1. Gene Aliases

NCAM1, Neural Cell Adhesion Molecule 1, NCAM, CD56, Antigen Recognized By Monoclonal Antibody 5.1H11, Neural Cell Adhesion Molecule, NCAM, CD56 Antigen, N-CAM-1, NCAM-1, MSK39

[https://www.genecards.org/cgi-bin/carddisp.pl?gene=NCAM1&keywords=ncam1].

2. Association with Toxicity and/or Disease at a Transcriptional Level

3. Summary of Protein Family and Structure

4. Proteins Known to Interact with Gene Product

Interactions with experimental support

Interactions with text mining support

5. Links to Gene Databases

6. GO Terms, MSigDB Signatures, Pathways Containing Gene with Descriptions of Gene Sets

Pathways:

GO terms:

animal organ regeneration [The regrowth of a lost or destroyed animal organ. GO:0031100]

axonal fasciculation [The collection of axons into a bundle of rods, known as a fascicle. GO:0007413]

calcium-independent cell-cell adhesion via plasma membrane cell-adhesion molecules [The attachment of one cell to another cell via adhesion molecules that do not require the presence of calcium for the interaction. GO:0016338]

calcium-mediated signaling [Any intracellular signal transduction in which the signal is passed on within the cell via calcium ions. GO:0019722]

cell adhesion [The attachment of a cell, either to another cell or to an underlying substrate such as the extracellular matrix, via cell adhesion molecules. GO:0007155]

cell surface receptor signaling pathway [The series of molecular signals initiated by activation of a receptor on the surface of a cell. The pathway begins with binding of an extracellular ligand to a cell surface receptor, or for receptors that signal in the absence of a ligand, by ligand-withdrawal or the activity of a constitutively active receptor. The pathway ends with regulation of a downstream cellular process, e.g. transcription. GO:0007166]

cellular response to inorganic substance [Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of an inorganic substance stimulus. GO:0071241]

cellular response to molecule of bacterial origin [Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a stimulus by molecules of bacterial origin such as peptides derived from bacterial flagellin. GO:0071219]

commissural neuron axon guidance [The process in which the migration of an axon growth cone of a commissural neuron is directed to its target in the brain in response to a combination of attractive and repulsive cues. GO:0071679]

epithelial to mesenchymal transition [A transition where an epithelial cell loses apical/basolateral polarity, severs intercellular adhesive junctions, degrades basement membrane components and becomes a migratory mesenchymal cell. GO:0001837]

homotypic cell-cell adhesion [The attachment of a cell to a second cell of the identical type via adhesion molecules.|Note that this term is not synonymous with 'homophilic cell adhesion ; GO:0007156'; the process may occur by homophilic or heterophilic mechanisms. GO:0034109]

learning or memory [The acquisition and processing of information and/or the storage and retrieval of this information over time. GO:0007611]

modulation of chemical synaptic transmission [Any process that modulates the frequency or amplitude of synaptic transmission, the process of communication from a neuron to a target (neuron, muscle, or secretory cell) across a synapse. Amplitude, in this case, refers to the change in postsynaptic membrane potential due to a single instance of synaptic transmission. GO:0050804]

multicellular organismal response to stress [Any process that results in a change in state or activity of a multicellular organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a stimulus indicating the organism is under stress. The stress is usually, but not necessarily, exogenous (e.g. temperature, humidity, ionizing radiation). GO:0033555]

negative regulation of programmed cell death [Any process that stops, prevents, or reduces the frequency, rate or extent of programmed cell death, cell death resulting from activation of endogenous cellular processes. GO:0043069]

neuron development [The process whose specific outcome is the progression of a neuron over time, from initial commitment of the cell to a specific fate, to the fully functional differentiated cell. GO:0048666]

neuron projection development [The process whose specific outcome is the progression of a neuron projection over time, from its formation to the mature structure. A neuron projection is any process extending from a neural cell, such as axons or dendrites (collectively called neurites). GO:0031175]

