MAGEA3

Summary

MAGEA3 (MAGE family member A3, HGNC:6801) is a protein-coding gene on chromosome Xq28, encoding Melanoma-associated antigen 3 (P43357). Activator of ubiquitin ligase activity of RING-type zinc finger-containing E3 ubiquitin-protein ligases that acts as a repressor of autophagy.

This gene is a member of the MAGEA gene family. The members of this family encode proteins with 50 to 80% sequence identity to each other. The promoters and first exons of the MAGEA genes show considerable variability, suggesting that the existence of this gene family enables the same function to be expressed under different transcriptional controls. The MAGEA genes are clustered at chromosomal location Xq28. They have been implicated in some hereditary disorders, such as dyskeratosis congenita.

Source: NCBI Gene 4102 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 68 total
• Druggable target: yes
• MANE Select transcript: NM_005362

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6801
Approved symbol	MAGEA3
Name	MAGE family member A3
Location	Xq28
Locus type	gene with protein product
Status	Approved
Aliases	HYPD, HIP8, MGC14613, CT1.3
Ensembl gene	ENSG00000221867
Ensembl biotype	protein_coding
OMIM	300174
Entrez	4102

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 4 protein_coding

ENST00000370278, ENST00000417212, ENST00000598245, ENST00000933889

RefSeq mRNA: 1 — MANE Select: NM_005362 NM_005362

CCDS: CCDS76045

Canonical transcript exons

ENST00000370278 — 3 exons

Exon	Start	End
ENSE00001707226	152698794	152698829
ENSE00001715379	152700622	152700687
ENSE00001886752	152700768	152702347

Expression profiles

Bgee: expression breadth broad, 30 present calls, max score 90.39.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.4000 / max 15.8044, expressed in 164 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
209867	0.4000	164

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	90.39	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	84.43	gold quality
right testis	UBERON:0004534	73.62	gold quality
testis	UBERON:0000473	73.59	gold quality
left testis	UBERON:0004533	72.33	gold quality
placenta	UBERON:0001987	44.37	gold quality
sural nerve	UBERON:0015488	40.13	gold quality
lower esophagus mucosa	UBERON:0035834	39.39	gold quality
colonic epithelium	UBERON:0000397	37.20	gold quality
ventricular zone	UBERON:0003053	36.48	gold quality
cortical plate	UBERON:0005343	36.47	gold quality
bone marrow cell	CL:0002092	36.16	gold quality
ganglionic eminence	UBERON:0004023	35.49	gold quality
skeletal muscle tissue	UBERON:0001134	33.38	gold quality
urinary bladder	UBERON:0001255	32.98	gold quality
muscle tissue	UBERON:0002385	32.29	gold quality
hindlimb stylopod muscle	UBERON:0004252	32.15	gold quality
bone marrow	UBERON:0002371	31.74	gold quality
liver	UBERON:0002107	31.26	gold quality
cortex of kidney	UBERON:0001225	30.88	gold quality
gastrocnemius	UBERON:0001388	30.80	gold quality
muscle of leg	UBERON:0001383	30.78	gold quality
right uterine tube	UBERON:0001302	30.76	gold quality
blood	UBERON:0000178	30.48	gold quality
stromal cell of endometrium	CL:0002255	29.87	gold quality
right coronary artery	UBERON:0001625	29.84	silver quality
right lobe of liver	UBERON:0001114	29.39	gold quality
fundus of stomach	UBERON:0001160	29.28	gold quality
prefrontal cortex	UBERON:0000451	29.04	gold quality
monocyte	CL:0000576	28.76	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-MTAB-8410	yes	187.75
E-MTAB-6142	no	319.99
E-ANND-3	no	1.15

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): MYC

miRNA regulators (miRDB)

27 targeting MAGEA3, 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-371B-5P	99.99	75.34	4759
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-4496	99.88	68.89	2236
HSA-MIR-137-3P	99.87	74.74	2401
HSA-MIR-4503	99.85	71.45	1869
HSA-MIR-383-3P	99.85	65.84	1359
HSA-MIR-448	99.79	72.37	2103
HSA-MIR-4694-3P	99.79	69.53	2640
HSA-MIR-567	99.63	68.57	1219
HSA-MIR-4261	99.59	70.30	3415
HSA-MIR-216A-5P	99.50	68.02	1288
HSA-MIR-513C-5P	99.50	68.42	1730
HSA-MIR-514B-5P	99.50	68.19	1766
HSA-MIR-147B-5P	99.45	70.62	2432
HSA-MIR-372-5P	99.41	69.11	2299
HSA-MIR-6507-5P	99.36	70.46	2524
HSA-MIR-892C-5P	99.16	70.56	2116
HSA-MIR-371A-5P	99.08	66.51	1914
HSA-MIR-31-5P	98.58	68.35	1239
HSA-MIR-12120	98.05	68.44	1768
HSA-MIR-526B-5P	97.41	67.99	1074
HSA-MIR-550B-3P	95.43	67.73	599
HSA-MIR-4301	95.00	65.22	554

