SPANXB1

Summary

SPANXB1 (SPANX family member B1, HGNC:14329) is a protein-coding gene on chromosome Xq27.1, encoding Sperm protein associated with the nucleus on the X chromosome B1 (Q9NS25).

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 family member contains an additional 18 nucleotides in its coding region compared to the other family members in the same gene cluster. This family member is also subject to gene copy number variation. Although the protein encoded by this gene contains consensus nuclear localization signals, the major site for subcellular localization of expressed protein is in the cytoplasmic droplets of ejaculated spermatozoa. This protein provides a biochemical marker for studying the unique structures in spermatazoa, while attempting to further define its role in spermatogenesis.

Source: NCBI Gene 728695 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 1 total — 1 pathogenic
• MANE Select transcript: NM_032461

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:14329
Approved symbol	SPANXB1
Name	SPANX family member B1
Location	Xq27.1
Locus type	gene with protein product
Status	Approved
Aliases	CT11.2
Ensembl gene	ENSG00000227234
Ensembl biotype	protein_coding
OMIM	300669
Entrez	728695

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000449283

RefSeq mRNA: 1 — MANE Select: NM_032461 NM_032461

CCDS: CCDS44006

Canonical transcript exons

ENST00000449283 — 2 exons

Exon	Start	End
ENSE00001596774	141003431	141003706
ENSE00001762599	141002594	141002783

Expression profiles

Bgee: expression breadth broad, 65 present calls, max score 93.36.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 3.6878 / max 330.9920, expressed in 103 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
209841	2.2350	94
209840	1.1993	83
209842	0.1832	66
209843	0.0702	33

Top tissues by expression

237 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
left testis	UBERON:0004533	93.36	gold quality
right testis	UBERON:0004534	91.47	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	91.03	gold quality
sperm	CL:0000019	90.00	gold quality
testis	UBERON:0000473	89.87	gold quality
male germ cell	CL:0000015	87.92	gold quality
adult organism	UBERON:0007023	68.13	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	68.01	gold quality
buccal mucosa cell	CL:0002336	56.27	gold quality
pancreatic ductal cell	CL:0002079	54.22	silver quality
left ventricle myocardium	UBERON:0006566	51.15	gold quality
orbitofrontal cortex	UBERON:0004167	50.84	gold quality
epithelial cell of pancreas	CL:0000083	50.20	gold quality
myocardium	UBERON:0002349	49.52	gold quality
Brodmann (1909) area 46	UBERON:0006483	49.30	gold quality
blood vessel layer	UBERON:0004797	49.29	gold quality
quadriceps femoris	UBERON:0001377	49.26	gold quality
cervix squamous epithelium	UBERON:0006922	49.20	gold quality
hair follicle	UBERON:0002073	49.18	gold quality
deltoid	UBERON:0001476	49.12	gold quality
olfactory bulb	UBERON:0002264	48.92	gold quality
choroid plexus epithelium	UBERON:0003911	48.89	gold quality
type B pancreatic cell	CL:0000169	48.83	gold quality
cardiac muscle of right atrium	UBERON:0003379	48.55	gold quality
CA1 field of hippocampus	UBERON:0003881	48.50	gold quality
vastus lateralis	UBERON:0001379	48.34	gold quality
upper arm skin	UBERON:0004263	48.06	gold quality
cervix epithelium	UBERON:0004801	48.04	gold quality
oviduct epithelium	UBERON:0004804	48.00	gold quality
tongue squamous epithelium	UBERON:0006919	47.92	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.28

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 7)

• correlation between SPAN-Xb gene expression and B-cell immune responses in myeloma and other hematologic malignancies (PMID:12393489)
• Human VCX/Y, SPANX, and CSAG2 gene families together with the murine SPANX gene and the CYPT family may share a common ancestor. (PMID:17342728)
• genetic variability of SPANX-B and SPANX-C in a sample of Sicilian male population including patients with melanoma of the skin and controls; Sixteen and 13 genetic classes were detected for SPANX-B and SPANX-C genes, respectively (PMID:18626316)
• SPANX-B (Xq27 region) gene dosage analysis in Down’s syndrome subjects with undescended testes (PMID:19417550)
• Copy number variation of the entire gene cluster containing all four SPANXA-E genes and with SPANXB, found exclusively in maturing sperm. Average CNV patterns did not differ between fertile and infertile men. (PMID:20073942)
• Epigenetic mechanisms underlying the dynamic expression of cancer-testis genes, PAGE2, -2B and SPANX-B, during mesenchymal-to-epithelial transition (PMID:25229454)
• Cancer Testis Antigen Promotes Triple Negative Breast Cancer Metastasis and is Traceable in the Circulating Extracellular Vesicles. (PMID:31406142)

