CTAG2

Summary

CTAG2 (cancer/testis antigen 2, HGNC:2492) is a protein-coding gene on chromosome Xq28, encoding Cancer/testis antigen 2 (O75638). In precision oncology, CTAG2 Overexpression confers sensitivity to Letetresgene Autoleucel in Multiple Myeloma (CIViC Level B).

This gene encodes an autoimmunogenic tumor antigen that belongs to the ESO/LAGE family of cancer-testis antigens. This protein is expressed in a wide array of cancers including melanoma, breast cancer, bladder cancer and prostate cancer. This protein is also expressed in normal testis tissue. An alternative open reading frame product of this gene has been described in PMID:10399963. This alternate protein, termed CAMEL, is a tumor antigen that is recognized by melanoma-specific cytotoxic T-lymphocytes. Alternate splicing results in multiple transcript variants.

Source: NCBI Gene 30848 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 51 total
• Precision-oncology evidence (CIViC): 1 curated variant–drug association
• MANE Select transcript: NM_172377

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2492
Approved symbol	CTAG2
Name	cancer/testis antigen 2
Location	Xq28
Locus type	gene with protein product
Status	Approved
Aliases	LAGE-1, CAMEL, LAGE1, ESO2, MGC3803, MGC138724, CT6.2a, CT6.2b, LAGE-1a, LAGE-1b
Ensembl gene	ENSG00000126890
Ensembl biotype	protein_coding
OMIM	300396
Entrez	30848

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000247306, ENST00000369585

RefSeq mRNA: 2 — MANE Select: NM_172377 NM_020994, NM_172377

CCDS: CCDS14759, CCDS35455

Canonical transcript exons

ENST00000369585 — 3 exons

Exon	Start	End
ENSE00001301877	154652497	154652631
ENSE00001685591	154651977	154652267
ENSE00001877190	154653247	154653579

Expression profiles

Bgee: expression breadth ubiquitous, 132 present calls, max score 84.92.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
tendon of biceps brachii	UBERON:0008188	84.92	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	84.71	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	83.53	gold quality
buccal mucosa cell	CL:0002336	80.21	silver quality
right testis	UBERON:0004534	74.53	gold quality
left testis	UBERON:0004533	73.70	gold quality
endometrium epithelium	UBERON:0004811	72.62	gold quality
testis	UBERON:0000473	71.37	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	71.02	gold quality
frontal pole	UBERON:0002795	69.09	silver quality
vastus lateralis	UBERON:0001379	68.98	gold quality
mucosa of stomach	UBERON:0001199	68.16	gold quality
quadriceps femoris	UBERON:0001377	67.58	gold quality
medial globus pallidus	UBERON:0002477	66.36	silver quality
cerebellar vermis	UBERON:0004720	66.08	silver quality
paraflocculus	UBERON:0005351	65.35	gold quality
middle frontal gyrus	UBERON:0002702	63.97	gold quality
diaphragm	UBERON:0001103	63.83	gold quality
globus pallidus	UBERON:0001875	63.79	silver quality
heart right ventricle	UBERON:0002080	62.78	gold quality
tongue squamous epithelium	UBERON:0006919	62.67	gold quality
cervix squamous epithelium	UBERON:0006922	62.46	gold quality
secondary oocyte	CL:0000655	61.50	gold quality
gluteal muscle	UBERON:0002000	59.70	gold quality
triceps brachii	UBERON:0001509	59.63	gold quality
orbitofrontal cortex	UBERON:0004167	59.04	gold quality
decidua	UBERON:0002450	58.95	gold quality
biceps brachii	UBERON:0001507	58.83	gold quality
vena cava	UBERON:0004087	58.21	silver quality
skeletal muscle tissue	UBERON:0001134	57.94	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.33

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

15 targeting CTAG2, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-1184	99.99	68.19	1458
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-4306	99.72	70.50	3630
HSA-MIR-4527	99.66	67.43	714
HSA-MIR-6503-5P	99.62	66.96	597
HSA-MIR-17-3P	99.55	66.77	1311
HSA-MIR-185-5P	99.35	68.60	2497
HSA-MIR-3692-5P	99.29	67.04	1421
HSA-MIR-3190-5P	98.87	64.89	1345
HSA-MIR-3135B	98.61	65.33	1470
HSA-MIR-193A-3P	98.59	66.36	769
HSA-MIR-193B-3P	98.59	66.62	748
HSA-MIR-6854-5P	96.77	65.96	848
HSA-MIR-1273C	95.96	65.86	66

Literature-anchored findings (GeneRIF, showing 14)

