MAGEA9

Summary

MAGEA9 (MAGE family member A9, HGNC:6807) is a protein-coding gene on chromosome Xq28, encoding Melanoma-associated antigen 9 (P43362). Not known, though may play a role in embryonal development and tumor transformation or aspects of tumor progression.

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 4108 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 1 total
• MANE Select transcript: NM_005365

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6807
Approved symbol	MAGEA9
Name	MAGE family member A9
Location	Xq28
Locus type	gene with protein product
Status	Approved
Aliases	MGC8421, CT1.9
Ensembl gene	ENSG00000123584
Ensembl biotype	protein_coding
OMIM	300342
Entrez	4108

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000243314

RefSeq mRNA: 1 — MANE Select: NM_005365 NM_005365

CCDS: CCDS14691

Canonical transcript exons

ENST00000243314 — 4 exons

Exon	Start	End
ENSE00001595600	149781930	149781995
ENSE00001656889	149785757	149785843
ENSE00001733088	149786002	149786070
ENSE00001786200	149786146	149787737

Expression profiles

Bgee: expression breadth broad, 17 present calls, max score 76.03.

Top tissues by expression

127 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	76.03	gold quality
right testis	UBERON:0004534	38.76	gold quality
colonic epithelium	UBERON:0000397	37.20	gold quality
ganglionic eminence	UBERON:0004023	37.13	gold quality
testis	UBERON:0000473	36.92	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
left testis	UBERON:0004533	35.06	gold quality
skeletal muscle tissue	UBERON:0001134	34.78	gold quality
granulocyte	CL:0000094	33.81	gold quality
placenta	UBERON:0001987	32.20	gold quality
hindlimb stylopod muscle	UBERON:0004252	32.15	gold quality
muscle tissue	UBERON:0002385	32.09	gold quality
bone marrow	UBERON:0002371	31.74	gold quality
sural nerve	UBERON:0015488	30.93	gold quality
tonsil	UBERON:0002372	30.21	gold quality
stromal cell of endometrium	CL:0002255	29.87	gold quality
lymph node	UBERON:0000029	29.84	gold quality
prefrontal cortex	UBERON:0000451	29.80	gold quality
vermiform appendix	UBERON:0001154	29.12	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	29.03	gold quality
liver	UBERON:0002107	28.53	gold quality
islet of Langerhans	UBERON:0000006	28.18	gold quality
right uterine tube	UBERON:0001302	28.18	gold quality
duodenum	UBERON:0002114	28.14	gold quality
urinary bladder	UBERON:0001255	27.48	gold quality
primary visual cortex	UBERON:0002436	27.23	gold quality
muscle of leg	UBERON:0001383	27.13	silver quality
leukocyte	CL:0000738	26.79	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.13

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

25 targeting MAGEA9, 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-3613-3P	100.00	76.36	7965
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-515-5P	99.92	69.82	2343
HSA-MIR-519E-5P	99.92	69.62	2358
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-202-3P	99.84	71.41	1290
HSA-MIR-4307	99.82	70.45	3374
HSA-MIR-3133	99.81	70.92	3506
HSA-MIR-4306	99.72	70.50	3630
HSA-MIR-3120-3P	99.54	70.28	2669
HSA-MIR-5009-3P	99.45	69.43	1341
HSA-MIR-4666A-5P	99.41	69.72	1887
HSA-MIR-519D-5P	99.41	69.30	2057
HSA-MIR-4644	99.35	69.12	2514
HSA-MIR-3164	99.02	68.39	1071
HSA-MIR-6820-3P	99.02	68.50	1035
HSA-MIR-31-5P	98.58	68.35	1239
HSA-MIR-6780A-3P	98.42	67.49	1518
HSA-MIR-556-5P	97.75	66.17	473
HSA-MIR-134-5P	97.11	66.52	976
HSA-MIR-3118	97.11	66.58	984
HSA-MIR-4433B-5P	95.91	66.56	727
HSA-MIR-550B-3P	95.43	67.73	599

Literature-anchored findings (GeneRIF, showing 12)

