MAGEF1

Summary

MAGEF1 (MAGE family member F1, HGNC:29639) is a protein-coding gene on chromosome 3q27.1, encoding Melanoma-associated antigen F1 (Q9HAY2). Enhances ubiquitin ligase activity of RING-type zinc finger-containing E3 ubiquitin ligases.

This intronless gene encodes a member of the MAGE superfamily. It is ubiquitously expressed in normal tissues and in tumor cells. This gene includes a microsatellite repeat in the coding region.

Source: NCBI Gene 64110 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 39 total
• MANE Select transcript: NM_022149

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:29639
Approved symbol	MAGEF1
Name	MAGE family member F1
Location	3q27.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000177383
Ensembl biotype	protein_coding
OMIM	609267
Entrez	64110

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000317897

RefSeq mRNA: 1 — MANE Select: NM_022149 NM_022149

CCDS: CCDS3269

Canonical transcript exons

ENST00000317897 — 1 exons

Exon	Start	End
ENSE00001277321	184710364	184712064

Expression profiles

Bgee: expression breadth ubiquitous, 265 present calls, max score 95.10.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 31.3617 / max 195.5517, expressed in 1762 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
45903	31.0777	1761
45904	0.2840	113

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
ganglionic eminence	UBERON:0004023	95.10	gold quality
adenohypophysis	UBERON:0002196	94.20	gold quality
pituitary gland	UBERON:0000007	93.79	gold quality
prefrontal cortex	UBERON:0000451	93.56	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	93.52	gold quality
ventricular zone	UBERON:0003053	93.50	gold quality
cerebellar vermis	UBERON:0004720	93.19	gold quality
calcaneal tendon	UBERON:0003701	93.18	gold quality
lateral nuclear group of thalamus	UBERON:0002736	92.96	gold quality
type B pancreatic cell	CL:0000169	92.52	silver quality
Brodmann (1909) area 9	UBERON:0013540	92.41	gold quality
cingulate cortex	UBERON:0003027	92.10	gold quality
anterior cingulate cortex	UBERON:0009835	92.10	gold quality
nucleus accumbens	UBERON:0001882	91.81	gold quality
pons	UBERON:0000988	91.66	gold quality
right frontal lobe	UBERON:0002810	91.64	gold quality
amygdala	UBERON:0001876	91.23	gold quality
cortical plate	UBERON:0005343	91.23	gold quality
embryo	UBERON:0000922	91.22	gold quality
islet of Langerhans	UBERON:0000006	91.18	gold quality
endocervix	UBERON:0000458	91.18	gold quality
cerebellar cortex	UBERON:0002129	91.03	gold quality
cerebellar hemisphere	UBERON:0002245	90.97	gold quality
putamen	UBERON:0001874	90.96	gold quality
hypothalamus	UBERON:0001898	90.86	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	90.67	gold quality
caudate nucleus	UBERON:0001873	90.62	gold quality
tendon	UBERON:0000043	90.56	gold quality
neocortex	UBERON:0001950	90.54	gold quality
right hemisphere of cerebellum	UBERON:0014890	90.49	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	10.97

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

28 targeting MAGEF1, 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-4668-3P	100.00	68.74	2635
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-8063	99.91	69.76	3146
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-6715A-3P	99.83	68.05	1473
HSA-MIR-944	99.82	70.85	3042
HSA-MIR-4659A-3P	99.80	72.62	4248
HSA-MIR-4659B-3P	99.80	72.62	4248
HSA-MIR-33A-3P	99.70	70.27	3362
HSA-MIR-7157-5P	99.66	69.33	1829
HSA-MIR-4310	99.59	68.84	2527
HSA-MIR-32-3P	99.36	68.20	2517
HSA-MIR-888-5P	99.30	70.15	1855
HSA-MIR-3190-5P	98.87	64.89	1345
HSA-MIR-4477A	98.83	69.75	2952
HSA-MIR-6715B-3P	98.80	68.07	1204
HSA-MIR-5000-3P	98.79	65.63	1251
HSA-MIR-519A-2-5P	98.78	71.74	1401
HSA-MIR-520B-5P	98.78	71.74	1401
HSA-MIR-500A-5P	98.76	69.13	1241
HSA-MIR-595	98.25	67.44	699

