MAGEC3

Summary

MAGEC3 (MAGE family member C3, HGNC:23798) is a protein-coding gene on chromosome Xq27.2, encoding Melanoma-associated antigen C3 (Q8TD91).

This gene is a member of the MAGEC gene family. The members of this family are not expressed in normal tissues, except for testis, and are expressed in tumors of various histological types. The MAGEC genes are clustered on chromosome Xq26-q27. Two transcript variants encoding distinct isoforms have been found for this gene.

Source: NCBI Gene 139081 — RefSeq curated summary.

At a glance

• GWAS associations: 6
• Clinical variants (ClinVar): 169 total
• MANE Select transcript: NM_138702

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:23798
Approved symbol	MAGEC3
Name	MAGE family member C3
Location	Xq27.2
Locus type	gene with protein product
Status	Approved
Aliases	HCA2, MAGE-C3, CT7.2
Ensembl gene	ENSG00000165509
Ensembl biotype	protein_coding
OMIM	300469
Entrez	139081

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 4 protein_coding

ENST00000298296, ENST00000409007, ENST00000443323, ENST00000483584

RefSeq mRNA: 2 — MANE Select: NM_138702 NM_138702, NM_177456

CCDS: CCDS14676, CCDS14677

Canonical transcript exons

ENST00000298296 — 8 exons

Exon	Start	End
ENSE00001093689	141881403	141881796
ENSE00001203325	141896882	141897486
ENSE00001203327	141895485	141895559
ENSE00001203333	141879175	141879431
ENSE00001203335	141865471	141865605
ENSE00001203340	141897629	141897832
ENSE00001203345	141838316	141838438
ENSE00003667150	141895269	141895407

Expression profiles

Bgee: expression breadth ubiquitous, 121 present calls, max score 79.39.

Top tissues by expression

235 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	79.39	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	73.40	gold quality
spinal cord	UBERON:0002240	70.41	gold quality
descending thoracic aorta	UBERON:0002345	69.22	gold quality
right coronary artery	UBERON:0001625	68.30	gold quality
thoracic aorta	UBERON:0001515	66.19	gold quality
ascending aorta	UBERON:0001496	65.95	gold quality
aorta	UBERON:0000947	64.38	gold quality
Brodmann (1909) area 9	UBERON:0013540	64.35	gold quality
right frontal lobe	UBERON:0002810	63.56	gold quality
popliteal artery	UBERON:0002250	63.28	gold quality
tibial artery	UBERON:0007610	63.21	gold quality
nucleus accumbens	UBERON:0001882	62.84	gold quality
hypothalamus	UBERON:0001898	61.87	gold quality
left coronary artery	UBERON:0001626	61.50	gold quality
substantia nigra	UBERON:0002038	61.39	gold quality
amygdala	UBERON:0001876	61.26	gold quality
coronary artery	UBERON:0001621	60.87	gold quality
anterior cingulate cortex	UBERON:0009835	60.65	gold quality
putamen	UBERON:0001874	60.18	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	59.32	gold quality
caudate nucleus	UBERON:0001873	58.97	gold quality
midbrain	UBERON:0001891	58.83	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	58.27	gold quality
Ammon’s horn	UBERON:0001954	57.98	gold quality
ventricular zone	UBERON:0003053	56.89	gold quality
forebrain	UBERON:0001890	56.19	gold quality
adenohypophysis	UBERON:0002196	55.86	gold quality
neocortex	UBERON:0001950	55.82	gold quality
ganglionic eminence	UBERON:0004023	55.82	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.45

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 2)

• The data support an important role for prostaglandin activation of sAC and PKA in H2O2-induced barrier disruption. (PMID:26857816)
• Nicotinic acid suppresses sebaceous lipogenesis of human sebocytes via activating hydroxycarboxylic acid receptor 2 (HCA2 ). (PMID:31273921)

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), 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 C3 — Q8TD91 (reviewed: Q8TD91)

Alternative names: Cancer/testis antigen 7.2, Hepatocellular carcinoma-associated antigen 2, MAGE-C3 antigen

All UniProt accessions (2): Q8TD91, Q3SYA6

UniProt curated annotations — full annotation on UniProt →

Tissue specificity. Expressed in testis. Not expressed in other normal tissues, but is expressed in tumors of different histological origins.

