GAGE2A

Summary

GAGE2A (G antigen 2A, HGNC:4099) is a protein-coding gene on chromosome Xp11.23, encoding G antigen 2A (Q6NT46).

At a glance

• Clinical variants (ClinVar): 29 total
• MANE Select transcript: NM_001127212

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4099
Approved symbol	GAGE2A
Name	G antigen 2A
Location	Xp11.23
Locus type	gene with protein product
Status	Approved
Aliases	CT4.2
Ensembl gene	ENSG00000189064
Ensembl biotype	protein_coding
OMIM	300720
Entrez	729447

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000362097, ENST00000938385

RefSeq mRNA: 1 — MANE Select: NM_001127212 NM_001127212

CCDS: CCDS48114

Canonical transcript exons

ENST00000362097 — 5 exons

Exon	Start	End
ENSE00001657972	49589496	49589603
ENSE00001659223	49590643	49590731
ENSE00001676134	49591197	49591317
ENSE00001676296	49596711	49596824
ENSE00001763169	49594118	49594243

Expression profiles

Bgee: expression breadth broad, 90 present calls, max score 97.77.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	97.77	gold quality
right testis	UBERON:0004534	96.50	gold quality
testis	UBERON:0000473	96.28	gold quality
left testis	UBERON:0004533	96.14	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	93.96	gold quality
lower esophagus mucosa	UBERON:0035834	48.91	gold quality
right uterine tube	UBERON:0001302	37.74	silver quality
right coronary artery	UBERON:0001625	37.59	gold quality
ectocervix	UBERON:0012249	37.48	gold quality
right lung	UBERON:0002167	37.47	silver quality
colonic epithelium	UBERON:0000397	37.20	gold quality
ventricular zone	UBERON:0003053	36.48	gold quality
cortical plate	UBERON:0005343	36.47	gold quality
bone marrow cell	CL:0002092	36.16	gold quality
ganglionic eminence	UBERON:0004023	35.49	gold quality
urinary bladder	UBERON:0001255	34.70	gold quality
uterine cervix	UBERON:0000002	34.41	gold quality
blood	UBERON:0000178	33.03	gold quality
hindlimb stylopod muscle	UBERON:0004252	32.15	gold quality
gastrocnemius	UBERON:0001388	31.91	gold quality
right adrenal gland	UBERON:0001233	31.78	gold quality
bone marrow	UBERON:0002371	31.74	gold quality
muscle of leg	UBERON:0001383	31.71	gold quality
endocervix	UBERON:0000458	31.22	gold quality
liver	UBERON:0002107	31.08	gold quality
sural nerve	UBERON:0015488	30.93	gold quality
right lobe of liver	UBERON:0001114	30.22	gold quality
stromal cell of endometrium	CL:0002255	29.87	gold quality
right adrenal gland cortex	UBERON:0035827	29.87	gold quality
multicellular organism	UBERON:0000468	29.23	gold quality

Single-cell (SCXA)

Detected in 8 experiment(s), a significant marker in 6.

Experiment	Marker?	Max mean expression
E-GEOD-134144	yes	2680.89
E-GEOD-124263	yes	2521.89
E-MTAB-3929	yes	982.70
E-MTAB-7249	yes	309.61
E-GEOD-81383	yes	256.58
E-MTAB-6524	yes	14.62
E-CURD-53	no	1159.27
E-ANND-3	no	0.32

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 1)

• Data show that EZH2 is a crucial regulator of GAGE2 expression. (PMID:19934278)

Cross-species orthologs

0 orthologs

Paralogs (22): PAGE1 (ENSG00000068985), PAGE4 (ENSG00000101951), XAGE2 (ENSG00000155622), PAGE5 (ENSG00000158639), XAGE3 (ENSG00000171402), XAGE5 (ENSG00000171405), PAGE3 (ENSG00000204279), XAGE1A (ENSG00000204379), XAGE1B (ENSG00000204382), GAGE1 (ENSG00000205777), 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 2A — Q6NT46 (reviewed: Q6NT46)

All UniProt accessions (1): Q6NT46

UniProt curated annotations — full annotation on UniProt →

Miscellaneous. This gene belongs to a multigene family expressed in a large variety of tumors whereas in normal tissues, expression is restricted to germ cells. These genes organized in clustered repeats, 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_001120684* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR008625	GAGE_fam	Family
IPR031320	GAGE	Domain

Pfam: PF05831

UniProt features (5 total): compositionally biased region 3, chain 1, region of interest 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6NT46-F1	66.09	0.00

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 5 (showing top): HELLER_HDAC_TARGETS_SILENCED_BY_METHYLATION_UP, ACEVEDO_METHYLATED_IN_LIVER_CANCER_DN, chrXp11, HELLER_HDAC_TARGETS_UP, HELLER_SILENCED_BY_METHYLATION_UP

GO Biological Process (0):

GO Molecular Function (0):

GO Cellular Component (0):

Protein interactions and networks

STRING

1373 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GAGE2A	MAGEA3	P43357	940
GAGE2A	MAGEA1	P43355	909
GAGE2A	KRTAP20-3	Q3LI60	591
GAGE2A	CT45A1	Q5HYN5	584
GAGE2A	XAGE1B	Q9HD64	576
GAGE2A	SPANXC	Q9NY87	575
GAGE2A	SPANXD	Q9BXN6	573
GAGE2A	PAGE4	O60829	507
GAGE2A	CT55	Q8WUE5	507
GAGE2A	MAGEA2B	P43356	507
GAGE2A	MAGEA4	P43358	507
GAGE2A	CTAG2	O75638	506
GAGE2A	A0A1W2PQG5	A0A1W2PQG5	480
GAGE2A	CSAG2	Q9Y5P2	480
GAGE2A	PASD1	Q8IV76	479

IntAct

0 interactions, top by confidence:

BioGRID (2): GAGE2A (Two-hybrid), GAGE2A (Two-hybrid)

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

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	25
Likely benign	4
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

661 predictions. Top by Δscore:

Variant	Effect	Δscore
X:49590641:A:AG	acceptor_gain	1.0000
X:49590642:G:GG	acceptor_gain	1.0000
X:49590642:G:GT	acceptor_gain	1.0000
X:49590642:GT:G	acceptor_gain	1.0000
X:49590642:GTGT:G	acceptor_gain	1.0000
X:49590728:GCGG:G	donor_gain	1.0000
X:49590729:CGGG:C	donor_loss	1.0000
X:49590729:CGGGT:C	donor_loss	1.0000
X:49590730:GG:G	donor_gain	1.0000
X:49590730:GGGT:G	donor_loss	1.0000
X:49590731:GG:G	donor_gain	1.0000
X:49590731:GGT:G	donor_loss	1.0000
X:49590732:G:A	donor_loss	1.0000
X:49590732:G:GG	donor_gain	1.0000
X:49590733:T:A	donor_loss	1.0000
X:49591170:A:AG	acceptor_gain	1.0000
X:49591170:ATTT:A	acceptor_gain	1.0000
X:49591171:T:G	acceptor_gain	1.0000
X:49591173:T:TA	acceptor_gain	1.0000
X:49591176:A:AG	acceptor_gain	1.0000
X:49591177:C:G	acceptor_gain	1.0000
X:49591178:A:AG	acceptor_gain	1.0000
X:49591179:C:G	acceptor_gain	1.0000
X:49591182:A:AG	acceptor_gain	1.0000
X:49591182:ACAC:A	acceptor_gain	1.0000
X:49591183:C:G	acceptor_gain	1.0000
X:49591184:A:AG	acceptor_gain	1.0000
X:49591184:AC:A	acceptor_gain	1.0000
X:49591185:C:A	acceptor_gain	1.0000
X:49591185:C:CA	acceptor_gain	1.0000

AlphaMissense

755 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:49591206:T:C	F31L	0.833
X:49591208:C:A	F31L	0.833
X:49591208:C:G	F31L	0.833
X:49590659:G:C	W3C	0.761
X:49590659:G:T	W3C	0.761
X:49590657:T:A	W3R	0.752
X:49590657:T:C	W3R	0.752
X:49590668:A:C	R6S	0.716
X:49590668:A:T	R6S	0.716
X:49590663:G:A	G5R	0.711
X:49590663:G:C	G5R	0.711
X:49590658:G:T	W3L	0.685
X:49590664:G:A	G5E	0.653
X:49590654:A:C	S2R	0.652
X:49590656:T:A	S2R	0.652
X:49590656:T:G	S2R	0.652
X:49590675:T:G	Y9D	0.646
X:49590673:C:T	T8I	0.590
X:49590675:T:C	Y9H	0.579

dbSNP variants (sampled 300 via entrez): RS111841783 (X:49589961 G>A), RS112425647 (X:49591401 T>C,G), RS112466482 (X:49592320 C>A), RS112597632 (X:49591627 C>T), RS113157222 (X:49591438 A>G), RS1157603054 (X:49591481 G>A), RS1160270774 (X:49591199 C>G,T), RS1161221776 (X:49595555 T>C), RS1162429186 (X:49595557 T>A), RS1164749603 (X:49590102 T>C), RS1164786579 (X:49591571 G>A), RS1166010346 (X:49591582 A>G), RS1166237520 (X:49590558 G>A), RS1166910845 (X:49595645 C>T), RS1169640019 (X:49595817 C>A,G,T)

Disease associations

OMIM: gene MIM:300720 | disease phenotypes: MIM:304790

GenCC curated gene-disease

Mondo (1): immune dysregulation-polyendocrinopathy-enteropathy-X-linked syndrome (MONDO:0010580)

Orphanet (1): Immune dysregulation-polyendocrinopathy-enteropathy-X-linked syndrome (Orphanet:37042)

HPO phenotypes

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

GWAS associations

0 associations (top):

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C580192	Immune Dysregulation, Polyendocrinopathy, Enteropathy, X-Linked Syndrome (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

2 total (human), top 2 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
picoxystrobin	decreases expression	1
Mitoxantrone	affects response to substance	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT01821781	PHASE2	ACTIVE_NOT_RECRUITING	Immune Disorder HSCT Protocol
NCT01998633	PHASE2	COMPLETED	Reduced Intensity Conditioning for Hemophagocytic Syndromes or Selected Primary Immune Deficiencies (BMT CTN 1204)
NCT07284641	PHASE2	RECRUITING	Hematopoietic Stem Cell Transplantation (HSCT) for Common Variable Immunodeficiency (CVID) and Other Autoimmune Manifestations of Primary Immune Regulatory Disorders (PIRD)
NCT05241444	PHASE1	RECRUITING	CD4^LVFOXP3 in Participants With IPEX
NCT04902807	Not specified	RECRUITING	Conception of a Diagnosis, Prognosis and Therapeutic Decision Tool for Patients With Autoimmunity and Inflammation