MAGEA4

Summary

MAGEA4 (MAGE family member A4, HGNC:6802) is a protein-coding gene on chromosome Xq28, encoding Melanoma-associated antigen 4 (P43358). Regulates cell proliferation through the inhibition of cell cycle arrest at the G1 phase.

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. Several variants encoding the same protein have been found for this gene.

Source: NCBI Gene 4103 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 58 total
• Druggable target: yes
• MANE Select transcript: NM_001011548

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6802
Approved symbol	MAGEA4
Name	MAGE family member A4
Location	Xq28
Locus type	gene with protein product
Status	Approved
Aliases	MAGE4A, MAGE4B, MAGE-41, MAGE-X2, MGC21336, CT1.4
Ensembl gene	ENSG00000147381
Ensembl biotype	protein_coding
OMIM	300175
Entrez	4103

Gene structure

Transcript identifiers

Ensembl transcripts: 34 — 34 protein_coding

ENST00000276344, ENST00000360243, ENST00000370335, ENST00000370340, ENST00000393920, ENST00000393921, ENST00000416020, ENST00000425182, ENST00000430273, ENST00000431963, ENST00000431971, ENST00000441865, ENST00000448295, ENST00000457310, ENST00000682265, ENST00000682728, ENST00000683901, ENST00000684668, ENST00000911914, ENST00000911915, ENST00000911916, ENST00000911917, ENST00000911918, ENST00000911919, ENST00000911920, ENST00000911921, ENST00000911922, ENST00000911923, ENST00000911924, ENST00000911925, ENST00000911926, ENST00000911927, ENST00000911928, ENST00000911929

RefSeq mRNA: 11 — MANE Select: NM_001011548 NM_001011548, NM_001011549, NM_001011550, NM_001386196, NM_001386197, NM_001386198, NM_001386199, NM_001386200, NM_001386202, NM_001386203, NM_002362

CCDS: CCDS14702

Canonical transcript exons

ENST00000276344 — 3 exons

Exon	Start	End
ENSE00001401864	151912889	151912969
ENSE00001725092	151923453	151923524
ENSE00003652014	151923600	151925170

Expression profiles

Bgee: expression breadth broad, 56 present calls, max score 85.65.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.7312 / max 200.4314, expressed in 77 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
198000	0.3913	70
197998	0.2916	54
197999	0.0484	11

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	85.65	gold quality
right testis	UBERON:0004534	85.25	gold quality
left testis	UBERON:0004533	84.54	gold quality
testis	UBERON:0000473	83.21	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	82.62	gold quality
decidua	UBERON:0002450	56.55	gold quality
placenta	UBERON:0001987	55.93	gold quality
mucosa of urinary bladder	UBERON:0001259	54.91	gold quality
hair follicle	UBERON:0002073	52.43	gold quality
adult organism	UBERON:0007023	51.71	silver quality
lower lobe of lung	UBERON:0008949	50.61	silver quality
frontal pole	UBERON:0002795	50.41	gold quality
quadriceps femoris	UBERON:0001377	50.30	gold quality
middle frontal gyrus	UBERON:0002702	50.30	gold quality
paraflocculus	UBERON:0005351	50.18	gold quality
Brodmann (1909) area 10	UBERON:0013541	50.18	gold quality
thymus	UBERON:0002370	50.08	gold quality
vastus lateralis	UBERON:0001379	49.48	gold quality
Brodmann (1909) area 46	UBERON:0006483	49.30	gold quality
blood vessel layer	UBERON:0004797	49.29	gold quality
epithelial cell of pancreas	CL:0000083	49.26	gold quality
cerebellar vermis	UBERON:0004720	49.25	gold quality
cervix squamous epithelium	UBERON:0006922	49.20	gold quality
olfactory bulb	UBERON:0002264	48.92	gold quality
choroid plexus epithelium	UBERON:0003911	48.89	gold quality
myocardium	UBERON:0002349	48.87	gold quality
type B pancreatic cell	CL:0000169	48.83	gold quality
pancreatic ductal cell	CL:0002079	48.83	silver quality
tibialis anterior	UBERON:0001385	48.72	silver quality
cardiac muscle of right atrium	UBERON:0003379	48.55	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-GEOD-124263	yes	540.75
E-GEOD-134144	yes	30.10
E-ANND-3	no	1.15

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CTCFL

miRNA regulators (miRDB)

