MAGEH1

Summary

MAGEH1 (MAGE family member H1, HGNC:24092) is a protein-coding gene on chromosome Xp11.21, encoding Melanoma-associated antigen H1 (Q9H213). In precision oncology, MAGEH1 EXPRESSION is associated with resistance to Gemcitabine in Bile Duct Adenocarcinoma (CIViC Level D).

This gene belongs to the non-CT (non cancer/testis) subgroup of the melanoma-associated antigen (MAGE) superfamily. The encoded protein is likely associated with apoptosis, cell cycle arrest, growth inhibition or cell differentiation. The protein may be involved in the atRA (all-trans retinoic acid) signaling through the STAT1-alpha (signal transducer and activator of transcription 1-alpha) pathway.

Source: NCBI Gene 28986 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 24 total
• Precision-oncology evidence (CIViC): 1 curated variant–drug association
• MANE Select transcript: NM_014061

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:24092
Approved symbol	MAGEH1
Name	MAGE family member H1
Location	Xp11.21
Locus type	gene with protein product
Status	Approved
Aliases	APR1
Ensembl gene	ENSG00000187601
Ensembl biotype	protein_coding
OMIM	300548
Entrez	28986

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000342972

RefSeq mRNA: 1 — MANE Select: NM_014061 NM_014061

CCDS: CCDS14369

Canonical transcript exons

ENST00000342972 — 1 exons

Exon	Start	End
ENSE00001380673	55452127	55453566

Expression profiles

Bgee: expression breadth ubiquitous, 278 present calls, max score 98.99.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 30.0268 / max 377.5970, expressed in 1714 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
196465	25.5111	1706
196467	3.1576	987
196466	0.6999	396
196469	0.2990	123
196468	0.2038	102
209711	0.1555	55

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
corpus epididymis	UBERON:0004359	98.99	gold quality
cortical plate	UBERON:0005343	96.72	gold quality
endothelial cell	CL:0000115	95.91	gold quality
adrenal tissue	UBERON:0018303	95.85	gold quality
pons	UBERON:0000988	95.61	gold quality
Brodmann (1909) area 9	UBERON:0013540	95.60	gold quality
hypothalamus	UBERON:0001898	95.46	gold quality
superior vestibular nucleus	UBERON:0007227	95.35	gold quality
cerebellar vermis	UBERON:0004720	95.33	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	95.16	gold quality
tibia	UBERON:0000979	94.76	gold quality
adenohypophysis	UBERON:0002196	94.55	gold quality
pituitary gland	UBERON:0000007	94.47	gold quality
prefrontal cortex	UBERON:0000451	94.47	gold quality
seminal vesicle	UBERON:0000998	94.35	gold quality
ventral tegmental area	UBERON:0002691	94.32	gold quality
medulla oblongata	UBERON:0001896	94.28	gold quality
type B pancreatic cell	CL:0000169	94.17	silver quality
cingulate cortex	UBERON:0003027	94.11	gold quality
anterior cingulate cortex	UBERON:0009835	94.11	gold quality
dorsal plus ventral thalamus	UBERON:0001897	94.06	gold quality
orbitofrontal cortex	UBERON:0004167	94.03	gold quality
subthalamic nucleus	UBERON:0001906	93.91	gold quality
cerebral cortex	UBERON:0000956	93.89	gold quality
frontal cortex	UBERON:0001870	93.89	gold quality
inferior vagus X ganglion	UBERON:0005363	93.89	gold quality
substantia nigra pars compacta	UBERON:0001965	93.82	gold quality
neocortex	UBERON:0001950	93.81	gold quality
right frontal lobe	UBERON:0002810	93.78	gold quality
forebrain	UBERON:0001890	93.70	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-CURD-46	yes	14.02
E-ANND-3	yes	13.15
E-CURD-97	no	975.69