Literature-anchored findings (GeneRIF, showing 40)

• Identification of immunodominant regions among promiscuous HLA-DR-restricted CD4+ T-cell epitopes on the tumor antigen MAGE-3 (PMID:12393675)
• This melanoma-associated marker was detected in melanoma cell lines. (PMID:12710945)
• Spontaneous in vivo priming of MAGE-specific T cell response and high frequency of MAGE1 and MAGE3 expression in hepatocellular carcinoma makes this antigen potential candidate for MAGE-specific immunotherapy in hepatocellular carcinoma. (PMID:14672620)
• first evidence that the naturally processed MAGE-3(271-279) can be isolated and identified from the tumor tissue of hepatocellular carcinoma patient (PMID:15885805)
• Present, by immunocytochemistry, in normal prostate, prostatic hypertrophy and prostate cancer. (PMID:16114059)
• The newly identified MAGE-3(113)-peptide epitope is naturally processed and presented as the CTL epitope on MAGE-3-expressing GI cancer cells, indicating that anti-MAGE-3 immune targeting with the MAGE-3(113) peptide is a promising approach for treatment. (PMID:16446550)
• Detection of aberrant methylation patterns of MAGEs CpG islands using Methylation-special PCR may be useful for diagnosis of Hepatocellular Carcinoma. (PMID:16516880)
• MAGE-A3 gene mRNA is expressed at the mRNA level in a proportion of human leukemias. (PMID:16806467)
• The promoter hypomethylation of MAGE-A1 and MAGE-A3 genes up-regulates their expression in colorectal carcinomas as well as in gastric cancers and might play a significant role in the development and progression of human colorectal carcinomas. (PMID:17007017)
• the MAGE-A3 and MAGE-C2 gene promoter regions are de-methylated in the presence of activated KIT but become methylated on inhibition of KIT, consistent with the downregulation of mRNA and protein (PMID:17495964)
• These data show, for the first time, the involvement of methyl-CpG binding domain proteins in the regulation of the MAGE-A genes. (PMID:17634428)
• Gene expression profiling identified the cancer/testis antigen MAGE-A3/6 as a novel target of FGFR2-IIIb signaling. (PMID:17699848)
• Measurement of Melan-A, gp100, MAGE-3, MIA and tyrosinase represents a prognostic factor and a method for early detection of metastasis and treatment response of melanoma patients. (PMID:18181974)
• Multiple simultaneous detection of MAGE-A [subtypes] more specific and sensitive than detection of single MAGE-A antigen for the diagnostic and prognostic evaluation of oral squamous cell carcinoma (PMID:18197853)
• MAGEC1/CT7, MAGEA3/6 and LAGE-1 are good candidates for immunotherapy, since together they cover 85% of our MM cases. (PMID:18237105)
• the repertoire of MAGE-A3 epitopes recognized in vivo by CD4+ T cells are influenced by endosomal proteases (PMID:18316621)
• MAGE-A3 as a target of FGFR2-IIIb and estrogen action and provide evidence for a common histone-modifying network in the control of the balance between opposing signals. (PMID:18381936)
• MAGE-A3 may have a role in melanoma and could be used in a therapeutic vaccine (PMID:18483279)
• The high expression rates of MAGE-1 and MAGE-3 genes in IHCC suggests the MAGE-1 and MAGE-3 gene may be a target for immunotherapy in IHCC patients. (PMID:18505125)
• MAGE A3 is a functional integrator of diverse signals, including FGFR2 and FN, to modulate cancer progression. (PMID:18829569)
• Its expression is significantly associated with prognostic factors in poor outcome of the non-small cell lung cancer (PMID:18982744)
• Increase in cytoplasmic MAGEA3 is associated with thyroid cancer. (PMID:19261683)
• In stage III melanomas the expression of MAGE-3, either alone or in association with the expression of other tumour-specific antigens at a transcriptional level, is a good prognostic factor for higher disease-free survival. (PMID:19326132)
• MAGE-A3/6 and NY-ESO-1 were expressed in 50.0% (66/132) and 18.2% (24/132) of non-small-cell lung carcinomas, respectively. (PMID:19795170)
• MAGE-A3, a cancer-testis antigen, plays an important role in the survival of multiple myeloma cells. (PMID:20015885)
• results showed that MAGE-A3 gene expression was frequent in NHL patients and decreased after effective chemotherapy, suggesting that MAGE-A3 can be used as a tumor marker for circulating lymphoma cells in patients with NHL. (PMID:20036422)
• Tumor-specific antigen MAGE may play a role in the occurrence and development of ovarian cancer and can be used as one of the important indicators for early diagnosis, efficacy evaluation and prognostic determination of ovarian cancer. (PMID:20423514)
• Report immunohistochemical expression of MAGE-A3 in renal oncocytoma and chromophobe renal cell carcinoma. (PMID:20591578)
• Molecular upstaging of MAGE-A3 using rt-pcr was correlated with prognosis in melanoma patients (PMID:21135695)
• RT-PCR assays of MAGE-A3 and MAGE-A4 in blood of breast cancer (BC) patients may have prognostic and predictive implications, and they are promising specific tumor markers of BC (PMID:21264495)
• MAGE3 expression mediated by demethylation of MAGE3 promoter induce progression of non-small cell lung cancer. (PMID:21273595)
• we found that the SSX4 and MAGE-A3 genes are frequently expressed in brain tumor cell lines (PMID:21347689)
• High MAGE-3 gene expression is associated with metastases in hepatitis C virus patients complicated by hepatocellular carcinoma. (PMID:21452042)
• Primary tumors with and without lymph node metastases showed no significant differences in MAGE-A 3/4 (P=0.672) and NY-ESO-1 (P=0.444) expression (PMID:21556122)
• MAGE-A3 was detected in a significantly higher percentage of relapsed patients compared with newly diagnosed, establishing a novel correlation with progression of disease. (PMID:21565982)
• MAGE-A3 gene may have a clinical relevance and important role as a risk factor in the development of acute myeloid leukemia (PMID:21804405)
• Expression of MAGE I proteins, MAGE-A3 or MAGE-C2, relieved repression of a reporter gene by ZNF382 and MAGE I expression relieved KAP1 mediated ID1 repression. (PMID:21876767)
• Report MAGEA1-A6 expression and MAGE A3 methylation in sputum suggests presence of lung cancer cells or precancerous cells. (PMID:22134685)
• Data indicate the association of MAGE-A3 expression and poor prognosis in diffuse large B-cell lymphoma (DLBCL) patients. (PMID:22183072)
• Cancer/testis antigens are novel targets of immunotherapy for adult T-cell leukemia/lymphoma. (PMID:22323448)

