MAGED1

Summary

MAGED1 (MAGE family member D1, HGNC:6813) is a protein-coding gene on chromosome Xp11.22, encoding Melanoma-associated antigen D1 (Q9Y5V3). Involved in the apoptotic response after nerve growth factor (NGF) binding in neuronal cells.

This gene is a member of the melanoma antigen gene (MAGE) family. Most of the genes of this family encode tumor specific antigens that are not expressed in normal adult tissues except testis. Although the protein encoded by this gene shares strong homology with members of the MAGE family, it is expressed in almost all normal adult tissues. This gene has been demonstrated to be involved in the p75 neurotrophin receptor mediated programmed cell death pathway. Three transcript variants encoding two different isoforms have been found for this gene.

Source: NCBI Gene 9500 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 174 total
• Druggable target: yes
• MANE Select transcript: NM_006986

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6813
Approved symbol	MAGED1
Name	MAGE family member D1
Location	Xp11.22
Locus type	gene with protein product
Status	Approved
Aliases	NRAGE, DLXIN-1
Ensembl gene	ENSG00000179222
Ensembl biotype	protein_coding
OMIM	300224
Entrez	9500

Gene structure

Transcript identifiers

Ensembl transcripts: 49 — 43 protein_coding, 6 protein_coding_CDS_not_defined

ENST00000326587, ENST00000375695, ENST00000375722, ENST00000375772, ENST00000470461, ENST00000473931, ENST00000482188, ENST00000482599, ENST00000485420, ENST00000494718, ENST00000898263, ENST00000898264, ENST00000898265, ENST00000898266, ENST00000898267, ENST00000898268, ENST00000898269, ENST00000898270, ENST00000898271, ENST00000898272, ENST00000898273, ENST00000898274, ENST00000898275, ENST00000898276, ENST00000898277, ENST00000898278, ENST00000898279, ENST00000898280, ENST00000898281, ENST00000898282, ENST00000898283, ENST00000898284, ENST00000898285, ENST00000898286, ENST00000939076, ENST00000939077, ENST00000939078, ENST00000939079, ENST00000939080, ENST00000939081, ENST00000939082, ENST00000943445, ENST00000943446, ENST00000943447, ENST00000943448, ENST00000943449, ENST00000943450, ENST00000943451, ENST00000943452

RefSeq mRNA: 3 — MANE Select: NM_006986 NM_001005332, NM_001005333, NM_006986

CCDS: CCDS14337, CCDS35279

Canonical transcript exons

ENST00000326587 — 13 exons

Exon	Start	End
ENSE00001268937	51897795	51897886
ENSE00001269022	51898114	51898193
ENSE00001429859	51893623	51893755
ENSE00003461571	51898285	51898327
ENSE00003495162	51900182	51900296
ENSE00003496899	51898581	51898643
ENSE00003508513	51895053	51895760
ENSE00003565662	51897547	51897626
ENSE00003611842	51897208	51897271
ENSE00003633808	51894269	51894349
ENSE00003639183	51896409	51897077
ENSE00003643845	51901553	51901938
ENSE00003903935	51902146	51902354

Expression profiles

Bgee: expression breadth ubiquitous, 290 present calls, max score 99.16.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 258.5167 / max 2124.7771, expressed in 1809 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
196373	208.1122	1688
196367	48.0434	1766
209687	0.7947	565
196385	0.5510	321
196384	0.5131	301
196382	0.3089	138
196374	0.1934	72

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
ventricular zone	UBERON:0003053	99.16	gold quality
stromal cell of endometrium	CL:0002255	99.06	gold quality
ganglionic eminence	UBERON:0004023	99.04	gold quality
embryo	UBERON:0000922	98.99	gold quality
pituitary gland	UBERON:0000007	98.97	gold quality
adenohypophysis	UBERON:0002196	98.95	gold quality
tibia	UBERON:0000979	98.90	gold quality
frontal pole	UBERON:0002795	98.74	gold quality
cortical plate	UBERON:0005343	98.72	gold quality
middle temporal gyrus	UBERON:0002771	98.71	gold quality
right adrenal gland cortex	UBERON:0035827	98.54	gold quality
right adrenal gland	UBERON:0001233	98.50	gold quality
adrenal tissue	UBERON:0018303	98.46	gold quality
left adrenal gland cortex	UBERON:0035825	98.36	gold quality
islet of Langerhans	UBERON:0000006	98.34	gold quality
left adrenal gland	UBERON:0001234	98.29	gold quality
paraflocculus	UBERON:0005351	98.28	gold quality
adrenal cortex	UBERON:0001235	98.26	gold quality
adrenal gland	UBERON:0002369	98.10	gold quality
middle frontal gyrus	UBERON:0002702	98.09	gold quality
corpus epididymis	UBERON:0004359	98.09	gold quality
hypothalamus	UBERON:0001898	98.05	gold quality
placenta	UBERON:0001987	98.05	gold quality
periodontal ligament	UBERON:0008266	98.05	gold quality
Brodmann (1909) area 10	UBERON:0013541	98.00	gold quality
prefrontal cortex	UBERON:0000451	97.95	gold quality
right frontal lobe	UBERON:0002810	97.92	gold quality
cerebellar vermis	UBERON:0004720	97.89	gold quality
frontal cortex	UBERON:0001870	97.83	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	97.80	gold quality

Single-cell (SCXA)

Detected in 7 experiment(s), a significant marker in 6.

Experiment	Marker?	Max mean expression
E-MTAB-7008	yes	590.23
E-MTAB-6701	yes	117.64
E-ANND-3	yes	18.68
E-HCAD-13	yes	11.44
E-MTAB-9801	yes	6.09
E-MTAB-6678	yes	3.96
E-MTAB-7052	no	391.80

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

25 targeting MAGED1, 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-3148	99.97	75.06	6478
HSA-MIR-545-3P	99.95	70.74	2783
HSA-MIR-450B-5P	99.92	71.48	3175
HSA-MIR-548E-5P	99.89	72.73	4486
HSA-MIR-1323	99.83	69.89	2471
HSA-MIR-4668-5P	99.79	70.58	3782
HSA-MIR-4649-3P	99.56	66.90	1783
HSA-MIR-3120-3P	99.54	70.28	2669
HSA-MIR-4762-3P	99.43	69.72	2363
HSA-MIR-4777-5P	99.33	67.53	1148
HSA-MIR-421	98.90	67.04	1883
HSA-MIR-760	98.81	66.65	1392
HSA-MIR-3188	98.58	65.60	878
HSA-MIR-4709-5P	98.51	67.25	1335
HSA-MIR-4766-3P	98.48	67.94	1347
HSA-MIR-4252	98.45	66.37	987
HSA-MIR-4704-3P	98.28	69.33	1300
HSA-MIR-4457	98.09	67.12	1274
HSA-MIR-6783-5P	97.67	67.21	1528
HSA-MIR-8057	97.64	66.54	897
HSA-MIR-3157-5P	97.41	67.61	998
HSA-MIR-517-5P	97.13	68.43	781
HSA-MIR-3059-3P	96.71	67.08	606
HSA-MIR-6822-3P	96.60	66.06	680
HSA-MIR-1251-5P	95.78	64.10	374

Literature-anchored findings (GeneRIF, showing 27)

• A RING finger protein Praja1 regulates Dlx5-dependent transcription through its ubiquitin ligase activity for the Dlx/Msx-interacting MAGE/Necdin family protein, Dlxin-1. (PMID:11959851)
• hNRAGE arrests cell growth through a p53 dependent pathway. hNRAGE also increases the p53 protein level as well as its phosphorylation (Ser392). (PMID:15094062)
• The expression pattern of Maged1 roughly summarizes that of Maged2 and Maged3 (PMID:15162511)
• MAGE-D1 protein expression was reduced in 6 of 16 breast carcinoma cell lines as compared with untransformed immortal mammary epithelial cell lines; suppression of MAGE-D1 expression may be involved in the tumorigenesis of some sporadic breast cancers. (PMID:15930293)
• demonstrate the importance of human NRAGE in homotypic cell-to-cell adhesion and illuminate the mechanism of human NRAGE in the process of inhibition of cell adhesion (PMID:16125672)
• Data show that hNRAGE gene can inhibit the growth of 293 cells. (PMID:16388736)
• studies indicate for the first time that NRAGE could suppress metastasis of melanoma and pancreatic cancer probably through downregulation of MMP-2 (PMID:17140727)
• MAGE-D1 might be a novel inhibitor of angiogenesis in vitro and in vivo. (PMID:17149546)
• These findings provide new insight into the ability of MAGE-D1 to suppress the motility and adhesion response of tumor cells by interfering with actin cytoskeleton reorganization and hypoxia inducible factor 1-dependent gene expression. (PMID:17453828)
• Che-1 interacts with NRAGE and NRAGE overexpression downregulates endogenous Che-1 by targeting it for proteasome-dependent degradation. (PMID:17488777)
• Enhanced expression of MAGE-D1 by gene transfer could reverse the malignant phenotypes of breast cancer cells. (PMID:19639218)
• Data report that NRAGE, via the same XIAP-Tak1-Tab1 complex, is required for the phosphorylation of IKK -alpha/beta and subsequent transcriptional activation of the p65 subunit of NF-kappaB. (PMID:20100315)
• NRAGE may participate in the formation of radioresistance of TE13R120 cells by changing its subcellular localization, but its relationship with cell apoptosis has not been confirmed. (PMID:20868560)
• we establish the roles for Dlxin-1, one as an anti-tumorigenic and anti-invasive protein in high-grade gliomas and the other as an inducer of differentiation of glioma stem cells. (PMID:21109781)
• Univariate and multivariate analyses indicated that MAGED1 expression was an independent prognostic factor in colorectal carcinoma (PMID:22935435)
• MAGE-D1 plays important roles in the central nervous system in both developmental and adult stages. (PMID:23314527)
• High NRAGE expression is associated with esophageal carcinomas. (PMID:24710624)
• The ectopic subcellular localization of NRAGE mediated nuclear translocation of beta-catenin. (PMID:26738870)
• The nuclear localized NRAGE interacts with RNF8 and BARD1 to mediate the resistance of esophageal carcinomas cells against DNA-damaging agents. (PMID:27035619)
• MAGED1 binds and positively regulates the transcriptional activity of family members SIM1, SIM2, NPAS4 and ARNT2, but does not interact with AhR, HIF1alpha and ARNT. This interaction is mediated by PAS repeat regions which also form the interface for bHLH PAS dimerisation, and accordingly MAGED1 is not found in complex with bHLH PAS dimers. (PMID:27472814)
• Loss of GSPT2 and/or MAGED1 function may contribute to the intellectual disability. (PMID:28414775)
• our surprise, NRAGE induces nuclear localization of beta-catenin and increases its DNA binding ability. Further studies reveal that NRAGE leads to the modification of beta-catenin/Arm with O-linked beta-N-acetylglucosamine (O-GlcNAc), and failure of the association between beta-catenin/Arm and pygopus(pygo) protein, which is required for transcriptional activation of Wnt target genes. Therefore, our findings suggest a … (PMID:28427939)
• these results demonstrate the effective anti-autophagic of NRAGE in non-small-cell lung cancer cells through AMPK/Ulk1/Atg13 autophagy signaling pathways. Therefore, NRAGE could be used as a potential therapeutic target for lung cancer. (PMID:28639909)
• Our results indicate that NRAGE subcellular localization is related to radiation resistance of esophageal carcinoma cell and EMT may be involved in NRAGE subcellular location. (PMID:29516958)
• NRAGE upregulation was correlated with advanced TNM stage, local invasion, and poor survival. Importantly, NRAGE could serve as an independent prognostic factor in patients with gastric cancer. (PMID:29778424)
• NRAGE is significantly upregulated in patients with Hepatocellular Carcinoma. It could possibly be a novel diagnostic biomarker for HCC early detection. (PMID:30508943)
• Knockdown of NRAGE Impairs Homologous Recombination Repair and Sensitizes Hepatoblastoma Cells to Ionizing Radiation. (PMID:31916845)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	ndnl2	ENSDARG00000058212
mus_musculus	Maged1	ENSMUSG00000025151
rattus_norvegicus	Maged1	ENSRNOG00000006756
drosophila_melanogaster	MAGE	FBGN0037481

Paralogs (37): MAGEC2 (ENSG00000046774), TRO (ENSG00000067445), MAGEB2 (ENSG00000099399), MAGED2 (ENSG00000102316), MAGEB4 (ENSG00000120289), MAGEA9 (ENSG00000123584), MAGEA10 (ENSG00000124260), MAGEA4 (ENSG00000147381), MAGED4 (ENSG00000154545), MAGEC1 (ENSG00000155495), MAGEA8 (ENSG00000156009), MAGEC3 (ENSG00000165509), MAGEB6 (ENSG00000176746), MAGEB18 (ENSG00000176774), MAGEF1 (ENSG00000177383), MAGEB10 (ENSG00000177689), NDN (ENSG00000182636), MAGEB17 (ENSG00000182798), MAGEA2B (ENSG00000183305), NSMCE3 (ENSG00000185115), MAGEA11 (ENSG00000185247), MAGEE2 (ENSG00000186675), MAGED4B (ENSG00000187243), MAGEH1 (ENSG00000187601), MAGEB5 (ENSG00000188408), MAGEB16 (ENSG00000189023), MAGEA6 (ENSG00000197172), MAGEA1 (ENSG00000198681), MAGEB3 (ENSG00000198798), MAGEE1 (ENSG00000198934), MAGEA12 (ENSG00000213401), MAGEB1 (ENSG00000214107), MAGEA3 (ENSG00000221867), MAGEB6B (ENSG00000232030), MAGEL2 (ENSG00000254585), MAGEA9B (ENSG00000267978), MAGEA2 (ENSG00000268606)

Protein

Protein identifiers

Melanoma-associated antigen D1 — Q9Y5V3 (reviewed: Q9Y5V3)

Alternative names: MAGE tumor antigen CCF, MAGE-D1 antigen, Neurotrophin receptor-interacting MAGE homolog

All UniProt accessions (1): Q9Y5V3

UniProt curated annotations — full annotation on UniProt →

Function. Involved in the apoptotic response after nerve growth factor (NGF) binding in neuronal cells. Inhibits cell cycle progression, and facilitates NGFR-mediated apoptosis. May act as a regulator of the function of DLX family members. May enhance ubiquitin ligase activity of RING-type zinc finger-containing E3 ubiquitin-protein ligases. Proposed to act through recruitment and/or stabilization of the Ubl-conjugating enzyme (E2) at the E3:substrate complex. Plays a role in the circadian rhythm regulation. May act as RORA co-regulator, modulating the expression of core clock genes such as BMAL1 and NFIL3, induced, or NR1D1, repressed.

Subunit / interactions. Interacts with DLX5, DLX7 and MSX2 and forms homomultimers. Interacts with UNC5A. Interacts with TRIM28 and PJA1. Interacts with NGFR/p75NTR and RORA.

Subcellular location. Cytoplasm. Cell membrane. Nucleus.

Tissue specificity. Expressed in bone marrow stromal cells from both multiple myeloma patients and healthy donors. Seems to be ubiquitously expressed.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9Y5V3-1	1	yes
Q9Y5V3-2	2

RefSeq proteins (3): NP_001005332, NP_001005333, NP_008917* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002190	MHD_dom	Domain
IPR037445	MAGE	Family
IPR041898	MAGE_WH1	Homologous_superfamily
IPR041899	MAGE_WH2	Homologous_superfamily

Pfam: PF01454

UniProt features (42 total): repeat 22, compositionally biased region 8, region of interest 6, chain 1, domain 1, modified residue 1, splice variant 1, sequence variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9Y5V3-F1	51.21	0.17

Functional residue map

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

Post-translational modifications (1): 92

Function

Pathways and Gene Ontology

Reactome pathways

10 pathways

ID	Pathway
R-HSA-193648	NRAGE signals death through JNK
R-HSA-418889	Caspase activation via Dependence Receptors in the absence of ligand
R-HSA-9768919	NPAS4 regulates expression of target genes
R-HSA-109581	Apoptosis
R-HSA-162582	Signal Transduction
R-HSA-193704	p75 NTR receptor-mediated signalling
R-HSA-204998	Cell death signalling via NRAGE, NRIF and NADE
R-HSA-5357769	Caspase activation via extrinsic apoptotic signalling pathway
R-HSA-5357801	Programmed Cell Death
R-HSA-73887	Death Receptor Signaling

MSigDB gene sets: 321 (showing top): VALK_AML_WITH_FLT3_ITD, GOBP_CIRCADIAN_RHYTHM, GOBP_NEGATIVE_REGULATION_OF_EPITHELIAL_CELL_PROLIFERATION, GOBP_MORPHOGENESIS_OF_AN_EPITHELIUM, BORCZUK_MALIGNANT_MESOTHELIOMA_UP, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_REGULATION_OF_MORPHOGENESIS_OF_A_BRANCHING_STRUCTURE, TGCGCANK_UNKNOWN, GCANCTGNY_MYOD_Q6, KAAB_HEART_ATRIUM_VS_VENTRICLE_UP, GOZGIT_ESR1_TARGETS_DN, CHIANG_LIVER_CANCER_SUBCLASS_UNANNOTATED_DN, REACTOME_NRAGE_SIGNALS_DEATH_THROUGH_JNK, MITSIADES_RESPONSE_TO_APLIDIN_DN, GOBP_CIRCADIAN_REGULATION_OF_GENE_EXPRESSION

GO Biological Process (14): negative regulation of transcription by RNA polymerase II (GO:0000122), regulation of DNA-templated transcription (GO:0006355), circadian regulation of gene expression (GO:0032922), protein localization to nucleus (GO:0034504), regulation of circadian rhythm (GO:0042752), regulation of apoptotic process (GO:0042981), negative regulation of epithelial cell proliferation (GO:0050680), positive regulation of branching involved in ureteric bud morphogenesis (GO:0090190), negative regulation of protein localization to nucleus (GO:1900181), positive regulation of apoptotic signaling pathway (GO:2001235), regulation of transcription by RNA polymerase II (GO:0006357), negative regulation of DNA-templated transcription (GO:0045892), positive regulation of DNA-templated transcription (GO:0045893), rhythmic process (GO:0048511)

GO Molecular Function (3): transcription coactivator activity (GO:0003713), identical protein binding (GO:0042802), protein binding (GO:0005515)

GO Cellular Component (7): chromatin (GO:0000785), nucleus (GO:0005634), cytosol (GO:0005829), plasma membrane (GO:0005886), protein-containing complex (GO:0032991), cytoplasm (GO:0005737), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-8 pathways:

Category	Pathways
Cell death signalling via NRAGE, NRIF and NADE	1
Caspase activation via extrinsic apoptotic signalling pathway	1
Transcriptional Regulation by NPAS4	1
Programmed Cell Death	1
Death Receptor Signaling	1
p75 NTR receptor-mediated signalling	1
Apoptosis	1
Signal Transduction	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
DNA-templated transcription	3
regulation of DNA-templated transcription	3
transcription by RNA polymerase II	2
regulation of gene expression	2
circadian rhythm	2
regulation of transcription by RNA polymerase II	1
negative regulation of DNA-templated transcription	1
regulation of RNA biosynthetic process	1
protein localization to organelle	1
regulation of biological process	1
apoptotic process	1
regulation of programmed cell death	1
negative regulation of cell population proliferation	1
epithelial cell proliferation	1
regulation of epithelial cell proliferation	1
branching involved in ureteric bud morphogenesis	1
positive regulation of multicellular organismal process	1
regulation of branching involved in ureteric bud morphogenesis	1
positive regulation of morphogenesis of an epithelium	1
protein localization to nucleus	1
regulation of protein localization to nucleus	1
negative regulation of protein localization	1
positive regulation of signal transduction	1
positive regulation of apoptotic process	1
apoptotic signaling pathway	1
regulation of apoptotic signaling pathway	1
negative regulation of RNA biosynthetic process	1
positive regulation of RNA biosynthetic process	1
biological_process	1
transcription coregulator activity	1
positive regulation of DNA-templated transcription	1
protein binding	1
binding	1
chromosome	1
intracellular membrane-bounded organelle	1
cytoplasm	1
membrane	1
cell periphery	1
cellular_component	1

Protein interactions and networks

STRING

1086 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MAGED1	PJA1	Q8NG27	992
MAGED1	NGFR	P08138	942
MAGED1	DLX5	P56178	864
MAGED1	XIAP	P98170	834
MAGED1	PJA2	O43164	718
MAGED1	TAB1	Q15750	700
MAGED1	BEX3	Q00994	677
MAGED1	UNC5A	Q6ZN44	602
MAGED1	AATF	Q9NY61	591
MAGED1	TUBB2A	Q13885	541
MAGED1	NGF	P01138	536
MAGED1	NTRK1	P04629	526
MAGED1	UBE2D2	P51669	525
MAGED1	CENPVL1	A0A0U1RR11	516
MAGED1	TUBB	P05218	497

IntAct

518 interactions, top by confidence:

A	B	Type	Score
MAGED1	CA8	psi-mi:“MI:0915”(physical association)	0.810
MAGED1	KRTAP19-5	psi-mi:“MI:0915”(physical association)	0.810
KRTAP19-5	MAGED1	psi-mi:“MI:0915”(physical association)	0.810
CA8	MAGED1	psi-mi:“MI:0915”(physical association)	0.810
BHLHE40	MAGED1	psi-mi:“MI:0915”(physical association)	0.720
MAGED1	BAG3	psi-mi:“MI:0915”(physical association)	0.720
MAGED1	SMAP2	psi-mi:“MI:0915”(physical association)	0.720
TFG	MAGED1	psi-mi:“MI:0915”(physical association)	0.720
RHOXF2	MAGED1	psi-mi:“MI:0915”(physical association)	0.720
MAGED1	TFG	psi-mi:“MI:0915”(physical association)	0.720
MDFI	MAGED1	psi-mi:“MI:0915”(physical association)	0.720
SMAP2	MAGED1	psi-mi:“MI:0915”(physical association)	0.720
MAGED1	MDFI	psi-mi:“MI:0915”(physical association)	0.720
MAGED1	BHLHE40	psi-mi:“MI:0915”(physical association)	0.720
BAG3	MAGED1	psi-mi:“MI:0915”(physical association)	0.720
HGS	MAGED1	psi-mi:“MI:0915”(physical association)	0.720

BioGRID (372): MAGED1 (Two-hybrid), MAGED1 (Two-hybrid), MAGED1 (Two-hybrid), MAGED1 (Two-hybrid), MAGED1 (Two-hybrid), MAGED1 (Two-hybrid), MAGED1 (Two-hybrid), MAGED1 (Two-hybrid), MAGED1 (Two-hybrid), MAGED1 (Two-hybrid), BAG3 (Two-hybrid), AKAP9 (Two-hybrid), TFG (Two-hybrid), RBPMS (Two-hybrid), RBFOX2 (Two-hybrid)

ESM2 similar proteins: A0A1B0GTS1, A0A1B0GWH4, A0A1L8HTT5, A1A5P9, A3A8Q4, A6H8Z2, A6QLI5, D3YZV8, F1N4E5, P12977, P62521, P86174, Q12816, Q3KST2, Q5JTV8, Q5PQX1, Q5R6R8, Q5R7A3, Q5RFC2, Q5XIV2, Q66HD8, Q69138, Q6A058, Q6I6G8, Q6ITT4, Q6PCZ4, Q6ZU67, Q76N89, Q7L311, Q7T3T8, Q7TQI8, Q80VM8, Q86V59, Q8C627, Q8K4P8, Q921T2, Q96DT7, Q96JG8, Q96P26, Q9BE64

Diamond homologs: A0A0J9YX57, A1A5P9, A2A368, A2A9R3, A6NCF6, A6QLI5, A8MXT2, O15479, O15480, O15481, O60732, P25233, P43355, P43356, P43357, P43358, P43360, P43361, P43362, P43363, P43364, P43365, P43366, Q12816, Q4R998, Q5PPP4, Q5RFC2, Q6AY37, Q6ITT4, Q6PCZ4, Q8BQR7, Q8N7X4, Q8TD90, Q8TD91, Q96JG8, Q96LZ2, Q96M61, Q96MG7, Q99608, Q9BE18

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
MAGED1	up-regulates	CDKN1A
MAGED1	up-regulates	Skeletal_muscle_differentiation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 107 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
Post NMDA receptor activation events	5	14.4×	5e-03
Regulation of HSF1-mediated heat shock response	7	13.7×	3e-04
Activation of NMDA receptors and postsynaptic events	5	13.0×	5e-03
Loss of Nlp from mitotic centrosomes	5	11.2×	5e-03
Loss of proteins required for interphase microtubule organization from the centrosome	5	11.2×	5e-03
AURKA Activation by TPX2	5	10.7×	5e-03
ISG15 antiviral mechanism	5	10.6×	5e-03
Recruitment of NuMA to mitotic centrosomes	6	9.8×	5e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	81
Likely benign	7
Benign	4

Top pathogenic / likely-pathogenic (0)

SpliceAI

2144 predictions. Top by Δscore:

Variant	Effect	Δscore
X:51803116:AGGTG:A	donor_loss	1.0000
X:51803118:G:GG	donor_gain	1.0000
X:51803119:T:A	donor_loss	1.0000
X:51895052:GGCT:G	acceptor_gain	1.0000
X:51895758:AAGG:A	donor_loss	1.0000
X:51895759:AGGTG:A	donor_loss	1.0000
X:51895761:GTGA:G	donor_loss	1.0000
X:51895762:T:A	donor_loss	1.0000
X:51897203:CCCA:C	acceptor_loss	1.0000
X:51897205:CA:C	acceptor_loss	1.0000
X:51897206:A:AC	acceptor_loss	1.0000
X:51897206:A:AG	acceptor_gain	1.0000
X:51897206:AG:A	acceptor_gain	1.0000
X:51897207:G:GT	acceptor_gain	1.0000
X:51897207:GG:G	acceptor_gain	1.0000
X:51897207:GGC:G	acceptor_gain	1.0000
X:51897207:GGCA:G	acceptor_gain	1.0000
X:51897207:GGCAA:G	acceptor_gain	1.0000
X:51897270:AG:A	donor_loss	1.0000
X:51897271:GG:G	donor_loss	1.0000
X:51897272:GT:G	donor_loss	1.0000
X:51897273:T:G	donor_loss	1.0000
X:51897541:CTACA:C	acceptor_loss	1.0000
X:51897542:TACA:T	acceptor_loss	1.0000
X:51897543:ACAG:A	acceptor_loss	1.0000
X:51897544:CA:C	acceptor_loss	1.0000
X:51897545:A:AG	acceptor_gain	1.0000
X:51897545:AGA:A	acceptor_loss	1.0000
X:51897546:G:GC	acceptor_gain	1.0000
X:51897546:GA:G	acceptor_gain	1.0000

