CSAG2

Summary

CSAG2 (CSAG family member 2, HGNC:16847) is a protein-coding gene on chromosome Xq28, encoding Chondrosarcoma-associated gene 2/3 protein (Q9Y5P2). Drug-resistance related protein, its expression is associated with the chemotherapy resistant and neoplastic phenotype.

Predicted to be involved in response to xenobiotic stimulus.

Source: NCBI Gene 102723547 — RefSeq curated summary.

At a glance

• MANE Select transcript: NM_001395334

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16847
Approved symbol	CSAG2
Name	CSAG family member 2
Location	Xq28
Locus type	gene with protein product
Status	Approved
Aliases	TRAG3, CT24.2
Ensembl gene	ENSG00000268902
Ensembl biotype	protein_coding
OMIM	301096
Entrez	102723547

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 3 protein_coding_CDS_not_defined, 2 protein_coding

ENST00000598036, ENST00000638741, ENST00000640702, ENST00000715562, ENST00000715563

RefSeq mRNA: 1 — MANE Select: NM_001395334 NM_001395334

CCDS: CCDS94689

Canonical transcript exons

ENST00000638741 — 2 exons

Exon	Start	End
ENSE00003978283	152708799	152709273
ENSE00003978284	152708261	152708640

Expression profiles

Bgee: expression breadth broad, 71 present calls, max score 69.76.

Top tissues by expression

112 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	69.76	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	50.14	gold quality
colonic epithelium	UBERON:0000397	48.80	gold quality
lymph node	UBERON:0000029	45.62	gold quality
bone marrow cell	CL:0002092	42.81	gold quality
primary visual cortex	UBERON:0002436	41.12	silver quality
right testis	UBERON:0004534	41.08	gold quality
tonsil	UBERON:0002372	40.94	gold quality
spleen	UBERON:0002106	39.10	gold quality
substantia nigra	UBERON:0002038	38.78	gold quality
granulocyte	CL:0000094	38.24	gold quality
prefrontal cortex	UBERON:0000451	37.93	gold quality
superior frontal gyrus	UBERON:0002661	37.14	gold quality
putamen	UBERON:0001874	36.72	gold quality
Brodmann (1909) area 9	UBERON:0013540	36.62	gold quality
ventricular zone	UBERON:0003053	36.48	gold quality
Ammon’s horn	UBERON:0001954	36.47	gold quality
cortical plate	UBERON:0005343	36.47	gold quality
bone marrow	UBERON:0002371	36.45	gold quality
placenta	UBERON:0001987	35.97	gold quality
urinary bladder	UBERON:0001255	35.63	gold quality
ganglionic eminence	UBERON:0004023	35.49	gold quality
liver	UBERON:0002107	35.46	silver quality
vermiform appendix	UBERON:0001154	35.42	gold quality
cerebral cortex	UBERON:0000956	35.22	gold quality
testis	UBERON:0000473	35.03	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	34.89	gold quality
frontal cortex	UBERON:0001870	34.87	gold quality
anterior cingulate cortex	UBERON:0009835	34.58	gold quality
amygdala	UBERON:0001876	34.18	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-HCAD-35	yes	395.79
E-ANND-3	no	0.48

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 6)

• DNA demethylation is an important epigenetic mechanism that regulates the TRAG-3 tumor antigen in human tumors (PMID:15120907)
• As the TRAG-3 gene is located on Xq28, which is the same locus as the MAGE gene family, we found a frequent synchronous expression pattern with TRAG-3 and MAGE-3 in esophageal cancer. (PMID:16685391)
• TRAG-3-specific CD4+ T cells recognize in vitro not only peptide pulsed antigen presenting cells but also autologous dendritic cells loaded with the TRAG-3 protein. (PMID:16888034)
• Human VCX/Y, SPANX, and CSAG2 gene families together with the murine SPANX gene and the CYPT family may share a common ancestor. (PMID:17342728)
• TRAG3 was significantly higher in T24-L and T24-B than T24-P. TRAG3 gene expression is likely controlled by DNA methylation but not histone acetylation (PMID:20734393)
• CSAG2 is a cancer-specific activator of SIRT1. (PMID:32761762)

Cross-species orthologs

0 orthologs

Paralogs (2): CSAG1 (ENSG00000198930), CSAG3 (ENSG00000268916)

Protein

Protein identifiers

Chondrosarcoma-associated gene 2/3 protein — Q9Y5P2 (reviewed: Q9Y5P2)

Alternative names: Cancer/testis antigen 24.2, Taxol-resistant-associated gene 3 protein

All UniProt accessions (2): A0A1W2PPV0, A0A1W2PQG5

UniProt curated annotations — full annotation on UniProt →

Function. Drug-resistance related protein, its expression is associated with the chemotherapy resistant and neoplastic phenotype. May also be linked to the malignant phenotype.

