MAG

myelin associated glycoprotein, the group of I-set domain containing|C2-set domain containing|Sialic acid binding Ig like lectins

Basic information

Region (hg38): 19:35292124-35313807

Previous symbols: [ "GMA" ]

Links

ENSG00000105695 ∙ NCBI:4099 ∙ OMIM:159460 ∙ HGNC:6783 ∙ Uniprot:P20916 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• hereditary spastic paraplegia 75 (Strong), mode of inheritance: AR
• hereditary spastic paraplegia 75 (Supportive), mode of inheritance: AR
• complex hereditary spastic paraplegia (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Spastic paraplegia, autosomal recessive 75	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Neurologic	24482476; 26179919

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the MAG gene.

• Hereditary spastic paraplegia 75 (219 variants)
• Inborn genetic diseases (33 variants)
• not provided (30 variants)
• Hereditary spastic paraplegia (3 variants)
• not specified (3 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the MAG gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			1	71	10	82
missense			113	7	4	124
nonsense	2	1	1			4
start loss						0
frameshift		1	1			2
inframe indel		1	1			2
splice donor/acceptor (+/-2bp)						0
splice region			3	5	1	9
non coding			2	21	9	32
Total	2	3	119	99	23

Variants in MAG

This is a list of pathogenic ClinVar variants found in the MAG region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
19-35295422-C-T		Hereditary spastic paraplegia 75	Likely benign (Dec 10, 2023)
19-35295423-G-A		Hereditary spastic paraplegia 75 • MAG-related disorder	Likely benign (Aug 10, 2023)
19-35295423-G-C		Hereditary spastic paraplegia 75	Likely benign (May 15, 2023)
19-35295426-A-G		Hereditary spastic paraplegia 75	Likely benign (Mar 01, 2023)
19-35295442-A-G			Uncertain significance (Jun 01, 2016)
19-35295448-A-G		Hereditary spastic paraplegia 75	Uncertain significance (Nov 22, 2022)
19-35295459-C-A		Hereditary spastic paraplegia 75	Uncertain significance (Sep 14, 2023)
19-35295460-G-A		Hereditary spastic paraplegia 75	Uncertain significance (Apr 18, 2022)
19-35295474-G-A		Hereditary spastic paraplegia 75	Likely benign (Oct 13, 2022)
19-35295594-C-T		Hereditary spastic paraplegia 75	Likely benign (Apr 10, 2023)
19-35295596-C-T		Hereditary spastic paraplegia 75	Benign (Jan 08, 2024)
19-35295597-T-A		Hereditary spastic paraplegia 75	Likely benign (Mar 13, 2022)
19-35295598-C-T		Hereditary spastic paraplegia 75	Likely benign (May 27, 2022)
19-35295600-T-C		Hereditary spastic paraplegia 75	Likely benign (Jul 06, 2022)
19-35295603-T-G		Hereditary spastic paraplegia 75	Likely benign (Dec 11, 2023)
19-35295609-G-T		not specified • Hereditary spastic paraplegia 75	Benign/Likely benign (Mar 01, 2024)
19-35295618-C-A		Hereditary spastic paraplegia 75	Likely benign (Apr 05, 2023)
19-35295627-C-T		Hereditary spastic paraplegia 75	Uncertain significance (Dec 23, 2017)
19-35295671-C-T		Hereditary spastic paraplegia 75	Uncertain significance (Jul 19, 2023)
19-35295677-C-T		Hereditary spastic paraplegia 75	Likely benign (Oct 15, 2020)
19-35295682-C-T		Hereditary spastic paraplegia 75	Uncertain significance (Feb 16, 2021)
19-35295686-C-A		Hereditary spastic paraplegia 75	Likely benign (Nov 28, 2022)
19-35295693-C-T		Hereditary spastic paraplegia 75	Uncertain significance (Jun 05, 2022)
19-35295694-G-A		Hereditary spastic paraplegia 75	Uncertain significance (Jun 29, 2023)
19-35295718-G-A		Hereditary spastic paraplegia 75	Uncertain significance (May 04, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
MAG	protein_coding	protein_coding	ENST00000392213	9	21680

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.492	0.508	125733	0	15	125748	0.0000596

