CAGE1

Summary

CAGE1 (cancer antigen 1, HGNC:21622) is a protein-coding gene on chromosome 6p24.3, encoding Cancer-associated gene 1 protein (Q8TC20).

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 115 total — 2 pathogenic
• MANE Select transcript: NM_001170692

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:21622
Approved symbol	CAGE1
Name	cancer antigen 1
Location	6p24.3
Locus type	gene with protein product
Status	Approved
Aliases	bA69L16.7, CT95
Ensembl gene	ENSG00000164304
Ensembl biotype	protein_coding
OMIM	608304
Entrez	285782

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 6 protein_coding, 2 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000296742, ENST00000338150, ENST00000379918, ENST00000442019, ENST00000458291, ENST00000502583, ENST00000509324, ENST00000512086, ENST00000512691

RefSeq mRNA: 3 — MANE Select: NM_001170692 NM_001170692, NM_001170693, NM_205864

CCDS: CCDS47367, CCDS54964, CCDS54965

Canonical transcript exons

ENST00000502583 — 14 exons

Exon	Start	End
ENSE00002045662	7326659	7326899
ENSE00002085871	7389202	7389742
ENSE00003489320	7373073	7374131
ENSE00003516635	7386979	7387196
ENSE00003540771	7356025	7356129
ENSE00003549401	7365468	7365575
ENSE00003571064	7378617	7379020
ENSE00003612124	7385785	7385872
ENSE00003618299	7368688	7368798
ENSE00003620674	7329849	7329888
ENSE00003635717	7334022	7334090
ENSE00003653387	7369919	7370065
ENSE00003674504	7365804	7365884
ENSE00003685076	7355041	7355111

Expression profiles

Bgee: expression breadth broad, 53 present calls, max score 76.88.

FANTOM5 (CAGE): breadth broad, TPM avg 0.7793 / max 28.5991, expressed in 349 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
71618	0.6549	329
71617	0.1244	51

Top tissues by expression

187 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	76.88	gold quality
sperm	CL:0000019	73.57	gold quality
left testis	UBERON:0004533	71.03	gold quality
testis	UBERON:0000473	69.93	gold quality
right testis	UBERON:0004534	69.83	gold quality
lower lobe of lung	UBERON:0008949	59.67	silver quality
bone marrow cell	CL:0002092	51.58	gold quality
adult organism	UBERON:0007023	48.61	gold quality
buccal mucosa cell	CL:0002336	45.66	gold quality
bone marrow	UBERON:0002371	45.65	gold quality
colonic epithelium	UBERON:0000397	45.30	gold quality
right coronary artery	UBERON:0001625	45.27	gold quality
skin of hip	UBERON:0001554	44.93	silver quality
monocyte	CL:0000576	44.56	silver quality
mucosa of transverse colon	UBERON:0004991	44.47	silver quality
leukocyte	CL:0000738	44.23	silver quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	43.37	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	43.31	gold quality
secondary oocyte	CL:0000655	42.57	gold quality
vermiform appendix	UBERON:0001154	42.30	gold quality
nasal cavity mucosa	UBERON:0001826	41.92	silver quality
right uterine tube	UBERON:0001302	41.71	silver quality
caecum	UBERON:0001153	41.64	gold quality
islet of Langerhans	UBERON:0000006	41.62	gold quality
endometrium	UBERON:0001295	41.47	gold quality
vastus lateralis	UBERON:0001379	41.41	gold quality
quadriceps femoris	UBERON:0001377	41.37	gold quality
superficial temporal artery	UBERON:0001614	41.33	gold quality
mammalian vulva	UBERON:0000997	41.31	gold quality
palpebral conjunctiva	UBERON:0001812	41.10	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.18

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 5)

• identification and characterization of CAGE-1 gene; displays testis-specific expression among normal tissues, and wide expression among various cancer tissues and cancer cell lines (PMID:12531476)
• The different patterns of aberrant methylation of the CAGE-1 gene in the various histopathological cancer types of the urinary bladder point to a role in tumor cell differentiation. (PMID:16964403)
• CTSP-1 should be considered a promising candidate for cancer immunotherapy (PMID:17114284)
• The present data suggest that promoter methylation of the 14-3-3 sigma and CAGE-1 genes plays a crucial role during the phenotypical morphogenesis of vesical adenocarcinomas including signet ring cell carcinomas by an epigenetic mechanism. (PMID:17786288)
• CAGE and miR-200b form a feedback regulatory loop. (PMID:24174534)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Cage1	ENSMUSG00000044566
rattus_norvegicus	Cage1	ENSRNOG00000024111

Protein

Protein identifiers

Cancer-associated gene 1 protein — Q8TC20 (reviewed: Q8TC20)

Alternative names: Cancer/testis antigen 3

All UniProt accessions (4): D6R9A7, Q8TC20, D6RCC6, E7EUJ7

UniProt curated annotations — full annotation on UniProt →

Tissue specificity. Testis-specific expression in normal tissues, but wide expression among cancer tissues and cell lines.

