PRSS58

Summary

PRSS58 (serine protease 58, HGNC:39125) is a protein-coding gene on chromosome 7q34, encoding Serine protease 58 (Q8IYP2).

This gene encodes a member of the trypsin family of serine proteases. This gene and several related trypsinogen genes are localized to the T cell receptor beta locus on chromosome 7. This gene was previously described as a trypsinogen-like pseudogene, but it is now thought to be a protein-coding gene.

Source: NCBI Gene 136541 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 44 total
• MANE Select transcript: NM_001001317

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:39125
Approved symbol	PRSS58
Name	serine protease 58
Location	7q34
Locus type	gene with protein product
Status	Approved
Aliases	TRYX3
Ensembl gene	ENSG00000258223
Ensembl biotype	protein_coding
Entrez	136541

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000547058, ENST00000552471

RefSeq mRNA: 1 — MANE Select: NM_001001317 NM_001001317

CCDS: CCDS5871

Canonical transcript exons

ENST00000547058 — 6 exons

Exon	Start	End
ENSE00001864190	142252143	142252370
ENSE00002346052	142255055	142255311
ENSE00002346873	142257668	142257748
ENSE00002373941	142257991	142258058
ENSE00002414149	142255535	142255673
ENSE00002414800	142252472	142252611

Expression profiles

Bgee: expression breadth broad, 21 present calls, max score 94.12.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0317 / max 30.6012, expressed in 3 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
86604	0.0262	3
86605	0.0055	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	94.12	gold quality
left testis	UBERON:0004533	85.22	gold quality
testis	UBERON:0000473	84.55	gold quality
right testis	UBERON:0004534	84.18	gold quality
smooth muscle tissue	UBERON:0001135	40.62	gold quality
blood	UBERON:0000178	38.93	gold quality
colonic epithelium	UBERON:0000397	37.20	gold quality
ventricular zone	UBERON:0003053	36.48	gold quality
cortical plate	UBERON:0005343	36.47	gold quality
bone marrow cell	CL:0002092	36.16	gold quality
body of pancreas	UBERON:0001150	35.85	silver quality
ganglionic eminence	UBERON:0004023	35.49	gold quality
muscle tissue	UBERON:0002385	34.93	gold quality
pancreas	UBERON:0001264	33.67	silver quality
myometrium	UBERON:0001296	33.50	gold quality
skeletal muscle tissue	UBERON:0001134	33.38	gold quality
hindlimb stylopod muscle	UBERON:0004252	32.15	gold quality
bone marrow	UBERON:0002371	31.74	gold quality
sural nerve	UBERON:0015488	30.93	gold quality
monocyte	CL:0000576	30.00	gold quality
stromal cell of endometrium	CL:0002255	29.87	gold quality
prefrontal cortex	UBERON:0000451	29.79	gold quality
leukocyte	CL:0000738	29.78	gold quality
liver	UBERON:0002107	28.91	gold quality
tonsil	UBERON:0002372	28.77	gold quality
duodenum	UBERON:0002114	28.14	gold quality
uterine cervix	UBERON:0000002	27.77	gold quality
lymph node	UBERON:0000029	27.57	gold quality
left uterine tube	UBERON:0001303	27.36	silver quality
endocervix	UBERON:0000458	26.76	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Cross-species orthologs

14 orthologs

Organism	Symbol	Gene ID
danio_rerio	hp	ENSDARG00000051890
mus_musculus	Prss58	ENSMUSG00000051936
rattus_norvegicus	Prss58	ENSRNOG00000013132
drosophila_melanogaster	CG9673	FBGN0030775
drosophila_melanogaster	CG4477	FBGN0035971
drosophila_melanogaster	CG17404	FBGN0038001
drosophila_melanogaster	CG12256	FBGN0038002
drosophila_melanogaster	CG3916	FBGN0038003
drosophila_melanogaster	CG17477	FBGN0038479
drosophila_melanogaster	CG4053	FBGN0038482
drosophila_melanogaster	CG31269	FBGN0051269
drosophila_melanogaster	CG32808	FBGN0052808
drosophila_melanogaster	Phae2	FBGN0263235
drosophila_melanogaster	Send2	FBGN0264253

Paralogs (12): PRSS54 (ENSG00000103023), KLK14 (ENSG00000129437), KLK8 (ENSG00000129455), TMPRSS4 (ENSG00000137648), KLK3 (ENSG00000142515), KLK1 (ENSG00000167748), KLK4 (ENSG00000167749), KLK2 (ENSG00000167751), KLK5 (ENSG00000167754), KLK11 (ENSG00000167757), KLK7 (ENSG00000169035), KLK12 (ENSG00000186474)

Protein

Protein identifiers

Serine protease 58 — Q8IYP2 (reviewed: Q8IYP2)

Alternative names: Trypsin-X3

All UniProt accessions (1): Q8IYP2

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Secreted.

