MAGEE1

Summary

MAGEE1 (MAGE family member E1, HGNC:24934) is a protein-coding gene on chromosome Xq13.3, encoding Melanoma-associated antigen E1 (Q9HCI5). May enhance ubiquitin ligase activity of RING-type zinc finger-containing E3 ubiquitin-protein ligases.

This gene encodes an alpha-dystrobrevin-associated MAGE (melanoma-associated antigen) protein, which is a member of the MAGE family. The protein contains a nuclear localization signal in the N-terminus, 30 12-amino acid repeats beginning at nt 60 with the consensus sequence ASEGPSTSVLPT, and two MAGE domains in the C-terminus. It may play a signaling role in brain, muscle, and peripheral nerve. This gene is located on X chromosome in a region containing loci linked to cognitive disability.

Source: NCBI Gene 57692 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 95 total
• MANE Select transcript: NM_020932

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:24934
Approved symbol	MAGEE1
Name	MAGE family member E1
Location	Xq13.3
Locus type	gene with protein product
Status	Approved
Aliases	KIAA1587, DAMAGE
Ensembl gene	ENSG00000198934
Ensembl biotype	protein_coding
OMIM	300759
Entrez	57692

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000361470

RefSeq mRNA: 1 — MANE Select: NM_020932 NM_020932

CCDS: CCDS14433

Canonical transcript exons

ENST00000361470 — 1 exons

Exon	Start	End
ENSE00001435360	76427710	76431342

Expression profiles

Bgee: expression breadth ubiquitous, 222 present calls, max score 98.93.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 6.8206 / max 233.0617, expressed in 1146 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
196771	6.6679	1142
196772	0.1527	84

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
endothelial cell	CL:0000115	98.93	gold quality
Brodmann (1909) area 23	UBERON:0013554	97.03	gold quality
pons	UBERON:0000988	96.13	gold quality
substantia nigra pars compacta	UBERON:0001965	94.93	gold quality
lateral nuclear group of thalamus	UBERON:0002736	94.51	gold quality
cerebellar vermis	UBERON:0004720	93.83	gold quality
middle temporal gyrus	UBERON:0002771	93.49	gold quality
superior vestibular nucleus	UBERON:0007227	93.23	gold quality
superior frontal gyrus	UBERON:0002661	93.15	gold quality
postcentral gyrus	UBERON:0002581	92.74	gold quality
parietal lobe	UBERON:0001872	92.73	gold quality
Brodmann (1909) area 46	UBERON:0006483	92.61	gold quality
entorhinal cortex	UBERON:0002728	92.44	gold quality
occipital lobe	UBERON:0002021	92.16	gold quality
primary visual cortex	UBERON:0002436	92.13	gold quality
substantia nigra pars reticulata	UBERON:0001966	91.26	gold quality
medulla oblongata	UBERON:0001896	90.86	gold quality
dorsal root ganglion	UBERON:0000044	90.24	gold quality
Brodmann (1909) area 9	UBERON:0013540	89.08	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	89.03	gold quality
prefrontal cortex	UBERON:0000451	88.97	gold quality
frontal cortex	UBERON:0001870	88.83	gold quality
ventral tegmental area	UBERON:0002691	88.61	gold quality
upper arm skin	UBERON:0004263	88.18	gold quality
cerebral cortex	UBERON:0000956	87.95	gold quality
neocortex	UBERON:0001950	87.87	gold quality
lateral globus pallidus	UBERON:0002476	87.73	gold quality
trigeminal ganglion	UBERON:0001675	86.95	gold quality
hypothalamus	UBERON:0001898	86.59	gold quality
dorsal plus ventral thalamus	UBERON:0001897	86.54	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.43

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): KLF2, TP53

miRNA regulators (miRDB)

30 targeting MAGEE1, 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-485-3P	99.98	70.68	1585
HSA-MIR-539-3P	99.98	70.74	1616
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-338-5P	99.92	72.34	2951
HSA-MIR-627-3P	99.90	71.42	3316
HSA-MIR-30A-3P	99.87	69.74	2928
HSA-MIR-30D-3P	99.87	69.92	2917
HSA-MIR-30E-3P	99.87	69.68	2942
HSA-MIR-1323	99.83	69.89	2471
HSA-MIR-498-5P	99.76	69.64	1807
HSA-MIR-4517	99.76	69.19	1867
HSA-MIR-3617-5P	99.75	69.41	1968
HSA-MIR-641	99.75	69.35	1975
HSA-MIR-4719	99.73	72.10	3329
HSA-MIR-4729	99.69	72.18	4233
HSA-MIR-3120-3P	99.54	70.28	2669
HSA-MIR-1324	99.46	66.57	1302
HSA-MIR-4777-5P	99.33	67.53	1148
HSA-MIR-4426	99.17	66.74	1949
HSA-MIR-4705	99.10	69.10	1091
HSA-MIR-6830-5P	99.01	68.73	1884
HSA-MIR-561-5P	98.25	68.13	1365
HSA-MIR-2467-5P	97.36	67.71	991
HSA-MIR-203B-5P	97.24	68.54	543
HSA-MIR-3194-5P	96.80	64.90	1027
HSA-MIR-4749-3P	96.40	66.24	798
HSA-MIR-5002-3P	95.75	67.04	542

