MEN1

Menin is a is_associated_with::protein that in humans is encoded by the MEN1 is_associated_with::gene. Menin is a putative is_associated_with::tumor suppressor associated with is_associated_with::multiple endocrine neoplasia type 1 (MEN-1 syndrome).

In vitro studies have shown that menin is localized to the nucleus, possesses two functional is_associated_with::nuclear localization signals, and inhibits transcriptional activation by JunD. However, the function of this protein is not known. Two messages have been detected on is_associated_with::northern blots but the larger message has not been characterized. Two variants of the shorter transcript have been identified where is_associated_with::alternative splicing affects the coding sequence. Five variants where alternative splicing takes place in the is_associated_with::5' UTR have also been identified.

History
In 1988, researchers at is_associated_with::Uppsala University Hospital and the is_associated_with::Karolinska Institute in is_associated_with::Stockholm mapped the MEN1 gene to the long arm of is_associated_with::chromosome 11. The gene was finally cloned in 1997.

Genomics
The gene is located on long arm of is_associated_with::chromosome 11 (11q13) between base pairs 64,570,985 and 64,578,765. It has 10 exons and encodes a 610-amino acid protein.

Over 1300 mutations have been reported to date (2010). The majority (>70%) of these are predicted to lead to truncated forms are scattered throughout the gene. Four - c.249_252delGTCT (deletion at codons 83-84), c.1546_1547insC (insertion at codon 516), c.1378C>T (Arg460Ter) and c.628_631delACAG (deletion at codons 210-211) have been reported to occur in 4.5%, 2.7%, 2.6% and 2.5% of families.

Clinical implications
The MEN1 phenotype is inherited via an autosomal-dominant pattern and is associated with neoplasms of the pituitary gland, the parathyroid gland, and the pancreas (the 3 "P"s). While these neoplasias are often benign (in contrast to tumours occurring in is_associated_with::MEN2A), they are adenomas and, therefore, produce endocrine phenotypes.

MEN1 pituitary tumours are adenomas of anterior cells, typically prolactinomas or growth hormone-secreting. Pancreatic tumours involve the islet cells, giving rise to gastrinomas or insulinomas. In rare cases, adrenal cortex tumours are also seen.

Interactions
MEN1 has been shown to interact with:
 * is_associated_with::FANCD2,
 * GFAP,
 * is_associated_with::JunD,
 * is_associated_with::NFKB1,
 * MLL,
 * is_associated_with::RPA2, and
 * VIM.