GAGE1

Summary

GAGE1 (G antigen 1, HGNC:4098) is a protein-coding gene on chromosome Xp11.23, encoding G antigen 1 (P0DTW1). Antigen, recognized on melanoma by autologous cytolytic T-lymphocytes.

This gene belongs to a family of genes that are expressed in a variety of tumors but not in normal tissues, except for the testis. The sequences of the family members are highly related but differ by scattered nucleotide substitutions. The antigenic peptide YRPRPRRY, which is also encoded by several other family members, is recognized by autologous cytolytic T lymphocytes. Nothing is presently known about the function of this protein. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 2543 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 5 total
• MANE Select transcript: NM_001040663

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4098
Approved symbol	GAGE1
Name	G antigen 1
Location	Xp11.23
Locus type	gene with protein product
Status	Approved
Aliases	CT4.1
Ensembl gene	ENSG00000205777
Ensembl biotype	protein_coding
OMIM	300594
Entrez	2543

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 1 protein_coding, 1 nonsense_mediated_decay

ENST00000381700, ENST00000381709

RefSeq mRNA: 1 — MANE Select: NM_001040663 NM_001040663

CCDS: CCDS43950

Canonical transcript exons

ENST00000381700 — 5 exons

Exon	Start	End
ENSE00001676190	49600167	49600258
ENSE00002267134	49605993	49608538
ENSE00003483988	49600724	49600844
ENSE00003557786	49603668	49603793
ENSE00003617584	49599020	49599127

Expression profiles

Bgee: expression breadth broad, 31 present calls, max score 94.16.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
buccal mucosa cell	CL:0002336	94.16	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	89.02	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	86.53	gold quality
right testis	UBERON:0004534	77.20	gold quality
left testis	UBERON:0004533	75.17	gold quality
testis	UBERON:0000473	74.75	gold quality
hair follicle	UBERON:0002073	61.06	gold quality
decidua	UBERON:0002450	56.55	gold quality
sural nerve	UBERON:0015488	55.20	gold quality
blood vessel layer	UBERON:0004797	49.29	gold quality
choroid plexus epithelium	UBERON:0003911	48.89	gold quality
stromal cell of endometrium	CL:0002255	48.07	gold quality
periodontal ligament	UBERON:0008266	47.14	gold quality
renal glomerulus	UBERON:0000074	46.86	gold quality
metanephric glomerulus	UBERON:0004736	46.77	gold quality
nephron tubule	UBERON:0001231	46.71	gold quality
middle temporal gyrus	UBERON:0002771	46.70	gold quality
nasal cavity epithelium	UBERON:0005384	46.19	gold quality
lower lobe of lung	UBERON:0008949	45.68	silver quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	45.35	gold quality
inferior olivary complex	UBERON:0002127	45.14	gold quality
palpebral conjunctiva	UBERON:0001812	44.31	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	43.37	gold quality
secondary oocyte	CL:0000655	42.57	gold quality
medulla oblongata	UBERON:0001896	41.74	gold quality
vastus lateralis	UBERON:0001379	41.41	gold quality
quadriceps femoris	UBERON:0001377	41.37	gold quality
superficial temporal artery	UBERON:0001614	41.33	gold quality
mucosa of paranasal sinus	UBERON:0005030	40.98	gold quality
jejunal mucosa	UBERON:0000399	40.59	gold quality

Single-cell (SCXA)

Detected in 6 experiment(s), a significant marker in 5.

Experiment	Marker?	Max mean expression
E-MTAB-3929	yes	455.63
E-GEOD-81383	yes	150.51
E-CURD-11	yes	61.80
E-MTAB-7249	yes	11.47
E-ANND-3	yes	3.29
E-CURD-53	no	717.39

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 5)

• MAGE-A1 and NY-ESO-1 are associated with highly proliferating germ cells, whereas GAGE proteins have a more general function in germ cells unrelated to any specific developmental stage (PMID:17208940)
• Tumor-specific antigen GAGE may play a role in the occurrence and development of ovarian cancer and can be used as one of the important indicators for early diagnosis, efficacy evaluation and prognostic determination of ovarian cancer. (PMID:20423514)
• High GAGE1 expression is associated with metastasis in Head and Neck Squamous Cell Carcinoma. (PMID:29577858)
• The circ_0016760/miR-1287/GAGE1 signaling might play vital roles in the tumorigenesis and progression of Non-small cell lung cancer (NSCLC). (PMID:30103946)
• These data illustrate that the GAGE1 protein exhibits moderate cancerrestricted pattern of expression and immunogenicity, laying the foundation for the application of GAGE1 in immunotherapy and for the diagnosis of HCC[hepatocellular carcinoma]. (PMID:30297572)