34 targeting MAGEA4, 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-4262	100.00	73.26	3931
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-1229-3P	99.97	66.49	906
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-1305	99.91	71.43	3443
HSA-MIR-4496	99.88	68.89	2236
HSA-MIR-3121-3P	99.82	71.96	3630
HSA-MIR-4799-5P	99.82	70.60	2663
HSA-MIR-448	99.79	72.37	2103
HSA-MIR-4261	99.59	70.30	3415
HSA-MIR-4649-3P	99.56	66.90	1783
HSA-MIR-7159-5P	99.53	72.12	2472
HSA-MIR-7849-3P	99.47	68.17	1224
HSA-MIR-5695	99.41	67.48	1047
HSA-MIR-4797-5P	99.39	68.01	1354
HSA-MIR-4427	99.34	70.33	1854
HSA-MIR-324-3P	99.26	66.31	1034
HSA-MIR-892C-5P	99.16	70.56	2116
HSA-MIR-216B-3P	98.55	67.19	1223
HSA-MIR-6834-3P	98.16	65.77	551
HSA-MIR-1285-5P	98.01	68.71	779
HSA-MIR-3691-3P	97.90	65.97	791
HSA-MIR-4670-3P	97.37	68.35	1378
HSA-MIR-759	96.16	66.77	873

Literature-anchored findings (GeneRIF, showing 40)

• MAGE-4 protein may have a role in development of hepatocellular carcinogenesis in cirrhotic patients (PMID:11985796)
• MAGE-A4 expression in bladder transitional cell carcinoma. (PMID:12209610)
• strong MAGE-A4 expression and to a lesser degree NY-ESO-1 expression is characteristic of the vast majority of uterine carcinosarcomas and a major subset of papillary serous carcinomas (PMID:12209997)
• MAGE-A4 binds to gankyrin and suppresses its oncogenic activity. (PMID:12525503)
• a cleaved form of MAGE-A4 binds to Miz-1 and induces apoptosis (PMID:14739298)
• MAGE-A4(143-151) and SAGE(715-723) are HLA-A2402-restricted CTL epitopes (PMID:16061876)
• Present, by immunocytochemistry, in normal prostate, prostatic hypertrophy and prostate cancer. (PMID:16114059)
• Expression may represent potential targets for cancer immunotherapy in patients with non small cell lung carcinoma. (PMID:16596224)
• Expressed in a large part of epithelial skin tumors with predominantly scattered immunoexpression pattern in organ-transplant recipients. (PMID:17214847)
• 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)
• Its expression is significantly associated with prognostic factors in poor outcome of the non-small cell lung cancer. (PMID:18982744)
• Overexpression of MAGE-A4 is associated with bladder cancer. (PMID:19533752)
• positive expression in patients with non-small cell lung cancer is associated with poorer overall survival (PMID:19545928)
• Report immunohistochemical expression of MAGE-A4 in renal oncocytoma and chromophobe renal cell carcinoma. (PMID:20591578)
• High MAGE-A4 gene expression is associated with head and neck squamous cell carcinoma (PMID:20715104)
• 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)
• High MAGE-4 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-A4 is identified as a specific biomarker of esophageal squamous cell carcinoma with a possible oncogenic role contributing to tumor progression. (PMID:21613820)
• novel HLA-A2-restricted T cell epitope derived from MAGE-4 was identified (PMID:21815906)
• Report MAGEA1-A6 expression in sputum suggests presence of lung cancer cells or precancerous cells. (PMID:22134685)
• Cancer/testis antigens are novel targets of immunotherapy for adult T-cell leukemia/lymphoma. (PMID:22323448)
• Detection of MAGE-4 transcripts in blood may help to predict the prognosis and monitoring of the response of HCV-infected hepatocellular carcinoma patients to therapy (PMID:22653756)
• MAGEA4 promotes growth by preventing cell cycle arrest and by inhibiting apoptosis mediated by the p53 transcriptional targets. (PMID:22842486)
• HLA class I loss in smokers or patients with the MAGE-A4 gene was a prognostic factors in non-small cell lung cancer . (PMID:23124547)
• Mage-A4 expression and serum identification is and potential therapeutic target in estrogen receptor negative breast cancer. (PMID:23172894)
• Expression of MAGE-A4 may make immunotherapeutic intervention possible in selected patients with thyroid cancer. (PMID:24238058)
• CTAs (MAGE-A4, NY-ESO-1, MAGE-A10) were more likely expressed in patients with squamous cell carcinoma of the lung and when CTAs combined with CD133, they can be better prognostic factors. (PMID:26191258)
• Anti-MAGEA4 exhibited the highest sensitivity for detecting early stage colorectal cancer (CRC) and advanced adenoma. (PMID:26909861)
• the crystal structures of MAGE-A3 and MAGE-A4 (PMID:26910052)
• some autoantibodies, such as anti-MAGEA4, anti-CTAG1 or anti-TP53 and their combinations could possibly contribute to the development of cancer early detection tests (not necessarily restricted to gastric cancer) when being combined with other markers. (PMID:27140836)
• MAGE-A4 depletion from MAGE-A4-expressing cancer cells destabilizes RAD18. (PMID:27377895)
• Results found concomitant overexpression of MAGEA4 and TWIST1 in esophageal squamous cell carcinoma (ESCC). Also, it showed a correlation between MAGEA4 and TWIST1 expression, which was found as indirect binding of TWIST1 to the E-boxes in the MAGEA4 promoter revealing transcriptional upregulation of MAGEA4 by TWIST1. (PMID:27533647)
• High MAGE-A4 expression is associated with Lung Cancer. (PMID:27793776)
• Results support the potential utility of NY-ESO-1, PRAME, and MAGEA4 as targets for immunotherapy and as ancillary prognostic parameters in synovial sarcomas. (PMID:27993576)
• Data show that overall survival (OS) was significantly lower for patients expressing pan-MAGE or MAGE-A1/A3/A4 in both independent cohorts. (PMID:28146422)
• Our results support…the potential utility of MAGEA4 as an ancillary diagnostic marker for synovial sarcoma (PMID:28744588)
• Study shows that whereas MAGEA4 expression by itself may be indicative of a poor prognosis in primary lung cancer, its prognostic value depends entirely on its subcellular localization and on the p53 status. The accumulation of nuclear MAGEA4 expression without p53 expression is significantly associated with poor survival, implying that MAGEA4 inhibits apoptosis and increases tumorigenesis. (PMID:29901069)
• Because of the significant correlation of MAGEA4 and indices of poor prognosis, the role of this CTA may be confirmed in Esophageal squamous cell carcinoma (ESCC) aggressiveness and metastasis. Therefore, MAGEA4 may be a promising therapeutic candidate for suppressing ESCC aggressiveness (PMID:30197348)
• T cell receptor interactions with human leukocyte antigen govern indirect peptide selectivity for the cancer testis antigen MAGE-A4. (PMID:32532817)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	ndnl2	ENSDARG00000058212
mus_musculus	Magea13	ENSMUSG00000046180
rattus_norvegicus	Magea13	ENSRNOG00000003532
drosophila_melanogaster	MAGE	FBGN0037481

