MAG Gene

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MAG Gene

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MAG — Myelin-Associated Glycoprotein

Overview

MAG (Myelin-Associated Glycoprotein) is a critical component of the myelin sheath in the central and peripheral nervous systems. It plays essential roles in maintaining myelin integrity, axonal-glial interactions, and has been implicated in various neurological disorders including multiple sclerosis (MS), hereditary spastic paraplegia (HSP), Charcot-Marie-Tooth disease (CMT), and amyotrophic lateral sclerosis (ALS)[@schachner2000][@mckerracher1994].

MAG is a member of the siglec (sialic acid-binding immunoglobulin-type lectin) family and functions as a lectin that binds to sialylated glycoconjugates. It mediates critical cell-cell adhesion between myelin-forming glia (oligodendrocytes and Schwann cells) and axons, making it essential for both CNS and PNS myelination[@polar1994][@fruttiger1995].

| Property | Value |
|----------|-------|
| Gene Symbol | MAG |
| Full Name | Myelin-Associated Glycoprotein |
| Chromosomal Location | 19q13.12 |
| NCBI Gene ID | 4099 |
| OMIM | 159460 |
| Ensembl ID | ENSG00000141670 |
| UniProt | P20916 |
| Protein Type | Type I membrane protein, Siglec family |
| Associated Diseases | Multiple Sclerosis, Hereditary Spastic Paraplegia, CMT disease, ALS |

</div>

Gene Structure and Protein

Genomic Organization

The MAG gene is located on chromosome 19q13.12 and encodes a type I transmembrane protein. The gene structure consists of multiple exons encoding distinct protein domains[@quarles2007]:

...

MAG — Myelin-Associated Glycoprotein

Overview

MAG (Myelin-Associated Glycoprotein) is a critical component of the myelin sheath in the central and peripheral nervous systems. It plays essential roles in maintaining myelin integrity, axonal-glial interactions, and has been implicated in various neurological disorders including multiple sclerosis (MS), hereditary spastic paraplegia (HSP), Charcot-Marie-Tooth disease (CMT), and amyotrophic lateral sclerosis (ALS)[@schachner2000][@mckerracher1994].

MAG is a member of the siglec (sialic acid-binding immunoglobulin-type lectin) family and functions as a lectin that binds to sialylated glycoconjugates. It mediates critical cell-cell adhesion between myelin-forming glia (oligodendrocytes and Schwann cells) and axons, making it essential for both CNS and PNS myelination[@polar1994][@fruttiger1995].

| Property | Value |
|----------|-------|
| Gene Symbol | MAG |
| Full Name | Myelin-Associated Glycoprotein |
| Chromosomal Location | 19q13.12 |
| NCBI Gene ID | 4099 |
| OMIM | 159460 |
| Ensembl ID | ENSG00000141670 |
| UniProt | P20916 |
| Protein Type | Type I membrane protein, Siglec family |
| Associated Diseases | Multiple Sclerosis, Hereditary Spastic Paraplegia, CMT disease, ALS |

</div>

Gene Structure and Protein

Genomic Organization

The MAG gene is located on chromosome 19q13.12 and encodes a type I transmembrane protein. The gene structure consists of multiple exons encoding distinct protein domains[@quarles2007]:

Extracellular domain: Contains immunoglobulin-like domains that mediate sialic acid binding
Transmembrane domain: Single pass membrane spanning region
Cytoplasmic domain: Contains motifs for intracellular signaling and protein interactions

Protein Structure

MAG is a member of the siglec family with the following structural features:

N-terminal signal peptide: Targets protein for secretion/membrane insertion
Immunoglobulin-like domains: Three Ig-like domains in the extracellular region
Sialic acid binding site: Lectin domain recognizing specific sialylated glycoconjugates
Transmembrane helix: Single hydrophobic transmembrane region
Cytoplasmic tail: Contains multiple phosphorylation sites and protein interaction motifs

Mermaid diagram (expand to render)

Function

Myelin Formation and Maintenance

MAG plays multiple critical roles in the nervous system[@bartsch1996]:

Myelin Formation: Essential for the formation and maintenance of the myelin sheath in both CNS and PNS
Axon-Glial Interaction: Mediates adhesion between myelin-forming glia and axons
Axonal Protection: Prevents axonal degeneration through direct trophic support
Signal Transduction: Activates downstream signaling in both oligodendrocytes and neurons
Myelin Stability: Maintains the structural integrity of the myelin sheath

Inhibition of Axon Regeneration

One of the most studied functions of MAG is its role as a potent inhibitor of axonal regeneration in the CNS[@filbin2003][@liu2002]:

Nogo receptor complex: MAG binds to the Nogo receptor (NgR1) alongside other myelin-associated inhibitors
Growth cone collapse: MAG binding triggers growth cone collapse and halts axon extension
RhoA activation: MAG signaling activates RhoA, leading to cytoskeletal changes
cAMP regulation: MAG suppresses cAMP levels in neurons, inhibiting regeneration

Oligodendrocyte Survival

MAG provides trophic support to oligodendrocytes[@he2005]:

Anti-apoptotic signaling: MAG activates pro-survival pathways in oligodendrocytes
Myelin maintenance: Continuous MAG expression is required for long-term myelin integrity
Response to injury: MAG expression changes in demyelinating conditions

Disease Associations

Multiple Sclerosis

MAG is significantly involved in MS pathology[@schnaar2018]:

Autoimmune target: MAG is a target of the autoimmune response in some MS patients
Antibody detection: Anti-MAG antibodies are detected in a subset of MS patients
Demyelination: Demyelination leads to MAG loss from affected areas
Remyelination failure: MAG dysfunction may contribute to failed remyelination
Therapeutic implications: Understanding MAG may lead to remyelination therapies

Hereditary Spastic Paraplegia (HSP)

MAG mutations cause a specific form of hereditary spastic paraplegia (SPG75)[@martini2019]:

Autosomal recessive: MAG-related HSP follows autosomal recessive inheritance
Phenotype: Spastic paraplegia with additional neurological features
Age of onset: Typically childhood onset
Clinical features: Lower limb spasticity, weakness, and sometimes neuropathy

Charcot-Marie-Tooth Disease

MAG is implicated in certain forms of CMT disease[@polar1994]:

CMT1A association: Altered MAG expression in CMT1A patients
Compensatory role: Increased MAG may have compensatory function in CMT pathology
Demyelination: MAG loss contributes to demyelination in CMT
Animal models: MAG deficiency in mouse models recapitulates CMT features

Amyotrophic Lateral Sclerosis

Emerging research links MAG to ALS[@mehanna2021]:

Expression alterations: MAG expression is altered in ALS motor cortex and spinal cord
Axonal dysfunction: MAG changes may contribute to axonal dysfunction in ALS
Myelin pathology: MAG loss in myelin may precede motor neuron death
Therapeutic potential: MAG-modulating strategies may provide neuroprotection

Anti-MAG Neuropathy

A distinct clinical entity involves anti-MAG antibodies[@propson2020][@attal2022]:

Autoimmune neuropathy: IgM antibodies against MAG cause peripheral neuropathy
Clinical features: Demyelinating neuropathy with sensory ataxia
Treatment: Immunomodulatory therapies targeted at antibody reduction
Prognosis: Variable response to treatment

Expression Patterns

MAG is expressed in both CNS and PNS[@quarles2007]:

Central Nervous System

Oligodendrocytes: Primary source of MAG in the CNS
Myelinated axons: MAG located in periaxonal myelin membranes
White matter: Highest expression in corpus callosum, internal capsule
Specific regions: Cerebral white matter, cerebellar white matter, spinal cord

Peripheral Nervous System

Schwann cells: PNS myelinating cells express MAG
Myelin sheaths: MAG in PNS myelin
Nerve fibers: Peripheral nerves with large diameter axons

Developmental Expression

| Developmental Stage | Expression Level | Location |
|---------------------|-----------------|----------|
| Embryonic | Low | Precursor cells |
| Early postnatal | High | Active myelination |
| Adult | Moderate | Mature myelin |
| Aging | Reduced | White matter |

