XAGE3

Summary

XAGE3 (X antigen family member 3, HGNC:14618) is a protein-coding gene on chromosome Xp11.22, encoding X antigen family member 3 (Q8WTP9).

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 expressed in placenta and fetal liver/spleen, and may function in inhibiting cancer cell growth. 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. Alternative splicing of this gene generates 2 transcript variants differing in the 5’ UTR.

Source: NCBI Gene 170626 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 8 total
• MANE Select transcript: NM_133179

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:14618
Approved symbol	XAGE3
Name	X antigen family member 3
Location	Xp11.22
Locus type	gene with protein product
Status	Approved
Aliases	XAGE-3, pp9012, CT12.3a, CT12.3b
Ensembl gene	ENSG00000171402
Ensembl biotype	protein_coding
OMIM	300740
Entrez	170626

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000346279, ENST00000375491

RefSeq mRNA: 2 — MANE Select: NM_133179 NM_130776, NM_133179

CCDS: CCDS14347

Canonical transcript exons

ENST00000346279 — 5 exons

Exon	Start	End
ENSE00001147135	52868006	52868083
ENSE00001620569	52864775	52864900
ENSE00001737896	52866433	52866538
ENSE00001789781	52867053	52867141
ENSE00001881229	52862528	52862640

Expression profiles

Bgee: expression breadth broad, 62 present calls, max score 96.46.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.6261 / max 316.5030, expressed in 16 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
199313	0.5136	13
199314	0.1125	11

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
placenta	UBERON:0001987	96.46	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	86.42	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	82.30	gold quality
buccal mucosa cell	CL:0002336	70.95	gold quality
decidua	UBERON:0002450	66.34	silver quality
tendon of biceps brachii	UBERON:0008188	66.03	gold quality
cerebellar vermis	UBERON:0004720	65.62	gold quality
vastus lateralis	UBERON:0001379	63.81	gold quality
upper arm skin	UBERON:0004263	63.71	gold quality
cartilage tissue	UBERON:0002418	60.97	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	60.90	gold quality
heart right ventricle	UBERON:0002080	60.07	gold quality
esophagus squamous epithelium	UBERON:0006920	59.48	gold quality
medial globus pallidus	UBERON:0002477	58.64	gold quality
vena cava	UBERON:0004087	58.17	gold quality
deltoid	UBERON:0001476	57.39	gold quality
jejunal mucosa	UBERON:0000399	57.18	gold quality
seminal vesicle	UBERON:0000998	57.07	gold quality
nasal cavity epithelium	UBERON:0005384	56.99	gold quality
biceps brachii	UBERON:0001507	56.05	gold quality
mucosa of sigmoid colon	UBERON:0004993	55.87	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	55.51	gold quality
jejunum	UBERON:0002115	55.50	gold quality
gingiva	UBERON:0001828	55.38	gold quality
kidney epithelium	UBERON:0004819	55.24	gold quality
parotid gland	UBERON:0001831	55.23	gold quality
globus pallidus	UBERON:0001875	54.70	gold quality
trabecular bone tissue	UBERON:0002483	54.57	gold quality
cardiac muscle of right atrium	UBERON:0003379	54.34	gold quality
parietal pleura	UBERON:0002400	54.24	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-HCAD-24	yes	2773.51
E-MTAB-6701	yes	2765.40
E-HCAD-23	yes	1998.42
E-ANND-3	no	1.12

Regulation

Is transcription factor: no

Cross-species orthologs

0 orthologs

Paralogs (22): PAGE1 (ENSG00000068985), PAGE4 (ENSG00000101951), XAGE2 (ENSG00000155622), PAGE5 (ENSG00000158639), 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 3 — Q8WTP9 (reviewed: Q8WTP9)

Alternative names: Cancer/testis antigen 12.3, G antigen family D member 4, Placenta-specific gene 6 protein

All UniProt accessions (1): Q8WTP9

UniProt curated annotations — full annotation on UniProt →

Similarity. Belongs to the GAGE family.

