SIM1 Gene - Single-minded Homolog 1
A basic helix-loop-helix transcription factor involved in neurogenesis and energy homeostasis
Gene Information Card
| Symbol | SIM1 |
|---|---|
| Full Name | Single-minded Homolog 1 (Drosophila) |
| Gene Type | Protein coding |
| Chromosomal Location | 6q16.3 |
| NCBI Gene ID | 6492 ncbi.nlm.nih.gov/gene/6492 |
| Ensembl ID | ENSG00000112210 |
| UniProt ID | P81133 |
| OMIM ID | 603128 |
| HGNC ID | 10882 |
| Aliases | bHLHe14, SIM, SIM1_HUMAN |
Description
SIM1 encodes a basic helix-loop-helix (bHLH) transcription factor that is a homolog of the Drosophila single-minded protein. It plays a critical role in the development of the paraventricular nucleus of the hypothalamus and is involved in regulating energy balance, feeding behavior, and neurogenesis. Mutations in SIM1 are associated with early-onset obesity and Prader-Willi-like syndrome.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Obesity, early-onset | Loss-of-function mutations impair hypothalamic development and leptin signaling | OMIM #601665; ClinVar |
| Prader-Willi-like syndrome | Haploinsufficiency of SIM1 leads to hyperphagia and obesity | OMIM #603128; NCBI Gene |
| Neurodevelopmental disorder | Disruption of SIM1 affects neuronal differentiation in the hypothalamus | UniProt; PubMed studies |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | High |
| Hypothalamus | 25.3 | High |
| Kidney | 3.2 | Low |
| Testis | 1.8 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | 8.4 | Neuronal lineage |
| HEK293 (embryonic kidney) | 2.1 | Low expression |
| HepG2 (liver) | 1.0 | Not detected |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.343C>T (p.Arg115Ter) | Nonsense | Rare | Loss of function; truncation of bHLH domain |
| c.467G>A (p.Arg156His) | Missense | 0.01% | Impaired DNA binding and transactivation |
| c.784_785del (p.Leu262fs) | Frameshift | Rare | Loss of function; premature stop |
Mutation functional classification
Loss of Function (LOF)
Most SIM1 mutations are loss-of-function, leading to haploinsufficiency and obesity.
Gain of Function (GOF)
No gain-of-function mutations reported in SIM1.
Dominant Negative (DN)
Some missense mutations may act as dominant-negative by dimerizing with wild-type ARNT.
View complete mutation data：
Gene Ontology (GO)
| • DNA-binding transcription factor activity | • RNA polymerase II cis-regulatory region sequence-specific DNA binding |
| • protein heterodimerization activity | • nucleus |
| • regulation of transcription by RNA polymerase II | • neuron differentiation |
| • feeding behavior |
Pathways
• HIF-1 signaling pathway
• Circadian rhythm
• Neurotrophin signaling pathway
Protein Summary
SIM1 is a 766-amino acid transcription factor containing a bHLH domain and a PAS domain. It heterodimerizes with ARNT (HIF1B) to regulate target genes involved in hypothalamic development and energy homeostasis. The protein is predominantly nuclear and expressed in the developing and adult brain.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| SIM1 Knockout HEK293 Cell Line | EDJ-KQ5750 | Human | 6492 | Details Get a Quote |
| SIM1 Knockout HeLa Cell Line | EDJ-KQ54471 | Human | 6492 | Details Get a Quote |
| SIM1 Knockout A-549 Cell Line | EDJ-KQ62957 | Human | 6492 | Details Get a Quote |
| SIM1 Knockout HCT 116 Cell Line | EDJ-KQ71430 | Human | 6492 | Details Get a Quote |
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