MAGEE2

Summary

MAGEE2 (MAGE family member E2, HGNC:24935) is a protein-coding gene on chromosome Xq13.3, encoding Melanoma-associated antigen E2 (Q8TD90).

This gene encodes a member of the E subfamily of MAGE (melanoma antigen-encoding gene) gene family. The gene is intronless and the encoded protein has two of the MAGE domains which are characteristic of MAGE family proteins.

Source: NCBI Gene 139599 — RefSeq curated summary.

At a glance

• Gene–disease (curated): male infertility with azoospermia or oligozoospermia due to single gene mutation (Moderate, GenCC)
• GWAS associations: 1
• Clinical variants (ClinVar): 78 total
• MANE Select transcript: NM_138703

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:24935
Approved symbol	MAGEE2
Name	MAGE family member E2
Location	Xq13.3
Locus type	gene with protein product
Status	Approved
Aliases	HCA3
Ensembl gene	ENSG00000186675
Ensembl biotype	protein_coding
OMIM	300760
Entrez	139599

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000373359

RefSeq mRNA: 1 — MANE Select: NM_138703 NM_138703

CCDS: CCDS14431

Canonical transcript exons

ENST00000373359 — 1 exons

Exon	Start	End
ENSE00001460378	75782987	75785254

Expression profiles

Bgee: expression breadth ubiquitous, 104 present calls, max score 86.74.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.1642 / max 8.9674, expressed in 84 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
199780	0.1642	84

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
endothelial cell	CL:0000115	86.74	gold quality
cortical plate	UBERON:0005343	78.83	gold quality
ganglionic eminence	UBERON:0004023	72.12	gold quality
Brodmann (1909) area 23	UBERON:0013554	71.46	gold quality
ventricular zone	UBERON:0003053	69.96	gold quality
cerebellar hemisphere	UBERON:0002245	69.89	gold quality
cerebellar cortex	UBERON:0002129	69.72	gold quality
right hemisphere of cerebellum	UBERON:0014890	69.54	gold quality
Brodmann (1909) area 9	UBERON:0013540	68.54	gold quality
cerebellum	UBERON:0002037	68.45	gold quality
prefrontal cortex	UBERON:0000451	66.80	gold quality
middle temporal gyrus	UBERON:0002771	66.53	silver quality
hypothalamus	UBERON:0001898	65.54	gold quality
primary visual cortex	UBERON:0002436	65.33	gold quality
anterior cingulate cortex	UBERON:0009835	65.23	gold quality
right frontal lobe	UBERON:0002810	64.91	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	64.65	gold quality
neocortex	UBERON:0001950	64.02	gold quality
frontal cortex	UBERON:0001870	63.18	gold quality
cerebral cortex	UBERON:0000956	61.71	gold quality
nucleus accumbens	UBERON:0001882	60.68	gold quality
brain	UBERON:0000955	59.61	gold quality
forebrain	UBERON:0001890	59.02	gold quality
occipital lobe	UBERON:0002021	58.96	gold quality
islet of Langerhans	UBERON:0000006	58.73	gold quality
amygdala	UBERON:0001876	56.83	gold quality
caudate nucleus	UBERON:0001873	56.50	gold quality
putamen	UBERON:0001874	55.70	gold quality
Ammon’s horn	UBERON:0001954	54.69	gold quality
Brodmann (1909) area 46	UBERON:0006483	53.64	silver quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.47

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

25 targeting MAGEE2, 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-5011-5P	100.00	83.46	5820
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-568	99.98	69.86	2084
HSA-MIR-4760-3P	99.93	70.50	2385
HSA-MIR-5010-3P	99.83	70.60	2357
HSA-MIR-4645-3P	99.76	69.33	993
HSA-MIR-4320	99.75	65.80	793
HSA-MIR-2113	99.58	71.22	1521
HSA-MIR-302B-5P	99.50	69.49	1857
HSA-MIR-302D-5P	99.50	69.34	1863
HSA-MIR-4728-3P	99.47	68.94	981
HSA-MIR-12113	99.32	67.54	1072
HSA-MIR-223-5P	99.24	68.82	1206
HSA-MIR-664A-3P	99.22	71.08	2696
HSA-MIR-4539	98.78	67.18	888
HSA-MIR-619-3P	98.38	65.58	693
HSA-MIR-599	98.32	66.99	1037
HSA-MIR-1225-3P	97.29	64.60	876
HSA-MIR-616-3P	96.82	66.99	784

