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CDKN1C gene
URL of this page: https://medlineplus.gov/genetics/gene/cdkn1c/

CDKN1C gene

cyclin dependent kinase inhibitor 1C

Normal Function

The CDKN1C gene provides instructions for making a protein that helps regulate growth. This protein acts as a tumor suppressor, which means that it keeps cells from growing and dividing too fast or in an uncontrolled way. It is also active before birth; it regulates growth and prevents the developing fetus from becoming too large.

In most cases, one copy of each gene is derived from the sperm cell and one copy is derived from the egg cell. Both copies are typically active, or "turned on," in cells. However, the activity of the CDKN1C gene differs depending on whether the gene comes from the sperm cell or the egg cell. In most tissues, the copy of the gene that comes from the egg cell is more active than the copy that comes from the sperm cell. This sort of parent-specific difference in gene activation is called genomic imprinting.

A nearby region of DNA undergoes a process called methylation in which small molecules called methyl groups are used to regulate the genomic imprinting of the CDKN1C gene. This region is known as an imprinting center or imprinting control region. In most cases, this imprinting center is methylated only when it comes from the egg cell. 

Health Conditions Related to Genetic Changes

Beckwith-Wiedemann syndrome

Beckwith-Wiedemann syndrome is a growth disorder that affects many parts of the body. Many cases of Beckwith-Wiedemann syndrome occur when the CDKN1C imprinting center derived from the egg cell has too few methyl groups attached (hypomethylation). Hypomethylation of the imprinting center disrupts the regulation of several genes, including CDKN1C. Because this gene normally restrains cell growth and division, a reduction in its activity leads to the overgrowth seen in people with Beckwith-Wiedemann syndrome.

In some cases, Beckwith-Wiedemann syndrome is caused by duplications of a small amount of DNA from the CDKN1C imprinting center. These duplications impair the imprinting center’s ability to regulate the activity of several genes, including CDKN1C.

Beckwith-Wiedemann syndrome can also be caused by variants (also called mutations) within the CDKN1C gene. Some of these genetic changes alter single protein building blocks (amino acids) or delete a small number of amino acids from the protein. This causes the cells to produce a version of the CDKN1C protein that does not function as it should. These variants are called "loss-of-function variants" because they reduce the protein's ability to control growth effectively. The resulting problems with growth regulation cause the characteristic signs and symptoms seen in people with Beckwith-Wiedemann syndrome.

More About This Health Condition

IMAGe syndrome

Variants in the CDKN1C gene cause IMAGe syndrome, a disorder that affects the growth of many parts of the body and is named for its main features: intrauterine growth restriction, metaphyseal dysplasia, adrenal hypoplasia congenita, and genital anomalies. The condition is characterized by slow growth before and after birth, skeletal abnormalities, and hormonal changes. IMAGe syndrome occurs only when the variant is present on the copy of the gene derived from the egg cell.

The CDKN1C gene variants that cause IMAGe syndrome replace single amino acids in a region known as the proliferating cell nuclear antigen (PCNA)-binding domain near the end of the gene. These variants appear to increase the stability of the CDKN1C protein, preventing it from being broken down when it is no longer needed. These changes increase the amount of the protein that is available to restrain cell growth and division. Because these variants enhance the protein's usual function, they are described as "gain-of-function variants." The excess CDKN1C protein leads to IMAGe syndrome by impairing normal growth and development.

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Silver-Russell syndrome

Variants in the CDKN1C gene are a rare cause of Silver-Russell syndrome, a condition that is characterized by slow growth before and after birth. The CDKN1C gene variants that cause Silver-Russell syndrome affect the copy of the gene that is derived from the egg cell. As in IMAGe syndrome, these variants enhance the protein's usual function and are described as "gain-of-function variants." As a result, the CDKN1C protein has increased activity, which leads to impaired growth. 

More About This Health Condition

Other Names for This Gene

  • BWCR
  • KIP2
  • p57
  • p57KIP2

Additional Information & Resources

Tests Listed in the Genetic Testing Registry

Scientific Articles on PubMed

Catalog of Genes and Diseases from OMIM

Gene and Variant Databases

References

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