SAGE1

Summary

SAGE1 (sarcoma antigen 1, HGNC:30369) is a protein-coding gene on chromosome Xq26.3, encoding Sarcoma antigen 1 (Q9NXZ1).

This gene belongs to a class of genes that are activated in tumors. These genes are expressed in tumors of different histologic types but not in normal tissues, except for spermatogenic cells and, for some, placenta. The proteins encoded by these genes appear to be strictly tumor specific, and hence may be excellent sources of antigens for cancer immunotherapy. This gene is expressed in sarcomas.

Source: NCBI Gene 55511 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 131 total — 1 pathogenic
• MANE Select transcript: NM_001381902

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:30369
Approved symbol	SAGE1
Name	sarcoma antigen 1
Location	Xq26.3
Locus type	gene with protein product
Status	Approved
Aliases	SAGE, CT14
Ensembl gene	ENSG00000181433
Ensembl biotype	protein_coding
OMIM	300359
Entrez	55511

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000324447, ENST00000370709

RefSeq mRNA: 2 — MANE Select: NM_001381902 NM_001381902, NM_018666

CCDS: CCDS14652

Canonical transcript exons

ENST00000370709 — 20 exons

Exon	Start	End
ENSE00001266175	135911579	135911953
ENSE00001266222	135907701	135907841
ENSE00001266238	135906411	135906551
ENSE00001266252	135905252	135905392
ENSE00001266261	135904477	135904569
ENSE00001597111	135906024	135906164
ENSE00001618285	135908477	135908617
ENSE00001630680	135906926	135907066
ENSE00001659041	135911192	135911332
ENSE00001678117	135908864	135909004
ENSE00001717583	135901559	135901691
ENSE00001722075	135912321	135912414
ENSE00001725800	135910030	135910170
ENSE00001747641	135907313	135907453
ENSE00001763122	135908089	135908229
ENSE00001767284	135910415	135910555
ENSE00001783969	135909639	135909779
ENSE00001913147	135912798	135913062
ENSE00003473089	135896243	135896329
ENSE00003919560	135893716	135893781

Expression profiles

Bgee: expression breadth broad, 39 present calls, max score 86.68.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.4656 / max 75.9113, expressed in 77 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
197643	0.4485	76
197642	0.0170	8

Top tissues by expression

245 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	86.68	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	79.26	gold quality
hair follicle	UBERON:0002073	71.68	gold quality
right testis	UBERON:0004534	66.40	gold quality
testis	UBERON:0000473	65.12	gold quality
left testis	UBERON:0004533	64.64	gold quality
kidney epithelium	UBERON:0004819	64.00	gold quality
diaphragm	UBERON:0001103	63.59	gold quality
nephron tubule	UBERON:0001231	62.17	gold quality
metanephric glomerulus	UBERON:0004736	62.02	gold quality
cervix squamous epithelium	UBERON:0006922	61.79	gold quality
tongue squamous epithelium	UBERON:0006919	61.29	gold quality
mucosa of paranasal sinus	UBERON:0005030	58.27	gold quality
buccal mucosa cell	CL:0002336	57.67	silver quality
endothelial cell	CL:0000115	57.63	gold quality
decidua	UBERON:0002450	56.93	gold quality
epithelium of nasopharynx	UBERON:0001951	56.38	gold quality
vastus lateralis	UBERON:0001379	55.47	gold quality
vena cava	UBERON:0004087	55.28	gold quality
quadriceps femoris	UBERON:0001377	54.70	gold quality
lower lobe of lung	UBERON:0008949	52.01	silver quality
cervix epithelium	UBERON:0004801	51.75	gold quality
left ventricle myocardium	UBERON:0006566	51.50	gold quality
oviduct epithelium	UBERON:0004804	49.99	gold quality
Brodmann (1909) area 46	UBERON:0006483	49.95	gold quality
myocardium	UBERON:0002349	49.49	gold quality
cardiac muscle of right atrium	UBERON:0003379	49.24	gold quality
olfactory bulb	UBERON:0002264	48.92	gold quality
type B pancreatic cell	CL:0000169	48.83	gold quality
epithelial cell of pancreas	CL:0000083	48.66	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.09

