MAGT1

Summary

MAGT1 (magnesium transporter 1, HGNC:28880) is a protein-coding gene on chromosome Xq21.1, encoding Dolichyl-diphosphooligosaccharide–protein glycosyltransferase subunit MAGT1 (Q9H0U3). Accessory component of the STT3B-containing form of the N-oligosaccharyl transferase (OST) complex which catalyzes the transfer of a high mannose oligosaccharide from a lipid-linked oligosaccharide donor to an asparagine residue within an Asn-X-Ser/Thr consensus motif in nascent…. It is haploinsufficient (ClinGen: sufficient evidence).

This gene encodes a ubiquitously expressed magnesium cation transporter protein that localizes to the cell membrane. This protein also associates with N-oligosaccharyl transferase and therefore may have a role in N-glycosylation. Mutations in this gene cause a form of X-linked intellectual disability (XLID). This gene may have multiple in-frame translation initiation sites, one of which would encode a shorter protein with an N-terminus containing a signal peptide at amino acids 1-29.

Source: NCBI Gene 84061 — RefSeq curated summary.

At a glance

• Gene–disease (curated): X-linked immunodeficiency with magnesium defect, Epstein-Barr virus infection and neoplasia (Definitive, ClinGen) — +2 more curated relationships
• Clinical variants (ClinVar): 303 total — 28 pathogenic, 17 likely-pathogenic
• Phenotypes (HPO): 31
• Druggable target: yes
• Dosage sensitivity (ClinGen): haploinsufficiency sufficient evidence, triplosensitivity no evidence
• MANE Select transcript: NM_001367916

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:28880
Approved symbol	MAGT1
Name	magnesium transporter 1
Location	Xq21.1
Locus type	gene with protein product
Status	Approved
Aliases	DKFZp564K142, IAP, OST3B, MRX95, SLC58A1
Ensembl gene	ENSG00000102158
Ensembl biotype	protein_coding
OMIM	300715
Entrez	84061

Gene structure

Transcript identifiers

Ensembl transcripts: 14 — 9 protein_coding, 3 nonsense_mediated_decay, 2 retained_intron

ENST00000358075, ENST00000373336, ENST00000476168, ENST00000618282, ENST00000685002, ENST00000685015, ENST00000685353, ENST00000688650, ENST00000689137, ENST00000689519, ENST00000691172, ENST00000691993, ENST00000692161, ENST00000944450

RefSeq mRNA: 2 — MANE Select: NM_001367916 NM_001367916, NM_032121

CCDS: CCDS14436, CCDS94636

Canonical transcript exons

ENST00000618282 — 10 exons

Exon	Start	End
ENSE00001596103	77855501	77855590
ENSE00001597195	77853901	77853964
ENSE00001677328	77856733	77856873
ENSE00001765457	77841246	77841320
ENSE00001804472	77830805	77830895
ENSE00003544361	77857357	77857497
ENSE00003617103	77870808	77870925
ENSE00003684941	77875428	77875597
ENSE00003742628	77825747	77829235
ENSE00003745509	77895309	77895435

Expression profiles

Bgee: expression breadth ubiquitous, 282 present calls, max score 98.91.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 37.5988 / max 532.6378, expressed in 1816 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
199798	36.1518	1816
199799	1.0913	692
199800	0.2089	82
209740	0.1468	62

Top tissues by expression

287 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
palpebral conjunctiva	UBERON:0001812	98.91	gold quality
corpus epididymis	UBERON:0004359	98.46	gold quality
esophagus squamous epithelium	UBERON:0006920	98.43	gold quality
tibia	UBERON:0000979	98.35	gold quality
parotid gland	UBERON:0001831	98.21	gold quality
germinal epithelium of ovary	UBERON:0001304	98.07	gold quality
pericardium	UBERON:0002407	97.91	gold quality
decidua	UBERON:0002450	97.80	gold quality
visceral pleura	UBERON:0002401	97.62	gold quality
parietal pleura	UBERON:0002400	97.60	gold quality
seminal vesicle	UBERON:0000998	97.37	gold quality
jejunal mucosa	UBERON:0000399	97.29	gold quality
trachea	UBERON:0003126	97.12	gold quality
heart right ventricle	UBERON:0002080	97.11	gold quality
urethra	UBERON:0000057	97.04	gold quality
synovial joint	UBERON:0002217	96.91	gold quality
mucosa of sigmoid colon	UBERON:0004993	96.89	gold quality
penis	UBERON:0000989	96.88	gold quality
epithelium of esophagus	UBERON:0001976	96.85	gold quality
pylorus	UBERON:0001166	96.76	gold quality
cartilage tissue	UBERON:0002418	96.76	gold quality
oral cavity	UBERON:0000167	96.71	gold quality
buccal mucosa cell	CL:0002336	96.60	gold quality
caput epididymis	UBERON:0004358	96.56	gold quality
trigeminal ganglion	UBERON:0001675	96.52	gold quality
pharyngeal mucosa	UBERON:0000355	96.41	gold quality
cardia of stomach	UBERON:0001162	96.41	gold quality
mammary duct	UBERON:0001765	96.38	gold quality
renal medulla	UBERON:0000362	96.32	gold quality
adult organism	UBERON:0007023	96.30	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	14.83
E-GEOD-93593	yes	13.58