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), MAGED4B (ENSG00000187243), MAGEH1 (ENSG00000187601), MAGEB5 (ENSG00000188408), MAGEB16 (ENSG00000189023), MAGEA6 (ENSG00000197172), MAGEA1 (ENSG00000198681), MAGEB3 (ENSG00000198798), MAGEE1 (ENSG00000198934), MAGEA12 (ENSG00000213401), MAGEB1 (ENSG00000214107), MAGEB6B (ENSG00000232030), MAGEL2 (ENSG00000254585), MAGEA9B (ENSG00000267978), MAGEA2 (ENSG00000268606)

Protein

Protein identifiers

Melanoma-associated antigen 3 — P43357 (reviewed: P43357)

Alternative names: Antigen MZ2-D, Cancer/testis antigen 1.3, MAGE-3 antigen

All UniProt accessions (2): P43357, E7EMU0

UniProt curated annotations — full annotation on UniProt →

Function. Activator of ubiquitin ligase activity of RING-type zinc finger-containing E3 ubiquitin-protein ligases that acts as a repressor of autophagy. May enhance ubiquitin ligase activity of TRIM28 and stimulate p53/TP53 ubiquitination by TRIM28. Proposed to act through recruitment and/or stabilization of the Ubl-conjugating enzyme (E2) at the E3:substrate complex. May play a role in embryonal development and tumor transformation or aspects of tumor progression. In vitro promotes cell viability in melanoma cell lines. Antigen recognized on a melanoma by autologous cytolytic T-lymphocytes.

Subunit / interactions. Interacts with TRIM28.

Tissue specificity. Expressed in many tumors of several types, such as melanoma, head and neck squamous cell carcinoma, lung carcinoma and breast carcinoma, but not in normal tissues except for testes and placenta. Never expressed in kidney tumors, Leukemias and lymphomas.

