MAGEA12

Summary

MAGEA12 (MAGE family member A12, HGNC:6799) is a protein-coding gene on chromosome Xq28, encoding Melanoma-associated antigen 12 (P43365). Not known, though may play a role tumor transformation or progression.

This gene is closely related to several other genes clustered on chromosome X. These genes may be overexpressed in tumors. Multiple alternatively spliced variants encoding the same protein have been identified.

Source: NCBI Gene 4111 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 45 total
• MANE Select transcript: NM_001166387

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6799
Approved symbol	MAGEA12
Name	MAGE family member A12
Location	Xq28
Locus type	gene with protein product
Status	Approved
Aliases	CT1.12
Ensembl gene	ENSG00000213401
Ensembl biotype	protein_coding
OMIM	300177
Entrez	4111

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 4 protein_coding

ENST00000357916, ENST00000393869, ENST00000393900, ENST00000916248

RefSeq mRNA: 3 — MANE Select: NM_001166387 NM_001166386, NM_001166387, NM_005367

CCDS: CCDS76048

Canonical transcript exons

ENST00000393869 — 3 exons

Exon	Start	End
ENSE00001404637	152736087	152737669
ENSE00002313486	152735148	152735253
ENSE00003849171	152733757	152733859

Expression profiles

Bgee: expression breadth broad, 48 present calls, max score 89.02.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.2870 / max 22.0364, expressed in 143 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
198004	0.2492	139
198005	0.0378	16

Top tissues by expression

254 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	89.02	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	85.27	gold quality
endothelial cell	CL:0000115	64.65	gold quality
right testis	UBERON:0004534	60.22	gold quality
testis	UBERON:0000473	59.80	gold quality
left testis	UBERON:0004533	58.16	gold quality
decidua	UBERON:0002450	56.55	gold quality
mucosa of urinary bladder	UBERON:0001259	55.89	gold quality
hair follicle	UBERON:0002073	52.43	gold quality
adult organism	UBERON:0007023	51.55	silver quality
tibialis anterior	UBERON:0001385	50.77	silver quality
quadriceps femoris	UBERON:0001377	49.37	gold quality
ileal mucosa	UBERON:0000331	49.32	silver quality
Brodmann (1909) area 46	UBERON:0006483	49.30	gold quality
cervix squamous epithelium	UBERON:0006922	49.20	gold quality
olfactory bulb	UBERON:0002264	48.92	gold quality
thymus	UBERON:0002370	48.90	gold quality
myocardium	UBERON:0002349	48.87	gold quality
type B pancreatic cell	CL:0000169	48.83	gold quality
vastus lateralis	UBERON:0001379	48.64	gold quality
oviduct epithelium	UBERON:0004804	48.56	gold quality
cardiac muscle of right atrium	UBERON:0003379	48.55	gold quality
deltoid	UBERON:0001476	48.52	gold quality
CA1 field of hippocampus	UBERON:0003881	48.50	gold quality
left ventricle myocardium	UBERON:0006566	48.24	gold quality
orbitofrontal cortex	UBERON:0004167	48.20	gold quality
upper arm skin	UBERON:0004263	48.06	gold quality
cervix epithelium	UBERON:0004801	48.04	gold quality
putamen	UBERON:0001874	48.02	gold quality
tongue squamous epithelium	UBERON:0006919	47.92	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-CURD-53	no	110.79
E-ANND-3	no	0.81

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): MBD1, MBD2, TCF3, TFCP2

miRNA regulators (miRDB)

27 targeting MAGEA12, 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-513B-5P	99.99	69.96	2150
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-3910	99.95	71.13	2227
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-383-3P	99.85	65.84	1359
HSA-MIR-202-3P	99.84	71.41	1290
HSA-MIR-6515-3P	99.82	68.19	1933
HSA-MIR-4694-3P	99.79	69.53	2640
HSA-MIR-3714	99.71	70.74	2671
HSA-MIR-4261	99.59	70.30	3415
HSA-MIR-5571-5P	99.49	66.99	1764
HSA-MIR-147B-5P	99.45	70.62	2432
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-1294	98.91	69.26	1030
HSA-MIR-9986	98.91	69.28	1024
HSA-MIR-1227-5P	98.65	65.32	1549
HSA-MIR-31-5P	98.58	68.35	1239
HSA-MIR-4773	98.35	67.30	1710
HSA-MIR-6509-3P	98.32	67.33	1343
HSA-MIR-3680-5P	98.06	66.20	394
HSA-MIR-12120	98.05	68.44	1768
HSA-MIR-5586-3P	95.51	67.00	805
HSA-MIR-550B-3P	95.43	67.73	599

Literature-anchored findings (GeneRIF, showing 8)

