MAG

Summary

MAG (myelin associated glycoprotein, HGNC:6783) is a protein-coding gene on chromosome 19q13.1, encoding Myelin-associated glycoprotein (P20916). 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.

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.

Source: NCBI Gene 4099 — RefSeq curated summary.

At a glance

• Gene–disease (curated): complex hereditary spastic paraplegia (Definitive, ClinGen) — +1 more curated relationship
• Clinical variants (ClinVar): 374 total — 8 pathogenic, 7 likely-pathogenic (top 9% of genes corpus-wide)
• GTEx eGene: eQTL in 30 tissues, sQTL in 5 (q < 0.05)
• Drug target: yes — 1 curated mechanism-of-action drug
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 0.73 (unconstrained)
• MANE Select transcript: NM_002361
• Interaction hub: 1,844 STRING partners (top 9% of genes corpus-wide)

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6783
Approved symbol	MAG
Name	myelin associated glycoprotein
Location	19q13.1
Locus type	gene with protein product
Status	Approved
Aliases	SIGLEC4A, SIGLEC-4A, S-MAG, SIGLEC4
Ensembl gene	ENSG00000105695
Ensembl biotype	protein_coding
OMIM	159460
Entrez	4099

Gene structure

Transcript identifiers

Ensembl transcripts: 26 — 18 protein_coding, 6 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined, 1 retained_intron

MANE Select: ENST00000392213

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 3, TSL 2: 1, TSL 4: 4

ENST00000392213, ENST00000361922, ENST00000537831, ENST00000593348, ENST00000595791, ENST00000597035, ENST00000597162, ENST00000600291, ENST00000872031, ENST00000872032, ENST00000872033, ENST00000872034, ENST00000872035, ENST00000872036, ENST00000918346, ENST00000946899, ENST00001001745, ENST00001001746, ENST00001001748, ENST00001037004, ENST00001037007, ENST00001037008, ENST00001112685, ENST00001120473, ENST00001131006, ENST00001136668

RefSeq mRNA: 3 — MANE Select: NM_002361 NM_001199216, NM_002361, NM_080600

CCDS: CCDS12455, CCDS12456, CCDS56090

Canonical transcript exons

ENST00000392213 — 11 exons

Exon	Start	End
ENSE00000700261	35309874	35310161
ENSE00000700264	35302448	35302708
ENSE00000700266	35300147	35300404
ENSE00000700268	35299554	35299850
ENSE00002306928	35292161	35292204
ENSE00002447006	35295386	35295454
ENSE00002469293	35294235	35294290
ENSE00003514513	35295613	35295981
ENSE00003619273	35311918	35312017
ENSE00003628719	35310547	35310643
ENSE00003849685	35313290	35313807

Expression profiles

Bgee: expression breadth ubiquitous, 187 present calls, max score 99.50.

FANTOM5 (CAGE): breadth broad, TPM avg 15.3725 / max 1845.3212, expressed in 291 samples.

Highest expression (Bgee): C1 segment of cervical spinal cord, spinal cord, inferior vagus X ganglion, middle frontal gyrus, corpus callosum.

Genetic regulation across tissues (GTEx eQTL / sQTL)

MAG is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 30 tissues and its splicing (sQTL) in 5 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 35 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Thyroid	eqtl	1.7e-105	-1.14	19:35309759:G:T
Lung	eqtl	4.1e-79	-1.21	19:35309759:G:T
Colon Transverse	eqtl	2.1e-53	-1.09	19:35309759:G:T
Adipose Visceral Omentum	eqtl	3.3e-48	-1.02	19:35309759:G:T
Spleen	eqtl	9.2e-43	-1.39	19:35309759:G:T
Colon Sigmoid	eqtl	5.4e-40	-1.07	19:35309759:G:T
Pituitary	eqtl	1.2e-39	-0.97	19:35309759:G:T
Esophagus Muscularis	eqtl	1.1e-34	-0.87	19:35309759:G:T
Adrenal Gland	eqtl	7.2e-32	-0.97	19:35309759:G:T
Stomach	eqtl	3.4e-30	-0.96	19:35309759:G:T
Pancreas	eqtl	1.7e-28	-1.07	19:35309759:G:T
Esophagus Mucosa	eqtl	3.2e-27	-0.77	19:35309759:G:T
Prostate	eqtl	4.6e-27	-0.96	19:35309759:G:T
Small Intestine Terminal Ileum	eqtl	5.9e-26	-1.18	19:35309759:G:T
Breast Mammary Tissue	eqtl	5.5e-21	-0.65	19:35309759:G:T
Nerve Tibial	eqtl	1.2e-20	+0.29	19:35277925:T:C
Liver	eqtl	1.0e-18	-1.02	19:35309759:G:T
Heart Atrial Appendage	eqtl	2.3e-16	+0.65	19:35277925:T:C
Artery Aorta	eqtl	2.8e-16	-0.69	19:35309759:G:T
Spleen	sqtl	8.9e-16	+1.10	19:35309759:G:T

FANTOM5 promoters

9 alternative TSS:

Promoter ID	TPM avg	Samples expressed
175279	14.1447	117
175299	0.3009	110
175303	0.2584	80
175301	0.2547	81
175277	0.1424	55
175300	0.1041	40
175302	0.0823	23
175280	0.0521	25
175278	0.0330	25