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.13	348	413	0.843	0.0000283	3996
Missense in Polyphen		71	113.28	0.62675		1114
Synonymous	0.184	192	195	0.983	0.0000150	1333
Loss of Function	3.84	6	27.9	0.215	0.00000159	277

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000292	0.0000292
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.0000467	0.0000462
European (Non-Finnish)	0.000106	0.000105
Middle Eastern	0.00	0.00
South Asian	0.0000327	0.0000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Adhesion molecule that mediates interactions between myelinating cells and neurons by binding to neuronal sialic acid- containing gangliosides and to the glycoproteins RTN4R and RTN4RL2 (By similarity). Not required for initial myelination, but seems to play a role in the maintenance of normal axon myelination. Protects motoneurons against apoptosis, also after injury; protection against apoptosis is probably mediated via interaction with neuronal RTN4R and RTN4RL2. Required to prevent degeneration of myelinated axons in adults; this probably depends on binding to gangliosides on the axon cell membrane (By similarity). Negative regulator of neurite outgrowth; in dorsal root ganglion neurons the inhibition is mediated primarily via binding to neuronal RTN4R or RTN4RL2 and to a lesser degree via binding to neuronal gangliosides. In cerebellar granule cells the inhibition is mediated primarily via binding to neuronal gangliosides. In sensory neurons, inhibition of neurite extension depends only partially on RTN4R, RTN4RL2 and gangliosides. Inhibits axon longitudinal growth (By similarity). Inhibits axon outgrowth by binding to RTN4R (By similarity). Preferentially binds to alpha- 2,3-linked sialic acid. Binds ganglioside Gt1b (By similarity). {ECO:0000250|UniProtKB:P07722, ECO:0000250|UniProtKB:P20917}.
• Disease: DISEASE: Spastic paraplegia 75, autosomal recessive (SPG75) [MIM:616680]: A form of spastic paraplegia, a neurodegenerative disorder characterized by a slow, gradual, progressive weakness and spasticity of the lower limbs. Rate of progression and the severity of symptoms are quite variable. Initial symptoms may include difficulty with balance, weakness and stiffness in the legs, muscle spasms, and dragging the toes when walking. In some forms of the disorder, bladder symptoms (such as incontinence) may appear, or the weakness and stiffness may spread to other parts of the body. SPG75 is characterized by onset in early childhood and is associated with mild to moderate cognitive impairment. {ECO:0000269|PubMed:24482476, ECO:0000269|PubMed:26179919, ECO:0000269|PubMed:27606346}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Cell adhesion molecules (CAMs) - Homo sapiens (human);Glial Cell Differentiation;Spinal Cord Injury;MECP2 and Associated Rett Syndrome;Signal Transduction;Cell surface interactions at the vascular wall;Hemostasis;Death Receptor Signalling;Axonal growth inhibition (RHOA activation);p75NTR regulates axonogenesis;p75 NTR receptor-mediated signalling;Basigin interactions;p75(NTR)-mediated signaling (Consensus)

Recessive Scores

• pRec: 0.267

Intolerance Scores

• loftool: 0.476
• rvis_EVS: -0.2
• rvis_percentile_EVS: 39.21

Haploinsufficiency Scores

• pHI: 0.965
• hipred: Y
• hipred_score: 0.671
• ghis: 0.507

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.871

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Mag
• Phenotype: adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); homeostasis/metabolism phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); hematopoietic system phenotype; hearing/vestibular/ear phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); immune system phenotype

Gene ontology

• Biological process: cell adhesion;negative regulation of neuron projection development;transmission of nerve impulse;central nervous system myelination;negative regulation of axon extension;axon regeneration;positive regulation of myelination;negative regulation of neuron apoptotic process;positive regulation of astrocyte differentiation;negative regulation of axonogenesis;leukocyte migration;cellular response to mechanical stimulus;cell-cell adhesion via plasma-membrane adhesion molecules
• Cellular component: cytoplasm;plasma membrane;integral component of plasma membrane;paranode region of axon;myelin sheath adaxonal region;myelin sheath;compact myelin;Schmidt-Lanterman incisure;membrane raft;mesaxon
• Molecular function: signaling receptor binding;protein kinase binding;carbohydrate binding;sialic acid binding;protein homodimerization activity;ganglioside GT1b binding