Paralogs (37): MAGEC2 (ENSG00000046774), TRO (ENSG00000067445), MAGEB2 (ENSG00000099399), MAGED2 (ENSG00000102316), MAGEB4 (ENSG00000120289), MAGEA9 (ENSG00000123584), MAGEA10 (ENSG00000124260), 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), MAGEA3 (ENSG00000221867), MAGEB6B (ENSG00000232030), MAGEL2 (ENSG00000254585), MAGEA9B (ENSG00000267978), MAGEA2 (ENSG00000268606)

Protein

Protein identifiers

Melanoma-associated antigen 4 — P43358 (reviewed: P43358)

Alternative names: Cancer/testis antigen 1.4, MAGE-4 antigen, MAGE-41 antigen, MAGE-X2 antigen

All UniProt accessions (8): P43358, A0A804HIU4, A0A804HK84, C9J9C2, C9JIR1, C9JK50, C9JUM7, C9JZJ5

UniProt curated annotations — full annotation on UniProt →

Function. Regulates cell proliferation through the inhibition of cell cycle arrest at the G1 phase. Also negatively regulates p53-mediated apoptosis.

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.

RefSeq proteins (11): NP_001011548, NP_001011549, NP_001011550, NP_001373125, NP_001373126, NP_001373127, NP_001373128, NP_001373129, NP_001373131, NP_001373132, NP_002353 (=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 (35 total): helix 12, sequence conflict 6, strand 6, sequence variant 4, turn 2, compositionally biased region 2, chain 1, domain 1, region of interest 1

Structure

Experimental structures (PDB)

9 structures.

