MEN1

MEN1 Full Name

multiple endocrine neoplasia I

MEN1 Introduction

MEN1 encodes menin, a tumor suppressor originally identified through positional cloning of the gene responsible for multiple endocrine neoplasia type 1, an autosomal dominant syndrome characterized by tumors of the parathyroid, anterior pituitary, and pancreatic islets. Menin is a nuclear protein of ~70 kDa that interacts with transcription factors, chromatin modifiers, and DNA-repair proteins, integrating endocrine, proliferative, and DNA-damage signals. The gene maps to chromosome 11q13.1, a region frequently lost or rearranged in endocrine tumors and in certain leukemias.

Figure 1. The structure of MEN1.

Transcriptional Scaffold and Genome-Stability Factor
Menin serves as a scaffold that recruits chromatin-modifying complexes—including MLL (KMT2A) histone methyltransferases, HDAC complexes, and the LEDGF/p75 fusion cofactor—to specific target genes. In endocrine tissues, menin binds the transcription factors JUND and NF-Y and represses their activity, restraining proliferation of parathyroid and pituitary cells. Menin also regulates DNA double-strand-break repair through interaction with the MRE11–RAD50–NBS1 complex and the replication fork protein LEDGF/p75, helping to maintain genome stability in actively dividing endocrine cells.

Multiple Endocrine Neoplasia Type 1 and Beyond
Germline heterozygous loss-of-function mutations in MEN1 cause multiple endocrine neoplasia type 1, with affected individuals developing primary hyperparathyroidism, anterior pituitary adenomas, and pancreatic neuroendocrine tumors, often by middle age. Somatic MEN1 mutations are also observed in sporadic parathyroid adenomas and in insulinomas. Beyond classic endocrine tumors, MEN1 has been implicated in mixed lineage leukemia through its interaction with the MLL fusion oncoprotein, and MEN1 expression modulates responsiveness to menin–MLL interaction inhibitors in acute leukemia. Menin is therefore a key biomarker and target across both endocrine and hematologic malignancies.

Alternate Names for MEN1

MEN1; multiple endocrine neoplasia I; MEAI; SCG2; menin;