SPANXC

Summary

SPANXC (SPANX family member C, HGNC:14331) is a protein-coding gene on chromosome Xq27.2, encoding Sperm protein associated with the nucleus on the X chromosome C (Q9NY87).

Temporally regulated transcription and translation of several testis-specific genes is required to initiate the series of molecular and morphological changes in the male germ cell lineage necessary for the formation of mature spermatozoa. This gene is a member of the SPANX family, which is located in a gene cluster on chromosome X. The SPANX genes encode differentially expressed testis-specific proteins that localize to various subcellular compartments. This particular gene encodes a protein that localizes to the nucleus and is expressed in highly metastatic cell lines, making the protein a potential diagnostic and prognostic marker. The protein belongs to a family of cancer/testis antigens and represents a potential target for cancer immunotherapy.

Source: NCBI Gene 64663 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 3 total
• MANE Select transcript: NM_022661

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:14331
Approved symbol	SPANXC
Name	SPANX family member C
Location	Xq27.2
Locus type	gene with protein product
Status	Approved
Aliases	CTp11, CT11.3
Ensembl gene	ENSG00000198573
Ensembl biotype	protein_coding
OMIM	300330
Entrez	64663

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000358993

RefSeq mRNA: 1 — MANE Select: NM_022661 NM_022661

CCDS: CCDS14673

Canonical transcript exons

ENST00000358993 — 2 exons

Exon	Start	End
ENSE00001881872	141241463	141241738
ENSE00001907049	141242386	141242517

Expression profiles

Bgee: expression breadth broad, 39 present calls, max score 95.32.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0222 / max 11.4296, expressed in 6 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
200746	0.0222	6

Top tissues by expression

99 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	95.32	gold quality
testis	UBERON:0000473	72.86	gold quality
left testis	UBERON:0004533	72.47	gold quality
right testis	UBERON:0004534	67.05	gold quality
lower esophagus mucosa	UBERON:0035834	46.33	silver quality
colonic epithelium	UBERON:0000397	37.20	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
skeletal muscle tissue	UBERON:0001134	35.60	gold quality
ganglionic eminence	UBERON:0004023	35.49	gold quality
muscle tissue	UBERON:0002385	32.69	gold quality
hindlimb stylopod muscle	UBERON:0004252	32.15	gold quality
bone marrow	UBERON:0002371	31.74	gold quality
descending thoracic aorta	UBERON:0002345	31.30	gold quality
sural nerve	UBERON:0015488	30.93	gold quality
stromal cell of endometrium	CL:0002255	29.87	gold quality
superior frontal gyrus	UBERON:0002661	29.16	gold quality
prefrontal cortex	UBERON:0000451	29.04	gold quality
endocervix	UBERON:0000458	28.57	silver quality
uterine cervix	UBERON:0000002	28.51	silver quality
duodenum	UBERON:0002114	28.14	gold quality
right lobe of liver	UBERON:0001114	27.77	silver quality
lymph node	UBERON:0000029	27.57	gold quality
urinary bladder	UBERON:0001255	27.31	gold quality
tonsil	UBERON:0002372	27.05	gold quality
leukocyte	CL:0000738	26.70	silver quality
monocyte	CL:0000576	26.61	silver quality
islet of Langerhans	UBERON:0000006	26.55	gold quality
muscle of leg	UBERON:0001383	26.53	silver quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.24

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 6)

• SPANXC was found in ejaculated spermatozoa and spermatids. (PMID:15139967)
• genetic variability of SPANX-B & SPANX-C in a sample of Sicilian male population including patients with cutaneous melanoma; statistical significant difference for a particular class of SPANX-C gene was found comparing patients with melanoma & controls (PMID:18626316)
• SPANX-C gene dosage analysis in Down’s syndrome subjects with undescended testes (PMID:19417550)
• study reports the isolation of AKAP3 and CTp11 Cancer/testis antigens from hepatocellular carcinoma patient sera (PMID:22941507)
• High SPANXC expression is associated with breast cancer invasion. (PMID:26895102)
• Our study examined SPANX-C expression levels in primary uveal melanoma both with and without metastasis to assess if they can be used to predict metastasis. A significantly high expression of SPANX-C was seen in patients with metastasis compared to patients without metastasis. (PMID:31072624)

Cross-species orthologs

0 orthologs

Paralogs (4): SPANXD (ENSG00000196406), SPANXA1 (ENSG00000198021), SPANXA2 (ENSG00000203926), SPANXB1 (ENSG00000227234)

Protein

Protein identifiers

Sperm protein associated with the nucleus on the X chromosome C — Q9NY87 (reviewed: Q9NY87)

Alternative names: Cancer/testis antigen 11.3, Cancer/testis-associated protein CTp11, Nuclear-associated protein SPAN-Xc, SPANX family member C

All UniProt accessions (1): Q9NY87

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Cytoplasm. Nucleus.

