XAGE1B

Summary

XAGE1B (X antigen family member 1B, HGNC:25400) is a protein-coding gene on chromosome Xp11.22, encoding X antigen family member 1 (Q9HD64).

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 Ewing’s sarcoma, alveolar rhabdomyosarcoma and normal testis. The protein encoded by this gene contains a nuclear localization signal and 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, in addition to alternative transcription start sites, results in multiple transcript variants.

Source: NCBI Gene 653067 — RefSeq curated summary.

At a glance

• Druggable target: yes
• MANE Select transcript: NM_001097604

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25400
Approved symbol	XAGE1B
Name	X antigen family member 1B
Location	Xp11.22
Locus type	gene with protein product
Status	Approved
Aliases	CT12.1b, CT12.1c, CT12.1d
Ensembl gene	ENSG00000204382
Ensembl biotype	protein_coding
OMIM	300289
Entrez	653067

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 4 protein_coding, 2 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000375612, ENST00000375613, ENST00000375616, ENST00000494039, ENST00000518075, ENST00000519579, ENST00000888691

RefSeq mRNA: 4 — MANE Select: NM_001097604 NM_001097604, NM_001097605, NM_001421805, NM_001421806

CCDS: CCDS48126, CCDS48128

Canonical transcript exons

ENST00000375616 — 4 exons

Exon	Start	End
ENSE00001612816	52516980	52517063
ENSE00003484838	52512077	52512187
ENSE00003520407	52514778	52514904
ENSE00003591900	52515432	52515573

Expression profiles

Bgee: expression breadth broad, 89 present calls, max score 91.57.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.6451 / max 70.0721, expressed in 137 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
209692	0.6451	137
209693	0.0279	11
209694	0.0242	11
209695	0.0073	4

Top tissues by expression

118 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	91.57	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	86.99	gold quality
testis	UBERON:0000473	68.40	gold quality
right testis	UBERON:0004534	65.93	gold quality
left testis	UBERON:0004533	65.08	gold quality
upper lobe of left lung	UBERON:0008952	47.46	gold quality
lung	UBERON:0002048	45.62	gold quality
tonsil	UBERON:0002372	45.47	gold quality
lower esophagus mucosa	UBERON:0035834	44.48	silver quality
monocyte	CL:0000576	42.67	gold quality
leukocyte	CL:0000738	42.05	gold quality
right lung	UBERON:0002167	41.76	gold quality
bone marrow cell	CL:0002092	40.77	gold quality
apex of heart	UBERON:0002098	39.64	silver quality
lymph node	UBERON:0000029	39.56	gold quality
placenta	UBERON:0001987	39.37	gold quality
duodenum	UBERON:0002114	39.18	gold quality
bone marrow	UBERON:0002371	38.03	gold quality
calcaneal tendon	UBERON:0003701	37.70	gold quality
ectocervix	UBERON:0012249	37.41	gold 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
vermiform appendix	UBERON:0001154	36.46	gold quality
sural nerve	UBERON:0015488	36.44	gold quality
liver	UBERON:0002107	36.04	gold quality
cortex of kidney	UBERON:0001225	36.00	gold quality
ganglionic eminence	UBERON:0004023	35.49	gold quality
skeletal muscle tissue	UBERON:0001134	35.27	gold quality
right uterine tube	UBERON:0001302	34.83	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-GEOD-134144	yes	637.48
E-CURD-11	no	96.72
E-ANND-3	no	0.65

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 11)

• The XAGE family of cancer/testis-associated genes: alignment and expression profile in normal tissues, melanoma lesions and Ewing’s sarcoma (PMID:11992404)
• transcription of the XAGE-1 gene is initiated from two distinct start sites, resulting in two overlapping transcripts, XAGE-1a and XAGE-1b; XAGE-1 is expressed in a diverse range of cancers (PMID:12479262)
• Activation of human cancer/testis antigen gene, XAGE-1, in tumor cells is correlated with CpG island hypomethylation. (PMID:15800911)
• XAGE-1 expression in normal and cancerous tissues is regulated by methylation of the CpG island in the gene promoter (PMID:15800911)
• XAGE-1b is highly and strongly expressed in lung adenocarcinoma and immunogenic in patients (PMID:16061866)
• XAGE-1b is a promising target molecule for a cancer vaccine against lung cancer. (PMID:17335148)
• XAGE-1b gene is highly expressed in lung adenocarcinoma. (PMID:17666327)
• XAGE-1 gene is highly expressed in lung adenocarcinoma. (PMID:20704819)
• The findings suggest that production of the XAGE1 (GAGED2a) antibody predicts good prognosis for patients with lung adenocarcinoma as an immune biomarker (PMID:25124687)
• We investigated tumor-infiltrating CD4 and CD8 T cells and the expression of PD-L1, Galectin-9, and XAGE1 in stage I to IIIA lung adenocarcinomas using a tissue microarray to deduce their contribution to overall survival, and our data showed that PD-L1 expression was a positive indicator, whereas Galectin-9 and XAGE1 expression was negative. (PMID:27799141)
• In 22 melanoma patients with stage III lymph node metastasis, overall survival was significantly higher in the XAGE-1b and NY-ESO-1 double-negative group than in the other groups. (PMID:28105694)