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

134 targeting MAGT1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-34C-5P	99.97	70.45	1577
HSA-MIR-449B-5P	99.97	70.26	1580
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-3910	99.95	71.13	2227
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-548AB	99.95	71.31	3488
HSA-MIR-548A-5P	99.94	71.27	3482
HSA-MIR-548AD-5P	99.94	71.23	3502

Functional genomics

ClinGen dosage: haploinsufficiency 3 (sufficient evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 20)

• identifed a novel gene that encodes a protein involved with Mg2+-evoked transport, MagT1; results suggest that MagT1 may provide a selective and regulated pathway for Mg2+ transport in epithelial cells[MagT1] (PMID:15804357)
• study shows that mutations in two OTase-subunit genes, N33/TUSC3 and IAP result in autosomal-recessive nonsyndromic mental retardation (PMID:18455129)
• MagT1 is universally expressed in all tissues and its expression level is up-regulated in low extracellular Mg(2+). Knockdown of either MagT1 or TUSC3 protein significantly lowers the total and free intracellular Mg(2+) concentrations in cell lines. (PMID:19717468)
• Data show that gene expression of the Mg(2+) selective transporter MagT1 is upregulated in TRPM7(-/-) cells. (PMID:21627970)
• A deficiency in magnesium transporter 1 (MAGT1), an Mg(2+)-specific transporter, leads to the absence of a T cell antigen receptor-stimulated Mg(2+)flux and an attenuation of T cell activation. (PMID:21983175)
• A 0.8 kb intronic duplication in MAGT1 and a single base pair deletion in the last exon of ATRX were identified in a family with five males demonstrating intellectual disability (ID) and unusual skin findings (e.g., generalized pruritus). (PMID:24130152)
• evaluation of MAGT1 and AKAP13 expression in clinical hepatocellular carcinoma tissues by immunohistochemistry suggested that both proteins were strongly expressed in tumor tissues with significantly higher average immunoreactive scores of Remmele and Stegner (IRS) than in non-tumor tissues (PMID:26617690)
• MAGT1 expression is defective in CD8+positive T cells of chronic hepatitis B patients. (PMID:29051561)
• TRPM7 and MagT1 are upregulated in osteogenic differentiation and silencing either one accelerates osteogenic differentiation, partly through the activation of autophagy. .. These results underpin the contribution of magnesium, TRPM7 and MagT1 to autophagy and osteoblastogenesis. (PMID:30385806)
• This study demonstrates that the simultaneous downregulation of TRPM7 and MagT1 inhibits cell growth and activates autophagy, which is required in the early phases of osteoblastogenesis. (PMID:30952425)
• microRNA-199a-5p suppresses glioma progression by inhibiting MAGT1. (PMID:31038761)
• Authors observed that MAGT1-dependent glycosylation is sensitive to Mg(2+) levels and that reduced Mg(2+) impairs immune-cell function via the loss of specific glycoproteins. Findings reveal that defects in protein glycosylation and gene expression underlie immune defects in an inherited disease due to MAGT1 deficiency. (PMID:31337704)
• TRPM7 and MagT1 regulate the proliferation of osteoblast-like SaOS-2 cells through different mechanisms. (PMID:32633723)
• miR-199a-5p targeted regulation of MAGT1 expression in the functional depletion of CD8(+)T cells in HBV infection. (PMID:33210605)
• CRISPR-targeted MAGT1 insertion restores XMEN patient hematopoietic stem cells and lymphocytes. (PMID:34086870)
• MAGT1 is required for HeLa cell proliferation through regulating p21 expression, S-phase progress, and ERK/p38 MAPK MYC axis. (PMID:34499581)
• Identification of a novel MAGT1 mutation supports a diagnosis of XMEN disease. (PMID:35264785)
• Long non-coding RNA FLVCR1-AS1 functions as a ceRNA to aggravate cervical cancer cell growth by the miR-381-3p/MAGT1 axis. (PMID:35430713)
• Transcription factor KLF16 activates MAGT1 to regulate the tumorigenesis and progression of breast cancer. (PMID:35796007)
• HLH and Recurrent EBV Lymphoma as the presenting manifestation of MAGT1 Deficiency: A Systematic Review of the Expanding Disease Spectrum. (PMID:38896122)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	magt1	ENSDARG00000058062
mus_musculus	Magt1	ENSMUSG00000031232
rattus_norvegicus	Magt1	ENSRNOG00000051408
drosophila_melanogaster	Ostgamma	FBGN0032015
caenorhabditis_elegans		WBGENE00022793