Top tissues by expression

showing 100 of 285 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
C1 segment of cervical spinal cord	UBERON:0006469	99.50	gold quality
spinal cord	UBERON:0002240	99.36	gold quality
inferior vagus X ganglion	UBERON:0005363	99.25	gold quality
middle frontal gyrus	UBERON:0002702	99.19	gold quality
corpus callosum	UBERON:0002336	98.71	gold quality
pons	UBERON:0000988	98.26	gold quality
superior vestibular nucleus	UBERON:0007227	97.99	gold quality
subthalamic nucleus	UBERON:0001906	97.97	gold quality
lateral globus pallidus	UBERON:0002476	97.91	gold quality
medulla oblongata	UBERON:0001896	97.35	gold quality
ventral tegmental area	UBERON:0002691	97.29	gold quality
substantia nigra pars reticulata	UBERON:0001966	96.96	gold quality
dorsal plus ventral thalamus	UBERON:0001897	96.61	gold quality
putamen	UBERON:0001874	96.29	gold quality
Brodmann (1909) area 10	UBERON:0013541	96.19	gold quality
substantia nigra pars compacta	UBERON:0001965	95.64	gold quality
amygdala	UBERON:0001876	95.21	gold quality
midbrain	UBERON:0001891	95.10	gold quality
substantia nigra	UBERON:0002038	94.81	gold quality
inferior olivary complex	UBERON:0002127	94.73	gold quality
caudate nucleus	UBERON:0001873	94.69	gold quality
Ammon’s horn	UBERON:0001954	94.15	gold quality
lateral nuclear group of thalamus	UBERON:0002736	94.01	gold quality
hypothalamus	UBERON:0001898	93.20	gold quality
parietal lobe	UBERON:0001872	92.89	gold quality
cranial nerve II	UBERON:0000941	92.87	gold quality
frontal pole	UBERON:0002795	92.79	gold quality
postcentral gyrus	UBERON:0002581	92.58	gold quality
left ovary	UBERON:0002119	92.13	gold quality
nucleus accumbens	UBERON:0001882	92.11	gold quality
prefrontal cortex	UBERON:0000451	91.93	gold quality
Brodmann (1909) area 9	UBERON:0013540	91.44	gold quality
temporal lobe	UBERON:0001871	90.42	gold quality
frontal cortex	UBERON:0001870	90.38	gold quality
right frontal lobe	UBERON:0002810	90.35	gold quality
telencephalon	UBERON:0001893	90.33	gold quality
Brodmann (1909) area 46	UBERON:0006483	90.27	gold quality
paraflocculus	UBERON:0005351	89.66	gold quality
right ovary	UBERON:0002118	89.58	gold quality
sural nerve	UBERON:0015488	89.00	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	88.94	gold quality
cerebral cortex	UBERON:0000956	88.22	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	88.05	gold quality
neocortex	UBERON:0001950	87.93	gold quality
tibial nerve	UBERON:0001323	87.59	gold quality
cingulate cortex	UBERON:0003027	87.58	gold quality
anterior cingulate cortex	UBERON:0009835	87.51	gold quality
forebrain	UBERON:0001890	87.19	gold quality
globus pallidus	UBERON:0001875	87.04	gold quality
central nervous system	UBERON:0001017	87.01	gold quality
ovary	UBERON:0000992	86.85	gold quality
brain	UBERON:0000955	86.60	gold quality
CA1 field of hippocampus	UBERON:0003881	85.82	gold quality
superior frontal gyrus	UBERON:0002661	85.79	gold quality
adult organism	UBERON:0007023	84.39	gold quality
medial globus pallidus	UBERON:0002477	84.24	gold quality
entorhinal cortex	UBERON:0002728	83.78	gold quality
occipital lobe	UBERON:0002021	83.61	gold quality
cerebellar vermis	UBERON:0004720	83.25	gold quality
right hemisphere of cerebellum	UBERON:0014890	82.02	gold quality
orbitofrontal cortex	UBERON:0004167	82.01	gold quality
cerebellum	UBERON:0002037	80.97	gold quality
cerebellar cortex	UBERON:0002129	80.79	gold quality
cerebellar hemisphere	UBERON:0002245	80.67	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	79.84	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	79.59	silver quality
primary visual cortex	UBERON:0002436	79.37	gold quality
right uterine tube	UBERON:0001302	78.26	gold quality
trigeminal ganglion	UBERON:0001675	77.90	gold quality
vena cava	UBERON:0004087	76.05	silver quality
dorsal root ganglion	UBERON:0000044	74.02	gold quality
olfactory bulb	UBERON:0002264	71.40	silver quality
parotid gland	UBERON:0001831	70.05	gold quality
triceps brachii	UBERON:0001509	68.16	gold quality
left adrenal gland cortex	UBERON:0035825	68.02	gold quality
left adrenal gland	UBERON:0001234	67.44	gold quality
adrenal cortex	UBERON:0001235	66.96	gold quality
gluteal muscle	UBERON:0002000	66.77	gold quality
body of tongue	UBERON:0011876	66.73	gold quality
right adrenal gland	UBERON:0001233	66.71	gold quality
adrenal tissue	UBERON:0018303	65.94	gold quality
saphenous vein	UBERON:0007318	65.90	gold quality
adrenal gland	UBERON:0002369	65.80	gold quality
pharyngeal mucosa	UBERON:0000355	65.69	gold quality
endometrium epithelium	UBERON:0004811	64.65	gold quality
right adrenal gland cortex	UBERON:0035827	64.54	gold quality
synovial joint	UBERON:0002217	64.10	gold quality
trachea	UBERON:0003126	64.09	gold quality
cardia of stomach	UBERON:0001162	64.04	silver quality
tongue	UBERON:0001723	63.83	gold quality
nipple	UBERON:0002030	63.58	gold quality
pericardium	UBERON:0002407	63.54	gold quality
biceps brachii	UBERON:0001507	63.52	gold quality
pylorus	UBERON:0001166	63.11	gold quality
right lobe of thyroid gland	UBERON:0001119	62.87	gold quality
quadriceps femoris	UBERON:0001377	62.86	gold quality
vastus lateralis	UBERON:0001379	62.05	gold quality
superior surface of tongue	UBERON:0007371	61.91	gold quality
heart right ventricle	UBERON:0002080	61.70	gold quality
penis	UBERON:0000989	61.31	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-ENAD-20	yes	279.31
E-HCAD-25	yes	62.24
E-GEOD-84465	yes	13.24
E-ANND-3	no	1.79

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 134 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Corpus callosum	tissue	843.2
Spinal cord	tissue	579.9
Caudate putamen	tissue	494.2
Medulla oblongata	tissue	474.3
Midbrain	tissue	400.6
Substantia nigra	tissue	375.7
Nucleus accumbens	tissue	334.3
Thalamus	tissue	290.1
Superior colliculi	tissue	281.3
Pons	tissue	260.9
Locus coeruleus	tissue	244.7
Putamen	tissue	242.0
Ventral forebrain	tissue	225.8
Periaqueductal gray	tissue	207.2
Hippocampus	tissue	197.8	low
Frontal cortex	tissue	186.4
Hypothalamus	tissue	170.7
Hippocampal formation	tissue	164.9
Septum	tissue	131.0
Postcentral gyrus	tissue	129.5
Cerebral cortex	tissue	103.7	high
Somatosensory cortex	tissue	103.7
Occipital cortex	tissue	94.1
Retrosplenial cortex	tissue	89.2
Amygdala	tissue	81.2
Motor cortex	tissue	70.0
Basal ganglia	tissue	69.6	low
Insular cortex	tissue	68.5
Retrosplenial and cingulate cortex	tissue	58.9
Prefrontal cortex	tissue	54.2
Olfactory bulb	tissue	50.4
Temporal cortex	tissue	49.2
Entorhinal cortex	tissue	43.7
Cerebellum	tissue	33.3	high
Choroid plexus	tissue	28.2
Hippocampus	tissue	18.4	medium
Cerebral cortex	tissue	17.0	medium
Superior colliculi	tissue	17.0
Somatosensory cortex	tissue	17.0
Ovary	tissue	17.0	not detected
Locus coeruleus	tissue	16.6
Thalamus	tissue	16.0
Motor cortex	tissue	15.5
Choroid plexus	tissue	14.8
Occipital cortex	tissue	14.3
Prefrontal cortex	tissue	14.0
Insular cortex	tissue	14.0
Midbrain	tissue	13.9
Pons	tissue	13.8
Temporal cortex	tissue	13.8
Nucleus accumbens	tissue	13.7
Hippocampal formation	tissue	13.7
Entorhinal cortex	tissue	13.7
Substantia nigra	tissue	13.6
Retrosplenial cortex	tissue	13.6
Postcentral gyrus	tissue	13.5
Retrosplenial and cingulate cortex	tissue	13.1
Spinal cord	tissue	12.9
Hypothalamus	tissue	12.7
Medulla oblongata	tissue	12.4

Brain sub-regions (HPA Brain Atlas): detected in 380; highest nTPM — Parieto-temporal junction (white matter) (1500.4), Temporal white matter (1235.6), Corpus callosum, splenium (white matter) (1136.6), Cerebellar white matter (1045.3), Corpus callosum, genu (white matter) (1027.7).

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

Targeting MAG by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 47 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-12118	100.00	65.88	1270
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-6758-5P	100.00	66.21	1470
HSA-MIR-6856-5P	100.00	65.47	1298
HSA-MIR-3173-3P	99.98	66.49	1217
HSA-MIR-6891-5P	99.98	66.53	1372
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-95-5P	99.89	72.17	3973
HSA-MIR-6780A-5P	99.88	66.69	2776
HSA-LET-7A-2-3P	99.87	70.53	1921
HSA-MIR-4447	99.85	67.81	2900
HSA-LET-7G-3P	99.85	70.43	1929
HSA-MIR-6842-5P	99.80	67.54	1587
HSA-MIR-7110-5P	99.80	67.84	1712
HSA-MIR-204-5P	99.79	71.62	2439
HSA-MIR-211-5P	99.79	71.65	2440
HSA-MIR-1273H-5P	99.77	66.32	2471
HSA-MIR-30B-3P	99.70	65.76	2325
HSA-MIR-3689A-3P	99.70	65.73	2306
HSA-MIR-3689B-3P	99.70	65.71	2311
HSA-MIR-3689C	99.70	65.71	2311
HSA-MIR-6779-5P	99.70	65.76	2363
HSA-MIR-4729	99.69	72.18	4233
HSA-MIR-6887-3P	99.66	67.83	1778
HSA-MIR-4472	99.56	66.08	1478
HSA-MIR-6832-3P	99.52	70.44	1726
HSA-MIR-486-3P	99.51	66.82	1901
HSA-MIR-1324	99.46	66.57	1302

Functional genomics

gnomAD constraint: pLI 5.3e-05, LOEUF 0.734, missense Z 0.573 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000392213 — one region, missense o/e 0.93.