RefSeq proteins (2): NP_570132, NP_573440* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR008625	GAGE_fam	Family
IPR031320	GAGE	Domain

Pfam: PF05831

UniProt features (5 total): compositionally biased region 2, chain 1, region of interest 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8WTP9-F1	65.70	0.00

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 15 (showing top): KORKOLA_CHORIOCARCINOMA, chrXp11, ZWANG_EGF_INTERVAL_UP, ZNF618_TARGET_GENES, DESCARTES_MAIN_FETAL_CSH1_CSH2_POSITIVE_CELLS, DESCARTES_FETAL_ADRENAL_CSH1_CSH2_POSITIVE_CELLS, GSE17974_0H_VS_4H_IN_VITRO_ACT_CD4_TCELL_UP, GSE18791_CTRL_VS_NEWCASTLE_VIRUS_DC_1H_DN, GSE18791_UNSTIM_VS_NEWCATSLE_VIRUS_DC_6H_UP, PERCHARD_ALSPAC_PREDICTIVE_PREHYPERTENSION_COMBINED, GSE2405_HEAT_KILLED_VS_LIVE_A_PHAGOCYTOPHILUM_STIM_NEUTROPHIL_24H_DN, GSE22601_DOUBLE_NEGATIVE_VS_CD8_SINGLE_POSITIVE_THYMOCYTE_DN, ODONNELL_TFRC_TARGETS_DN, GSE21678_WT_VS_FOXO1_FOXO3_KO_TREG_UP, GSE25088_WT_VS_STAT6_KO_MACROPHAGE_UP

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

262 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
XAGE3	XAGE1B	Q9HD64	947
XAGE3	ACTL8	Q9H568	667
XAGE3	SPANXN4	Q5MJ08	571
XAGE3	OIP5	O43482	506
XAGE3	SPATA31D4	Q6ZUB0	448
XAGE3	MAGEB10	Q96LZ2	435
XAGE3	MAGEB4	O15481	431
XAGE3	PSG6	Q00889	418
XAGE3	CTCFL	Q8NI51	418
XAGE3	SPANXN3	Q5MJ09	398
XAGE3	MAGEC1	O60732	395
XAGE3	TMPRSS12	Q86WS5	394
XAGE3	MAGEA4	P43358	392
XAGE3	MRFAP1L1	Q96HT8	391
XAGE3	SSX7	Q7RTT5	380

IntAct

30 interactions, top by confidence:

A	B	Type	Score
GMCL1	XAGE3	psi-mi:“MI:0915”(physical association)	0.800
XAGE3	GMCL1	psi-mi:“MI:0915”(physical association)	0.800
FLJ13057	XAGE3	psi-mi:“MI:0915”(physical association)	0.560
XAGE3	FLJ13057	psi-mi:“MI:0915”(physical association)	0.560
LCE2C	XAGE3	psi-mi:“MI:0915”(physical association)	0.560
DEFA5	NUDT19	psi-mi:“MI:0914”(association)	0.530
GAST	ZZEF1	psi-mi:“MI:0914”(association)	0.530
GTSE1	GAST	psi-mi:“MI:0914”(association)	0.530
XAGE3	WIZ	psi-mi:“MI:0914”(association)	0.530
XAGE3	CFTR	psi-mi:“MI:0915”(physical association)	0.510
CFTR	XAGE3	psi-mi:“MI:0915”(physical association)	0.510
XAGE3	HTT	psi-mi:“MI:0915”(physical association)	0.510
HTT	XAGE3	psi-mi:“MI:0915”(physical association)	0.510
LYZL1	XAGE3	psi-mi:“MI:0915”(physical association)	0.400
XAGE3	PSMG1	psi-mi:“MI:0914”(association)	0.350
DSCR4	GAST	psi-mi:“MI:0914”(association)	0.350
XAGE3	GMCL1	psi-mi:“MI:0915”(physical association)	0.000
XAGE3	LCE2C	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (38): XAGE3 (Two-hybrid), ZNF644 (Affinity Capture-MS), METAP1D (Affinity Capture-MS), WIZ (Affinity Capture-MS), EHMT2 (Affinity Capture-MS), EHMT1 (Affinity Capture-MS), XAGE3 (Affinity Capture-MS), RSPRY1 (Affinity Capture-MS), XAGE3 (Affinity Capture-MS), GMCL1 (Affinity Capture-MS), XAGE3 (Affinity Capture-MS), RNPEPL1 (Affinity Capture-MS), PSMG2 (Affinity Capture-MS), CROCCP2 (Affinity Capture-MS), PSMG1 (Affinity Capture-MS)

