MAGED4B

Summary

MAGED4B (MAGE family member D4B, HGNC:22880) 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.

This gene is a member of the MAGED gene family. It is expressed only in brain and ovary, and some transcript variants of this gene are specifically expressed in glioma cells. This gene is clustered with other MAGED genes on chromosome Xp11. Alternatively spliced transcript variants encoding different isoforms have been described for this gene.

Source: NCBI Gene 81557 — RefSeq curated summary.

At a glance

• MANE Select transcript: NM_030801

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:22880
Approved symbol	MAGED4B
Name	MAGE family member D4B
Location	Xp11.22
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000187243
Ensembl biotype	protein_coding
OMIM	300765
Entrez	81557

Gene structure

Transcript identifiers

Ensembl transcripts: 24 — 17 protein_coding, 3 retained_intron, 2 protein_coding_CDS_not_defined, 2 nonsense_mediated_decay

ENST00000335504, ENST00000360134, ENST00000470594, ENST00000471617, ENST00000481096, ENST00000481193, ENST00000485287, ENST00000486010, ENST00000486469, ENST00000490581, ENST00000497164, ENST00000514560, ENST00000867078, ENST00000867079, ENST00000867080, ENST00000940544, ENST00000940545, ENST00000940546, ENST00000940547, ENST00000940548, ENST00000963321, ENST00000963322, ENST00000963323, ENST00000963324

RefSeq mRNA: 4 — MANE Select: NM_030801 NM_001242362, NM_030801, NM_177535, NM_177537

CCDS: CCDS14338, CCDS35281, CCDS56602

Canonical transcript exons

ENST00000335504 — 13 exons

Exon	Start	End
ENSE00001739636	52066865	52067698
ENSE00001936570	52069130	52069183
ENSE00002058470	52067963	52068203
ENSE00003461740	52061827	52062038
ENSE00003474672	52064501	52064543
ENSE00003482589	52062987	52063101
ENSE00003489994	52064047	52064109
ENSE00003492981	52066250	52066453
ENSE00003512866	52062234	52062664
ENSE00003522432	52065810	52065889
ENSE00003558409	52065330	52065421
ENSE00003647260	52064629	52064708
ENSE00003677196	52066083	52066146

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 98.85.

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	98.85	gold quality
ventricular zone	UBERON:0003053	98.65	gold quality
ganglionic eminence	UBERON:0004023	98.54	gold quality
pituitary gland	UBERON:0000007	98.06	gold quality
hypothalamus	UBERON:0001898	98.00	gold quality
adenohypophysis	UBERON:0002196	97.99	gold quality
nucleus accumbens	UBERON:0001882	97.65	gold quality
amygdala	UBERON:0001876	97.25	gold quality
temporal lobe	UBERON:0001871	97.21	gold quality
caudate nucleus	UBERON:0001873	96.20	gold quality
putamen	UBERON:0001874	96.10	gold quality
Ammon’s horn	UBERON:0001954	95.98	gold quality
anterior cingulate cortex	UBERON:0009835	95.97	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	95.46	gold quality
substantia nigra	UBERON:0002038	95.29	gold quality
cerebral cortex	UBERON:0000956	95.18	gold quality
stromal cell of endometrium	CL:0002255	95.08	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	95.05	gold quality
Brodmann (1909) area 9	UBERON:0013540	95.01	gold quality
right frontal lobe	UBERON:0002810	94.87	gold quality
prefrontal cortex	UBERON:0000451	94.80	gold quality
brain	UBERON:0000955	94.68	gold quality
frontal cortex	UBERON:0001870	94.65	gold quality
superior frontal gyrus	UBERON:0002661	92.82	gold quality
primary visual cortex	UBERON:0002436	92.75	gold quality
endocervix	UBERON:0000458	90.24	gold quality
right ovary	UBERON:0002118	89.88	gold quality
left ovary	UBERON:0002119	89.10	gold quality
body of uterus	UBERON:0009853	88.79	gold quality
ovary	UBERON:0000992	88.71	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-HCAD-13	yes	78.37
E-GEOD-36552	yes	34.10
E-ANND-3	yes	3.05
E-HCAD-5	no	17.73

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

14 targeting MAGED4B, 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 5)

• The MAGE-E1 gene is composed of 13 exons, and three of these (exon 2, exon 3 and exon 12) are alternatively spliced in each variant (E1a-c). MAGE-E1 gene is located in Xp11 through the analysis of radiation hybrid panels. (PMID:11602350)
• MAGE-D4 plays some roles in tumor cells proliferation in NSCLC, but MAGE-D4 expression status did not provided a prognostic significance. (PMID:16225959)
• MAGE-D4B was found to correlate with tumor progression and to be an independent prognostic marker for poor outcome in term of relapse-free and overall survival, with potential predictive relevance in relation to response to chemotherapy (PMID:21618523)
• Our data suggest that MAGED4B over-expression is a driver in oral carcinogenesis (PMID:22459352)
• Overexpression of MAGE-D4 may be a predictive marker of early recurrence and mortality in patients with hepatocellular carcinoma (HCC). (PMID:24068544)

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), MAGED4 (ENSG00000154545), 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), 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 (4): D6RBW3, Q96JG8, H0Y8Z3, H0Y937

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_001229291, NP_110428, NP_803879, NP_803881 (=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: 47 (showing top): HORIUCHI_WTAP_TARGETS_DN, MODULE_255, MODULE_317, SATO_SILENCED_BY_DEACETYLATION_IN_PANCREATIC_CANCER, ROZANOV_MMP14_TARGETS_UP, KINSEY_TARGETS_OF_EWSR1_FLII_FUSION_DN, LIAO_METASTASIS, ACEVEDO_METHYLATED_IN_LIVER_CANCER_DN, MODULE_69, NAKAYAMA_SOFT_TISSUE_TUMORS_PCA1_DN, chrXp11, GOBP_NEGATIVE_REGULATION_OF_TRANSCRIPTION_BY_RNA_POLYMERASE_II, GOBP_NEGATIVE_REGULATION_OF_NUCLEOBASE_CONTAINING_COMPOUND_METABOLIC_PROCESS, MODULE_37, ELVIDGE_HIF1A_TARGETS_DN