Cross-species orthologs

0 orthologs

Paralogs (22): PAGE1 (ENSG00000068985), PAGE4 (ENSG00000101951), XAGE2 (ENSG00000155622), PAGE5 (ENSG00000158639), XAGE3 (ENSG00000171402), XAGE5 (ENSG00000171405), GAGE2A (ENSG00000189064), PAGE3 (ENSG00000204279), XAGE1A (ENSG00000204379), XAGE1B (ENSG00000204382), GAGE12G (ENSG00000215269), GAGE10 (ENSG00000215274), GAGE12E (ENSG00000216649), GAGE12J (ENSG00000224659), GAGE12H (ENSG00000224902), GAGE12D (ENSG00000227488), PAGE2 (ENSG00000234068), GAGE12F (ENSG00000236362), GAGE12C (ENSG00000237671), PAGE2B (ENSG00000238269), GAGE13 (ENSG00000274274), GAGE2E (ENSG00000275113)

Protein

Protein identifiers

G antigen 1 — P0DTW1 (reviewed: P0DTW1)

Alternative names: Antigen MZ2-F, Cancer/testis antigen 4.1

All UniProt accessions (2): P0DTW1, A0A158RFV5

UniProt curated annotations — full annotation on UniProt →

Function. Antigen, recognized on melanoma by autologous cytolytic T-lymphocytes.

Tissue specificity. Expressed in a variety of tumor tissues but not in normal tissues, except testis.

Miscellaneous. This gene belongs to a family of genes organized in clustered repeats. They have a high degree of predicted sequence identity, but differ by scattered single nucleotide substitution. Their sequences contain either the antigenic peptide YYWPRPRRY or YRPRPRRY which is recognized by cytotoxic T-cells.

Similarity. Belongs to the GAGE family.

RefSeq proteins (1): NP_001035753* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR008625	GAGE_fam	Family
IPR031320	GAGE	Domain

Pfam: PF05831

UniProt features (6 total): compositionally biased region 2, sequence conflict 2, chain 1, region of interest 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P0DTW1-F1	62.61	0.00

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 56 (showing top): DACOSTA_UV_RESPONSE_VIA_ERCC3_UP, SATO_SILENCED_BY_DEACETYLATION_IN_PANCREATIC_CANCER, BLALOCK_ALZHEIMERS_DISEASE_UP, LIAO_METASTASIS, HELLER_HDAC_TARGETS_SILENCED_BY_METHYLATION_UP, MODULE_113, PIEPOLI_LGI1_TARGETS_UP, MATTIOLI_MULTIPLE_MYELOMA_SUBGROUPS, ACEVEDO_METHYLATED_IN_LIVER_CANCER_DN, AIYAR_COBRA1_TARGETS_UP, BROWNE_HCMV_INFECTION_14HR_UP, LIANG_SILENCED_BY_METHYLATION_2, MODULE_13, chrXp11, MODULE_41

GO Biological Process (1): biological_process (GO:0008150)

GO Molecular Function (2): molecular_function (GO:0003674), protein binding (GO:0005515)

GO Cellular Component (1): cellular_component (GO:0005575)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
binding	1

Protein interactions and networks

STRING

0 interactions, top by confidence (×1000):

IntAct

3 interactions, top by confidence:

A	B	Type	Score
GAGE8	WIZ	psi-mi:“MI:0914”(association)	0.350
GAGE1	UBB	psi-mi:“MI:0914”(association)	0.350

ESM2 similar proteins: A0A0U1RQG5, A1L429, A6NDE8, A6NER3, A6NGK3, E1AZ71, O08664, O60829, O75459, O76087, P0C2W7, P0CL80, P0CL81, P0CL82, P0DSO3, P0DTW1, P52651, P62521, P86478, P86479, P86480, P86481, P86496, Q13066, Q13069, Q13070, Q17QW4, Q28181, Q2T9P9, Q32PA2, Q4V321, Q4V326, Q5JQC4, Q5U2Y8, Q62100, Q63803, Q64256, Q6NT46, Q6X7S9, Q7Z2X7