Isoforms (2)

UniProt ID	Names	Canonical?
Q8TD91-1	1	yes
Q8TD91-2	2

RefSeq proteins (2): NP_619647, NP_803251 (=MANE)

Domains & families (InterPro)

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

UniProt features (17 total): sequence variant 4, splice variant 3, modified residue 3, domain 2, compositionally biased region 2, chain 1, sequence conflict 1, region of interest 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8TD91-F1	43.92	0.00

Functional residue map

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

Post-translational modifications (3): 478, 484, 485

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 20 (showing top): chrXq27, GOBP_NEGATIVE_REGULATION_OF_TRANSCRIPTION_BY_RNA_POLYMERASE_II, GOBP_NEGATIVE_REGULATION_OF_NUCLEOBASE_CONTAINING_COMPOUND_METABOLIC_PROCESS, ATF2_S_UP.V1_UP, ATF2_UP.V1_UP, NOTCH_DN.V1_DN, HMGA1_TARGET_GENES, ZNF410_TARGET_GENES, GSE1432_CTRL_VS_IFNG_1H_MICROGLIA_DN, GR_Q6_01, DESCARTES_FETAL_MUSCLE_SATELLITE_CELLS, GSE29615_CTRL_VS_LAIV_FLU_VACCINE_PBMC_UP, GOBP_NEGATIVE_REGULATION_OF_RNA_BIOSYNTHETIC_PROCESS, GSE36476_YOUNG_VS_OLD_DONOR_MEMORY_CD4_TCELL_40H_TSST_ACT_UP, GSE3982_DC_VS_NEUTROPHIL_LPS_STIM_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

516 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MAGEC3	CNKSR2	Q8WXI2	647
MAGEC3	KDM5C	P41229	499
MAGEC3	SPANXN4	Q5MJ08	480
MAGEC3	KDM6A	O15550	465
MAGEC3	DDX3X	O00571	448
MAGEC3	TMEM89	A2RUT3	447
MAGEC3	SPANXD	Q9BXN6	447
MAGEC3	EOLA2	Q96DE9	419
MAGEC3	CXorf51A	A0A1B0GTR3	418
MAGEC3	SPANXA1	Q9NS26	407
MAGEC3	CAPN6	Q9Y6Q1	395
MAGEC3	ATRX	P46100	381
MAGEC3	GARIN5A	Q6IPT2	373
MAGEC3	VGLL1	Q99990	373
MAGEC3	EOLA1	Q8TE69	372

IntAct

2 interactions, top by confidence:

A	B	Type	Score
MAGEC3	CFTR	psi-mi:“MI:0915”(physical association)	0.370

BioGRID (9): MAGEC3 (Two-hybrid), MAGEC3 (Two-hybrid), MAGEC3 (Two-hybrid), TCF24 (Two-hybrid), MAGEC3 (Two-hybrid), MAGEC3 (Two-hybrid), MAGEC3 (Proximity Label-MS), MAGEC3 (PCA), MAGEC3 (Protein-peptide)

ESM2 similar proteins: A0A0J9YX57, A0A3B3IT33, A2A368, A2A9R3, A6NCF6, A6NLI5, A8MXT2, C9J1S8, K7N6K2, O15479, O15480, O15481, O19110, P0CW00, P14373, P43355, P43356, P43357, P43358, P43360, P43361, P43362, P43363, P43364, P43365, P43366, Q01534, Q2LKW6, Q4R998, Q5D7H7, Q5D7I1, Q5D7I6, Q5VTA0, Q62158, Q62191, Q6AY37, Q8BQR7, Q8N7X4, Q8R4Y0, Q8TD91

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

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	82
Likely benign	12
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

1807 predictions. Top by Δscore:

Variant	Effect	Δscore
X:141896870:T:TA	acceptor_gain	1.0000
X:141896871:G:A	acceptor_gain	1.0000
X:141846026:GTT:G	acceptor_gain	0.9900
X:141870052:G:GT	donor_gain	0.9900
X:141870052:G:T	donor_gain	0.9900
X:141897031:T:TA	acceptor_gain	0.9900
X:141846025:A:AG	acceptor_gain	0.9800
X:141846026:G:GG	acceptor_gain	0.9800
X:141896178:TGCA:T	acceptor_loss	0.9800
X:141896180:CAGG:C	acceptor_loss	0.9800
X:141896181:A:AG	acceptor_gain	0.9800
X:141896181:A:C	acceptor_loss	0.9800
X:141896182:G:GG	acceptor_gain	0.9800
X:141896755:G:GT	donor_gain	0.9800
X:141896761:G:GT	donor_gain	0.9800
X:141896764:G:GT	donor_gain	0.9800
X:141896276:GGTG:G	donor_loss	0.9700
X:141896277:G:T	donor_loss	0.9700
X:141896278:T:G	donor_loss	0.9700
X:141896677:C:G	acceptor_gain	0.9700
X:141896750:A:G	donor_gain	0.9700
X:141896758:G:GT	donor_gain	0.9700
X:141897032:G:A	acceptor_gain	0.9700
X:141838375:G:GG	donor_gain	0.9600
X:141846026:GTTGT:G	acceptor_gain	0.9600
X:141846718:GA:G	donor_gain	0.9600
X:141846720:G:GG	donor_gain	0.9600
X:141882144:TG:T	donor_gain	0.9600
X:141896181:AG:A	acceptor_gain	0.9600
X:141896182:GG:G	acceptor_gain	0.9600

AlphaMissense

4246 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:141881572:G:C	A229P	0.962
X:141881471:T:C	L195P	0.953
X:141881728:A:C	S281R	0.953
X:141881730:T:A	S281R	0.953
X:141881730:T:G	S281R	0.953
X:141897418:A:C	S554R	0.948
X:141897420:T:A	S554R	0.948
X:141897420:T:G	S554R	0.948
X:141897158:T:C	L467P	0.947
X:141897662:T:C	F588L	0.945
X:141897664:T:A	F588L	0.945
X:141897664:T:G	F588L	0.945
X:141881551:T:C	F222L	0.941
X:141881553:T:A	F222L	0.941
X:141881553:T:G	F222L	0.941
X:141838352:T:C	F13L	0.938
X:141838354:C:A	F13L	0.938
X:141838354:C:G	F13L	0.938
X:141897238:T:C	F494L	0.938
X:141897240:T:A	F494L	0.938
X:141897240:T:G	F494L	0.938
X:141897698:T:C	F600L	0.936
X:141897700:T:A	F600L	0.936
X:141897700:T:G	F600L	0.936
X:141881467:T:C	F194L	0.934
X:141881469:T:A	F194L	0.934
X:141881469:T:G	F194L	0.934
X:141897154:T:C	F466L	0.934
X:141897156:T:A	F466L	0.934
X:141897156:T:G	F466L	0.934

dbSNP variants (sampled 300 via entrez): RS1000040476 (X:141846484 A>G), RS1000121902 (X:141885757 G>C), RS1000240356 (X:141841640 G>A), RS1000323586 (X:141866863 A>G), RS1000324302 (X:141850307 C>A,G,T), RS1000441669 (X:141838974 C>T), RS1000471346 (X:141885528 C>G,T), RS1000488792 (X:141864129 A>C,T), RS1000567476 (X:141887791 T>G), RS1000644579 (X:141856589 A>G), RS1000712812 (X:141858387 A>C), RS1000793556 (X:141858519 CTTTAT>C), RS1000904595 (X:141869258 T>C), RS1000952682 (X:141880100 C>T), RS1001027787 (X:141879783 C>G,T)

Disease associations

OMIM: gene MIM:300469 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST006484_8	Type 2 diabetes	5.000000e-07
GCST009391_1250	Metabolite levels	3.000000e-06
GCST009391_292	Metabolite levels	3.000000e-06
GCST009391_320	Metabolite levels	4.000000e-06
GCST009391_329	Metabolite levels	8.000000e-06
GCST009391_376	Metabolite levels	9.000000e-06

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0010423	triacylglycerol 54:5 measurement
EFO:0010425	triacylglycerol 54:7 measurement
EFO:0010431	triacylglycerol 56:4 measurement
EFO:0010432	triacylglycerol 56:5 measurement
EFO:0010436	triacylglycerol 56:9 measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

9 total (human), top 9 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases methylation	2
Aflatoxin B1	decreases methylation	2
sodium arsenite	increases expression	1
benzo(e)pyrene	decreases methylation	1
Grape Seed Proanthocyanidins	affects cotreatment, increases expression	1
Catechin	affects cotreatment, increases expression	1
Endosulfan	increases expression	1
Methapyrilene	decreases methylation	1
Okadaic Acid	decreases expression	1

Clinical trials (associated diseases)

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