AlphaMissense

5101 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:51897221:T:A	V479D	1.000
X:51897550:T:G	M497R	1.000
X:51897606:G:C	A516P	1.000
X:51897619:T:C	L520P	1.000
X:51897798:T:C	F524L	1.000
X:51897800:T:A	F524L	1.000
X:51897800:T:G	F524L	1.000
X:51897811:T:C	L528P	1.000
X:51898155:T:C	L567P	1.000
X:51898157:G:C	G568R	1.000
X:51898158:G:A	G568D	1.000
X:51898167:T:C	F571S	1.000
X:51898176:G:T	G574V	1.000
X:51898293:T:A	W583R	1.000
X:51898293:T:C	W583R	1.000
X:51898295:G:C	W583C	1.000
X:51898295:G:T	W583C	1.000
X:51898303:T:C	L586P	1.000
X:51900187:T:C	L617P	1.000
X:51900231:T:C	F632L	1.000
X:51900232:T:C	F632S	1.000
X:51900233:C:A	F632L	1.000
X:51900233:C:G	F632L	1.000
X:51900237:T:A	W634R	1.000
X:51900237:T:C	W634R	1.000
X:51900238:G:C	W634S	1.000
X:51900239:G:C	W634C	1.000
X:51900239:G:T	W634C	1.000
X:51900240:G:C	G635R	1.000
X:51900269:G:C	K644N	1.000

dbSNP variants (sampled 300 via entrez): RS1000077883 (X:51811691 C>T), RS1000214017 (X:51881458 C>G,T), RS1000275595 (X:51873296 C>T), RS1000375412 (X:51802936 A>G), RS1000468023 (X:51821171 T>C), RS1000551857 (X:51814491 A>G), RS1000574155 (X:51884130 G>A), RS1000603029 (X:51875531 A>G), RS1000727305 (X:51802542 A>T), RS1000822876 (X:51860113 A>C), RS1000924881 (X:51852074 C>T), RS1001075707 (X:51842045 A>G), RS1001119288 (X:51861884 G>C), RS1001254409 (X:51854878 T>A), RS1001264942 (X:51862791 A>G)

Disease associations

OMIM: gene MIM:300224 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST011354_45	Bell’s palsy	6.000000e-06

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4742325 (PROTEIN-PROTEIN INTERACTION)

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Cyclosporine	decreases expression	4
Air Pollutants	decreases expression, increases abundance, increases expression	3
Benzo(a)pyrene	affects methylation, decreases expression	3
Valproic Acid	affects expression, decreases expression, increases expression	3
bisphenol A	affects expression, decreases expression	2
cobaltous chloride	decreases expression	2
Fluorouracil	affects response to substance	2
Aflatoxin B1	increases methylation, decreases expression, decreases methylation	2
Particulate Matter	decreases expression, increases abundance	2
aristolochic acid I	decreases expression	1
FR900359	increases phosphorylation	1
TAK-243	increases sumoylation	1
dicrotophos	increases expression	1
pirinixic acid	affects binding, decreases expression, increases activity	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
sodium arsenite	affects cotreatment, decreases expression, increases abundance	1
manganese chloride	affects cotreatment, decreases expression, increases abundance	1
benzo(e)pyrene	increases methylation	1
aflatoxin B2	increases methylation	1
columbamine	decreases expression	1
cyanoginosin LR	decreases expression	1
chloropicrin	increases expression	1
jinfukang	increases reaction, increases expression	1
Acetaminophen	decreases expression	1
Arsenic	affects cotreatment, decreases expression, increases abundance	1
Azathioprine	decreases expression	1
Cisplatin	increases reaction, increases expression	1
Cyclophosphamide	affects response to substance	1
Dexamethasone	decreases expression	1
Manganese	affects cotreatment, decreases expression, increases abundance	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
CHEMBL4713751	Binding	Protac activity at CRBN/MAGED1 in human BxPC-3 cells assessed as MAGED1 degradation incubated for 16 hrs by proteomic analysis	Discovery of a Napabucasin PROTAC as an Effective Degrader of the E3 Ligase ZFP91. — J Med Chem

Clinical trials (associated diseases)

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