Diamond homologs: A1L429, A6NDE8, A6NER3, A6NGK3, O75459, O76087, P0CL80, P0CL81, P0CL82, P0DSO3, P0DTW1, Q13066, Q13069, Q13070, Q4V321, Q4V326, Q6NT46, Q8WTP9, Q96GT9, Q9UEU5, Q8WWM1, Q5JUK9, Q5JRK9, Q7Z2X7, Q9HD64

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	3
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

646 predictions. Top by Δscore:

Variant	Effect	Δscore
X:49600700:T:A	acceptor_gain	1.0000
X:49600703:A:AG	acceptor_gain	1.0000
X:49600704:C:G	acceptor_gain	1.0000
X:49600705:A:AG	acceptor_gain	1.0000
X:49600706:C:G	acceptor_gain	1.0000
X:49600709:A:AG	acceptor_gain	1.0000
X:49600709:ACAC:A	acceptor_gain	1.0000
X:49600710:C:G	acceptor_gain	1.0000
X:49600711:A:AG	acceptor_gain	1.0000
X:49600711:AC:A	acceptor_gain	1.0000
X:49600712:C:CA	acceptor_gain	1.0000
X:49600712:C:G	acceptor_gain	1.0000
X:49600716:T:G	acceptor_gain	1.0000
X:49600811:G:GT	donor_gain	1.0000
X:49600857:G:T	donor_gain	1.0000
X:49603663:TTAA:T	acceptor_loss	1.0000
X:49603665:A:AG	acceptor_gain	1.0000
X:49603665:AAG:A	acceptor_gain	1.0000
X:49603665:AAGG:A	acceptor_gain	1.0000
X:49603666:A:G	acceptor_gain	1.0000
X:49603666:AG:A	acceptor_gain	1.0000
X:49603666:AGG:A	acceptor_gain	1.0000
X:49603667:G:GC	acceptor_gain	1.0000
X:49603667:GG:G	acceptor_gain	1.0000
X:49603667:GGG:G	acceptor_gain	1.0000
X:49603667:GGGCC:G	acceptor_gain	1.0000
X:49603772:G:GT	donor_gain	1.0000
X:49603790:GAAG:G	donor_gain	1.0000
X:49603794:G:GA	donor_loss	1.0000
X:49600165:A:AG	acceptor_gain	0.9900

AlphaMissense

763 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:49600733:T:C	F32L	0.829
X:49600735:C:A	F32L	0.829
X:49600735:C:G	F32L	0.829
X:49600183:G:C	W3C	0.695
X:49600183:G:T	W3C	0.695
X:49600192:A:C	R6S	0.671
X:49600192:A:T	R6S	0.671
X:49600187:G:A	G5R	0.662
X:49600187:G:C	G5R	0.662
X:49600181:T:A	W3R	0.660
X:49600181:T:C	W3R	0.660
X:49600182:G:T	W3L	0.649
X:49600178:A:C	S2R	0.576
X:49600180:T:A	S2R	0.576
X:49600180:T:G	S2R	0.576
X:49600188:G:A	G5E	0.566

dbSNP variants (sampled 300 via entrez): RS1002859072 (X:49607746 C>T), RS1016723267 (X:49608643 G>A), RS1016733137 (X:49608234 G>T), RS1020740167 (X:49607486 C>T), RS1025156111 (X:49607361 T>C), RS1025205633 (X:49607050 C>T), RS1025444825 (X:49609036 C>A), RS1025537953 (X:49608666 T>A,G), RS1029438975 (X:49608197 A>C,G), RS1029904018 (X:49607861 A>G), RS1033759459 (X:49607443 A>C,G), RS1033961998 (X:49607779 A>G,T), RS1037686007 (X:49607640 C>A), RS1037779124 (X:49607262 C>T), RS1038111917 (X:49608998 C>T)

Disease associations

OMIM: gene MIM:300594 | 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

4 total (human), top 4 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Aripiprazole	increases expression	1
Benzo(a)pyrene	decreases methylation	1
Ozone	increases expression	1
Particulate Matter	increases expression	1

Clinical trials (associated diseases)

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