SPANXN4

Summary

SPANXN4 (SPANX family member N4, HGNC:33177) is a protein-coding gene on chromosome Xq27.3, encoding Sperm protein associated with the nucleus on the X chromosome N4 (Q5MJ08).

This gene represents one of several duplicated family members that are located on the X chromosome. This gene family encodes proteins that play a role in spermiogenesis. These proteins represent a specific subgroup of cancer/testis-associated antigens, and they may be candidates for tumor vaccines. This family member belongs to a subgroup of related genes that are present in all primates and rats and mice, and thus, it represents one of the ancestral family members.

Source: NCBI Gene 441525 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 21 total
• MANE Select transcript: NM_001009613

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:33177
Approved symbol	SPANXN4
Name	SPANX family member N4
Location	Xq27.3
Locus type	gene with protein product
Status	Approved
Aliases	SPANX-N4, CT11.9
Ensembl gene	ENSG00000189326
Ensembl biotype	protein_coding
OMIM	300667
Entrez	441525

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000370504, ENST00000446864

RefSeq mRNA: 1 — MANE Select: NM_001009613 NM_001009613

CCDS: CCDS48178

Canonical transcript exons

ENST00000446864 — 2 exons

Exon	Start	End
ENSE00003978131	143034025	143034311
ENSE00003978132	143025928	143026092

Expression profiles

Bgee: expression breadth broad, 19 present calls, max score 98.12.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.1144 / max 62.2088, expressed in 35 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
197892	0.1144	35

Top tissues by expression

103 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	98.12	gold quality
left testis	UBERON:0004533	86.05	gold quality
testis	UBERON:0000473	85.28	gold quality
right testis	UBERON:0004534	84.38	gold quality
monocyte	CL:0000576	68.86	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	66.48	gold quality
leukocyte	CL:0000738	65.14	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
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
sural nerve	UBERON:0015488	30.93	gold quality
stromal cell of endometrium	CL:0002255	29.87	gold quality
prefrontal cortex	UBERON:0000451	29.31	gold quality
duodenum	UBERON:0002114	28.14	gold quality
liver	UBERON:0002107	28.04	gold quality
lymph node	UBERON:0000029	27.57	gold quality
tonsil	UBERON:0002372	27.05	gold quality
islet of Langerhans	UBERON:0000006	26.55	gold quality
vermiform appendix	UBERON:0001154	26.42	gold quality
muscle of leg	UBERON:0001383	26.27	gold quality
gall bladder	UBERON:0002110	25.98	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	25.89	gold quality
placenta	UBERON:0001987	25.81	gold quality
gastrocnemius	UBERON:0001388	25.36	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.31

Regulation

Is transcription factor: no

Cross-species orthologs

0 orthologs

Paralogs (4): SPANXN3 (ENSG00000189252), SPANXN1 (ENSG00000203923), SPANXN5 (ENSG00000204363), SPANXN2 (ENSG00000268988)

Protein

Protein identifiers

Sperm protein associated with the nucleus on the X chromosome N4 — Q5MJ08 (reviewed: Q5MJ08)

Alternative names: Nuclear-associated protein SPAN-Xn4, SPANX family member N4

All UniProt accessions (2): Q5MJ08, X6R7N2

UniProt curated annotations — full annotation on UniProt →

Similarity. Belongs to the SPAN-X family.

RefSeq proteins (1): NP_001009613* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR010007	SPAN-X_fam	Family

Pfam: PF07458

UniProt features (7 total): compositionally biased region 4, chain 1, region of interest 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q5MJ08-F1	69.71	0.00

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 1 (showing top): chrXq27

GO Biological Process (0):

GO Molecular Function (0):

GO Cellular Component (0):

Protein interactions and networks

STRING

204 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SPANXN4	SPANXA1	Q9NS26	917
SPANXN4	SPANXD	Q9BXN6	655
SPANXN4	EOLA2	Q96DE9	574
SPANXN4	XAGE3	Q8WTP9	571
SPANXN4	CXorf51A	A0A1B0GTR3	571
SPANXN4	TENT5D	Q8NEK8	545
SPANXN4	FAM133A	Q8N9E0	541
SPANXN4	MAGEC3	Q8TD91	480
SPANXN4	PRR32	B1ATL7	478
SPANXN4	XAGE1B	Q9HD64	473
SPANXN4	SSX7	Q7RTT5	471
SPANXN4	XAGE5	Q8WWM1	448
SPANXN4	EOLA1	Q8TE69	447
SPANXN4	HSFX4	A0A1B0GTS1	419
SPANXN4	ZNF157	P51786	417

IntAct

6 interactions, top by confidence:

A	B	Type	Score
SRPK1	SPANXN4	psi-mi:“MI:0217”(phosphorylation reaction)	0.440
CSAG1	NAP1L4	psi-mi:“MI:0914”(association)	0.350
CSAG2	CAMK2D	psi-mi:“MI:0914”(association)	0.350
SPANXN4	UBA6	psi-mi:“MI:0914”(association)	0.350
	EBAG9	psi-mi:“MI:0914”(association)	0.350

BioGRID (54): FTO (Affinity Capture-MS), UBE2R2 (Affinity Capture-MS), INTS9 (Affinity Capture-MS), HNRNPLL (Affinity Capture-MS), GINS1 (Affinity Capture-MS), LANCL2 (Affinity Capture-MS), MAPK1 (Affinity Capture-MS), MAPK3 (Affinity Capture-MS), ADO (Affinity Capture-MS), C9orf41 (Affinity Capture-MS), PNPO (Affinity Capture-MS), RBBP4 (Affinity Capture-MS), MINA (Affinity Capture-MS), PBK (Affinity Capture-MS), SNX27 (Affinity Capture-MS)

ESM2 similar proteins: A0A097SRV6, A0A0J1BDH3, O41801, P04605, P0C1K3, P0C766, P0CG34, P0CG35, P0DX04, P12692, P15633, P15835, P18758, P20065, P21113, P21117, P21752, P21753, P26351, P26352, P33248, P33735, P33736, P33737, P34338, P34493, P53768, P60743, P75605, Q12026, Q4UKT5, Q54CC7, Q55GR5, Q5MJ07, Q5MJ08, Q5VSR9, Q66H17, Q6I7R5, Q6SJ84, Q6SJ91

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

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	19
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

222 predictions. Top by Δscore:

Variant	Effect	Δscore
X:143026018:G:GT	donor_gain	0.9900
X:143026053:G:GT	donor_gain	0.9900
X:143026085:TTGAC:T	donor_gain	0.9700
X:143034023:A:AG	acceptor_gain	0.9700
X:143034024:G:GG	acceptor_gain	0.9700
X:143026068:A:G	donor_gain	0.9600
X:143034024:GAA:G	acceptor_gain	0.9500
X:143026089:CAAGG:C	donor_loss	0.9400
X:143026090:AAGGT:A	donor_loss	0.9400
X:143026091:AG:A	donor_loss	0.9400
X:143026092:G:GT	donor_loss	0.9400
X:143026093:G:GA	donor_loss	0.9400
X:143026094:T:A	donor_loss	0.9400
X:143026087:GACAA:G	donor_loss	0.9000
X:143034020:A:AG	acceptor_gain	0.9000
X:143026102:T:G	donor_gain	0.8600
X:143026107:TTTTG:T	donor_gain	0.8500
X:143026085:T:G	donor_gain	0.8400
X:143026088:ACAAG:A	donor_gain	0.8400
X:143034024:GA:G	acceptor_gain	0.8400
X:143026018:G:T	donor_gain	0.8200
X:143034021:C:G	acceptor_gain	0.8200
X:143034019:TACCA:T	acceptor_loss	0.7600
X:143034020:ACCAG:A	acceptor_loss	0.7600
X:143034022:CA:C	acceptor_loss	0.7600
X:143034024:G:A	acceptor_loss	0.7600
X:143026116:G:T	donor_gain	0.7300
X:143034011:T:A	acceptor_loss	0.7300
X:143034024:GAAGA:G	acceptor_gain	0.6900
X:143026097:G:C	donor_loss	0.6800

AlphaMissense

659 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:143034106:T:C	F54L	0.868
X:143034108:T:A	F54L	0.868
X:143034108:T:G	F54L	0.868
X:143034117:G:C	R57S	0.704
X:143034117:G:T	R57S	0.704
X:143034101:T:C	L52S	0.686
X:143034104:T:A	V53E	0.600

dbSNP variants (sampled 300 via entrez): RS1000189910 (X:143029464 T>G), RS1000766408 (X:143036431 T>C), RS1001344676 (X:143038182 G>A,T), RS1001780497 (X:143030604 A>C), RS1002099569 (X:143030018 G>A), RS1002191420 (X:143029449 T>C), RS1002350710 (X:143036350 C>A,T), RS1002376429 (X:143028845 T>C), RS1002702352 (X:143032098 GTCT>G), RS1003143247 (X:143032407 G>A), RS1003193148 (X:143027689 C>T), RS1003497747 (X:143027367 G>A), RS1003545251 (X:143025679 G>A), RS1003773237 (X:143034316 T>G), RS1004679782 (X:143033055 C>A)

Disease associations

OMIM: gene MIM:300667 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST003804_1	Non-response to bupropion and depression	2.000000e-17
GCST006284_6	Plasma proprotein convertase subtilisin/kexin type 9 levels in stable coronary artery disease	1.000000e-07

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0006899	PCSK9 protein measurement

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
Benzo(a)pyrene	decreases methylation	1
Valproic Acid	decreases methylation	1

Clinical trials (associated diseases)

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