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FB2026_01
,
released March 12, 2026
This report describes Cowden syndrome 1 (CWS1), also known as PTEN hamartoma tumor syndrome; this disease exhibits autosomal dominant inheritance. The human gene implicated in CWS1 is PTEN, a lipid and protein phosphatase with diverse regulatory functions. There is a single orthologous gene in Drosophila, Dmel\Pten, for which an extensive collection of genetic reagents has been generated, including loss-of-function mutations, RNAi-targeting constructs, alleles caused by insertional mutagenesis, and overexpression constructs.
UAS constructs of the wild-type human Hsap\PTEN gene have been introduced into flies; heterologous rescue (functional complementation) has been demonstrated for the overgrowth phenotype of hypomorphic mutations of Dmel\Pten. Recently, a large number of mutations analogous to variants implicated in human disease have been introduced as transgenic Hsap\PTEN constructs. See the 'Disease-Implicated Variants' table, below, for tested variants associated with Cowden syndrome 1. See the Hsap\PTEN gene report for a complete list of tested variants.
There are over 100 missense and nonsense mutations of human PTEN implicated in several different diseases. As part of a large-scale assessment of such variants an assay in Drosophila was employed. Ubiquitous expression of wild-type Hsap\PTEN results in delayed eclosion; expression of a complete loss-of-function variant of Hsap\PTEN does not. This allows an assessment of degree of wild-type function for PTEN variants found in human; 86 variants have been assessed in this assay.
[updated Apr.2024 by FlyBase; FBrf0222196]
[COWDEN SYNDROME 1; CWS1](https://omim.org/entry/158350)
[PHOSPHATASE AND TENSIN HOMOLOG; PTEN](https://omim.org/entry/601728)
Cowden syndrome-1 is a hamartomatous disorder characterized by macrocephaly, facial trichilemmomas, acral keratoses, papillomatous papules, and an increased risk for the development of breast, thyroid, and endometrial carcinoma. Bannayan-Riley-Ruvalcaba syndrome (BRRS), previously thought be distinct, shared clinical characteristics with Cowden syndrome, such as hamartomatous polyps of the gastrointestinal tract, mucocutaneous lesions, and increased risk of developing neoplasms, but had the additional features of developmental delay, macrocephaly, lipomas, hemangiomas, and pigmented speckled macules of the glans penis in males. Because features of BRRS and Cowden syndrome have been found in individuals within the same family with the same PTEN mutation, Cowden syndrome-1 and BRRS are considered to be the same disorder with variable expression and age-related penetrance (summary by Marsh et al., 1999, pubmed:10400993; Lachlan et al., 2007, pubmed:17526800; Blumenthal and Dennis, 2008, pubmed:18781191). [from MIM:158350; 2020.09.14]
Cowden syndrome-1 (CWS1) is caused by heterozygous germline mutation in the PTEN gene. [from MIM:158350; 2020.09.14]
The PTEN gene encodes a ubiquitously expressed tumor suppressor dual-specificity phosphatase that antagonizes the PI3K signaling pathway through its lipid phosphatase activity and negatively regulates the MAPK pathway through its protein phosphatase activity (summary by Pezzolesi, et al., 2007; pubmed:17341483). [from MIM:601728; 2020.09.14]
One to one: 1 human gene to 1 Drosophila gene.
High-scoring ortholog of human PTEN (1 Drosophila to 1 human). Dmel\Pten shares 39% identity and 54% similarity with the human gene.