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), 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 1 — Q9HD64 (reviewed: Q9HD64)

Alternative names: Cancer/testis antigen 12.1, G antigen family D member 2

All UniProt accessions (1): Q9HD64

UniProt curated annotations — full annotation on UniProt →

Tissue specificity. In normal tissues, highly expressed in testis. Expressed also in many different types of cancers: highly expressed in breast cancer, prostate cancer and many types of lung cancers, including squamous cell carcinoma, small cell carcinoma, non-small cell carcinoma, and adenocarcinoma, as well as in Ewing’s cell lines, in some Ewing’s sarcoma patient samples, and in one of one alveolar rhabdomyosarcoma patient sample.

Miscellaneous. According to PubMed:11992404, the transcription of XAGE1A is regulated by methylation of the CpG island in the promoter, and four alternative RNA splicing variants, XAGE-1a, b, c have been identified. XAGE-1a and XAGE-1b mRNAs are produced by alternative promoter usage. However, for both isoforms, the translation initiator codon remains the same, generating an identical protein. XAGE-1b is the predominant transcript, compared to XAGE-1a.

Similarity. Belongs to the GAGE family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9HD64-2	B, XAGE-1a, XAGE-1b	yes
Q9HD64-4	D, XAGE-1d

RefSeq proteins (4): NP_001091073, NP_001091074, NP_001408734, NP_001408735 (=MANE)

Domains & families (InterPro)

UniProt features (6 total): cross-link 3, chain 1, modified residue 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9HD64-F1	50.68	0.00

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 (4): 20, 12, 61, 65

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 17 (showing top): VERHAAK_AML_WITH_NPM1_MUTATED_DN, MODULE_493, KIM_RESPONSE_TO_TSA_AND_DECITABINE_UP, SHEDDEN_LUNG_CANCER_GOOD_SURVIVAL_A4, ACEVEDO_METHYLATED_IN_LIVER_CANCER_DN, VALK_AML_CLUSTER_16, chrXp11, ZWANG_TRANSIENTLY_UP_BY_2ND_EGF_PULSE_ONLY, MIR5588_5P, MIR4720_5P, MIR4799_3P, YEGNASUBRAMANIAN_PROSTATE_CANCER, SATO_SILENCED_BY_METHYLATION_IN_PANCREATIC_CANCER_1, ROSS_AML_WITH_MLL_FUSIONS, SATO_SILENCED_EPIGENETICALLY_IN_PANCREATIC_CANCER

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

364 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
XAGE1B	XAGE3	Q8WTP9	947
XAGE1B	XAGE2	Q96GT9	923
XAGE1B	MAGEC1	O60732	726
XAGE1B	CTAG1A	P78358	667
XAGE1B	MAGEA1	P43355	591
XAGE1B	CT45A1	Q5HYN5	582
XAGE1B	GAGE4	P0DSO3	577
XAGE1B	GAGE2A	Q6NT46	576
XAGE1B	ADAM29	Q9UKF5	557
XAGE1B	SPANXA1	Q9NS26	526
XAGE1B	CTAG2	O75638	506
XAGE1B	CT55	Q8WUE5	506
XAGE1B	MAGEA3	P43357	505
XAGE1B	PAGE4	O60829	480
XAGE1B	MAGEA10	P43363	480
XAGE1B	MAGEA4	P43358	480

IntAct

30 interactions, top by confidence:

A	B	Type	Score
PSMC3	PSMD9	psi-mi:“MI:0914”(association)	0.940
XAGE1A	YAF2	psi-mi:“MI:0915”(physical association)	0.670
XAGE1A	BANP	psi-mi:“MI:0915”(physical association)	0.560
XAGE1A	SETBP1	psi-mi:“MI:0915”(physical association)	0.560
SETBP1	XAGE1A	psi-mi:“MI:0915”(physical association)	0.560
BANP	XAGE1A	psi-mi:“MI:0915”(physical association)	0.560
TSPYL2	XAGE1A	psi-mi:“MI:0915”(physical association)	0.560
RYBP	XAGE1A	psi-mi:“MI:0915”(physical association)	0.560
YY1	XAGE1A	psi-mi:“MI:0915”(physical association)	0.560
XAGE1A	THAP12	psi-mi:“MI:0914”(association)	0.530
CAPN2	MYO9A	psi-mi:“MI:0914”(association)	0.530
XAGE1A	UBE2O	psi-mi:“MI:0915”(physical association)	0.370
MAD2L2		psi-mi:“MI:0914”(association)	0.350
M		psi-mi:“MI:0914”(association)	0.350
EAF1	C1orf226	psi-mi:“MI:0914”(association)	0.350
FTL		psi-mi:“MI:0914”(association)	0.350
PCDHGB4	AAMP	psi-mi:“MI:0914”(association)	0.350
YAF2	MGAM	psi-mi:“MI:0914”(association)	0.350
XAGE1A	TSPYL2	psi-mi:“MI:0915”(physical association)	0.000
XAGE1A	RYBP	psi-mi:“MI:0915”(physical association)	0.000
YY1	XAGE1A	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (56): XAGE1E (Two-hybrid), YAF2 (Two-hybrid), SETBP1 (Two-hybrid), BANP (Two-hybrid), TERF2 (Affinity Capture-MS), FAT4 (Affinity Capture-MS), ZBTB10 (Affinity Capture-MS), CABIN1 (Affinity Capture-MS), FAT3 (Affinity Capture-MS), FZD3 (Affinity Capture-MS), CELSR2 (Affinity Capture-MS), PCDH7 (Affinity Capture-MS), ZNF511 (Affinity Capture-MS), HIRA (Affinity Capture-MS), PCDHGC3 (Affinity Capture-MS)

ESM2 similar proteins: A0A023PYH0, A0A0P0BQD2, A0A0P0BUQ6, A0A0P0BZQ8, A0A0P0C6M6, A0A0P0CC97, A2RG89, A8AKK2, B4F0U2, B5XJY1, C0H3U7, C0HJW9, C0HKF4, C0R305, O60092, P0C0P8, P0CAQ7, P0DG88, P0DG89, P0DV82, P14610, P19564, P22834, P26874, P59037, P67307, P81473, Q02781, Q0AIJ1, Q0ATU3, Q1J8A6, Q1JDC8, Q1JIF2, Q1JNA1, Q21DF9, Q2V4N5, Q3E740, Q3E816, Q47U34, Q48V42

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

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

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

Top pathogenic / likely-pathogenic (0)

SpliceAI

0 predictions. Top by Δscore:

AlphaMissense

536 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:52515448:A:G	I27T	0.855
X:52515484:A:G	I15T	0.809
X:52514893:C:A	W36C	0.804
X:52514893:C:G	W36C	0.804
X:52514816:A:G	I62T	0.761
X:52515454:A:G	I25T	0.756
X:52514895:A:G	W36R	0.741
X:52514895:A:T	W36R	0.741
X:52515484:A:C	I15S	0.739
X:52514816:A:T	I62K	0.726
X:52515492:T:A	K12N	0.715
X:52515492:T:G	K12N	0.715
X:52515448:A:T	I27K	0.711
X:52515454:A:C	I25S	0.696
X:52514818:C:A	K61N	0.684
X:52514818:C:G	K61N	0.684
X:52515481:A:G	L16P	0.661
X:52515448:A:C	I27R	0.660
X:52514816:A:C	I62R	0.655
X:52515490:A:T	V13D	0.627
X:52515491:C:G	V13L	0.616
X:52514894:C:G	W36S	0.607
X:52515450:C:A	R26S	0.591
X:52515450:C:G	R26S	0.591
X:52514872:G:C	C43W	0.576
X:52514888:A:T	V38E	0.568
X:52515484:A:T	I15N	0.567
X:52515493:T:A	K12I	0.564

dbSNP variants (sampled 300 via entrez): RS112243563 (X:52513686 G>A), RS1158309326 (X:52512287 T>C), RS1162684179 (X:52512106 A>G,T), RS1167064480 (X:52511853 T>G), RS1169396957 (X:52512786 G>A), RS1174211773 (X:52512595 C>G,T), RS1177887471 (X:52512313 A>G), RS1179077055 (X:52512143 C>T), RS1180359379 (X:52511926 C>T), RS1187845300 (X:52512844 C>T), RS1192289726 (X:52512616 A>C), RS1192877715 (X:52512198 A>G), RS1196699688 (X:52512415 G>C), RS1199030202 (X:52511980 G>C,T), RS1200909573 (X:52512890 C>G)

Disease associations

OMIM: gene MIM:300289 | 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: yes

ChEMBL targets (1): CHEMBL4295952 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

6 total (human), top 6 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
abrine	increases expression	1
Decitabine	increases expression	1
Arsenic Trioxide	increases expression	1
Fluorouracil	affects response to substance	1
Aflatoxin B1	decreases methylation	1
Okadaic Acid	increases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4118613	Binding	Binding affinity to XAGE1B in human NCI-H23 cells at 1 uM by mass spectrometry based pull down assay	Studies of TAK1-centered polypharmacology with novel covalent TAK1 inhibitors. — Bioorg Med Chem

Clinical trials (associated diseases)

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