Literature-anchored findings (GeneRIF, showing 2)

• a new dystrobrevin-associated protein that may play a signaling role in brain, muscle, and peripheral nerve (PMID:14623885)
• Data suggest that lipid homeostasis may be altered in carriers of selected HCA1 missense variants. (PMID:23268337)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	ndnl2	ENSDARG00000058212
mus_musculus	Magee1	ENSMUSG00000031227
rattus_norvegicus	Magee1	ENSRNOG00000002660
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), MAGEA12 (ENSG00000213401), MAGEB1 (ENSG00000214107), MAGEA3 (ENSG00000221867), MAGEB6B (ENSG00000232030), MAGEL2 (ENSG00000254585), MAGEA9B (ENSG00000267978), MAGEA2 (ENSG00000268606)

Protein

Protein identifiers

Melanoma-associated antigen E1 — Q9HCI5 (reviewed: Q9HCI5)

Alternative names: Alpha-dystrobrevin-associated MAGE Protein, Hepatocellular carcinoma-associated protein 1, MAGE-E1 antigen

All UniProt accessions (1): Q9HCI5

UniProt curated annotations — full annotation on UniProt →

Function. May enhance ubiquitin ligase activity of RING-type zinc finger-containing E3 ubiquitin-protein ligases. Proposed to act through recruitment and/or stabilization of the Ubl-conjugating enzyme (E2) at the E3:substrate complex.

Subunit / interactions. Interacts with DTNA. Interacts with TRIM28.

Subcellular location. Cytoplasm. Perinuclear region. Nucleus. Cell membrane.

RefSeq proteins (1): NP_065983* (*=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 (17 total): compositionally biased region 8, sequence variant 4, domain 2, region of interest 2, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9HCI5-F1	55.48	0.03

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 72 (showing top): SHEPARD_CRASH_AND_BURN_MUTANT_UP, GOCC_NEURON_PROJECTION, HAMAI_APOPTOSIS_VIA_TRAIL_DN, GOCC_POSTSYNAPSE, GOCC_SYNAPSE, GOCC_POSTSYNAPTIC_MEMBRANE, GOCC_PLASMA_MEMBRANE_REGION, GOCC_SOMATODENDRITIC_COMPARTMENT, GOCC_SYNAPTIC_MEMBRANE, chrXq13, GOBP_NEGATIVE_REGULATION_OF_TRANSCRIPTION_BY_RNA_POLYMERASE_II, GOBP_NEGATIVE_REGULATION_OF_NUCLEOBASE_CONTAINING_COMPOUND_METABOLIC_PROCESS, GOCC_DENDRITIC_TREE, MIR335_3P, MIR5696

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 (7): nucleus (GO:0005634), plasma membrane (GO:0005886), dendrite (GO:0030425), postsynaptic membrane (GO:0045211), perinuclear region of cytoplasm (GO:0048471), cytoplasm (GO:0005737), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
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
membrane	1
cell periphery	1
neuron projection	1
dendritic tree	1
synaptic membrane	1
postsynapse	1
cytoplasm	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

576 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MAGEE1	DTNA	Q9Y4J8	709
MAGEE1	SNTA1	Q13424	587
MAGEE1	C4BPB	P20851	456
MAGEE1	EMCN	Q9ULC0	413
MAGEE1	CAGE1	Q8TC20	408
MAGEE1	CEACAM1	P13688	400
MAGEE1	C4BPA	P04003	391
MAGEE1	GAGE12J	A6NER3	373
MAGEE1	ZMYND19	Q96E35	354
MAGEE1	MAGED4B	Q96JG8	348
MAGEE1	SSX5	O60225	321
MAGEE1	TMEM168	Q9H0V1	321
MAGEE1	ZNF558	Q96NG5	311
MAGEE1	ZNF280C	Q8ND82	306
MAGEE1	TTC14	Q96N46	305

IntAct

23 interactions, top by confidence:

A	B	Type	Score
TUBGCP5	TUBG1	psi-mi:“MI:0914”(association)	0.840
EID2B	MAGEE1	psi-mi:“MI:0915”(physical association)	0.770
MCC	MAGEE1	psi-mi:“MI:0915”(physical association)	0.670
MAGEE1	MCC	psi-mi:“MI:0914”(association)	0.670
USP7	MAGEE1	psi-mi:“MI:0407”(direct interaction)	0.590
MAGEE1	TRIM28	psi-mi:“MI:0915”(physical association)	0.520
MAGEE1	MCC	psi-mi:“MI:0914”(association)	0.350
RASA1		psi-mi:“MI:0914”(association)	0.350
PEBP1	PRPSAP2	psi-mi:“MI:0914”(association)	0.350
YJEFN3	HSPA8	psi-mi:“MI:0914”(association)	0.350
MAGEE1	FYN	psi-mi:“MI:0914”(association)	0.350
MCC	CIBAR1	psi-mi:“MI:0914”(association)	0.350
BACH1	ENC1	psi-mi:“MI:0914”(association)	0.350
EID2B	MAGEE1	psi-mi:“MI:0915”(physical association)	0.000
MAGEE1	MCC	psi-mi:“MI:0915”(physical association)	0.000
MAGEE1	msrP	psi-mi:“MI:0915”(physical association)	0.000
USP7	MAGEE1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (49): MAGEE1 (Affinity Capture-MS), MAGEE1 (Affinity Capture-MS), EID2 (Affinity Capture-MS), CRAMP1L (Affinity Capture-MS), MCC (Affinity Capture-MS), YLPM1 (Affinity Capture-MS), BCAS3 (Affinity Capture-MS), CWF19L2 (Affinity Capture-MS), C16orf70 (Affinity Capture-MS), GATAD2B (Affinity Capture-MS), KIDINS220 (Affinity Capture-MS), MAGEE1 (Two-hybrid), MAGEE1 (Two-hybrid), MAGEE1 (Affinity Capture-MS), MAGEE1 (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

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	90
Likely benign	4
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

0 predictions. Top by Δscore:

AlphaMissense

6185 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:76429843:T:C	L638S	1.000
X:76430311:T:C	L794P	1.000
X:76430512:T:C	L861P	1.000
X:76429423:T:C	L498P	0.999
X:76429435:T:C	L502P	0.999
X:76429438:T:C	L503P	0.999
X:76429549:T:C	L540P	0.999
X:76429560:T:C	F544L	0.999
X:76429562:T:A	F544L	0.999
X:76429562:T:G	F544L	0.999
X:76429740:T:A	W604R	0.999
X:76429740:T:C	W604R	0.999
X:76429742:G:C	W604C	0.999
X:76429742:G:T	W604C	0.999
X:76429750:T:C	L607P	0.999
X:76429810:T:C	L627P	0.999
X:76429824:T:C	F632L	0.999
X:76429825:T:C	F632S	0.999
X:76429826:T:A	F632L	0.999
X:76429826:T:G	F632L	0.999
X:76429888:T:C	F653S	0.999
X:76429893:T:A	W655R	0.999
X:76429893:T:C	W655R	0.999
X:76429895:G:C	W655C	0.999
X:76429895:G:T	W655C	0.999
X:76429896:G:C	G656R	0.999
X:76429936:T:C	L669P	0.999
X:76429941:T:C	F671L	0.999
X:76429943:C:A	F671L	0.999
X:76429943:C:G	F671L	0.999

dbSNP variants (sampled 300 via entrez): RS1000589097 (X:76427866 C>A), RS1000938436 (X:76428162 A>T), RS1004099932 (X:76429266 G>A,T), RS1005050225 (X:76427705 A>C), RS1005103969 (X:76427253 G>A,T), RS1007550286 (X:76431016 G>C,T), RS1008015423 (X:76430331 G>C,T), RS1008732111 (X:76425771 T>C), RS1009624485 (X:76431302 G>A), RS1010846963 (X:76425868 A>G,T), RS1013251531 (X:76428755 C>T), RS1013305094 (X:76428306 A>C), RS1014266198 (X:76426628 T>C), RS1014316672 (X:76426233 G>C), RS1019209604 (X:76427290 G>A,C)

Disease associations

OMIM: gene MIM:300759 | 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

34 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases expression	3
triphenyl phosphate	affects expression	1
bisphenol A	decreases expression	1
trichostatin A	decreases expression	1
2,4,5,2’,4’,5’-hexachlorobiphenyl	decreases expression	1
3,4,5,3’,4’-pentachlorobiphenyl	decreases expression	1
perfluorooctanoic acid	decreases expression	1
potassium chromate(VI)	increases expression	1
avobenzone	increases expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
2-palmitoylglycerol	increases expression	1
nutlin 3	affects cotreatment, increases expression	1
ICG 001	increases expression	1
abrine	decreases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
jinfukang	increases expression, affects cotreatment	1
NSC 689534	affects binding, decreases expression	1
Sunitinib	increases expression	1
Leflunomide	decreases expression	1
Benzo(a)pyrene	affects methylation	1
Cisplatin	increases expression, affects cotreatment	1
Copper	affects binding, decreases expression	1
Dactinomycin	affects cotreatment, increases expression	1
Doxorubicin	decreases expression	1
Estradiol	affects cotreatment, increases expression	1
Ivermectin	decreases expression	1
Lead	affects expression	1
Tobacco Smoke Pollution	decreases expression	1
Urethane	affects expression	1

Clinical trials (associated diseases)

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