Tissue specificity. Weakly expressed in kidney. Expressed in various tumor cell lines including carcinomas, myeloid and lymphoid malignancies, melanomas and prostate cancer. Overexpressed in taxol-resistant breast cancer line MDA 435TR and the doxorubicin-resistant multiple myelanoma lines RPMI-8226/Dox40 and RPMI-8226/MDR10V.

Isoforms (3)

UniProt ID	Names	Canonical?
Q9Y5P2-1	1, Long, TRAG-3L	yes
Q9Y5P2-2	2, Short, TRAG-3S
Q9Y5P2-3	3

RefSeq proteins (1): NP_001382263* (*=MANE)

Domains & families (InterPro)

UniProt features (10 total): sequence conflict 5, splice variant 3, chain 1, region of interest 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9Y5P2-F1	56.41	0.00

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 7 (showing top): chrXq28, SIRNA_EIF4GI_DN, AUNG_GASTRIC_CANCER, LEE_LIVER_CANCER_SURVIVAL_UP, NADERI_BREAST_CANCER_PROGNOSIS_UP, HELLER_SILENCED_BY_METHYLATION_UP, GOBP_RESPONSE_TO_XENOBIOTIC_STIMULUS

GO Biological Process (1): response to xenobiotic stimulus (GO:0009410)

GO Molecular Function (0):

GO Cellular Component (0):

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
response to chemical	1

Protein interactions and networks

STRING

410 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CSAG2	MAGEA3	P43357	721
CSAG2	MAGEA2B	P43356	670
CSAG2	MAGEA10	P43363	657
CSAG2	CTAG2	O75638	575
CSAG2	MAGEA12	P43365	570
CSAG2	CTAG1A	P78358	542
CSAG2	CT47A11	Q5JQC4	507
CSAG2	CT45A1	Q5HYN5	506
CSAG2	SPANXA1	Q9NS26	505
CSAG2	GAGE2A	Q6NT46	480
CSAG2	CT55	Q8WUE5	479
CSAG2	PASD1	Q8IV76	473
CSAG2	PRAME	P78395	448
CSAG2	MAGEB6	Q8N7X4	447
CSAG2	SSX4	O60224	446

IntAct

8 interactions, top by confidence:

A	B	Type	Score
SIRT1	CSAG2	psi-mi:“MI:0915”(physical association)	0.640
CSAG2	SIRT1	psi-mi:“MI:0915”(physical association)	0.640
CSAG2	SIRT1	psi-mi:“MI:0403”(colocalization)	0.640
CSAG2	TP53	psi-mi:“MI:0197”(deacetylation reaction)	0.440
CSAG2	CAMK2D	psi-mi:“MI:0914”(association)	0.350

BioGRID (1): CSAG3 (Biochemical Activity)

ESM2 similar proteins: A0A1B0GVR7, A0A6G7KUU3, A0PJW8, B1AK76, B8UU74, D3ZF18, O12159, O15926, O46660, O95567, P03424, P05900, P05901, P05913, P0C8P5, P0DPG3, P12452, P19718, P20877, P20920, P26035, P28970, P32544, P33482, P35977, P92524, Q02781, Q1X6Y8, Q1X6Y9, Q2M2E5, Q2YDM5, Q32M92, Q5K130, Q5TBE3, Q5VTH2, Q66104, Q6S6S5, Q6ZSB3, Q77MS7, Q8AII0

Diamond homologs: Q6PB30, Q9Y5P2

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
CSAG2	“up-regulates activity”	SIRT1	binding

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

743 predictions. Top by Δscore:

