CASK: Calcium/Calmodulin Dependent Serine Protein Kinase
A multi-functional scaffold and kinase protein critical for synaptic development and intellectual disability
Gene Information Card
| Symbol | CASK |
|---|---|
| Full Name | Calcium/calmodulin dependent serine protein kinase |
| Gene Type | Protein coding |
| Chromosomal Location | Xp11.4 |
| NCBI Gene ID | 8573 ncbi.nlm.nih.gov/gene/8573 |
| Ensembl ID | ENSG00000147044 |
| UniProt ID | O14936 |
| OMIM ID | 300172 |
| HGNC ID | 1497 |
| Aliases | CMG, FGS4, LIN2, MRXSNA, TNRC8, CAGH39, CAMGUK, MICPCH |
Description
The CASK gene encodes a calcium/calmodulin-dependent serine protein kinase that belongs to the membrane-associated guanylate kinase (MAGUK) family. CASK acts as a scaffold protein at neuronal synapses, interacting with multiple partners including neurexins, syndecans, and transcription factors. It is essential for brain development, synaptic plasticity, and neuronal migration. Loss-of-function mutations in CASK cause X-linked intellectual disability with or without microcephaly, pontocerebellar hypoplasia, and optic atrophy.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Intellectual disability, X-linked, with or without microcephaly (MRXSNA) | Loss-of-function mutations in CASK disrupt synaptic scaffolding and kinase activity, impairing neuronal development and synaptic function. | ClinVar, OMIM |
| Microcephaly with pontocerebellar hypoplasia (MICPCH) | Severe loss-of-function or null mutations in CASK lead to reduced brain growth and cerebellar hypoplasia. | OMIM, ClinVar |
| FG syndrome 4 (FGS4) | Missense mutations in CASK may alter protein interactions, contributing to a syndromic form of intellectual disability. | OMIM |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 38.5 | High |
| Cerebral cortex | 45.2 | High |
| Cerebellum | 42.1 | High |
| Heart | 6.3 | Low |
| Liver | 2.1 | Not detected |
| Kidney | 4.8 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | 32.7 | Neuronal model |
| U-87 MG (glioblastoma) | 28.4 | Glial model |
| HEK 293 (embryonic kidney) | 12.1 | Non-neuronal |
| HeLa (cervical carcinoma) | 8.5 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1A>G (p.Met1?) | Start loss | Rare | Loss of protein expression; severe phenotype |
| c.1024C>T (p.Arg342*) | Nonsense | Rare | Truncation; loss of kinase and scaffold domains |
| c.1685G>A (p.Arg562Gln) | Missense | Rare | Impaired neurexin binding; intellectual disability |
| c.2272_2273del (p.Leu758Glufs*12) | Frameshift | Rare | Loss of C-terminal domain; severe MICPCH |
Mutation functional classification
Loss of Function (LOF)
Most CASK mutations are loss-of-function, leading to reduced protein stability, impaired scaffolding, or abolished kinase activity. This results in X-linked intellectual disability and microcephaly.
Gain of Function (GOF)
No gain-of-function mutations have been reported for CASK.
Dominant Negative (DN)
Some missense mutations may act in a dominant-negative manner by disrupting protein-protein interactions without complete loss of expression, but evidence is limited.
View complete mutation data：
Gene Ontology (GO)
| • GO:0004674 | • GO:0005516 |
| • GO:0005524 | • GO:0007268 |
| • GO:0007416 | • GO:0019901 |
| • GO:0030154 | • GO:0045202 |
| • GO:0050808 |
Pathways
• Neurexin-neuroligin signaling
• Synaptic vesicle cycle
• MAGUK scaffold assembly
• Calcium/calmodulin-dependent kinase signaling
Protein Summary
CASK is a 926-amino acid multi-domain protein containing an N-terminal calcium/calmodulin-dependent kinase domain, two L27 domains, a PDZ domain, an SH3 domain, and a C-terminal guanylate kinase (GUK) domain. It functions as both a kinase and a scaffold, linking cell adhesion molecules (neurexins, syndecans) to the cytoskeleton and signaling complexes. CASK also translocates to the nucleus to regulate gene expression via TBR1 interaction. Its structure enables dynamic roles in synapse formation, maintenance, and plasticity.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| CASK Knockout HEK293 Cell Line | EDJ-KQ6290 | Human | 8573 | Details Get a Quote |
| CASKIN1 Knockout HEK293 Cell Line | EDJ-KQ11931 | Human | 57524 | Details Get a Quote |
| CASKIN2 Knockout HEK293 Cell Line | EDJ-KQ12731 | Human | 57513 | Details Get a Quote |
| CASK Knockout A-549 Cell Line | EDJ-KQ30192 | Human | 8573 | Details Get a Quote |
| CASK Knockout HCT 116 Cell Line | EDJ-KQ30193 | Human | 8573 | Details Get a Quote |
| CASK Knockout HeLa Cell Line | EDJ-KQ30194 | Human | 8573 | Details Get a Quote |
| CASKIN2 Knockout A-549 Cell Line | EDJ-KQ41828 | Human | 57513 | Details Get a Quote |
| CASKIN2 Knockout HCT 116 Cell Line | EDJ-KQ41829 | Human | 57513 | Details Get a Quote |
| CASKIN2 Knockout HeLa Cell Line | EDJ-KQ41830 | Human | 57513 | Details Get a Quote |
| CASKIN1 Knockout HeLa Cell Line | EDJ-KQ56857 | Human | 57524 | Details Get a Quote |
| CASKIN1 Knockout A-549 Cell Line | EDJ-KQ65370 | Human | 57524 | Details Get a Quote |
| CASKIN1 Knockout HCT 116 Cell Line | EDJ-KQ73808 | Human | 57524 | Details Get a Quote |
| CASK Knockout HAP1 Cell Line | EDC08145 | Human | 8573 | Details Get a Quote |
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