Literature-anchored findings (GeneRIF, showing 23)

• Myelin destruction with preferential loss of MAG is found in autopsy brains with acute white matter ischemia as well as in HSV- and CMV-encephalitis. (PMID:12528815)
• Possible association of MAG and schizophrenia in a Chinese Han cohort of family trios (PMID:15820319)
• Our findings of a significant associations between schizophrenia and the MAG gene suggest that this gene may be involved in susceptibility to schizophrenia in the Chinese Han population. (PMID:16039057)
• Expression of MAG, CNP and OLIG2 did not differ between patients with schizophrenia and controls in the grey or white matter (PMID:17964117)
• These results support the hypothesis that the adhesive interactions between MUC1 and MAG are of biological significance in pancreatic cancer perineural invasion. (PMID:17974963)
• Twenty of 46 patients with IgM amyloidosis (7 with and 13 without polyneuropathy) had elevation of anti-MAG or SGPG by enzyme-linked immunosorbent assay (PMID:18236455)
• This finding provides support for potential association of the CNP gene but not the MAG gene in schizophrenia in a Caucasian population. (PMID:18496213)
• In our patient, propriospinal myoclonus was associated with anti-MAG polyneuropathy, but the causal relationship remains unclear. (PMID:18816614)
• RNF10 is a trans-acting protein regulating MAG expression and is required for myelin formation. (PMID:18941509)
• Taken together, these findings suggest that in anti-MAG neuropathy patients, IgM deposits are entrapped within cutaneous perineurium-ensheathed nerve bundles where they accumulate in the endoneurial space. (PMID:19151627)
• ELISA is more sensitive than Western blot to diagnose anti-myelin-associated glycoprotein related polyneuropathy, although a positive serology may be found in other forms of polyneuropathy as well. (PMID:19720975)
• polysialylated NCAM persistence, up-regulated polysialyltransferase-1 mRNA and previously uncovered defective myelin-associated glycoprotein may be early pathogenetic events in adult-onset autosomal-dominant leukodystrophy (PMID:19725832)
• Distal acquired demyelinating symmetric neuropathy without anti-MAG antibodies is more likely to be considered a variant of chronic inflammatory demyelinating polyradiculoneuropathy, including a hematological or immunological condition. (PMID:21199182)
• Primary mitochondrial respiratory chain defects affecting the white matter, and unrelated to inflammation, are associated with MAG loss and central nervous system demyelination. (PMID:22491194)
• Results show that MAG is important for axon-glia contact in a model for Charcot-Marie-Tooth disease type 1A, and suggest that its increased expression in patients has a compensatory role in the disease pathology (PMID:22940629)
• Increased serum levels of MAG (and MBP) were found in autistic patients with allergic manifestations compared to those without these manifestations. (PMID:23726766)
• LRP1 assembles unique co-receptor systems to initiate cell signaling in response to tissue-type plasminogen activator and myelin-associated glycoprotein. (PMID:24129569)
• polyneuropathy associated with anti-MAG antibodies is less homogeneous. (PMID:26065001)
• This study identify involvement of myelin-associated glycoprotein in this family with a disorder affecting the central and peripheral nervous system, and suggest that loss of the protein function is responsible for the unique clinical phenotype (PMID:26179919)
• we observed two-way correlations between the MOG and MAG levels and the fractional anisotropy and mean diffusivity values in the white matter of the left middle frontal lobe, right inferior parietal lobe, and right supplementary motor area in major depressive disorder patients (PMID:29477585)
• Clinical and laboratory features of anti-MAG neuropathy without monoclonal gammopathy. (PMID:30992531)
• Recessive null-allele variants in MAG associated with spastic ataxia, nystagmus, neuropathy, and dystonia. (PMID:32629324)
• Myelin-associated proteins are potential diagnostic markers in patients with primary brain tumour. (PMID:34601991)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	mag	ENSDARG00000104023
mus_musculus	Mag	ENSMUSG00000036634
rattus_norvegicus	Mag	ENSRNOG00000021023

Paralogs (16): CD22 (ENSG00000012124), SIGLEC1 (ENSG00000088827), SIGLEC8 (ENSG00000105366), CD33 (ENSG00000105383), SIGLEC6 (ENSG00000105492), SIGLEC9 (ENSG00000129450), SIGLEC10 (ENSG00000142512), TMEM25 (ENSG00000149582), SIGLEC11 (ENSG00000161640), SIGLEC16 (ENSG00000161643), SIGLEC7 (ENSG00000168995), SIGLECL1 (ENSG00000179213), SIGLEC15 (ENSG00000197046), SIGLEC14 (ENSG00000254415), SIGLEC12 (ENSG00000254521), SIGLEC5 (ENSG00000268500)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:96912) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 23 distinct phenotype terms.

Mouse phenotype (MP)	Records
abnormal axon morphology	6
abnormal myelination	2
decreased locomotor activity	2
decreased startle reflex	2
axon degeneration	2
decreased leukocyte cell number	1
tremors	1
demyelination	1
convulsive seizures	1
abnormal oligodendrocyte morphology	1
abnormal Schwann cell morphology	1
impaired coordination	1
abnormal gait	1
abnormal grooming behavior	1
decreased coping response	1
decreased aggression towards mice	1
abnormal myelin sheath morphology	1
abnormal auditory brainstem response	1
increased B cell proliferation	1
decreased prepulse inhibition	1
abnormal sleep behavior	1
tomacula	1
dysmyelination	1

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Pongo abelii	Q5RDJ4	99.8%	Diamond
Macaca fascicularis	Q9N008	99.8%	Diamond
Coturnix japonica	Q92154	46.3%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
FFAR1	protein-coding	2864
FFAR3	protein-coding	2865
HAMP	protein-coding	57817
CD22	protein-coding	933
LSR	protein-coding	51599
USF2	protein-coding	7392
MIR5196	ncRNA	100847070
GPR42	protein-coding	2866

Protein

Protein identifiers

Myelin-associated glycoprotein — P20916 (reviewed: P20916)

Alternative names: Siglec-4a

All UniProt accessions (4): P20916, M0QZU4, M0R3B9, M0R3I4

UniProt curated annotations — full annotation on UniProt →

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. 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. 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. Inhibits axon outgrowth by binding to RTN4R. Preferentially binds to alpha-2,3-linked sialic acid. Binds ganglioside Gt1b.

Subunit / interactions. Monomer and homodimer. Interacts (via the first three N-terminal Ig-like domains) with RTN4R and RTN4RL2. Interacts with RTN4R. Interacts with isoform 2 of BSG. Interacts with the palmitolyated form of CADM4.

Subcellular location. Cell membrane. Membrane raft.

Tissue specificity. Both isoform 1 and isoform 2 are detected in myelinated structures in the central and peripheral nervous system, in periaxonal myelin and at Schmidt-Lanterman incisures. Detected in optic nerve, in oligodendroglia and in periaxonal myelin sheaths. Detected in compact myelin (at protein level). Both isoform 1 and isoform 2 are detected in the central and peripheral nervous system.

Post-translational modifications. N-glycosylated. Phosphorylated on tyrosine residues. Ubiquitinated, leading to proteasomal degradation.

Disease relevance. 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. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the immunoglobulin superfamily. SIGLEC (sialic acid binding Ig-like lectin) family.

Isoforms (3)

UniProt ID	Names	Canonical?
P20916-1	1, L-MAG	yes
P20916-2	2, S-MAG
P20916-3	3

RefSeq proteins (3): NP_001186145, NP_002352, NP_542167 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003598	Ig_sub2	Domain
IPR003599	Ig_sub	Domain
IPR007110	Ig-like_dom	Domain
IPR013162	CD80_C2-set	Domain
IPR013783	Ig-like_fold	Homologous_superfamily
IPR036179	Ig-like_dom_sf	Homologous_superfamily
IPR051036	SIGLEC	Family

Pfam: PF08205, PF13927

UniProt features (43 total): glycosylation site 8, disulfide bond 7, domain 5, sequence variant 4, region of interest 3, binding site 3, modified residue 3, topological domain 2, splice variant 2, signal peptide 1, chain 1, site 1, lipid moiety-binding region 1, transmembrane region 1, sequence conflict 1

Structure

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P20916-F1	80.53	0.61

Human Protein Atlas

Protein class: Enzymes, ENZYME proteins, Hydrolases, Predicted intracellular proteins, Cancer-related genes, Candidate cancer biomarkers, Mutated cancer genes, Mutational cancer driver genes, Disease related genes, Potential drug targets, Human disease related genes, Congenital malformations, Congenital malformations of skin, Other congenital malformations, Essential proteins

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): nucleoplasm; cytosol

Antibody reliability (HPA): IH approved · IF supported

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (1)

Position	Role
332	not glycosylated

Ligand- & substrate-binding residues (3)

Position	Role
65–67	a ganglioside GT1b (d18:1(4E))
118	a ganglioside GT1b (d18:1(4E))
124–128	a ganglioside GT1b (d18:1(4E))

Post-translational modifications (4)

Type	Positions
Phosphoserine	545, 547, 549
S-palmitoyl cysteine	531

Disulfide bonds (7)

Type	Positions
Disulfide bond	37–165, 42–100, 159–217, 261–305, 347–392, 421–430, 432–488

Glycosylation sites (8)

Type	Positions
N-linked (glcnac…) asparagine	99, 106, 223, 246, 315, 406, 450, 454

Function

Pathways and Gene Ontology

Reactome pathways

0 curated (TAS) of 11; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

11 pathways:

ID	Pathway	Evidence
R-HSA-193634	Axonal growth inhibition (RHOA activation)	—
R-HSA-210991	Basigin interactions	—
R-HSA-202733	Cell surface interactions at the vascular wall	—
R-HSA-73887	Death Receptor Signaling	—
R-HSA-1266738	Developmental Biology	—
R-HSA-9619665	EGR2 and SOX10-mediated initiation of Schwann cell myelination	—
R-HSA-109582	Hemostasis	—
R-HSA-9675108	Nervous system development	—
R-HSA-162582	Signal Transduction	—
R-HSA-193704	p75 NTR receptor-mediated signalling	—
R-HSA-193697	p75NTR regulates axonogenesis	—

MSigDB gene sets: 310 (showing top): GOBP_NEGATIVE_REGULATION_OF_NEURON_APOPTOTIC_PROCESS, GOBP_NEGATIVE_REGULATION_OF_CELL_DEVELOPMENT, GOBP_NEGATIVE_REGULATION_OF_NEURON_DIFFERENTIATION, GOBP_NEURON_PROJECTION_EXTENSION, GOBP_NEGATIVE_REGULATION_OF_AXON_EXTENSION, GOBP_REGULATION_OF_DEVELOPMENTAL_GROWTH, GOBP_CELLULAR_RESPONSE_TO_EXTERNAL_STIMULUS, GOBP_NEGATIVE_REGULATION_OF_CELL_GROWTH, ASTON_MAJOR_DEPRESSIVE_DISORDER_DN, GOBP_POSITIVE_REGULATION_OF_GLIAL_CELL_DIFFERENTIATION, GOBP_GROWTH, GOBP_GLIAL_CELL_DEVELOPMENT, GOBP_REGENERATION, GOBP_NEUROGENESIS, GOBP_REGULATION_OF_MYELINATION

GO Biological Process (14): cell adhesion (GO:0007155), negative regulation of neuron projection development (GO:0010977), substantia nigra development (GO:0021762), negative regulation of axon extension (GO:0030517), positive regulation of myelination (GO:0031643), central nervous system myelin formation (GO:0032289), negative regulation of neuron apoptotic process (GO:0043524), negative regulation of neuron differentiation (GO:0045665), positive regulation of astrocyte differentiation (GO:0048711), cellular response to mechanical stimulus (GO:0071260), cell-cell adhesion (GO:0098609), nervous system development (GO:0007399), central nervous system myelination (GO:0022010), myelination (GO:0042552)

GO Molecular Function (8): signaling receptor binding (GO:0005102), protein kinase binding (GO:0019901), carbohydrate binding (GO:0030246), sialic acid binding (GO:0033691), protein homodimerization activity (GO:0042803), ganglioside GT1b binding (GO:1905576), protein binding (GO:0005515), lipid binding (GO:0008289)

GO Cellular Component (9): plasma membrane (GO:0005886), paranode region of axon (GO:0033270), myelin sheath adaxonal region (GO:0035749), myelin sheath (GO:0043209), compact myelin (GO:0043218), Schmidt-Lanterman incisure (GO:0043220), membrane raft (GO:0045121), mesaxon (GO:0097453), membrane (GO:0016020)

Reactome top-level categories

8 top-level categories:

Category	Pathways
p75NTR regulates axonogenesis	1
Cell surface interactions at the vascular wall	1
Nervous system development	1
p75 NTR receptor-mediated signalling	1
Death Receptor Signaling	1
Hemostasis	1
Signal Transduction	1
Developmental Biology	1

GO top-level categories

51 GO namespaces:

Category	Terms
cellular anatomical structure	6
binding	3
myelination	2
carboxylic acid binding	2
myelin sheath	2
cellular process	1
regulation of neuron projection development	1
neuron projection development	1
negative regulation of cell projection organization	1
midbrain development	1
neural nucleus development	1
negative regulation of cell growth	1
regulation of axon extension	1
negative regulation of developmental growth	1
axon extension	1
negative regulation of axonogenesis	1
regulation of myelination	1
positive regulation of nervous system process	1
positive regulation of cellular process	1
central nervous system myelination	1
myelin assembly	1
negative regulation of apoptotic process	1
regulation of neuron apoptotic process	1
neuron apoptotic process	1
neuron differentiation	1
negative regulation of cell differentiation	1
regulation of neuron differentiation	1
positive regulation of glial cell differentiation	1
astrocyte differentiation	1
regulation of astrocyte differentiation	1
response to mechanical stimulus	1
cellular response to abiotic stimulus	1
cellular response to external stimulus	1
cell adhesion	1
system development	1
animal gross anatomical part developmental process	1
oligodendrocyte development	1
axon ensheathment in central nervous system	1
axon ensheathment	1
protein binding	1
kinase binding	1
carbohydrate derivative binding	1
identical protein binding	1
protein dimerization activity	1
ganglioside binding	1
membrane	1
cell periphery	1
main axon	1
compact myelin	1
membrane microdomain	1
ensheathing process	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 4 of 31 annotations. The rest are phylogenetic / computational / electronic (IEA).

