KSR2 Gene (Kinase Suppressor of Ras 2)
A scaffold protein modulating RAS-MAPK signaling and metabolic regulation
Gene Information Card
| Symbol | KSR2 |
|---|---|
| Full Name | Kinase Suppressor of Ras 2 |
| Gene Type | Protein coding |
| Chromosomal Location | 12q24.22 |
| NCBI Gene ID | 283455 ncbi.nlm.nih.gov/gene/283455 |
| Ensembl ID | ENSG00000171435 |
| UniProt ID | Q6VAB6 |
| OMIM ID | 610737 |
| HGNC ID | 18677 |
| Aliases | hKSR2, KSR2_HUMAN |
Description
KSR2 (Kinase Suppressor of Ras 2) is a scaffold protein that assembles components of the RAS-MAPK signaling cascade, including RAF, MEK, and ERK. It facilitates signal transduction from growth factor receptors to downstream effectors, regulating cell proliferation, differentiation, and metabolism. KSR2 is also implicated in energy homeostasis and insulin sensitivity.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Obesity, early-onset, susceptibility to | Loss-of-function mutations impair RAS-MAPK signaling, leading to reduced energy expenditure and increased food intake | PMID: 23064227, ClinVar |
| Insulin resistance, type 2 diabetes | Disrupted KSR2-mediated signaling alters insulin sensitivity and glucose metabolism | PMID: 23064227, OMIM #610737 |
| Developmental delay, intellectual disability | KSR2 mutations may affect neuronal signaling and synaptic plasticity | ClinVar, PMID: 23064227 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | Medium |
| Adipose tissue | 8.3 | Low |
| Pancreas | 6.1 | Low |
| Skeletal muscle | 4.7 | Low |
| Liver | 3.2 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 15.2 | Moderate expression |
| HeLa | 10.8 | Low expression |
| SH-SY5Y | 18.4 | Neuronal cell line, higher expression |
| HepG2 | 5.1 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1094C>T (p.Thr365Met) | Missense | 0.01% | Loss of function, reduced ERK activation |
| c.1462C>T (p.Arg488*) | Nonsense | <0.01% | Truncation, loss of scaffold function |
| c.1789G>A (p.Gly597Arg) | Missense | 0.005% | Impaired MEK binding |
Mutation functional classification
Loss of Function (LOF)
Most KSR2 mutations reduce or abolish scaffold activity, impairing RAS-MAPK signaling.
Gain of Function (GOF)
No gain-of-function mutations reported.
Dominant Negative (DN)
Some missense variants may act dominant-negative by sequestering pathway components.
View complete mutation data：
Gene Ontology (GO)
| • GO:0005078 ~ MAP-kinase scaffold activity | • GO:0000165 ~ MAPK cascade |
| • GO:0005515 ~ protein binding | • GO:0005886 ~ plasma membrane |
| • GO:0005737 ~ cytoplasm |
Pathways
• RAS-MAPK signaling pathway (Reactome R-HSA-5673001)
• Signaling by RAF/MAP kinases (Reactome R-HSA-5675220)
• MAPK1/MAPK3 signaling (Reactome R-HSA-5684996)
Protein Summary
KSR2 is a 950-amino acid scaffold protein that coordinates the assembly of RAF, MEK, and ERK kinases, facilitating efficient signal transduction through the RAS-MAPK cascade. It contains conserved domains including a CA1 (coiled-coil) region, a CA2 (proline-rich) region, and a CA3 (kinase-like) domain. KSR2 is expressed in brain, adipose tissue, and pancreas, and plays a critical role in energy balance and insulin action. Loss-of-function mutations are associated with early-onset obesity, insulin resistance, and developmental delay.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| KSR2 Knockout HEK293 Cell Line | EDJ-KQ1277 | Human | 283455 | Details Get a Quote |
| CNKSR2 Knockout HEK293 Cell Line | EDJ-KQ7704 | Human | 22866 | Details Get a Quote |
| CNKSR2 Knockout A-549 Cell Line | EDJ-KQ33092 | Human | 22866 | Details Get a Quote |
| KSR2 Knockout A-549 Cell Line | EDJ-KQ20665 | Human | 283455 | Details Get a Quote |
| KSR2 Knockout HCT 116 Cell Line | EDJ-KQ20666 | Human | 283455 | Details Get a Quote |
| CNKSR2 Knockout HeLa Cell Line | EDJ-KQ55646 | Human | 22866 | Details Get a Quote |
| KSR2 Knockout HeLa Cell Line | EDJ-KQ59396 | Human | 283455 | Details Get a Quote |
| CNKSR2 Knockout HCT 116 Cell Line | EDJ-KQ72593 | Human | 22866 | Details Get a Quote |
| KSR2 Knockout HAP1 Cell Line | EDC08138 | Human | 283455 | Details Get a Quote |
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