PDB	Method	Resolution (Å)
6TRN	X-RAY DIFFRACTION	1.35
1I4F	X-RAY DIFFRACTION	1.4
2WA0	X-RAY DIFFRACTION	2.3
9BD3	X-RAY DIFFRACTION	2.58
8ES8	ELECTRON MICROSCOPY	2.65
6TRO	X-RAY DIFFRACTION	3
8FJA	ELECTRON MICROSCOPY	3
8ES9	ELECTRON MICROSCOPY	3.25
7UOA	X-RAY DIFFRACTION	3.5

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P43358-F1	77.86	0.58

Antibody-complex structures (SAbDab): 1 — 8FJA

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 76 (showing top): MODULE_52, MODULE_118, KIM_RESPONSE_TO_TSA_AND_DECITABINE_UP, MODULE_379, SHETH_LIVER_CANCER_VS_TXNIP_LOSS_PAM5, GOBP_REGULATION_OF_CELL_CYCLE, HELLER_HDAC_TARGETS_SILENCED_BY_METHYLATION_UP, LIANG_SILENCED_BY_METHYLATION_UP, MODULE_242, MODULE_18, MODULE_38, MODULE_104, GOBP_POSITIVE_REGULATION_OF_CELL_CYCLE, LIANG_SILENCED_BY_METHYLATION_2, GOMF_HISTONE_DEACETYLASE_BINDING

GO Biological Process (3): negative regulation of transcription by RNA polymerase II (GO:0000122), negative regulation of apoptotic process (GO:0043066), positive regulation of cell cycle (GO:0045787)

GO Molecular Function (2): histone deacetylase binding (GO:0042826), 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
apoptotic process	1
regulation of apoptotic process	1
negative regulation of programmed cell death	1
cell cycle	1
positive regulation of cellular process	1
regulation of cell cycle	1
enzyme binding	1
binding	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

762 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MAGEA4	CTAG1A	P78358	925
MAGEA4	CTAG2	O75638	891
MAGEA4	RAD18	Q9NS91	714
MAGEA4	PRAME	P78395	670
MAGEA4	SSX4	O60224	621
MAGEA4	HLA-A	P01891	608
MAGEA4	GAGE4	P0DSO3	608
MAGEA4	SSX1	Q16384	593
MAGEA4	ADGRA3	Q8IWK6	517
MAGEA4	CT45A1	Q5HYN5	516
MAGEA4	GAGE2A	Q6NT46	507
MAGEA4	SDCCAG8	Q86SQ7	490
MAGEA4	CT83	Q5H943	480
MAGEA4	XAGE1B	Q9HD64	480
MAGEA4	PMEL	P40967	479

IntAct

94 interactions, top by confidence:

A	B	Type	Score
UQCRB	MAGEA4	psi-mi:“MI:0915”(physical association)	0.850
MAGEA4	UQCRB	psi-mi:“MI:0915”(physical association)	0.850
MAGEA4	RAD18	psi-mi:“MI:0915”(physical association)	0.800
MAGEA4	TSPYL4	psi-mi:“MI:0915”(physical association)	0.800
MAGEA4	TEKT4	psi-mi:“MI:0915”(physical association)	0.740
UBXN6	MAGEA4	psi-mi:“MI:0915”(physical association)	0.670
MAGEA4	TRIM69	psi-mi:“MI:0915”(physical association)	0.670
MAGEA4	UBXN6	psi-mi:“MI:0915”(physical association)	0.670
TRIM69	MAGEA4	psi-mi:“MI:0915”(physical association)	0.670
MAGEA4	AMOT	psi-mi:“MI:0915”(physical association)	0.660
ARL4C	RGS12	psi-mi:“MI:0914”(association)	0.640
UQCRB	COX7A2L	psi-mi:“MI:0914”(association)	0.640
PSMD10	MAGEA4	psi-mi:“MI:0915”(physical association)	0.580
	MAGEA4	psi-mi:“MI:0915”(physical association)	0.560
MAGEA4		psi-mi:“MI:0915”(physical association)	0.560
MAGEA4	TXN2	psi-mi:“MI:0915”(physical association)	0.560
AMOT	MAGEA4	psi-mi:“MI:0915”(physical association)	0.560
MAGEA4	PICK1	psi-mi:“MI:0915”(physical association)	0.560
COX8A	MAGEA4	psi-mi:“MI:0915”(physical association)	0.560
MAGEA4	TRIM69	psi-mi:“MI:0915”(physical association)	0.560
MAGEA4	TSPYL	psi-mi:“MI:0915”(physical association)	0.560
MAGEA4	HDDC3	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (124): MAGEA4 (Two-hybrid), TK1 (Two-hybrid), UQCRB (Two-hybrid), WBP2 (Two-hybrid), AMOTL2 (Two-hybrid), UBXN6 (Two-hybrid), BEX2 (Two-hybrid), TIGD5 (Two-hybrid), TRIM69 (Two-hybrid), TEKT4 (Two-hybrid), AMOT (Two-hybrid), UQCRB (Affinity Capture-MS), PPP1R13L (Affinity Capture-MS), MAGEB16 (Affinity Capture-MS), MAGEA9B (Affinity Capture-MS)

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

0 interactions.