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

37 targeting MAGEH1, 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-548P	99.98	72.25	3784
HSA-MIR-512-3P	99.97	67.35	1049
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-3119	99.92	71.34	2390
HSA-MIR-1305	99.91	71.43	3443
HSA-MIR-302A-3P	99.89	71.23	1777
HSA-MIR-302B-3P	99.89	71.23	1777
HSA-MIR-302C-3P	99.89	71.20	1778
HSA-MIR-302D-3P	99.89	71.25	1777
HSA-MIR-4496	99.88	68.89	2236
HSA-MIR-373-3P	99.84	70.68	1668
HSA-MIR-520E-3P	99.84	70.55	1698
HSA-MIR-372-3P	99.83	70.58	1691
HSA-MIR-520A-3P	99.83	70.59	1687
HSA-MIR-520B-3P	99.83	70.56	1699
HSA-MIR-520C-3P	99.83	70.56	1699
HSA-MIR-520D-3P	99.83	70.78	1676
HSA-MIR-4719	99.73	72.10	3329
HSA-MIR-3158-5P	99.65	67.51	1763
HSA-MIR-4261	99.59	70.30	3415
HSA-MIR-17-3P	99.55	66.77	1311
HSA-MIR-147B-5P	99.45	70.62	2432
HSA-MIR-377-3P	99.37	70.18	1905
HSA-MIR-130A-5P	99.33	70.26	2623
HSA-MIR-376A-3P	99.06	69.17	1128
HSA-MIR-376B-3P	99.06	69.17	1128
HSA-MIR-513B-3P	98.76	68.12	1577
HSA-MIR-4718	98.55	68.61	814
HSA-MIR-676-5P	98.49	68.87	1492

Literature-anchored findings (GeneRIF, showing 5)

• The induction of APR-1 expression caused apoptosis of melanoma cells via the interaction with the juxtamembrane region of p75 neurotrophin receptor. (PMID:21418516)
• Data indicate that the neonatal detection test sensitivity obtained was 95% with a positive predictive value of 1 in the analyses for both the arylsulfatase E (ARSE) and melanoma antigen family H1 (MAGEH1) genes. (PMID:25366798)
• our data showed that Apr-1 plays a crucial role in cell proliferation by controlling cell cycle progression, implying a tumor-suppressor function of Apr-1 in cholangiocarcinoma carcinogenesis (PMID:26572808)
• MAGEH1 expression was downregulated in HCC tumor tissues compared with adjacent normal liver tissues and in samples from patients with tumor recurrence. MAGEH1 reduced HCC cell proliferation, migration and invasion ability. (PMID:29316827)
• MAGEH1 interacts with GADD45G and induces renal tubular cell apoptosis. (PMID:34788311)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	ndnl2	ENSDARG00000058212
mus_musculus	Mageh1	ENSMUSG00000047238
rattus_norvegicus	Mageh1	ENSRNOG00000003178
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), 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 H1 — Q9H213 (reviewed: Q9H213)

Alternative names: Apoptosis-related protein 1, MAGE-H1 antigen, Restin

All UniProt accessions (1): Q9H213

RefSeq proteins (1): NP_054780* (*=MANE)

Domains & families (InterPro)

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

Pfam: PF01454

UniProt features (7 total): compositionally biased region 3, chain 1, domain 1, region of interest 1, modified residue 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9H213-F1	67.07	0.11

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 (1): 195

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 104 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_UP, ACEVEDO_LIVER_CANCER_WITH_H3K27ME3_UP, OSWALD_HEMATOPOIETIC_STEM_CELL_IN_COLLAGEN_GEL_UP, ONDER_CDH1_TARGETS_2_UP, PID_P75_NTR_PATHWAY, DBP_Q6, VECCHI_GASTRIC_CANCER_EARLY_DN, ONDER_CDH1_SIGNALING_VIA_CTNNB1, ACEVEDO_METHYLATED_IN_LIVER_CANCER_DN, DR3_Q4, TGGAAA_NFAT_Q4_01, VECCHI_GASTRIC_CANCER_ADVANCED_VS_EARLY_UP, SAMOLS_TARGETS_OF_KHSV_MIRNAS_DN, GOCC_NUCLEOLUS, QI_PLASMACYTOMA_DN

GO Biological Process (2): negative regulation of transcription by RNA polymerase II (GO:0000122), apoptotic process (GO:0006915)

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
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
binding	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