Literature-anchored findings (GeneRIF, showing 1)

• MAGE-F1 specifies the cytosolic iron-sulfur assembly pathway protein MMS19 for ubiquitination and degradation. (PMID:29225034)

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), MAGEA9 (ENSG00000123584), MAGEA10 (ENSG00000124260), MAGEA4 (ENSG00000147381), MAGED4 (ENSG00000154545), MAGEC1 (ENSG00000155495), MAGEA8 (ENSG00000156009), MAGEC3 (ENSG00000165509), MAGEB6 (ENSG00000176746), MAGEB18 (ENSG00000176774), 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 F1 — Q9HAY2 (reviewed: Q9HAY2)

Alternative names: MAGE-F1 antigen

All UniProt accessions (1): Q9HAY2

UniProt curated annotations — full annotation on UniProt →

Function. Enhances ubiquitin ligase activity of RING-type zinc finger-containing E3 ubiquitin ligases. Proposed to act through recruitment and/or stabilization of the E2 ubiquitin-conjugating enzyme at the E3:substrate complex. MAGEF1-NSMCE1 ubiquitin ligase complex promotes proteasomal degradation of MMS19, a key component of the cytosolic iron-sulfur protein assembly (CIA) machinery. Down-regulation of MMS19 impairs the activity of several DNA repair and metabolism enzymes such as ERCC2/XPD, FANCJ, RTEL1 and POLD1 that require iron-sulfur clusters as cofactors. May negatively regulate genome integrity by inhibiting homologous recombination-mediated double-strand break DNA repair.

Subunit / interactions. Interacts (via MAGE domain) with RING-type zinc finger-containing E3 ubiquitin-protein ligases LNX1, TRIM27 and NSMCE1; the interaction is direct.

Tissue specificity. Ubiquitous.

RefSeq proteins (1): NP_071432* (*=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 (10 total): sequence conflict 3, compositionally biased region 2, chain 1, domain 1, region of interest 1, sequence variant 1, mutagenesis site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9HAY2-F1	81.11	0.59

Functional residue map

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

Mutagenesis-validated functional residues (1):

Position	Phenotype
87–88	loss of interaction with nsmce1.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 113 (showing top): GOBP_REGULATION_OF_DOUBLE_STRAND_BREAK_REPAIR, GOBP_REGULATION_OF_DNA_RECOMBINATION, GOBP_NEGATIVE_REGULATION_OF_DNA_REPAIR, GOBP_NEGATIVE_REGULATION_OF_DNA_RECOMBINATION, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOBP_REGULATION_OF_DOUBLE_STRAND_BREAK_REPAIR_VIA_HOMOLOGOUS_RECOMBINATION, GOBP_REGULATION_OF_DNA_REPAIR, GOBP_REGULATION_OF_RESPONSE_TO_STRESS, GOBP_DNA_DAMAGE_RESPONSE, GOBP_POST_TRANSLATIONAL_PROTEIN_MODIFICATION, GOBP_REGULATION_OF_CELLULAR_RESPONSE_TO_STRESS, MARTINEZ_RESPONSE_TO_TRABECTEDIN_DN, GOBP_RECOMBINATIONAL_REPAIR, DANG_BOUND_BY_MYC, GOBP_PROTEIN_CATABOLIC_PROCESS

GO Biological Process (6): negative regulation of transcription by RNA polymerase II (GO:0000122), ubiquitin-dependent protein catabolic process (GO:0006511), protein ubiquitination (GO:0016567), negative regulation of double-strand break repair via homologous recombination (GO:2000042), regulation of macromolecule metabolic process (GO:0060255), regulation of primary metabolic process (GO:0080090)

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 metabolic process	2
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
negative regulation of DNA-templated transcription	1
protein ubiquitination	1
modification-dependent protein catabolic process	1
protein modification by small protein conjugation	1
double-strand break repair via homologous recombination	1
regulation of double-strand break repair via homologous recombination	1
negative regulation of DNA recombination	1
negative regulation of double-strand break repair	1
macromolecule metabolic process	1
primary metabolic process	1
binding	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

374 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MAGEF1	CSAG1	Q6PB30	824
MAGEF1	NPAS4	Q8IUM7	782
MAGEF1	MMS19	Q96T76	554
MAGEF1	NSMCE4A	Q9NXX6	552
MAGEF1	PHF7	Q9BWX1	508
MAGEF1	MAGEA3	P43357	491
MAGEF1	EID3	Q8N140	483
MAGEF1	SMC5	Q8IY18	465
MAGEF1	MAGEA2B	P43356	455
MAGEF1	MAGEC2	Q9UBF1	443
MAGEF1	ARSF	P54793	418
MAGEF1	GTPBP6	O43824	399
MAGEF1	UQCC4	Q4G0I0	395
MAGEF1	SMC6	Q96SB8	395
MAGEF1	PLCXD1	Q9NUJ7	394

IntAct

16 interactions, top by confidence:

A	B	Type	Score
MDFI	MAGEF1	psi-mi:“MI:0915”(physical association)	0.670
MAGEF1	NSMCE1	psi-mi:“MI:0915”(physical association)	0.560
EID1	MAGEF1	psi-mi:“MI:0915”(physical association)	0.400
EID2	MAGEF1	psi-mi:“MI:0915”(physical association)	0.400
EID2B	MAGEF1	psi-mi:“MI:0915”(physical association)	0.400
MAGEF1	TRIM27	psi-mi:“MI:0915”(physical association)	0.400
PIPSL	C1orf226	psi-mi:“MI:0914”(association)	0.350
FTL	SH3PXD2B	psi-mi:“MI:0914”(association)	0.350
LHFPL2	SRC	psi-mi:“MI:0914”(association)	0.350
MAGEF1	SMCHD1	psi-mi:“MI:0914”(association)	0.350
FTL		psi-mi:“MI:0914”(association)	0.350

BioGRID (46): MAGEF1 (Two-hybrid), MAGEF1 (Affinity Capture-MS), TRAIP (Two-hybrid), PHF7 (Two-hybrid), MAGEF1 (Negative Genetic), MAGEF1 (Affinity Capture-Western), NSMCE1 (Affinity Capture-Western), MAGEF1 (Reconstituted Complex), MMS19 (Reconstituted Complex), NSMCE1 (Reconstituted Complex), HDAC6 (Affinity Capture-MS), MRPL4 (Affinity Capture-MS), PGRMC1 (Affinity Capture-MS), TFAM (Affinity Capture-MS), TPP1 (Affinity Capture-MS)

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

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	36
Likely benign	1
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

177 predictions. Top by Δscore:

Variant	Effect	Δscore
3:184711200:C:T	acceptor_gain	0.9200
3:184711200:C:CT	acceptor_gain	0.7600
3:184711001:CGGTA:C	donor_gain	0.7500
3:184710838:TATG:T	donor_gain	0.6200
3:184710839:ATGA:A	donor_gain	0.6200
3:184710992:AGGGC:A	donor_gain	0.6000
3:184711201:A:T	acceptor_gain	0.5800
3:184710944:CTGG:C	donor_gain	0.5700
3:184710835:A:AC	donor_gain	0.5600
3:184710836:C:CC	donor_gain	0.5600
3:184710839:A:AC	donor_gain	0.5500
3:184710943:A:AC	donor_gain	0.5500
3:184710944:C:CC	donor_gain	0.5500
3:184710840:T:C	donor_gain	0.5300
3:184710845:CAGG:C	donor_gain	0.5300
3:184710846:AGGA:A	donor_gain	0.5300
3:184711199:C:CT	acceptor_gain	0.5100
3:184711189:C:G	acceptor_gain	0.4900
3:184711100:C:T	acceptor_gain	0.4800
3:184711149:T:A	acceptor_gain	0.4800
3:184711006:CTGCA:C	donor_gain	0.4700
3:184710846:A:AC	donor_gain	0.4600
3:184711005:A:AC	donor_gain	0.4600
3:184711006:C:CC	donor_gain	0.4600
3:184711706:T:TA	donor_gain	0.4600
3:184710832:A:AC	donor_gain	0.4500
3:184710996:C:CA	donor_gain	0.4400
3:184710690:ATCCT:A	acceptor_gain	0.4300
3:184711158:GCTGC:G	acceptor_gain	0.4300
3:184711164:G:GT	acceptor_gain	0.4300