Cross-species orthologs

0 orthologs

Paralogs (4): SPANXD (ENSG00000196406), SPANXA1 (ENSG00000198021), SPANXC (ENSG00000198573), SPANXA2 (ENSG00000203926)

Protein

Protein identifiers

Sperm protein associated with the nucleus on the X chromosome B1 — Q9NS25 (reviewed: Q9NS25)

Alternative names: Cancer/testis antigen 11.2, Nuclear-associated protein SPAN-Xb, SPANX family member B1, SPANX family member F1

All UniProt accessions (1): Q9NS25

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_115850* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR010007	SPAN-X_fam	Family

Pfam: PF07458

UniProt features (6 total): compositionally biased region 2, 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-Q9NS25-F1	68.80	0.18

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 24 (showing top): GOBP_MALE_GAMETE_GENERATION, GOBP_CELLULAR_PROCESS_INVOLVED_IN_REPRODUCTION_IN_MULTICELLULAR_ORGANISM, GOBP_DEVELOPMENTAL_PROCESS_INVOLVED_IN_REPRODUCTION, SENESE_HDAC1_TARGETS_UP, ACEVEDO_METHYLATED_IN_LIVER_CANCER_DN, KAN_RESPONSE_TO_ARSENIC_TRIOXIDE, MAHADEVAN_IMATINIB_RESISTANCE_UP, MODULE_49, chrXq27, FORTSCHEGGER_PHF8_TARGETS_DN, TAVAZOIE_METASTASIS, SNAI1_TARGET_GENES, ZBTB12_TARGET_GENES, ZFP28_TARGET_GENES, ZNF274_TARGET_GENES

GO Biological Process (1): spermatid development (GO:0007286)

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
germ cell development	1
spermatid differentiation	1
binding	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
cellular anatomical structure	1

Protein interactions and networks

STRING

472 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SPANXB1	LGALS4	P56470	649
SPANXB1	SRY	Q05066	572
SPANXB1	XAGE2	Q96GT9	447
SPANXB1	GAGE2A	Q6NT46	446
SPANXB1	CT45A1	Q5HYN5	418
SPANXB1	CTAG1A	P78358	417
SPANXB1	GAGE4	P0DSO3	406
SPANXB1	SPA17	Q15506	403
SPANXB1	ASPH	Q12797	386
SPANXB1	CFL1	P23528	374
SPANXB1	MAGEA2B	P43356	373
SPANXB1	MAGEC1	O60732	370
SPANXB1	SEMG1	P04279	370
SPANXB1	MAGEB1	P43366	370
SPANXB1	MAGEB2	O15479	370

IntAct

20 interactions, top by confidence:

A	B	Type	Score
ARID4B	SPANXB1	psi-mi:“MI:0915”(physical association)	0.560
UBL5	SPANXB1	psi-mi:“MI:0915”(physical association)	0.560
SNX32	SPANXB1	psi-mi:“MI:0915”(physical association)	0.560
NTAQ1	SPANXB1	psi-mi:“MI:0915”(physical association)	0.560
SPANXB1	SNX1	psi-mi:“MI:0915”(physical association)	0.500
	AP3B1	psi-mi:“MI:0914”(association)	0.350
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
PCDHB11	CLGN	psi-mi:“MI:0914”(association)	0.350
TP53BP1	PSMD14	psi-mi:“MI:2364”(proximity)	0.270
SPANXB1	SNX32	psi-mi:“MI:0915”(physical association)	0.000
NTAQ1	SPANXB1	psi-mi:“MI:0915”(physical association)	0.000
ARID4B	SPANXB1	psi-mi:“MI:0915”(physical association)	0.000
UBL5	SPANXB1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (14): SPANXB1 (Two-hybrid), SPANXB1 (Two-hybrid), SPANXB1 (Two-hybrid), SPANXB1 (Two-hybrid), SPANXA2 (Affinity Capture-MS), PAPSS2 (Affinity Capture-MS), SNX1 (Affinity Capture-MS), BPGM (Affinity Capture-MS), CBWD1 (Affinity Capture-MS), SPANXD (Affinity Capture-MS), TUBB8 (Affinity Capture-MS), SNX5 (Affinity Capture-MS), HMGCS1 (Affinity Capture-MS), SPANXB1 (Two-hybrid)

