MAG

Chr 19AR

myelin associated glycoprotein

Also known as: GMA, S-MAG, SIGLEC-4A, SIGLEC4, SIGLEC4A, SPG75

NCBI Gene: 4099ENSG00000105695UniProt: P20916

The protein encoded by this gene is a type I membrane protein and member of the immunoglobulin superfamily. It is thought to be involved in the process of myelination. It is a lectin that binds to sialylated glycoconjugates and mediates certain myelin-neuron cell-cell interactions. Three alternatively spliced transcripts encoding different isoforms have been described for this gene. [provided by RefSeq, Nov 2010]

Primary Disease Associations & Inheritance

Spastic paraplegia 75, autosomal recessiveMIM #616680
AR
388
ClinVar variants
32
Pathogenic / LP
0.49
pLI score
1
Active trials
Clinical Summary— MAG
🧬
Gene-Disease Validity (ClinGen)
complex hereditary spastic paraplegia · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.21) despite low pLI — interpret in context.
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ClinVar Variants
32 Pathogenic / Likely Pathogenic· 182 VUS of 388 total submissions
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Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.42LOEUF
pLI 0.492
Z-score 3.84
OE 0.21 (0.12–0.42)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
1.13Z-score
OE missense 0.84 (0.77–0.92)
348 obs / 412.9 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.21 (0.12–0.42)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.84 (0.77–0.92)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.98
0≤1.21.6
LoF obs/exp: 6 / 27.9Missense obs/exp: 348 / 412.9Syn Z: 0.18

ClinVar Variant Classifications

388 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic24
Likely Pathogenic8
VUS182
Likely Benign147
Benign21
Conflicting6
24
Pathogenic
8
Likely Pathogenic
182
VUS
147
Likely Benign
21
Benign
6
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
1
3
20
0
24
Likely Pathogenic
5
1
2
0
8
VUS
1
171
9
1
182
Likely Benign
0
7
33
107
147
Benign
0
3
10
8
21
Conflicting
—6
Total718574116388

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

MAG · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Spastic paraplegia 75, autosomal recessive

MIM #616680

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Antibodies in Autoimmune Neuropathies: What to Test, How to Test, Why to Test.
Pascual-Goñi E et al.·Neurology
2024Review
Paraproteinemic neuropathies.
Traub R et al.·Muscle Nerve
2024Review
Anti-MAG neuropathy: From biology to clinical management.
Steck AJ·J Neuroimmunol
2021Review
Anti-MAG neuropathy: historical aspects, clinical-pathological correlations, and considerations for future therapeutical trials.
Latov N et al.·Arq Neuropsiquiatr
2024Review
Therapeutic Monoclonal Antibody Therapies in Chronic Autoimmune Demyelinating Neuropathies.
Briani C et al.·Neurotherapeutics
2022Review
Paraproteinemic Neuropathies.
Beydoun SR et al.·Continuum (Minneap Minn)
2023Review
Neuropathy with anti-myelin-associated glycoprotein antibodies: update on diagnosis, pathophysiology and management.
Min YG et al.·J Neurol Neurosurg Psychiatry
2025Review
Paraneoplastic neuropathies.
Antoine JC et al.·Curr Opin Neurol
2017Review
Two coral fluorescent proteins of distinct colors for sharp visualization of cell-cycle progression.
Ando R et al.·Cell Struct Funct
2023
Paraproteinaemic neuropathies.
Steck AJ et al.·Brain Pathol
1999Review
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Impact of the MAG III protocol (F+0 vs. F+20) used on indication for pyeloplasty, time to surgery and radiation burden in high-grade hydronephrosis.
Haid B et al.·J Pediatr Urol
2026
Prevalence and Patterns of Cranial Nerve Involvement in CIDP, Autoimmune Nodopathy, MMN, and Anti-MAG Neuropathy: A Multicenter Korea/UK Study of 582 Patients.
Min YG et al.·Eur J Neurol
2026🔓 Open AccessCohort
2Pipe starts with a question: matching you with the correct pipeline for MAG reconstruction.
Yepes-García J et al.·mSystems
2026🔓 Open Access
MAG-PSIR mismatch in a patient with multi-territory myocardial infarcts with and without acute ischemic edema.
Tsang DA et al.·Int J Cardiovasc Imaging
2026
Automated Mag-Net Enrichment Unlocks Deep and Cost-Effective LC-MS Plasma Proteomics.
Järvinen E et al.·J Proteome Res
2026🔓 Open Access
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
AML, ChildhoodAcute Myeloid Leukemia

Clinical Study of Induction Therapy Options Based on Molecular Subtyping and MRD in Children and Adolescents With AML

RECRUITING
NCT06221683Phase PHASE2Children's Hospital of Soochow UniversityStarted 2024-01-01
HomoharringtonineCytarabineEtoposide

External Resources

Links to major genomics databases and tools