Disease & clinical

Cancer significance

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	45
Likely benign	13
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

827 predictions. Top by Δscore:

Variant	Effect	Δscore
X:151923520:GATCT:G	donor_gain	1.0000
X:151923525:G:GG	donor_gain	1.0000
X:151923521:ATCT:A	donor_gain	0.9900
X:151923522:TCT:T	donor_gain	0.9900
X:151923529:G:GG	donor_gain	0.9900
X:151923599:GGCCT:G	acceptor_gain	0.9900
X:151923525:G:A	donor_loss	0.9800
X:151923526:T:TG	donor_loss	0.9800
X:151923595:CGTA:C	acceptor_loss	0.9800
X:151923597:TAG:T	acceptor_loss	0.9800
X:151923679:GAAGA:G	acceptor_gain	0.9800
X:151923452:G:C	acceptor_loss	0.9700
X:151923598:A:AG	acceptor_gain	0.9700
X:151923599:G:GG	acceptor_gain	0.9700
X:151923673:T:TA	acceptor_gain	0.9700
X:151912965:ACAAG:A	donor_loss	0.9600
X:151912967:AAGGT:A	donor_loss	0.9600
X:151912969:GGTG:G	donor_loss	0.9600
X:151912971:T:A	donor_loss	0.9600
X:151923523:CT:C	donor_gain	0.9600
X:151923451:A:AG	acceptor_gain	0.9500
X:151923452:G:GG	acceptor_gain	0.9500
X:151912939:G:T	donor_gain	0.9100
X:151923521:A:G	donor_gain	0.9100
X:151923599:GGC:G	acceptor_gain	0.8900
X:151923674:G:GC	acceptor_gain	0.8900
X:151914139:A:AG	acceptor_gain	0.8800
X:151923679:GAA:G	acceptor_gain	0.8800
X:151923449:TCAGG:T	acceptor_gain	0.8700
X:151923599:GGCC:G	acceptor_gain	0.8700

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000372180 (X:151913095 C>A,T), RS1000707115 (X:151919897 G>A), RS1000742114 (X:151912674 C>T), RS1000948948 (X:151923089 G>A), RS1001213320 (X:151913551 G>A), RS1001580871 (X:151913231 C>T), RS1001881389 (X:151920134 C>G,T), RS1002180685 (X:151911477 T>C), RS1002616535 (X:151911693 G>T), RS1002846415 (X:151919907 C>A), RS1002879040 (X:151920268 G>T), RS1003499860 (X:151922140 C>T), RS1003552690 (X:151921661 T>A,C), RS1003840688 (X:151911646 C>G,T), RS1004465742 (X:151924044 C>T)

Disease associations

OMIM: gene MIM:300175 | 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): CHEMBL4296022 (SINGLE PROTEIN)

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

ChEMBL bioactivities

19 potent at pChembl≥5 of 19 total, top 19 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.90	IC50	1.26	nM	CHEMBL5199001
8.67	IC50	2.15	nM	CHEMBL5188210
8.19	Kd	6.5	nM	CHEMBL5187815
8.01	Kd	9.7	nM	CHEMBL5188210
7.97	IC50	10.6	nM	CHEMBL5208958
7.93	Kd	11.8	nM	CHEMBL5187815
7.86	IC50	13.9	nM	CHEMBL5182108
7.43	Kd	36.8	nM	CHEMBL5188210
7.32	Kd	47.4	nM	CHEMBL5199001
7.26	Kd	55.5	nM	CHEMBL5199001
7.17	IC50	67.5	nM	CHEMBL5197762
6.99	IC50	103.1	nM	CHEMBL5187977
6.83	IC50	147.6	nM	CHEMBL5175619
6.72	IC50	190.1	nM	CHEMBL5197324
6.06	IC50	862.2	nM	CHEMBL5189065
5.72	IC50	1893	nM	CHEMBL5174657
5.66	IC50	2212	nM	CHEMBL5188864
5.65	IC50	2228	nM	CHEMBL5175748
5.21	IC50	6184	nM	CHEMBL5202217

