SPACA3

Summary

SPACA3 (sperm acrosome associated 3, HGNC:16260) is a protein-coding gene on chromosome 17q11.2, encoding Sperm acrosome membrane-associated protein 3 (Q8IXA5). Sperm surface membrane protein that may be involved in sperm-egg plasma membrane adhesion and fusion during fertilization.

The protein encoded by this gene is a sperm surface protein that may be involved in adhesion to the egg prior to fertilization. While the encoded protein has significant similarity to lysozyme at the amino acid level, it has no detectable bacteriocidal activity. Several transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 124912 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 52 total
• MANE Select transcript: NM_173847

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16260
Approved symbol	SPACA3
Name	sperm acrosome associated 3
Location	17q11.2
Locus type	gene with protein product
Status	Approved
Aliases	ALLP17, SLLP1, LYC3, LYZL3, CT54
Ensembl gene	ENSG00000141316
Ensembl biotype	protein_coding
OMIM	612749
Entrez	124912

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 3 protein_coding, 2 protein_coding_CDS_not_defined

ENST00000269053, ENST00000394637, ENST00000394638, ENST00000485015, ENST00000580599

RefSeq mRNA: 3 — MANE Select: NM_173847 NM_001317225, NM_001317226, NM_173847

CCDS: CCDS11275, CCDS82105

Canonical transcript exons

ENST00000269053 — 5 exons

Exon	Start	End
ENSE00000947759	32996843	32997001
ENSE00003573647	32995409	32995717
ENSE00003639885	32997445	32997523
ENSE00003660266	32997712	32997877
ENSE00003849782	32991847	32991972

Expression profiles

Bgee: expression breadth ubiquitous, 112 present calls, max score 96.39.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0486 / max 57.2878, expressed in 3 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
160271	0.0305	3
160272	0.0108	3
160270	0.0073	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
left testis	UBERON:0004533	96.39	gold quality
right testis	UBERON:0004534	96.28	gold quality
sperm	CL:0000019	94.96	gold quality
testis	UBERON:0000473	93.17	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	84.73	gold quality
adult organism	UBERON:0007023	75.85	gold quality
body of pancreas	UBERON:0001150	71.98	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	68.95	gold quality
buccal mucosa cell	CL:0002336	66.38	gold quality
tibialis anterior	UBERON:0001385	65.84	silver quality
tendon of biceps brachii	UBERON:0008188	63.27	gold quality
pancreas	UBERON:0001264	61.67	gold quality
myocardium	UBERON:0002349	60.22	gold quality
pancreatic ductal cell	CL:0002079	59.93	silver quality
endothelial cell	CL:0000115	59.46	gold quality
parotid gland	UBERON:0001831	58.67	gold quality
deltoid	UBERON:0001476	56.03	silver quality
ileal mucosa	UBERON:0000331	55.24	silver quality
epithelial cell of pancreas	CL:0000083	54.64	gold quality
cardiac muscle of right atrium	UBERON:0003379	54.34	gold quality
left ventricle myocardium	UBERON:0006566	54.23	gold quality
kidney epithelium	UBERON:0004819	53.93	gold quality
upper arm skin	UBERON:0004263	53.52	gold quality
medial globus pallidus	UBERON:0002477	52.93	gold quality
cerebellar vermis	UBERON:0004720	52.03	gold quality
mucosa of transverse colon	UBERON:0004991	51.92	gold quality
globus pallidus	UBERON:0001875	50.91	gold quality
quadriceps femoris	UBERON:0001377	48.99	gold quality
middle temporal gyrus	UBERON:0002771	48.46	gold quality
amniotic fluid	UBERON:0000173	47.63	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	8.13

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 5)

• SLLP1 could be a potential receptor for the egg oligosaccharide residue N-acetylglucosamine, which is present in the extracellular matrix over the egg plasma membrane (PMID:12606493)
• SLLP1 is capable of eliciting B-cell immune responses in vivo in cancer-bearing individuals. (PMID:15475442)
• Authors present evidence that the variants could affect the expression levels or function of SPRASA, thereby affecting a couple’s fertility. (PMID:24872021)
• The levels of antibodies reactive with SPRASA were elevated in infertile women. (PMID:25038051)
• SLLP1 represents a promising target for the immunotherapy of multiple myeloma. (PMID:26088750)