• May provide suitable targets for immunotherapy of renal cell carcinoma. (PMID:15900605)
• Overexpression of MAGE-A9 is associated with bladder cancer. (PMID:19533752)
• MAGE-A9 and MAGE-A11 are tumor-specific antigens and not only DNA hypermethylation but also histone deacetylation is responsible for the mechanism underlying MAGE-A9 and MAGE-A11 gene silencing. (PMID:24316396)
• These data are the first to indicate that MAGE-A9 expression is a valuable prognostic biomarker for HCC and that high MAGE-A9 expression suggests unfavorable survival outcomes in HCC patients (PMID:25315972)
• High expression of MAGE-A9 indicates unfavorable survival outcome in laryngeal squamous cell carcinoma patients. (PMID:25400753)
• The data suggest that MAGE-A9 expression is correlated with malignant attributes of invasive ductal breast cancer (PMID:25445503)
• The results showed that the high expression of MAGE-A9 protein in NSCLC tumor cells were commonly present in squamous cell carcinomas. It was also related to larger tumor diameter, lymph node metastasis and later stage grouping with TNM classification (PMID:25755744)
• High expression levels of MAGE-A9 are correlated with lung adenocarcinoma. (PMID:26717042)
• The overall survival of laryngeal squamous cell carcinoma patients with positive MAGE-A1, MAGE-A9, or MAGE-A11 expression was lower than the patients without MAGE-A1, MAGE-A9, or MAGE-A11 expression. (PMID:26766421)
• potential X-linked candidate for the CNV67-related spermatogenic failure phenotype (PMID:28339631)
• MAGE-A9 overexpression promoted cell proliferation, colony formation, migration, chemoresistance, and tumorigenicity in the context of EpCAM+ HCC cells, whereas MAGE-A9 knockdown significantly inhibited anchorage-dependent and spheroid colony formation and in vivo tumorigenicity. (PMID:29138811)
• Long Non-Coding RNA (lncRNA) Metastasis-Associated Lung Adenocarcinoma Transcript 1 (MALAT1) Promotes Cell Proliferation and Migration by Regulating miR-143-3p and MAGE Family Member A9 (MAGEA9) in Oral Squamous Cell Carcinoma. (PMID:32879299)

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), 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), MAGEA3 (ENSG00000221867), MAGEB6B (ENSG00000232030), MAGEL2 (ENSG00000254585), MAGEA9B (ENSG00000267978), MAGEA2 (ENSG00000268606)

Protein

Protein identifiers

Melanoma-associated antigen 9 — P43362 (reviewed: P43362)

Alternative names: Cancer/testis antigen 1.9, MAGE-9 antigen

All UniProt accessions (1): P43362

UniProt curated annotations — full annotation on UniProt →

Function. Not known, though may play a role in embryonal development and tumor transformation or aspects of tumor progression.

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 (1): NP_005356* (*=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 (9 total): sequence conflict 3, compositionally biased region 2, chain 1, domain 1, region of interest 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P43362-F1	77.17	0.50

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 80 (showing top): MULLIGHAN_NPM1_SIGNATURE_3_UP, MORF_FLT1, MORF_MSH3, MORF_BRCA1, MORF_ESR1, ACEVEDO_LIVER_CANCER_WITH_H3K27ME3_UP, MORF_RAD51L3, KIM_RESPONSE_TO_TSA_AND_DECITABINE_UP, MODULE_379, MORF_CTSB, MORF_IL4, MORF_PRKCA, HELLER_HDAC_TARGETS_SILENCED_BY_METHYLATION_UP, MORF_THPO, MORF_ETV3

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

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
enzyme binding	1
binding	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

306 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MAGEA9	CTAG2	O75638	594
MAGEA9	CTAG1A	P78358	541
MAGEA9	HSFX4	A0A1B0GTS1	446
MAGEA9	TMEM86A	Q8N2M4	433
MAGEA9	MAGEC1	O60732	411
MAGEA9	GET3	O43681	405
MAGEA9	TMEM185A	Q8NFB2	398
MAGEA9	TSPAN2	O60636	396
MAGEA9	EOLA1	Q8TE69	393
MAGEA9	VIPR1	P32241	370
MAGEA9	EOLA2	Q96DE9	365
MAGEA9	SSX1	Q16384	360
MAGEA9	CXorf51A	A0A1B0GTR3	356
MAGEA9	OR4D5	Q8NGN0	348
MAGEA9	SPACA5B	Q96QH8	326

IntAct

20 interactions, top by confidence:

A	B	Type	Score
MAGEA9	APPL1	psi-mi:“MI:0915”(physical association)	0.740
APPL1	MAGEA9	psi-mi:“MI:0915”(physical association)	0.740
MAGEA4	MAGEB16	psi-mi:“MI:0914”(association)	0.530
NSA2	TYW5	psi-mi:“MI:0914”(association)	0.530
MAGEA10	POTEF	psi-mi:“MI:0914”(association)	0.530
MAGEA1	MAGEB3	psi-mi:“MI:0914”(association)	0.530
MAGEA1	ANKHD1	psi-mi:“MI:0914”(association)	0.350
MAGEA9	CIBAR1	psi-mi:“MI:0914”(association)	0.350
MAGEA9	MED19	psi-mi:“MI:0914”(association)	0.350
SAP30BP	TYW5	psi-mi:“MI:0914”(association)	0.350
MAGEA1	ANKRD17	psi-mi:“MI:0914”(association)	0.350
COMMD10	MAGEA9	psi-mi:“MI:0914”(association)	0.350
CRH	CST4	psi-mi:“MI:0914”(association)	0.350

BioGRID (225): APPL1 (Two-hybrid), MAGEA9B (Affinity Capture-MS), MAGEA9B (Affinity Capture-MS), MAGEA9B (Affinity Capture-MS), MAGEA9B (Affinity Capture-MS), MAGEA9B (Affinity Capture-MS), MAGEA9B (Affinity Capture-MS), MAGEA9B (Affinity Capture-MS), MAGEA9B (Affinity Capture-MS), RNF40 (Affinity Capture-MS), ZFC3H1 (Affinity Capture-MS), EAPP (Affinity Capture-MS), FAM91A1 (Affinity Capture-MS), MAGEA9B (Affinity Capture-MS), HELZ2 (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