4 experimentally-supported GO terms:

GO term	NS	Evidence
substantia nigra development	BP	high-throughput mutant
compact myelin	CC	direct assay
myelin sheath	CC	direct assay
plasma membrane	CC	direct assay

Protein interactions and networks

STRING

showing 15 of 1,844 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MAG	OMG	P23515	965
MAG	MBP	P02686	956
MAG	RTN4R	Q9BZR6	918
MAG	RTN4	Q9NQC3	918
MAG	PLP1	P04400	852
MAG	CNP	P09543	841
MAG	MPZL1	O95297	824
MAG	MOG	Q16653	786
MAG	LINGO1	Q96FE5	725
MAG	NGFR	P08138	697
MAG	EGR2	P11161	688
MAG	BDNF	P23560	677
MAG	MAL	P21145	649
MAG	RTN4RL2	Q86UN3	637
MAG	GAP43	P17677	632

IntAct

Human interaction partners of MAG in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

10 partners by confidence:

Partner	Interaction type	MIscore	Records
SIGLEC15	physical association	0.400	2
SIGLEC8	physical association	0.400	2
SIGLEC9	physical association	0.400	2
CD33	physical association	0.400	1
IGSF10	physical association	0.400	1
IL18BP	physical association	0.400	1
IL6R	physical association	0.400	1
MXRA5	physical association	0.400	1
SCN2B	physical association	0.400	1
PLCB3	association	0.350	1

BioGRID (17 interactions; top human partners by supporting records): PRNP (Affinity Capture-MS; 2 records), APP (Reconstituted Complex), COL1A1 (Reconstituted Complex), COL2A1 (Reconstituted Complex), COL3A1 (Reconstituted Complex), COL4A1 (Reconstituted Complex), COL5A1 (Reconstituted Complex), COL6A1 (Reconstituted Complex), COL9A1 (Reconstituted Complex), FYN (Reconstituted Complex), IQCB1 (Affinity Capture-MS), MAP1B (Affinity Capture-Western), MARS2 (Affinity Capture-MS), NRAS (Proximity Label-MS), PLCB3 (Affinity Capture-MS)

SIGNOR signaling

3 signaling interactions:

A	Effect	B	Mechanism
FYN	“up-regulates activity”	MAG	phosphorylation
SMO	“up-regulates quantity”	MAG	“transcriptional regulation”
MAG	up-regulates	Myelination

Disease & clinical

Genetic variants

Variant evidence for MAG: 374 ClinVar records (15 pathogenic / likely pathogenic). Per-variant detail is on Sugi Variant.

ClinVar

374 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	8
Likely pathogenic	7
Uncertain significance	180
Likely benign	142
Benign	17

Top pathogenic / likely-pathogenic (15)

Showing all 15 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
488543	NM_002361.4(MAG):c.517_521dup (p.Trp174Ter)	Pathogenic	criteria provided, single submitter	1
657878	NM_002361.4(MAG):c.328G>T (p.Glu110Ter)	Pathogenic	criteria provided, single submitter	1
976659	NM_002361.4(MAG):c.1126C>T (p.Gln376Ter)	Pathogenic	criteria provided, single submitter	1
1478560	NM_002361.4(MAG):c.719dup (p.Val241fs)	Pathogenic	criteria provided, single submitter	1
4703049	NM_002361.4(MAG):c.1273C>T (p.Arg425Ter)	Pathogenic	criteria provided, single submitter	1
435794	NM_002361.4(MAG):c.416-6_418dup	Likely pathogenic	criteria provided, single submitter	1
2585566	NM_002361.4(MAG):c.470del (p.Val157fs)	Likely pathogenic	criteria provided, single submitter	1
2857234	NM_002361.4(MAG):c.1520-3_1520-2del	Likely pathogenic	criteria provided, single submitter	1
3643289	NM_002361.4(MAG):c.1616+1G>A	Likely pathogenic	criteria provided, single submitter	1
3644099	NM_002361.4(MAG):c.1232-3_1240del	Likely pathogenic	criteria provided, single submitter	1
4278447	NM_002361.4(MAG):c.1231+3G>C	Likely pathogenic	criteria provided, single submitter	1
120188	NM_002361.4(MAG):c.1288T>G (p.Cys430Gly)	Pathogenic	no assertion criteria provided	1
218187	NM_002361.4(MAG):c.399C>G (p.Ser133Arg)	Pathogenic	no assertion criteria provided	1
3764543	NM_002361.4(MAG):c.337G>A (p.Gly113Arg)	Pathogenic	no assertion criteria provided	1
3256730	NM_002361.4(MAG):c.809T>C (p.Leu270Pro)	Likely pathogenic	no assertion criteria provided	1

Per-variant reference — Sugi Variant

Explore MAG’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

AlphaMissense

1,442 missense substitutions predicted likely pathogenic (of 4,045 scored), across 379 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
M26	9	0.871	0.991
N396	8	0.995	1.000
N309	8	0.976	0.999
D120	8	0.972	0.990
F117	8	0.966	0.998
F444	8	0.964	0.999
F523	8	0.962	0.993
F44	8	0.956	0.998
N492	8	0.943	0.998
F33	8	0.935	0.996
S63	8	0.906	0.995
F204	8	0.893	0.990
F405	8	0.858	0.973
H56	8	0.855	0.958
H82	8	0.825	0.890
N68	8	0.818	0.976
C42	7	0.997	0.999
C347	7	0.996	0.999
C392	7	0.996	0.999
C488	7	0.996	0.999

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

2 prognostic cancer types:

Cancer	Prognostic	p-value
Kidney Renal Clear Cell Carcinoma (TCGA)	favorable	4.09e-05
Kidney Renal Papillary Cell Carcinoma (TCGA)	favorable	0.000944

Disease associations

OMIM: gene MIM:159460 | disease phenotypes: MIM:616680, MIM:119530

GenCC curated gene-disease

2 curated gene-disease records:

Disease	Classification	Inheritance	Records
hereditary spastic paraplegia 75	Strong	Autosomal recessive	2
complex hereditary spastic paraplegia	Strong	Autosomal recessive

ClinGen Gene-Disease Validity

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

1 validity classifications:

Disease	Classification	Inheritance
complex hereditary spastic paraplegia	Definitive	AR

Genomics England panels (PanelApp)

Clinical diagnostic gene panels including this gene (10 panels, 10 green/diagnostic-grade). Confidence: green = diagnostic, amber = moderate.

10 panels:

Panel	Rating
Ataxia and cerebellar anomalies - childhood onset	green
Hereditary ataxia and cerebellar anomalies, childhood onset	green
Hereditary neuropathy or pain disorder	green
Hereditary spastic paraplegia	green
Hereditary spastic paraplegia, childhood onset	green
Hypotonic infant	green
Intellectual disability	green
Leukodystrophy, childhood onset	green
Optic neuropathy	green
Paediatric disorders	green

Mondo (3): hereditary spastic paraplegia 75 (MONDO:0014729), orofacial cleft 1 (MONDO:0007335), complex hereditary spastic paraplegia (MONDO:0015150)

Orphanet (1): Autosomal recessive spastic paraplegia type 75 (Orphanet:459056)

MeSH disease descriptors

1 disease descriptors:

Descriptor	Name	Tree numbers
C566121	Orofacial Cleft 1 *(supp.)*

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5807 (SINGLE PROTEIN)

Drugs by curated mechanism of action (ChEMBL)

Drugs whose curated ChEMBL mechanism of action targets the MAG protein itself — single-protein targets only (drugs acting on a protein family or complex that merely includes it are excluded). Includes antibodies and oligonucleotides that bioactivity screening does not capture.

