SPANXA1

Summary

SPANXA1 (sperm protein associated with the nucleus, X-linked, family member A1, HGNC:11218) is a protein-coding gene on chromosome Xq27.2, encoding Sperm protein associated with the nucleus on the X chromosome A (Q9NS26).

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 of cancer/testis-associated genes, which are located in a cluster on chromosome X. The SPANX genes encode differentially expressed testis-specific proteins that localize to various subcellular compartments. This particular gene maps to chromosome X in a head-to-head orientation with SPANX family member A2, which appears to be a duplication of the A1 locus. The protein encoded by this gene targets to the nucleus where it associates with nuclear vacuoles and the redundant nuclear envelope. Based on its association with these poorly characterized regions of the sperm nucleus, this protein provides a biochemical marker to study unique structures in spermatazoa while attempting to further define its role in spermatogenesis.

Source: NCBI Gene 30014 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 2 total
• MANE Select transcript: NM_013453

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11218
Approved symbol	SPANXA1
Name	sperm protein associated with the nucleus, X-linked, family member A1
Location	Xq27.2
Locus type	gene with protein product
Status	Approved
Aliases	NAP-X, SPAN-Xa, SPAN-Xb, CT11.1
Ensembl gene	ENSG00000198021
Ensembl biotype	protein_coding
OMIM	300305
Entrez	30014

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000370519

RefSeq mRNA: 1 — MANE Select: NM_013453 NM_013453

CCDS: CCDS14674

Canonical transcript exons

ENST00000370519 — 2 exons

Exon	Start	End
ENSE00001839811	141583674	141583959
ENSE00003978260	141584607	141584738

Expression profiles

Bgee: expression breadth broad, 14 present calls, max score 92.26.

Top tissues by expression

119 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	92.26	gold quality
left testis	UBERON:0004533	54.55	gold quality
testis	UBERON:0000473	54.40	gold quality
right testis	UBERON:0004534	53.59	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	51.59	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
sural nerve	UBERON:0015488	35.89	gold quality
ganglionic eminence	UBERON:0004023	35.49	gold quality
skeletal muscle tissue	UBERON:0001134	33.38	gold quality
hindlimb stylopod muscle	UBERON:0004252	32.15	gold quality
bone marrow	UBERON:0002371	31.74	gold quality
muscle tissue	UBERON:0002385	31.06	gold quality
right coronary artery	UBERON:0001625	30.85	silver quality
stromal cell of endometrium	CL:0002255	29.87	gold quality
descending thoracic aorta	UBERON:0002345	29.85	gold quality
prefrontal cortex	UBERON:0000451	29.23	gold quality
thoracic aorta	UBERON:0001515	28.85	silver quality
ascending aorta	UBERON:0001496	28.68	silver quality
duodenum	UBERON:0002114	28.14	gold quality
liver	UBERON:0002107	28.04	gold quality
placenta	UBERON:0001987	27.97	silver quality
monocyte	CL:0000576	27.81	gold quality
leukocyte	CL:0000738	27.79	gold quality
lymph node	UBERON:0000029	27.57	gold quality
tonsil	UBERON:0002372	27.05	gold quality
blood	UBERON:0000178	26.82	gold quality
islet of Langerhans	UBERON:0000006	26.55	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.82

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 6)

• Multi-gene family; cancer-testis antigen; SPAN-X protein associated with nuclear envelope of human spermatids and spermatozoa. (PMID:10906052)
• Over expression of SPAN-x protein is associated with nonlymphatic metastatic melanomas (PMID:14734458)
• In conclusion, these data suggest that the SpanX protein family is not exclusively expressed post-meiotically and that seminomas and embryonal carcinomas may originate from SpanX-positive carcinoma-in-situ cell. (PMID:16390498)
• High SPANXA expression is associated with breast cancer invasion. (PMID:26895102)
• Silencing SPANXA increased c-JUN mRNA expression and blockage of c-JUN led to SNAI2 down-regulation. Results clearly characterized SPANXA as an EMT inhibitor by suppressing c-JUN-SNAI2 axis in lung adenocarcinoma. (PMID:27323831)
• Hypomethylated SPANXA1/A2 promotes the metastasis of head and neck squamous cell carcinoma. (PMID:33175201)

Cross-species orthologs

0 orthologs

Paralogs (4): SPANXD (ENSG00000196406), SPANXC (ENSG00000198573), SPANXA2 (ENSG00000203926), SPANXB1 (ENSG00000227234)

Protein

Protein identifiers

Sperm protein associated with the nucleus on the X chromosome A — Q9NS26 (reviewed: Q9NS26)

Alternative names: Cancer/testis antigen 11.1, Nuclear-associated protein SPAN-Xa, SPANX family member A

All UniProt accessions (1): Q9NS26

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Cytoplasm. Nucleus.

