The MEN1 gene, located on chromosome 11q13, encodes menin, a ubiquitously expressed nuclear scaffold protein that functions as a tumor suppressor . Menin plays critical roles in epigenetic regulation through histone modification, transcriptional control, DNA repair, and apoptosis . MEN1 functions as a tumor suppressor following the Knudson "two-hit" model, where biallelic inactivation leads to tumorigenesis . Germline mutations of MEN1 cause multiple endocrine neoplasia type 1 (MEN1), an autosomal dominant disorder with >95% penetrance by age 50, characterized by tumors of the parathyroid glands (present in ≥95% of patients), pancreatic islet cells, and the anterior pituitary . Over 1,300 MEN1 mutations have been identified, the majority (>70%) predicted to produce truncated, nonfunctional menin proteins . Somatic MEN1 mutations are also observed in sporadic nonfamilial endocrine tumors . Familial isolated hyperparathyroidism may represent a mild phenotypic variant of MEN1 caused by MEN1 mutations . The absence of clear genotype-phenotype correlations highlights the complexity of menin's molecular interactions in tumor suppression.