1 curated-mechanism drugs:

Drug	Modality	Max phase
REFANEZUMAB	Antibody	2

PharmGKB: 1 entry (CPIC guideline: no)

Binding affinities (BindingDB)

25 measured of 29 human assays (29 total across all organisms); most potent 25 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
CHEMBL1836190	IC50	9 nM
(2R,4S,5R,6R)-2-(biphenyl-4-ylmethoxy)-6-((1R,2R)-1,2-dihydroxy-3-(2-(4’-hydroxybiphenyl-4-yl)acetamido)propyl)-4-hydroxy-5-(2-hydroxyacetamido)tetrahydro-2H-pyran-2-carboxylic acid	IC50	70 nM
CHEMBL1836336	IC50	79 nM
benzyl 3,5,9-trideoxy-5-glycolamido-9-(4’-hydroxy-4-biphenyl)acetamido-D-glycero-alpha-D-galacto-2-nonulopyranosidonic acid	IC50	130 nM
p-Methoxyphenyl (3,5,9-trideoxy-5-glycolamido-9-(4-hydroxy-4-biphenyl)-methylamino-D-glycero-alpha-D-galacto-2-nonulopyranosylonicacid)-(2->6)-beta-D-galactopyranoside	IC50	240 nM
CHEMBL1836306	IC50	300 nM
CHEMBL1836340	IC50	300 nM
CHEMBL4788433	KD	335 nM
CHEMBL4780037	KD	458 nM
CHEMBL1836335	IC50	610 nM
CHEMBL1836337	IC50	640 nM
CHEMBL1836334	IC50	650 nM
CHEMBL1836339	IC50	750 nM
Benzyl 3,5,9-trideoxy-5-glycolamido-9-(4’-hydroxy-4-biphenyl)methylamino-D-glycero-alpha-D-galacto-2-nonulopyranosidonic acid	IC50	820 nM
p-Methoxyphenyl (3,5,9-trideoxy-5-glycolamido-9-(4’-hydroxy-4-biphenyl)-acetamido-D-glycero-alpha-D-galacto-2-nonulopyranosylonicacid)-(2->6)-beta-D-galactopyranoside	IC50	900 nM
CHEMBL1836338	IC50	1100 nM
(4-Biphenyl)methyl 3,5,9-trideoxy-5-glycolamido-9-(4’-hydroxy-4-biphenyl)methylamino-D-glycero-alpha-D-galacto-2-nonulopyranosidonic acid	IC50	1120 nM
CHEMBL1836310	IC50	1200 nM
CHEMBL1836313	IC50	1200 nM
(Sodium 5-Acetamido-9-(4-chlorobenzamido)-3,5,9-trideoxy-D-glycero-alpha-D-galacto-2-nonulopyranosynate)-(2->3)-beta-D-galactopyranosyl-(1->3)-1,5-anhydro-6-O-(biphenyl-4-yl-methyl)-2-deoxy-D-lyxo-hexitol	KD	2830 nM
(Sodium 5-Acetamido-9-benzamido-3,5,9-trideoxy-D-glyceror-alpha-D-galacto-2-nonulopyranosynate)-(2->3)-beta-D-galactopyranosyl-(1->3)-1,5-anhydro-6-O-(biphenyl-4-yl-methyl)-2-deoxy-Dlyxo-hexitol	KD	5000 nM
CHEMBL1833997	IC50	7900 nM
2-(Trimethylsilyl)ethyl (Sodium 5-Acetamido-9-benzamido-3,5,9-trideoxy-D-glycero-alpha-D-galacto-2-nonulopyranosynate)-(2->3)-beta-D-galactopyranosyl-(1->3)-beta-D-galactopyranoside	KD	32600 nM
CHEMBL1836309	IC50	52000 nM
CHEMBL1836308	IC50	272000 nM

ChEMBL bioactivities

25 potent at pChembl≥5 of 33 total, top 25 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.05	IC50	9	nM	CHEMBL1836190
7.82	Kd	15	nM	CHEMBL1836190
7.10	IC50	79	nM	CHEMBL1836336
6.89	Kd	130	nM	CHEMBL1836336
6.52	IC50	300	nM	CHEMBL1836306
6.52	IC50	300	nM	CHEMBL1836340
6.32	Kd	480	nM	CHEMBL1836340
6.30	Kd	500	nM	CHEMBL1836312
6.21	IC50	610	nM	CHEMBL1836335
6.19	IC50	650	nM	CHEMBL1836334
6.19	IC50	640	nM	CHEMBL1836337
6.12	IC50	750	nM	CHEMBL1836339
6.00	Kd	1000	nM	CHEMBL1836334
6.00	Kd	1000	nM	CHEMBL1836335
6.00	Kd	1000	nM	CHEMBL1836337
5.96	IC50	1100	nM	CHEMBL1836338
5.92	IC50	1200	nM	CHEMBL1836310
5.92	IC50	1200	nM	CHEMBL1836313
5.92	Kd	1200	nM	CHEMBL1836339
5.75	Kd	1760	nM	CHEMBL1836338
5.72	Kd	1900	nM	CHEMBL1836313
5.55	Kd	2830	nM	CHEMBL507374
5.30	Kd	5000	nM	CHEMBL454284
5.10	IC50	7900	nM	CHEMBL1833997
5.03	IC50	9270	nM	CHEMBL1684363

