SPANXD

Summary

SPANXD (SPANX family member D, HGNC:14332) is a protein-coding gene on chromosome Xq27.2, encoding Sperm protein associated with the nucleus on the X chromosome D (Q9BXN6).

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 encodes a sperm protein that is associated with the nucleus but, although a role in spermatogenesis is suggested, the specific function of this family member has not yet been determined. Polymorphisms in this gene may be associated with prostate cancer susceptibility.

Source: NCBI Gene 64648 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 39 total
• MANE Select transcript: NM_032417

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:14332
Approved symbol	SPANXD
Name	SPANX family member D
Location	Xq27.2
Locus type	gene with protein product
Status	Approved
Aliases	CT11.4
Ensembl gene	ENSG00000196406
Ensembl biotype	protein_coding
OMIM	300670
Entrez	64648

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000370515

RefSeq mRNA: 1 — MANE Select: NM_032417 NM_032417

CCDS: CCDS14675

Canonical transcript exons

ENST00000370515 — 2 exons

Exon	Start	End
ENSE00001826931	141698334	141698739
ENSE00001930437	141697411	141697686

Expression profiles

Bgee: expression breadth broad, 17 present calls, max score 83.12.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0315 / max 8.5181, expressed in 11 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
200747	0.0315	11

Top tissues by expression

117 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	83.12	gold quality
right testis	UBERON:0004534	82.95	gold quality
left testis	UBERON:0004533	82.61	gold quality
testis	UBERON:0000473	82.21	gold quality
sural nerve	UBERON:0015488	45.90	gold 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
ganglionic eminence	UBERON:0004023	35.49	gold quality
skeletal muscle tissue	UBERON:0001134	33.38	gold quality
bone marrow	UBERON:0002371	33.15	gold quality
primary visual cortex	UBERON:0002436	31.84	gold quality
muscle tissue	UBERON:0002385	31.06	gold quality
stromal cell of endometrium	CL:0002255	29.87	gold quality
placenta	UBERON:0001987	29.45	gold quality
lymph node	UBERON:0000029	29.15	gold quality
tonsil	UBERON:0002372	28.81	gold quality
duodenum	UBERON:0002114	28.14	gold quality
urinary bladder	UBERON:0001255	27.78	gold quality
islet of Langerhans	UBERON:0000006	26.55	gold quality
descending thoracic aorta	UBERON:0002345	26.48	gold quality
vermiform appendix	UBERON:0001154	26.42	gold quality
omental fat pad	UBERON:0010414	26.42	gold quality
leukocyte	CL:0000738	26.38	gold quality
monocyte	CL:0000576	26.26	gold quality
blood	UBERON:0000178	26.14	gold quality
muscle of leg	UBERON:0001383	26.09	gold quality
gall bladder	UBERON:0002110	25.98	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	25.89	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.98

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 1)

• High SPANXD expression is associated with breast cancer invasion. (PMID:26895102)

Cross-species orthologs

0 orthologs

Paralogs (4): SPANXA1 (ENSG00000198021), SPANXC (ENSG00000198573), SPANXA2 (ENSG00000203926), SPANXB1 (ENSG00000227234)

Protein

Protein identifiers

Sperm protein associated with the nucleus on the X chromosome D — Q9BXN6 (reviewed: Q9BXN6)

Alternative names: Cancer/testis antigen 11.4, Nuclear-associated protein SPAN-Xd, SPANX family member D

All UniProt accessions (1): Q9BXN6

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Cytoplasm. Nucleus.

Tissue specificity. Detected in testis, sperm and a melanoma cell line.

Similarity. Belongs to the SPAN-X family.

RefSeq proteins (1): NP_115793* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR010007	SPAN-X_fam	Family

Pfam: PF07458

UniProt features (4 total): 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-Q9BXN6-F1	69.81	0.08

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 4 (showing top): ACEVEDO_METHYLATED_IN_LIVER_CANCER_DN, LU_EZH2_TARGETS_UP, chrXq27, FORTSCHEGGER_PHF8_TARGETS_DN

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

464 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SPANXD	SPANXN4	Q5MJ08	655
SPANXD	SRY	Q05066	653
SPANXD	SPANXN3	Q5MJ09	583
SPANXD	GAGE2A	Q6NT46	573
SPANXD	XAGE2	Q96GT9	570
SPANXD	LGALS4	P56470	549
SPANXD	GAGE4	P0DSO3	540
SPANXD	FATE1	Q969F0	506
SPANXD	MAGEB2	O15479	479
SPANXD	XAGE1B	Q9HD64	479
SPANXD	FMR1NB	Q8N0W7	478
SPANXD	RNF225	M0QZC1	476
SPANXD	SPA17	Q15506	453
SPANXD	MAGEC3	Q8TD91	447
SPANXD	MAGEA4	P43358	446