• 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)
• results of this study may indicate Melanoma associated-A12 antigen(MAGE-A12)as a diagnostic marker for early detection of oral squamous cell carcinoma (PMID:18057533)
• 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)
• To identify novel CTL epitopes from MAGE-A6 and MAGE-A12 antigens. (PMID:22707303)
• Data show the Differences in high resolution melting analysis in promoters of tumor markers neuronal membrane glycoprotein M6-B, melanoma antigen family A12 and immunoglobulin superfamily Fc receptor indicated invasiveness of hepatocellular carcinoma. (PMID:23950870)
• over-expression of MAGEA12 in a subset of gastric cancers was associated with later stage and reduced survival (PMID:28043151)
• MAGEA12-mediated down-regulation of p21 may be involved in cutaneous squamous cell carcinoma pathogenesis and MAGEA12 may serve as a molecular biomarker in cSCC. (PMID:30952725)
• Resveratrol acts via melanoma-associated antigen A12 (MAGEA12)/protein kinase B (Akt) signaling to inhibit the proliferation of oral squamous cell carcinoma cells. (PMID:34085601)

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), 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), MAGEB1 (ENSG00000214107), MAGEA3 (ENSG00000221867), MAGEB6B (ENSG00000232030), MAGEL2 (ENSG00000254585), MAGEA9B (ENSG00000267978), MAGEA2 (ENSG00000268606)

Protein

Protein identifiers

Melanoma-associated antigen 12 — P43365 (reviewed: P43365)

Alternative names: Cancer/testis antigen 1.12, MAGE-12 antigen, MAGE12F antigen

All UniProt accessions (1): P43365

UniProt curated annotations — full annotation on UniProt →

Function. Not known, though may play a role tumor transformation or progression. In vitro promotes cell viability in melanoma cell lines.

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.

RefSeq proteins (3): NP_001159858, NP_001159859, NP_005358 (=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-P43365-F1	72.49	0.46

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 39 (showing top): RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, HERNANDEZ_ABERRANT_MITOSIS_BY_DOCETACEL_4NM_UP, BROWNE_HCMV_INFECTION_48HR_DN, MATTIOLI_MULTIPLE_MYELOMA_SUBGROUPS, LIANG_SILENCED_BY_METHYLATION_2, GOMF_HISTONE_DEACETYLASE_BINDING, chrXq28, GOBP_NEGATIVE_REGULATION_OF_TRANSCRIPTION_BY_RNA_POLYMERASE_II, GOBP_NEGATIVE_REGULATION_OF_NUCLEOBASE_CONTAINING_COMPOUND_METABOLIC_PROCESS, SMID_BREAST_CANCER_RELAPSE_IN_BONE_DN, KRAS.AMP.LUNG_UP.V1_UP, ZNF184_TARGET_GENES, MIR6809_3P, MIR4261, MIR147B_5P

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

524 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MAGEA12	CTAG1A	P78358	668
MAGEA12	CSAG1	Q6PB30	605
MAGEA12	TTN	Q8WZ42	573
MAGEA12	CSAG2	Q9Y5P2	570
MAGEA12	CTAG2	O75638	541
MAGEA12	PMEL	P40967	515
MAGEA12	GAGE4	P0DSO3	503
MAGEA12	A0A1W2PQG5	A0A1W2PQG5	480
MAGEA12	CTAGE1	Q96RT6	474
MAGEA12	PRAME	P78395	472
MAGEA12	GAGE2A	Q6NT46	447
MAGEA12	HLA-A	P01891	447
MAGEA12	CT45A1	Q5HYN5	436
MAGEA12	XAGE2	Q96GT9	413
MAGEA12	UBQLN1	Q9UMX0	407

IntAct

121 interactions, top by confidence:

A	B	Type	Score
NANOS2	MAGEA12	psi-mi:“MI:0915”(physical association)	0.780
MAGEA12	NANOS2	psi-mi:“MI:0915”(physical association)	0.780
MAGEA12	NPPA	psi-mi:“MI:0915”(physical association)	0.720
MAGEA12	C16orf87	psi-mi:“MI:0915”(physical association)	0.720
MAGEA12	CLIP4	psi-mi:“MI:0915”(physical association)	0.720
MAGEA12	FNDC11	psi-mi:“MI:0915”(physical association)	0.720
MTFR1L	MAGEA12	psi-mi:“MI:0915”(physical association)	0.720
MAGEA12	POLL	psi-mi:“MI:0915”(physical association)	0.720
C16orf87	MAGEA12	psi-mi:“MI:0915”(physical association)	0.720
FNDC11	MAGEA12	psi-mi:“MI:0915”(physical association)	0.720
NPPA	MAGEA12	psi-mi:“MI:0915”(physical association)	0.720
MAGEA12	MTFR1L	psi-mi:“MI:0915”(physical association)	0.720

