MAGED4

Summary

MAGED4 (MAGE family member D4, HGNC:23793) is a protein-coding gene on chromosome Xp11.22, encoding Melanoma-associated antigen D4 (Q96JG8). May enhance ubiquitin ligase activity of RING-type zinc finger-containing E3 ubiquitin-protein ligases.

Predicted to be involved in negative regulation of transcription by RNA polymerase II. Predicted to be active in nucleus.

Source: NCBI Gene 728239 — RefSeq curated summary.

At a glance

• MANE Select transcript: NM_001272063

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:23793
Approved symbol	MAGED4
Name	MAGE family member D4
Location	Xp11.22
Locus type	gene with protein product
Status	Approved
Aliases	MAGE1, MGC3210, KIAA1859, MAGE-E1
Ensembl gene	ENSG00000154545
Ensembl biotype	protein_coding
OMIM	300702
Entrez	728239

Gene structure

Transcript identifiers

Ensembl transcripts: 24 — 19 protein_coding, 3 protein_coding_CDS_not_defined, 2 retained_intron

ENST00000375626, ENST00000467526, ENST00000471932, ENST00000474812, ENST00000477634, ENST00000479281, ENST00000497348, ENST00000497416, ENST00000498483, ENST00000599522, ENST00000880895, ENST00000880896, ENST00000880897, ENST00000880898, ENST00000880899, ENST00000880900, ENST00000924627, ENST00000924628, ENST00000924629, ENST00000924630, ENST00000924631, ENST00000924632, ENST00000953414, ENST00000953415

RefSeq mRNA: 4 — MANE Select: NM_001272063 NM_001098800, NM_001272061, NM_001272062, NM_001272063

CCDS: CCDS48116, CCDS65261, CCDS94608

Canonical transcript exons

ENST00000471932 — 13 exons

Exon	Start	End
ENSE00001923584	52184888	52184965
ENSE00003089131	52191431	52191861
ENSE00003164743	52192057	52192268
ENSE00003545134	52185892	52186132
ENSE00003711651	52186397	52187230
ENSE00003714053	52190994	52191108
ENSE00003715737	52189986	52190048
ENSE00003726930	52187642	52187845
ENSE00003730460	52188206	52188285
ENSE00003738659	52188674	52188765
ENSE00003742690	52187949	52188012
ENSE00003752612	52189552	52189594
ENSE00003753045	52189387	52189466

Expression profiles

Bgee: expression breadth ubiquitous, 133 present calls, max score 97.31.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 3.6013 / max 51.4260, expressed in 1022 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
196386	2.3604	879
196387	1.2409	725

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cortical plate	UBERON:0005343	97.31	gold quality
ganglionic eminence	UBERON:0004023	96.17	gold quality
ventricular zone	UBERON:0003053	95.45	gold quality
stromal cell of endometrium	CL:0002255	94.80	gold quality
hypothalamus	UBERON:0001898	92.49	gold quality
pituitary gland	UBERON:0000007	91.85	gold quality
adenohypophysis	UBERON:0002196	90.55	gold quality
amygdala	UBERON:0001876	89.09	gold quality
temporal lobe	UBERON:0001871	88.99	gold quality
nucleus accumbens	UBERON:0001882	88.98	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	88.30	gold quality
Ammon’s horn	UBERON:0001954	87.22	gold quality
substantia nigra	UBERON:0002038	87.21	gold quality
anterior cingulate cortex	UBERON:0009835	86.98	gold quality
superior frontal gyrus	UBERON:0002661	86.42	gold quality
cerebral cortex	UBERON:0000956	85.78	gold quality
right frontal lobe	UBERON:0002810	85.65	gold quality
brain	UBERON:0000955	85.38	gold quality
frontal cortex	UBERON:0001870	85.21	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	84.70	gold quality
prefrontal cortex	UBERON:0000451	84.64	gold quality
caudate nucleus	UBERON:0001873	84.56	gold quality
putamen	UBERON:0001874	83.35	gold quality
Brodmann (1909) area 9	UBERON:0013540	83.29	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	83.25	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	82.23	gold quality
right ovary	UBERON:0002118	81.88	gold quality
islet of Langerhans	UBERON:0000006	81.30	gold quality
primary visual cortex	UBERON:0002436	80.32	gold quality
ovary	UBERON:0000992	80.03	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-HCAD-13	yes	80.70
E-HCAD-5	yes	18.21
E-GEOD-99795	no	34.33
E-ANND-3	no	2.76

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

14 targeting MAGED4, 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-6077	99.99	68.04	2299
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-141-3P	99.94	72.79	2421
HSA-MIR-200A-3P	99.94	72.68	2420
HSA-MIR-6835-3P	99.93	70.49	2904
HSA-MIR-450B-5P	99.92	71.48	3175
HSA-MIR-4698	99.84	71.41	4303
HSA-MIR-379-3P	99.69	69.60	1524
HSA-MIR-411-3P	99.69	69.63	1524
HSA-MIR-891B	99.59	69.81	1083
HSA-MIR-6165	99.44	67.12	1389
HSA-MIR-4457	98.09	67.12	1274
HSA-MIR-3200-5P	97.34	65.97	826
HSA-MIR-4435	95.90	65.47	1201

Literature-anchored findings (GeneRIF, showing 7)

• Results suggest that MAGE-D4 overexpression influences tumor progression, and MADE-D4 can be a prognostic marker and a potential molecular target in squamous cell esophageal cancer. (PMID:24147998)
• MAGED4 (mRNA and protein) is frequently and highly expressed in glioma and is partly regulated by DNA methylation. (PMID:24870746)
• MAGE-D4 is highly expressed in glioma and can develop specifically humoral response in glioma patients. (PMID:24966945)
• These findings suggest MAGE-D4 may serve as a potentially prognostic biomarker and an attractive target of immunotherapy in colorectal cancer (PMID:25120768)
• Preoperative serum MAGED4 was significantly higher in esophageal squamous cell carcinoma patients than in controls. (PMID:25951896)
• The MAGE-D4 polyclonal antibody with high specificity and sensitivity has been successfully prepared. (PMID:28031124)
• High MAGED4 expression is associated with Esophageal Squamous Cell Carcinoma. (PMID:31704827)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
danio_rerio	ndnl2	ENSDARG00000058212
drosophila_melanogaster	MAGE	FBGN0037481

Paralogs (37): MAGEC2 (ENSG00000046774), TRO (ENSG00000067445), MAGEB2 (ENSG00000099399), MAGED2 (ENSG00000102316), MAGEB4 (ENSG00000120289), MAGEA9 (ENSG00000123584), MAGEA10 (ENSG00000124260), MAGEA4 (ENSG00000147381), MAGEC1 (ENSG00000155495), MAGEA8 (ENSG00000156009), MAGEC3 (ENSG00000165509), MAGEB6 (ENSG00000176746), MAGEB18 (ENSG00000176774), MAGEF1 (ENSG00000177383), MAGEB10 (ENSG00000177689), MAGED1 (ENSG00000179222), 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 D4 — Q96JG8 (reviewed: Q96JG8)

Alternative names: MAGE-D4 antigen, MAGE-E1 antigen

All UniProt accessions (3): Q96JG8, A0A804HHZ9, A0A804HKI1

UniProt curated annotations — full annotation on UniProt →

Function. 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.

Subunit / interactions. Interacts with TRIM27.

Tissue specificity. Expressed only in brain and ovary among normal tissues. Isoform 1 and isoform 2 are specifically expressed in glioma cells among cancer cells. Detected in some renal cell carcinoma samples.

Isoforms (4)

UniProt ID	Names	Canonical?
Q96JG8-1	1, MAGE-E1a	yes
Q96JG8-2	2, MAGE-E1b
Q96JG8-3	3, MAGE-E1c
Q96JG8-4	4

RefSeq proteins (4): NP_001092270, NP_001258990, NP_001258991, NP_001258992* (*=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 (19 total): compositionally biased region 6, region of interest 5, splice variant 4, sequence conflict 2, chain 1, domain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96JG8-F1	54.47	0.08

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 14 (showing top): STAEGE_EWING_FAMILY_TUMOR, DELYS_THYROID_CANCER_DN, GCM_BMPR2, chrXp11, GOBP_NEGATIVE_REGULATION_OF_TRANSCRIPTION_BY_RNA_POLYMERASE_II, GOBP_NEGATIVE_REGULATION_OF_NUCLEOBASE_CONTAINING_COMPOUND_METABOLIC_PROCESS, KIM_MYCN_AMPLIFICATION_TARGETS_DN, MIR450B_5P, MIR6835_3P, MIR891B, HE_LIM_SUN_FETAL_LUNG_C3_INTERMEDIATE_LYMPHATIC_ENDO_CELL, HE_LIM_SUN_FETAL_LUNG_C3_LYMPHATIC_ENDOTHELIAL_CELL, HE_LIM_SUN_FETAL_LUNG_C3_SCG3_POS_LYMPHATIC_ENDOTHELIAL_CELL, GOBP_NEGATIVE_REGULATION_OF_RNA_BIOSYNTHETIC_PROCESS

GO Biological Process (1): negative regulation of transcription by RNA polymerase II (GO:0000122)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (1): nucleus (GO:0005634)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
negative regulation of DNA-templated transcription	1
binding	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

544 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MAGED4	HSPA4	P34932	887
MAGED4	CTAG1A	P78358	696
MAGED4	PMEL	P40967	690
MAGED4	IL13RA2	Q14627	678
MAGED4	GAGE4	P0DSO3	666
MAGED4	TUBB2A	Q13885	606
MAGED4	TUBB	P05218	586
MAGED4	TYR	P14679	583
MAGED4	PRAME	P78395	571
MAGED4	SSX4	O60224	541
MAGED4	CD8A	P01732	538
MAGED4	SSX1	Q16384	507
MAGED4	ICAM1	P05362	501
MAGED4	OIP5	O43482	476
MAGED4	CTAG2	O75638	474

IntAct

45 interactions, top by confidence:

A	B	Type	Score
RCCD1	SPAG9	psi-mi:“MI:0914”(association)	0.640
TSPYL6	USP12	psi-mi:“MI:0914”(association)	0.640
LCN2	MAGED4B	psi-mi:“MI:0915”(physical association)	0.560
CEND1	MAGED4B	psi-mi:“MI:0915”(physical association)	0.560
INCA1	MAGED4B	psi-mi:“MI:0915”(physical association)	0.560
MAGED4B	FAM86C1P	psi-mi:“MI:0915”(physical association)	0.560
PJA1	SMC5	psi-mi:“MI:0914”(association)	0.530
SPSB2	ARHGEF10	psi-mi:“MI:0914”(association)	0.530
SPSB4	ARHGEF10	psi-mi:“MI:0914”(association)	0.530
MAGED4B	NSMCE4A	psi-mi:“MI:0915”(physical association)	0.400
MAGED4B	EID3	psi-mi:“MI:0915”(physical association)	0.400
TRIM27	MAGED4B	psi-mi:“MI:0915”(physical association)	0.400
MAGED4B	MAPK8IP2	psi-mi:“MI:0915”(physical association)	0.370
CHM	POLR3A	psi-mi:“MI:0914”(association)	0.350
P		psi-mi:“MI:0914”(association)	0.350
M		psi-mi:“MI:0914”(association)	0.350
TXNIP	ZSWIM8	psi-mi:“MI:0914”(association)	0.350
PTGES3	KIFBP	psi-mi:“MI:0914”(association)	0.350
AP2M1	C1orf226	psi-mi:“MI:0914”(association)	0.350
DUSP16	MEIOC	psi-mi:“MI:0914”(association)	0.350
PTGES3	SBNO1	psi-mi:“MI:0914”(association)	0.350
SPSB4	CCDC85C	psi-mi:“MI:0914”(association)	0.350
TSPYL6	ZSWIM8	psi-mi:“MI:0914”(association)	0.350
HASPIN	TP73	psi-mi:“MI:0914”(association)	0.350
ARHGAP36	PJA2	psi-mi:“MI:0914”(association)	0.350
NSMCE3	PJA2	psi-mi:“MI:0914”(association)	0.350
RNASEH1	NKTR	psi-mi:“MI:0914”(association)	0.350
WDR5B	HSPA8	psi-mi:“MI:0914”(association)	0.350
AP2M1	PER1	psi-mi:“MI:0914”(association)	0.350

BioGRID (44): MAGED4B (Affinity Capture-MS), MAGED4B (Affinity Capture-MS), MAGED4B (Affinity Capture-MS), MAGED4B (Affinity Capture-MS), MAGED4B (Affinity Capture-MS), MAGED4B (Affinity Capture-MS), MAGED4 (Affinity Capture-MS), MAGED4B (Two-hybrid), MAGED4B (Two-hybrid), MAGED4B (Two-hybrid), MAGED4B (Two-hybrid), INCA1 (Two-hybrid), MAGED4B (Affinity Capture-MS), MAGED4B (Affinity Capture-MS), MAGED4B (Affinity Capture-MS)

