XAGE2

Summary

XAGE2 (X antigen family member 2, HGNC:4112) is a protein-coding gene on chromosome Xp11.22, encoding X antigen family member 2 (Q96GT9).

This gene is a member of the XAGE subfamily, which belongs to the GAGE family. The GAGE genes are expressed in a variety of tumors and in some fetal and reproductive tissues. This gene is strongly expressed in normal testis, and in Ewing’s sarcoma, rhabdomyosarcoma, a breast cancer and a germ cell tumor. The protein encoded by this gene shares a sequence similarity with other GAGE/PAGE proteins. Because of the expression pattern and the sequence similarity, this protein also belongs to a family of CT (cancer-testis) antigens.

Source: NCBI Gene 9502 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 1 total
• MANE Select transcript: NM_130777

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4112
Approved symbol	XAGE2
Name	X antigen family member 2
Location	Xp11.22
Locus type	gene with protein product
Status	Approved
Aliases	XAGE-2, CT12.2
Ensembl gene	ENSG00000155622
Ensembl biotype	protein_coding
OMIM	300416
Entrez	9502

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 4 protein_coding

ENST00000286049, ENST00000962144, ENST00000962145, ENST00000962146

RefSeq mRNA: 1 — MANE Select: NM_130777 NM_130777

CCDS: CCDS59525

Canonical transcript exons

ENST00000286049 — 5 exons

Exon	Start	End
ENSE00001631419	52370007	52370095
ENSE00001637310	52370567	52370672
ENSE00001675516	52369021	52369214
ENSE00001788507	52372544	52372669
ENSE00001911244	52375569	52375680

Expression profiles

Bgee: expression breadth broad, 51 present calls, max score 94.16.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 2.7196 / max 752.2440, expressed in 78 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
201295	1.8426	59
196391	0.7816	45
209689	0.0955	22

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
placenta	UBERON:0001987	94.16	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	90.93	gold quality
decidua	UBERON:0002450	84.05	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	83.08	gold quality
tibialis anterior	UBERON:0001385	76.35	silver quality
pancreatic ductal cell	CL:0002079	76.29	silver quality
amniotic fluid	UBERON:0000173	75.19	silver quality
deltoid	UBERON:0001476	74.38	gold quality
cerebellar vermis	UBERON:0004720	71.52	gold quality
cartilage tissue	UBERON:0002418	70.32	gold quality
myocardium	UBERON:0002349	70.31	gold quality
gingival epithelium	UBERON:0001949	70.17	gold quality
cardiac muscle of right atrium	UBERON:0003379	69.64	gold quality
ileal mucosa	UBERON:0000331	69.49	silver quality
left ventricle myocardium	UBERON:0006566	69.46	gold quality
pericardium	UBERON:0002407	68.16	silver quality
body of tongue	UBERON:0011876	67.06	gold quality
substantia nigra pars compacta	UBERON:0001965	67.01	gold quality
cardia of stomach	UBERON:0001162	66.97	gold quality
vena cava	UBERON:0004087	66.79	gold quality
lateral nuclear group of thalamus	UBERON:0002736	66.77	gold quality
pylorus	UBERON:0001166	66.76	gold quality
thymus	UBERON:0002370	66.62	silver quality
substantia nigra pars reticulata	UBERON:0001966	66.55	gold quality
biceps brachii	UBERON:0001507	66.50	gold quality
pharyngeal mucosa	UBERON:0000355	66.36	gold quality
trachea	UBERON:0003126	66.30	silver quality
pons	UBERON:0000988	66.29	gold quality
lateral globus pallidus	UBERON:0002476	66.29	gold quality
gingiva	UBERON:0001828	66.26	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-MTAB-6701	yes	1983.74
E-MTAB-3929	yes	85.68
E-MTAB-6678	yes	16.78
E-ANND-3	no	2.11

Regulation

Is transcription factor: no

Cross-species orthologs

0 orthologs

Paralogs (22): PAGE1 (ENSG00000068985), PAGE4 (ENSG00000101951), PAGE5 (ENSG00000158639), XAGE3 (ENSG00000171402), XAGE5 (ENSG00000171405), GAGE2A (ENSG00000189064), 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

X antigen family member 2 — Q96GT9 (reviewed: Q96GT9)

Alternative names: Cancer/testis antigen 12.2, G antigen family D member 3

All UniProt accessions (1): Q96GT9

UniProt curated annotations — full annotation on UniProt →

Similarity. Belongs to the GAGE family.