ESM2 similar proteins: A0A1B0GTR3, A0A7H0DN82, A7RR34, E9PVX6, O14598, O60356, O60829, O94243, P04605, P04614, P05909, P0C1K0, P0C765, P0C766, P0DPH9, P17285, P17759, P18098, P19416, P20290, P24109, P46012, P46583, Q06428, Q07555, Q08561, Q09821, Q1L9C7, Q32PF3, Q3KP22, Q5M948, Q5M951, Q5MJ08, Q5RCI9, Q6P8I4, Q758T8, Q76632, Q7M2N1, Q7TP40, Q80WR5

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

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

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

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
160897	GRCh38/hg38 Xp22.33-q28(chrX:10679-156022206)x3	Pathogenic

SpliceAI

19 predictions. Top by Δscore:

Variant	Effect	Δscore
X:141002780:GACG:G	donor_gain	1.0000
X:141002782:CGGT:C	donor_loss	1.0000
X:141002783:GGT:G	donor_loss	1.0000
X:141002784:G:C	donor_loss	1.0000
X:141002784:G:GG	donor_gain	1.0000
X:141002785:T:A	donor_loss	1.0000
X:141002779:AGACG:A	donor_gain	0.9900
X:141002780:GACGG:G	donor_gain	0.9900
X:141002798:TTTTG:T	donor_gain	0.9900
X:141002781:ACG:A	donor_gain	0.9600
X:141002782:CG:C	donor_gain	0.9600
X:141002783:GG:G	donor_gain	0.9600
X:141002763:GCCAA:G	donor_gain	0.9300
X:141002793:T:G	donor_gain	0.8400
X:141002799:TTTGA:T	donor_gain	0.4700
X:141002788:GATT:G	donor_gain	0.4000
X:141002786:A:C	donor_loss	0.3700
X:141002730:A:T	donor_gain	0.2600
X:141002781:A:T	donor_gain	0.2600

AlphaMissense

680 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:141003617:T:C	F93L	0.945
X:141003619:C:A	F93L	0.945
X:141003619:C:G	F93L	0.945
X:141003529:G:C	R63S	0.770
X:141003529:G:T	R63S	0.770
X:141003588:T:C	I83T	0.770
X:141003627:T:C	I96T	0.765
X:141003526:G:C	R62S	0.738
X:141003526:G:T	R62S	0.738
X:141003516:T:A	V59D	0.734
X:141003521:T:G	Y61D	0.732
X:141003583:C:A	N81K	0.714
X:141003583:C:G	N81K	0.714
X:141003567:A:T	D76V	0.699
X:141003588:T:G	I83S	0.697
X:141003627:T:A	I96K	0.684
X:141003567:A:C	D76A	0.683
X:141003566:G:C	D76H	0.676
X:141003568:C:A	D76E	0.675
X:141003568:C:G	D76E	0.675
X:141003519:G:C	R60P	0.668
X:141003618:T:C	F93S	0.666
X:141003510:T:C	L57P	0.660
X:141003522:A:C	Y61S	0.655
X:141003538:A:C	K66N	0.642
X:141003538:A:T	K66N	0.642
X:141003618:T:G	F93C	0.639
X:141003627:T:G	I96R	0.637
X:141003567:A:G	D76G	0.628
X:141003582:A:T	N81I	0.624

dbSNP variants (sampled 300 via entrez): RS1156272288 (X:141000776 C>T), RS1156411595 (X:141001702 G>C), RS1156947343 (X:141004166 G>A), RS1157399882 (X:141002670 G>A,C), RS1157436917 (X:141003443 C>G,T), RS1157533088 (X:141003800 AG>A), RS1157816689 (X:141002297 T>C), RS1158011889 (X:141003071 G>A), RS1161024464 (X:141002732 C>A,G,T), RS1161772291 (X:141001798 G>A), RS1161915558 (X:141001139 C>A,G), RS1162914738 (X:141002150 T>C), RS1163040779 (X:141002872 C>T), RS1163107555 (X:141002025 G>A), RS1163546956 (X:141001667 G>C)

Disease associations

OMIM: gene MIM:300669 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST006532_1	Esophageal adenocarcinoma x pack-years of smoking exposure interaction	6.000000e-07

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0006526	pack-years measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

15 total (human), top 15 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
propionaldehyde	increases expression	1
2-methyl-4-isothiazolin-3-one	increases expression	1
beta-lapachone	increases expression	1
sodium arsenite	increases expression	1
butyraldehyde	increases expression	1
tobacco tar	decreases expression	1
cupric oxide	increases expression	1
pentanal	increases expression	1
2-palmitoylglycerol	increases expression	1
Aldehydes	increases expression	1
Benzo(a)pyrene	increases expression	1
Silver	increases expression	1
Thiram	increases expression	1
Copper Sulfate	increases expression	1
Particulate Matter	decreases expression	1

Clinical trials (associated diseases)

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