Paralogs (1): TUSC3 (ENSG00000104723)

Protein

Protein identifiers

Dolichyl-diphosphooligosaccharide–protein glycosyltransferase subunit MAGT1 — Q9H0U3 (reviewed: Q9H0U3)

Alternative names: Implantation-associated protein, Magnesium transporter protein 1

All UniProt accessions (8): Q9H0U3, A0A087WU53, A0A8I5KUC4, A0A8I5KY62, A0A8I5KYH1, A0A8I5QJJ8, A0A8I5QJM4, A0A8I5QKX7

UniProt curated annotations — full annotation on UniProt →

Function. Accessory component of the STT3B-containing form of the N-oligosaccharyl transferase (OST) complex which catalyzes the transfer of a high mannose oligosaccharide from a lipid-linked oligosaccharide donor to an asparagine residue within an Asn-X-Ser/Thr consensus motif in nascent polypeptide chains. Involved in N-glycosylation of STT3B-dependent substrates. Specifically required for the glycosylation of a subset of acceptor sites that are near cysteine residues; in this function seems to act redundantly with TUSC3. In its oxidized form proposed to form transient mixed disulfides with a glycoprotein substrate to facilitate access of STT3B to the unmodified acceptor site. Also has oxidoreductase-independent functions in the STT3B-containing OST complex possibly involving substrate recognition. Could indirectly play a role in Mg(2+) transport in epithelial cells.

Subunit / interactions. Accessory component of the STT3B-containing form of the oligosaccharyltransferase (OST) complex. OST exists in two different complex forms which contain common core subunits RPN1, RPN2, OST48, OST4, DAD1 and TMEM258, either STT3A or STT3B as catalytic subunits, and form-specific accessory subunits. OST can form stable complexes with the Sec61 complex or with both the Sec61 and TRAP complexes. The association of TUSC3 or MAGT1 with the STT3B-containing complex seems to be mutually exclusvice.

Subcellular location. Cell membrane. Endoplasmic reticulum. Endoplasmic reticulum membrane.

Tissue specificity. Ubiquitous. Expressed at very low levels in brain, lung and kidney.

Disease relevance. Immunodeficiency, X-linked, with magnesium defect, Epstein-Barr virus infection and neoplasia (XMEN) [MIM:300853] A disease characterized by CD4 lymphopenia, severe chronic viral infections, and defective T-lymphocyte activation. The disease is caused by variants affecting the gene represented in this entry. Congenital disorder of glycosylation 1CC (CDG1CC) [MIM:301031] A form of congenital disorder of glycosylation, a multisystem disorder caused by a defect in glycoprotein biosynthesis and characterized by under-glycosylated serum glycoproteins. Congenital disorders of glycosylation result in a wide variety of clinical features, such as defects in the nervous system development, psychomotor retardation, dysmorphic features, hypotonia, coagulation disorders, and immunodeficiency. The broad spectrum of features reflects the critical role of N-glycoproteins during embryonic development, differentiation, and maintenance of cell functions. CDG1CC is an X-linked recessive form mainly characterized by intellectual and developmental disability. The disease is caused by variants affecting the gene represented in this entry.

Induction. Up-regulated by low extracellular Mg(2+).

Pathway. Protein modification; protein glycosylation.

Similarity. Belongs to the OST3/OST6 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9H0U3-1	1	yes
Q9H0U3-2	2

RefSeq proteins (2): NP_001354845, NP_115497 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR021149	MAGT1/OST3/OST6	Family
IPR036249	Thioredoxin-like_sf	Homologous_superfamily

Pfam: PF04756

UniProt features (31 total): sequence variant 6, topological domain 5, helix 4, transmembrane region 4, splice variant 2, mutagenesis site 2, sequence conflict 2, signal peptide 1, chain 1, domain 1, glycosylation site 1, disulfide bond 1, strand 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
6S7T	ELECTRON MICROSCOPY	3.5

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9H0U3-F1	85.84	0.44

Functional residue map

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

Disulfide bonds (1): 87–90

Glycosylation sites (1): 71

Mutagenesis-validated functional residues (2):

Position	Phenotype
87	reduces n-glycosylation of cysteine-proximal acceptor sites; when associated with s-90.
90	reduces n-glycosylation of cysteine-proximal acceptor sites; when associated with s-87.