Miscellaneous. May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.

Isoforms (5)

UniProt ID	Names	Canonical?
Q8TC20-1	1	yes
Q8TC20-2	2
Q8TC20-3	3
Q8TC20-4	4
Q8TC20-5	5

RefSeq proteins (3): NP_001164163, NP_001164164, NP_995586 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR029381	CAGE1_N	Domain
IPR052686	CAGE1_homolog	Family

Pfam: PF15066

UniProt features (15 total): splice variant 5, sequence conflict 4, sequence variant 2, chain 1, region of interest 1, coiled-coil region 1, compositionally biased region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8TC20-F1	63.17	0.33

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 46 (showing top): MIDORIKAWA_AMPLIFIED_IN_LIVER_CANCER, chr6p24, CCCAGAG_MIR326, MARSON_BOUND_BY_FOXP3_UNSTIMULATED, SANSOM_APC_TARGETS, YAUCH_HEDGEHOG_SIGNALING_PARACRINE_UP, BARX1_TARGET_GENES, CEBPZ_TARGET_GENES, ELF2_TARGET_GENES, FEV_TARGET_GENES, HHEX_TARGET_GENES, KAT5_TARGET_GENES, SUPT16H_TARGET_GENES, ZNF423_TARGET_GENES, ZNF581_TARGET_GENES

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

712 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CAGE1	CTAG1A	P78358	840
CAGE1	CNDP2	Q96KP4	791
CAGE1	RAB11B	Q15907	791
CAGE1	DKKL1	Q9UK85	761
CAGE1	ADAM2	P78326	660
CAGE1	CTXN1	P60606	620
CAGE1	MAGEC1	O60732	609
CAGE1	ACRBP	Q8NEB7	606
CAGE1	KLK3	P07288	604
CAGE1	BRDT	Q58F21	548
CAGE1	RAB1A	P11476	541
CAGE1	SAGE1	Q9NXZ1	505
CAGE1	MAGEC2	Q9UBF1	480
CAGE1	CEACAM5	P06731	479
CAGE1	DDX43	Q9NXZ2	476

IntAct

24 interactions, top by confidence:

A	B	Type	Score
TPM1	CAGE1	psi-mi:“MI:0915”(physical association)	0.560
MPPED2	CAGE1	psi-mi:“MI:0915”(physical association)	0.560
TXLNB	CAGE1	psi-mi:“MI:0915”(physical association)	0.560
CAGE1	HAUS1	psi-mi:“MI:0915”(physical association)	0.560
CAGE1	MRFAP1L1	psi-mi:“MI:0915”(physical association)	0.560
TBC1D23	CAGE1	psi-mi:“MI:0915”(physical association)	0.560
CAGE1	TPM1	psi-mi:“MI:0915”(physical association)	0.560
MRFAP1L1	CAGE1	psi-mi:“MI:0915”(physical association)	0.560
CAGE1	TBC1D23	psi-mi:“MI:0915”(physical association)	0.560
CAGE1	MPPED2	psi-mi:“MI:0915”(physical association)	0.560
HAUS1	CAGE1	psi-mi:“MI:0915”(physical association)	0.560
ECE1	CAGE1	psi-mi:“MI:0915”(physical association)	0.370

BioGRID (24): CAGE1 (Two-hybrid), CAGE1 (Two-hybrid), CAGE1 (Two-hybrid), CAGE1 (Two-hybrid), CAGE1 (Two-hybrid), CAGE1 (Two-hybrid), PPFIA1 (Two-hybrid), CAGE1 (Two-hybrid), CAGE1 (Two-hybrid), CAGE1 (Two-hybrid), CAGE1 (Two-hybrid), CAGE1 (Two-hybrid), CAGE1 (Two-hybrid), CAGE1 (Two-hybrid), CAGE1 (Two-hybrid)

ESM2 similar proteins: A1L2H3, A2AKX3, A5D8S0, B0S6S9, D3Z987, E1BC15, O43303, O60673, O95405, P56715, Q03188, Q2M2Z5, Q3MHH3, Q3V089, Q569L8, Q5BQN8, Q5CZC0, Q5DTT3, Q5R9I1, Q5VWN6, Q61493, Q641I1, Q6NS59, Q6NSW3, Q6ZP01, Q6ZU52, Q7TSH4, Q7Z333, Q7Z3T8, Q80U44, Q80U59, Q86UW6, Q86WS4, Q86XD8, Q8IXS0, Q8MJ03, Q8MJ04, Q8MJ06, Q8N1H7, Q8N7Z5

Diamond homologs: Q5IR70, Q66HB6, Q8TC20, Q95JR0

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	0
Uncertain significance	99
Likely benign	9
Benign	0