Tissue specificity. Detected in testis and sperm.

Similarity. Belongs to the SPAN-X family.

RefSeq proteins (1): NP_038481* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR010007	SPAN-X_fam	Family

Pfam: PF07458

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

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NS26-F1	66.54	0.02

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 25 (showing top): SATO_SILENCED_BY_DEACETYLATION_IN_PANCREATIC_CANCER, GOBP_MALE_GAMETE_GENERATION, GOBP_DEVELOPMENTAL_PROCESS_INVOLVED_IN_REPRODUCTION, SENESE_HDAC1_TARGETS_UP, ACEVEDO_METHYLATED_IN_LIVER_CANCER_DN, MODULE_47, SHEN_SMARCA2_TARGETS_DN, KAN_RESPONSE_TO_ARSENIC_TRIOXIDE, MAHADEVAN_IMATINIB_RESISTANCE_UP, MASRI_RESISTANCE_TO_TAMOXIFEN_AND_AROMATASE_INHIBITORS_DN, chrXq27, DALESSIO_TSA_RESPONSE, SHEDDEN_LUNG_CANCER_GOOD_SURVIVAL_A12, FORTSCHEGGER_PHF8_TARGETS_DN, ZWANG_TRANSIENTLY_UP_BY_2ND_EGF_PULSE_ONLY

GO Biological Process (1): spermatogenesis (GO:0007283)

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
developmental process involved in reproduction	1
male gamete generation	1
binding	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
cellular anatomical structure	1

Protein interactions and networks

STRING

561 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SPANXA1	SPANXN4	Q5MJ08	917
SPANXA1	AKAP4	Q5JQC9	745
SPANXA1	TSN	Q15631	711
SPANXA1	SRY	Q05066	682
SPANXA1	LGALS4	P56470	669
SPANXA1	CT45A1	Q5HYN5	608
SPANXA1	GAGE4	P0DSO3	581
SPANXA1	MAGEA1	P43355	573
SPANXA1	CTAG1A	P78358	526
SPANXA1	XAGE1B	Q9HD64	526
SPANXA1	MAGEC1	O60732	507
SPANXA1	CT47A11	Q5JQC4	507
SPANXA1	CXorf51A	A0A1B0GTR3	505
SPANXA1	CSAG2	Q9Y5P2	505
SPANXA1	CTAGE1	Q96RT6	479

IntAct

15 interactions, top by confidence:

A	B	Type	Score
SETBP1	SPANXA1	psi-mi:“MI:0915”(physical association)	0.560
SPANXA1	SETBP1	psi-mi:“MI:0915”(physical association)	0.560
EML2	SPANXA1	psi-mi:“MI:0915”(physical association)	0.560
SPANXA1	UBB	psi-mi:“MI:0914”(association)	0.530
CSAG1	NAP1L4	psi-mi:“MI:0914”(association)	0.350
CSAG2	CAMK2D	psi-mi:“MI:0914”(association)	0.350
SPANXB1	PAPSS2	psi-mi:“MI:0914”(association)	0.350
SPANXA1	SETBP1	psi-mi:“MI:0915”(physical association)	0.000
EML2	SPANXA1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (17): SPANXA1 (Two-hybrid), SPANXA2 (Affinity Capture-MS), GTF2F1 (Affinity Capture-MS), UBB (Affinity Capture-MS), BRCA2 (Affinity Capture-MS), SPANXA2 (Positive Genetic), SPANXA1 (Positive Genetic), SPANXA1 (Two-hybrid), SPANXA2 (Two-hybrid), SPANXA1 (Two-hybrid), SPANXA2 (Two-hybrid), SPANXA1 (Positive Genetic), SPANXA2 (Positive Genetic), SPANXA2 (Affinity Capture-MS), BRCA2 (Affinity Capture-MS)