PubChem BioAssay actives

22 with measured affinity, of 38 total; 16 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
2-[(3S,6S,9S,12S,15S,18S,21S,24R,27S,33R,36S,39S,42S,45R)-21,42-bis(3-carbamimidamidopropyl)-33-carbamoyl-39-[(1R)-1-hydroxyethyl]-9,15,27,36-tetrakis[(4-hydroxyphenyl)methyl]-6-(1H-imidazol-5-ylmethyl)-3,18-bis(2-methylpropyl)-2,5,8,11,14,17,20,23,26,29,35,38,41,44-tetradecaoxo-24-(sulfanylmethyl)-31-thia-1,4,7,10,13,16,19,22,25,28,34,37,40,43-tetradecazabicyclo[43.3.0]octatetracontan-12-yl]acetic acid	1910263: Inhibition of Eu-W1024 streptavidin-labeled MAGEA4 (unknown origin) expressed in Escherichia coli BL21-(DE3) incubated for 30 to 60 mins by LANCE TR-FRET assay	ic50	0.0010	uM
(3S,6S,9S,12S,15S,18S,21S,24S,27S,30S,36R,39S,42R)-9-(2-amino-2-oxoethyl)-3,12-dibenzyl-6,18-bis(3-carbamimidamidopropyl)-15,39-bis[(1R)-1-hydroxyethyl]-24-[(1S)-1-hydroxyethyl]-30-[(4-hydroxyphenyl)methyl]-21-(2-methylpropyl)-2,5,8,11,14,17,20,23,26,29,32,38,41-tridecaoxo-27-propan-2-yl-34-thia-1,4,7,10,13,16,19,22,25,28,31,37,40-tridecazabicyclo[40.3.0]pentatetracontane-36-carboxamide	1910263: Inhibition of Eu-W1024 streptavidin-labeled MAGEA4 (unknown origin) expressed in Escherichia coli BL21-(DE3) incubated for 30 to 60 mins by LANCE TR-FRET assay	ic50	0.0013	uM
2-[(3R,6S,9S,12S,15S,18S,21S,24S,27S,30S)-6-(2-amino-2-oxoethyl)-27-[(2S)-butan-2-yl]-3-carbamoyl-24-[3-(diaminomethylideneamino)propyl]-12,18,30-tris[(4-hydroxyphenyl)methyl]-9-(1H-imidazol-5-ylmethyl)-21-(2-methylpropyl)-5,8,11,14,17,20,23,26,29,32-decaoxo-1-thia-4,7,10,13,16,19,22,25,28,31-decazacyclotritriacont-15-yl]acetic acid	1910263: Inhibition of Eu-W1024 streptavidin-labeled MAGEA4 (unknown origin) expressed in Escherichia coli BL21-(DE3) incubated for 30 to 60 mins by LANCE TR-FRET assay	ic50	0.0022	uM
2-[(3R,6S,9S,12S,15S,18S,21S,24S,27S,30S)-27-[(2S)-butan-2-yl]-3-carbamoyl-24-[3-(diaminomethylideneamino)propyl]-12,18,30-tris[(4-hydroxyphenyl)methyl]-9-(1H-imidazol-5-ylmethyl)-6-methyl-21-(2-methylpropyl)-5,8,11,14,17,20,23,26,29,32-decaoxo-1-thia-4,7,10,13,16,19,22,25,28,31-decazacyclotritriacont-15-yl]acetic acid	1910263: Inhibition of Eu-W1024 streptavidin-labeled MAGEA4 (unknown origin) expressed in Escherichia coli BL21-(DE3) incubated for 30 to 60 mins by LANCE TR-FRET assay	ic50	0.0106	uM
2-[(3R,6S,9S,12S,15S,18S,21S,24S,27S,30S)-6-(2-amino-2-oxoethyl)-27-[(2S)-butan-2-yl]-3-carbamoyl-24-[3-(diaminomethylideneamino)propyl]-12,18,30-tris[(4-hydroxyphenyl)methyl]-9-methyl-21-(2-methylpropyl)-5,8,11,14,17,20,23,26,29,32-decaoxo-1-thia-4,7,10,13,16,19,22,25,28,31-decazacyclotritriacont-15-yl]acetic acid	1910263: Inhibition of Eu-W1024 streptavidin-labeled MAGEA4 (unknown origin) expressed in Escherichia coli BL21-(DE3) incubated for 30 to 60 mins by LANCE TR-FRET assay	ic50	0.0139	uM
(3R,6S,9S,12S,15S,18S,21S,24S,27S,30S)-6-(2-amino-2-oxoethyl)-27-[(2S)-butan-2-yl]-24-[3-(diaminomethylideneamino)propyl]-12,18,30-tris[(4-hydroxyphenyl)methyl]-9-(1H-imidazol-5-ylmethyl)-15-methyl-21-(2-methylpropyl)-5,8,11,14,17,20,23,26,29,32-decaoxo-1-thia-4,7,10,13,16,19,22,25,28,31-decazacyclotritriacontane-3-carboxamide	1910263: Inhibition of Eu-W1024 streptavidin-labeled MAGEA4 (unknown origin) expressed in Escherichia coli BL21-(DE3) incubated for 30 to 60 mins by LANCE TR-FRET assay	ic50	0.0675	uM
