SPANXA2

Summary

SPANXA2 (SPANX family member A2, HGNC:14328) 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 A1 and appears to be a duplication of that 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 728712 — RefSeq curated summary.

At a glance

• MANE Select transcript: NM_145662

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:14328
Approved symbol	SPANXA2
Name	SPANX family member A2
Location	Xq27.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000203926
Ensembl biotype	protein_coding
OMIM	300493
Entrez	728712

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000370518

RefSeq mRNA: 1 — MANE Select: NM_145662 NM_145662

CCDS: CCDS44007

Canonical transcript exons

ENST00000370518 — 2 exons

Exon	Start	End
ENSE00001821050	141590487	141590762
ENSE00001909387	141589708	141589839

Expression profiles

Bgee: expression breadth broad, 55 present calls, max score 95.00.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.1476 / max 98.5367, expressed in 29 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
197884	0.1476	29

Top tissues by expression

104 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	95.00	gold quality
right testis	UBERON:0004534	92.78	gold quality
left testis	UBERON:0004533	92.61	gold quality
testis	UBERON:0000473	92.19	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	87.60	gold quality
ventricular zone	UBERON:0003053	42.02	gold quality
colonic epithelium	UBERON:0000397	37.20	gold quality
cortical plate	UBERON:0005343	36.47	gold quality
bone marrow cell	CL:0002092	36.16	gold quality
ganglionic eminence	UBERON:0004023	35.49	gold quality
skeletal muscle tissue	UBERON:0001134	33.38	gold quality
thoracic aorta	UBERON:0001515	32.75	gold quality
ascending aorta	UBERON:0001496	32.38	gold quality
hindlimb stylopod muscle	UBERON:0004252	32.15	gold quality
liver	UBERON:0002107	32.13	gold quality
descending thoracic aorta	UBERON:0002345	31.77	gold quality
bone marrow	UBERON:0002371	31.74	gold quality
popliteal artery	UBERON:0002250	31.51	gold quality
tibial artery	UBERON:0007610	31.48	gold quality
left uterine tube	UBERON:0001303	31.26	gold quality
muscle tissue	UBERON:0002385	31.06	gold quality
sural nerve	UBERON:0015488	30.93	gold quality
stromal cell of endometrium	CL:0002255	29.87	gold quality
primary visual cortex	UBERON:0002436	29.76	gold quality
prefrontal cortex	UBERON:0000451	29.32	gold quality
tonsil	UBERON:0002372	29.08	gold quality
duodenum	UBERON:0002114	28.14	gold quality
right coronary artery	UBERON:0001625	27.70	gold quality
lymph node	UBERON:0000029	27.57	gold quality
right lobe of liver	UBERON:0001114	27.49	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 1)

• Hypomethylated SPANXA1/A2 promotes the metastasis of head and neck squamous cell carcinoma. (PMID:33175201)

Cross-species orthologs

0 orthologs

Paralogs (4): SPANXD (ENSG00000196406), SPANXA1 (ENSG00000198021), SPANXC (ENSG00000198573), 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_663695* (*=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: 9 (showing top): GOBP_MALE_GAMETE_GENERATION, GOBP_DEVELOPMENTAL_PROCESS_INVOLVED_IN_REPRODUCTION, MAHADEVAN_IMATINIB_RESISTANCE_UP, chrXq27, PURBEY_TARGETS_OF_CTBP1_NOT_SATB1_DN, IBRAHIM_NRF2_UP, GOBP_SEXUAL_REPRODUCTION, GOBP_REPRODUCTIVE_PROCESS, GOBP_MULTICELLULAR_ORGANISMAL_REPRODUCTIVE_PROCESS

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
SPANXA2	SPANXN4	Q5MJ08	917
SPANXA2	AKAP4	Q5JQC9	745
SPANXA2	TSN	Q15631	711
SPANXA2	SRY	Q05066	682
SPANXA2	LGALS4	P56470	669
SPANXA2	CT45A1	Q5HYN5	608
SPANXA2	GAGE4	P0DSO3	581
SPANXA2	MAGEA1	P43355	573
SPANXA2	CTAG1A	P78358	526
SPANXA2	XAGE1B	Q9HD64	526
SPANXA2	MAGEC1	O60732	507
SPANXA2	CT47A11	Q5JQC4	507
SPANXA2	CXorf51A	A0A1B0GTR3	505
SPANXA2	CSAG2	Q9Y5P2	505
SPANXA2	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

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

139 predictions. Top by Δscore:

Variant	Effect	Δscore
X:141589836:GATG:G	donor_gain	0.9900
X:141589837:ATGGT:A	donor_loss	0.9900
X:141589840:G:GA	donor_loss	0.9900
X:141589840:G:GG	donor_gain	0.9900
X:141589841:T:G	donor_loss	0.9900
X:141589854:TTCTG:T	donor_gain	0.9900
X:141590483:T:G	acceptor_loss	0.9900
X:141590484:C:CC	acceptor_gain	0.9900
X:141590484:C:CG	acceptor_loss	0.9900
X:141590486:ATCTG:A	acceptor_loss	0.9900
X:141590487:CAT:C	acceptor_gain	0.9900
X:141590481:TAACA:T	acceptor_loss	0.9700
X:141590482:AACAG:A	acceptor_loss	0.9700
X:141590484:CA:C	acceptor_loss	0.9700
X:141590485:A:AG	acceptor_gain	0.9700
X:141590485:A:T	acceptor_loss	0.9700
X:141590486:G:GC	acceptor_loss	0.9700
X:141590486:G:GG	acceptor_gain	0.9700
X:141590486:GAT:G	acceptor_gain	0.9700
X:141590487:CATC:C	acceptor_gain	0.9700
X:141590488:GCAT:G	acceptor_gain	0.9700
X:141590486:AT:A	acceptor_gain	0.9600
X:141590489:GGCAT:G	acceptor_gain	0.9600
X:141590481:T:TC	acceptor_gain	0.9500
X:141590485:AGAT:A	acceptor_gain	0.9300
X:141590486:GATG:G	acceptor_gain	0.9300
X:141589849:T:G	donor_gain	0.9100
X:141590473:T:TA	acceptor_gain	0.9100
X:141590481:T:C	acceptor_gain	0.9100
X:141590486:GA:G	acceptor_gain	0.9100

AlphaMissense

649 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:141590673:T:C	F87L	0.892
X:141590675:C:A	F87L	0.892
X:141590675:C:G	F87L	0.892
X:141590683:T:C	I90T	0.730
X:141590644:T:C	I77T	0.728
X:141590572:T:A	V53D	0.711
X:141590585:G:C	R57S	0.704
X:141590585:G:T	R57S	0.704
X:141589815:T:G	C16W	0.682
X:141590644:T:G	I77S	0.670
X:141590648:C:A	N78K	0.646
X:141590648:C:G	N78K	0.646
X:141590577:T:G	Y55D	0.634
X:141590639:C:A	N75K	0.629
X:141590639:C:G	N75K	0.629
X:141590683:T:A	I90K	0.623
X:141590582:G:C	R56S	0.621
X:141590582:G:T	R56S	0.621
X:141590594:A:C	K60N	0.617
X:141590594:A:T	K60N	0.617
X:141590638:A:T	N75I	0.598
X:141590623:A:T	D70V	0.593
X:141590683:T:G	I90R	0.573
X:141590622:G:C	D70H	0.572
X:141590623:A:C	D70A	0.571

dbSNP variants (sampled 300 via entrez): RS111829226 (X:141589621 C>A), RS113927121 (X:141588421 G>A), RS1156881214 (X:141588088 T>G), RS1158998613 (X:141588529 A>C,G,T), RS1160025272 (X:141589323 A>G), RS1161094907 (X:141588814 G>A,T), RS1161210928 (X:141588196 T>C,G), RS1162338332 (X:141587943 G>A), RS1164019613 (X:141588727 A>G), RS1164362898 (X:141588434 T>A), RS1166194036 (X:141588982 G>A), RS1166794235 (X:141588876 C>T), RS1167316558 (X:141589544 G>A,C), RS1167434430 (X:141589232 G>A), RS1168533449 (X:141588291 T>C)

Disease associations

OMIM: gene MIM:300493 | 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

2 total (human), top 2 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases expression	1
Okadaic Acid	increases expression	1

Clinical trials (associated diseases)

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