SPACA1

Summary

SPACA1 (sperm acrosome associated 1, HGNC:14967) is a protein-coding gene on chromosome 6q15, encoding Sperm acrosome membrane-associated protein 1 (Q9HBV2). Plays a role in acrosome formation and establishment of normal sperm morphology during spermatogenesis.

The correlation of anti-sperm antibodies with cases of unexplained infertility implicates a role for these antibodies in blocking fertilization. Improved diagnosis and treatment of immunologic infertility, as well as identification of proteins for targeted contraception, are dependent on the identification and characterization of relevant sperm antigens. The protein expressed by this gene is recognized by anti-sperm antibodies from infertile males. Furthermore, antibodies generated against the recombinant protein block in vitro fertilization. This protein localizes to the acrosomal membrane of spermatids and mature spermatozoa where it is thought to play a role in acrosomal morphogenesis and in sperm-egg binding and fusion, respectively.

Source: NCBI Gene 81833 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 55 total — 1 pathogenic
• Phenotypes (HPO): 7
• MANE Select transcript: NM_030960

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:14967
Approved symbol	SPACA1
Name	sperm acrosome associated 1
Location	6q15
Locus type	gene with protein product
Status	Approved
Aliases	SAMP32
Ensembl gene	ENSG00000118434
Ensembl biotype	protein_coding
OMIM	612739
Entrez	81833

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 2 protein_coding_CDS_not_defined, 1 protein_coding

ENST00000237201, ENST00000462227, ENST00000462690

RefSeq mRNA: 1 — MANE Select: NM_030960 NM_030960

CCDS: CCDS5014

Canonical transcript exons

ENST00000237201 — 7 exons

Exon	Start	End
ENSE00000798169	88047841	88048113
ENSE00000798170	88053946	88054002
ENSE00000798171	88057612	88057713
ENSE00000798172	88058716	88058822
ENSE00000798174	88064099	88064219
ENSE00003496116	88059453	88059588
ENSE00003691395	88066182	88066838

Expression profiles

Bgee: expression breadth broad, 31 present calls, max score 92.42.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0886 / max 101.0430, expressed in 4 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
68845	0.0799	4
68844	0.0086	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
left testis	UBERON:0004533	92.42	gold quality
right testis	UBERON:0004534	92.01	gold quality
testis	UBERON:0000473	88.70	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	84.62	gold quality
sperm	CL:0000019	79.87	silver quality
male germ cell	CL:0000015	77.39	silver quality
diaphragm	UBERON:0001103	72.21	gold quality
buccal mucosa cell	CL:0002336	64.00	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	63.10	gold quality
bone marrow cell	CL:0002092	61.30	gold quality
endothelial cell	CL:0000115	60.93	gold quality
epithelial cell of pancreas	CL:0000083	60.25	gold quality
tongue squamous epithelium	UBERON:0006919	58.38	gold quality
decidua	UBERON:0002450	56.55	gold quality
vena cava	UBERON:0004087	56.39	gold quality
hair follicle	UBERON:0002073	54.07	gold quality
parietal pleura	UBERON:0002400	53.69	gold quality
myocardium	UBERON:0002349	53.41	gold quality
pleura	UBERON:0000977	53.33	gold quality
visceral pleura	UBERON:0002401	53.31	gold quality
pancreatic ductal cell	CL:0002079	53.10	silver quality
nasal cavity epithelium	UBERON:0005384	51.75	gold quality
gingival epithelium	UBERON:0001949	50.30	gold quality
ileal mucosa	UBERON:0000331	50.11	silver quality
Brodmann (1909) area 46	UBERON:0006483	49.30	gold quality
quadriceps femoris	UBERON:0001377	49.22	gold quality
cervix squamous epithelium	UBERON:0006922	49.20	gold quality
vastus lateralis	UBERON:0001379	49.08	gold quality
olfactory bulb	UBERON:0002264	48.92	gold quality
type B pancreatic cell	CL:0000169	48.83	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.96

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

59 targeting SPACA1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-548AB	99.95	71.31	3488
HSA-MIR-548A-5P	99.94	71.27	3482
HSA-MIR-548AD-5P	99.94	71.23	3502
HSA-MIR-548AE-5P	99.94	71.23	3502
HSA-MIR-548AK	99.94	71.24	3488
HSA-MIR-548AM-5P	99.94	71.24	3488
HSA-MIR-548AP-5P	99.94	71.14	3489
HSA-MIR-548AQ-5P	99.94	71.34	3426
HSA-MIR-548AR-5P	99.94	71.28	3515
HSA-MIR-548AS-5P	99.94	71.22	3482
HSA-MIR-548AU-5P	99.94	71.24	3488
HSA-MIR-548AY-5P	99.94	71.23	3502
HSA-MIR-548B-5P	99.94	71.23	3502
HSA-MIR-548BB-5P	99.94	71.27	3509
HSA-MIR-548C-5P	99.94	71.24	3488
HSA-MIR-548D-5P	99.94	71.23	3502
HSA-MIR-548H-5P	99.94	71.24	3488
HSA-MIR-548I	99.94	71.25	3481
HSA-MIR-548J-5P	99.94	71.14	3489
HSA-MIR-548O-5P	99.94	71.24	3488
HSA-MIR-548W	99.94	71.24	3488
HSA-MIR-548Y	99.94	71.28	3514
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-345-3P	99.89	70.23	1421
HSA-MIR-577	99.78	69.13	2479