PubChem BioAssay actives

25 with measured affinity, of 89 total; 16 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
disodium;(2R,4S,5R,6R)-5-acetamido-2-[[(2R,3R,4R,5R,6S)-5-acetamido-4-[(2R,3R,4S,5S,6R)-4-[(2S,4S,5R,6R)-5-acetamido-2-carboxylato-4-hydroxy-6-[(1R,2R)-1,2,3-trihydroxypropyl]oxan-2-yl]oxy-3,5-dihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-6-[(2R,3S)-3-acetamido-4-methoxy-4-oxobutan-2-yl]oxy-3-hydroxyoxan-2-yl]methoxy]-6-[(1R,2R)-3-[(4-fluorobenzoyl)amino]-1,2-dihydroxypropyl]-4-hydroxyoxane-2-carboxylate	620752: Inhibition of MAG -Fc chimera expressed in CHO cells using NeuAc alpha2-3Galbeta1-4GlcNAc-R coupled biotinylated polyacrylamide after 30 mins by ELISA	ic50	0.0090	uM
sodium (2S,4S,5R,6R)-5-acetamido-2-[(2R,3R,4S,5S,6R)-2-[(2S,3R,4R,5R,6R)-3-acetamido-2-[(2R,3S)-3-acetamido-4-methoxy-4-oxobutan-2-yl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-3,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-6-[(1R,2R)-3-[(4-fluorobenzoyl)amino]-1,2-dihydroxypropyl]-4-hydroxyoxane-2-carboxylate	620752: Inhibition of MAG -Fc chimera expressed in CHO cells using NeuAc alpha2-3Galbeta1-4GlcNAc-R coupled biotinylated polyacrylamide after 30 mins by ELISA	ic50	0.0790	uM
disodium;(2R,4S,5R,6R)-5-acetamido-2-[[(2R,3R,4R,5R,6S)-5-acetamido-4-[(2R,3R,4S,5S,6R)-4-[(2S,4S,5R,6R)-5-acetamido-2-carboxylato-6-[(1R,2R)-3-[(4-fluorobenzoyl)amino]-1,2-dihydroxypropyl]-4-hydroxyoxan-2-yl]oxy-3,5-dihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-6-[(2R,3S)-3-acetamido-4-methoxy-4-oxobutan-2-yl]oxy-3-hydroxyoxan-2-yl]methoxy]-4-hydroxy-6-[(1R,2R)-1,2,3-trihydroxypropyl]oxane-2-carboxylate	620752: Inhibition of MAG -Fc chimera expressed in CHO cells using NeuAc alpha2-3Galbeta1-4GlcNAc-R coupled biotinylated polyacrylamide after 30 mins by ELISA	ic50	0.3000	uM
disodium;(2R,4S,5R,6R)-5-acetamido-2-[[(2R,3R,4R,5R,6S)-5-acetamido-4-[(2R,3R,4S,5S,6R)-4-[(2S,4S,5R,6R)-5-acetamido-2-carboxylato-4-hydroxy-6-[(1R,2R)-1,2,3-trihydroxypropyl]oxan-2-yl]oxy-3,5-dihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-6-[(1S,2R)-1-amino-1-carboxypropan-2-yl]oxy-3-hydroxyoxan-2-yl]methoxy]-4-hydroxy-6-[(1R,2R)-1,2,3-trihydroxypropyl]oxane-2-carboxylate	620751: Inhibition of MAG	ic50	0.3000	uM
sodium (2R,4S,5R,6R)-6-[(1R,2R)-3-benzamido-1,2-dihydroxypropyl]-2-[(2,3-difluorophenyl)methoxy]-5-[(2-fluoroacetyl)amino]-4-hydroxyoxane-2-carboxylate	620750: Binding affinity to MAG	kd	0.5000	uM
sodium (2S,4S,5R,6R)-5-acetamido-2-[(2R,3R,4S,5S,6R)-2-[(2S,3R,4R,5R,6R)-3-acetamido-2-[(2R,3S)-3-acetamido-4-methoxy-4-oxobutan-2-yl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-3,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-6-[(1R,2R)-3-[(4-chlorobenzoyl)amino]-1,2-dihydroxypropyl]-4-hydroxyoxane-2-carboxylate	620752: Inhibition of MAG -Fc chimera expressed in CHO cells using NeuAc alpha2-3Galbeta1-4GlcNAc-R coupled biotinylated polyacrylamide after 30 mins by ELISA	ic50	0.6100	uM
sodium (2R,4S,5R,6R)-5-acetamido-2-[[(2R,3R,4R,5R,6S)-5-acetamido-6-[(2R,3S)-3-acetamido-4-methoxy-4-oxobutan-2-yl]oxy-3-hydroxy-4-[(2R,3R,4S,5R,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxyoxan-2-yl]methoxy]-6-[(1R,2R)-3-[(4-chlorobenzoyl)amino]-1,2-dihydroxypropyl]-4-hydroxyoxane-2-carboxylate	620752: Inhibition of MAG -Fc chimera expressed in CHO cells using NeuAc alpha2-3Galbeta1-4GlcNAc-R coupled biotinylated polyacrylamide after 30 mins by ELISA	ic50	0.6400	uM
sodium (2S,4S,5R,6R)-5-acetamido-2-[(2R,3R,4S,5S,6R)-2-[(2S,3R,4R,5R,6R)-3-acetamido-2-[(2R,3S)-3-acetamido-4-methoxy-4-oxobutan-2-yl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-3,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-6-[(1R,2R)-3-benzamido-1,2-dihydroxypropyl]-4-hydroxyoxane-2-carboxylate	620752: Inhibition of MAG -Fc chimera expressed in CHO cells using NeuAc alpha2-3Galbeta1-4GlcNAc-R coupled biotinylated polyacrylamide after 30 mins by ELISA	ic50	0.6500	uM
disodium;(2R,4S,5R,6R)-5-acetamido-2-[[(2R,3R,4R,5R,6S)-5-acetamido-4-[(2R,3R,4S,5S,6R)-4-[(2S,4S,5R,6R)-5-acetamido-2-carboxylato-4-hydroxy-6-[(1R,2R)-1,2,3-trihydroxypropyl]oxan-2-yl]oxy-3,5-dihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-6-[(2R,3S)-3-acetamido-4-methoxy-4-oxobutan-2-yl]oxy-3-hydroxyoxan-2-yl]methoxy]-4-hydroxy-6-[(1R,2R)-1,2,3-trihydroxypropyl]oxane-2-carboxylate	620752: Inhibition of MAG -Fc chimera expressed in CHO cells using NeuAc alpha2-3Galbeta1-4GlcNAc-R coupled biotinylated polyacrylamide after 30 mins by ELISA	ic50	0.7500	uM
sodium (2R,4S,5R,6R)-5-acetamido-2-[[(2R,3R,4R,5R,6S)-5-acetamido-6-[(2R,3S)-3-acetamido-4-methoxy-4-oxobutan-2-yl]oxy-3-hydroxy-4-[(2R,3R,4S,5R,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxyoxan-2-yl]methoxy]-6-[(1R,2R)-3-[(4-fluorobenzoyl)amino]-1,2-dihydroxypropyl]-4-hydroxyoxane-2-carboxylate	620752: Inhibition of MAG -Fc chimera expressed in CHO cells using NeuAc alpha2-3Galbeta1-4GlcNAc-R coupled biotinylated polyacrylamide after 30 mins by ELISA	ic50	1.1000	uM
sodium (2S,4S,5R,6R)-5-acetamido-2-[(2R,3R,4S,5S,6R)-2-[(2S,3R,4R,5R,6R)-3-acetamido-2-[(2R,3S)-3-acetamido-4-methoxy-4-oxobutan-2-yl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-3,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-4-hydroxy-6-[(1R,2R)-1,2,3-trihydroxypropyl]oxane-2-carboxylate	620752: Inhibition of MAG -Fc chimera expressed in CHO cells using NeuAc alpha2-3Galbeta1-4GlcNAc-R coupled biotinylated polyacrylamide after 30 mins by ELISA	ic50	1.2000	uM
sodium (2S,4S,5R,6R)-5-acetamido-2-[(2R,3R,4S,5S,6R)-2-[(2S,3R,4R,5R,6R)-3-acetamido-2-[(1S,2R)-1-amino-1-carboxypropan-2-yl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-3,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-4-hydroxy-6-[(1R,2R)-1,2,3-trihydroxypropyl]oxane-2-carboxylate	620751: Inhibition of MAG	ic50	1.2000	uM
sodium (2S,4S,5R,6R)-5-acetamido-6-[(1S,2R)-3-[(4-chlorobenzoyl)amino]-1,2-dihydroxypropyl]-2-[(2R,3S,4S,5R,6R)-3,5-dihydroxy-2-(hydroxymethyl)-6-[(2R,3R,4R)-3-hydroxy-2-[(4-phenylphenoxy)methyl]oxan-4-yl]oxyoxan-4-yl]oxy-4-hydroxyoxane-2-carboxylate	346346: Binding affinity to human IgG Fc-domain tagged MAG N-terminal domain expressed in CHO cells by surface plasmon resonance	kd	2.8300	uM
sodium (2S,4S,5R,6R)-5-acetamido-6-[(1S,2R)-3-benzamido-1,2-dihydroxypropyl]-2-[(2R,3S,4S,5R,6R)-3,5-dihydroxy-2-(hydroxymethyl)-6-[(2R,3R,4R)-3-hydroxy-2-[(4-phenylphenoxy)methyl]oxan-4-yl]oxyoxan-4-yl]oxy-4-hydroxyoxane-2-carboxylate	346346: Binding affinity to human IgG Fc-domain tagged MAG N-terminal domain expressed in CHO cells by surface plasmon resonance	kd	5.0000	uM
sodium (2R,4S,5R,6R)-5-acetamido-2-[[(2R,3R,4R,5R,6S)-5-acetamido-6-[(2R,3S)-3-acetamido-4-methoxy-4-oxobutan-2-yl]oxy-3-hydroxy-4-[(2R,3R,4S,5R,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxyoxan-2-yl]methoxy]-4-hydroxy-6-[(1R,2R)-1,2,3-trihydroxypropyl]oxane-2-carboxylate	620752: Inhibition of MAG -Fc chimera expressed in CHO cells using NeuAc alpha2-3Galbeta1-4GlcNAc-R coupled biotinylated polyacrylamide after 30 mins by ELISA	ic50	7.9000	uM
(2R,4S,5R,6R)-6-[(1R,2R)-1,2-dihydroxy-3-[[4-(4-hydroxyphenyl)phenyl]methylamino]propyl]-4-hydroxy-5-[(2-hydroxyacetyl)amino]-2-phenylmethoxyoxane-2-carboxylic acid	578489: Inhibition of human MAG after 1 hr by competitive ELISA	ic50	9.2700	uM

CTD chemical–gene interactions

14 total (human), top 14 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Estradiol	affects binding, increases expression	2
aristolochic acid I	increases expression	1
bisphenol A	decreases methylation	1
sodium arsenite	increases expression	1
bisphenol S	increases expression	1
Leflunomide	increases expression	1
Atrazine	increases expression	1
Benzo(a)pyrene	affects methylation, increases methylation	1
Cadmium	decreases expression, increases abundance	1
Testosterone	decreases expression	1
Tretinoin	increases expression	1
Urethane	decreases expression	1
Valproic Acid	increases methylation	1
Cadmium Chloride	increases abundance, decreases expression	1

ChEMBL screening assays

12 unique, capped per target: 12 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1686889	Binding	Inhibition of human MAG after 1 hr by competitive ELISA	CD22-antagonists with nanomolar potency: the synergistic effect of hydrophobic groups at C-2 and C-9 of sialic acid scaffold. — *Bioorg Med Chem*

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.