• CD4+ T cell clones specific for alternatively translated tumor antigen CAMEL have been isolated from the peripheral blood of a melanoma patient; CAMEL(81-102) is described as a naturally processed epitope recognized and presented by HLA-DR11 and HLA-DR12. (PMID:12538712)
• Data showed aberrant expression of NY-ESO-1 and LAGE-1 by IHC/RT-PCR in a significant proportion of epithelial ovarian cancer patients. (PMID:14522938)
• Data support the immunogenicity of NY-ESO-1/LAGE-1 ORF2 gene products and clearly demonstrate their capability to stimulate T-helper 1 type CD4+ T cells. (PMID:14559844)
• LAGE-1 expression was more frequently found in squamous cell carcinoma than in adenocarcinoma. (PMID:15061963)
• Isolation of CD4+ T cell clones from T cell cultures of two healthy donors leads to identification of four naturally processed HLA-DR-binding CAMEL epitopes, interesting peptides to investigate for future cancer immunotherapy. (PMID:15067093)
• first peptide epitope recognized by sera from a wide spectrum of cancer patients but not healthy donors (PMID:15540228)
• LAGE-1 expression was detected in esophageal cancer by cDNA RDA. LAGE-1 might have the potential to be a target antigen for anti-tumoral immunotherapy in esophageal cancers because of its tumor-specific expression similar to that of MAGE-A1. (PMID:16446548)
• There is a high frequency of the LAGE-1 gene allele with SNPs in coding regions in cancer patients. (PMID:17899192)
• MAGEC1/CT7, MAGEA3/6 and LAGE-1 are good candidates for immunotherapy, since together they cover 85% of the multiple myeloma cases. (PMID:18237105)
• We evaluated the correlations among the expression levels of NY-ESO-1, LAGE-1 and SSX-1 and clinical parameters in hepatocellular carcinoma patients (PMID:19212631)
• Spontaneous LAGE-1-specific CD4-positive T cells isolated from patients with advanced LAGE-1-positive/NY-ESO-1-positive melanoma are directed against three promiscuous and immunodominant epitopes. (PMID:21131422)
• LAGE-1a and NY-ESO-1 homology cannot be easily exploited in an anti-NY-ESO-1 vaccine given the low frequency of protein expression detected by IHC or serum analysis. (PMID:21247062)
• NYESO-1/LAGE-1s and PRAME are targets for antigen specific T cells in chondrosarcoma following treatment with 5-Aza-2-deoxycitabine (PMID:22384167)
• The tumor suppressor function of LSAMP is most likely exerted by reducing the proliferation rate of the tumor cells, possibly by indirectly upregulating one or more of the genes HES1, CTAG2 or KLF10. (PMID:24885297)

Cross-species orthologs

9 orthologs

Organism	Symbol	Gene ID
danio_rerio		ENSDARG00000116344
mus_musculus	Ctag2	ENSMUSG00000031181
mus_musculus	Ctag2l2	ENSMUSG00000079532
mus_musculus	Ctag2l1	ENSMUSG00000079536
rattus_norvegicus	Ctag2	ENSRNOG00000012560
rattus_norvegicus	Ctag2l1	ENSRNOG00000060839
rattus_norvegicus	Ctag2l2	ENSRNOG00000061511
rattus_norvegicus	Ctag2l2	ENSRNOG00000066963
drosophila_melanogaster	Tcs6	FBGN0260224

Paralogs (3): CTAG1B (ENSG00000184033), LAGE3 (ENSG00000196976), CTAG1A (ENSG00000268651)

Protein

Protein identifiers

Cancer/testis antigen 2 — O75638 (reviewed: O75638)

Alternative names: Autoimmunogenic cancer/testis antigen NY-ESO-2, Cancer/testis antigen 6.2, L antigen family member 1

All UniProt accessions (1): O75638

UniProt curated annotations — full annotation on UniProt →

Tissue specificity. Testis and very low level in placenta and in some uterus samples. Observed in 25-50% of tumor samples of melanomas, non-small-cell lung carcinomas, bladder, prostate and head and neck cancers.

Polymorphism. At least three different alleles exist. The allele defined by Arg-6 and Glu-89 is associated with a risk of gastric cancer.

Similarity. Belongs to the CTAG/PCC1 family.

Isoforms (2)

UniProt ID	Names	Canonical?
O75638-1	LAGE-1B, LAGE-1L	yes
O75638-2	LAGE-1A, LAGE-1S

RefSeq proteins (2): NP_066274, NP_758965* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR015419	CTAG/Pcc1	Family

Pfam: PF09341

UniProt features (11 total): compositionally biased region 3, sequence variant 3, region of interest 2, chain 1, sequence conflict 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O75638-F1	47.90	0.00

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 40 (showing top): YAGI_AML_WITH_INV_16_TRANSLOCATION, GOBP_TRNA_METABOLIC_PROCESS, GOCC_MICROTUBULE_ORGANIZING_CENTER, PUJANA_CHEK2_PCC_NETWORK, GOCC_CENTROSOME, GOBP_TRNA_THREONYLCARBAMOYLADENOSINE_METABOLIC_PROCESS, TGGAAA_NFAT_Q4_01, MARTENS_TRETINOIN_RESPONSE_UP, chrXq28, ZWANG_TRANSIENTLY_UP_BY_2ND_EGF_PULSE_ONLY, P53_DN.V1_UP, PRC1_BMI_UP.V1_DN, DCA_UP.V1_DN, PIEPOLI_LGI1_TARGETS_DN, KRAS.600_UP.V1_DN

GO Biological Process (1): tRNA threonylcarbamoyladenosine metabolic process (GO:0070525)

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

GO Cellular Component (1): centrosome (GO:0005813)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
tRNA metabolic process	1
binding	1
centriole	1
microtubule organizing center	1

Protein interactions and networks

STRING

380 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CTAG2	MAGEA4	P43358	891
CTAG2	MAGEA3	P43357	868
CTAG2	MAGEA6	P43360	825
CTAG2	MAGEA2B	P43356	787
CTAG2	MAGEA1	P43355	716
CTAG2	MAGEC1	O60732	696
CTAG2	GAGE4	P0DSO3	672
CTAG2	MAGEA10	P43363	663
CTAG2	SSX4	O60224	625
CTAG2	SSX1	Q16384	621
CTAG2	CT47A11	Q5JQC4	616
CTAG2	MAGEA9B	P43362	594
CTAG2	HLA-A	P01891	588
CTAG2	A0A1W2PQG5	A0A1W2PQG5	580
CTAG2	CSAG2	Q9Y5P2	575

IntAct

13 interactions, top by confidence:

A	B	Type	Score
CTAG2	TRIP6	psi-mi:“MI:0915”(physical association)	0.670
TRIP6	CTAG2	psi-mi:“MI:0915”(physical association)	0.670
UBQLN1	CTAG2	psi-mi:“MI:0915”(physical association)	0.560
UBQLN1	CTAG2	psi-mi:“MI:0915”(physical association)	0.370
Bag2		psi-mi:“MI:0914”(association)	0.350
CTAG2	PCNT	psi-mi:“MI:0914”(association)	0.350
CTAG2	ASMTL	psi-mi:“MI:0914”(association)	0.350
CTAG2	LAMB2	psi-mi:“MI:0914”(association)	0.350

BioGRID (36): CTAG2 (Two-hybrid), CTAG2 (Two-hybrid), CTAG2 (Affinity Capture-MS), CTAG2 (Affinity Capture-MS), CTAG2 (Two-hybrid), CTAG2 (Two-hybrid), UBQLN1 (Two-hybrid), TSEN2 (Two-hybrid), PRKAA2 (Two-hybrid), SMCP (Two-hybrid), AXIN2 (Two-hybrid), CTAG2 (Affinity Capture-MS), SASS6 (Affinity Capture-MS), NSMCE4A (Affinity Capture-MS), TBC1D9 (Affinity Capture-MS)

ESM2 similar proteins: A0A0U1RRK4, A0A1W2PPE3, A0A1W2PR82, A0A2Z4LIS9, A2VE02, A4D1S0, A5PKC7, A5PL33, A6H7B4, A6NEL2, A6QP24, A6QPM6, A8MTW9, A8MYA2, D3ZAQ5, D4AAA5, E7EW31, O75474, O75638, O89113, O94850, P0C7X2, P14652, P50617, P70339, Q2KIS6, Q3UN58, Q5JPB2, Q5VZ46, Q6GQX2, Q6NZ36, Q6ZSJ8, Q6ZW13, Q76NI1, Q7TNS8, Q80TS7, Q86UU5, Q8IWN7, Q8N6K4, Q8N944

Diamond homologs: O75638, P78358, Q14657, Q9CR70

SIGNOR signaling

0 interactions.

