CNTNAP1
Contactin Associated Protein 1: A Key Node in Neural Myelination and Nodal Architecture
Gene Information Card
| Symbol | CNTNAP1 |
|---|---|
| Full Name | Contactin Associated Protein 1 |
| Gene Type | Protein coding |
| Chromosomal Location | 17q21.2 |
| NCBI Gene ID | 26047 ncbi.nlm.nih.gov/gene/26047 |
| Ensembl ID | ENSG00000108797 |
| UniProt ID | P78357 |
| OMIM ID | 602346 |
| HGNC ID | 2171 |
| Aliases | Caspr, Neurexin IV, NRXN4, p190 |
Description
CNTNAP1 encodes Contactin Associated Protein 1 (Caspr), a transmembrane protein essential for the formation and maintenance of paranodal junctions between axons and glial cells. These junctions flank the nodes of Ranvier and are critical for saltatory conduction in myelinated neurons. Caspr interacts with contactin (CNTN) and neurofascin (NFASC) to organize the paranodal septate-like junctions. Loss-of-function mutations in CNTNAP1 cause severe peripheral and central nervous system dysmyelination disorders.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Congenital hypomyelinating neuropathy (CHN) | Biallelic loss-of-function mutations disrupt paranodal junction assembly, leading to impaired myelination and axonal degeneration. | ClinVar, OMIM |
| Arthrogryposis multiplex congenita (AMC) with neuropathy | CNTNAP1 mutations cause severe fetal hypokinesia, joint contractures, and peripheral nerve hypomyelination. | OMIM, PubMed |
| Lethal congenital contracture syndrome (LCCS) | Homozygous truncating variants result in complete loss of Caspr, causing prenatal lethality with severe contractures and brain anomalies. | OMIM, PubMed |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.8 | High |
| Spinal cord | 10.5 | High |
| Peripheral nerve | 9.2 | High |
| Heart | 3.1 | Low |
| Skeletal muscle | 2.4 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | 15.3 | High expression; used in neuronal differentiation studies |
| U-87 MG (glioblastoma) | 8.7 | Moderate expression |
| HEK293 (embryonic kidney) | 0.5 | Very low; not endogenous |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1117C>T (p.Arg373*) | Nonsense | Rare | Premature stop; loss of protein function |
| c.2023G>A (p.Gly675Arg) | Missense | Rare | Disrupts paranodal localization; hypomorphic |
| c.1A>G (p.Met1?) | Start loss | Rare | No translation initiation; complete loss of function |
| c.2440_2441del (p.Leu814Valfs*3) | Frameshift | Rare | Truncated protein; loss of C-terminal domain |
Mutation functional classification
Loss of Function (LOF)
Most CNTNAP1 mutations are loss-of-function (nonsense, frameshift, start loss) leading to absent or non-functional Caspr protein, resulting in severe congenital neuropathies.
Gain of Function (GOF)
No gain-of-function mutations have been reported for CNTNAP1.
Dominant Negative (DN)
No dominant-negative mutations have been described; all pathogenic variants are recessive.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Paranodal junction assembly (Reactome: R-HSA-447043)
• Cell junction organization (Reactome: R-HSA-446728)
• Developmental biology (Reactome: R-HSA-1266738)
Protein Summary
Contactin Associated Protein 1 (Caspr) is a 1381-amino acid transmembrane glycoprotein belonging to the neurexin family. It contains a large extracellular domain with laminin G, EGF-like, and fibrinogen-like repeats, a single transmembrane helix, and a short cytoplasmic tail. Caspr localizes to paranodal junctions where it binds contactin and neurofascin 155, forming a complex that separates voltage-gated sodium channels at the node from potassium channels in the juxtaparanodal region. This molecular fence is essential for rapid saltatory conduction. Loss of Caspr leads to disrupted paranodal septa, mislocalization of ion channels, and slowed nerve conduction.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| CNTNAP1 Knockout HEK293 Cell Line | EDJ-KQ6263 | Human | 8506 | Details Get a Quote |
| CNTNAP1 Knockout A-549 Cell Line | EDJ-KQ30148 | Human | 8506 | Details Get a Quote |
| CNTNAP1 Knockout HCT 116 Cell Line | EDJ-KQ30149 | Human | 8506 | Details Get a Quote |
| CNTNAP1 Knockout HeLa Cell Line | EDJ-KQ30150 | Human | 8506 | Details Get a Quote |