Similarity. Belongs to the peptidase S1 family.

RefSeq proteins (1): NP_001001317* (*=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
IPR043504

Pfam: PF00089

UniProt features (12 total): disulfide bond 4, active site 3, glycosylation site 2, signal peptide 1, chain 1, domain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8IYP2-F1	90.25	0.83

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): 56 (charge relay system); 101 (charge relay system); 195 (charge relay system)

Disulfide bonds (4): 165–180, 191–215, 41–57, 133–201

Glycosylation sites (2): 156, 173

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 44 (showing top): GSE45365_NK_CELL_VS_CD8_TCELL_UP, GOBP_POSITIVE_REGULATION_OF_REPRODUCTIVE_PROCESS, GOCC_SECRETORY_GRANULE, GOBP_PROTEIN_MATURATION, GOBP_REGULATION_OF_REPRODUCTIVE_PROCESS, GOCC_SECRETORY_VESICLE, GOBP_PROTEOLYSIS, GOMF_PEPTIDASE_ACTIVITY, YAO_TEMPORAL_RESPONSE_TO_PROGESTERONE_CLUSTER_2, GSE13522_CTRL_VS_T_CRUZI_G_STRAIN_INF_SKIN_DN, ZNF486_TARGET_GENES, GSE13485_DAY1_VS_DAY21_YF17D_VACCINE_PBMC_UP, GSE13738_RESTING_VS_BYSTANDER_ACTIVATED_CD4_TCELL_UP, GSE15659_TREG_VS_TCONV_UP, GSE15930_STIM_VS_STIM_AND_IFNAB_24H_CD8_T_CELL_DN

GO Biological Process (3): proteolysis (GO:0006508), protein maturation (GO:0051604), positive regulation of reproductive process (GO:2000243)

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

GO Cellular Component (3): obsolete extracellular space (GO:0005615), secretory granule (GO:0030141), extracellular region (GO:0005576)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein metabolic process	2
gene expression	1
reproductive process	1
positive regulation of biological process	1
regulation of reproductive process	1
endopeptidase activity	1
serine-type peptidase activity	1
hydrolase activity	1
catalytic activity, acting on a protein	1
peptidase activity	1
serine hydrolase activity	1
catalytic activity	1
endomembrane system	1
secretory vesicle	1
cellular anatomical structure	1

Protein interactions and networks

STRING

900 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PRSS58	SPINK1	P00995	944
PRSS58	PALB2	Q86YC2	787
PRSS58	HTRA4	P83105	769
PRSS58	STK11	Q15831	725
PRSS58	CFTR	P13569	696
PRSS58	HOXA6	P31267	641
PRSS58	PRSS1	P07477	631
PRSS58	CPA1	P15085	630
PRSS58	PALLD	Q8WX93	626
PRSS58	BRCA2	P51587	621
PRSS58	CDKN2A	P42771	570
PRSS58	PMS2	P54278	567
PRSS58	HOXA4	Q00056	549
PRSS58	MLH1	P40692	542
PRSS58	MSH2	P43246	541

IntAct

0 interactions, top by confidence:

BioGRID (1): PRSS58 (Affinity Capture-MS)

ESM2 similar proteins: A0A1I9KNP0, A4D1T9, A8QL53, A8QL57, B0ZT25, D8MIA0, D8MIA1, D8MIA2, D8MIA3, E5AJX2, E5L0E3, J3S832, J3S833, O13058, O13062, O13069, O93267, P00739, P06866, P0CG03, P11033, P19007, P47797, Q072L6, Q32KU2, Q32LI2, Q4R7Y7, Q5R5F6, Q60574, Q61646, Q62558, Q6IE06, Q6P326, Q6T6S7, Q71QH5, Q71QI2, Q71QI4, Q71QI5, Q71QI7, Q71QJ0

Diamond homologs: A4D1T9, O35205, P00760, P00761, P00762, P00763, P00764, P06868, P06871, P06872, P07146, P07477, P07478, P08426, P12788, P16049, P19799, P32821, P32822, P35030, P35031, P35032, P35033, P70059, Q29463, Q32KU2, Q32LI2, Q4R7Y7, Q5K2P8, Q5K2P9, Q5K4E3, Q5M8S2, Q6IE06, Q7JIG6, Q8BW11, Q8IYP2, Q8NHM4, Q90627, Q90628, Q90629

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	41
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

439 predictions. Top by Δscore:

Variant	Effect	Δscore
7:142252466:TTTTA:T	donor_loss	1.0000
7:142252467:TTTA:T	donor_loss	1.0000
7:142252468:TTA:T	donor_loss	1.0000
7:142252469:TAC:T	donor_loss	1.0000
7:142252471:C:G	donor_loss	1.0000
7:142252490:T:TA	donor_gain	1.0000
7:142252609:TGT:T	acceptor_gain	1.0000
7:142252610:GT:G	acceptor_gain	1.0000
7:142252612:C:CC	acceptor_gain	1.0000
7:142252367:CTTC:C	acceptor_gain	0.9900
7:142252376:A:T	acceptor_gain	0.9900
7:142252470:A:AC	donor_gain	0.9900
7:142252471:C:CC	donor_gain	0.9900
7:142252607:TTTGT:T	acceptor_gain	0.9900
7:142252608:TTGT:T	acceptor_gain	0.9900
7:142252608:TTGTC:T	acceptor_gain	0.9900
7:142252609:TGTC:T	acceptor_gain	0.9900
7:142252610:GTCT:G	acceptor_gain	0.9900
7:142252611:TC:T	acceptor_gain	0.9900
7:142252612:C:CG	acceptor_loss	0.9900
7:142252612:C:T	acceptor_gain	0.9900
7:142252613:T:A	acceptor_gain	0.9900
7:142252613:T:C	acceptor_loss	0.9900
7:142253400:T:TA	donor_gain	0.9900
7:142255059:A:AC	donor_gain	0.9900
7:142257665:C:CG	donor_loss	0.9900
7:142257666:A:AC	donor_gain	0.9900
7:142257666:A:AT	donor_loss	0.9900
7:142257667:C:CC	donor_gain	0.9900
7:142257667:C:T	donor_loss	0.9900

AlphaMissense

1582 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:142255077:C:A	W138C	0.998
7:142255077:C:G	W138C	0.998
7:142252509:C:G	C180S	0.996
7:142252510:A:T	C180S	0.996
7:142252554:C:G	C165S	0.996
7:142252555:A:T	C165S	0.996
7:142252248:C:A	W233C	0.995
7:142252248:C:G	W233C	0.995
7:142252510:A:G	C180R	0.995
7:142255079:A:G	W138R	0.995
7:142255079:A:T	W138R	0.995
7:142255093:C:G	C133S	0.995
7:142255094:A:T	C133S	0.995
7:142255566:A:G	W50R	0.995
7:142255566:A:T	W50R	0.995
7:142255092:G:C	C133W	0.994
7:142255094:A:G	C133R	0.994
7:142255180:A:G	L104P	0.993
7:142255212:G:C	F93L	0.992
7:142255212:G:T	F93L	0.992
7:142255214:A:G	F93L	0.992
7:142252508:A:C	C180W	0.991
7:142255292:C:A	G67W	0.990
7:142252509:C:T	C180Y	0.989
7:142252555:A:G	C165R	0.989
7:142255544:C:G	C57S	0.989
7:142255545:A:T	C57S	0.989
7:142255586:C:T	G43E	0.989
7:142255189:T:A	D101V	0.988
7:142255545:A:G	C57R	0.988

dbSNP variants (sampled 300 via entrez): RS1000426631 (7:142258599 T>C), RS1001208090 (7:142253905 T>C), RS1001284575 (7:142257068 G>A), RS1001302936 (7:142253646 A>C), RS1001864912 (7:142257869 G>A,T), RS1001954043 (7:142258888 T>C), RS1002339080 (7:142257734 C>A,T), RS1003650722 (7:142254977 C>A,T), RS1004026423 (7:142256986 A>T), RS1004078724 (7:142256820 T>G), RS1005564613 (7:142252742 C>T), RS1005682750 (7:142258330 G>A,T), RS1005730490 (7:142258082 T>A,C), RS1005749536 (7:142252072 T>C), RS1006029911 (7:142259576 A>C)

Disease associations

OMIM: gene `` | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST005790_8	Rosacea symptom severity	2.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0009180	rosacea severity 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
Resveratrol	affects cotreatment, decreases expression	1
Benzo(a)pyrene	increases methylation	1
Plant Extracts	affects cotreatment, decreases expression	1
Valproic Acid	decreases methylation	1
Aflatoxin B1	decreases methylation	1

Clinical trials (associated diseases)

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