Variant	Effect	Δscore
X:152714679:CAAGG:C	donor_loss	1.0000
X:152714681:AGGT:A	donor_loss	1.0000
X:152714683:G:C	donor_loss	1.0000
X:152714684:T:G	donor_loss	1.0000
X:152716957:GATCT:G	donor_gain	1.0000
X:152716962:G:GG	donor_gain	1.0000
X:152717039:CAG:C	acceptor_loss	1.0000
X:152717040:A:AG	acceptor_gain	1.0000
X:152717041:G:GG	acceptor_gain	1.0000
X:152717041:GGCCT:G	acceptor_gain	1.0000
X:152716959:TCT:T	donor_gain	0.9900
X:152716959:TCTG:T	donor_loss	0.9900
X:152716960:CTGTA:C	donor_loss	0.9900
X:152716961:TG:T	donor_loss	0.9900
X:152716962:GTA:G	donor_loss	0.9900
X:152716963:T:TC	donor_loss	0.9900
X:152716964:A:AG	donor_loss	0.9900
X:152716965:AGTA:A	donor_loss	0.9900
X:152716966:G:GG	donor_gain	0.9900
X:152717041:GGC:G	acceptor_gain	0.9900
X:152714679:C:T	donor_gain	0.9800
X:152714683:G:GG	donor_gain	0.9800
X:152716958:ATCT:A	donor_gain	0.9800
X:152716960:CT:C	donor_gain	0.9800
X:152716966:G:C	donor_loss	0.9800
X:152717040:AG:A	acceptor_gain	0.9800
X:152717041:GG:G	acceptor_gain	0.9800
X:152717041:GGCC:G	acceptor_gain	0.9800
X:152714678:GCAAG:G	donor_gain	0.9700
X:152716393:GAT:G	donor_gain	0.9700

AlphaMissense

822 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:152709005:A:C	F36L	0.966
X:152709005:A:T	F36L	0.966
X:152709007:A:G	F36L	0.966
X:152709109:A:G	W2R	0.920
X:152709109:A:T	W2R	0.920
X:152708637:G:C	F106L	0.907
X:152708637:G:T	F106L	0.907
X:152708639:A:G	F106L	0.907
X:152709041:G:C	F24L	0.906
X:152709041:G:T	F24L	0.906
X:152709043:A:G	F24L	0.906
X:152708984:G:C	F43L	0.898
X:152708984:G:T	F43L	0.898
X:152708986:A:G	F43L	0.898
X:152709006:A:G	F36S	0.893
X:152709056:G:C	F19L	0.872
X:152709056:G:T	F19L	0.872
X:152709058:A:G	F19L	0.872
X:152709103:C:G	G4R	0.864
X:152709006:A:C	F36C	0.860
X:152708998:A:G	C39R	0.840
X:152709107:C:A	W2C	0.839
X:152709107:C:G	W2C	0.839
X:152708996:G:C	C39W	0.829
X:152709099:A:T	L5H	0.806
X:152709099:A:G	L5P	0.802
X:152709087:A:T	V9D	0.798
X:152708993:C:A	W40C	0.795
X:152708993:C:G	W40C	0.795
X:152709042:A:G	F24S	0.786

dbSNP variants (sampled 300 via entrez): RS112223342 (X:152710245 G>A), RS113506057 (X:152708044 A>C), RS1156377608 (X:152759895 AC>A), RS1156660272 (X:152710747 A>G), RS1156728302 (X:152708807 G>A), RS1156870224 (X:152707963 G>C), RS1158065707 (X:152760326 C>G), RS1158353267 (X:152709631 G>GAGAA), RS1158405268 (X:152708291 T>C), RS1158548327 (X:152759561 G>A), RS1158963610 (X:152708354 G>A), RS1160188614 (X:152708051 T>C,G), RS1160654544 (X:152759984 C>G,T), RS1161008099 (X:152708215 C>A,G), RS1161016747 (X:152709080 A>T)

Disease associations

OMIM: gene MIM:301096 | 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

9 total (human), top 9 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
propionaldehyde	increases expression	1
butyraldehyde	increases expression	1
pentanal	increases expression	1
ICG 001	increases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Aldehydes	increases expression	1
Benzo(a)pyrene	increases expression	1
Plant Extracts	affects cotreatment, decreases expression	1
Copper Sulfate	affects expression	1

Clinical trials (associated diseases)

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