Menin

Menin is a nuclear protein encoded by the MEN1 gene in humans. It functions as a tumor suppressor and is expressed broadly in many tissues. The MEN1 gene is located on chromosome 11q13. Menin participates in transcriptional regulation by acting as a scaffold that links transcription factors to histone-modifying enzymes. Notably, it interacts with the MLL1 and MLL2 histone H3 lysine 4 methyltransferase complexes and with transcription factors such as JunD, to modulate chromatin state and gene expression. Through these interactions, menin influences cell proliferation, differentiation, and apoptosis.

Mutations in MEN1, typically loss-of-function, lead to MEN1 syndrome, an autosomal dominant multiple endocrine neoplasia characterized by tumors in the parathyroid glands, anterior pituitary, and pancreatic islets. Affected individuals may also develop adrenal cortical tumors and other neuroendocrine or non-endocrine tumors. Penetrance increases with age; the phenotype is highly variable.

Diagnosis generally involves genetic testing for MEN1 mutations in affected individuals or high-risk relatives, along with clinical and biochemical surveillance for endocrine tumors. Management focuses on treating tumors as they arise and on regular surveillance to detect new lesions early. This can include surgical resection of adenomas or hyperplasias, endocrinologic management, and targeted therapies for malignant tumors when appropriate. Genetic counseling is advised for families with MEN1 mutations.

In summary, menin acts as a nuclear tumor suppressor that coordinates transcriptional regulation through interactions with transcription factors and histone-modifying enzymes, and its loss leads to a predisposition to multiple endocrine tumors.