adenoma with a USP8 variant is surgical removal of the tumor (transsphenoidal surgery). If surgery is not fully effective or the tumor recurs, radiation therapy or medications to lower cortisol production may be used.
Yes, somatic variants are acquired during a person's lifetime and are present only in the tumor cells, not in the germline (sperm or egg cells). Therefore, Cushing disease caused by a somatic USP8 variant is generally not inherited and cannot be passed on to offspring.
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.

Meyahealth

Ⓒ 2026. All rights reserved by MEYA

About UsTerms & PolicyFAQ