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

4 targeting SAGE1, 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-6515-3P	99.82	68.19	1933
HSA-MIR-1299	99.77	71.24	2389
HSA-MIR-3202	99.66	67.70	2737
HSA-MIR-4756-3P	99.62	66.30	1319

Literature-anchored findings (GeneRIF, showing 4)

• MAGE-A4(143-151) and SAGE(715-723) are HLA-A2402-restricted CTL epitopes (PMID:16061876)
• ADAM2, CALR3 and SAGE1 cancer/testis antigens are not promising targets for immunotherapy of breast and lung cancer. (PMID:26252478)
• MAGE-A4, NY-ESO-1 and SAGE mRNA expression rates and co-expression relationships in solid tumours. (PMID:32600281)
• SAGE1: a Potential Target Antigen for Lung Cancer T-Cell Immunotherapy. (PMID:34465596)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
drosophila_melanogaster	IntS6	FBGN0261383
caenorhabditis_elegans		WBGENE00000994

Paralogs (11): INTS6 (ENSG00000102786), INTS6L (ENSG00000165359), CT45A5 (ENSG00000228836), CT45A1 (ENSG00000268940), CT45A3 (ENSG00000269096), CT45A10 (ENSG00000269586), CT45A9 (ENSG00000270946), CT45A2 (ENSG00000271449), CT45A7 (ENSG00000273696), CT45A8 (ENSG00000278085), CT45A6 (ENSG00000278289)

Protein

Protein identifiers

Sarcoma antigen 1 — Q9NXZ1 (reviewed: Q9NXZ1)

Alternative names: Cancer/testis antigen 14

All UniProt accessions (1): Q9NXZ1

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Nucleus.

Tissue specificity. Expressed mainly in bladder, lung, head and neck carcinomas. Not expressed in normal tissues except for testis.

RefSeq proteins (2): NP_001368831, NP_061136 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR029307	INT_SG_DDX_CT_C	Domain
IPR051113	Integrator_subunit6	Family

Pfam: PF15300

UniProt features (9 total): modified residue 3, sequence variant 2, chain 1, region of interest 1, compositionally biased region 1, cross-link 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
8HPP	X-RAY DIFFRACTION	3

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NXZ1-F1	51.15	0.03

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): 45, 64, 238, 778

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 37 (showing top): GOBP_SNRNA_PROCESSING, MODULE_95, GOCC_NUCLEAR_BODY, GOCC_INTEGRATOR_COMPLEX, chrXq26, PURBEY_TARGETS_OF_CTBP1_NOT_SATB1_DN, MODULE_163, GOBP_SNRNA_METABOLIC_PROCESS, CHAMP1_TARGET_GENES, GSE15659_NAIVE_CD4_TCELL_VS_RESTING_TREG_DN, GSE15659_NAIVE_CD4_TCELL_VS_NONSUPPRESSIVE_TCELL_DN, GSE15659_NAIVE_CD4_TCELL_VS_ACTIVATED_TREG_DN, GSE15659_RESTING_TREG_VS_NONSUPPRESSIVE_TCELL_DN, GSE15659_RESTING_VS_ACTIVATED_TREG_DN, GSE15659_NONSUPPRESSIVE_TCELL_VS_ACTIVATED_TREG_DN

GO Biological Process (1): snRNA 3’-end processing (GO:0034472)

GO Molecular Function (0):

GO Cellular Component (4): nucleus (GO:0005634), nucleoplasm (GO:0005654), nuclear body (GO:0016604), integrator complex (GO:0032039)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
snRNA processing	1
RNA 3’-end processing	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
cellular anatomical structure	1
nucleoplasm	1
intracellular membraneless organelle	1
nuclear protein-containing complex	1

