CTNNB1 gene

The CTNNB1 gene provides instructions for making the beta-catenin protein, which is essential for cell-to-cell adhesion and the Wnt signaling pathway.

Normal Function

The CTNNB1 gene provides instructions for making a protein called beta-catenin. This protein is present in many types of cells and tissues, primarily found at junctions that connect neighboring cells (adherens junctions). Beta-catenin plays an important role in sticking cells together (cell adhesion) and in communication between cells.

The beta-catenin protein is also an essential part of the Wnt signaling pathway. Certain proteins in this pathway attach (bind) to beta-catenin, which triggers a multistep process that allows the protein to move into the cell nucleus. Once in the nucleus, beta-catenin interacts with other proteins to control the activity (expression) of specific genes. The Wnt signaling pathway promotes the growth and division (proliferation) of cells and helps determine the specialized functions a cell will have (differentiation). In adult tissues, this pathway plays a role in the maintenance and renewal of stem cells.

Additionally, beta-catenin plays an important role in the normal function of hair follicles, specifically in the matrix cells that divide and mature to form the hair shaft.

Health Conditions Related to Genetic Changes

Desmoid tumor

Variants in the CTNNB1 gene can cause a type of aggressive but noncancerous (benign) growth called a desmoid tumor. These variants are somatic, meaning they are acquired during a person's lifetime and are present only in tumor cells. These variants usually occur in exon 3, leading to an altered beta-catenin protein that is not broken down when it is no longer needed. The resulting buildup of beta-catenin promotes uncontrolled cell proliferation.

Pilomatricoma

Somatic "gain-of-function" variants in the CTNNB1 gene cause pilomatricomas, which are benign skin tumors associated with hair follicles. These variants cause the beta-catenin protein to be constitutively active, leading to abnormal activation of genes that increase the proliferation and differentiation of hair follicle matrix cells. A very small percentage of these tumors are cancerous, known as pilomatrix carcinoma.

Wilms tumor

Somatic variants in the CTNNB1 gene have been found in Wilms tumor, a rare form of kidney cancer occurring almost exclusively in children. These variants result in an overly active protein that increases Wnt signaling, leading to unchecked proliferation of kidney cells.

Other cancers

Somatic variants in the CTNNB1 gene have been identified in several other cancers, including liver, thyroid, ovarian, skin, colorectal, and endometrial cancers, as well as medulloblastoma. Because these variants can cause normal cells to become cancerous, the CTNNB1 gene is classified as an oncogene.

CTNNB1 neurodevelopmental disorder

Variants in one copy of the CTNNB1 gene present in all cells can cause a neurodevelopmental disorder characterized by intellectual disabilities. Other signs and symptoms may include:

• Vision problems (including exudative vitreoretinopathy)
• Movement problems
• Microcephaly (unusually small head size)
• Behavioral issues
• Feeding difficulties
• Slow growth before birth
• Scoliosis

This disorder is caused by a non-functional version of the beta-catenin protein, which impairs the ability of brain cells to grow and connect properly.

Other Names for This Gene

• beta-catenin
• catenin beta-1
• CTNB1_HUMAN
• CTNNB

Genomic Location

The CTNNB1 gene is found on chromosome 3.