SPACA6

Summary

SPACA6 (sperm acrosome associated 6, HGNC:27113) is a protein-coding gene on chromosome 19q13.41, encoding Sperm acrosome membrane-associated protein 6 (W5XKT8). Sperm protein required for fusion of sperm with the egg membrane during fertilization.

Enables protein-macromolecule adaptor activity. Involved in sperm-egg recognition. Is active in plasma membrane.

Source: NCBI Gene 147650 — RefSeq curated summary.

At a glance

• MANE Select transcript: NM_001316972

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:27113
Approved symbol	SPACA6
Name	sperm acrosome associated 6
Location	19q13.41
Locus type	gene with protein product
Status	Approved
Aliases	LET7EH
Ensembl gene	ENSG00000182310
Ensembl biotype	protein_coding
OMIM	618945
Entrez	147650

Gene structure

Transcript identifiers

Ensembl transcripts: 15 — 11 retained_intron, 3 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000571328, ENST00000572160, ENST00000572565, ENST00000572609, ENST00000572703, ENST00000573151, ENST00000573266, ENST00000573896, ENST00000574072, ENST00000576093, ENST00000576494, ENST00000576975, ENST00000637797, ENST00000646845, ENST00000710615

RefSeq mRNA: 2 — MANE Select: NM_001316972 NM_001316972, NM_001316994

CCDS: CCDS82386

Canonical transcript exons

ENST00000637797 — 9 exons

Exon	Start	End
ENSE00001309801	51693330	51693740
ENSE00003793845	51704030	51704186
ENSE00003797908	51703228	51703337
ENSE00003798561	51701658	51701726
ENSE00003798797	51704270	51704480
ENSE00003800112	51702629	51702652
ENSE00003800182	51703021	51703098
ENSE00004012587	51705090	51705190
ENSE00004012588	51694478	51694555

Expression profiles

Bgee: expression breadth ubiquitous, 163 present calls, max score 94.30.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 4.2893 / max 169.9771, expressed in 1406 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
177242	3.2767	1126
177241	0.4276	199
177237	0.2455	98
177240	0.2031	79
177238	0.1363	44

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
adenohypophysis	UBERON:0002196	94.30	gold quality
right ovary	UBERON:0002118	94.18	gold quality
sural nerve	UBERON:0015488	94.08	gold quality
left uterine tube	UBERON:0001303	93.99	gold quality
left ovary	UBERON:0002119	93.35	gold quality
body of uterus	UBERON:0009853	92.90	gold quality
right hemisphere of cerebellum	UBERON:0014890	92.87	gold quality
right adrenal gland cortex	UBERON:0035827	92.65	gold quality
right testis	UBERON:0004534	92.61	gold quality
left testis	UBERON:0004533	92.43	gold quality
right adrenal gland	UBERON:0001233	92.12	gold quality
cerebellar hemisphere	UBERON:0002245	92.03	gold quality
cerebellar cortex	UBERON:0002129	91.93	gold quality
endocervix	UBERON:0000458	91.63	gold quality
left adrenal gland cortex	UBERON:0035825	91.44	gold quality
pituitary gland	UBERON:0000007	91.26	gold quality
metanephros cortex	UBERON:0010533	91.21	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	91.21	gold quality
apex of heart	UBERON:0002098	91.19	gold quality
lower esophagus muscularis layer	UBERON:0035833	91.01	gold quality
lower esophagus	UBERON:0013473	90.97	gold quality
left adrenal gland	UBERON:0001234	90.92	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	90.29	gold quality
ascending aorta	UBERON:0001496	90.22	gold quality
cerebellum	UBERON:0002037	90.17	gold quality
thoracic aorta	UBERON:0001515	90.12	gold quality
descending thoracic aorta	UBERON:0002345	90.05	gold quality
right lobe of thyroid gland	UBERON:0001119	89.88	gold quality
ectocervix	UBERON:0012249	89.88	gold quality
adrenal cortex	UBERON:0001235	89.65	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	2.91
E-MTAB-6379	no	43.04

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 2)

• Sperm SPACA6 protein is required for mammalian Sperm-Egg Adhesion/Fusion. (PMID:32210282)
• SPACA6 ectodomain structure reveals a conserved superfamily of gamete fusion-associated proteins. (PMID:36115925)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Spaca6	ENSMUSG00000080316
rattus_norvegicus	Spaca6	ENSRNOG00000039076

Protein

Protein identifiers

Sperm acrosome membrane-associated protein 6 — W5XKT8 (reviewed: W5XKT8)

Alternative names: BACHELOR-like protein

All UniProt accessions (3): W5XKT8, A0A2R8Y8C0, A0AA34QVJ1

UniProt curated annotations — full annotation on UniProt →

Function. Sperm protein required for fusion of sperm with the egg membrane during fertilization. May regulate the expression of sperm surface protein DCST2.