Literature-anchored findings (GeneRIF, showing 4)

• SAMP32 was associated with the inner acrosomal membrane and recombinant SAMP32 reacted with serum from an infertile man suggesting that it is isoantigenic (PMID:11870081)
• Human posterior head 20 (hPH20) and homo sapiens sperm acrosome associated 1 (hSPACA1) immunocontraceptive epitopes reduced fertility in male/female mice. (PMID:25209425)
• Spaca1 role in male infertility.Distribution of SPACA1 in the sperm affects the outcomes of conventional in vitro fertilization. (PMID:27185107)
• Bioinformatic prediction of the structure and characteristics of human sperm acrosome membrane-associated protein 1 (hSAMP32) and evaluation of its antifertility function in vivo. (PMID:33220718)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Spaca1	ENSMUSG00000028264
rattus_norvegicus	Spaca1	ENSRNOG00000008232

Protein

Protein identifiers

Sperm acrosome membrane-associated protein 1 — Q9HBV2 (reviewed: Q9HBV2)

Alternative names: Sperm acrosomal membrane-associated protein 32

All UniProt accessions (1): Q9HBV2

UniProt curated annotations — full annotation on UniProt →

Function. Plays a role in acrosome formation and establishment of normal sperm morphology during spermatogenesis. Important for male fertility.

Subunit / interactions. Interacts with CYLC1; the interaction may be relevant for proper acrosome attachment to the nuclear envelope. Interacts with CFAP65.

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

Tissue specificity. Testis specific.

Post-translational modifications. N-glycosylated.

Disease relevance. Spermatogenic failure 85 (SPGF85) [MIM:620490] An autosomal recessive male infertility disorder characterized by globozoospermia and reduced progressive sperm motility. The disease may be caused by variants affecting the gene represented in this entry.

RefSeq proteins (1): NP_112222* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR037878	SPACA1	Family

UniProt features (16 total): modified residue 3, compositionally biased region 3, sequence variant 2, topological domain 2, region of interest 2, signal peptide 1, chain 1, glycosylation site 1, transmembrane region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9HBV2-F1	71.63	0.39

Functional residue map

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

Post-translational modifications (3): 256, 269, 290

Glycosylation sites (1): 31

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 103 (showing top): chr6q15, GOCC_SECRETORY_GRANULE, GOBP_VESICLE_ORGANIZATION, GOBP_MALE_GAMETE_GENERATION, GOBP_SECRETORY_GRANULE_ORGANIZATION, GOBP_CELLULAR_COMPONENT_ASSEMBLY_INVOLVED_IN_MORPHOGENESIS, GOBP_ACROSOME_ASSEMBLY, GOBP_ORGANELLE_ASSEMBLY, GOBP_CELLULAR_PROCESS_INVOLVED_IN_REPRODUCTION_IN_MULTICELLULAR_ORGANISM, GOBP_ENDOMEMBRANE_SYSTEM_ORGANIZATION, GOBP_DEVELOPMENTAL_PROCESS_INVOLVED_IN_REPRODUCTION, WEBER_METHYLATED_HCP_IN_SPERM_UP, WEBER_METHYLATED_HCP_IN_FIBROBLAST_DN, GOCC_ACROSOMAL_MEMBRANE, GOCC_SECRETORY_VESICLE

GO Biological Process (2): acrosome assembly (GO:0001675), spermatogenesis (GO:0007283)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (5): inner acrosomal membrane (GO:0002079), acrosomal membrane (GO:0002080), acrosomal vesicle (GO:0001669), membrane (GO:0016020), cytoplasmic vesicle (GO:0031410)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
developmental process involved in reproduction	2
spermatid development	1
cellular component assembly involved in morphogenesis	1
cellular process involved in reproduction in multicellular organism	1
secretory granule organization	1
organelle assembly	1
male gamete generation	1
binding	1
acrosomal membrane	1
cytoplasmic vesicle membrane	1
acrosomal vesicle	1
secretory granule membrane	1
secretory granule	1
cellular anatomical structure	1
cytoplasm	1
intracellular vesicle	1