ESM2 similar proteins: A0A494C086, A0A494C0Z2, A0A494C191, A0JPH4, A6NHP3, A6NIY4, A6NJR5, A6NLX3, A6NNV3, A6QLI5, B0BNE4, O08918, O60543, O70302, O75916, P0CI01, P0DTA3, P0DUD1, P0DUD2, P0DUD3, P0DUD4, P0DUX0, P0DUX1, P0DV79, P24864, P39949, P49805, Q12967, Q495Y7, Q495Y8, Q4VXA5, Q4ZIN3, Q5IBH6, Q5IBH7, Q5MJ70, Q5SYB0, Q5XIQ2, Q5ZJR9, Q61457, Q6AYG1

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

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 53 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.

GO biological processes:

GO term	Partners	Fold	FDR
protein sumoylation	5	34.5×	3e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

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

Top pathogenic / likely-pathogenic (0)

SpliceAI

2200 predictions. Top by Δscore:

Variant	Effect	Δscore
X:52185910:T:TA	acceptor_gain	1.0000
X:52187640:A:AG	acceptor_gain	1.0000
X:52187641:G:GG	acceptor_gain	1.0000
X:52187932:T:G	acceptor_gain	1.0000
X:52187944:TCCA:T	acceptor_loss	1.0000
X:52187946:CAGG:C	acceptor_loss	1.0000
X:52187947:A:AG	acceptor_gain	1.0000
X:52187947:AG:A	acceptor_gain	1.0000
X:52187948:G:GA	acceptor_gain	1.0000
X:52187948:GG:G	acceptor_gain	1.0000
X:52187948:GGC:G	acceptor_gain	1.0000
X:52187948:GGCA:G	acceptor_gain	1.0000
X:52187948:GGCAA:G	acceptor_gain	1.0000
X:52188009:GCAG:G	donor_gain	1.0000
X:52188010:CAGG:C	donor_loss	1.0000
X:52188011:AGGTA:A	donor_loss	1.0000
X:52188012:GGTA:G	donor_loss	1.0000
X:52188013:G:GG	donor_gain	1.0000
X:52188201:T:TA	acceptor_gain	1.0000
X:52188202:GCAG:G	acceptor_loss	1.0000
X:52188203:CAGA:C	acceptor_loss	1.0000
X:52188204:A:AG	acceptor_gain	1.0000
X:52188204:AG:A	acceptor_loss	1.0000
X:52188205:G:GT	acceptor_gain	1.0000
X:52188205:GA:G	acceptor_gain	1.0000
X:52188205:GAC:G	acceptor_gain	1.0000
X:52188205:GACA:G	acceptor_gain	1.0000
X:52188205:GACAT:G	acceptor_gain	1.0000
X:52188668:A:AG	acceptor_gain	1.0000
X:52188669:C:CA	acceptor_gain	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 160 via entrez): RS112352914 (X:52191946 G>A,C), RS1557383693 (X:52185236 A>C), RS1557383696 (X:52186550 G>A), RS1557383697 (X:52187819 C>G), RS1557383700 (X:52188866 C>G), RS1557383702 (X:52189433 G>A), RS1557383703 (X:52189482 T>C), RS1557383705 (X:52189540 C>T), RS1557383707 (X:52189899 G>A), RS1557383708 (X:52190477 G>A), RS1557383710 (X:52191439 C>A), RS1557383711 (X:52191441 G>A), RS1557383714 (X:52191525 A>G), RS1557383716 (X:52191559 C>T), RS1557383717 (X:52191570 C>T)

Disease associations

OMIM: gene MIM:300702 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

12 total (human), top 12 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Estradiol	affects cotreatment, decreases expression	2
Progesterone	affects cotreatment, decreases expression	2
tri-o-cresyl phosphate	increases expression	1
ciglitazone	affects binding, increases expression	1
picene	increases expression	1
bisphenol B	increases expression	1
Caffeine	affects phosphorylation	1
Diazinon	increases methylation	1
Diethylhexyl Phthalate	decreases expression	1
Doxorubicin	decreases expression	1
Valproic Acid	increases methylation	1
Okadaic Acid	increases expression	1

Clinical trials (associated diseases)

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