KSR1

Chr 17

kinase suppressor of ras 1

Also known as: KSR, RSU2

NCBI Gene: 8844ENSG00000141068UniProt: Q8IVT5

Enables 14-3-3 protein binding activity and ATP binding activity. Involved in positive regulation of MAPK cascade. Located in cytosol; endoplasmic reticulum; and membrane. Part of protein-containing complex. Implicated in breast adenocarcinoma. Biomarker of breast cancer. [provided by Alliance of Genome Resources, Jul 2025]

154
ClinVar variants
6
Pathogenic / LP
0.07
pLI score
0
Active trials
Clinical Summary— KSR1
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.26) despite low pLI — interpret in context.
📋
ClinVar Variants
6 Pathogenic / Likely Pathogenic· 122 VUS of 154 total submissions
Some data sources returned errors (1)

clinvar: Error: NCBI fetch failed: 429 https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esummary.fcgi

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.44LOEUF
pLI 0.070
Z-score 4.28
OE 0.26 (0.16–0.44)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
2.00Z-score
OE missense 0.74 (0.68–0.81)
360 obs / 483.9 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.26 (0.16–0.44)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.74 (0.68–0.81)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.05
0≤1.21.6
LoF obs/exp: 10 / 38.7Missense obs/exp: 360 / 483.9Syn Z: -0.54

ClinVar Variant Classifications

154 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic5
Likely Pathogenic1
VUS122
Likely Benign4
5
Pathogenic
1
Likely Pathogenic
122
VUS
4
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
5
0
5
Likely Pathogenic
0
0
1
0
1
VUS
0
115
7
0
122
Likely Benign
0
1
3
0
4
Benign
0
0
0
0
0
Total0116160132

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

KSR1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
VRK2 kinase pathogenic pathways in cancer and neurological diseases.
Lazo PA·Biochim Biophys Acta Mol Cell Res
2025Review
KSR1- and ERK-dependent translational regulation of the epithelial-to-mesenchymal transition.
Rao C et al.·Elife
2021
Epigenomic response to albuterol treatment in asthma-relevant airway epithelial cells.
Perez-Garcia J et al.·Clin Epigenetics
2023
KSR1 regulates BRCA1 degradation and inhibits breast cancer growth.
Stebbing J et al.·Oncogene
2015
Kinase Suppressor of RAS 1 (KSR1) Maintains the Transformed Phenotype of BRAFV600E Mutant Human Melanoma Cells.
Liu Z et al.·Int J Mol Sci
2023
LINC02167 stabilizes KSR1 mRNA in an m(5)C-dependent manner to regulate the ERK/MAPK signaling pathway and promotes colorectal cancer metastasis.
Qi J et al.·J Exp Clin Cancer Res
2025
Proteomic profile of KSR1-regulated signalling in response to genotoxic agents in breast cancer.
Zhang H et al.·Breast Cancer Res Treat
2015
Identification of B-KSR1, a novel brain-specific isoform of KSR1 that functions in neuronal signaling.
Müller J et al.·Mol Cell Biol
2000
Downregulation of KSR1 in pancreatic cancer xenografts by antisense oligonucleotide correlates with tumor drug uptake.
Zhang J et al.·Cancer Biol Ther
2008
Targeting oncogenic Raf protein-serine/threonine kinases in human cancers.
Roskoski R Jr·Pharmacol Res
2018Review
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools