PRSS55

Summary

PRSS55 (serine protease 55, HGNC:30824) is a protein-coding gene on chromosome 8p23.1, encoding Serine protease 55 (Q6UWB4). Probable serine protease, which plays a crucial role in the fertility of male mice including sperm migration and sperm-egg interaction.

This gene encodes a member of a group of membrane-anchored chymotrypsin (S1)-like serine proteases. The enocoded protein is primarily expressed in the Leydig and Sertoli cells of the testis and may be involved in male fertility. Alternate splicing results in multiple transcript variants.

Source: NCBI Gene 203074 — RefSeq curated summary.

At a glance

• GWAS associations: 12
• Clinical variants (ClinVar): 4 total
• MANE Select transcript: NM_198464

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:30824
Approved symbol	PRSS55
Name	serine protease 55
Location	8p23.1
Locus type	gene with protein product
Status	Approved
Aliases	T-SP1, UNQ9391, CT153
Ensembl gene	ENSG00000184647
Ensembl biotype	protein_coding
OMIM	615144
Entrez	203074

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 2 protein_coding, 1 nonsense_mediated_decay

ENST00000328655, ENST00000518641, ENST00000522210

RefSeq mRNA: 2 — MANE Select: NM_198464 NM_001197020, NM_198464

CCDS: CCDS56523, CCDS5976

Canonical transcript exons

ENST00000328655 — 5 exons

Exon	Start	End
ENSE00001293055	10529507	10529699
ENSE00001800596	10538476	10538819
ENSE00002249594	10531295	10531545
ENSE00003545452	10532906	10533048
ENSE00003842310	10525532	10525739

Expression profiles

Bgee: expression breadth broad, 49 present calls, max score 90.86.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0223 / max 26.1629, expressed in 3 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
87368	0.0223	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	90.86	gold quality
right testis	UBERON:0004534	86.75	gold quality
left testis	UBERON:0004533	86.65	gold quality
testis	UBERON:0000473	85.95	gold quality
cerebellar cortex	UBERON:0002129	55.47	gold quality
cerebellar hemisphere	UBERON:0002245	55.47	gold quality
cerebellum	UBERON:0002037	55.44	gold quality
right hemisphere of cerebellum	UBERON:0014890	54.72	gold quality
primary visual cortex	UBERON:0002436	51.33	gold quality
amygdala	UBERON:0001876	47.66	gold quality
temporal lobe	UBERON:0001871	47.40	gold quality
Brodmann (1909) area 9	UBERON:0013540	46.62	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	46.12	gold quality
putamen	UBERON:0001874	46.01	gold quality
Ammon’s horn	UBERON:0001954	45.94	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	44.99	gold quality
cortex of kidney	UBERON:0001225	44.98	gold quality
caudate nucleus	UBERON:0001873	44.89	gold quality
anterior cingulate cortex	UBERON:0009835	44.79	gold quality
right frontal lobe	UBERON:0002810	44.71	gold quality
brain	UBERON:0000955	44.39	gold quality
adult mammalian kidney	UBERON:0000082	44.28	gold quality
substantia nigra	UBERON:0002038	44.12	gold quality
cerebral cortex	UBERON:0000956	43.62	gold quality
kidney	UBERON:0002113	43.10	gold quality
right lobe of liver	UBERON:0001114	42.50	silver quality
colonic epithelium	UBERON:0000397	42.17	gold quality
superior frontal gyrus	UBERON:0002661	42.06	gold quality
liver	UBERON:0002107	41.92	silver quality
frontal cortex	UBERON:0001870	41.65	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.15

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 1)

• T-SP1 protein was detectable in prostate cancer and in some ovarian cancer tissues, indicating tumor-related synthesis of T-SP1 (PMID:18844450)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	f9a	ENSDARG00000010097
danio_rerio	habp2	ENSDARG00000057498
mus_musculus	Prss55	ENSMUSG00000034623
rattus_norvegicus	Prss55	ENSRNOG00000047258
drosophila_melanogaster	CG31266	FBGN0051266
drosophila_melanogaster	CG31267	FBGN0051267

Paralogs (16): F7 (ENSG00000057593), F11 (ENSG00000088926), F9 (ENSG00000101981), HGFAC (ENSG00000109758), F10 (ENSG00000126218), KLK10 (ENSG00000129451), F12 (ENSG00000131187), C1RL (ENSG00000139178), C1R (ENSG00000159403), KLKB1 (ENSG00000164344), C1S (ENSG00000182326), CFD (ENSG00000197766), CFI (ENSG00000205403), PRSS51 (ENSG00000253649), HP (ENSG00000257017), HPR (ENSG00000261701)

Protein

Protein identifiers

Serine protease 55 — Q6UWB4 (reviewed: Q6UWB4)

Alternative names: Testis serine protease 1

All UniProt accessions (2): Q6UWB4, H0YBF5

UniProt curated annotations — full annotation on UniProt →

Function. Probable serine protease, which plays a crucial role in the fertility of male mice including sperm migration and sperm-egg interaction.

Subcellular location. Cell membrane. Cytoplasm. Cytosol Cytoplasm. Cytosol.

Tissue specificity. Only detected in testis. Expressed in spermatogonia, spermatocytes, spermatids, Leydig and Sertoli cells. Expressed in prostate cancer and ovarian cancer (at protein level).

Similarity. Belongs to the peptidase S1 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q6UWB4-1	1	yes
Q6UWB4-2	2

RefSeq proteins (2): NP_001183949, NP_940866* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001254	Trypsin_dom	Domain
IPR001314	Peptidase_S1A	Family
IPR009003	Peptidase_S1_PA	Homologous_superfamily
IPR018114	TRYPSIN_HIS	Active_site
IPR033116	TRYPSIN_SER	Active_site
IPR043504

Pfam: PF00089

UniProt features (19 total): disulfide bond 4, active site 3, sequence variant 2, signal peptide 1, chain 1, glycosylation site 1, splice variant 1, sequence conflict 1, propeptide 1, domain 1, region of interest 1, compositionally biased region 1, lipid moiety-binding region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6UWB4-F1	76.06	0.46

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 (3): 108 (charge relay system); 156 (charge relay system); 250 (charge relay system)

Post-translational modifications (1): 325

Disulfide bonds (4): 93–109, 189–256, 222–235, 246–276

Glycosylation sites (1): 240

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 42 (showing top): GOBP_SINGLE_FERTILIZATION, GOCC_SECRETORY_GRANULE, GOBP_PROTEIN_MATURATION, GOBP_CILIUM_MOVEMENT, GOBP_SPERM_EGG_RECOGNITION, GOBP_CILIUM_OR_FLAGELLUM_DEPENDENT_CELL_MOTILITY, GOBP_FERTILIZATION, GOBP_CELL_CELL_RECOGNITION, GOBP_BINDING_OF_SPERM_TO_ZONA_PELLUCIDA, GOCC_SECRETORY_VESICLE, GOCC_SIDE_OF_MEMBRANE, GOBP_PROTEOLYSIS, GOCC_ACROSOMAL_VESICLE, GOMF_PEPTIDASE_ACTIVITY, GOBP_PROTEIN_PROCESSING

GO Biological Process (3): proteolysis (GO:0006508), binding of sperm to zona pellucida (GO:0007339), flagellated sperm motility (GO:0030317)

GO Molecular Function (4): serine-type endopeptidase activity (GO:0004252), serine-type peptidase activity (GO:0008236), peptidase activity (GO:0008233), hydrolase activity (GO:0016787)

GO Cellular Component (6): acrosomal vesicle (GO:0001669), cytosol (GO:0005829), plasma membrane (GO:0005886), side of membrane (GO:0098552), cytoplasm (GO:0005737), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
membrane	2
protein metabolic process	1
sperm-egg recognition	1
cilium-dependent cell motility	1
cilium movement involved in cell motility	1
sperm motility	1
endopeptidase activity	1
serine-type peptidase activity	1
peptidase activity	1
serine hydrolase activity	1
hydrolase activity	1
catalytic activity, acting on a protein	1
catalytic activity	1
secretory granule	1
cytoplasm	1
cell periphery	1
leaflet of membrane bilayer	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

642 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PRSS55	PRSS37	A4D1T9	686
PRSS55	TSSK4	Q6SA08	558
PRSS55	TEX55	Q96M34	549
PRSS55	PDILT	Q8N807	547
PRSS55	SPMIP9	Q96LM6	539
PRSS55	TEX101	Q9BY14	532
PRSS55	RNASE10	Q5GAN6	530
PRSS55	FAM170B	A6NMN3	497
PRSS55	TPPP2	P59282	480
PRSS55	PMIS2	A0A1W2PS18	472
PRSS55	MAGEB10	Q96LZ2	451
PRSS55	RP1L1	Q8IWN7	447
PRSS55	CALR3	Q96L12	442
PRSS55	RCBTB2	O95199	436
PRSS55	ADAM2	P78326	428

IntAct

0 interactions, top by confidence:

ESM2 similar proteins: A0A1B0GVH4, A1L453, A4D1T9, A6H6T1, A8MTI9, A8QL53, A8QL57, B5U6Y3, E5RG02, O35453, O70169, P00745, P04070, P08709, P0CG03, P0DJE9, P22891, Q14BX2, Q28278, Q28661, Q2F9P2, Q2F9P4, Q2TV78, Q3V0Q7, Q402U7, Q4R7Y7, Q5FBW1, Q5M8S2, Q6AXZ6, Q6AY28, Q6IE62, Q6IE63, Q6PEW0, Q6UWB4, Q76HL1, Q7M756, Q7M761, Q7RTY5, Q7RTY7, Q7Z5A4

Diamond homologs: A0A182C2Z2, B8V7S0, O08762, O60235, P00747, P00760, P00762, P00765, P00766, P00767, P00774, P03951, P03952, P04070, P04813, P05981, P06867, P06871, P06872, P07146, P07338, P07477, P08217, P08426, P08519, P12545, P14272, P15944, P17538, P19799, P20231, P20918, P26262, P27435, P29786, P35033, P40313, P47796, P50342, P56677

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

4 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

608 predictions. Top by Δscore:

Variant	Effect	Δscore
8:10532898:T:TA	acceptor_gain	1.0000
8:10532899:G:A	acceptor_gain	1.0000
8:10532904:A:AG	acceptor_gain	1.0000
8:10532905:G:GG	acceptor_gain	1.0000
8:10532905:GCT:G	acceptor_gain	1.0000
8:10525737:GTG:G	donor_gain	0.9900
8:10525740:G:GG	donor_gain	0.9900
8:10525740:G:T	donor_loss	0.9900
8:10525741:T:G	donor_loss	0.9900
8:10525742:GAGTA:G	donor_loss	0.9900
8:10529506:GAAT:G	acceptor_gain	0.9900
8:10531278:T:A	acceptor_gain	0.9900
8:10531519:TGGC:T	donor_gain	0.9900
8:10532900:GGCCA:G	acceptor_loss	0.9900
8:10532901:GCCAG:G	acceptor_loss	0.9900
8:10532902:CCA:C	acceptor_loss	0.9900
8:10532903:CA:C	acceptor_loss	0.9900
8:10532904:AGCT:A	acceptor_gain	0.9900
8:10532905:GC:G	acceptor_gain	0.9900
8:10532905:GCTG:G	acceptor_gain	0.9900
8:10532905:GCTGA:G	acceptor_gain	0.9900
8:10532907:T:A	acceptor_gain	0.9900
8:10525743:AGTAC:A	donor_loss	0.9800
8:10529487:A:AG	acceptor_gain	0.9800
8:10529505:A:AG	acceptor_gain	0.9800
8:10529506:G:GG	acceptor_gain	0.9800
8:10529506:GA:G	acceptor_gain	0.9800
8:10531279:G:A	acceptor_gain	0.9800
8:10531293:A:AG	acceptor_gain	0.9800
8:10531294:G:GG	acceptor_gain	0.9800

AlphaMissense

2295 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
8:10531529:G:C	W194C	0.991
8:10531529:G:T	W194C	0.991
8:10529656:T:A	W102R	0.986
8:10529656:T:C	W102R	0.986
8:10529595:G:C	W81C	0.985
8:10529595:G:T	W81C	0.985
8:10531419:G:C	A158P	0.985
8:10529593:T:A	W81R	0.984
8:10529593:T:C	W81R	0.984
8:10531426:T:C	L160P	0.982
8:10529587:T:C	F79L	0.981
8:10529589:T:A	F79L	0.981
8:10529589:T:G	F79L	0.981
8:10533010:T:A	C235S	0.981
8:10533011:G:C	C235S	0.981
8:10538616:G:C	W294C	0.981
8:10538616:G:T	W294C	0.981
8:10529658:G:C	W102C	0.980
8:10529658:G:T	W102C	0.980
8:10538545:A:C	S271R	0.980
8:10538547:C:A	S271R	0.980
8:10538547:C:G	S271R	0.980
8:10531389:T:C	F148L	0.977
8:10531391:T:A	F148L	0.977
8:10531391:T:G	F148L	0.977
8:10531312:T:A	V122D	0.973
8:10531512:T:C	C189R	0.973
8:10531514:C:G	C189W	0.971
8:10538614:T:A	W294R	0.970
8:10538614:T:C	W294R	0.970

dbSNP variants (sampled 300 via entrez): RS1000147299 (8:10551701 T>C), RS1000188299 (8:10548042 G>A,C), RS1000254746 (8:10534792 G>A), RS1000311002 (8:10548233 G>A,C), RS1000405630 (8:10537599 T>C,G), RS1000411318 (8:10531005 C>T), RS1000586208 (8:10547399 G>C), RS1000686826 (8:10524257 G>A,C), RS1000748484 (8:10524763 C>G), RS1000782380 (8:10544310 C>A,G), RS1000906666 (8:10540645 G>A), RS1000965777 (8:10526658 G>C), RS1000990367 (8:10537704 C>G,T), RS1001123062 (8:10540852 G>A), RS1001166471 (8:10548081 T>C,G)

Disease associations

OMIM: gene MIM:615144 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

12 associations (top):

Study	Trait	p-value
GCST001762_543	Obesity-related traits	4.000000e-06
GCST007327_195	Smoking status (ever vs never smokers)	2.000000e-11
GCST007709_159	General factor of neuroticism	4.000000e-10
GCST007709_166	General factor of neuroticism	7.000000e-10
GCST010002_269	Refractive error	1.000000e-24
GCST010703_306	Brain morphology (MOSTest)	5.000000e-26
GCST011461_4	Barrett’s esophagus or Esophageal adenocarcinoma	7.000000e-09
GCST011462_4	Barrett’s esophagus or esophageal adenocarcinoma x sex interaction (2df test)	2.000000e-08
GCST012226_260	Waist circumference adjusted for body mass index	7.000000e-09
GCST012228_460	Waist-hip index	5.000000e-09
GCST012230_551	Waist-to-hip ratio adjusted for BMI	7.000000e-09
GCST012231_52	A body shape index	5.000000e-08

EFO canonical traits (6, from GWAS)

EFO ID	Trait name
EFO:0004318	smoking behavior
EFO:0007660	neuroticism measurement
EFO:0004346	neuroimaging measurement
EFO:0008343	sex interaction measurement
EFO:0007789	BMI-adjusted waist circumference
EFO:0007788	BMI-adjusted waist-hip ratio

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
pirinixic acid	affects binding, increases activity, increases expression	1
bisphenol A	affects cotreatment, decreases methylation	1
gallium arsenide	increases expression	1
Fulvestrant	affects cotreatment, decreases methylation	1
Benzo(a)pyrene	affects methylation, increases methylation	1
Lead	decreases expression	1
Permethrin	increases expression	1

Clinical trials (associated diseases)

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