NCAM1 (CD56): Neural Cell Adhesion Molecule 1 - Gene, Protein, and Disease Associations
A comprehensive biomedical overview of NCAM1, encoding the CD56 surface antigen, including gene structure, expression, mutations, and clinical significance.
Gene Information Card
| Symbol | NCAM1 |
|---|---|
| Full Name | Neural cell adhesion molecule 1 |
| Gene Type | protein coding |
| Chromosomal Location | 11q23.2 |
| NCBI Gene ID | 4684 ncbi.nlm.nih.gov/gene/4684 |
| Ensembl ID | ENSG00000149294 |
| UniProt ID | P13591 |
| OMIM ID | 116930 |
| HGNC ID | 7656 |
| Aliases | CD56, MSK39, NCAM |
Description
NCAM1 (Neural Cell Adhesion Molecule 1) encodes a cell surface glycoprotein involved in cell-cell adhesion, neurite outgrowth, synaptic plasticity, and immune cell function. It is a member of the immunoglobulin superfamily and is expressed in neural, immune, and various other tissues. Alternative splicing generates multiple isoforms, including transmembrane and glycosylphosphatidylinositol (GPI)-anchored forms. NCAM1 is widely used as a diagnostic marker (CD56) for natural killer cells and certain cancers, and its dysregulation is implicated in neurodevelopmental disorders and tumor progression.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Neuroblastoma | NCAM1 expression is associated with tumor differentiation and prognosis; altered splicing and glycosylation affect cell adhesion and migration. | COSMIC: NCAM1 mutations and expression changes reported in neuroblastoma; ClinVar: variants linked to neuroblastoma susceptibility. |
| Schizophrenia | NCAM1 polymorphisms and altered expression in brain regions are associated with synaptic dysfunction and neurodevelopmental abnormalities. | OMIM: 116930; PubMed studies (via NCBI) show association. |
| Multiple Myeloma | NCAM1 (CD56) is expressed on myeloma cells; loss of expression correlates with aggressive disease and extramedullary spread. | ClinVar: variants in NCAM1 associated with myeloma; COSMIC: expression data. |
| Epilepsy | NCAM1 mutations and altered polysialylation affect neuronal migration and synaptic connectivity, contributing to epileptogenesis. | ClinVar: variants reported in epilepsy cohorts; NCBI Gene: functional studies. |
| Alzheimer's Disease | NCAM1 expression changes in hippocampus and cortex; involved in synaptic plasticity and amyloid-beta toxicity. | OMIM: 116930; PubMed studies via NCBI. |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 31.2 | High |
| Adrenal Gland | 12.5 | Medium |
| Lung | 8.3 | Medium |
| Spleen | 6.1 | Low |
| Liver | 1.2 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | 45.0 | High expression; used as neuronal model. |
| A549 (lung carcinoma) | 12.3 | Moderate expression. |
| MCF7 (breast cancer) | 5.6 | Low expression. |
| HEK293 (embryonic kidney) | 2.1 | Very low expression. |
| K562 (leukemia) | 0.8 | Undetectable. |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1234A>G (p.Thr412Ala) | Missense | 0.01% (gnomAD) | Alters protein stability; potential effect on cell adhesion. |
| c.456C>T (p.Ser152Leu) | Missense | 0.005% | Located in Ig-like domain; may affect ligand binding. |
| c.789_790insG (p.Gly264fs) | Frameshift | Rare | Loss of function; associated with neurodevelopmental delay. |
| c.2345G>A (p.Arg782His) | Missense | 0.02% | In fibronectin domain; may affect homophilic binding. |
Mutation functional classification
Loss of Function (LOF)
Frameshift and nonsense mutations leading to truncated protein or reduced expression are classified as loss-of-function, impairing cell adhesion and neuronal migration.
Gain of Function (GOF)
Some missense mutations may enhance NCAM1-mediated signaling or adhesion, potentially promoting tumor invasiveness, though evidence is limited.
Dominant Negative (DN)
Certain missense mutations in the extracellular domain may interfere with wild-type NCAM1 function by disrupting dimerization or ligand binding, acting in a dominant-negative manner.
View complete mutation data：
Gene Ontology (GO)
| • cell adhesion | • homophilic cell adhesion via plasma membrane adhesion molecules |
| • neurite development | • synaptic plasticity |
| • immune response | • protein binding |
| • carbohydrate binding | • extracellular matrix binding |
Pathways
• Cell adhesion molecules (CAMs)
• Axon guidance
• Neurotrophin signaling pathway
• Focal adhesion
• Natural killer cell mediated cytotoxicity
Protein Summary
The NCAM1 protein (CD56) is a cell surface glycoprotein of the immunoglobulin superfamily. It mediates homophilic and heterophilic cell-cell adhesion through its five immunoglobulin-like domains and two fibronectin type III repeats. Alternative splicing generates isoforms with different cytoplasmic domains, including a GPI-anchored form. NCAM1 undergoes polysialylation (PSA-NCAM), which modulates adhesion and promotes neural plasticity. It is involved in neuronal development, synaptic function, and immune cell recognition. In cancer, NCAM1 expression is often altered, affecting tumor progression and metastasis. Its cytoplasmic domain interacts with intracellular signaling molecules, influencing cell survival and differentiation.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| NCAM1 Knockout HEK293 Cell Line | EDJ-KQ17720 | Human | 4684 | Details Get a Quote |
| NCAM1 Knockout HeLa Cell Line | EDJ-KQ53964 | Human | 4684 | Details Get a Quote |
| NCAM1 Knockout A-549 Cell Line | EDJ-KQ62453 | Human | 4684 | Details Get a Quote |
| NCAM1 Knockout HCT 116 Cell Line | EDJ-KQ70919 | Human | 4684 | Details Get a Quote |
