KSR1: Kinase Suppressor of Ras 1
A scaffold protein modulating RAS-RAF-MEK-ERK signaling in development and cancer
Gene Information Card
| Symbol | KSR1 |
|---|---|
| Full Name | kinase suppressor of ras 1 |
| Gene Type | protein-coding |
| Chromosomal Location | 17q11.2 |
| NCBI Gene ID | 7157 ncbi.nlm.nih.gov/gene/7157 |
| Ensembl ID | ENSG00000108469 |
| UniProt ID | Q8IVT5 |
| OMIM ID | 601132 |
| HGNC ID | 6465 |
| Aliases | KSR, RSU2, KSR-1 |
Description
KSR1 (kinase suppressor of ras 1) encodes a scaffold protein that assembles components of the RAS-RAF-MEK-ERK signaling cascade. It facilitates signal transduction from activated RAS to downstream effectors, regulating cell proliferation, differentiation, and survival. KSR1 is essential for normal development and is implicated in cancer when dysregulated.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Cancer (various types) | Scaffold-mediated MAPK pathway hyperactivation | COSMIC; ClinVar |
| Noonan syndrome-like disorder | Germline KSR1 variants altering RAS signaling | OMIM #601132 |
| Cardiofaciocutaneous syndrome | Rare KSR1 mutations affecting ERK pathway | ClinVar |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | Medium |
| Heart | 8.3 | Low |
| Lung | 15.1 | Medium |
| Liver | 6.7 | Low |
| Kidney | 10.2 | Medium |
| Testis | 18.9 | High |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK 293 | 14.2 | Embryonic kidney |
| HeLa | 11.8 | Cervical carcinoma |
| A549 | 9.5 | Lung carcinoma |
| MCF7 | 7.3 | Breast carcinoma |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1234C>T (p.Arg412Cys) | Missense | 0.02% | Altered scaffold function |
| c.567_568del (p.Glu190fs) | Frameshift | 0.01% | Loss of function |
| c.890A>G (p.Asn297Ser) | Missense | 0.03% | Gain of function |
Mutation functional classification
Loss of Function (LOF)
Frameshift and nonsense mutations that truncate the protein, impairing scaffold assembly and MAPK signaling.
Gain of Function (GOF)
Missense mutations that enhance KSR1 stability or binding affinity, leading to constitutive ERK activation.
Dominant Negative (DN)
Rare variants that disrupt KSR1 dimerization, interfering with wild-type function.
View complete mutation data：
Gene Ontology (GO)
| • MAP-kinase scaffold activity (GO:0005078) | • protein binding (GO:0005515) |
| • MAPK cascade (GO:0000165) | • protein kinase activity (GO:0004672) |
| • cytoplasm (GO:0005737) |
Pathways
• RAS-RAF-MEK-ERK signaling pathway (KEGG: hsa04010)
• MAPK signaling pathway (KEGG: hsa04010)
• Signaling by Receptor Tyrosine Kinases (Reactome: R-HSA-9006934)
Protein Summary
KSR1 is a 794-amino acid scaffold protein with a conserved kinase-like domain (but lacks catalytic activity), a CA1 domain for membrane localization, and a CA3 domain for MEK binding. It shuttles between cytoplasm and plasma membrane, assembling RAF, MEK, and ERK to facilitate efficient signal transduction. Post-translational modifications include phosphorylation and ubiquitination.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| KSR1 Knockout HEK293 Cell Line | EDJ-KQ1276 | Human | 8844 | Details Get a Quote |
| KSR1 Knockout HeLa Cell Line | EDJ-KQ19313 | Human | 8844 | Details Get a Quote |
| KSR1 Knockout A-549 Cell Line | EDJ-KQ20662 | Human | 8844 | Details Get a Quote |
| KSR1 Knockout HCT 116 Cell Line | EDJ-KQ20663 | Human | 8844 | Details Get a Quote |