2-[(3R,6S,9S,12S,15S,18S,21S,24S,27S,30S)-6-(2-amino-2-oxoethyl)-27-[(2S)-butan-2-yl]-3-carbamoyl-12,18,30-tris[(4-hydroxyphenyl)methyl]-9-(1H-imidazol-5-ylmethyl)-24-methyl-21-(2-methylpropyl)-5,8,11,14,17,20,23,26,29,32-decaoxo-1-thia-4,7,10,13,16,19,22,25,28,31-decazacyclotritriacont-15-yl]acetic acid	1910263: Inhibition of Eu-W1024 streptavidin-labeled MAGEA4 (unknown origin) expressed in Escherichia coli BL21-(DE3) incubated for 30 to 60 mins by LANCE TR-FRET assay	ic50	0.1031	uM
(3R,6S,9S,12S,15S,18S,21S,24S,27S,30S)-27-[(2S)-butan-2-yl]-24-[3-(diaminomethylideneamino)propyl]-12,18,30-tris[(4-hydroxyphenyl)methyl]-6,9,15-trimethyl-21-(2-methylpropyl)-5,8,11,14,17,20,23,26,29,32-decaoxo-1-thia-4,7,10,13,16,19,22,25,28,31-decazacyclotritriacontane-3-carboxamide	1910263: Inhibition of Eu-W1024 streptavidin-labeled MAGEA4 (unknown origin) expressed in Escherichia coli BL21-(DE3) incubated for 30 to 60 mins by LANCE TR-FRET assay	ic50	0.1475	uM
2-[(3R,12S,15S,18S,21S,24S,27S,30S)-27-[(2S)-butan-2-yl]-3-carbamoyl-24-[3-(diaminomethylideneamino)propyl]-12,18,30-tris[(4-hydroxyphenyl)methyl]-21-(2-methylpropyl)-5,8,11,14,17,20,23,26,29,32-decaoxo-1-thia-4,7,10,13,16,19,22,25,28,31-decazacyclotritriacont-15-yl]acetic acid	1910263: Inhibition of Eu-W1024 streptavidin-labeled MAGEA4 (unknown origin) expressed in Escherichia coli BL21-(DE3) incubated for 30 to 60 mins by LANCE TR-FRET assay	ic50	0.1901	uM
2-[(3R,6S,9S,12S,15S,18S,21S,24S,27S,30S)-6-(2-amino-2-oxoethyl)-27-[(2S)-butan-2-yl]-3-carbamoyl-24-[3-(diaminomethylideneamino)propyl]-18,30-bis[(4-hydroxyphenyl)methyl]-9-(1H-imidazol-5-ylmethyl)-12-methyl-21-(2-methylpropyl)-5,8,11,14,17,20,23,26,29,32-decaoxo-1-thia-4,7,10,13,16,19,22,25,28,31-decazacyclotritriacont-15-yl]acetic acid	1910263: Inhibition of Eu-W1024 streptavidin-labeled MAGEA4 (unknown origin) expressed in Escherichia coli BL21-(DE3) incubated for 30 to 60 mins by LANCE TR-FRET assay	ic50	0.8622	uM
2-[(3R,6S,9S,12S,15S,18S,21S,24S,27S,30S)-6-(2-amino-2-oxoethyl)-27-[(2S)-butan-2-yl]-3-carbamoyl-24-[3-(diaminomethylideneamino)propyl]-12,18-bis[(4-hydroxyphenyl)methyl]-9-(1H-imidazol-5-ylmethyl)-30-methyl-21-(2-methylpropyl)-5,8,11,14,17,20,23,26,29,32-decaoxo-1-thia-4,7,10,13,16,19,22,25,28,31-decazacyclotritriacont-15-yl]acetic acid	1910263: Inhibition of Eu-W1024 streptavidin-labeled MAGEA4 (unknown origin) expressed in Escherichia coli BL21-(DE3) incubated for 30 to 60 mins by LANCE TR-FRET assay	ic50	1.8927	uM
2-[(3R,6S,9S,12S,15S,18S,21S,24S,27S,30S)-6-(2-amino-2-oxoethyl)-27-[(2S)-butan-2-yl]-3-carbamoyl-24-[3-(diaminomethylideneamino)propyl]-12,18,30-tris[(4-hydroxyphenyl)methyl]-9-(1H-imidazol-5-ylmethyl)-21-methyl-5,8,11,14,17,20,23,26,29,32-decaoxo-1-thia-4,7,10,13,16,19,22,25,28,31-decazacyclotritriacont-15-yl]acetic acid	1910263: Inhibition of Eu-W1024 streptavidin-labeled MAGEA4 (unknown origin) expressed in Escherichia coli BL21-(DE3) incubated for 30 to 60 mins by LANCE TR-FRET assay	ic50	2.2118	uM