AlphaMissense

2003 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:184711435:A:C	F129L	0.993
3:184711435:A:T	F129L	0.993
3:184711437:A:G	F129L	0.993
3:184711098:C:G	G242R	0.989
3:184711101:A:G	W241R	0.989
3:184711101:A:T	W241R	0.989
3:184711051:G:C	F257L	0.988
3:184711051:G:T	F257L	0.988
3:184711053:A:G	F257L	0.988
3:184711015:C:A	W269C	0.984
3:184711015:C:G	W269C	0.984
3:184711069:C:A	K251N	0.984
3:184711069:C:G	K251N	0.984
3:184711099:C:A	W241C	0.984
3:184711099:C:G	W241C	0.984
3:184711201:A:C	F207L	0.984
3:184711201:A:T	F207L	0.984
3:184711203:A:G	F207L	0.984
3:184711106:A:G	F239S	0.979
3:184711564:G:C	F86L	0.979
3:184711564:G:T	F86L	0.979
3:184711566:A:G	F86L	0.979
3:184711017:A:G	W269R	0.978
3:184711017:A:T	W269R	0.978
3:184711169:A:G	F218S	0.977
3:184711313:A:G	L170S	0.976
3:184711097:C:T	G242D	0.974
3:184711168:A:C	F218L	0.974
3:184711168:A:T	F218L	0.974
3:184711170:A:G	F218L	0.974

dbSNP variants (sampled 300 via entrez): RS1000925168 (3:184712047 G>T), RS1000955878 (3:184711880 C>T), RS1002731349 (3:184711990 G>A), RS1003581129 (3:184710154 G>A), RS1003618962 (3:184710517 T>C), RS1003735084 (3:184710848 G>A,C,T), RS1003814202 (3:184710310 C>T), RS1004453471 (3:184710142 C>A,G,T), RS1005583077 (3:184710556 C>T), RS1006835045 (3:184714007 T>G), RS1007731985 (3:184710127 G>A), RS1007804709 (3:184712527 A>G), RS1007835933 (3:184712263 A>C), RS1009762862 (3:184710146 G>A), RS1010036098 (3:184713878 A>G)

Disease associations

OMIM: gene MIM:609267 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST003999_2	Nose size	2.000000e-15
GCST006904_10	Cerebral amyloid deposition (PET imaging)	6.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0007707	cerebral amyloid deposition measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

24 total (human), top 24 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
GSK-J4	decreases expression	1
TAK-243	increases sumoylation	1
bisphenol A	affects cotreatment, decreases methylation	1
kojic acid	increases expression	1
sodium arsenite	decreases expression	1
cobaltous chloride	decreases expression	1
nickel sulfate	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
Temozolomide	increases expression	1
Fulvestrant	affects cotreatment, decreases methylation	1
Acetaminophen	decreases expression	1
Benzo(a)pyrene	increases methylation	1
Cisplatin	increases expression	1
Diethylstilbestrol	decreases expression	1
Dinitrochlorobenzene	decreases expression	1
Oxazolone	decreases expression	1
Phenobarbital	affects expression	1
Thiram	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Urethane	decreases expression	1
Cyclosporine	decreases expression	1
Copper Sulfate	decreases expression	1
Vitamin K 3	affects expression	1

Clinical trials (associated diseases)

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