XAGE1A

Summary

XAGE1A (X antigen family member 1A, HGNC:4111) 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 653220 — RefSeq curated summary.

At a glance

• Druggable target: yes
• MANE Select transcript: NM_001097594

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4111
Approved symbol	XAGE1A
Name	X antigen family member 1A
Location	Xp11.22
Locus type	gene with protein product
Status	Approved
Aliases	XAGE-1, CT12.1a
Ensembl gene	ENSG00000204379
Ensembl biotype	protein_coding
OMIM	300742
Entrez	653220

Gene structure

Transcript identifiers

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

ENST00000375595, ENST00000375600, ENST00000375602, ENST00000496463

RefSeq mRNA: 4 — MANE Select: NM_001097594 NM_001097594, NM_001097596, NM_001421805, NM_001421806

CCDS: CCDS75982, CCDS75983

Canonical transcript exons

ENST00000375602 — 4 exons

Exon	Start	End
ENSE00002260049	52495808	52495909
ENSE00003518742	52497985	52498111
ENSE00003618040	52500702	52500812
ENSE00003650803	52497316	52497457

Expression profiles

Bgee: expression breadth broad, 93 present calls, max score 98.20.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.2076 / max 98.4160, expressed in 6 samples.

FANTOM5 promoters (9 alternative TSS)

Promoter ID	TPM avg	Samples expressed
209692	0.6451	137
209700	0.1446	6
209693	0.0279	11
209697	0.0272	6
209694	0.0242	11
209701	0.0237	6
209698	0.0082	5
209695	0.0073	4
209699	0.0038	2

Top tissues by expression

126 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	98.20	gold quality
right testis	UBERON:0004534	97.49	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	96.82	gold quality
testis	UBERON:0000473	96.74	gold quality
left testis	UBERON:0004533	96.53	gold quality
tonsil	UBERON:0002372	46.07	gold quality
calcaneal tendon	UBERON:0003701	44.66	gold quality
upper lobe of left lung	UBERON:0008952	41.73	gold quality
duodenum	UBERON:0002114	40.12	gold quality
cortex of kidney	UBERON:0001225	39.90	gold quality
lung	UBERON:0002048	39.50	gold quality
skin of leg	UBERON:0001511	38.76	gold quality
colonic epithelium	UBERON:0000397	37.20	gold quality
metanephros cortex	UBERON:0010533	36.77	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
descending thoracic aorta	UBERON:0002345	36.13	silver quality
zone of skin	UBERON:0000014	36.10	gold quality
liver	UBERON:0002107	35.90	gold quality
vermiform appendix	UBERON:0001154	35.74	gold quality
ganglionic eminence	UBERON:0004023	35.49	gold quality
skeletal muscle tissue	UBERON:0001134	35.11	gold quality
lymph node	UBERON:0000029	34.83	gold quality
right lobe of liver	UBERON:0001114	33.40	silver quality
muscle tissue	UBERON:0002385	33.34	gold quality
blood	UBERON:0000178	33.29	gold quality
muscle of leg	UBERON:0001383	32.43	gold quality
skin of abdomen	UBERON:0001416	32.17	gold quality
hindlimb stylopod muscle	UBERON:0004252	32.15	gold quality

Single-cell (SCXA)

Detected in 6 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-MTAB-6653	yes	984.03
E-GEOD-134144	yes	968.12
E-MTAB-8530	yes	906.84
E-GEOD-124263	yes	827.75
E-CURD-53	no	550.82
E-ANND-3	no	0.65

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 11)

• Recognition of XAGE-1b on OU-LU-6 tumor by the CD4-expressing tumor-infiltrating lymphocytes was studied. (PMID:17332921)
• A 12-mer peptide XAGE-1b(37-48) as a new XAGE-1b epitope restricted to HLA-DRB1*0410 was identified. (PMID:17704638)
• The findings suggest that XAGE-1b and HLA class I expression elicited a CD8+ T-cell response against minimal residual disease after surgery and resulted in prolonged survival of non-small cell lung cancer patients. (PMID:18752338)
• the XAGE-1b gene was expressed at the mRNA level in a proportion of human acute leukemia (PMID:20178013)
• Our results suggest that GAGE, XAGE1 and SSX4 might each have a role in melanoma progression (PMID:23625514)
• XAGE-1b gene was able to influence angiogenesis directly or indirectly, leading to tumorigenesis and metastasis of ACC. (PMID:24008415)
• Data indicate the involvement of immunoglobulin allotypes immunoglobulin gamma and kappa chains in immunity to a cancer-testis antigen, which has important implications for XAGE-1b-based immunotherapeutic interventions in lung adenocarcinoma. (PMID:24304136)
• Strong immune responses to the cancer testis antigen XAGE-1b have been found in non-small cell lung cancer Caucasian patients. (PMID:26937656)
• In patients with Colon cancer, the expression of XAGE-1 gene was related to a favorable prognosis. (PMID:28631709)
• High XAGE1 expression is associated with metastasis in Head and Neck Squamous Cell Carcinoma. (PMID:29577858)
• Measurable Residual Disease Monitoring of SPAG6, ST18, PRAME, and XAGE1A Expression in Peripheral Blood May Detect Imminent Relapse in Childhood Acute Myeloid Leukemia. (PMID:34600138)

Cross-species orthologs

0 orthologs

Paralogs (22): PAGE1 (ENSG00000068985), PAGE4 (ENSG00000101951), XAGE2 (ENSG00000155622), PAGE5 (ENSG00000158639), XAGE3 (ENSG00000171402), XAGE5 (ENSG00000171405), GAGE2A (ENSG00000189064), PAGE3 (ENSG00000204279), 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 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_001091063, NP_001091065, 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: 5 (showing top): PATIL_LIVER_CANCER, CHANG_IMMORTALIZED_BY_HPV31_UP, FALVELLA_SMOKERS_WITH_LUNG_CANCER, chrXp11, NAKAMURA_LUNG_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
XAGE1A	XAGE3	Q8WTP9	947
XAGE1A	XAGE2	Q96GT9	923
XAGE1A	MAGEC1	O60732	726
XAGE1A	CTAG1A	P78358	667
XAGE1A	MAGEA1	P43355	591
XAGE1A	CT45A1	Q5HYN5	582
XAGE1A	GAGE4	P0DSO3	577
XAGE1A	GAGE2A	Q6NT46	576
XAGE1A	ADAM29	Q9UKF5	557
XAGE1A	SPANXA1	Q9NS26	526
XAGE1A	CTAG2	O75638	506
XAGE1A	CT55	Q8WUE5	506
XAGE1A	MAGEA3	P43357	505
XAGE1A	PAGE4	O60829	480
XAGE1A	MAGEA10	P43363	480
XAGE1A	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

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1157979394 (X:52499600 TGAA>T), RS1158849674 (X:52498656 A>G), RS1160493813 (X:52499574 C>T), RS1164051255 (X:52499350 A>G), RS1170007928 (X:52499185 T>G), RS1174550425 (X:52498981 C>A), RS1176087062 (X:52498784 G>A), RS1177919250 (X:52499402 C>T), RS1185095627 (X:52499365 A>C,G), RS1188487446 (X:52499222 C>T), RS1189509433 (X:52498833 C>T), RS1193230735 (X:52499017 T>C), RS1197507942 (X:52499278 C>G,T), RS1198677966 (X:52499269 T>C), RS1199001654 (X:52499675 A>G)

Disease associations

OMIM: gene MIM:300742 | 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

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

Chemical	Actions (top 5)	PubMed papers
Decitabine	increases expression	2
2-amino-9H-pyrido(2,3-b)indole	increases expression	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.