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
MAGED4B	HSPA4	P34932	887
MAGED4B	CTAG1A	P78358	696
MAGED4B	PMEL	P40967	690
MAGED4B	IL13RA2	Q14627	678
MAGED4B	GAGE4	P0DSO3	666
MAGED4B	TUBB2A	Q13885	606
MAGED4B	TUBB	P05218	586
MAGED4B	TYR	P14679	583
MAGED4B	PRAME	P78395	571
MAGED4B	SSX4	O60224	541
MAGED4B	CD8A	P01732	538
MAGED4B	SSX1	Q16384	507
MAGED4B	ICAM1	P05362	501
MAGED4B	OIP5	O43482	476
MAGED4B	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 52 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	35.2×	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

2223 predictions. Top by Δscore:

Variant	Effect	Δscore
X:52062232:A:AC	donor_gain	1.0000
X:52062233:C:CT	donor_gain	1.0000
X:52062662:ATT:A	acceptor_gain	1.0000
X:52062663:TT:T	acceptor_gain	1.0000
X:52062665:C:CC	acceptor_gain	1.0000
X:52062981:CCTTA:C	donor_loss	1.0000
X:52062982:CTTA:C	donor_loss	1.0000
X:52062983:TTAC:T	donor_loss	1.0000
X:52062984:TA:T	donor_loss	1.0000
X:52062985:A:AC	donor_gain	1.0000
X:52062985:A:AT	donor_loss	1.0000
X:52062986:C:CC	donor_gain	1.0000
X:52063098:GTAC:G	acceptor_loss	1.0000
X:52063101:CCT:C	acceptor_gain	1.0000
X:52063103:T:C	acceptor_gain	1.0000
X:52063103:T:TC	acceptor_gain	1.0000
X:52063107:C:CT	acceptor_gain	1.0000
X:52063108:A:AC	acceptor_gain	1.0000
X:52063108:A:C	acceptor_gain	1.0000
X:52064041:ACTT:A	donor_loss	1.0000
X:52064043:TTA:T	donor_loss	1.0000
X:52064044:TACT:T	donor_loss	1.0000
X:52064045:A:AC	donor_gain	1.0000
X:52064045:A:C	donor_loss	1.0000
X:52064045:ACTT:A	donor_gain	1.0000
X:52064046:C:CC	donor_gain	1.0000
X:52064046:CT:C	donor_gain	1.0000
X:52064046:CTT:C	donor_gain	1.0000
X:52064046:CTTC:C	donor_gain	1.0000
X:52064046:CTTCT:C	donor_gain	1.0000

AlphaMissense

4864 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:52063046:A:G	W576R	1.000
X:52063046:A:T	W576R	1.000
X:52062640:A:G	W604R	0.999
X:52062640:A:T	W604R	0.999
X:52063043:C:G	G577R	0.999
X:52063051:A:G	F574S	0.999
X:52063096:A:G	L559P	0.999
X:52065830:C:G	A458P	0.999
X:52066114:C:A	K427N	0.999
X:52066114:C:G	K427N	0.999
X:52066124:A:G	L424P	0.999
X:52063003:A:G	L590P	0.998
X:52063042:C:A	G577V	0.998
X:52063044:C:A	W576C	0.998
X:52063044:C:G	W576C	0.998
X:52065416:A:C	F466L	0.998
X:52065416:A:T	F466L	0.998
X:52065418:A:G	F466L	0.998
X:52065817:A:G	L462P	0.998
X:52065832:C:G	R457P	0.998
X:52062638:C:A	W604C	0.997
X:52062638:C:G	W604C	0.997
X:52062991:G:T	A594D	0.997
X:52063014:C:A	K586N	0.997
X:52063014:C:G	K586N	0.997
X:52063042:C:T	G577D	0.997
X:52063045:C:G	W576S	0.997
X:52063096:A:T	L559Q	0.997
X:52064059:A:G	F553S	0.997
X:52064665:C:G	G510R	0.997

dbSNP variants (sampled 41 via entrez): RS1460390489 (X:52069413 TCTCCTC>T), RS1557375829 (X:52062017 C>T), RS1557375832 (X:52062226 A>ACT), RS1557375834 (X:52063567 C>T), RS1557375835 (X:52063618 C>T), RS1557375836 (X:52064196 C>T), RS1557375837 (X:52064399 G>A), RS1557375838 (X:52064613 A>G), RS1557375840 (X:52064662 C>T), RS1557375842 (X:52065229 G>C), RS1557375844 (X:52066276 G>C), RS1557375845 (X:52067545 C>T), RS1557375847 (X:52068324 CG>C,CGG), RS1557375849 (X:52068630 G>A), RS1569556708 (X:52070626 T>TA)

Disease associations

OMIM: gene MIM:300765 | 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

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
butyraldehyde	increases expression	1
ciglitazone	affects binding, increases expression	1
abrine	decreases expression	1
Amiodarone	increases expression	1
Cyclophosphamide	affects response to substance	1
Fluorouracil	affects response to substance	1
Mitoxantrone	affects response to substance	1
Oxygen	increases expression	1
Silicon Dioxide	decreases expression	1
Valproic Acid	increases methylation	1
Okadaic Acid	increases expression	1
Copper Sulfate	decreases expression	1

Clinical trials (associated diseases)

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