SPESP1

Summary

SPESP1 (sperm equatorial segment protein 1, HGNC:15570) is a protein-coding gene on chromosome 15q23, encoding Sperm equatorial segment protein 1 (Q6UW49). Involved in fertilization ability of sperm.

The encoded protein is a human alloantigen involved in sperm-egg binding and fusion.

Source: NCBI Gene 246777 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 53 total
• MANE Select transcript: NM_145658

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:15570
Approved symbol	SPESP1
Name	sperm equatorial segment protein 1
Location	15q23
Locus type	gene with protein product
Status	Approved
Aliases	SP-ESP
Ensembl gene	ENSG00000258484
Ensembl biotype	protein_coding
OMIM	609399
Entrez	246777

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 4 protein_coding, 2 protein_coding_CDS_not_defined

ENST00000310673, ENST00000560188, ENST00000561467, ENST00000864106, ENST00000965693, ENST00000965694

RefSeq mRNA: 1 — MANE Select: NM_145658 NM_145658

CCDS: CCDS10230

Canonical transcript exons

ENST00000310673 — 2 exons

Exon	Start	End
ENSE00001180456	68945599	68946811
ENSE00002571115	68930525	68930717

Expression profiles

Bgee: expression breadth ubiquitous, 190 present calls, max score 94.73.

FANTOM5 (CAGE): breadth broad, TPM avg 2.7570 / max 186.7492, expressed in 851 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
147424	2.7570	851
147421	1.6429	889
147425	0.1864	80

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sperm	CL:0000019	94.73	gold quality
right testis	UBERON:0004534	93.69	gold quality
left testis	UBERON:0004533	93.56	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	93.10	gold quality
testis	UBERON:0000473	92.47	gold quality
adult organism	UBERON:0007023	85.51	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	85.20	gold quality
placenta	UBERON:0001987	81.06	gold quality
calcaneal tendon	UBERON:0003701	75.65	gold quality
secondary oocyte	CL:0000655	73.88	gold quality
islet of Langerhans	UBERON:0000006	73.38	gold quality
right adrenal gland cortex	UBERON:0035827	73.37	gold quality
left ventricle myocardium	UBERON:0006566	72.94	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	72.31	gold quality
gall bladder	UBERON:0002110	71.65	gold quality
right atrium auricular region	UBERON:0006631	71.17	gold quality
cardiac atrium	UBERON:0002081	70.95	gold quality
cortical plate	UBERON:0005343	70.95	gold quality
heart right ventricle	UBERON:0002080	70.85	silver quality
right adrenal gland	UBERON:0001233	70.68	gold quality
right coronary artery	UBERON:0001625	70.64	gold quality
left adrenal gland	UBERON:0001234	69.96	gold quality
spinal cord	UBERON:0002240	69.94	gold quality
hindlimb stylopod muscle	UBERON:0004252	69.88	gold quality
cauda epididymis	UBERON:0004360	69.59	silver quality
mucosa of transverse colon	UBERON:0004991	69.49	gold quality
corpus epididymis	UBERON:0004359	69.10	gold quality
metanephros cortex	UBERON:0010533	68.71	gold quality
smooth muscle tissue	UBERON:0001135	68.70	gold quality
adrenal tissue	UBERON:0018303	68.66	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-GEOD-134144	yes	31.04
E-ANND-3	no	2.02

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

23 targeting SPESP1, 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-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-96-5P	99.95	72.80	2140
HSA-MIR-12133	99.92	71.82	2006
HSA-MIR-1271-5P	99.91	71.99	1972
HSA-MIR-4671-3P	99.88	72.46	1045
HSA-MIR-6885-3P	99.75	70.36	3187
HSA-MIR-6505-5P	99.73	69.25	1595
HSA-MIR-425-5P	99.59	67.67	900
HSA-MIR-4643	99.49	67.63	1791
HSA-MIR-122B-5P	99.46	70.81	1457
HSA-MIR-5697	99.39	67.74	1249
HSA-MIR-329-5P	99.27	68.11	1597
HSA-MIR-642A-3P	99.23	67.67	1258
HSA-MIR-642B-3P	99.23	67.67	1258
HSA-MIR-4279	99.19	66.70	2437
HSA-MIR-4464	98.95	67.73	820
HSA-MIR-4748	98.95	67.53	810
HSA-MIR-7158-3P	98.46	66.45	728
HSA-MIR-34A-3P	96.80	67.70	805

Literature-anchored findings (GeneRIF, showing 4)

• Equatorial segment protein (ESP), a novel 349-amino acid concanavalin-A-binding protein encoded by a two-exon gene (SP-ESP) located on chromosome 15 at q22, has been localized to the equatorial segment of ejaculated human sperm. (PMID:12773409)
• human alloantigen involved in sperm-egg binding and fusion (PMID:17978344)
• A stealth antigen SPESP1, which is epigenetically silenced in tumors, is a suitable target for cancer immunotherapy. (PMID:34009705)
• Testosterone enhances taurine synthesis by upregulating androgen receptor and cysteine sulfinic acid decarboxylase expressions in male mouse liver. (PMID:36749568)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Spesp1	ENSMUSG00000046846
rattus_norvegicus	Spesp1	ENSRNOG00000025359

Protein

Protein identifiers

Sperm equatorial segment protein 1 — Q6UW49 (reviewed: Q6UW49)

Alternative names: Equatorial segment protein, Glycosylated 38 kDa sperm protein C-7/8

All UniProt accessions (1): Q6UW49

UniProt curated annotations — full annotation on UniProt →

Function. Involved in fertilization ability of sperm.

Subcellular location. Cytoplasmic vesicle. Secretory vesicle. Acrosome.

Tissue specificity. Highly expressed in testis, where it is localized in the acrosome of postmeiotic stages of spermiogenesis (round and elongating spermatids and in ejaculated spermatozoa) (at protein level). Poorly expressed in placenta and fetal lung.

Post-translational modifications. Glycosylated. In testis there are two predominant forms of 77- and 67-kDa and a form of 47-kDa, whereas in epididymal sperm from caput, corpus, and cauda there are two forms of 47- and 43-kDa. Testis forms contain complex carbohydrate residues. Epididymal sperm forms are N-glycosylated. Then undergoes significant glycosylation in the testis and that the majority of these glycoconjugates are removed by the time sperm reach the caput epididymis.

Similarity. Belongs to the SPESP1 family.

RefSeq proteins (1): NP_663633* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR026743	Equatorial_segment	Family

Pfam: PF15754

UniProt features (9 total): sequence variant 3, sequence conflict 3, signal peptide 1, chain 1, glycosylation site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6UW49-F1	57.69	0.09

Functional residue map

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

Glycosylation sites (1): 128

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 68 (showing top): GOBP_SINGLE_FERTILIZATION, GOCC_SECRETORY_GRANULE, GOBP_MEMBRANE_FUSION, GOBP_PLASMA_MEMBRANE_ORGANIZATION, MARTINEZ_RB1_TARGETS_UP, MARTINEZ_RB1_TARGETS_DN, GOBP_SPERM_EGG_RECOGNITION, GOBP_CELLULAR_PROCESS_INVOLVED_IN_REPRODUCTION_IN_MULTICELLULAR_ORGANISM, GOBP_ENDOMEMBRANE_SYSTEM_ORGANIZATION, GOBP_ACROSOME_REACTION, GOBP_PLASMA_MEMBRANE_FUSION, GOBP_MEMBRANE_ORGANIZATION, GOBP_FERTILIZATION, chr15q23, VECCHI_GASTRIC_CANCER_EARLY_DN

GO Biological Process (4): acrosome reaction (GO:0007340), fusion of sperm to egg plasma membrane involved in single fertilization (GO:0007342), fertilization (GO:0009566), sperm-egg recognition (GO:0035036)

GO Molecular Function (0):

GO Cellular Component (5): acrosomal vesicle (GO:0001669), microtubule cytoskeleton (GO:0015630), intercellular bridge (GO:0045171), mitotic spindle (GO:0072686), cytoplasmic vesicle (GO:0031410)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
single fertilization	3
reproductive process	2
membrane fusion involved in acrosome reaction	1
acrosomal vesicle exocytosis	1
cellular process involved in reproduction in multicellular organism	1
sexual reproduction	1
cell-cell recognition	1
secretory granule	1
cytoskeleton	1
cellular anatomical structure	1
spindle	1
cytoplasm	1
intracellular vesicle	1

Protein interactions and networks

STRING

468 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SPESP1	ZPBP	Q9BS86	681
SPESP1	SPACA1	Q9HBV2	664
SPESP1	ZAN	Q9Y493	664
SPESP1	IZUMO1	Q8IYV9	581
SPESP1	SPACA3	Q8IXA5	573
SPESP1	SPAM1	P38567	547
SPESP1	ZP1	P60852	544
SPESP1	ODF1	Q14990	499
SPESP1	IZUMO4	Q1ZYL8	495
SPESP1	TSSK4	Q6SA08	485
SPESP1	ZP4	Q12836	460
SPESP1	ACRBP	Q8NEB7	454
SPESP1	SPATA6	Q9NWH7	451
SPESP1	C11orf42	Q8N5U0	447
SPESP1	IGSF8	Q969P0	425

IntAct

0 interactions, top by confidence:

BioGRID (3): SPESP1 (Synthetic Growth Defect), SPESP1 (Affinity Capture-RNA), SPESP1 (Affinity Capture-Luminescence)