peripheral nervous system axon regeneration [The regrowth of axons outside the central nervous system (outside the brain and spinal cord) following an axonal injury. GO:0014012]

positive regulation of calcium-mediated signaling [Any process that activates or increases the frequency, rate or extent of calcium-mediated signaling. GO:0050850]

positive regulation of cardiac muscle cell proliferation [Any process that activates or increases the frequency, rate or extent of cardiac muscle cell proliferation. GO:0060045]

regulation of exocyst assembly [Any process that modulates the frequency, rate or extent of exocyst assembly.|Note that the assembly is regulated by several small GTPases of the Rab and Rho families. GO:0001928]

regulation of semaphorin-plexin signaling pathway [Any process that modulates the frequency, rate or extent of semaphorin-plexin signaling pathway. GO:2001260]

response to activity [Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of an activity stimulus. GO:0014823]

response to cocaine [Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a cocaine stimulus. Cocaine is a crystalline alkaloid obtained from the leaves of the coca plant. GO:0042220]

response to inorganic substance [Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of an inorganic substance stimulus. GO:0010035]

response to lead ion [Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a lead ion stimulus. GO:0010288]

response to xenobiotic stimulus [Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a stimulus from a xenobiotic, a compound foreign to the organim exposed to it. It may be synthesized by another organism (like ampicilin) or it can be a synthetic chemical. GO:0009410]

thalamus development [The process in which the thalamus changes over time, from its initial formation to its mature state. GO:0021794]

MSigDB Signatures:

WP_CARDIAC_PROGENITOR_DIFFERENTIATION: Cardiac progenitor differentiation [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/WP_CARDIAC_PROGENITOR_DIFFERENTIATION.html]

REACTOME_NERVOUS_SYSTEM_DEVELOPMENT: Nervous system development [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/REACTOME_NERVOUS_SYSTEM_DEVELOPMENT.html]

WP_PRION_DISEASE_PATHWAY: Prion disease pathway [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/WP_PRION_DISEASE_PATHWAY.html]

REACTOME_L1CAM_INTERACTIONS: L1CAM interactions [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/REACTOME_L1CAM_INTERACTIONS.html]

REACTOME_DEVELOPMENTAL_BIOLOGY: Developmental Biology [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/REACTOME_DEVELOPMENTAL_BIOLOGY.html]

KEGG_CELL_ADHESION_MOLECULES_CAMS: Cell adhesion molecules (CAMs) [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/KEGG_CELL_ADHESION_MOLECULES_CAMS.html]

REACTOME_EXTRACELLULAR_MATRIX_ORGANIZATION: Extracellular matrix organization [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/REACTOME_EXTRACELLULAR_MATRIX_ORGANIZATION.html]

KEGG_PRION_DISEASES: Prion diseases [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/KEGG_PRION_DISEASES.html]

REACTOME_MAPK_FAMILY_SIGNALING_CASCADES: MAPK family signaling cascades [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/REACTOME_MAPK_FAMILY_SIGNALING_CASCADES.html]

REACTOME_NCAM1_INTERACTIONS: NCAM1 interactions [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/REACTOME_NCAM1_INTERACTIONS.html]

REACTOME_INTERFERON_GAMMA_SIGNALING: Interferon gamma signaling [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/REACTOME_INTERFERON_GAMMA_SIGNALING.html]

7. Gene Descriptions

NCBI Gene Summary: This gene encodes a cell adhesion protein which is a member of the immunoglobulin superfamily. The encoded protein is involved in cell-to-cell interactions as well as cell-matrix interactions during development and differentiation. The encoded protein plays a role in the development of the nervous system by regulating neurogenesis, neurite outgrowth, and cell migration. This protein is also involved in the expansion of T lymphocytes, B lymphocytes and natural killer (NK) cells which play an important role in immune surveillance. This protein plays a role in signal transduction by interacting with fibroblast growth factor receptors, N-cadherin and other components of the extracellular matrix and by triggering signalling cascades involving FYN-focal adhesion kinase (FAK), mitogen-activated protein kinase (MAPK), and phosphatidylinositol 3-kinase (PI3K). One prominent isoform of this gene, cell surface molecule CD56, plays a role in several myeloproliferative disorders such as acute myeloid leukemia and differential expression of this gene is associated with differential disease progression. For example, increased expression of CD56 is correlated with lower survival in acute myeloid leukemia patients whereas increased severity of COVID-19 is correlated with decreased abundance of CD56-expressing NK cells in peripheral blood. Alternative splicing results in multiple transcript variants encoding distinct protein isoforms. [provided by RefSeq, Aug 2020]

GeneCards Summary: NCAM1 (Neural Cell Adhesion Molecule 1) is a Protein Coding gene. Diseases associated with NCAM1 include Bile Duct Cancer and Plasma Cell Leukemia. Among its related pathways are RAF/MAP kinase cascade and Nervous system development. Gene Ontology (GO) annotations related to this gene include identical protein binding. An important paralog of this gene is NCAM2.

UniProtKB/Swiss-Prot Summary: This protein is a cell adhesion molecule involved in neuron-neuron adhesion, neurite fasciculation, outgrowth of neurites, etc. Acts as a receptor for rabies virus. Acts as a receptor for Zika virus.

8. Cellular Location of Gene Product

Cytoplasmic expression in the CNS, peripheral nerves, adrenal gland, heart and gastric chief cells. Mainly localized to the plasma membrane. In addition localized to the cytosol. Predicted location: Secreted, Membrane, Intracellular (different isoforms) [https://www.proteinatlas.org/ENSG00000149294/subcellular]

9. Mechanistic Information

Summary

The NCAM1 gene, encoding a cell adhesion protein is important for cell-to-cell and cell-matrix interactions, and plays a crucial role in the structural and functional integrity of the heart [CS: 9]. Specifically, NCAM1 is involved in the maintenance and repair of cardiac tissues by influencing the behavior of various cell types integral to cardiac function [CS: 8]. For instance, in the ventricular conduction system, NCAM1 is highly enriched in mature Purkinje cells, which are essential for the proper patterning and function of the heart's electrical conduction system [CS: 7]. In the context of myocardial infarction, the upregulation of NCAM1 could facilitate the repair and regeneration of damaged cardiac tissue by enhancing cell adhesion and communication, thereby counteracting the deleterious effects of the infarction [CS: 6].

Disruption in NCAM1 expression can lead to defects in Purkinje cell gene expression, adversely affecting ventricular conduction and potentially contributing to cardiac conduction diseases [CS: 7]. Additionally, NCAM1's role in the regulation of immune cells, such as T lymphocytes, B lymphocytes, and NK cells, is vital in the heart's response to injury, such as in myocardial infarction [CS: 8]. Here, NCAM1-mediated modulation of these immune cells can facilitate the clearing of damaged tissue and support repair processes, thereby playing a significant role in the heart's recovery from injury and maintaining its structural and functional integrity [CS: 7].

10. Upstream Regulators

11. Tissues/Cell Type Where Genes are Overexpressed

Tissue type enchanced: brain, heart muscle (tissue enhanced) [https://www.proteinatlas.org/ENSG00000149294/tissue]

Cell type enchanced: astrocytes, excitatory neurons, inhibitory neurons, oligodendrocyte precursor cells, oligodendrocytes, schwann cells (cell type enhanced) [https://www.proteinatlas.org/ENSG00000149294/single+cell+type]

12. Role of Gene in Other Tissues

13. Chemicals Known to Elicit Transcriptional Response of Biomarker in Tissue of Interest

Compounds that increase expression of the gene:

Compounds that decrease expression of the gene:

14. DisGeNet Biomarker Associations to Disease in Organ of Interest