Tissue specificity. Detected in testis, melanoma and bladder carcinoma.

Similarity. Belongs to the SPAN-X family.

RefSeq proteins (1): NP_073152* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR010007	SPAN-X_fam	Family

Pfam: PF07458

UniProt features (7 total): sequence conflict 3, chain 1, region of interest 1, short sequence motif 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NY87-F1	68.76	0.00

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 14 (showing top): ACEVEDO_METHYLATED_IN_LIVER_CANCER_DN, MAHADEVAN_IMATINIB_RESISTANCE_UP, chrXq27, DALESSIO_TSA_RESPONSE, NOTCH_DN.V1_DN, KRAS.600.LUNG.BREAST_UP.V1_UP, GSE29618_PRE_VS_DAY7_FLU_VACCINE_BCELL_UP, SATO_SILENCED_EPIGENETICALLY_IN_PANCREATIC_CANCER, GSE2585_THYMIC_MACROPHAGE_VS_MTEC_UP, GSE25088_CTRL_VS_IL4_STIM_STAT6_KO_MACROPHAGE_UP, GSE25088_CTRL_VS_ROSIGLITAZONE_STIM_STAT6_KO_MACROPHAGE_UP, GSE42021_TREG_PLN_VS_CD24LO_TREG_THYMUS_DN, GSE42021_CD24HI_VS_CD24LOW_TCONV_THYMUS_UP, GSE46606_UNSTIM_VS_CD40L_IL2_IL5_3DAY_STIMULATED_IRF4_KO_BCELL_UP

GO Biological Process (0):

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

GO Cellular Component (2): nucleus (GO:0005634), cytoplasm (GO:0005737)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
binding	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
cellular anatomical structure	1

Protein interactions and networks

STRING

424 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SPANXC	GAGE2A	Q6NT46	575
SPANXC	XAGE2	Q96GT9	570
SPANXC	GAGE4	P0DSO3	522
SPANXC	SSX1	Q16384	507
SPANXC	FATE1	Q969F0	506
SPANXC	MAGEC2	Q9UBF1	476
SPANXC	XAGE1B	Q9HD64	473
SPANXC	SPA17	Q15506	453
SPANXC	MAGEA4	P43358	448
SPANXC	MAGEA1	P43355	446
SPANXC	MAGED4B	Q96JG8	446
SPANXC	MAGEB2	O15479	438
SPANXC	MAGEC1	O60732	419
SPANXC	CTAG1A	P78358	419
SPANXC	MAGEA2B	P43356	419

IntAct

9 interactions, top by confidence:

A	B	Type	Score
SETBP1	SPANXC	psi-mi:“MI:0915”(physical association)	0.560
SPANXC	SETBP1	psi-mi:“MI:0915”(physical association)	0.560
HTT	SPANXC	psi-mi:“MI:0915”(physical association)	0.560
SPANXC	ZC3H11A	psi-mi:“MI:0914”(association)	0.350
PCDHB11	CLGN	psi-mi:“MI:0914”(association)	0.350

ESM2 similar proteins: A0A087WXM9, A0A1S4GMU2, A0A2K1J5A5, A0A2K1JJ00, A0JM83, A2BIL8, A4IGV6, B4GBA9, F1MF21, H2KZ49, O94542, P24109, P40167, P46012, P46946, Q01030, Q06813, Q0P4S0, Q28DZ0, Q290S5, Q3KQW6, Q3ZBP0, Q4QY64, Q4V7J0, Q5E9A0, Q5M948, Q5M951, Q5MJ08, Q5RCX3, Q5RD08, Q69YH5, Q6AXY9, Q6NWJ0, Q703I1, Q80WR5, Q8IYL3, Q8L7I1, Q93ZL5, Q96QE3, Q9BXN6

