CNKSR2: Connector Enhancer of Kinase Suppressor of Ras 2
A scaffold protein in synaptic RAS signaling and neurodevelopmental disorders
Gene Information Card
| Symbol | CNKSR2 |
|---|---|
| Full Name | Connector Enhancer of Kinase Suppressor of Ras 2 |
| Gene Type | Protein coding |
| Chromosomal Location | Xp22.12 |
| NCBI Gene ID | 22866 ncbi.nlm.nih.gov/gene/22866 |
| Ensembl ID | ENSG00000124491 |
| UniProt ID | Q8WXI2 |
| OMIM ID | 300724 |
| HGNC ID | 19701 |
| Aliases | CNK2, MAGUIN, KSR2-binding protein |
Description
CNKSR2 (Connector Enhancer of Kinase Suppressor of Ras 2) encodes a multidomain scaffold protein that modulates RAS-MAPK signaling at the postsynaptic density. It is highly expressed in the brain and plays a critical role in synaptic plasticity, dendritic spine morphogenesis, and neuronal development. Loss-of-function mutations in CNKSR2 cause X-linked intellectual disability with or without epilepsy.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| X-linked intellectual disability with epilepsy | Loss-of-function mutations impair RAS-MAPK signaling and synaptic plasticity | ClinVar, OMIM |
| Epileptic encephalopathy, early infantile | Deleterious variants disrupt postsynaptic scaffold function | ClinVar, OMIM |
| Autism spectrum disorder | Rare missense variants may alter synaptic signaling | ClinVar |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain (cerebral cortex) | 12.5 | High |
| Brain (cerebellum) | 9.8 | Medium |
| Testis | 4.2 | Low |
| Heart | 1.1 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | 15.3 | High expression |
| U-87 MG (glioblastoma) | 8.7 | Moderate |
| HEK293 (embryonic kidney) | 2.1 | Low |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1282C>T (p.Arg428*) | Nonsense | Rare | Loss of function; truncated protein |
| c.2023_2024del (p.Glu675fs) | Frameshift | Rare | Loss of function; premature stop |
| c.155G>A (p.Arg52Gln) | Missense | Rare | Likely damaging; altered scaffold interaction |
Mutation functional classification
Loss of Function (LOF)
Nonsense, frameshift, and splice-site variants leading to truncated or absent CNKSR2 protein; associated with intellectual disability and epilepsy.
Gain of Function (GOF)
Not reported.
Dominant Negative (DN)
Not reported; X-linked inheritance suggests hemizygous loss in males.
View complete mutation data：
Gene Ontology (GO)
| • scaffold protein activity | • RAS protein signal transduction |
| • synaptic signaling | • dendritic spine morphogenesis |
| • postsynaptic density assembly |
Pathways
• RAS-MAPK signaling pathway
• Ephrin receptor signaling
• Synaptic plasticity
Protein Summary
CNKSR2 is a 1,032-amino-acid scaffold protein containing SAM, PH, PDZ, and proline-rich domains. It localizes to the postsynaptic density and interacts with KSR2, RAF, and MEK to regulate ERK signaling. The protein is essential for activity-dependent synaptic plasticity and dendritic spine maintenance.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| 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 |
| CNKSR2 Knockout HeLa Cell Line | EDJ-KQ55646 | Human | 22866 | Details Get a Quote |
| CNKSR2 Knockout HCT 116 Cell Line | EDJ-KQ72593 | Human | 22866 | Details Get a Quote |
