The detailed entries of the Imprinted Gene Catalogue database were created by Benjamin Tycko, Columbia University, New York and are updated by Ian Morison


Detailed entry for Gene:



Human Chr11p15.5
Mouse Chr7 (distal)




The paternal allele of Cdkn1c/p57(Kip2) is repressed; maternal allele active in multiple fetal tissues of mice and humans, but the imprint is "leaky" (partial repression) in human tissues (Chung WY et al, 1996; Hatada I et al, 1996; Hatada I et al, 1995; Matsuoka S et al, 1996).

Gene Product:

The Cdkn1c/p57(Kip2) gene encodes a cyclin-dependent kinase inhibitor, with tissue-specific variations in its expression (Matsuoka S et al, 1995).

Functional Data:

The Chr11p15.5 imprinted domain coincides with two human disease loci: the somatic overgrowth and cancer predisposition disorder Beckwith-Wiedemann syndrome (BWS), and a Wilms' tumor locus (WT2). The p57KIP2/CDKN1C gene has been evaluated as a candidate for both phenotypes. Expression of p57 protein in transfected tumor cells blocks cell growth (O'Keefe D et al, 1997; Tsugu A et al, 2000). Developmental abnormalities, paradoxically without net overgrowth, are seen in p57Kip2 knockout mouse embryos (Yan Y et al, 1997; Zhang P et al, 1997). The lack of overgrowth is accounted for by an apoptotic cellular response to loss of a cell cycle checkpoint (Yan Y et al, 1997; Takahashi K et al, 2000). However, mouse conceptuses with a double knockout of p57Kip2 and H19, accompanied by loss of imprinting of Igf2, showed placental overgrowth (Caspary T et al, 1999). Maternally transmitted mutations in CDKN1C have been found in a small subset (~10 percent) of cases of BWS, indicating that this gene can cause this syndrome (O'Keefe D et al, 1997; Algar E et al, 2000; Hatada I et al, 1996; Hatada I et al, 1997; Lam WW et al, 1999; Lee MP et al, 1997; Li M et al, 2001). However, such mutations are rare or absent in Wilms' tumors and other BWS-associated malignancies such as hepatoblastoma (O'Keefe D et al, 1997; Hartmann W et al, 2000). Wilms' tumors show reduced, but not absent, expression of p57Kip2 mRNA relative to normal fetal kidneys (Taniguchi T et al, 1997; Overall ML et al, 1996; Orlow I et al, 1996). Consistent with these observations, a genotype-phenotype correlation exists in BWS, such that individuals with CDKN1C mutations apparently do not have a high risk of Wilms' tumor (Engel JR et al, 2000)


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