Diamond homologs: Q0ZNK1, Q5MJ07, Q5MJ08, Q5MJ09, Q5MJ10, Q5VSR9, Q6SJ82, Q6SJ84, Q6SJ91, Q9BXN6, Q9NS26, Q9NY87, Q9NS25

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

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

Top pathogenic / likely-pathogenic (0)

SpliceAI

68 predictions. Top by Δscore:

Variant	Effect	Δscore
X:141242284:T:TA	donor_gain	0.9600
X:141241751:C:CT	acceptor_gain	0.9300
X:141242304:T:TA	donor_gain	0.9300
X:141241752:A:T	acceptor_gain	0.9200
X:141242302:ATT:A	donor_gain	0.8500
X:141242285:C:A	donor_gain	0.8000
X:141242284:TCC:T	donor_gain	0.7900
X:141242399:T:TA	donor_gain	0.7600
X:141242421:T:A	donor_gain	0.7600
X:141242396:A:AA	donor_loss	0.6900
X:141242397:C:A	donor_loss	0.6900
X:141242398:C:A	donor_loss	0.6900
X:141242399:T:A	donor_loss	0.6900
X:141242238:AG:A	donor_gain	0.6500
X:141242283:TTC:T	donor_gain	0.6100
X:141242225:C:T	donor_gain	0.5600
X:141242427:TC:T	donor_gain	0.5600
X:141241815:T:TA	donor_gain	0.5500
X:141242035:C:CT	donor_gain	0.5200
X:141242219:C:A	donor_gain	0.5100
X:141242078:C:A	donor_gain	0.5000
X:141241923:G:GC	donor_gain	0.4700
X:141242221:C:CT	donor_gain	0.4600
X:141242222:T:TT	donor_gain	0.4600
X:141242229:A:C	donor_gain	0.4400
X:141242032:TAACC:T	donor_gain	0.4200
X:141242033:AACCA:A	donor_gain	0.4200
X:141242034:A:C	donor_gain	0.4000
X:141242217:ACC:A	donor_gain	0.4000
X:141242218:CCC:C	donor_gain	0.4000

AlphaMissense

643 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:141241550:G:C	F87L	0.867
X:141241550:G:T	F87L	0.867
X:141241552:A:G	F87L	0.867
X:141241581:A:G	I77T	0.695
X:141242410:A:C	C16W	0.634
X:141241581:A:C	I77S	0.632
X:141241640:C:A	R57S	0.630
X:141241640:C:G	R57S	0.630
X:141241577:G:C	N78K	0.622
X:141241577:G:T	N78K	0.622
X:141241653:A:T	V53D	0.618
X:141241643:C:A	R56S	0.609
X:141241643:C:G	R56S	0.609
X:141241586:G:C	N75K	0.596
X:141241586:G:T	N75K	0.596
X:141241648:A:C	Y55D	0.592
X:141241542:A:G	I90T	0.587

dbSNP variants (sampled 300 via entrez): RS113495682 (X:141241125 T>A), RS1156518244 (X:141243367 T>G), RS1158311197 (X:141243963 A>T), RS1159107824 (X:141240973 C>G), RS1160215750 (X:141244394 G>A), RS1160926899 (X:141242464 T>C,G), RS1160962601 (X:141243543 A>C), RS1161502474 (X:141241744 A>G), RS1163409718 (X:141241340 A>G), RS1164960484 (X:141241876 G>A,T), RS1165947480 (X:141243911 C>A), RS1166751115 (X:141243674 A>G), RS1167805786 (X:141242574 A>AC), RS1167942967 (X:141243065 C>T), RS1168033821 (X:141244187 A>G)

Disease associations

OMIM: gene MIM:300330 | 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

18 total (human), top 18 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
mercuric bromide	increases expression, affects cotreatment	2
Benzo(a)pyrene	decreases methylation, increases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
methylmercuric chloride	increases expression	1
sodium arsenite	increases expression	1
tobacco tar	decreases expression	1
perfluoro-n-nonanoic acid	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
Resveratrol	decreases expression, affects cotreatment	1
Fluorouracil	affects response to substance	1
Plant Extracts	decreases expression, affects cotreatment	1
Thiram	increases expression	1
Valproic Acid	increases expression	1
Aflatoxin B1	increases expression	1
Cadmium Chloride	increases expression	1
Copper Sulfate	affects expression	1
p-Chloromercuribenzoic Acid	increases expression	1

Clinical trials (associated diseases)

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