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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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KSR1
kinase suppressor of ras 1
Chromosome 17 · 17q11.2
NCBI Gene: 8844Ensembl: ENSG00000141068.17HGNC: HGNC:6465UniProt: A0A2R8Y5H9
92PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Kinase
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
protein-containing complexprotein bindingATP bindingpositive regulation of MAPK cascadecancerNoonan syndromeCostello syndromehypertrophic cardiomyopathy
✦AI Summary

KSR1 (kinase suppressor of Ras 1) functions primarily as a molecular scaffold protein that facilitates signal transduction in the Ras-Raf-MEK-ERK pathway 1. As a scaffold, KSR1 assembles different cellular components to promote phosphorylation of Raf family members and activation of downstream MAP kinases 1. KSR1 acts as an allosteric activator of BRAF by binding to MEK1/MEK2, forming dimers with BRAF that enhance BRAF-mediated phosphorylation of MEK proteins 2. The protein exhibits dual functionality, possessing both pseudokinase and active kinase properties, with its kinase activity becoming activated under specific pathological conditions such as inflammatory bowel disease 34. KSR1 is significantly overexpressed in various cancers, including colon tumors and small cell lung cancer, where it promotes tumor cell survival by regulating Myc and PGC1β expression 5. In small cell lung cancer, KSR1 mediates tumor initiation and cisplatin resistance, with knockout preventing resistance in >90% of cells 6. KSR1 also contributes to fibrotic diseases by promoting cell proliferation, migration, and fibrosis through the MEK/ERK signaling pathway 7. These findings establish KSR1 as a critical regulator in both normal cellular signaling and disease pathogenesis.

Sources cited
1
KSR1 functions as a scaffold protein in the ERK1/2 MAP kinase cascade
PMID: 22569528
2
KSR1 acts as an allosteric activator of BRAF through MEK1/MEK2 binding and dimerization
PMID: 35508574
3
KSR1 kinase activity is activated during inflammatory bowel disease
PMID: 15520853
4
KSR1 has dual functionality as both pseudokinase and scaffolding protein
PMID: 23863182
5
KSR1 is overexpressed in colon tumors and promotes survival through Myc and PGC1β regulation
PMID: 27273865
6
KSR1 mediates tumor initiation and cisplatin resistance in small cell lung cancer
PMID: 39927878
7
KSR1 promotes fibrosis and cell migration through MEK/ERK signaling pathway
PMID: 40089092
Disease Associationsⓘ20
cancerOpen Targets
0.60Moderate
Noonan syndromeOpen Targets
0.55Moderate
Costello syndromeOpen Targets
0.54Moderate
hypertrophic cardiomyopathyOpen Targets
0.54Moderate
Crohn's diseaseOpen Targets
0.37Weak
cardiofaciocutaneous syndromeOpen Targets
0.37Weak
neurodegenerative diseaseOpen Targets
0.31Weak
neuroinflammatory disorderOpen Targets
0.31Weak
ulcerative colitisOpen Targets
0.27Weak
sclerosing cholangitisOpen Targets
0.27Weak
ovarian neoplasmOpen Targets
0.25Weak
ankylosing spondylitisOpen Targets
0.24Weak
psoriasisOpen Targets
0.24Weak
DysmetriaOpen Targets
0.18Weak
colorectal carcinomaOpen Targets
0.09Suggestive
neoplasmOpen Targets
0.09Suggestive
osteosarcomaOpen Targets
0.07Suggestive
breast cancerOpen Targets
0.07Suggestive
hypotrichosis simplexOpen Targets
0.06Suggestive
Alopecia universalisOpen Targets
0.05Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
CLEC4MProtein interaction100%MAPK3Protein interaction99%ARRB1Protein interaction99%ARRB2Protein interaction99%PLK3Protein interaction95%LSP1Protein interaction95%
Tissue Expression6 tissues
Ovary
100%
Lung
100%
Bone Marrow
80%
Brain
40%
Liver
25%
Heart
24%
Gene Interaction Network
Click a node to explore
KSR1CLEC4MMAPK3ARRB1ARRB2PLK3LSP1
PROTEIN STRUCTURE
Preparing viewer…
PDB5VYK · 1.75 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.48Moderately Constrained
pLIⓘ
0.99Intolerant
Observed/Expected LoF0.35 [0.26–0.48]
RankingsWhere KSR1 stands among ~20K protein-coding genes
  • #5,196of 20,598
    Most Researched92
  • #2,813of 17,882
    Most Constrained (LOEUF)0.48 · top quartile
Genes detectedKSR1
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
ERK1/2 MAP kinases: structure, function, and regulation.
PMID: 22569528
Pharmacol Res · 2012
1.00
2
KSR1 and EPHB4 Regulate Myc and PGC1β To Promote Survival of Human Colon Tumors.
PMID: 27273865
Mol Cell Biol · 2016
0.90
3
KSR1 Mediates Small Cell Lung Carcinoma Tumor Initiation and Cisplatin Resistance.
PMID: 39927878
Mol Cancer Res · 2025
0.80
4
The KSR1/MEK/ERK signaling pathway promotes the progression of intrauterine adhesions.
PMID: 40089092
Cell Signal · 2025
0.70
5
The dual function of KSR1: a pseudokinase and beyond.
PMID: 23863182
Biochem Soc Trans · 2013
0.60