Function

Pathways and Gene Ontology

Reactome pathways

18 pathways

ID	Pathway
R-HSA-446203	Asparagine N-linked glycosylation
R-HSA-5223345	Miscellaneous transport and binding events
R-HSA-6798695	Neutrophil degranulation
R-HSA-9694548	Maturation of spike protein
R-HSA-9918432	Maturation of DENV proteins
R-HSA-9931295	PD-L1(CD274) glycosylation and translocation to plasma membrane
R-HSA-1643685	Disease
R-HSA-168249	Innate Immune System
R-HSA-168256	Immune System
R-HSA-382551	Transport of small molecules
R-HSA-392499	Metabolism of proteins
R-HSA-5663205	Infectious disease
R-HSA-597592	Post-translational protein modification
R-HSA-9679506	SARS-CoV Infections
R-HSA-9694516	SARS-CoV-2 Infection
R-HSA-9694635	Translation of Structural Proteins
R-HSA-9772573	Late SARS-CoV-2 Infection Events
R-HSA-9824446	Viral Infection Pathways

MSigDB gene sets: 274 (showing top): REACTOME_INNATE_IMMUNE_SYSTEM, GOBP_COGNITION, CCAWYNNGAAR_UNKNOWN, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, GOCC_VACUOLAR_MEMBRANE, GOCC_SECRETORY_GRANULE, MODULE_151, GOBP_PROTEIN_N_LINKED_GLYCOSYLATION, GOBP_MAGNESIUM_ION_TRANSPORT, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, GOBP_MONOATOMIC_CATION_TRANSPORT, GTGCCTT_MIR506, GAZDA_DIAMOND_BLACKFAN_ANEMIA_PROGENITOR_DN, GOBP_CARBOHYDRATE_DERIVATIVE_BIOSYNTHETIC_PROCESS, ACEVEDO_LIVER_TUMOR_VS_NORMAL_ADJACENT_TISSUE_DN

GO Biological Process (7): protein N-linked glycosylation (GO:0006487), magnesium ion transport (GO:0015693), obsolete protein N-linked glycosylation via asparagine (GO:0018279), cognition (GO:0050890), transmembrane transport (GO:0055085), magnesium ion transmembrane transport (GO:1903830), obsolete protein glycosylation (GO:0006486)

GO Molecular Function (1): magnesium ion transmembrane transporter activity (GO:0015095)

GO Cellular Component (7): endoplasmic reticulum (GO:0005783), endoplasmic reticulum membrane (GO:0005789), plasma membrane (GO:0005886), oligosaccharyltransferase complex (GO:0008250), membrane (GO:0016020), azurophil granule membrane (GO:0035577), oligosaccharyltransferase complex B (GO:0160227)

Reactome top-level categories

Rollup of top-14 pathways:

Category	Pathways
Post-translational protein modification	1
Transport of small molecules	1
Innate Immune System	1
Translation of Structural Proteins	1
Dengue Virus Genome Translation and Replication	1
Regulation of PD-L1(CD274) Post-translational modification	1
Immune System	1
Disease	1
Metabolism of proteins	1
Viral Infection Pathways	1
SARS-CoV Infections	1
Late SARS-CoV-2 Infection Events	1
SARS-CoV-2 Infection	1
Infectious disease	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
glycoprotein biosynthetic process	1
metal ion transport	1
nervous system process	1
transport	1
cellular process	1
magnesium ion transport	1
monoatomic cation transmembrane transport	1
metal ion transmembrane transporter activity	1
magnesium ion transmembrane transport	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
membrane	1
cell periphery	1
endoplasmic reticulum membrane	1
membrane protein complex	1
endoplasmic reticulum protein-containing complex	1
transferase complex	1
cellular anatomical structure	1
lysosomal membrane	1
secretory granule membrane	1
azurophil granule	1
oligosaccharyltransferase complex	1

Protein interactions and networks

STRING

1276 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MAGT1	STT3B	Q8TCJ2	899
MAGT1	STT3A	P46977	891
MAGT1	DAD1	P46966	878
MAGT1	RPN1	P04843	834
MAGT1	DDOST	P39656	826
MAGT1	RPN2	P04844	810
MAGT1	NIPAL3	Q6P499	789
MAGT1	SLC41A1	Q8IVJ1	764
MAGT1	TMEM258	P61165	763
MAGT1	NIPAL1	Q6NVV3	757
MAGT1	NIPAL2	Q9H841	755
MAGT1	OST4	P0C6T2	754
MAGT1	NIPAL4	Q0D2K0	733
MAGT1	NIPA2	Q8N8Q9	732
MAGT1	KRTCAP2	Q8N6L1	731

IntAct

141 interactions, top by confidence:

A	B	Type	Score
TSPAN5	ADAM10	psi-mi:“MI:0914”(association)	0.800
TCTN2	CLGN	psi-mi:“MI:0914”(association)	0.780
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
LDLRAD4	NEDD4	psi-mi:“MI:0914”(association)	0.690
CD27	TCAF2	psi-mi:“MI:0914”(association)	0.640
LRRC32	SMPD2	psi-mi:“MI:0914”(association)	0.640
CANX	PGRMC1	psi-mi:“MI:0914”(association)	0.570
RPN1	APBB1	psi-mi:“MI:0914”(association)	0.530
POMK	TMEM120B	psi-mi:“MI:0914”(association)	0.530
POGLUT1	CLGN	psi-mi:“MI:0914”(association)	0.530
RPN2	SMPD2	psi-mi:“MI:0914”(association)	0.530
SLC39A4	TMEM120B	psi-mi:“MI:0914”(association)	0.530
NPDC1	TCAF2	psi-mi:“MI:0914”(association)	0.530
C3orf18	SPAG9	psi-mi:“MI:0914”(association)	0.530
TOR1AIP1	TXN	psi-mi:“MI:0914”(association)	0.530
TUBA1A	TUBAL3	psi-mi:“MI:2364”(proximity)	0.420
NRAP	MAGT1	psi-mi:“MI:0915”(physical association)	0.400
ZFP14	MAGT1	psi-mi:“MI:0915”(physical association)	0.400
SPMIP7	MAGT1	psi-mi:“MI:0915”(physical association)	0.400
TOP2A	MAGT1	psi-mi:“MI:0915”(physical association)	0.400
LIMCH1	MAGT1	psi-mi:“MI:0915”(physical association)	0.400
PSMC3IP	MAGT1	psi-mi:“MI:0915”(physical association)	0.400
GNL2	MAGT1	psi-mi:“MI:0915”(physical association)	0.400
CLK3	MAGT1	psi-mi:“MI:0915”(physical association)	0.400
RGSL1	MAGT1	psi-mi:“MI:0915”(physical association)	0.400
COX10	MAGT1	psi-mi:“MI:0915”(physical association)	0.400
RAPGEF4	MAGT1	psi-mi:“MI:0915”(physical association)	0.400
ERGIC2	MAGT1	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (407): MAGT1 (Affinity Capture-RNA), MAGT1 (Affinity Capture-RNA), MAGT1 (Affinity Capture-MS), MAGT1 (Affinity Capture-MS), COX4I1 (Co-fractionation), MAGT1 (Co-fractionation), MAGT1 (Co-fractionation), MAGT1 (Co-fractionation), MAGT1 (Co-fractionation), MAGT1 (Co-fractionation), MAGT1 (Co-fractionation), MAGT1 (Co-fractionation), MAGT1 (Co-fractionation), SSR1 (Co-fractionation), STT3B (Co-fractionation)

ESM2 similar proteins: A2XSY1, A6QP01, A8WG88, F1QR43, O18756, O35777, O65085, O94923, P51398, P62341, P62342, Q07984, Q0IHY5, Q0JDK9, Q13454, Q1H5H1, Q2M146, Q2TBU2, Q2UF96, Q32L57, Q39080, Q4R5B4, Q58E26, Q5R419, Q5RE31, Q5RF53, Q5XIK2, Q5ZJ06, Q5ZJN8, Q62186, Q63ZR0, Q6DFS0, Q6IQC7, Q6PBD1, Q7TNK0, Q7ZV50, Q802F2, Q8BTV1, Q9CQY5, Q9D710

Diamond homologs: O35777, P34669, Q13454, Q32L57, Q5RE31, Q5ZJ06, Q63ZR0, Q7ZV50, Q8BTV1, Q9CQY5, Q9H0U3

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
MAGT1	“form complex”	“OST-B complex”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 178 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
PD-L1(CD274) glycosylation and translocation to plasma membrane	6	24.7×	2e-05
Maturation of spike protein	9	19.0×	5e-07
Regulation of CDH1 posttranslational processing and trafficking to plasma membrane	7	18.7×	2e-05
Maturation of DENV proteins	8	13.4×	2e-05
Antimicrobial mechanism of IFN-stimulated genes	6	9.4×	3e-03
Defective CFTR causes cystic fibrosis	5	8.7×	1e-02
The role of GTSE1 in G2/M progression after G2 checkpoint	6	7.7×	7e-03
Cilium Assembly	8	6.9×	2e-03

GO biological processes:

GO term	Partners	Fold	FDR
obsolete protein N-linked glycosylation via asparagine	5	22.3×	2e-03
ERAD pathway	9	10.8×	2e-04
protein N-linked glycosylation	6	10.5×	5e-03
smoothened signaling pathway	7	8.4×	5e-03
response to ethanol	8	7.8×	3e-03
positive regulation of cell migration	12	4.9×	3e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	28
Likely pathogenic	17
Uncertain significance	139
Likely benign	69
Benign	27

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1074386	NM_001367916.1(MAGT1):c.490G>T (p.Glu164Ter)	Pathogenic
1074984	NM_001367916.1(MAGT1):c.507G>A (p.Trp169Ter)	Pathogenic
1220528	NM_001367916.1(MAGT1):c.678dup (p.Val227fs)	Pathogenic
1220529	NM_001367916.1(MAGT1):c.707G>A (p.Trp236Ter)	Pathogenic
145142	GRCh38/hg38 Xq21.1(chrX:77798947-77887557)x2	Pathogenic
1458559	NM_001367916.1(MAGT1):c.909T>A (p.Cys303Ter)	Pathogenic
1527846	NM_001367916.1(MAGT1):c.484dup (p.Ser162fs)	Pathogenic
2120336	NM_001367916.1(MAGT1):c.751_752dup (p.Gly252fs)	Pathogenic
2808207	NM_001367916.1(MAGT1):c.462T>A (p.Tyr154Ter)	Pathogenic
2844435	NM_001367916.1(MAGT1):c.607_610del (p.Val203fs)	Pathogenic
29981	NM_001367916.1(MAGT1):c.826_826+9del	Pathogenic
29982	NM_001367916.1(MAGT1):c.313C>T (p.Arg105Ter)	Pathogenic
3245416	NC_000023.10:g.(?77126285)(77126442_?)del	Pathogenic
3728820	NM_001367916.1(MAGT1):c.502dup (p.Arg168fs)	Pathogenic
4071550	NM_001367916.1(MAGT1):c.493C>T (p.Gln165Ter)	Pathogenic
4726786	NM_001367916.1(MAGT1):c.418del (p.Ile140fs)	Pathogenic
539316	NM_001367916.1(MAGT1):c.127C>T (p.Gln43Ter)	Pathogenic
578831	NM_001367916.1(MAGT1):c.348dup (p.Ala117fs)	Pathogenic
625836	NM_001367916.1(MAGT1):c.972A>C (p.Lys324Asn)	Pathogenic
625837	NM_001367916.1(MAGT1):c.895C>T (p.Arg299Ter)	Pathogenic
625838	NM_001367916.1(MAGT1):c.842T>G (p.Leu281Ter)	Pathogenic
649134	NM_001367916.1(MAGT1):c.641_642insGA (p.Phe214fs)	Pathogenic
662023	NM_001367916.1(MAGT1):c.676_680del (p.Phe226fs)	Pathogenic
689408	NM_001367916.1(MAGT1):c.502del (p.Arg168fs)	Pathogenic
689409	NM_001367916.1(MAGT1):c.616C>T (p.Arg206Ter)	Pathogenic
689410	NM_001367916.1(MAGT1):c.459dup (p.Tyr154fs)	Pathogenic
844382	NM_001367916.1(MAGT1):c.272+1G>C	Pathogenic
976322	NM_001367916.1(MAGT1):c.948G>A (p.Trp316Ter)	Pathogenic
1067533	NC_000023.10:g.(?77084697)(77131114_?)del	Likely pathogenic
1348310	NM_001367916.1(MAGT1):c.673-1G>A	Likely pathogenic

SpliceAI

1763 predictions. Top by Δscore:

Variant	Effect	Δscore
X:77830891:CATTA:C	acceptor_gain	1.0000
X:77830896:C:CC	acceptor_gain	1.0000
X:77841244:A:AC	donor_gain	1.0000
X:77841245:C:CC	donor_gain	1.0000
X:77853904:A:C	donor_gain	1.0000
X:77855494:C:A	donor_gain	1.0000
X:77855589:CA:C	acceptor_gain	1.0000
X:77855591:C:CC	acceptor_gain	1.0000
X:77856869:CTAAT:C	acceptor_gain	1.0000
X:77856870:TAAT:T	acceptor_gain	1.0000
X:77856872:AT:A	acceptor_gain	1.0000
X:77856874:C:CC	acceptor_gain	1.0000
X:77857355:A:AC	donor_gain	1.0000
X:77857356:C:CC	donor_gain	1.0000
X:77870806:A:AC	donor_gain	1.0000
X:77870806:ACC:A	donor_loss	1.0000
X:77870807:C:CC	donor_gain	1.0000
X:77870807:CCAT:C	donor_gain	1.0000
X:77870943:C:CT	acceptor_gain	1.0000
X:77875426:A:AC	donor_gain	1.0000
X:77875427:C:CC	donor_gain	1.0000
X:77875429:TGCAA:T	donor_gain	1.0000
X:77875441:A:AC	donor_gain	1.0000
X:77875442:C:CC	donor_gain	1.0000
X:77875594:CCAT:C	acceptor_gain	1.0000
X:77875595:CATC:C	acceptor_gain	1.0000
X:77875596:ATC:A	acceptor_loss	1.0000
X:77875597:TC:T	acceptor_loss	1.0000
X:77875598:C:CA	acceptor_loss	1.0000
X:77875598:C:CC	acceptor_gain	1.0000

AlphaMissense

2218 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:77855552:G:C	N237K	1.000
X:77855552:G:T	N237K	1.000
X:77855555:C:A	W236C	1.000
X:77855555:C:G	W236C	1.000
X:77855557:A:G	W236R	1.000
X:77855557:A:T	W236R	1.000
X:77855565:C:T	G233D	1.000
X:77857478:G:T	P137Q	1.000
X:77857479:G:A	P137S	1.000
X:77857481:G:T	A136D	1.000
X:77870814:A:C	F128L	1.000
X:77870814:A:T	F128L	1.000
X:77870816:A:G	F128L	1.000
X:77875431:C:T	C90Y	1.000
X:77875440:C:T	C87Y	1.000
X:77830815:A:G	Y328H	0.999
X:77830825:T:A	K324N	0.999
X:77830825:T:G	K324N	0.999
X:77830826:T:A	K324I	0.999
X:77830827:T:C	K324E	0.999
X:77830834:A:C	F321L	0.999
X:77830834:A:T	F321L	0.999
X:77830836:A:G	F321L	0.999
X:77830880:C:T	G306D	0.999
X:77830881:C:G	G306R	0.999
X:77841302:C:T	G282E	0.999
X:77841303:C:G	G282R	0.999
X:77841303:C:T	G282R	0.999
X:77853921:G:A	T269I	0.999
X:77853923:T:A	E268D	0.999

dbSNP variants (sampled 300 via entrez): RS1000130478 (X:77826718 C>G), RS1000211348 (X:77839172 C>T), RS1000301615 (X:77894065 T>C), RS1000332186 (X:77894784 G>T), RS1000408561 (X:77847429 C>T), RS1000526892 (X:77885213 C>T), RS1000589676 (X:77875148 C>T), RS1000797090 (X:77830912 G>A), RS1000903834 (X:77855459 A>T), RS1000936303 (X:77856016 C>T), RS1000966006 (X:77885553 T>G), RS1001018934 (X:77846253 G>A), RS1001213315 (X:77848371 G>A,T), RS1001303005 (X:77839679 T>C), RS1001335633 (X:77840107 A>G)

Disease associations

OMIM: gene MIM:300715 | disease phenotypes: MIM:300853, MIM:301031

GenCC curated gene-disease

Disease	Classification	Inheritance
X-linked immunodeficiency with magnesium defect, Epstein-Barr virus infection and neoplasia	Strong	X-linked
intellectual disability, X-linked 95	Limited	X-linked

ClinGen Gene-Disease Validity (2)

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

Disease	Classification	Inheritance
X-linked immunodeficiency with magnesium defect, Epstein-Barr virus infection and neoplasia	Definitive	XL
X-linked intellectual disability	Disputed	XL

Mondo (4): X-linked immunodeficiency with magnesium defect, Epstein-Barr virus infection and neoplasia (MONDO:0010455), congenital disorder of glycosylation, type ICC (MONDO:0026729), congenital disorder of glycosylation (MONDO:0015286), intellectual disability, X-linked 95 (MONDO:0010413)

Orphanet (2): XMEN (Orphanet:317476), Congenital disorder of glycosylation (Orphanet:137)

HPO phenotypes

31 total (30 of 31 shown, HPO-id order):

HPO	Term
HP:0000403	Recurrent otitis media
HP:0001249	Intellectual disability
HP:0001263	Global developmental delay
HP:0001419	X-linked recessive inheritance
HP:0001744	Splenomegaly
HP:0001973	Autoimmune thrombocytopenia
HP:0002110	Bronchiectasis
HP:0002205	Recurrent respiratory infections
HP:0002240	Hepatomegaly
HP:0002665	Lymphoma
HP:0002716	Lymphadenopathy
HP:0002721	Immunodeficiency
HP:0002837	Recurrent bronchitis
HP:0002848	Decreased specific anti-polysaccharide antibody level
HP:0003621	Juvenile onset
HP:0003642	Type I transferrin isoform profile
HP:0004429	Recurrent viral infections
HP:0005419	Decreased T cell activation
HP:0005523	Lymphoproliferative disorder
HP:0011108	Recurrent sinusitis
HP:0011462	Young adult onset
HP:0012189	Hodgkin lymphoma
HP:0012191	B-cell lymphoma
HP:0020072	Persistent EBV viremia
HP:0031268	Decreased CD69 upregulation upon TCR activation
HP:0032170	Severe varicella zoster infection
HP:0032204	Chronic active Epstein-Barr virus infection
HP:0032218	Decreased CD4+ T cell proportion
HP:0032247	Persistent CMV viremia
HP:0033222	Inverted CD4:CD8 ratio