646 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MAGEH1	ATRAID	Q6UW56	871
MAGEH1	NGFR	P08138	806
MAGEH1	PRY	O14603	774
MAGEH1	TMEM37	Q8WXS4	591
MAGEH1	DDX54	Q8TDD1	544
MAGEH1	LAYN	Q6UX15	515
MAGEH1	NGF	P01138	492
MAGEH1	NTSR1	P30989	491
MAGEH1	SORT1	Q99523	470
MAGEH1	MAG	P20916	470
MAGEH1	ARHGDIA	P52565	435
MAGEH1	OMG	P23515	429
MAGEH1	RTN4R	Q9BZR6	421
MAGEH1	ZC3H8	Q8N5P1	402
MAGEH1	CKAP2	Q8WWK9	398

IntAct

41 interactions, top by confidence:

A	B	Type	Score
ZSCAN9	MAGEH1	psi-mi:“MI:0915”(physical association)	0.560
MAGEH1	TNIP1	psi-mi:“MI:0915”(physical association)	0.560
MAGEH1	HMBOX1	psi-mi:“MI:0915”(physical association)	0.560
MAGEH1	TRIM41	psi-mi:“MI:0915”(physical association)	0.560
MAGEH1	ZSCAN9	psi-mi:“MI:0915”(physical association)	0.560
TRIM41	MAGEH1	psi-mi:“MI:0915”(physical association)	0.560
HMBOX1	MAGEH1	psi-mi:“MI:0915”(physical association)	0.560
SH2B2	MAGEH1	psi-mi:“MI:0915”(physical association)	0.560
PRKCA	MAGEH1	psi-mi:“MI:0915”(physical association)	0.560
MAGEH1	YWHAG	psi-mi:“MI:0915”(physical association)	0.560
MAGEH1	SETDB1	psi-mi:“MI:0915”(physical association)	0.560
KAT5	MAGEH1	psi-mi:“MI:0915”(physical association)	0.560
LMO3	MAGEH1	psi-mi:“MI:0915”(physical association)	0.560
MAGEH1	HNRNPC	psi-mi:“MI:0915”(physical association)	0.400
ELN	MAGEH1	psi-mi:“MI:0915”(physical association)	0.370

BioGRID (27): MAGEH1 (Two-hybrid), MAGEH1 (Two-hybrid), HMBOX1 (Two-hybrid), TRIM41 (Two-hybrid), MOAP1 (Two-hybrid), MAGEH1 (Two-hybrid), MAGEH1 (Two-hybrid), MAGEH1 (Two-hybrid), MAGEH1 (Affinity Capture-Western), NGFR (Affinity Capture-Western), MAGEH1 (Proximity Label-MS), MAGEH1 (Two-hybrid), GADD45G (Reconstituted Complex), MAGEH1 (Affinity Capture-Western), GADD45G (Affinity Capture-Western)

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

Cancer significance

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	23
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

107 predictions. Top by Δscore:

Variant	Effect	Δscore
X:55452722:G:GT	donor_gain	0.7100
X:55452722:G:T	donor_gain	0.6300
X:55452844:TG:T	donor_gain	0.6200
X:55452845:GG:G	donor_gain	0.6200
X:55453102:GGTCC:G	donor_gain	0.6200
X:55452696:G:GT	donor_gain	0.6100
X:55452988:TTG:T	donor_gain	0.5300
X:55452711:A:T	donor_gain	0.4900
X:55452804:GG:G	donor_gain	0.4900
X:55452805:GG:G	donor_gain	0.4900
X:55452897:A:T	donor_gain	0.4900
X:55453312:A:AG	acceptor_gain	0.4900
X:55453313:G:GG	acceptor_gain	0.4900
X:55452956:T:G	donor_gain	0.4800
X:55452827:GCCC:G	donor_gain	0.4400
X:55452828:CCCC:C	donor_gain	0.4400
X:55453103:GTCC:G	donor_gain	0.4400
X:55453104:TCCT:T	donor_gain	0.4400
X:55452848:G:GG	donor_gain	0.4200
X:55452786:GAAGA:G	donor_gain	0.4100
X:55452791:GTTT:G	donor_gain	0.4100
X:55452847:A:AG	donor_gain	0.4100
X:55452987:GT:G	donor_gain	0.4100
X:55452789:GA:G	donor_gain	0.4000
X:55452696:G:T	donor_gain	0.3900
X:55452802:GAGG:G	donor_gain	0.3900
X:55452726:T:G	donor_gain	0.3800
X:55452916:C:T	donor_gain	0.3800
X:55452786:G:GT	donor_gain	0.3700
X:55452793:T:A	donor_gain	0.3700

