SPACA4

Summary

SPACA4 (sperm acrosome associated 4, HGNC:16441) is a protein-coding gene on chromosome 19q13.33, encoding Sperm acrosome membrane-associated protein 4 (Q8TDM5). Sperm surface membrane protein that is essential for effective sperm-zona pellucida binding and penetration during fertilization.

Involved in binding activity of sperm to zona pellucida. Located in inner acrosomal membrane and outer acrosomal membrane.

Source: NCBI Gene 171169 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 1 total
• MANE Select transcript: NM_133498

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16441
Approved symbol	SPACA4
Name	sperm acrosome associated 4
Location	19q13.33
Locus type	gene with protein product
Status	Approved
Aliases	SAMP14
Ensembl gene	ENSG00000177202
Ensembl biotype	protein_coding
OMIM	609932
Entrez	171169

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000321762

RefSeq mRNA: 1 — MANE Select: NM_133498 NM_133498

CCDS: CCDS12725

Canonical transcript exons

ENST00000321762 — 1 exons

Exon	Start	End
ENSE00001242862	48606742	48607714

Expression profiles

Bgee: expression breadth broad, 86 present calls, max score 95.96.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.1678 / max 153.3689, expressed in 3 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
176805	0.1603	3
176806	0.0075	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
left testis	UBERON:0004533	95.96	gold quality
right testis	UBERON:0004534	95.79	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	93.38	gold quality
testis	UBERON:0000473	92.15	gold quality
sperm	CL:0000019	89.30	gold quality
pancreatic ductal cell	CL:0002079	85.32	silver quality
lower esophagus mucosa	UBERON:0035834	81.49	gold quality
mucosa of transverse colon	UBERON:0004991	77.84	gold quality
parotid gland	UBERON:0001831	73.87	gold quality
adult organism	UBERON:0007023	70.87	gold quality
tibialis anterior	UBERON:0001385	68.26	silver quality
transverse colon	UBERON:0001157	66.55	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	65.72	gold quality
minor salivary gland	UBERON:0001830	65.34	gold quality
esophagus mucosa	UBERON:0002469	64.69	gold quality
saliva-secreting gland	UBERON:0001044	64.24	gold quality
small intestine Peyer’s patch	UBERON:0003454	63.88	gold quality
mouth mucosa	UBERON:0003729	63.64	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	63.14	gold quality
ileal mucosa	UBERON:0000331	62.54	silver quality
nasal cavity epithelium	UBERON:0005384	62.45	gold quality
rectum	UBERON:0001052	62.31	gold quality
myocardium	UBERON:0002349	62.29	gold quality
small intestine	UBERON:0002108	61.67	gold quality
body of stomach	UBERON:0001161	61.46	gold quality
cartilage tissue	UBERON:0002418	61.29	gold quality
deltoid	UBERON:0001476	60.32	gold quality
mucosa of stomach	UBERON:0001199	59.46	gold quality
upper leg skin	UBERON:0004262	59.14	silver quality
stomach	UBERON:0000945	58.35	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.86

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

39 targeting SPACA4, 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-5011-5P	100.00	83.46	5820
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-4650-5P	99.98	64.69	999
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-106A-5P	99.90	73.94	2683
HSA-MIR-302A-3P	99.89	71.23	1777
HSA-MIR-302B-3P	99.89	71.23	1777
HSA-MIR-302C-3P	99.89	71.20	1778
HSA-MIR-302D-3P	99.89	71.25	1777
HSA-MIR-17-5P	99.89	73.83	2665
HSA-MIR-106B-5P	99.88	74.72	2795
HSA-MIR-20A-5P	99.88	74.76	2769
HSA-MIR-20B-5P	99.88	74.01	2621
HSA-MIR-519D-3P	99.88	73.97	2607
HSA-MIR-526B-3P	99.88	74.06	2587
HSA-MIR-93-5P	99.88	73.98	2606
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-373-3P	99.84	70.68	1668
HSA-MIR-520E-3P	99.84	70.55	1698
HSA-MIR-372-3P	99.83	70.58	1691
HSA-MIR-520A-3P	99.83	70.59	1687
HSA-MIR-520B-3P	99.83	70.56	1699
HSA-MIR-520C-3P	99.83	70.56	1699
HSA-MIR-520D-3P	99.83	70.78	1676
HSA-MIR-2681-5P	99.75	67.64	1655
HSA-MIR-4306	99.72	70.50	3630
HSA-MIR-1296-3P	99.72	64.04	636
HSA-MIR-4729	99.69	72.18	4233

Literature-anchored findings (GeneRIF, showing 1)

• SAMP14 represents a GPI-anchored putative receptor in the Ly-6/uPAR family that is exposed on the inner acrosomal membrane after the acrosome reaction. (PMID:12788941)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	lye	ENSDARG00000116617
mus_musculus	Spaca4	ENSMUSG00000070563
rattus_norvegicus	Spaca4	ENSRNOG00000021037

Protein

Protein identifiers

Sperm acrosome membrane-associated protein 4 — Q8TDM5 (reviewed: Q8TDM5)

Alternative names: Sperm acrosomal membrane-associated protein 14

All UniProt accessions (2): Q8TDM5, A0A140VJU1

UniProt curated annotations — full annotation on UniProt →

Function. Sperm surface membrane protein that is essential for effective sperm-zona pellucida binding and penetration during fertilization.