55 trials:

NCT	Phase	Status	Title
NCT07542548	Phase 4	COMPLETED	D-Cycloserine for Serine Palmitoyltransferase Inhibition
NCT07803276	Phase 4	RECRUITING	Comparison Between Palpatory and Ultrasound-guided Methods for Botulinum Toxin Administration in Spastic Paraplegia
NCT03961906	Phase 2	COMPLETED	Physiotherapy in Hereditary Spastic Paraplegia
NCT04768166	Phase 2	COMPLETED	Testing Miglustat Administration in Subjects With Spastic Paraplegia 11
NCT06117020	Phase 1	COMPLETED	Single and Multiple Ascending Dose Study of MTR-601 in Healthy Individuals
NCT02604186	Phase 2/3	COMPLETED	Effects of Botulinum Toxin Injections in Patients With Hereditary Spastic Paraplegia
NCT05518188	Phase 1/2	RECRUITING	Melpida: Recombinant Adeno-associated Virus (Serotype 9) Encoding a Codon Optimized Human AP4M1 Transgene (hAP4M1opt)
NCT06948019	Phase 1/2	NOT_YET_RECRUITING	Safety and Efficacy of AAV9/AP4B1 (BFB-101) For Patients With AP4B1-related Hereditary Spastic Paraplegia Type 47 (SPG47)
NCT06478238	Early Phase 1	RECRUITING	Calcium Folinate Treatment of Spastic Paraplegia 56
NCT00023075	Not specified	COMPLETED	Nuclear Magnetic Spectroscopy Imaging to Evaluate Primary Lateral Sclerosis, Hereditary Spastic Paraplegia and Amyotrophic Lateral Sclerosis
NCT00136630	Not specified	COMPLETED	Natural History, Genetic Bases and Phenotype-genotype Correlations in Autosomal Dominant Spinocerebellar Degenerations
NCT00140829	Not specified	COMPLETED	SPATAX: Clinical and Genetic Analysis of Cerebellar Ataxias and Spastic Paraplegias
NCT00677768	Not specified	COMPLETED	Validation of Biomarkers in Amyotrophic Lateral Sclerosis (ALS)
NCT01568658	Not specified	ACTIVE_NOT_RECRUITING	Genetic and Physical Study of Childhood Nerve and Muscle Disorders
NCT02327845	Not specified	ACTIVE_NOT_RECRUITING	Phenotype, Genotype & Biomarkers in ALS and Related Disorders
NCT02852278	Not specified	COMPLETED	A Patient Centric Motor Neuron Disease Activities of Daily Living Scale
NCT02859428	Not specified	TERMINATED	Disease Natural History and Biomarkers of SPG3A, SPG4A, and SPG31
NCT03104088	Not specified	COMPLETED	Studying Cognition in SPG4
NCT03206190	Not specified	RECRUITING	The preSPG4 Study - Studying the Prodromal and Early Phase of SPG4
NCT03627416	Not specified	COMPLETED	Repetitive Transcranial Magnetic Stimulation as Therapy in Hereditary Spastic Paraplegia and Adrenomyeloneuropathy
NCT03981276	Not specified	RECRUITING	Phenotypes, Biomarkers and Pathophysiology in Hereditary Spastic Paraplegias and Related Disorders
NCT04006418	Not specified	RECRUITING	A Registered Cohort Study on Spastic Paraplegia
NCT04180098	Not specified	COMPLETED	Improving Gait Adaptability in Hereditary Spastic Paraplegia
NCT04256681	Not specified	COMPLETED	SNAP: Measurement of the Subjective Perception of the Symptom in Hereditary Spastic Paraparesis (HSP)
NCT04712812	Not specified	RECRUITING	Registry and Natural History Study for Early Onset Hereditary Spastic Paraplegia
NCT04875416	Not specified	ACTIVE_NOT_RECRUITING	Phenotype, Genotype and Biomarkers 2
NCT04912609	Not specified	COMPLETED	Trehalose Administration in Subjects With Spastic Paraplegia 11 (3AL-SPG11)
NCT05354622	Not specified	RECRUITING	Hereditary Spastic Paraplegia Genomic Sequencing Initiative (HSPseq)
NCT05373082	Not specified	COMPLETED	Identification of Modifying Factors in Hereditary Spastic Paraplegia
NCT05411627	Not specified	WITHDRAWN	A Pilot Study of Shockwave Therapy in HSP
NCT05432999	Not specified	COMPLETED	Extracorporeal Shockwave Therapy for Spasticity in People With Spinal Cord Injury
NCT05613114	Not specified	COMPLETED	Effect of Dalfampridine in Patients With Hereditary Spastic Paraplegia
NCT05767268	Not specified	COMPLETED	Assessment of the Psychophysical State During Rehabilitation Treatment With Lokomat
NCT05848271	Not specified	RECRUITING	Natural History Study of Patients with HPDL Mutations
NCT06156813	Not specified	RECRUITING	Turkish Lower-Extremity Motor Activity Log (LE-MAL)
NCT06229626	Not specified	RECRUITING	Evaluation of an Intensive Training Program for Patients with Hereditary Spastic Paraparesis SPG4/Spast
NCT06260982	Not specified	UNKNOWN	Cognitive Disorders in Hereditary Spastic Paraplegia Type 4
NCT06553976	Not specified	RECRUITING	Spastic Paraplegia - Centers of Excellence Research Network
NCT06572046	Not specified	RECRUITING	STOP-HSP.Net: a Registry for Hereditary Spastic Paraplegia as an Integration Tool for Future Therapeutic Strategies
NCT06573866	Not specified	ACTIVE_NOT_RECRUITING	Enhancement of Quality of Work And Life
NCT06680063	Not specified	COMPLETED	Correlation Between Clinical Assessment and Neurophysiological Assessment in Spinal Cord Injury
NCT06728787	Not specified	RECRUITING	Robot-assisted Walking Treatment in Hereditary Spastic Paraplegia (HSP)
NCT06740006	Not specified	COMPLETED	Retrospective Study on the WalkOn AFO in Children or Teenagers With Neurological Pathologies
NCT06742697	Not specified	RECRUITING	Flexibility, Resistance, Aerobic, Movement Execution Training in Adults With Hereditary Spastic Paraplegia
NCT06844734	Not specified	RECRUITING	A Prospective Cohort Study of ITB Treatment for HSP
NCT06936163	Not specified	RECRUITING	A Prospective Cohort Study of Surgical Treatment for Foot Deformities in HSP
NCT07090057	Not specified	RECRUITING	The Effect of Targeting the Plantaris Muscle-tendon in Surgical Correction of Ankle Equinus in Children
NCT07136844	Not specified	RECRUITING	Gait Analysis Parameter and Upper Limb Evaluation in Adult Patients With Neurological or Metabolic Pathology
NCT07352085	Not specified	COMPLETED	Exoskeleton-assisted Neurorehabilitation
NCT07417943	Not specified	RECRUITING	Neuromodulation to Enhance Motor Function in HSP
NCT07478172	Not specified	RECRUITING	Effects of Whole-body Electrical Muscle Stimulation Exercise on Adults With Neuromuscular Disease
NCT07561359	Not specified	ENROLLING_BY_INVITATION	12-Week Strength and Functional Exercise Program for Hereditary Spastic Paraplegia Trial (HSPMOVE)
NCT07706517	Not specified	COMPLETED	Assessing Transition Practices for Children With Disabilities: Pathways to a Successful Adulthood
NCT07798674	Not specified	RECRUITING	TreatHSP Platform: Adaptive Natural History Platform for Ataxias, HSPs, and Spastic Ataxias
NCT07799233	Not specified	COMPLETED	Dental-Oral and Craniofacial Characteristics of Hereditary Spastic Paraplegia: A Preliminary Study

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for MAG across ~30M SureChEMBL compounds — explore on Sugi Predict.