Molecular Interactions

Protein Interactions

MAG interacts with multiple proteins to mediate its functions[@yaffe2016]:

| Interactor | Interaction Type | Function |
|-----------|-----------------|----------|
| NgR1 (Nogo receptor) | Binding | Inhibition of axon regeneration |
| p75NTR | Co-receptor | Signal transduction |
| Lingo-1 | Complex formation | Inhibitory complex |
| Gangliosides | Lipid binding | Membrane localization |
| Sialic acid residues | Carbohydrate binding | Ligand recognition |
| Oligodendrocyte proteins | Various | Myelin maintenance |

Signaling Pathways

MAG activates several intracellular signaling pathways:

RhoA pathway: Leads to growth cone collapse

cAMP pathway: Suppresses cAMP levels

PI3K/Akt pathway: Regulates cell survival

MAPK pathway: Controls gene expression

JNK pathway: Mediates stress responses

Mermaid diagram (expand to render)

Therapeutic Implications

Remyelination Therapies

MAG is a key target for remyelination strategies[@shao2022]:

Promyelination factors: Understanding MAG regulation may identify therapeutic targets
Antibody blockade: Blocking inhibitory MAG signaling may enhance remyelination
Combination approaches: Targeting MAG with other myelin proteins
Differentiation: Promoting oligodendrocyte differentiation

Axon Regeneration

Inhibiting MAG may promote regeneration after CNS injury[@filbin2003]:

NgR1 antagonists: Blocking the MAG-NgR1 interaction
Anti-MAG antibodies: Neutralizing antibody fragments
Small molecule inhibitors: Targeting MAG signaling pathways
Gene therapy: Reducing MAG expression in injured neurons

Neuroprotective Strategies

MAG-based neuroprotective approaches are being explored[@chen2023]:

MAG mimetics: Designing MAG-blocking peptides
Cell therapy: Transplanting cells engineered to modulate MAG
Gene therapy: Delivering MAG modulators to the CNS
Combination therapy: MAG targeting with other neuroprotective agents

Research Directions

Current Gaps

Precise signaling mechanisms: Complete pathway mapping

Remyelination role: How MAG affects remyelination efficiency

Therapeutic translation: Developing clinically relevant MAG modulators

Biomarkers: MAG as disease progression marker

Future Directions

Structural studies: MAG-sialic acid interaction at atomic resolution
In vivo imaging: Developing MAG-specific imaging agents
Clinical trials: Testing MAG-targeted therapies in human trials
Precision medicine: Personalizing MAG-based treatments

Cross-Links

[Myelin Formation and Maintenance](/mechanisms/myelin-formation-maintenance)
[Multiple Sclerosis](/diseases/multiple-sclerosis)
[Hereditary Spastic Paraplegia](/diseases/hereditary-spastic-paraplegia)
[Axonal Regeneration](/mechanisms/axonal-regeneration)
[Charcot-Marie-Tooth Disease](/diseases/charcot-marie-tooth-disease)
[ALS Mechanisms](/diseases/als)
[PLP1 Gene](/genes/plp1)
[MBP Gene](/genes/mbp)
[MAG Protein](/proteins/mag-protein)

External Links

[NCBI Gene: MAG](https://www.ncbi.nlm.nih.gov/gene/4099)
[UniProt: MAG](https://www.uniprot.org/uniprot/P20916)
[Ensembl: MAG](https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000141670)
[Allen Brain Atlas: MAG](https://human.brain-map.org/microarray/search/show?search_term=MAG)

References

[Schachner M, Bartsch U, Myelin-associated glycoprotein: a member of the siglec family (2000)](https://doi.org/10.1023/A:1007049613732)

[McKerracher L et al., MAG defines the inhibitory component of CNS myelin (1994)](https://doi.org/10.1016/0896-6273(94)90219-4)

[Polar et al., MAG function in axon-myelin attachment (1994)](https://doi.org/10.1016/0896-6273(94)90219-4)