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	1
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

519 predictions. Top by Δscore:

Variant	Effect	Δscore
X:149786066:GACCT:G	donor_gain	1.0000
X:149786071:G:GG	donor_gain	1.0000
X:149786145:GGCCT:G	acceptor_gain	1.0000
X:149786140:CCCCA:C	acceptor_loss	0.9900
X:149786144:A:AC	acceptor_loss	0.9900
X:149786144:A:AG	acceptor_gain	0.9900
X:149786145:G:A	acceptor_loss	0.9900
X:149786145:G:GG	acceptor_gain	0.9900
X:149786068:CCT:C	donor_gain	0.9800
X:149786145:GGC:G	acceptor_gain	0.9800
X:149785999:CAG:C	acceptor_loss	0.9700
X:149786000:A:AC	acceptor_loss	0.9700
X:149786001:G:GA	acceptor_loss	0.9700
X:149786069:CT:C	donor_gain	0.9600
X:149786144:AG:A	acceptor_gain	0.9600
X:149786145:GG:G	acceptor_gain	0.9600
X:149786067:ACCT:A	donor_gain	0.9500
X:149786067:ACCTG:A	donor_loss	0.9500
X:149786068:CCTGT:C	donor_loss	0.9500
X:149786069:CTG:C	donor_loss	0.9500
X:149786070:TGTAA:T	donor_loss	0.9500
X:149786071:GTAA:G	donor_loss	0.9500
X:149786072:TAAGT:T	donor_loss	0.9500
X:149786073:A:AG	donor_loss	0.9500
X:149786074:AGT:A	donor_loss	0.9500
X:149786145:GGCC:G	acceptor_gain	0.9500
X:149786075:G:C	donor_loss	0.9400
X:149783890:G:T	donor_gain	0.9100
X:149781994:AG:A	donor_loss	0.9000
X:149781995:GGTAA:G	donor_loss	0.9000

AlphaMissense

2078 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:149787019:T:C	F270S	0.975
X:149787018:T:C	F270L	0.962
X:149787020:C:A	F270L	0.962
X:149787020:C:G	F270L	0.962
X:149786983:G:C	R258P	0.936
X:149787024:T:A	W272R	0.936
X:149787024:T:C	W272R	0.936
X:149786646:T:C	F146L	0.928
X:149786648:T:A	F146L	0.928
X:149786648:T:G	F146L	0.928
X:149787026:G:C	W272C	0.927
X:149787026:G:T	W272C	0.927
X:149786691:T:C	F161L	0.923
X:149786693:T:A	F161L	0.923
X:149786693:T:G	F161L	0.923
X:149787019:T:G	F270C	0.919
X:149786955:T:A	W249R	0.917
X:149786955:T:C	W249R	0.917
X:149787027:G:C	G273R	0.911
X:149786611:T:C	M134T	0.907
X:149786881:T:C	L224S	0.902
X:149786611:T:G	M134R	0.886
X:149786576:A:C	K122N	0.885
X:149786576:A:T	K122N	0.885
X:149786566:T:C	L119P	0.881
X:149786554:T:C	L115S	0.878
X:149786873:G:C	W221C	0.875
X:149786873:G:T	W221C	0.875
X:149786869:T:G	I220S	0.871
X:149787028:G:A	G273D	0.870

dbSNP variants (sampled 300 via entrez): RS111482377 (X:149780314 G>A), RS113451770 (X:149785673 T>C), RS1157711845 (X:149784354 A>C), RS1157951497 (X:149787593 T>C), RS1158922292 (X:149787277 C>T), RS1159690570 (X:149783686 C>T), RS1161655408 (X:149784813 G>A), RS1163283513 (X:149784682 G>A), RS1164785750 (X:149784672 C>A,T), RS1165021544 (X:149783597 C>G), RS1166286993 (X:149782907 G>T), RS1166895187 (X:149787088 A>G), RS1168635069 (X:149786896 T>G), RS1169310437 (X:149787945 G>C), RS1169988508 (X:149784605 G>GA,GT)

Disease associations

OMIM: gene MIM:300342 | 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

13 total (human), top 13 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Decitabine	affects expression, affects reaction, increases expression	2
3,3’-diindolylmethane	decreases reaction, increases expression	1
4-phenylbutyric acid	affects expression, affects reaction	1
apicidin	affects expression, affects reaction	1
entinostat	affects reaction, affects expression	1
Resveratrol	affects cotreatment, decreases expression	1
Acetaminophen	increases expression	1
Benztropine	affects cotreatment, decreases expression	1
Cuprizone	affects cotreatment, decreases expression	1
Estradiol	decreases reaction, increases expression	1
Plant Extracts	affects cotreatment, decreases expression	1
Tetrachlorodibenzodioxin	decreases reaction, increases expression	1
Valproic Acid	increases methylation	1

Clinical trials (associated diseases)

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