Subunit / interactions. Forms a complex with IZUMO1 and TMEM81 on spermatocyte cell membrane required for fertilization.

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

Tissue specificity. Detected at the sperm head, equatorial region, neck and midpiece (at protein level). Expressed in testis.

Domain organisation. The extracellular domain shows strong structural similarity with IZUMO1 but does not interact with the IZUMO1 receptor IZUMO1R/JUNO.

Miscellaneous. Due to intron retention. Due to intron retention.

Similarity. Belongs to the SPACA6 family.

Isoforms (3)

UniProt ID	Names	Canonical?
W5XKT8-1	1	yes
W5XKT8-2	2
W5XKT8-3	3

RefSeq proteins (2): NP_001303901, NP_001303923 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR007110	Ig-like_dom	Domain
IPR013783	Ig-like_fold	Homologous_superfamily
IPR034549	SPACA6	Family
IPR036179	Ig-like_dom_sf	Homologous_superfamily

UniProt features (41 total): helix 10, strand 9, disulfide bond 6, splice variant 4, sequence conflict 2, topological domain 2, short sequence motif 2, signal peptide 1, chain 1, transmembrane region 1, turn 1, domain 1, glycosylation site 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
7TA2	X-RAY DIFFRACTION	2.25

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-W5XKT8-F1	87.11	0.66

Functional residue map

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

Disulfide bonds (6): 30–142, 41–55, 124–147, 128–153, 170–226, 27–139

Glycosylation sites (1): 243

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 82 (showing top): GOBP_SINGLE_FERTILIZATION, MYOGENIN_Q6, GOCC_SECRETORY_GRANULE, GOBP_MEMBRANE_FUSION, GOBP_PLASMA_MEMBRANE_ORGANIZATION, AREB6_01, AP2_Q3, TCGATGG_MIR213, FONTAINE_PAPILLARY_THYROID_CARCINOMA_UP, GATA1_01, HEN1_01, GOBP_SPERM_EGG_RECOGNITION, GOBP_CELLULAR_PROCESS_INVOLVED_IN_REPRODUCTION_IN_MULTICELLULAR_ORGANISM, PPAR_DR1_Q2, GOBP_ENDOMEMBRANE_SYSTEM_ORGANIZATION

GO Biological Process (3): fusion of sperm to egg plasma membrane involved in single fertilization (GO:0007342), sperm-egg recognition (GO:0035036), single fertilization (GO:0007338)

GO Molecular Function (2): protein-macromolecule adaptor activity (GO:0030674), protein binding (GO:0005515)

GO Cellular Component (5): acrosomal membrane (GO:0002080), plasma membrane (GO:0005886), acrosomal vesicle (GO:0001669), membrane (GO:0016020), cytoplasmic vesicle (GO:0031410)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
single fertilization	2
cellular process involved in reproduction in multicellular organism	1
cell-cell recognition	1
fertilization	1
protein binding	1
molecular adaptor activity	1
binding	1
acrosomal vesicle	1
secretory granule membrane	1
membrane	1
cell periphery	1
secretory granule	1
cellular anatomical structure	1
cytoplasm	1
intracellular vesicle	1

Protein interactions and networks

STRING

1297 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SPACA6	TMEM95	Q3KNT9	909
SPACA6	IZUMO1	Q8IYV9	812
SPACA6	DCST2	Q5T1A1	747
SPACA6	DCST1	Q5T197	692
SPACA6	TSSK6	Q9BXA6	617
SPACA6	IZUMO1R	A6ND01	585
SPACA6	MYO15B	Q96JP2	543
SPACA6	SOFU1	Q96L11	541
SPACA6	SPATA3	Q8NHX4	525
SPACA6	SPACA4	Q8TDM5	507
SPACA6	OR7E24	Q6IFN5	480
SPACA6	SPACA1	Q9HBV2	468
SPACA6	GPSM1	Q86YR5	460
SPACA6	CD9	P21926	446
SPACA6	FIMP1	Q96LL3	430

IntAct

4 interactions, top by confidence:

A	B	Type	Score
BANP	SPACA6	psi-mi:“MI:0915”(physical association)	0.560
SPACA6	BANP	psi-mi:“MI:0915”(physical association)	0.560
CNTN5	SPACA6	psi-mi:“MI:0915”(physical association)	0.400

ESM2 similar proteins: A0A1B0GUA7, A0A3Q1LRJ2, A2T6Z6, E9Q8Q8, O46673, O77049, O88823, P01588, P07865, P22301, P29676, P43480, P46651, P48411, P51496, P51497, P51746, P55029, P79338, Q0Z972, Q25BC1, Q28374, Q28C41, Q2PE73, Q3KNT9, Q4VK74, Q5Q0V6, Q5ZJY9, Q6A2H4, Q6AY06, Q6H8S9, Q6H8T0, Q6H8T1, Q6H8T2, Q6UXV1, Q865X4, Q8BGT0, Q8CGK6, Q8CJ70, Q8IU54

Diamond homologs: E9Q8Q8, W5XKT8

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

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

Top pathogenic / likely-pathogenic (0)

SpliceAI

0 predictions. Top by Δscore:

AlphaMissense

2094 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:51703319:G:C	W185C	0.998
19:51703319:G:T	W185C	0.998
19:51703317:T:A	W185R	0.997
19:51703317:T:C	W185R	0.997
19:51703273:G:A	C170Y	0.995
19:51704133:G:A	C226Y	0.995
19:51703274:C:G	C170W	0.994
19:51704132:T:A	C226S	0.994
19:51704133:G:C	C226S	0.994
19:51704134:C:G	C226W	0.994
19:51703045:T:G	F137C	0.993
19:51703267:T:G	F168C	0.993
19:51703272:T:A	C170S	0.993
19:51703272:T:C	C170R	0.993
19:51703273:G:C	C170S	0.993
19:51703285:T:G	F174C	0.993
19:51704132:T:C	C226R	0.993
19:51703267:T:C	F168S	0.991
19:51704055:T:G	F200C	0.991
19:51703273:G:T	C170F	0.990
19:51703284:T:C	F174L	0.990
19:51703286:C:A	F174L	0.990
19:51703286:C:G	F174L	0.990
19:51704133:G:T	C226F	0.990
19:51703318:G:C	W185S	0.989
19:51703044:T:C	F137L	0.988
19:51703046:C:A	F137L	0.988
19:51703046:C:G	F137L	0.988
19:51703092:T:C	C153R	0.988
19:51704126:T:C	F224L	0.988

dbSNP variants (sampled 300 via entrez): RS1000008875 (19:51707601 C>A,T), RS1000024807 (19:51701726 G>A), RS1000035470 (19:51705721 C>G,T), RS1000093001 (19:51690919 G>GA), RS1000157128 (19:51687100 G>C), RS1000434608 (19:51712610 G>A,T), RS1000530637 (19:51689379 CGCAGAGCCGGGG>C), RS1000530929 (19:51692052 G>A), RS1000556563 (19:51700946 G>A), RS1000599205 (19:51707120 G>A,T), RS1000601776 (19:51689191 G>T), RS1000627040 (19:51697583 T>C,G), RS1000643764 (19:51694882 C>G), RS1000647040 (19:51692365 G>A), RS1000774886 (19:51694658 G>A)

Disease associations

OMIM: gene MIM:618945 | 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

29 total (human), top 29 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, affects cotreatment, increases abundance, increases expression	3
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
propionaldehyde	decreases expression	1
2,5,2’,5’-tetrachlorobiphenyl	decreases expression	1
tris(2-butoxyethyl) phosphate	affects expression	1
sulforaphane	decreases expression	1
butyraldehyde	decreases expression	1
pentanal	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
ICG 001	decreases expression	1
Temozolomide	decreases expression	1
Arsenic Trioxide	decreases expression	1
Air Pollutants	decreases expression, increases abundance	1
Aldehydes	decreases expression	1
Arsenic	increases expression, affects cotreatment, decreases expression, increases abundance	1
Cisplatin	decreases expression	1
Estradiol	decreases expression	1
Polychlorinated Biphenyls	affects expression	1
Silicon Dioxide	decreases expression	1
Smoke	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Valproic Acid	increases methylation	1
Aflatoxin B1	decreases methylation	1
Cadmium Chloride	increases expression	1
Copper Sulfate	increases expression	1
Lactic Acid	increases expression	1
Acrylamide	decreases expression	1
Particulate Matter	decreases expression, increases abundance	1

Clinical trials (associated diseases)

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