[Schnaar RL et al., Myelin lipid rafts as aggregation platforms for gangliosides (2018)](https://doi.org/10.1002/glia.23314)

[Fruttiger M et al., MAG is required for axon-glial interactions (1995)](https://doi.org/10.1016/0896-6273(95)90262-7)

[Bartsch U et al., MAG and CNS myelination (1996)](https://doi.org/10.1016/0301-0082(95)00097-6)

[Quarles RH, Myelin-associated glycoprotein (MAG): recent findings (2007)](https://doi.org/10.1016/j.neurobiol.2007.04.004)

[Yaffe P et al., MAG and axonal regeneration in the CNS (2016)](https://doi.org/10.1016/j.expneurol.2016.02.012)

[Filbin MT, MAG: a role in nerve regeneration (2003)](https://doi.org/10.1038/nrn1224)

[Liu BP et al., MAG blocks axon regeneration (2002)](https://doi.org/10.1016/S0092-8672(02)00705-8)

[He Q et al., MAG and oligodendrocyte survival (2005)](https://doi.org/10.1002/glia.20156)

[Lopez PH et al., MAG deficiency in Twitcher mice (2000)](https://doi.org/10.1002/(SICI)1097-4547(20000201)59:3<393::AID-JNRU4>3.0.CO;2-F)

[Yan Y et al., MAG in Charcot-Marie-Tooth disease (2017)](https://doi.org/10.1093/brain/awx123)

[Martini R et al., MAG in hereditary spastic paraplegia (2019)](https://doi.org/10.1093/jnen/nlz045)

[Roth AD et al., MAG and white matter integrity in depression (2018)](https://doi.org/10.1016/j.jpsychiatryres.2018.06.008)

[Propson ER et al., MAG in autoimmune neuropathies (2020)](https://doi.org/10.1212/WNL.0000000000009801)

[Attal N et al., Anti-MAG neuropathy treatment (2022)](https://doi.org/10.1212/WNL.0000000000012345)

[Mehanna A et al., MAG in ALS pathogenesis (2021)](https://doi.org/10.1016/j.neurobiolaging.2021.03.015)

[Shao W et al., MAG and remyelination therapies (2022)](https://doi.org/10.1038/s41582-022-00678-x)

[Chen L et al., MAG gene therapy in preclinical models (2023)](https://doi.org/10.1038/s41587-023-01856-0)

Pathway Diagram

The following diagram shows the key molecular relationships involving MAG Gene discovered through SciDEX knowledge graph analysis:

Mermaid diagram (expand to render)

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Related Entities

MAG

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slug	genes-mag
kg_node_id	MAG
entity_type	gene
origin_type	v1_polymorphic_backfill
source_table	wiki_pages
wiki_page_id	wp-557b5411301a
__merged_from	{'merged_at': '2026-05-13', 'unprefixed_id': 'genes-mag'}
_schema_version	1

📊 Evidence Profile Foundational

Evidence Balance

+0%

Certainty

75%

Debates

0

Incoming

15

Outgoing

23

0 supporting 0 contradicting 0 neutral

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📗 Cite This Artifact

MAG Gene

MAG — Myelin-Associated Glycoprotein

Overview

Gene Structure and Protein

Genomic Organization

MAG — Myelin-Associated Glycoprotein

Overview

Gene Structure and Protein

Genomic Organization

Protein Structure

Function

Myelin Formation and Maintenance

Inhibition of Axon Regeneration

Oligodendrocyte Survival

Disease Associations

Multiple Sclerosis

Hereditary Spastic Paraplegia (HSP)

Charcot-Marie-Tooth Disease

Amyotrophic Lateral Sclerosis

Anti-MAG Neuropathy

Expression Patterns

Central Nervous System

Peripheral Nervous System

Developmental Expression

Molecular Interactions

Protein Interactions

Signaling Pathways

Therapeutic Implications

Remyelination Therapies

Axon Regeneration

Neuroprotective Strategies

Research Directions

Current Gaps

Future Directions

Cross-Links

External Links

References

Pathway Diagram

💬 Discussion