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, Q96GU1, Q9HD64

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

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

Top pathogenic / likely-pathogenic (0)

SpliceAI

323 predictions. Top by Δscore:

Variant	Effect	Δscore
X:52864769:GCATA:G	donor_loss	1.0000
X:52864770:CATAC:C	donor_loss	1.0000
X:52864771:ATAC:A	donor_loss	1.0000
X:52864772:TACCT:T	donor_loss	1.0000
X:52864773:A:C	donor_loss	1.0000
X:52864773:ACCT:A	donor_gain	1.0000
X:52864774:CCTC:C	donor_gain	1.0000
X:52864776:T:TA	donor_gain	1.0000
X:52864898:GCA:G	acceptor_gain	1.0000
X:52864898:GCAC:G	acceptor_loss	1.0000
X:52864899:CA:C	acceptor_gain	1.0000
X:52864899:CAC:C	acceptor_gain	1.0000
X:52864900:ACTAA:A	acceptor_loss	1.0000
X:52864901:C:CC	acceptor_gain	1.0000
X:52864901:CTAA:C	acceptor_loss	1.0000
X:52864902:T:G	acceptor_loss	1.0000
X:52866420:C:A	donor_gain	1.0000
X:52867048:CTCA:C	donor_loss	1.0000
X:52867049:TCACC:T	donor_loss	1.0000
X:52867050:CACCA:C	donor_loss	1.0000
X:52867051:A:AC	donor_gain	1.0000
X:52867052:C:CC	donor_gain	1.0000
X:52867052:CCAG:C	donor_gain	1.0000
X:52864896:AGGCA:A	acceptor_gain	0.9900
X:52864897:GGCA:G	acceptor_gain	0.9900
X:52866424:T:TA	donor_gain	0.9900
X:52866425:C:A	donor_gain	0.9900
X:52866444:G:C	donor_gain	0.9900
X:52864774:CCT:C	donor_gain	0.9800
X:52866419:T:A	donor_gain	0.9800

AlphaMissense

713 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:52867116:T:A	R6S	0.785
X:52867116:T:G	R6S	0.785
X:52867127:A:G	W3R	0.755
X:52867127:A:T	W3R	0.755
X:52867125:C:A	W3C	0.737
X:52867125:C:G	W3C	0.737
X:52867121:C:G	G5R	0.687
X:52867121:C:T	G5R	0.687
X:52867104:C:A	R10S	0.674
X:52867104:C:G	R10S	0.674
X:52864791:A:C	F99L	0.653
X:52864791:A:T	F99L	0.653
X:52864793:A:G	F99L	0.653
X:52867126:C:A	W3L	0.633
X:52867117:C:G	R6T	0.621
X:52867120:C:T	G5E	0.614
X:52867109:A:C	Y9D	0.606
X:52867105:C:A	R10M	0.585
X:52867114:G:A	S7L	0.584
X:52867111:G:A	T8I	0.580
X:52867126:C:G	W3S	0.570

dbSNP variants (sampled 300 via entrez): RS1007957187 (X:52862461 C>A), RS1014774726 (X:52862864 T>C), RS1019438059 (X:52862063 G>A), RS1019892743 (X:52862485 C>A,T), RS1023014799 (X:52862867 T>C), RS1026866002 (X:52862520 A>C), RS1040774436 (X:52862774 G>A,C), RS1043285987 (X:52862344 A>C), RS1048251034 (X:52862821 A>G), RS1052070535 (X:52862739 G>A), RS111336508 (X:52862277 G>A), RS111338598 (X:52862163 C>A,T), RS111341711 (X:52862237 C>T), RS111661570 (X:52863373 A>G), RS111844599 (X:52867805 C>T)

Disease associations

OMIM: gene MIM:300740 | 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
GCST002606_20	Prostate cancer	9.000000e-10
GCST002606_39	Prostate cancer	3.000000e-11

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

7 total (human), top 7 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
pentanal	decreases expression	1
CGP 52608	affects binding, increases reaction	1
clothianidin	increases expression	1
Acetaminophen	decreases expression	1
Benzo(a)pyrene	affects methylation, decreases methylation	1
Cyclosporine	increases expression	1
Cadmium Chloride	decreases expression	1

Clinical trials (associated diseases)

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