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

Tissue specificity. Testis specific. Expressed in spermatozoa.

Similarity. Belongs to the SPACA4/bouncer family.

RefSeq proteins (1): NP_598005* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR016054	LY6_UPA_recep-like	Domain
IPR045860	Snake_toxin-like_sf	Homologous_superfamily
IPR046354	SPACA4/Bouncer	Family

Pfam: PF00021

UniProt features (10 total): disulfide bond 5, signal peptide 1, chain 1, propeptide 1, domain 1, lipid moiety-binding region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8TDM5-F1	81.89	0.54

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 (1): 97

Disulfide bonds (5): 23–47, 26–34, 41–65, 71–90, 91–96

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-163125	Post-translational modification: synthesis of GPI-anchored proteins
R-HSA-392499	Metabolism of proteins
R-HSA-597592	Post-translational protein modification

MSigDB gene sets: 61 (showing top): GSE45365_NK_CELL_VS_CD11B_DC_UP, GOBP_SINGLE_FERTILIZATION, GOCC_SECRETORY_GRANULE, GOBP_SPERM_EGG_RECOGNITION, WEBER_METHYLATED_LCP_IN_SPERM_UP, GOBP_FERTILIZATION, GOBP_CELL_CELL_RECOGNITION, GOBP_BINDING_OF_SPERM_TO_ZONA_PELLUCIDA, GOCC_ACROSOMAL_MEMBRANE, GOCC_SECRETORY_VESICLE, MARSON_BOUND_BY_FOXP3_UNSTIMULATED, GOCC_SECRETORY_GRANULE_MEMBRANE, GOCC_SIDE_OF_MEMBRANE, GOCC_ACROSOMAL_VESICLE, MOREAUX_MULTIPLE_MYELOMA_BY_TACI_UP

GO Biological Process (4): cell adhesion (GO:0007155), binding of sperm to zona pellucida (GO:0007339), fertilization (GO:0009566), sperm-egg recognition (GO:0035036)

GO Molecular Function (0):

GO Cellular Component (8): inner acrosomal membrane (GO:0002079), outer acrosomal membrane (GO:0002081), extracellular region (GO:0005576), plasma membrane (GO:0005886), membrane (GO:0016020), side of membrane (GO:0098552), acrosomal vesicle (GO:0001669), cytoplasmic vesicle (GO:0031410)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Post-translational protein modification	1
Metabolism of proteins	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
acrosomal membrane	2
cytoplasmic vesicle membrane	2
membrane	2
cellular process	1
sperm-egg recognition	1
sexual reproduction	1
reproductive process	1
single fertilization	1
cell-cell recognition	1
cell periphery	1
leaflet of membrane bilayer	1
secretory granule	1
cytoplasm	1
intracellular vesicle	1

Protein interactions and networks

STRING

498 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SPACA4	PLAUR	Q03405	820
SPACA4	SPATA3	Q8NHX4	677
SPACA4	TEX101	Q9BY14	660
SPACA4	LY6L	H3BQJ8	629
SPACA4	SPATS1	Q496A3	624
SPACA4	GARIN1B	Q96KD3	623
SPACA4	PATE3	B3GLJ2	620
SPACA4	LYPD5	Q6UWN5	595
SPACA4	LYPD4	Q6UWN0	585
SPACA4	TMEM225	Q6GV28	582
SPACA4	IZUMO1	Q8IYV9	576
SPACA4	PATE2	Q6UY27	575
SPACA4	LY6K	Q17RY6	573
SPACA4	PATE4	P0C8F1	573
SPACA4	SPACA1	Q9HBV2	571
SPACA4	PINLYP	A6NC86	571

IntAct

4 interactions, top by confidence:

A	B	Type	Score
SPACA4	GRN	psi-mi:“MI:0914”(association)	0.530
SPACA4	HSPA5	psi-mi:“MI:0914”(association)	0.350
TEX101	GGT3P	psi-mi:“MI:0914”(association)	0.350

BioGRID (15): MVK (Affinity Capture-MS), HSPA5 (Affinity Capture-MS), NIF3L1 (Affinity Capture-MS), FAM120A (Affinity Capture-MS), GRN (Affinity Capture-MS), MVK (Affinity Capture-MS), GRN (Affinity Capture-MS), NIF3L1 (Affinity Capture-MS), HSPA5 (Affinity Capture-MS), GALNS (Affinity Capture-MS), NLN (Affinity Capture-MS), SPACA4 (Affinity Capture-MS), NLN (Affinity Capture-MS), GRN (Affinity Capture-MS), MVK (Affinity Capture-MS)