BioGRID (39): MAGEA12 (Two-hybrid), NPPA (Two-hybrid), ZNF33B (Two-hybrid), SCMH1 (Two-hybrid), POLL (Two-hybrid), ABI3 (Two-hybrid), TBC1D19 (Two-hybrid), MTFR1L (Two-hybrid), C20orf195 (Two-hybrid), FASTKD3 (Two-hybrid), CLIP4 (Two-hybrid), MTFR2 (Two-hybrid), KANSL1 (Two-hybrid), NANOS2 (Two-hybrid), C16orf87 (Two-hybrid)

ESM2 similar proteins: A0A0G2JMD5, A0A0J9YX57, A2A368, A2A9R3, A6NCF6, A6NK02, A8MXT2, D9I2F9, D9I2G3, D9I2H0, O15479, O15480, O15481, O60809, O95521, P14373, P25233, P43355, P43356, P43357, P43358, P43360, P43361, P43362, P43363, P43364, P43365, P43366, Q2LKU9, Q2LKW6, Q4R998, Q5PPP4, Q5SWL7, Q62191, Q6AY37, Q6AZZ1, Q8BQR7, Q8BVP1, Q8K243, Q8N7X4

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

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	40
Likely benign	5
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

434 predictions. Top by Δscore:

Variant	Effect	Δscore
X:152733858:C:CT	donor_loss	1.0000
X:152733860:TAC:T	donor_loss	1.0000
X:152733861:TTA:T	donor_loss	1.0000
X:152733858:C:CC	donor_gain	0.9900
X:152733859:A:AC	donor_gain	0.9900
X:152733854:G:A	donor_gain	0.9800
X:152733858:CCTTG:C	donor_gain	0.9800
X:152733827:C:A	donor_gain	0.9600
X:152734361:C:CA	donor_gain	0.9600
X:152736083:T:A	acceptor_loss	0.9600
X:152736084:CTGAA:C	acceptor_loss	0.9600
X:152733851:T:TA	donor_gain	0.9500
X:152735145:CTGGA:C	acceptor_loss	0.9300
X:152735146:TCTGG:T	acceptor_loss	0.9300
X:152734365:C:A	donor_gain	0.9000
X:152733858:CC:C	donor_gain	0.8800
X:152733859:AC:A	donor_gain	0.8800
X:152736084:C:CC	acceptor_gain	0.8500
X:152735145:C:CC	acceptor_gain	0.8400
X:152734832:C:A	donor_gain	0.8300
X:152735143:G:C	acceptor_loss	0.8300
X:152736072:G:C	acceptor_loss	0.8000
X:152735254:C:CC	donor_loss	0.7900
X:152735255:T:TA	donor_loss	0.7900
X:152735256:CT:C	donor_loss	0.7900
X:152735259:CTTCT:C	donor_loss	0.7900
X:152734554:C:CA	donor_gain	0.7800
X:152735251:C:G	donor_loss	0.7800
X:152736082:G:C	acceptor_loss	0.7800
X:152734591:T:TA	donor_gain	0.7700

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS111344124 (X:152737395 A>G), RS111942589 (X:152733616 G>C,T), RS111946653 (X:152732998 G>C), RS112142853 (X:152732819 T>C), RS112210250 (X:152734522 G>A), RS112383352 (X:152732878 T>C,G), RS112733171 (X:152732500 C>G,T), RS112975238 (X:152736742 A>G,T), RS113255279 (X:152737156 T>C), RS113496515 (X:152732541 C>A), RS1156315015 (X:152735768 C>A), RS1156431260 (X:152734902 G>A), RS1156642244 (X:152734180 CA>C), RS1156813690 (X:152733707 T>C), RS1157848426 (X:152737301 T>C)

Disease associations

OMIM: gene MIM:300177 | 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

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

Chemical	Actions (top 5)	PubMed papers
Decitabine	affects expression, increases expression	2
Valproic Acid	increases expression, increases methylation	2
Mitomycin	decreases expression, increases response to substance, affects response to substance, affects binding	2
butyraldehyde	increases expression	1
abrine	increases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Temozolomide	increases expression	1
Atrazine	increases expression	1
Benzo(a)pyrene	affects methylation	1
Cisplatin	affects binding, decreases expression, increases response to substance	1
Etoposide	affects response to substance	1
Fluorouracil	decreases expression, affects response to substance	1
Methotrexate	increases expression	1
Plant Extracts	affects cotreatment, decreases expression	1
Aflatoxin B1	increases methylation	1

Clinical trials (associated diseases)

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