Disease & clinical

Cancer significance

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	35
Likely benign	5
Benign	6

Top pathogenic / likely-pathogenic (0)

SpliceAI

439 predictions. Top by Δscore:

Variant	Effect	Δscore
X:154652473:T:TA	donor_gain	1.0000
X:154652474:C:A	donor_gain	1.0000
X:154652479:T:TA	donor_gain	0.9900
X:154652495:A:AC	donor_gain	0.9900
X:154652496:C:CC	donor_gain	0.9900
X:154652601:C:CT	acceptor_gain	0.9900
X:154653246:CAA:C	donor_gain	0.9900
X:154653272:T:TA	donor_gain	0.9800
X:154653294:T:A	donor_gain	0.9800
X:154652491:A:AC	donor_gain	0.9700
X:154652492:C:CC	donor_gain	0.9700
X:154652511:G:A	donor_gain	0.9700
X:154653221:T:TA	donor_gain	0.9700
X:154653298:T:TA	donor_gain	0.9700
X:154653411:T:A	donor_gain	0.9700
X:154652268:C:CC	acceptor_gain	0.9600
X:154652274:G:C	acceptor_gain	0.9600
X:154653174:TG:T	donor_gain	0.9600
X:154653459:T:TA	donor_gain	0.9600
X:154652265:CGG:C	acceptor_gain	0.9500
X:154652450:C:CT	donor_gain	0.9500
X:154652498:TAA:T	donor_gain	0.9500
X:154652499:AAA:A	donor_gain	0.9500
X:154652527:T:TA	donor_gain	0.9500
X:154652531:TCAGA:T	donor_gain	0.9500
X:154652601:C:T	acceptor_gain	0.9500
X:154653171:TCTTG:T	donor_gain	0.9500
X:154653247:A:AT	donor_gain	0.9500
X:154652274:G:GC	acceptor_gain	0.9400
X:154652500:A:C	donor_gain	0.9400

AlphaMissense

1127 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:154652613:G:C	F96L	0.994
X:154652613:G:T	F96L	0.994
X:154652615:A:G	F96L	0.994
X:154652524:A:G	F126S	0.977
X:154652614:A:G	F96S	0.975
X:154652529:C:A	K124N	0.974
X:154652529:C:G	K124N	0.974
X:154652523:G:C	F126L	0.971
X:154652523:G:T	F126L	0.971
X:154652525:A:G	F126L	0.971
X:154652597:C:G	A102P	0.963
X:154652626:A:G	I92T	0.961
X:154652614:A:C	F96C	0.955
X:154652626:A:C	I92S	0.945
X:154652512:C:A	G130V	0.932
X:154652626:A:T	I92N	0.928
X:154652615:A:T	F96I	0.927
X:154652599:T:A	E101V	0.924
X:154652524:A:C	F126C	0.911
X:154652600:C:T	E101K	0.905
X:154652590:A:G	L104P	0.903
X:154652518:A:T	V128E	0.898
X:154652599:T:C	E101G	0.897
X:154652615:A:C	F96V	0.888
X:154652587:A:T	V105D	0.887
X:154652509:T:A	N131I	0.880
X:154652620:A:G	M94T	0.877
X:154652508:G:C	N131K	0.874
X:154652508:G:T	N131K	0.874
X:154652530:T:A	K124M	0.849

dbSNP variants (sampled 300 via entrez): RS1005459161 (X:154654621 A>C,G,T), RS1012920766 (X:154655407 G>C,T), RS1018563147 (X:154654640 G>A), RS1026507215 (X:154655534 G>A), RS1029418580 (X:154655082 C>T), RS1029721382 (X:154654688 T>C), RS1033009211 (X:154654727 A>G), RS1039738617 (X:154655311 A>C,G), RS1046163678 (X:154654533 G>A,T), RS1046796480 (X:154654853 T>C), RS1050926685 (X:154655319 G>A), RS111519604 (X:154654319 C>T), RS111856137 (X:154652913 TC>T), RS111939162 (X:154653354 C>T), RS112780678 (X:154652295 A>C,G)

Disease associations

OMIM: gene MIM:300396 | 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
GCST001873_11	Red blood cell traits	4.000000e-19
GCST004334_12	Mean corpuscular hemoglobin	2.000000e-29

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004305	erythrocyte count
EFO:0004527	mean corpuscular hemoglobin

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

Clinical evidence (CIViC)

Drug × variant × indication: 1 predictive associations from 1 curated evidence items.

Variant	Therapy	Indication	Effect	Level	CIViC
CTAG2 Overexpression	Letetresgene Autoleucel	Multiple Myeloma	Sensitivity/Response	CIViC B	EID2941

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
Decitabine	affects expression, affects methylation, increases expression	2
bisphenol A	decreases methylation	1
CGP 52608	affects binding, increases reaction	1
Air Pollutants	increases abundance, increases expression	1
Benzo(a)pyrene	affects methylation	1
Particulate Matter	increases abundance, increases expression	1

Clinical trials (associated diseases)

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