RefSeq proteins (1): NP_570133* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR008625	GAGE_fam	Family
IPR031320	GAGE	Domain

Pfam: PF05831

UniProt features (4 total): region of interest 2, chain 1, compositionally biased region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96GT9-F1	64.59	0.00

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 5 (showing top): ACEVEDO_LIVER_CANCER_WITH_H3K27ME3_UP, ACEVEDO_METHYLATED_IN_LIVER_CANCER_DN, chrXp11, ZWANG_TRANSIENTLY_UP_BY_2ND_EGF_PULSE_ONLY, YAP1_DN

GO Biological Process (0):

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (0):

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
binding	1

Protein interactions and networks

STRING

232 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
XAGE2	XAGE1B	Q9HD64	923
XAGE2	SPANXD	Q9BXN6	570
XAGE2	SPANXC	Q9NY87	570
XAGE2	ERVV-1	B6SEH8	448
XAGE2	SPANXB1	Q9NS25	447
XAGE2	SPANXA1	Q9NS26	447
XAGE2	MAGEA12	P43365	413
XAGE2	CT45A1	Q5HYN5	402
XAGE2	MAGEB2	O15479	397
XAGE2	DNAJB8	Q8NHS0	379
XAGE2	CGB5	P01233	377
XAGE2	TEX15	Q9BXT5	377
XAGE2	MAGEA4	P43358	373
XAGE2	NBPF4	Q96M43	372
XAGE2	DKKL1	Q9UK85	370
XAGE2	SPA17	Q15506	370

IntAct

20 interactions, top by confidence:

A	B	Type	Score
XAGE2	GMCL1	psi-mi:“MI:0915”(physical association)	0.770
GMCL1	XAGE2	psi-mi:“MI:0915”(physical association)	0.770
FLJ13057	XAGE2	psi-mi:“MI:0915”(physical association)	0.560
GMCL2	XAGE2	psi-mi:“MI:0915”(physical association)	0.560
XAGE2	GMCL2	psi-mi:“MI:0915”(physical association)	0.560
XAGE2	EHMT2	psi-mi:“MI:0915”(physical association)	0.550
XAGE2	WIZ	psi-mi:“MI:0914”(association)	0.530
TERF2IP	XAGE2	psi-mi:“MI:0915”(physical association)	0.510
EPS8	XAGE2	psi-mi:“MI:0915”(physical association)	0.490
XAGE2	EPS8	psi-mi:“MI:0915”(physical association)	0.490
XAGE2	POT1	psi-mi:“MI:0915”(physical association)	0.370
TERF2IP	XAGE2	psi-mi:“MI:0915”(physical association)	0.000
XAGE2	GMCL1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (23): GMCL1 (Two-hybrid), GMCL1P1 (Two-hybrid), EHMT2 (Two-hybrid), XAGE2 (Two-hybrid), XAGE2 (Two-hybrid), WIZ (Affinity Capture-MS), EHMT2 (Affinity Capture-MS), ZNF644 (Affinity Capture-MS), EHMT1 (Affinity Capture-MS), GMCL1 (Affinity Capture-MS), CBX5 (Affinity Capture-MS), XAGE2 (Two-hybrid), WIZ (Affinity Capture-MS), GMCL1 (Affinity Capture-MS), EHMT1 (Affinity Capture-MS)

ESM2 similar proteins: A0A1B0GTR3, A0A7H0DN82, A7RR34, E9PVX6, O14598, O60356, O60829, O94243, P04605, P04614, P05909, P0C1K0, P0C765, P0C766, P0DPH9, P17285, P17759, P18098, P19416, P20290, P24109, P46012, P46583, Q06428, Q07555, Q08561, Q09821, Q1L9C7, Q32PF3, Q3KP22, Q5M948, Q5M951, Q5MJ08, Q5RCI9, Q6P8I4, Q758T8, Q76632, Q7M2N1, Q7TP40, Q80WR5