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	ndnl2	ENSDARG00000058212
mus_musculus	Magee2	ENSMUSG00000031224
rattus_norvegicus	Magee2	ENSRNOG00000021400
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), 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 E2 — Q8TD90 (reviewed: Q8TD90)

Alternative names: Hepatocellular carcinoma-associated protein 3, MAGE-E2 antigen

All UniProt accessions (1): Q8TD90

RefSeq proteins (1): NP_619648* (*=MANE)

Domains & families (InterPro)

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

Pfam: PF01454

UniProt features (4 total): domain 2, chain 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8TD90-F1	73.16	0.06

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 27 (showing top): GOBP_ANIMAL_ORGAN_MORPHOGENESIS, OCT1_07, GOBP_HEAD_DEVELOPMENT, GOBP_BRAIN_MORPHOGENESIS, YATGNWAAT_OCT_C, chrXq13, GOBP_NEGATIVE_REGULATION_OF_TRANSCRIPTION_BY_RNA_POLYMERASE_II, GOBP_NEGATIVE_REGULATION_OF_NUCLEOBASE_CONTAINING_COMPOUND_METABOLIC_PROCESS, RYBP_TARGET_GENES, MIR6867_5P, MIR4760_3P, MIR5010_3P, MIR302B_5P, MIR302D_5P, MIR12113

GO Biological Process (3): negative regulation of transcription by RNA polymerase II (GO:0000122), brain morphogenesis (GO:0048854), brain development (GO:0007420)

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
brain development	1
animal organ morphogenesis	1
central nervous system development	1
animal organ development	1
head development	1
binding	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

1182 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MAGEE2	RNF166	Q96A37	549
MAGEE2	FAM229B	Q4G0N7	543
MAGEE2	MNAT1	P51948	503
MAGEE2	ZSWIM7	Q19AV6	497
MAGEE2	GTPBP6	O43824	471
MAGEE2	CEP41	Q9BYV8	469
MAGEE2	SYTL1	Q8IYJ3	459
MAGEE2	EFCAB3	Q8N7B9	451
MAGEE2	MAGEC2	Q9UBF1	446
MAGEE2	EFCAB13	Q8IY85	428
MAGEE2	TERB1	Q8NA31	420
MAGEE2	TRAF6	Q9Y4K3	416
MAGEE2	HUWE1	Q7Z6Z7	372
MAGEE2	SPARC	P09486	371
MAGEE2	ZNF416	Q9BWM5	366

IntAct

6 interactions, top by confidence:

A	B	Type	Score
MAGEE2	ARIH1	psi-mi:“MI:0915”(physical association)	0.560
MAGEE2	VIM	psi-mi:“MI:0915”(physical association)	0.400
Mecom	ESYT2	psi-mi:“MI:0914”(association)	0.350
MAGEE2	PLD6	psi-mi:“MI:0914”(association)	0.350
CDC5L		psi-mi:“MI:0914”(association)	0.350

BioGRID (13): PCGF6 (Two-hybrid), RNF166 (Two-hybrid), TRAF6 (Two-hybrid), RNF166 (Affinity Capture-Western), TRAF6 (Affinity Capture-Western), TRIM31 (Affinity Capture-Western), MNAT1 (Two-hybrid), MAGEE2 (Affinity Capture-MS), ARIH1 (Affinity Capture-MS), PLD6 (Affinity Capture-MS), MAGEE2 (Affinity Capture-MS), MAGEE2 (Proximity Label-MS), ARIH1 (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

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	69
Likely benign	7
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

42 predictions. Top by Δscore:

Variant	Effect	Δscore
X:75783943:T:TG	acceptor_gain	0.4500
X:75784978:TC:T	donor_gain	0.3100
X:75785036:GGCTT:G	donor_loss	0.3100
X:75785037:GCTT:G	donor_loss	0.3100
X:75785038:CT:C	donor_loss	0.3100
X:75785039:T:TC	donor_loss	0.3100
X:75785040:TAC:T	donor_loss	0.3100
X:75785041:ACCAG:A	donor_loss	0.3100
X:75785042:CCAGA:C	donor_loss	0.3100
X:75784898:T:TA	acceptor_gain	0.2900
X:75785043:C:A	donor_loss	0.2900
X:75784869:GGCCT:G	acceptor_gain	0.2700
X:75784870:GCCTG:G	acceptor_gain	0.2700
X:75784931:CGA:C	acceptor_gain	0.2700
X:75784933:A:AC	acceptor_gain	0.2700
X:75784934:C:CC	acceptor_gain	0.2700
X:75785041:A:AC	donor_gain	0.2700
X:75785042:C:CC	donor_gain	0.2700
X:75785057:C:CT	acceptor_gain	0.2700
X:75783332:C:CT	donor_gain	0.2600
X:75783333:T:TT	donor_gain	0.2600
X:75784382:T:TA	donor_gain	0.2600
X:75784874:G:GT	acceptor_gain	0.2600
X:75783958:CCA:C	acceptor_gain	0.2500
X:75783944:C:A	acceptor_gain	0.2400
X:75784290:GCCCC:G	acceptor_gain	0.2300
X:75784879:GTGTT:G	acceptor_gain	0.2300
X:75783959:CA:C	acceptor_gain	0.2200
X:75784969:G:C	donor_gain	0.2200
X:75784977:T:C	donor_gain	0.2200

AlphaMissense

3472 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:75783610:A:G	L481S	0.983
X:75784300:A:G	F251S	0.982
X:75783653:A:G	W467R	0.980
X:75783653:A:T	W467R	0.980
X:75784295:A:G	W253R	0.980
X:75784295:A:T	W253R	0.980
X:75783599:C:G	A485P	0.978
X:75784768:A:G	L95S	0.977
X:75783569:A:G	W495R	0.975
X:75783569:A:T	W495R	0.975
X:75784096:A:T	V319D	0.974
X:75784345:A:G	L236S	0.974
X:75784347:G:C	F235L	0.972
X:75784347:G:T	F235L	0.972
X:75784349:A:G	F235L	0.972
X:75784658:C:G	A132P	0.972
X:75784293:C:A	W253C	0.971
X:75784293:C:G	W253C	0.971
X:75783986:C:G	A356P	0.970
X:75783567:C:A	W495C	0.967
X:75783567:C:G	W495C	0.967
X:75783827:C:G	G409R	0.967
X:75783973:A:G	L360P	0.967
X:75784042:A:G	L337P	0.967
X:75784299:G:C	F251L	0.967
X:75784299:G:T	F251L	0.967
X:75784301:A:G	F251L	0.967
X:75784660:C:G	R131P	0.966
X:75783920:A:C	Y378D	0.965
X:75784701:A:C	F117L	0.965

dbSNP variants (sampled 300 via entrez): RS1002821756 (X:75785589 G>T), RS1002832729 (X:75782625 C>G,T), RS1004248089 (X:75782601 A>G), RS1004832128 (X:75786147 G>A), RS1006183717 (X:75784327 T>G), RS1007629101 (X:75785183 G>T), RS1008411926 (X:75785420 A>T), RS1008633160 (X:75786638 C>T), RS1008999594 (X:75786360 A>G), RS1010362746 (X:75783810 C>T), RS1010850819 (X:75782733 C>T), RS1010895374 (X:75783530 C>T), RS1011049150 (X:75787170 T>C), RS1011485492 (X:75785223 C>G,T), RS1011885885 (X:75784955 C>T)

Disease associations

OMIM: gene MIM:300760 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
male infertility with azoospermia or oligozoospermia due to single gene mutation	Moderate	X-linked

Mondo (1): (MONDO:0018393)

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST006031_14	Potassium levels	3.000000e-08

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0009283	potassium measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

10 total (human), top 10 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
arsenite	increases methylation	1
butyraldehyde	increases expression	1
pentanal	increases expression	1
Benzo(a)pyrene	affects methylation, decreases methylation, increases methylation	1
Cadmium	decreases expression, increases abundance	1
Diethylhexyl Phthalate	decreases expression	1
Ivermectin	decreases expression	1
Valproic Acid	decreases methylation	1
Aflatoxin B1	decreases methylation	1
Cadmium Chloride	decreases expression, increases abundance	1

Clinical trials (associated diseases)

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