ESM2 similar proteins: A0JNB3, A0JNL5, A6NC86, H3BJG9, H3BQJ8, O55186, O94772, O95867, P05533, P0CW02, P0CW03, P0DTL4, P13987, P35456, P35459, P35460, P35461, P46657, P47777, P49616, P57096, P58019, Q03405, Q05588, Q14210, Q148C3, Q28216, Q28785, Q32PB3, Q4R5M8, Q5R510, Q63317, Q64253, Q6UWN5, Q6UX82, Q80ZQ0, Q8K1T6, Q8SQ46, Q8TDM5, Q924B5

Diamond homologs: Q32PB3, Q80ZQ0, Q8TDM5

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	0
Likely pathogenic	0
Uncertain significance	1
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

334 predictions. Top by Δscore:

Variant	Effect	Δscore
19:48606924:G:GT	donor_gain	0.9500
19:48606742:ATT:A	donor_gain	0.9300
19:48606933:G:T	donor_gain	0.9200
19:48606845:G:T	donor_gain	0.9100
19:48606924:G:T	donor_gain	0.9100
19:48607656:CA:C	acceptor_gain	0.9000
19:48607657:A:C	acceptor_gain	0.8900
19:48607655:CCA:C	acceptor_gain	0.8400
19:48606802:A:AC	donor_gain	0.8200
19:48607664:A:C	acceptor_gain	0.8200
19:48606933:G:GT	donor_gain	0.8100
19:48607193:GCCTT:G	acceptor_gain	0.8000
19:48606803:G:C	donor_gain	0.7800
19:48606903:T:TA	donor_gain	0.7800
19:48606779:GCTC:G	donor_loss	0.7300
19:48606780:CT:C	donor_loss	0.7300
19:48606781:TCACC:T	donor_loss	0.7300
19:48606782:CACCT:C	donor_loss	0.7300
19:48606783:A:AA	donor_loss	0.7300
19:48606784:C:CT	donor_loss	0.7300
19:48606785:C:G	donor_loss	0.7300
19:48607288:A:T	acceptor_gain	0.7300
19:48607284:C:T	acceptor_gain	0.7200
19:48606778:CGCT:C	donor_loss	0.7100
19:48606786:T:C	donor_loss	0.7100
19:48607093:A:C	donor_gain	0.7100
19:48607280:G:GT	acceptor_gain	0.7100
19:48606846:AC:A	donor_gain	0.7000
19:48606847:CC:C	donor_gain	0.7000
19:48606836:C:CA	donor_gain	0.6900

AlphaMissense

794 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:48607120:T:C	F48L	0.986
19:48607122:C:A	F48L	0.986
19:48607122:C:G	F48L	0.986
19:48607168:G:T	G64C	0.984
19:48607228:T:G	Y84D	0.976
19:48607157:T:A	V60D	0.972
19:48607051:T:C	F25L	0.971
19:48607053:C:A	F25L	0.971
19:48607053:C:G	F25L	0.971
19:48607099:T:A	C41S	0.971
19:48607100:G:C	C41S	0.971
19:48607117:T:A	C47S	0.971
19:48607118:G:C	C47S	0.971
19:48607052:T:G	F25C	0.970
19:48607121:T:G	F48C	0.968
19:48607167:A:C	K63N	0.967
19:48607167:A:T	K63N	0.967
19:48607264:T:A	C96S	0.962
19:48607265:G:C	C96S	0.962
19:48607119:C:G	C47W	0.961
19:48607171:T:A	C65S	0.961
19:48607172:G:C	C65S	0.961
19:48607229:A:G	Y84C	0.958
19:48607100:G:A	C41Y	0.957
19:48607117:T:C	C47R	0.953
19:48607168:G:C	G64R	0.953
19:48607054:T:A	C26S	0.952
19:48607055:G:C	C26S	0.952
19:48607055:G:A	C26Y	0.950
19:48607189:T:A	C71S	0.948

dbSNP variants (sampled 300 via entrez): RS1002689455 (19:48606704 C>T), RS1003024631 (19:48606969 C>A,G), RS1004006337 (19:48606903 T>A,G), RS1004333733 (19:48606109 G>A,C,T), RS1005234034 (19:48607545 G>A), RS1005265258 (19:48607870 C>T), RS1006816234 (19:48607504 G>A), RS1008824377 (19:48604902 T>C), RS1008905475 (19:48606402 G>T), RS1010193990 (19:48606922 G>A), RS1011266113 (19:48606953 G>T), RS1011289808 (19:48606752 C>T), RS1011748165 (19:48606076 C>G,T), RS1011842971 (19:48605802 C>T), RS1012262568 (19:48606530 C>A,T)

Disease associations

OMIM: gene MIM:609932 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST010134_4	Non-oily fish consumption	3.000000e-16
GCST010135_4	Oily fish consumption	2.000000e-16
GCST010140_48	Pork consumption	2.000000e-16

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0008111	diet measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

8 total (human), top 8 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
aristolochic acid I	increases expression	1
urushiol	increases expression	1
jinfukang	decreases expression	1
Atrazine	increases expression	1
Cisplatin	decreases expression	1
Estradiol	increases expression	1
Tobacco Smoke Pollution	decreases expression	1
Valproic Acid	increases methylation	1

Clinical trials (associated diseases)

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