Protein interactions and networks

STRING

830 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SPACA1	ZPBP	Q9BS86	828
SPACA1	IZUMO1	Q8IYV9	794
SPACA1	DPY19L2	Q6NUT2	766
SPACA1	SSMEM1	Q8WWF3	710
SPACA1	SPACA3	Q8IXA5	702
SPACA1	SPATA16	Q9BXB7	686
SPACA1	SPATA46	Q5T0L3	666
SPACA1	SPESP1	Q6UW49	664
SPACA1	CCDC62	Q6P9F0	624
SPACA1	GOPC	Q9HD26	589
SPACA1	TSSK4	Q6SA08	578
SPACA1	PICK1	Q9NRD5	578
SPACA1	SPAM1	P38567	571
SPACA1	SPACA4	Q8TDM5	571
SPACA1	VPS54	Q9P1Q0	563

IntAct

82 interactions, top by confidence:

A	B	Type	Score
ATP6V0C	SPACA1	psi-mi:“MI:0915”(physical association)	0.560
GIMAP5	SPACA1	psi-mi:“MI:0915”(physical association)	0.560
TMEM140	SPACA1	psi-mi:“MI:0915”(physical association)	0.560
PLN	SPACA1	psi-mi:“MI:0915”(physical association)	0.560
EMP1	SPACA1	psi-mi:“MI:0915”(physical association)	0.560
SERTM1	SPACA1	psi-mi:“MI:0915”(physical association)	0.560
SMIM3	SPACA1	psi-mi:“MI:0915”(physical association)	0.560
RPRM	SPACA1	psi-mi:“MI:0915”(physical association)	0.560
CD72	SPACA1	psi-mi:“MI:0915”(physical association)	0.560
CTXN3	SPACA1	psi-mi:“MI:0915”(physical association)	0.560
NSG1	SPACA1	psi-mi:“MI:0915”(physical association)	0.560
NRSN1	SPACA1	psi-mi:“MI:0915”(physical association)	0.560
BNIP3	SPACA1	psi-mi:“MI:0915”(physical association)	0.560
EMP3	SPACA1	psi-mi:“MI:0915”(physical association)	0.560
LSMEM2	SPACA1	psi-mi:“MI:0915”(physical association)	0.560
SMAGP	SPACA1	psi-mi:“MI:0915”(physical association)	0.560
SGCG	SPACA1	psi-mi:“MI:0915”(physical association)	0.560
THSD7B	SPACA1	psi-mi:“MI:0915”(physical association)	0.560
CACNG7	SPACA1	psi-mi:“MI:0915”(physical association)	0.560
SPACA1	AGPAT4	psi-mi:“MI:0915”(physical association)	0.560
SPACA1	TMEM140	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (188): TUBB3 (Affinity Capture-MS), C14orf2 (Affinity Capture-MS), LMBRD2 (Affinity Capture-MS), RAD51C (Affinity Capture-MS), SLC25A26 (Affinity Capture-MS), GOLIM4 (Affinity Capture-MS), C17orf80 (Affinity Capture-MS), IMPA2 (Affinity Capture-MS), LRFN1 (Affinity Capture-MS), GBF1 (Affinity Capture-MS), HEATR6 (Affinity Capture-MS), TRO (Affinity Capture-MS), GK (Affinity Capture-MS), ARFGEF2 (Affinity Capture-MS), DCP2 (Affinity Capture-MS)

ESM2 similar proteins: A0A2R8Y4Y8, A0A2R8YFL7, A0A2R8YFM6, A0A8J1K1A4, A5D791, E7FKV8, O77726, O88393, P20239, P20783, P26342, P35054, P40200, P47984, Q03167, Q05996, Q08DT3, Q17R60, Q2Q0J1, Q3MHP9, Q3U0X8, Q3V1M1, Q4FZG8, Q4V7E2, Q5BK49, Q5SY80, Q5XI99, Q6DFV8, Q6WRH9, Q6WRI0, Q6X784, Q7TST5, Q80VH0, Q86WS3, Q8JIR8, Q8R1W8, Q925U0, Q95KG7, Q9D9J7, Q9ET62

Diamond homologs: D5K8A9, Q2YDG7, Q9DA48, Q9HBV2

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	48
Likely benign	5
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
2577471	NM_030960.3(SPACA1):c.53G>A (p.Trp18Ter)	Pathogenic

SpliceAI

1032 predictions. Top by Δscore:

Variant	Effect	Δscore
6:88048109:GGATG:G	donor_gain	1.0000
6:88048110:GATGG:G	donor_gain	1.0000
6:88048111:A:T	donor_gain	1.0000
6:88053944:A:AG	acceptor_gain	1.0000
6:88053944:AGTT:A	acceptor_loss	1.0000
6:88053945:G:GG	acceptor_gain	1.0000
6:88053945:GT:G	acceptor_gain	1.0000
6:88054000:GTG:G	donor_gain	1.0000
6:88057710:GGCT:G	donor_gain	1.0000
6:88057711:GCTG:G	donor_gain	1.0000
6:88059448:A:G	acceptor_gain	1.0000
6:88059449:ATAGC:A	acceptor_loss	1.0000
6:88059450:TAGC:T	acceptor_loss	1.0000
6:88059451:A:AC	acceptor_loss	1.0000
6:88059451:A:AG	acceptor_gain	1.0000
6:88059452:G:GA	acceptor_gain	1.0000
6:88059452:G:GT	acceptor_loss	1.0000
6:88059452:GC:G	acceptor_gain	1.0000
6:88059452:GCA:G	acceptor_gain	1.0000
6:88059452:GCAAT:G	acceptor_gain	1.0000
6:88059586:GTG:G	donor_gain	1.0000
6:88059586:GTGGT:G	donor_loss	1.0000
6:88059587:TGGTA:T	donor_loss	1.0000
6:88059589:G:C	donor_loss	1.0000
6:88059590:T:A	donor_loss	1.0000
6:88059591:AAGT:A	donor_loss	1.0000
6:88053945:GTTT:G	acceptor_gain	0.9900
6:88053945:GTTTC:G	acceptor_gain	0.9900
6:88054001:TGGTA:T	donor_loss	0.9900
6:88054003:G:GG	donor_gain	0.9900

AlphaMissense

1923 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:88058801:G:C	W151C	0.997
6:88058801:G:T	W151C	0.997
6:88058799:T:A	W151R	0.996
6:88058799:T:C	W151R	0.996
6:88059525:T:A	C183S	0.995
6:88059526:G:C	C183S	0.995
6:88059567:T:C	F197L	0.994
6:88059569:C:A	F197L	0.994
6:88059569:C:G	F197L	0.994
6:88058787:T:C	F147L	0.992
6:88058789:C:A	F147L	0.992
6:88058789:C:G	F147L	0.992
6:88059555:G:C	A193P	0.992
6:88053987:T:A	C84S	0.991
6:88053988:G:C	C84S	0.991
6:88057647:T:A	C101S	0.991
6:88057648:G:C	C101S	0.991
6:88059525:T:C	C183R	0.991
6:88059527:T:G	C183W	0.991
6:88053987:T:C	C84R	0.990
6:88057668:T:A	C108S	0.990
6:88057669:G:C	C108S	0.990
6:88058717:G:C	W123C	0.990
6:88058717:G:T	W123C	0.990
6:88053989:C:G	C84W	0.989
6:88057668:T:C	C108R	0.989
6:88057689:T:A	C115S	0.989
6:88057690:G:C	C115S	0.989
6:88058760:T:C	C138R	0.989
6:88058762:T:G	C138W	0.989

dbSNP variants (sampled 300 via entrez): RS1000025312 (6:88052164 C>A,G,T), RS1000089501 (6:88044999 A>G), RS1000297305 (6:88057834 C>A,T), RS1000587066 (6:88045217 A>C), RS1000643946 (6:88062683 G>A), RS1000886381 (6:88056518 A>G,T), RS1001025737 (6:88050664 A>G), RS1001038873 (6:88051004 G>A), RS1001156492 (6:88065846 GA>G), RS1001166233 (6:88052940 CATTAA>C), RS1001277001 (6:88046582 C>T), RS1001310063 (6:88053185 C>G,T), RS1001379269 (6:88066499 C>T), RS1001936224 (6:88059224 A>T), RS1002148037 (6:88065960 A>G)

Disease associations

OMIM: gene MIM:612739 | disease phenotypes: MIM:620490

GenCC curated gene-disease

Mondo (1): spermatogenic failure 85 (MONDO:0957584)

Orphanet (0):

HPO phenotypes

7 total (7 of 7 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0003251	Male infertility
HP:0011462	Young adult onset
HP:0012205	Globozoospermia
HP:0012869	Acephalic spermatozoa
HP:0032560	Coiled sperm flagella
HP:0034011	Reduced progressive sperm motility

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST000110_8	Echocardiographic traits	2.000000e-06
GCST003069_6	Left superior temporal gyrus thickness (schizophrenia interaction)	9.000000e-06
GCST012317_6	Triglyceride levels x SSRI levels (escitalopram or citalopram) interaction in schizophrenia or bipolar disorder	3.000000e-06

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004295	left ventricular function
EFO:0004298	cardiovascular measurement
EFO:0004530	triglyceride measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

5 total (human), top 5 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	increases methylation	1
Benzo(a)pyrene	increases methylation	1
Folic Acid	increases expression	1
Sodium Selenite	decreases expression	1
Antirheumatic Agents	decreases expression	1

Clinical trials (associated diseases)

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