Protein interactions and networks

STRING

516 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SAGE1	DDX43	Q9NXZ2	869
SAGE1	SPA17	Q15506	815
SAGE1	MAGEC2	Q9UBF1	773
SAGE1	PRSS50	Q9UI38	771
SAGE1	PAGE5	Q96GU1	720
SAGE1	GAGE4	P0DSO3	714
SAGE1	ADAM2	P78326	690
SAGE1	MAGEA1	P43355	655
SAGE1	MAGEC1	O60732	625
SAGE1	LIPI	Q6XZB0	606
SAGE1	ACRBP	Q8NEB7	595
SAGE1	PER2	O15055	584
SAGE1	BMAL1	O00327	543
SAGE1	NXF2B	Q9GZY0	524
SAGE1	PABIR3	Q6P4D5	517

IntAct

4 interactions, top by confidence:

A	B	Type	Score
H2BC21	SMCHD1	psi-mi:“MI:0914”(association)	0.350
TP53BP1	PSMD14	psi-mi:“MI:2364”(proximity)	0.270
BRCA1	SMCHD1	psi-mi:“MI:2364”(proximity)	0.270

BioGRID (7): SAGE1 (Proximity Label-MS), SAGE1 (Proximity Label-MS), SAGE1 (Affinity Capture-MS), SAGE1 (Affinity Capture-MS), SAGE1 (Proximity Label-MS), SAGE1 (Proximity Label-MS), SAGE1 (Cross-Linking-MS (XL-MS))

ESM2 similar proteins: A0A087WUL8, A0A0J9YWL9, A0A0J9YY54, A0A0U1RQI7, A6NJ88, A6QL64, B4DH59, D3ZVV1, E9Q6E9, F1LWT0, O04492, O88799, P0DKJ7, P0DKJ8, P0DKL2, P0DPF3, P18583, P53353, Q08AG5, Q0P6D6, Q2EG98, Q3BBV2, Q4ZJZ1, Q5HY64, Q5JPF3, Q5QGU6, Q5TAG4, Q5TI25, Q5XHX6, Q6P3W6, Q6P902, Q6XPR3, Q6ZQX7, Q86T75, Q86VE3, Q86VQ3, Q8N2N9, Q8N660, Q8N693, Q96EQ9

Diamond homologs: A6NJ88, P0DMU7, P0DMU8, P0DMU9, P0DMV0, P0DMV1, P0DMV2, Q2TAF4, Q5DJT8, Q5HYN5, Q5JSJ4, Q5U4W6, Q6PCM2, Q7SYD9, Q8BND4, Q8NHU0, Q9NXZ1, Q9UL03, Q54Z23, Q9W485

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	80
Likely benign	27
Benign	10

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
1703579	GRCh37/hg19 Xp22.33-q28(chrX:1-155270560)	Pathogenic

SpliceAI

3162 predictions. Top by Δscore:

Variant	Effect	Δscore
X:135904588:G:GT	donor_gain	1.0000
X:135904599:A:AG	donor_gain	1.0000
X:135904603:G:GG	donor_gain	1.0000
X:135904618:A:AG	donor_gain	1.0000
X:135904618:A:G	donor_gain	1.0000
X:135905359:GCTG:G	donor_gain	1.0000
X:135905374:A:AG	donor_gain	1.0000
X:135905374:A:G	donor_gain	1.0000
X:135905385:GGATC:G	donor_gain	1.0000
X:135905386:GATC:G	donor_gain	1.0000
X:135905391:GC:G	donor_gain	1.0000
X:135905393:G:GG	donor_gain	1.0000
X:135905764:C:CG	donor_gain	1.0000
X:135905764:C:G	donor_gain	1.0000
X:135905775:GGA:G	donor_gain	1.0000
X:135906165:G:GG	donor_gain	1.0000
X:135906401:T:A	acceptor_gain	1.0000
X:135906402:G:A	acceptor_gain	1.0000
X:135906409:A:AG	acceptor_gain	1.0000
X:135906409:AGAT:A	acceptor_gain	1.0000
X:135906410:G:A	acceptor_loss	1.0000
X:135906410:G:GA	acceptor_gain	1.0000
X:135906410:GA:G	acceptor_gain	1.0000
X:135906410:GAT:G	acceptor_gain	1.0000
X:135906410:GATG:G	acceptor_gain	1.0000
X:135906410:GATGC:G	acceptor_gain	1.0000
X:135906547:TCCAT:T	donor_gain	1.0000
X:135906549:CAT:C	donor_gain	1.0000
X:135906549:CATGT:C	donor_loss	1.0000
X:135906550:AT:A	donor_gain	1.0000