Cross-species orthologs

13 orthologs

Organism	Symbol	Gene ID
mus_musculus	Spaca3	ENSMUSG00000053184
rattus_norvegicus	Spaca3	ENSRNOG00000006994
drosophila_melanogaster	LysB	FBGN0004425
drosophila_melanogaster	LysD	FBGN0004427
drosophila_melanogaster	LysE	FBGN0004428
drosophila_melanogaster	LysP	FBGN0004429
drosophila_melanogaster	LysS	FBGN0004430
drosophila_melanogaster	LysX	FBGN0004431
drosophila_melanogaster	CG16756	FBGN0029765
drosophila_melanogaster	CG7798	FBGN0034092
drosophila_melanogaster	CG16799	FBGN0034538
drosophila_melanogaster	CG11159	FBGN0034539
drosophila_melanogaster	CG30062	FBGN0050062

Paralogs (8): LYZ (ENSG00000090382), LYZL1 (ENSG00000120563), LYZL2 (ENSG00000151033), LYZL4 (ENSG00000157093), LALBA (ENSG00000167531), SPACA5B (ENSG00000171478), SPACA5 (ENSG00000171489), LYZL6 (ENSG00000275722)

Protein

Protein identifiers

Sperm acrosome membrane-associated protein 3 — Q8IXA5 (reviewed: Q8IXA5)

Alternative names: Cancer/testis antigen 54, Lysozyme-like acrosomal sperm-specific secretory protein ALLP-17, Lysozyme-like protein 3, Sperm lysozyme-like protein 1, Sperm protein reactive with antisperm antibodies

All UniProt accessions (3): A0A080YUZ7, E9PF91, Q8IXA5

UniProt curated annotations — full annotation on UniProt →

Function. Sperm surface membrane protein that may be involved in sperm-egg plasma membrane adhesion and fusion during fertilization. It could be a potential receptor for the egg oligosaccharide residue N-acetylglucosamine, which is present in the extracellular matrix over the egg plasma membrane. The processed form has no detectable bacteriolytic activity in vitro.

Subunit / interactions. Interacts with ASTL.

Subcellular location. Cytoplasmic vesicle. Secretory vesicle. Acrosome membrane Secreted.

Tissue specificity. The processed form is expressed in sperm (at protein level). Expressed in testis, epididymis and placenta.

Post-translational modifications. The processed form derives from the membrane form by proteolytic processing.

Similarity. Belongs to the glycosyl hydrolase 22 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q8IXA5-1	1	yes
Q8IXA5-2	2

RefSeq proteins (3): NP_001304154, NP_001304155, NP_776246* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000974	Glyco_hydro_22_lys	Family
IPR001916	Glyco_hydro_22	Family
IPR019799	Glyco_hydro_22_CS	Domain
IPR023346	Lysozyme-like_dom_sf	Homologous_superfamily

Pfam: PF00062

UniProt features (15 total): disulfide bond 4, sequence variant 3, chain 2, topological domain 2, splice variant 1, transmembrane region 1, domain 1, site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8IXA5-F1	82.40	0.63

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (1): 87–88 (cleavage; to produce processed form)

Disulfide bonds (4): 162–180, 93–213, 117–201, 151–166

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 83 (showing top): GOBP_REGULATION_OF_CELL_ACTIVATION, GOBP_SINGLE_FERTILIZATION, GOBP_POSITIVE_REGULATION_OF_ENDOCYTOSIS, GOBP_POSITIVE_REGULATION_OF_MACROPHAGE_ACTIVATION, GOCC_SECRETORY_GRANULE, GOBP_MEMBRANE_FUSION, GOBP_PLASMA_MEMBRANE_ORGANIZATION, GOBP_REGULATION_OF_MACROPHAGE_ACTIVATION, GOBP_VESICLE_MEDIATED_TRANSPORT, chr17q11, GOBP_REGULATION_OF_VESICLE_MEDIATED_TRANSPORT, GOBP_MYELOID_LEUKOCYTE_ACTIVATION, WANG_RECURRENT_LIVER_CANCER_DN, GOBP_SPERM_EGG_RECOGNITION, GOBP_POSITIVE_REGULATION_OF_CELL_ACTIVATION