2-[(3R,9S,12S,15S,18S,21S,24S,27S)-24-[(2S)-butan-2-yl]-3-carbamoyl-21-[3-(diaminomethylideneamino)propyl]-9,15,27-tris[(4-hydroxyphenyl)methyl]-18-(2-methylpropyl)-5,8,11,14,17,20,23,26,29-nonaoxo-1-thia-4,7,10,13,16,19,22,25,28-nonazacyclotriacont-12-yl]acetic acid	1910263: Inhibition of Eu-W1024 streptavidin-labeled MAGEA4 (unknown origin) expressed in Escherichia coli BL21-(DE3) incubated for 30 to 60 mins by LANCE TR-FRET assay	ic50	2.2279	uM
2-[(3R,6S,9S,12S,15S,18S,21S,24S,27S,30S)-6-(2-amino-2-oxoethyl)-3-carbamoyl-24-[3-(diaminomethylideneamino)propyl]-12,18,30-tris[(4-hydroxyphenyl)methyl]-9-(1H-imidazol-5-ylmethyl)-27-methyl-21-(2-methylpropyl)-5,8,11,14,17,20,23,26,29,32-decaoxo-1-thia-4,7,10,13,16,19,22,25,28,31-decazacyclotritriacont-15-yl]acetic acid	1910263: Inhibition of Eu-W1024 streptavidin-labeled MAGEA4 (unknown origin) expressed in Escherichia coli BL21-(DE3) incubated for 30 to 60 mins by LANCE TR-FRET assay	ic50	6.1837	uM
2-[(3R,6S,9S,12S,15S,18S,21S,24S)-21-[(2S)-butan-2-yl]-3-carbamoyl-18-[3-(diaminomethylideneamino)propyl]-6,12,24-tris[(4-hydroxyphenyl)methyl]-15-(2-methylpropyl)-5,8,11,14,17,20,23,26-octaoxo-1-thia-4,7,10,13,16,19,22,25-octazacycloheptacos-9-yl]acetic acid	1910263: Inhibition of Eu-W1024 streptavidin-labeled MAGEA4 (unknown origin) expressed in Escherichia coli BL21-(DE3) incubated for 30 to 60 mins by LANCE TR-FRET assay	ic50	10.0000	uM
(3S)-3-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S,3S)-2-[[(2S)-2-acetamido-3-(4-hydroxyphenyl)propanoyl]amino]-3-methylpentanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-4-methylpentanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-4-[[(2S)-1-[[(2S)-1-[[(2S)-4-amino-1-[[(2R)-1-amino-1-oxo-3-sulfanylpropan-2-yl]amino]-1,4-dioxobutan-2-yl]amino]-3-(1H-imidazol-5-yl)-1-oxopropan-2-yl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-4-oxobutanoic acid	1910263: Inhibition of Eu-W1024 streptavidin-labeled MAGEA4 (unknown origin) expressed in Escherichia coli BL21-(DE3) incubated for 30 to 60 mins by LANCE TR-FRET assay	ic50	10.0000	uM

CTD chemical–gene interactions

8 total (human), top 8 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, increases expression, increases methylation	4
Decitabine	affects expression, increases expression	2
bisphenol S	decreases expression	1
Resveratrol	decreases expression, affects cotreatment	1
Benzo(a)pyrene	affects methylation	1
Fluorouracil	affects response to substance	1
Lipopolysaccharides	affects expression, affects response to substance	1
Plant Extracts	affects cotreatment, decreases expression	1

ChEMBL screening assays

16 unique, capped per target: 16 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4118729	Binding	Binding affinity to MAGEA4 in human NCI-H23 cells at 1 uM by mass spectrometry based pull down assay	Studies of TAK1-centered polypharmacology with novel covalent TAK1 inhibitors. — Bioorg Med Chem

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D7J6	Ubigene A-375 MAGEA4 KO	Cancer cell line	Female
CVCL_E1FI	Abcam A-431 MAGEA4 KO	Cancer cell line	Female

Clinical trials (associated diseases)

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