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, Q96GU1, Q9HD64

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

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

Top pathogenic / likely-pathogenic (0)

SpliceAI

684 predictions. Top by Δscore:

Variant	Effect	Δscore
X:52370092:GCTT:G	donor_gain	1.0000
X:52370096:G:GG	donor_gain	1.0000
X:52370540:A:AG	acceptor_gain	1.0000
X:52370541:C:G	acceptor_gain	1.0000
X:52370542:A:AG	acceptor_gain	1.0000
X:52370543:C:G	acceptor_gain	1.0000
X:52370544:A:AG	acceptor_gain	1.0000
X:52370544:ATACT:A	acceptor_gain	1.0000
X:52370545:T:G	acceptor_gain	1.0000
X:52370546:A:AG	acceptor_gain	1.0000
X:52370546:ACT:A	acceptor_gain	1.0000
X:52370548:T:A	acceptor_gain	1.0000
X:52370562:CCCA:C	acceptor_loss	1.0000
X:52370563:CCAG:C	acceptor_loss	1.0000
X:52370564:CAGGA:C	acceptor_loss	1.0000
X:52370565:A:AG	acceptor_gain	1.0000
X:52370566:G:GA	acceptor_loss	1.0000
X:52370566:G:GG	acceptor_gain	1.0000
X:52370661:C:G	donor_gain	1.0000
X:52370668:TCAAG:T	donor_loss	1.0000
X:52370669:CAAGG:C	donor_loss	1.0000
X:52370671:AG:A	donor_loss	1.0000
X:52370672:GGTG:G	donor_loss	1.0000
X:52370673:G:C	donor_loss	1.0000
X:52370681:A:T	donor_gain	1.0000
X:52370685:G:GT	donor_gain	1.0000
X:52370686:A:T	donor_gain	1.0000
X:52372540:TTA:T	acceptor_loss	1.0000
X:52372541:TAGT:T	acceptor_loss	1.0000
X:52372542:A:AG	acceptor_gain	1.0000

AlphaMissense

719 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:52370032:A:C	R6S	0.697
X:52370032:A:T	R6S	0.697
X:52370027:G:A	G5R	0.636
X:52370027:G:C	G5R	0.636
X:52370023:G:C	W3C	0.633
X:52370023:G:T	W3C	0.633
X:52370021:T:A	W3R	0.631
X:52370021:T:C	W3R	0.631
X:52370044:G:C	R10S	0.601
X:52370044:G:T	R10S	0.601
X:52370022:G:T	W3L	0.587
X:52370028:G:A	G5E	0.578

dbSNP variants (sampled 300 via entrez): RS1001102424 (X:52371842 C>T), RS1001161064 (X:52371361 C>T), RS1001557594 (X:52367622 A>G), RS1001610082 (X:52367246 G>A), RS1001817154 (X:52375477 C>T), RS1002113603 (X:52373834 A>G), RS1002120946 (X:52375921 T>C), RS1002558895 (X:52369278 C>A), RS1002570792 (X:52373324 T>A,C), RS1002611020 (X:52369013 C>A), RS1004911376 (X:52371264 C>T), RS1004963569 (X:52370955 T>C), RS1005580765 (X:52375291 C>A,T), RS1005631849 (X:52374981 G>T), RS1005911647 (X:52373221 T>A)

Disease associations

OMIM: gene MIM:300416 | 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

17 total (human), top 17 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, increases methylation	3
mercuric bromide	affects cotreatment, increases expression	2
terbufos	increases methylation	1
sulforaphane	decreases expression	1
cobaltous chloride	increases expression	1
butyraldehyde	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	increases expression, affects cotreatment	1
dorsomorphin	affects cotreatment, increases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Arbutin	increases expression	1
Fonofos	increases methylation	1
Parathion	increases methylation	1
Phenylmercuric Acetate	increases expression	1
Plant Extracts	affects cotreatment, decreases expression	1
Cyclosporine	increases methylation	1
Sodium Selenite	decreases expression	1
Permethrin	decreases expression	1

Clinical trials (associated diseases)

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