KSR1
protein-codingkinase suppressor of ras 1, the group of RAF family
Gene summary
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]
- KSR
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~170.0 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to KSR1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001394583.1. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 3 | 3 | ||||
| missense | 119 | 1 | 120 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 0 | 0 | 123 | 1 | 0 | 124 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001381512.1 | 21 | MANE Select | |
| Ensembl | ENSP00000494552.1 | 21 | MANE Select | |
| RefSeq | NP_001354739.1 | 20 | Standard | |
| RefSeq | NP_001381513.1 | 15 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- C-type lectin receptor signaling pathway - Homo sapiens (human)
- Tuberculosis - Homo sapiens (human)
- Ras signaling pathway - Homo sapiens (human)
- EGF-Ncore
- TNF alpha Signaling Pathway
Biological Process
- MAPK cascade
- Ras protein signal transduction
- cAMP-mediated signaling
- regulation of cell population proliferation
- regulation of MAP kinase activity
Molecular Function
- protein kinase activity
- MAP-kinase scaffold activity
- protein binding
- ATP binding
- protein C-terminus binding
Cellular Component
- endoplasmic reticulum
- endoplasmic reticulum membrane
- cytosol
- membrane
- ruffle membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000398988
- Coding exons
- 19
- Length
- 169792
- Individuals with no LoFs
- 124647
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 14
- Defined
- 124661
- p
- 0.0000562
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 2.00 | 360 | 484 | 0.744 | 0.0000319 | 4911 |
| Missense (PolyPhen) | 123 | 183.59 | 0.66999 | 1826 | ||
| Synonymous | -0.543 | 213 | 203 | 1.05 | 0.0000140 | 1519 |
| Loss of Function | 4.28 | 10 | 38.7 | 0.258 | 0.00000191 | 445 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0.00012 | 0.00012 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.000056 | 0.000056 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000067 | 0.000062 | rare |
| South Asian | 0.000067 | 0.000065 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Scaffolding protein that is part of a multiprotein signaling complex. Promotes phosphorylation of Raf family members and activation of downstream MAP kinases. Promotes activation of MAPK1 and/or MAPK3, both in response to EGF and to cAMP. Does not have kinase activity by itself. {ECO:0000250|UniProtKB:Q61097}.;
Recessive Scores
- pRec
- 0.151
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.967
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |