ISL1: A Key Transcription Factor in Cardiac and Pancreatic Development
Comprehensive genomic and functional overview of ISL1, a LIM-homeodomain transcription factor essential for cardiac, pancreatic, and neural development.
Gene Information Card
| Symbol | ISL1 |
|---|---|
| Full Name | ISL LIM homeobox 1 |
| Gene Type | Protein-coding |
| Chromosomal Location | 5q11.1 |
| NCBI Gene ID | 3670 ncbi.nlm.nih.gov/gene/3670 |
| Ensembl ID | ENSG00000016082 |
| UniProt ID | P61371 |
| OMIM ID | 600366 |
| HGNC ID | 6132 |
| Aliases | Isl-1, ISLET1, insulin gene enhancer protein ISL-1 |
Description
ISL1 (ISL LIM homeobox 1) encodes a transcription factor containing two LIM domains and a homeobox domain. It is a key regulator of cardiac progenitor cell differentiation, pancreatic islet cell development, and motor neuron specification. ISL1 is essential for the formation of the heart, pancreas, and neural tissues, and its dysregulation is linked to congenital heart disease, type 2 diabetes, and certain cancers.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Congenital heart disease (CHD) | ISL1 haploinsufficiency disrupts cardiac progenitor cell proliferation and differentiation, leading to septal and outflow tract defects. | ClinVar, OMIM |
| Type 2 diabetes | ISL1 variants impair pancreatic beta-cell development and insulin gene expression, contributing to reduced insulin secretion. | NCBI Gene, OMIM |
| Maturity-onset diabetes of the young (MODY) | Rare ISL1 mutations cause autosomal dominant forms of diabetes through defective pancreatic development. | OMIM, ClinVar |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Heart | 12.5 | Medium |
| Pancreas | 8.3 | Medium |
| Brain | 6.1 | Low |
| Spinal cord | 4.7 | Low |
| Skeletal muscle | 2.1 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| Cardiac progenitor cells (CPCs) | 15.2 | High expression in undifferentiated CPCs |
| Pancreatic beta-cell lines (e.g., INS-1) | 10.8 | Key regulator of insulin transcription |
| Neuroblastoma cell lines (e.g., SH-SY5Y) | 5.4 | Moderate expression during neuronal differentiation |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.4C>T (p.Arg2Trp) | Missense | Rare | Reduced DNA-binding affinity and transcriptional activity |
| c.349G>A (p.Gly117Ser) | Missense | Rare | Impaired homeodomain function, associated with MODY |
| c.502_504del (p.Lys168del) | Deletion | Rare | Loss of LIM domain integrity, dominant-negative effect |
Mutation functional classification
Loss of Function (LOF)
Haploinsufficiency or missense mutations that reduce DNA binding or transcriptional activation lead to loss of function, contributing to congenital heart disease and diabetes.
Gain of Function (GOF)
Not well-documented; no common gain-of-function mutations reported in ISL1.
Dominant Negative (DN)
Deletion mutations affecting the LIM domain (e.g., p.Lys168del) can exert dominant-negative effects by interfering with wild-type ISL1 function.
View complete mutation data：
Gene Ontology (GO)
| • DNA-binding transcription factor activity | • RNA polymerase II cis-regulatory region sequence-specific DNA binding |
| • chromatin binding | • protein homodimerization activity |
| • cardiac cell fate specification | • pancreatic endocrine cell differentiation |
| • motor neuron axon guidance | • positive regulation of insulin secretion |
Pathways
• Cardiac progenitor cell differentiation pathway
• Pancreatic beta-cell development pathway
• Insulin gene regulation pathway
• LIM-homeodomain transcription factor network
Protein Summary
ISL1 is a 349-amino-acid transcription factor with two N-terminal LIM domains (zinc-binding) and a C-terminal homeodomain. It binds to specific DNA sequences (e.g., TAATTA) to regulate genes involved in cell fate determination, proliferation, and differentiation. In the heart, ISL1 marks cardiac progenitor cells and is critical for second heart field development. In the pancreas, it activates insulin and other beta-cell genes. Post-translational modifications include phosphorylation and sumoylation, which modulate its activity.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| ISL1 Knockout HEK293 Cell Line | EDJ-KQ5008 | Human | 3670 | Details Get a Quote |
| ISL1 Knockout HCT 116 Cell Line | EDJ-KQ27918 | Human | 3670 | Details Get a Quote |
| ISL1 Knockout HeLa Cell Line | EDJ-KQ27919 | Human | 3670 | Details Get a Quote |
| ISL1 Knockout A-549 Cell Line | EDJ-KQ62147 | Human | 3670 | Details Get a Quote |
Displaying Records 1 To 4 Of 4 Records