IntAct

13 interactions, top by confidence:

A	B	Type	Score
SPANXD	SETBP1	psi-mi:“MI:0915”(physical association)	0.560
SETBP1	SPANXD	psi-mi:“MI:0915”(physical association)	0.560
FLNA	SPANXD	psi-mi:“MI:0915”(physical association)	0.560
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
SPANXD	FLNA	psi-mi:“MI:0915”(physical association)	0.000
SPANXD	SETBP1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (6): SPANXD (Two-hybrid), SPANXD (Two-hybrid), SPANXD (Two-hybrid), FLNA (Two-hybrid), SPANXD (Affinity Capture-MS), SPANXD (Affinity Capture-MS)

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, Q9NS26, Q9NY87, Q9NS25

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	36
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

242 predictions. Top by Δscore:

Variant	Effect	Δscore
X:141697460:T:TA	donor_gain	1.0000
X:141697493:T:TA	donor_gain	1.0000
X:141697502:T:TA	donor_gain	1.0000
X:141697505:T:TA	donor_gain	1.0000
X:141697508:T:TA	donor_gain	1.0000
X:141698328:TCTTA:T	donor_loss	1.0000
X:141698329:CTTAC:C	donor_loss	1.0000
X:141698330:TTA:T	donor_loss	1.0000
X:141698331:TACC:T	donor_loss	1.0000
X:141698332:A:AC	donor_gain	1.0000
X:141698332:A:AT	donor_loss	1.0000
X:141698333:C:CC	donor_gain	1.0000
X:141698333:C:CT	donor_loss	1.0000
X:141698333:CCAT:C	donor_gain	1.0000
X:141697437:G:A	donor_gain	0.9900
X:141697457:G:C	donor_gain	0.9900
X:141697462:TTGC:T	donor_gain	0.9900
X:141697463:TGCT:T	donor_gain	0.9900
X:141697465:C:CT	donor_gain	0.9900
X:141697466:T:TT	donor_gain	0.9900
X:141697490:ATTT:A	donor_gain	0.9900
X:141697685:G:GG	acceptor_gain	0.9900
X:141697686:A:AG	acceptor_gain	0.9900
X:141698314:TCAGA:T	donor_gain	0.9900
X:141698331:TACCA:T	donor_loss	0.9900
X:141697511:T:TA	donor_gain	0.9800
X:141697684:CAT:C	acceptor_gain	0.9800
X:141697685:G:GT	acceptor_loss	0.9800
X:141697685:GAT:G	acceptor_gain	0.9800
X:141697686:A:T	acceptor_loss	0.9800

AlphaMissense

645 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:141697498:G:C	F87L	0.895
X:141697498:G:T	F87L	0.895
X:141697500:A:G	F87L	0.895
X:141697490:A:G	I90T	0.686
X:141697601:A:T	V53D	0.650
X:141697588:C:A	R57S	0.645
X:141697588:C:G	R57S	0.645
X:141697529:A:G	I77T	0.615
X:141698358:A:C	C16W	0.613
X:141697591:C:A	R56S	0.611
X:141697591:C:G	R56S	0.611
X:141697525:G:C	N78K	0.597
X:141697525:G:T	N78K	0.597
X:141697579:T:A	K60N	0.596
X:141697579:T:G	K60N	0.596
X:141697490:A:T	I90K	0.581
X:141697534:G:C	N75K	0.565
X:141697534:G:T	N75K	0.565

dbSNP variants (sampled 300 via entrez): RS1059178 (X:141697584 A>C), RS1059179 (X:141697582 A>C,G), RS1157205174 (X:141699681 C>T), RS1157228969 (X:141700535 G>A), RS1157706476 (X:141699137 A>G), RS1157863049 (X:141698383 C>G,T), RS1158154323 (X:141697014 C>G), RS1159199976 (X:141698781 C>A), RS1159568611 (X:141699439 C>A,G,T), RS1160089617 (X:141697999 C>T), RS1160807415 (X:141699734 A>T), RS1161012211 (X:141700603 T>G), RS1162471886 (X:141697264 C>A), RS1162886839 (X:141699370 T>A), RS1163057030 (X:141700474 GT>G,GTT)

Disease associations

OMIM: gene MIM:300670 | 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

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases expression	2
Benzo(a)pyrene	decreases methylation, increases expression	2
methylmercuric chloride	increases expression	1
maleic acid	increases expression	1
cupric oxide	increases expression	1
mercuric bromide	increases expression	1
clothianidin	increases expression	1
Resveratrol	increases expression	1
Decitabine	increases expression	1
Air Pollutants	increases expression	1
Cadmium	decreases expression	1
Plant Oils	increases expression	1
Valproic Acid	increases expression	1
Aflatoxin B1	increases expression	1
Copper Sulfate	increases expression	1

Clinical trials (associated diseases)

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