GWAS associations

0 associations (top):

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D018981	Congenital Disorders of Glycosylation	C16.320.565.202.125; C18.452.648.202.125
C567470	Mental Retardation, X-Linked 95 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6067103 (SINGLE PROTEIN)

PharmGKB: 1 entry (VIP=true, CPIC=false)

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: transporter — SLC58 MagT-like magnesium transporter family

ChEMBL bioactivities

4 potent at pChembl≥5 of 4 total, top 4 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.49	Kd	321.2	nM	CHEMBL3752910
6.49	ED50	321.2	nM	CHEMBL3752910
6.16	Kd	686.2	nM	CHEMBL5653589
6.16	ED50	686.2	nM	CHEMBL5653589

PubChem BioAssay actives

2 with measured affinity, of 4 total; 2 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
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148681: Binding affinity to human MAGT1 incubated for 45 mins by Kinobead based pull down assay	kd	0.3212	uM
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148681: Binding affinity to human MAGT1 incubated for 45 mins by Kinobead based pull down assay	kd	0.6862	uM

CTD chemical–gene interactions

33 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases expression	3
Valproic Acid	affects expression, increases expression	3
bisphenol F	increases expression, affects cotreatment	2
bisphenol S	affects expression, affects cotreatment, increases expression	2
dicrotophos	decreases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	affects cotreatment, increases expression	1
glycidyl methacrylate	decreases expression	1
trichostatin A	affects expression	1
di-n-butylphosphoric acid	affects expression	1
erucylphospho-N,N,N-trimethylpropylammonium	increases expression	1
ICG 001	increases expression	1
bisphenol B	increases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	increases expression	1
Temozolomide	decreases expression	1
Vorinostat	increases expression	1
Air Pollutants	decreases expression, increases abundance	1
Benzo(a)pyrene	affects methylation	1
Cadmium	increases abundance, increases expression	1
Clozapine	affects cotreatment, decreases expression	1
Cuprizone	affects cotreatment, decreases expression	1
Dexamethasone	affects cotreatment, increases expression	1
Doxorubicin	decreases expression	1
Indomethacin	affects cotreatment, increases expression	1
Ivermectin	decreases expression	1
Smoke	decreases expression	1
Vincristine	decreases expression	1
Zinc	increases expression	1
1-Methyl-3-isobutylxanthine	affects cotreatment, increases expression	1
Cyclosporine	increases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5651723	Binding	Binding affinity to human MAGT1 incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Cellosaurus cell lines

4 cell lines: 4 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B1WD	Abcam HeLa MAGT1 KO	Cancer cell line	Female
CVCL_D4G5	HCT116-MAGT1-KO-c6	Cancer cell line	Male
CVCL_D4G6	HCT116-MAGT1-KO-c8	Cancer cell line	Male
CVCL_XQ27	HAP1 MAGT1 (-)	Cancer cell line	Male

Clinical trials (associated diseases)

10 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT07572825	PHASE1	NOT_YET_RECRUITING	Assessing the Safety and Tolerability of NMN in DHDDS-CDG
NCT02496676	PHASE1/PHASE2	COMPLETED	Magnesium Supplementation in People With XMEN Syndrome
NCT02089789	Not specified	RECRUITING	Clinical and Basic Investigations Into Known and Suspected Congenital Disorders of Glycosylation
NCT02503267	Not specified	UNKNOWN	Incidence and Consequences of Disorders of Glycosylation in Patients With Conotruncal and Septal Heart Defects
NCT02955264	Not specified	COMPLETED	Using D-Galactose as a Food Supplement in Congenital Disorders of Glycosylation
NCT03250728	Not specified	COMPLETED	Role of the Endothelium in Stroke-like Episode Among CDG Patients
NCT03560570	Not specified	COMPLETED	Study of Hemostasis in Patients With Congenital Disorder of Glycosylation
NCT04198987	Not specified	COMPLETED	Dietary Monosaccharide Supplementation in Patients With Congenital Disorders of Glycosylation
NCT04199000	Not specified	RECRUITING	Clinical and Basic Investigations Into Congenital Disorders of Glycosylation
NCT04201067	Not specified	COMPLETED	Large-Scale Metabolomic Profiling for the Diagnosis of Inborn Errors of Metabolism