AlphaMissense

6024 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:135912392:T:C	F865L	0.992
X:135912394:T:A	F865L	0.992
X:135912394:T:G	F865L	0.992
X:135912827:T:C	L882P	0.990
X:135912407:G:C	A870P	0.989
X:135911924:T:C	L831S	0.988
X:135912799:T:C	F873L	0.983
X:135912801:T:A	F873L	0.983
X:135912801:T:G	F873L	0.983
X:135912387:T:A	V863D	0.982
X:135912393:T:C	F865S	0.981
X:135911944:T:C	F838L	0.980
X:135911946:T:A	F838L	0.980
X:135911946:T:G	F838L	0.980
X:135912383:T:C	F862L	0.979
X:135912385:T:A	F862L	0.979
X:135912385:T:G	F862L	0.979
X:135912384:T:C	F862S	0.972
X:135912827:T:A	L882H	0.970
X:135912335:T:C	F846L	0.967
X:135912337:C:A	F846L	0.967
X:135912337:C:G	F846L	0.967
X:135912803:A:T	K874I	0.965
X:135912839:T:C	L886P	0.965
X:135911916:A:C	K828N	0.959
X:135911916:A:T	K828N	0.959
X:135912333:T:C	I845T	0.958
X:135912815:T:C	L878S	0.958
X:135912333:T:G	I845S	0.956
X:135912345:T:C	L849P	0.955

dbSNP variants (sampled 300 via entrez): RS1000302091 (X:135892862 C>T), RS1001478751 (X:135892319 C>A), RS1001845807 (X:135892059 G>A), RS1002444008 (X:135893572 C>G), RS1006139820 (X:135912205 G>A), RS1007267485 (X:135910585 A>G), RS1007706268 (X:135911027 C>T), RS1008973105 (X:135893140 T>C), RS1009355060 (X:135892865 G>A,T), RS1010058538 (X:135892407 G>A,C,T), RS1010278238 (X:135892141 C>G), RS1012296593 (X:135911824 C>G,T), RS1017260853 (X:135910652 T>C,G), RS1018969993 (X:135893141 G>A), RS1020072444 (X:135892438 C>T)

Disease associations

OMIM: gene MIM:300359 | disease phenotypes: MIM:400045

GenCC curated gene-disease

Mondo (2): trisomy X (MONDO:0018066), 46,XX sex reversal 1 (MONDO:0100250)

Orphanet (1): Trisomy X syndrome (Orphanet:3375)

HPO phenotypes

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

GWAS associations

0 associations (top):

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C535318	Triple X syndrome (supp.)

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
sodium arsenite	affects splicing, decreases expression	1
benzo(e)pyrene	decreases methylation	1
Acetaminophen	affects expression	1
Benzo(a)pyrene	increases methylation	1
Methapyrilene	decreases methylation	1
Silicon Dioxide	increases expression	1
Cyclosporine	decreases expression	1
Aflatoxin B1	decreases methylation	1
Okadaic Acid	decreases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT01678261	Not specified	COMPLETED	X-chromosome Inactivation, Epigenetics and the Transcriptome
NCT03396562	Not specified	RECRUITING	The eXtroardinarY Babies Study: Natural History of Health and Neurodevelopment in Infants and Young Children With Sex Chromosome Trisomy