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
1708201	GRCh37/hg19 6p25.1-24.3(chr6:6854908-7465142)x3	Pathogenic
814784	GRCh37/hg19 6p25.1-24.3(chr6:5997521-8570039)x1	Pathogenic

SpliceAI

3200 predictions. Top by Δscore:

Variant	Effect	Δscore
6:7334091:C:CC	acceptor_gain	0.9900
6:7355039:A:AC	donor_gain	0.9900
6:7355040:C:CC	donor_gain	0.9900
6:7365462:TCTTA:T	donor_loss	0.9900
6:7365463:CTTAC:C	donor_loss	0.9900
6:7365464:TTAC:T	donor_loss	0.9900
6:7365465:TACCA:T	donor_loss	0.9900
6:7365466:A:AC	donor_gain	0.9900
6:7365467:C:CC	donor_gain	0.9900
6:7365504:AT:A	donor_gain	0.9900
6:7365505:T:C	donor_gain	0.9900
6:7373098:T:TA	donor_gain	0.9900
6:7373203:T:TA	donor_gain	0.9900
6:7379023:C:CT	acceptor_gain	0.9900
6:7379024:A:C	acceptor_gain	0.9900
6:7385776:GATAC:G	donor_loss	0.9900
6:7385777:ATAC:A	donor_loss	0.9900
6:7385778:TACT:T	donor_loss	0.9900
6:7385779:AC:A	donor_loss	0.9900
6:7385780:CT:C	donor_loss	0.9900
6:7385781:T:TC	donor_loss	0.9900
6:7385782:TACCA:T	donor_loss	0.9900
6:7385784:C:CT	donor_loss	0.9900
6:7385869:CGTT:C	acceptor_gain	0.9900
6:7385871:TTCTG:T	acceptor_loss	0.9900
6:7385872:TCTGT:T	acceptor_loss	0.9900
6:7385873:C:CC	acceptor_gain	0.9900
6:7385873:C:T	acceptor_loss	0.9900
6:7385874:T:A	acceptor_loss	0.9900
6:7389281:A:AC	donor_gain	0.9900

AlphaMissense

5649 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:7373749:A:G	L357P	0.959
6:7355068:A:G	L719P	0.947
6:7373632:A:G	L396P	0.936
6:7373842:A:G	L326P	0.936
6:7355081:C:G	A715P	0.933
6:7373800:A:G	L340P	0.930
6:7355070:C:A	R718S	0.905
6:7355070:C:G	R718S	0.905
6:7378923:A:C	F127L	0.903
6:7378923:A:T	F127L	0.903
6:7378925:A:G	F127L	0.903
6:7355080:G:T	A715D	0.899
6:7365478:A:G	L701P	0.898
6:7368728:A:G	L655P	0.898
6:7373624:A:G	S399P	0.887
6:7373221:A:G	L533P	0.885
6:7334078:T:A	R732S	0.876
6:7334078:T:G	R732S	0.876
6:7334067:A:G	L736S	0.873
6:7373728:A:G	L364S	0.869
6:7373716:T:A	K368I	0.866
6:7373884:A:G	L312S	0.862
6:7355110:A:T	V705D	0.860
6:7334088:A:G	L729S	0.857
6:7373701:A:G	L373P	0.856
6:7365490:A:G	L697P	0.855
6:7365508:A:G	L691P	0.854
6:7373455:A:G	L455P	0.850
6:7373557:T:G	Q421P	0.847
6:7373346:G:C	F491L	0.842

dbSNP variants (sampled 300 via entrez): RS1000007537 (6:7350057 T>C), RS1000106173 (6:7328452 G>A), RS1000115397 (6:7357170 C>T), RS1000144530 (6:7349815 C>G), RS1000159068 (6:7330343 C>T), RS1000169756 (6:7370874 A>G), RS1000175960 (6:7356631 G>T), RS1000253341 (6:7345305 T>C), RS1000307049 (6:7337121 G>A), RS1000365785 (6:7382959 T>C), RS1000448789 (6:7363248 G>A,T), RS1000480003 (6:7363059 A>G), RS1000558914 (6:7331658 G>A,C), RS1000562050 (6:7362231 T>C), RS1000586005 (6:7369709 C>T)

Disease associations

OMIM: gene MIM:608304 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST005024_54	Pursuit maintenance gain	2.000000e-06
GCST006291_86	Spherical equivalent or myopia (age of diagnosis)	1.000000e-09
GCST006467_1	Ewing sarcoma	1.000000e-18

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0008433	pursuit maintenance gain measurement
EFO:0004847	age at onset

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

5 total (human), top 5 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
trichostatin A	affects cotreatment, increases expression	1
pentanal	decreases expression	1
CGP 52608	affects binding, increases reaction	1
Decitabine	affects cotreatment, increases expression	1
Aldehydes	decreases expression	1

Clinical trials (associated diseases)

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