ESM2 similar proteins: A0A023PZB3, A0A182BSS2, A0A1B0GVD1, A0A3B7TNM4, B8QCG6, D3Z0R2, F4JYJ1, F5GUE5, H2A0P2, O32528, O56774, O62688, O62689, O62690, O94262, P0CV29, P0DMD1, P22388, P32772, P34290, P34507, P34566, P34890, P40745, P53074, P92560, Q00997, Q03233, Q03703, Q03937, Q09220, Q09280, Q09953, Q12418, Q19541, Q1KN19, Q1X6X8, Q3V0X1, Q54IV8, Q5I123

Diamond homologs: A0JPP4, Q32KL7, Q6UW49, Q95LJ2, Q9D5A0

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	49
Likely benign	4
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

714 predictions. Top by Δscore:

Variant	Effect	Δscore
15:68820696:A:AC	donor_gain	1.0000
15:68820697:C:CC	donor_gain	1.0000
15:68820697:CAT:C	donor_gain	1.0000
15:68820709:T:TA	donor_gain	1.0000
15:68930716:GA:G	donor_gain	1.0000
15:68930718:G:GG	donor_gain	1.0000
15:68820692:GCTCA:G	donor_loss	0.9900
15:68820693:CTCA:C	donor_loss	0.9900
15:68820694:TCAC:T	donor_loss	0.9900
15:68820696:ACAT:A	donor_gain	0.9900
15:68820696:ACATC:A	donor_loss	0.9900
15:68820697:C:CG	donor_loss	0.9900
15:68820697:CA:C	donor_gain	0.9900
15:68820697:CATC:C	donor_gain	0.9900
15:68818668:T:A	donor_gain	0.9800
15:68820697:CATCA:C	donor_gain	0.9800
15:68930713:TCCGA:T	donor_gain	0.9800
15:68930714:CCGAG:C	donor_loss	0.9800
15:68930715:CGAGT:C	donor_loss	0.9800
15:68930716:GAGT:G	donor_loss	0.9800
15:68930717:AG:A	donor_loss	0.9800
15:68930718:G:T	donor_loss	0.9800
15:68930719:T:G	donor_loss	0.9800
15:68930720:G:GG	donor_loss	0.9800
15:68930931:G:T	donor_gain	0.9800
15:68931061:C:G	donor_gain	0.9800
15:68820690:ATGCT:A	donor_loss	0.9700
15:68930656:G:GT	donor_gain	0.9700
15:68930715:CGA:C	donor_gain	0.9700
15:68930716:GAG:G	donor_gain	0.9700

AlphaMissense

2269 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
15:68946345:G:C	A271P	0.982
15:68945895:T:C	F121L	0.977
15:68945897:C:A	F121L	0.977
15:68945897:C:G	F121L	0.977
15:68945900:G:C	W122C	0.972
15:68945900:G:T	W122C	0.972
15:68946322:G:C	R263P	0.972
15:68946342:G:C	A270P	0.972
15:68946336:G:C	A268P	0.971
15:68946316:T:C	L261P	0.968
15:68945898:T:A	W122R	0.966
15:68945898:T:C	W122R	0.966
15:68945662:T:C	L43P	0.965
15:68946490:T:A	V319D	0.959
15:68946358:T:C	L275S	0.956
15:68946334:T:C	L267P	0.951
15:68946330:G:C	A266P	0.947
15:68946442:T:C	L303P	0.946
15:68946442:T:A	L303Q	0.944
15:68945932:T:C	L133S	0.942
15:68946328:T:C	L265P	0.942
15:68945653:T:C	L40S	0.941
15:68946324:A:C	S264R	0.938
15:68946326:C:A	S264R	0.938
15:68946326:C:G	S264R	0.938
15:68946339:G:C	A269P	0.936
15:68946223:T:C	I230T	0.931
15:68946535:T:C	L334S	0.929
15:68946442:T:G	L303R	0.927
15:68945896:T:G	F121C	0.916

dbSNP variants (sampled 300 via entrez): RS1000107522 (15:68944899 ACT>A), RS1000132071 (15:68939082 G>A), RS1000145988 (15:68929681 T>C), RS1000342206 (15:68942500 C>T), RS1000415861 (15:68942231 T>G), RS1000526810 (15:68941038 A>G), RS1000683104 (15:68934528 A>G), RS1000703577 (15:68933393 T>C), RS1000755147 (15:68934154 G>A,T), RS1000758559 (15:68940637 A>G), RS1000761327 (15:68934976 T>C,G), RS1000898071 (15:68929146 C>T), RS1000979324 (15:68941247 ATGC>A), RS1001351313 (15:68943912 G>A), RS1001368630 (15:68936434 T>A,C)

Disease associations

OMIM: gene MIM:609399 | 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

7 total (human), top 7 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression	1
Doxorubicin	decreases expression	1
Rotenone	decreases expression	1
Silicon Dioxide	decreases expression	1
Smoke	decreases expression	1
Valproic Acid	increases expression, increases methylation	1
Cadmium Chloride	decreases expression	1

Clinical trials (associated diseases)

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