ESM2 similar proteins: A1CQN6, A2QPT2, A3GGT2, A3GGV1, A5DNZ1, A5E203, A6ZMG4, A7A241, A7EXU7, A7TJT3, A7TSJ7, A8P353, B0DX25, B3LLZ8, C5E1C7, C7GWA2, C8ZEW0, F5HI87, O14218, P0C1T5, P13200, P34399, P43587, Q04438, Q09356, Q09599, Q0USF2, Q1DR50, Q2UPG7, Q3MKQ1, Q3YPH5, Q4R309, Q568K2, Q59ZU1, Q59ZW4, Q6C0K1, Q6CNA0, Q6DDH0, Q6FUM5, Q6GLB0

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

2 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

122 predictions. Top by Δscore:

Variant	Effect	Δscore
X:141583957:CAT:C	acceptor_gain	0.9700
X:141583957:CATCT:C	acceptor_loss	0.9700
X:141583959:TCTG:T	acceptor_loss	0.9700
X:141583960:C:CA	acceptor_loss	0.9700
X:141583960:C:CC	acceptor_gain	0.9700
X:141583961:T:A	acceptor_loss	0.9700
X:141583956:GCAT:G	acceptor_gain	0.9200
X:141583957:CATC:C	acceptor_gain	0.9200
X:141583958:AT:A	acceptor_gain	0.9000
X:141583955:GGCAT:G	acceptor_gain	0.8700
X:141583972:C:CT	acceptor_gain	0.8700
X:141584587:TCAGA:T	donor_gain	0.8500
X:141583963:T:TC	acceptor_gain	0.8400
X:141584606:CCAT:C	donor_gain	0.8400
X:141583963:T:C	acceptor_gain	0.8300
X:141583973:A:T	acceptor_gain	0.8200
X:141584036:T:TA	donor_gain	0.7800
X:141583962:G:GC	acceptor_gain	0.6200
X:141584601:TCTTA:T	donor_loss	0.5800
X:141584602:CTTAC:C	donor_loss	0.5800
X:141584603:TT:T	donor_loss	0.5800
X:141584604:TAC:T	donor_loss	0.5800
X:141584605:A:AT	donor_loss	0.5800
X:141584606:C:G	donor_loss	0.5800
X:141584600:GTCTT:G	donor_loss	0.5700
X:141584605:A:AC	donor_gain	0.5500
X:141584606:C:CC	donor_gain	0.5500
X:141584607:C:T	donor_loss	0.5500
X:141584597:A:C	donor_gain	0.5400
X:141584695:T:G	acceptor_gain	0.4800

AlphaMissense

649 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS111432085 (X:141584763 T>C), RS111462866 (X:141585484 A>G), RS111825908 (X:141584762 A>G), RS112143855 (X:141585250 C>T), RS112194721 (X:141584734 T>G), RS112363703 (X:141586736 A>G,T), RS112961592 (X:141584764 G>A), RS113016245 (X:141584822 G>C), RS113031460 (X:141584402 T>C), RS113626169 (X:141586156 T>C), RS1156470681 (X:141586675 T>C), RS1157188396 (X:141585982 G>C,T), RS1158284684 (X:141586361 AAATT>A), RS1158982310 (X:141585684 T>C), RS1159737865 (X:141585146 C>G)

Disease associations

OMIM: gene MIM:300305 | 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

14 total (human), top 14 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
propionaldehyde	increases expression	1
2-methyl-4-isothiazolin-3-one	increases expression	1
sodium arsenite	increases expression	1
butyraldehyde	increases expression	1
tobacco tar	decreases expression	1
tri-o-cresyl phosphate	decreases expression	1
cupric oxide	increases expression	1
Decitabine	increases expression	1
Benzo(a)pyrene	increases expression	1
Fluorouracil	affects response to substance	1
Indomethacin	increases expression	1
Plant Oils	increases expression	1
Silicon Dioxide	increases expression	1
Copper Sulfate	affects expression	1

Clinical trials (associated diseases)

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