INSM1

Description

The INSM1 (INSM transcriptional repressor 1) is a protein-coding gene located on chromosome 20.

Insulinoma-associated protein 1 is a protein that in humans is encoded by the INSM1 gene. Insulinoma-associated 1 (INSM1) gene is intronless and encodes a protein containing both a zinc finger DNA-binding domain and a putative prohormone domain. This gene is a sensitive marker for neuroendocrine differentiation of human lung tumors. INSM1 has been shown to interact with SORBS1.

INSM1 is a sequence-specific DNA-binding transcriptional regulator crucial for neurogenesis and neuroendocrine cell differentiation during embryonic/fetal development. It binds to the consensus sequence 5'-[TG][TC][TC][TT][GA]GGG[CG]A-3' in target promoters. Acting as a transcriptional repressor, INSM1 inhibits NEUROD1 and INS expression by interacting with cyclin CCND1 in a cell cycle-independent manner. It negatively regulates skeletal muscle-specific gene expression in pituitary endocrine cells by inhibiting the Notch signaling pathway. INSM1 represses target gene transcription by recruiting chromatin-modifying factors like HDAC1, HDAC2, HDAC3, KDM1A, and RCOR1 histone deacetylases. Autoregulation occurs as INSM1 binds to its own promoter. Competing with histone H3 for binding to the KDM1A/RCOR1 histone demethylase complex, INSM1 inhibits demethylation of histone H3 at 'Lys-4'. INSM1 promotes neuronal basal progenitor cell generation and expansion in the developing neocortex. It participates in endocrine cell differentiation in the developing anterior pituitary gland, pancreas, intestine, and peripheral nervous system's sympatho-adrenal cells. INSM1 promotes cell cycle signaling arrest and inhibits cellular proliferation.

INSM1 is also known as IA-1, IA1.

Associated Diseases

WES Whole Exome Sequencing