Post-translational modifications. Ubiquitinated by the DCX(DCAF12) complex specifically recognizes the diglutamate (Glu-Glu) at the C-terminus, leading to its degradation.

RefSeq proteins (1): NP_005353* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002190	MHD_dom	Domain
IPR021072	MAGE_N	Domain
IPR037445	MAGE	Family
IPR041898	MAGE_WH1	Homologous_superfamily
IPR041899	MAGE_WH2	Homologous_superfamily

Pfam: PF01454, PF12440

UniProt features (27 total): helix 12, strand 4, compositionally biased region 3, mutagenesis site 3, turn 2, chain 1, domain 1, region of interest 1

Structure

Experimental structures (PDB)

6 structures.

PDB	Method	Resolution (Å)
4V0P	X-RAY DIFFRACTION	2.07
1QEW	X-RAY DIFFRACTION	2.2
9BD2	X-RAY DIFFRACTION	2.24
9YTF	ELECTRON MICROSCOPY	2.6
5BRZ	X-RAY DIFFRACTION	2.62
8T9A	ELECTRON MICROSCOPY	3.17

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P43357-F1	72.25	0.45

Antibody-complex structures (SAbDab): 1 — 9YTF

Functional residue map

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

Mutagenesis-validated functional residues (3):

Position	Phenotype
170	abolishes hla-a1 binding.
176	abolishes hla-a1 binding.
314	abolished recognition by the dcx(dcaf12) complex and ubiquitination.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 100 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_UP, GSE37336_LY6C_POS_VS_NEG_NAIVE_CD4_TCELL_UP, GSE18804_BRAIN_VS_COLON_TUMORAL_MACROPHAGE_UP, GOBP_NEGATIVE_REGULATION_OF_RESPONSE_TO_ENDOPLASMIC_RETICULUM_STRESS, CHOI_ATL_ACUTE_STAGE, MODULE_52, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, GOBP_REGULATION_OF_AUTOPHAGY, GOBP_NEGATIVE_REGULATION_OF_PROTEOLYSIS, GOBP_RESPONSE_TO_ENDOPLASMIC_RETICULUM_STRESS, GOBP_NEGATIVE_REGULATION_OF_INTRACELLULAR_SIGNAL_TRANSDUCTION, MODULE_118, GOBP_NEGATIVE_REGULATION_OF_AUTOPHAGY, GOBP_PROTEIN_MATURATION, GOBP_NEGATIVE_REGULATION_OF_INTRINSIC_APOPTOTIC_SIGNALING_PATHWAY

GO Biological Process (4): negative regulation of transcription by RNA polymerase II (GO:0000122), negative regulation of autophagy (GO:0010507), negative regulation of protein processing (GO:0010955), negative regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway (GO:1902236)

GO Molecular Function (3): histone deacetylase binding (GO:0042826), caspase binding (GO:0089720), protein binding (GO:0005515)

GO Cellular Component (2): nucleus (GO:0005634), endoplasmic reticulum (GO:0005783)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
intracellular membrane-bounded organelle	2
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
negative regulation of DNA-templated transcription	1
autophagy	1
negative regulation of catabolic process	1
regulation of autophagy	1
protein processing	1
negative regulation of proteolysis	1
regulation of protein processing	1
negative regulation of protein maturation	1
intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress	1
regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway	1
negative regulation of response to endoplasmic reticulum stress	1
negative regulation of intrinsic apoptotic signaling pathway	1
enzyme binding	1
protease binding	1
binding	1
cytoplasm	1
endomembrane system	1

Protein interactions and networks

STRING

1258 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MAGEA3	TRIM28	Q13263	987
MAGEA3	CTAG1A	P78358	960
MAGEA3	GAGE4	P0DSO3	944
MAGEA3	GAGE2A	Q6NT46	940
MAGEA3	TYR	P14679	875
MAGEA3	CTAG2	O75638	868
MAGEA3	PMEL	P40967	857
MAGEA3	CSAG1	Q6PB30	806
MAGEA3	HLA-A	P01891	752
MAGEA3	TPTE	P56180	745
MAGEA3	CSAG2	Q9Y5P2	721
MAGEA3	TP53	P04637	706
MAGEA3	TTN	Q8WZ42	705
MAGEA3	PRAME	P78395	693
MAGEA3	CD8A	P01732	630

IntAct

57 interactions, top by confidence:

A	B	Type	Score
MAGEA3	STAMBPL1	psi-mi:“MI:0915”(physical association)	0.700
MAGEA3	BACC1	psi-mi:“MI:0915”(physical association)	0.670
MAGEA3	TRIM28	psi-mi:“MI:0915”(physical association)	0.650
TRIM28	MAGEA3	psi-mi:“MI:0915”(physical association)	0.650
STAMBPL1	PIK3C2A	psi-mi:“MI:0914”(association)	0.640
MAGEA3	PCYT1A	psi-mi:“MI:0915”(physical association)	0.560
MAGEA3	RUSC1	psi-mi:“MI:0915”(physical association)	0.560
	MAGEA3	psi-mi:“MI:0915”(physical association)	0.560
EXOC5	MAGEA3	psi-mi:“MI:0915”(physical association)	0.560
S100A9	MAGEA3	psi-mi:“MI:0915”(physical association)	0.560
MAGEA3	LSM2	psi-mi:“MI:0915”(physical association)	0.560
ACOT7	MAGEA3	psi-mi:“MI:0915”(physical association)	0.560
IQSEC1	MAGEA3	psi-mi:“MI:0915”(physical association)	0.560
MAGEA3	CINP	psi-mi:“MI:0915”(physical association)	0.560
MAGEA3	BCL7B	psi-mi:“MI:0915”(physical association)	0.560
MAGEA3	KIF27	psi-mi:“MI:0915”(physical association)	0.560
HTT	MAGEA3	psi-mi:“MI:0915”(physical association)	0.560
BACC1	SMARCA5	psi-mi:“MI:0914”(association)	0.530
DNM1L	MAGEA3	psi-mi:“MI:0915”(physical association)	0.370
ATG16L1	ESYT2	psi-mi:“MI:0914”(association)	0.350
MAGEA3	PALM3	psi-mi:“MI:0914”(association)	0.350
GRB10	SRC	psi-mi:“MI:0914”(association)	0.350

BioGRID (163): MAGEA3 (Two-hybrid), MAGEA3 (Two-hybrid), MAGEA3 (Affinity Capture-Western), CASP12 (Affinity Capture-Western), MAGEA3 (Affinity Capture-Western), MAGEA3 (Affinity Capture-Western), MAGEA3 (Two-hybrid), STAT1 (Affinity Capture-MS), STAT1 (Affinity Capture-Western), MAGEA3 (Affinity Capture-Western), MAGEA3 (Two-hybrid), MAGEA3 (Two-hybrid), MAGEA3 (Two-hybrid), MAGEA3 (Two-hybrid), MAGEA3 (Two-hybrid)

ESM2 similar proteins: A0A0J9YX57, A1A5P9, A2A368, A2A9R3, A8MXT2, B2KFW1, O15479, O15480, O15481, O15553, P0C6Y7, P10073, P17040, P25233, P43355, P43356, P43357, P43358, P43360, P43362, P43363, P43364, P43366, Q13342, Q16666, Q4R998, Q5PPP4, Q5RD14, Q6AY37, Q6PCZ4, Q8BQR7, Q8IWY8, Q8IX06, Q8N660, Q8N7X4, Q8TD90, Q96DU7, Q96LZ2, Q96M61, Q99608

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

3 interactions.

A	Effect	B	Mechanism
MAGEA3	“up-regulates activity”	TRIM28	binding
DCAF12	“down-regulates quantity by destabilization”	MAGEA3	binding
Cullin4-RBX1-DDB1	“down-regulates quantity by destabilization”	MAGEA3	polyubiquitination

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	49
Likely benign	10
Benign	7

Top pathogenic / likely-pathogenic (0)

SpliceAI

548 predictions. Top by Δscore:

Variant	Effect	Δscore
X:152698826:CAAG:C	donor_loss	1.0000
X:152698830:G:GA	donor_loss	1.0000
X:152700683:GATCT:G	donor_gain	1.0000
X:152700685:TCT:T	donor_gain	1.0000
X:152700688:G:GG	donor_gain	1.0000
X:152698825:GCAAG:G	donor_gain	0.9900
X:152698826:C:T	donor_gain	0.9900
X:152698830:G:GG	donor_gain	0.9900
X:152700684:ATCT:A	donor_gain	0.9900
X:152700686:CT:C	donor_gain	0.9900
X:152700686:CTGTA:C	donor_loss	0.9900
X:152700688:GT:G	donor_loss	0.9900
X:152700689:T:G	donor_loss	0.9900
X:152700690:AAGT:A	donor_loss	0.9900
X:152700691:AGT:A	donor_loss	0.9900
X:152700692:G:GG	donor_gain	0.9900
X:152700762:CCCCA:C	acceptor_loss	0.9900
X:152700764:CCA:C	acceptor_loss	0.9900
X:152700766:A:AG	acceptor_gain	0.9900
X:152700766:AGG:A	acceptor_loss	0.9900
X:152700767:G:A	acceptor_loss	0.9900
X:152700767:G:GG	acceptor_gain	0.9900
X:152700767:GGCCA:G	acceptor_gain	0.9900
X:152698799:G:T	donor_gain	0.9800
X:152700617:TTCA:T	acceptor_loss	0.9800
X:152700618:TCA:T	acceptor_loss	0.9800
X:152700619:CA:C	acceptor_loss	0.9800
X:152700620:A:AG	acceptor_gain	0.9800
X:152700621:G:GC	acceptor_loss	0.9800
X:152700621:G:GG	acceptor_gain	0.9800

AlphaMissense

2049 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:152701644:T:C	F271S	0.943
X:152701643:T:C	F271L	0.941
X:152701645:C:A	F271L	0.941
X:152701645:C:G	F271L	0.941
X:152701316:T:C	F162L	0.932
X:152701318:T:A	F162L	0.932
X:152701318:T:G	F162L	0.932
X:152701649:T:A	W273R	0.903
X:152701649:T:C	W273R	0.903
X:152701652:G:C	G274R	0.888
X:152701608:G:C	R259P	0.887
X:152701201:G:C	K123N	0.880
X:152701201:G:T	K123N	0.880
X:152701644:T:G	F271C	0.880
X:152701651:G:C	W273C	0.877
X:152701651:G:T	W273C	0.877
X:152701236:T:C	M135T	0.869
X:152701271:T:C	F147L	0.852
X:152701273:T:A	F147L	0.852
X:152701273:T:G	F147L	0.852
X:152701320:G:T	G163V	0.833
X:152701187:T:C	F119L	0.830
X:152701189:T:A	F119L	0.830
X:152701189:T:G	F119L	0.830
X:152701653:G:A	G274D	0.820
X:152701236:T:G	M135R	0.819
X:152701660:G:C	R276S	0.816
X:152701660:G:T	R276S	0.816
X:152701671:A:T	E280V	0.811
X:152701498:G:C	W222C	0.809

dbSNP variants (sampled 300 via entrez): RS1047232 (X:152766387 A>C,G), RS1047234 (X:152766383 C>A,T), RS112483246 (X:152696937 T>A,C), RS113065219 (X:152697495 G>A,C), RS113269944 (X:152702503 A>G), RS1157341385 (X:152771059 A>G), RS1157396209 (X:152702424 A>G), RS1157479924 (X:152700672 C>T), RS1157572637 (X:152699787 A>G), RS1157579855 (X:152769961 C>T), RS1157617735 (X:152767683 T>C), RS1157749045 (X:152766180 C>T), RS1158124562 (X:152697959 C>G), RS1158193737 (X:152697854 A>G), RS1159189735 (X:152701957 A>G,T)

Disease associations

OMIM: gene MIM:300174 | 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: yes

ChEMBL targets (1): CHEMBL4662941 (SINGLE PROTEIN)

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: other protein — Tumour-associated antigens

CTD chemical–gene interactions

15 total (human), top 15 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Decitabine	increases expression, affects expression	4
TAK-243	increases sumoylation	1
o,p’-DDT	increases expression	1
abrine	increases expression	1
mocetinostat	increases reaction, increases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Atrazine	decreases expression	1
Azacitidine	decreases methylation, increases expression, increases reaction	1
Benzo(a)pyrene	decreases methylation	1
Cisplatin	affects binding, decreases expression, increases response to substance	1
Clorgyline	increases expression	1
Plant Extracts	affects cotreatment, decreases expression	1
Valproic Acid	increases methylation	1
Aflatoxin B1	decreases methylation	1
Mitomycin	increases response to substance, affects binding, decreases expression	1

Cellosaurus cell lines

3 cell lines: 3 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B7Y3	Abcam Raji MAGEA3 KO	Cancer cell line	Male
CVCL_B9YT	Abcam THP-1 MAGEA3 KO	Cancer cell line	Male
CVCL_C7AJ	Abcam PC-3 MAGEA3 KO	Cancer cell line	Male

Clinical trials (associated diseases)

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