AlphaMissense

1430 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:55452811:T:C	L146P	0.998
X:55452856:T:C	F161S	0.998
X:55452661:T:C	L96S	0.997
X:55452909:T:C	F179L	0.997
X:55452911:T:A	F179L	0.997
X:55452911:T:G	F179L	0.997
X:55452682:G:T	G103V	0.996
X:55452706:T:A	V111D	0.996
X:55452781:T:A	V136D	0.996
X:55452793:T:C	F140S	0.996
X:55452861:T:A	W163R	0.996
X:55452861:T:C	W163R	0.996
X:55452863:G:C	W163C	0.996
X:55452863:G:T	W163C	0.996
X:55452864:G:A	G164R	0.996
X:55452864:G:C	G164R	0.996
X:55452865:G:A	G164E	0.996
X:55452672:T:C	F100L	0.995
X:55452674:C:A	F100L	0.995
X:55452674:C:G	F100L	0.995
X:55452691:C:A	A106D	0.995
X:55452708:T:A	W112R	0.995
X:55452708:T:C	W112R	0.995
X:55452710:G:C	W112C	0.995
X:55452710:G:T	W112C	0.995
X:55452792:T:C	F140L	0.995
X:55452794:T:A	F140L	0.995
X:55452794:T:G	F140L	0.995
X:55452893:A:C	K173N	0.995
X:55452893:A:T	K173N	0.995

dbSNP variants (sampled 300 via entrez): RS1000343355 (X:55451666 A>G,T), RS1005481725 (X:55453577 A>T), RS1005933950 (X:55453026 G>T), RS1006126666 (X:55453488 T>G), RS1009888782 (X:55450444 A>T), RS1010171540 (X:55451765 A>G), RS1010450499 (X:55452208 A>G), RS1011659112 (X:55452127 A>C,G), RS1012444345 (X:55451030 G>T), RS1013191186 (X:55453532 G>A,C), RS1014038199 (X:55451235 T>A), RS1014897448 (X:55451120 A>G), RS1015229837 (X:55453596 T>C), RS1015315589 (X:55450256 G>A), RS1015762624 (X:55450622 A>G)

Disease associations

OMIM: gene MIM:300548 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST002396_25	Smoking initiation	8.000000e-08

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0005670	smoking initiation

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

Clinical evidence (CIViC)

Drug × variant × indication: 1 predictive associations from 1 curated evidence items.

Variant	Therapy	Indication	Effect	Level	CIViC
MAGEH1 EXPRESSION	Gemcitabine	Bile Duct Adenocarcinoma	Resistance	CIViC D	EID950

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases expression, increases methylation	2
GSK-J4	decreases expression	1
FR900359	increases phosphorylation	1
propionaldehyde	increases expression	1
bisphenol A	affects cotreatment, increases expression	1
sodium arsenite	decreases expression	1
butyraldehyde	increases expression	1
potassium chromate(VI)	decreases expression	1
pentanal	increases expression	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	increases expression	1
nutlin 3	affects cotreatment, increases expression	1
abrine	decreases expression	1
jinfukang	increases expression, increases reaction	1
7-(benzylamino)-1,3,4,8-tetrahydropyrrolo(4,3,2-de)quinolin-8(1H)-one	decreases expression	1
Leflunomide	decreases expression	1
Air Pollutants	decreases expression, increases abundance	1
Aldehydes	increases expression	1
Camptothecin	increases expression	1
Cisplatin	increases expression, increases reaction	1
Dactinomycin	affects cotreatment, increases expression	1
Dexamethasone	affects cotreatment, increases expression	1
Doxorubicin	increases expression	1
Estradiol	increases expression	1
Indomethacin	affects cotreatment, increases expression	1
Smoke	decreases expression	1
Sodium Dodecyl Sulfate	increases expression	1
Tobacco Smoke Pollution	decreases expression	1
Tretinoin	increases expression	1
Valproic Acid	decreases methylation, increases expression	1

Clinical trials (associated diseases)

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