INSM1: Insulinoma-Associated Protein 1
Transcriptional regulator in neuroendocrine differentiation and tumorigenesis
Gene Information Card
| Symbol | INSM1 |
|---|---|
| Full Name | Insulinoma-Associated Protein 1 |
| Gene Type | Protein coding |
| Chromosomal Location | 20p11.23 |
| NCBI Gene ID | 3642 ncbi.nlm.nih.gov/gene/3642 |
| Ensembl ID | ENSG00000101204 |
| UniProt ID | Q01101 |
| OMIM ID | 600010 |
| HGNC ID | 6090 |
| Aliases | IA-1, IA1 |
Description
INSM1 (Insulinoma-Associated Protein 1) encodes a zinc-finger transcription factor that plays a critical role in neuroendocrine differentiation and development. It is expressed in developing neuroendocrine tissues and is frequently re-expressed in neuroendocrine tumors, serving as a diagnostic and prognostic biomarker. INSM1 regulates genes involved in cell cycle, apoptosis, and neuroendocrine lineage specification.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Neuroendocrine tumors (e.g., insulinoma, small cell lung carcinoma, medullary thyroid carcinoma) | Overexpression of INSM1 promotes neuroendocrine differentiation and tumor growth by activating downstream targets such as ASCL1 and inhibiting apoptosis | ClinVar, COSMIC, NCBI Gene |
| Pheochromocytoma | INSM1 is highly expressed in chromaffin cell-derived tumors, contributing to catecholamine synthesis and tumor progression | NCBI Gene, OMIM |
| Merkel cell carcinoma | INSM1 expression is a sensitive marker for Merkel cell carcinoma, aiding in differential diagnosis | ClinVar, COSMIC |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Pancreas | 12.5 | Medium |
| Adrenal gland | 8.3 | Low |
| Thyroid | 6.1 | Low |
| Lung | 2.4 | Not detected |
| Brain | 1.8 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| NCI-H69 (small cell lung cancer) | 45.2 | High expression; neuroendocrine lineage |
| BON-1 (pancreatic carcinoid) | 38.7 | High expression; insulinoma model |
| TT (medullary thyroid carcinoma) | 29.1 | High expression; neuroendocrine tumor |
| HEK293 (embryonic kidney) | 0.5 | Low/not detected; non-neuroendocrine |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1A>G (p.Met1?) | Missense | Rare | Loss of start codon; likely loss of function |
| c.100C>T (p.Arg34Trp) | Missense | Rare | Altered DNA-binding domain; reduced transcriptional activity |
| c.250G>A (p.Gly84Ser) | Missense | Rare | Unknown functional effect; reported in neuroendocrine tumors |
Mutation functional classification
Loss of Function (LOF)
Mutations affecting the zinc-finger domain or start codon reduce DNA binding and transcriptional activation, impairing neuroendocrine differentiation.
Gain of Function (GOF)
No confirmed gain-of-function mutations reported; overexpression in tumors is primarily due to transcriptional upregulation rather than activating mutations.
Dominant Negative (DN)
No dominant-negative mutations described in the literature.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Neuroendocrine differentiation pathway (ASCL1-INSM1 axis)
• Notch signaling pathway (INSM1 represses Notch targets)
• Cell cycle regulation (p21/CDKN1A modulation)
Protein Summary
INSM1 is a 510-amino acid zinc-finger transcription factor localized to the nucleus. It contains five C2H2-type zinc fingers that mediate sequence-specific DNA binding. INSM1 acts as both a transcriptional repressor and activator, regulating genes involved in neuroendocrine differentiation, cell cycle arrest, and apoptosis. It is a key marker for neuroendocrine tumors and is used in immunohistochemistry for diagnostic purposes.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| INSM1 Knockout HEK293 Cell Line | EDJ-KQ1916 | Human | 3642 | Details Get a Quote |
| INSM1 Knockout HeLa Cell Line | EDJ-KQ53668 | Human | 3642 | Details Get a Quote |
| INSM1 Knockout A-549 Cell Line | EDJ-KQ62142 | Human | 3642 | Details Get a Quote |
| INSM1 Knockout HCT 116 Cell Line | EDJ-KQ70633 | Human | 3642 | Details Get a Quote |
Displaying Records 1 To 4 Of 4 Records