GO Biological Process (5): fusion of sperm to egg plasma membrane involved in single fertilization (GO:0007342), sperm-egg recognition (GO:0035036), monocyte activation (GO:0042117), positive regulation of macrophage activation (GO:0043032), positive regulation of phagocytosis (GO:0050766)

GO Molecular Function (2): lysozyme activity (GO:0003796), protein binding (GO:0005515)

GO Cellular Component (8): acrosomal vesicle (GO:0001669), acrosomal membrane (GO:0002080), extracellular region (GO:0005576), secretory granule (GO:0030141), sperm flagellum (GO:0036126), acrosomal matrix (GO:0043159), membrane (GO:0016020), cytoplasmic vesicle (GO:0031410)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
single fertilization	2
acrosomal vesicle	2
cellular process involved in reproduction in multicellular organism	1
cell-cell recognition	1
myeloid leukocyte activation	1
positive regulation of leukocyte activation	1
macrophage activation	1
regulation of macrophage activation	1
phagocytosis	1
positive regulation of endocytosis	1
regulation of phagocytosis	1
hydrolase activity, hydrolyzing O-glycosyl compounds	1
peptidoglycan muralytic activity	1
binding	1
secretory granule	1
secretory granule membrane	1
endomembrane system	1
secretory vesicle	1
9+2 motile cilium	1
vacuole	1
cytoplasm	1
intracellular vesicle	1

Protein interactions and networks

STRING

654 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SPACA3	SPACA1	Q9HBV2	702
SPACA3	TMEM190	Q8WZ59	639
SPACA3	IZUMO1	Q8IYV9	576
SPACA3	SPESP1	Q6UW49	573
SPACA3	ACRBP	Q8NEB7	561
SPACA3	ZPBP	Q9BS86	560
SPACA3	LUZP4	Q9P127	552
SPACA3	HSPB3	Q12988	549
SPACA3	CCDC110	Q8TBZ0	544
SPACA3	MPEG1	Q2M385	522
SPACA3	ZNF165	P49910	507
SPACA3	ASTL	Q6HA08	505
SPACA3	SPMAP2	Q9P2T0	472
SPACA3	PRM2	P04554	469
SPACA3	LTF	P02788	462

IntAct

6 interactions, top by confidence:

A	B	Type	Score
SPACA3	HSPA5	psi-mi:“MI:0914”(association)	0.530
ZP3	SPACA3	psi-mi:“MI:0915”(physical association)	0.490
SPACA3	A2M	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (10): FKBP14 (Affinity Capture-MS), AADAT (Affinity Capture-MS), FKBP7 (Affinity Capture-MS), HSPA5 (Affinity Capture-MS), ANKRD46 (Affinity Capture-MS), FKBP14 (Affinity Capture-MS), HSPA5 (Affinity Capture-MS), AADAT (Affinity Capture-MS), FKBP7 (Affinity Capture-MS), SPACA3 (Two-hybrid)

ESM2 similar proteins: A2AE20, A6QQ77, B6VH75, B6VH76, B6VH77, B6VH79, D4ABW7, O08717, O15496, O75173, O75951, O88839, P00716, P01231, P04421, P04651, P09462, P11688, P12068, P30805, P51782, Q05820, Q0V8J4, Q13444, Q29RT1, Q2T9N7, Q32PD6, Q49KI5, Q5E985, Q5RFQ8, Q5U2X4, Q659U0, Q659U1, Q659U5, Q6EV78, Q6MG64, Q8BNJ2, Q8IXA5, Q923K1, Q96KX0

Diamond homologs: A0JNM6, A2AE20, A6QQ77, B6VH75, B6VH76, G3XDT7, O75951, P00697, P00698, P00699, P00700, P00701, P00702, P00703, P00704, P00705, P00706, P00707, P00708, P04421, P08905, P11375, P11376, P11941, P12066, P12067, P12068, P12069, P16973, P17607, P17897, P19849, P22910, P24364, P24533, P30201, P37712, P37713, P49663, P61626

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	41
Likely benign	5
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

740 predictions. Top by Δscore:

Variant	Effect	Δscore
17:32996841:AGG:A	acceptor_gain	1.0000
17:32996842:GGG:G	acceptor_gain	1.0000
17:32996866:A:G	acceptor_gain	1.0000
17:32996943:G:GT	donor_gain	1.0000
17:32996988:G:GT	donor_gain	1.0000
17:32996997:CTCAG:C	donor_loss	1.0000
17:32997000:AG:A	donor_loss	1.0000
17:32997001:GG:G	donor_loss	1.0000
17:32997002:G:A	donor_loss	1.0000
17:32997003:T:A	donor_loss	1.0000
17:32997438:A:AG	acceptor_gain	1.0000
17:32997439:C:G	acceptor_gain	1.0000
17:32997441:CCAG:C	acceptor_loss	1.0000
17:32997442:CA:C	acceptor_loss	1.0000
17:32997443:A:AG	acceptor_gain	1.0000
17:32997443:AG:A	acceptor_loss	1.0000
17:32997444:G:GG	acceptor_gain	1.0000
17:32997444:GAT:G	acceptor_gain	1.0000
17:32997444:GATT:G	acceptor_gain	1.0000
17:32997444:GATTT:G	acceptor_gain	1.0000
17:32997520:ACTGG:A	donor_loss	1.0000
17:32997524:G:GC	donor_loss	1.0000
17:32997525:TAA:T	donor_loss	1.0000
17:32991973:G:GG	donor_gain	0.9900
17:32995718:G:GG	donor_gain	0.9900
17:32996838:TGCAG:T	acceptor_loss	0.9900
17:32996840:CAGGG:C	acceptor_loss	0.9900
17:32996841:A:T	acceptor_loss	0.9900
17:32996841:AG:A	acceptor_gain	0.9900
17:32996842:GG:G	acceptor_gain	0.9900

AlphaMissense

1391 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:32997712:G:C	W194C	0.993
17:32997712:G:T	W194C	0.993
17:32997757:G:C	W209C	0.993
17:32997757:G:T	W209C	0.993
17:32996927:T:G	F143C	0.990
17:32997721:G:C	W197C	0.988
17:32997721:G:T	W197C	0.988
17:32996949:G:C	W150C	0.984
17:32996949:G:T	W150C	0.984
17:32996844:G:C	W115C	0.981
17:32996844:G:T	W115C	0.981
17:32996927:T:C	F143S	0.981
17:32997731:T:A	C201S	0.978
17:32997732:G:C	C201S	0.978
17:32996950:T:A	C151S	0.976
17:32996951:G:C	C151S	0.976
17:32997475:T:A	V178D	0.975
17:32996933:T:C	I145T	0.972
17:32996938:A:C	S147R	0.972
17:32996940:C:A	S147R	0.972
17:32996940:C:G	S147R	0.972
17:32997480:T:A	C180S	0.972
17:32997481:G:C	C180S	0.972
17:32996867:G:T	S123I	0.971
17:32996921:G:T	G141V	0.971
17:32996921:G:A	G141E	0.970
17:32997767:T:A	C213S	0.969
17:32997768:G:C	C213S	0.969
17:32996860:T:C	F121L	0.968
17:32996862:C:A	F121L	0.968

dbSNP variants (sampled 300 via entrez): RS1000081754 (17:32994532 T>C), RS1000543372 (17:32997068 T>A), RS1001159677 (17:32995082 C>T), RS1001583447 (17:32997596 C>T), RS1001743826 (17:32991044 G>A), RS1001906362 (17:32997379 A>T), RS1002107030 (17:32991824 C>A,T), RS1002174878 (17:32990777 C>A,T), RS1002974848 (17:32992279 C>T), RS1002991542 (17:32996514 G>A), RS1003153265 (17:32989945 A>T), RS1003305211 (17:32993221 G>A), RS1004114973 (17:32993453 G>A,T), RS1004984526 (17:32997633 T>C), RS1005120524 (17:32991279 C>T)

Disease associations

OMIM: gene MIM:612749 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST007682_2	Thyroxine levels	5.000000e-07
GCST008368_3	Plasma anti-thyroid peroxidase levels	9.000000e-07
GCST010002_122	Refractive error	7.000000e-44
GCST90002404_157	Red cell distribution width	4.000000e-11

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0009188	Red cell distribution width

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
Benzo(a)pyrene	increases methylation	1

Clinical trials (associated diseases)

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