PRSS50

Summary

PRSS50 (serine protease 50, HGNC:17910) is a protein-coding gene on chromosome 3p21.31, encoding Probable threonine protease PRSS50 (Q9UI38). May be involved in proteolysis through its threonine endopeptidase activity.

Enables threonine-type endopeptidase activity. Involved in proteolysis. Located in endoplasmic reticulum.

Source: NCBI Gene 29122 — automated summary from GO annotations (Alliance of Genome Resources).

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 74 total
• GTEx eGene: eQTL in 45 tissues, sQTL in 7 (q < 0.05)
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 1.01 (unconstrained)
• MANE Select transcript: NM_013270
• Notable: 74 clinical variants but no curated precision-oncology (CIViC) evidence yet

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17910
Approved symbol	PRSS50
Name	serine protease 50
Location	3p21.31
Locus type	gene with protein product
Status	Approved
Aliases	TSP50, CT20
Ensembl gene	ENSG00000283706
Ensembl biotype	protein_coding
OMIM	607950
Entrez	29122

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

MANE Select: ENST00000315170

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 1

ENST00000315170

RefSeq mRNA: 1 — MANE Select: NM_013270 NM_013270

CCDS: CCDS2745

Canonical transcript exons

ENST00000315170 — 6 exons

Exon	Start	End
ENSE00001291985	46717719	46717869
ENSE00001628208	46712117	46712482
ENSE00003810391	46712901	46713067
ENSE00003810676	46714218	46714501
ENSE00003811228	46717437	46717637
ENSE00003811374	46715535	46715697

Expression profiles

Bgee: expression breadth ubiquitous, 124 present calls, max score 94.18.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0761 / max 41.9509, expressed in 25 samples.

Highest expression (Bgee): testis, primordial germ cell in gonad, male germ line stem cell (sensu Vertebrata) in testis, pituitary gland, adenohypophysis.

Genetic regulation across tissues (GTEx eQTL / sQTL)

PRSS50 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 45 tissues and its splicing (sQTL) in 7 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 52 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Thyroid	sqtl	1.7e-54	+1.13	3:46714447:C:T
Thyroid	eqtl	6.0e-28	-0.75	3:46716355:A:G
Heart Left Ventricle	eqtl	2.1e-26	+1.02	3:46753595:G:A
Nerve Tibial	eqtl	4.6e-26	+1.77	3:46845370:A:ATT
Cells EBV-transformed lymphocytes	eqtl	1.6e-19	+0.85	3:46723787:C:T
Testis	sqtl	7.9e-19	-0.94	3:46714447:C:T
Esophagus Muscularis	eqtl	8.3e-19	+1.07	3:46845370:A:ATT
Heart Atrial Appendage	eqtl	4.2e-18	+0.99	3:46746199:T:G
Testis	eqtl	1.3e-16	-0.40	3:46714447:C:T
Colon Sigmoid	eqtl	1.2e-15	+1.19	3:46845370:A:ATT
Artery Tibial	eqtl	7.1e-15	+1.24	3:46845370:A:ATT
Pancreas	eqtl	1.9e-14	-0.93	3:46749896:G:A
Skin Sun Exposed Lower leg	eqtl	1.6e-13	-0.31	3:46740346:A:G
Whole Blood	eqtl	2.3e-13	-0.42	3:46740227:T:C
Brain Cerebellar Hemisphere	eqtl	1.9e-12	+1.13	3:46753595:G:A
Pituitary	eqtl	9.3e-12	+0.91	3:46746199:T:G
Esophagus Gastroesophageal Junction	eqtl	1.8e-11	+1.16	3:46845370:A:ATT
Pituitary	sqtl	4.9e-11	+1.07	3:46714447:C:T
Colon Transverse	eqtl	1.9e-10	+0.85	3:46845370:A:ATT
Brain Cerebellum	eqtl	2.7e-09	+1.19	3:46753595:G:A

FANTOM5 promoters

3 alternative TSS:

Promoter ID	TPM avg	Samples expressed
42000	0.0320	11
42001	0.0278	8
42002	0.0163	10

Top tissues by expression

showing 100 of 136 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
right testis	UBERON:0004534	94.18	gold quality
left testis	UBERON:0004533	93.06	gold quality
testis	UBERON:0000473	92.46	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	87.98	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	87.30	gold quality
pituitary gland	UBERON:0000007	83.58	gold quality
adenohypophysis	UBERON:0002196	82.57	gold quality
left lobe of thyroid gland	UBERON:0001120	81.92	gold quality
thyroid gland	UBERON:0002046	81.15	gold quality
right lobe of thyroid gland	UBERON:0001119	79.72	gold quality
endocervix	UBERON:0000458	68.15	gold quality
ventricular zone	UBERON:0003053	67.94	gold quality
right lobe of liver	UBERON:0001114	66.20	gold quality
body of pancreas	UBERON:0001150	66.11	gold quality
mucosa of stomach	UBERON:0001199	65.89	gold quality
metanephros cortex	UBERON:0010533	65.57	gold quality
prostate gland	UBERON:0002367	65.22	gold quality
left uterine tube	UBERON:0001303	64.39	gold quality
cortical plate	UBERON:0005343	63.91	gold quality
body of uterus	UBERON:0009853	63.86	gold quality
adult mammalian kidney	UBERON:0000082	63.36	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	62.91	gold quality
left ovary	UBERON:0002119	62.40	gold quality
lower esophagus mucosa	UBERON:0035834	62.08	gold quality
hypothalamus	UBERON:0001898	61.88	gold quality
vagina	UBERON:0000996	61.82	gold quality
fundus of stomach	UBERON:0001160	61.50	gold quality
popliteal artery	UBERON:0002250	61.43	gold quality
tibial artery	UBERON:0007610	61.38	gold quality
lower esophagus muscularis layer	UBERON:0035833	61.21	gold quality
lower esophagus	UBERON:0013473	61.19	gold quality
ectocervix	UBERON:0012249	61.10	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	60.99	gold quality
muscle layer of sigmoid colon	UBERON:0035805	60.88	gold quality
uterine cervix	UBERON:0000002	60.72	gold quality
hindlimb stylopod muscle	UBERON:0004252	60.69	gold quality
myometrium	UBERON:0001296	60.65	gold quality
descending thoracic aorta	UBERON:0002345	59.68	gold quality
cerebellar hemisphere	UBERON:0002245	59.55	gold quality
ovary	UBERON:0000992	59.45	gold quality
saliva-secreting gland	UBERON:0001044	59.39	gold quality
fallopian tube	UBERON:0003889	59.35	gold quality
cerebellum	UBERON:0002037	59.24	gold quality
right ovary	UBERON:0002118	59.24	gold quality
cerebellar cortex	UBERON:0002129	59.23	gold quality
minor salivary gland	UBERON:0001830	58.79	gold quality
kidney	UBERON:0002113	58.71	gold quality
ganglionic eminence	UBERON:0004023	58.61	gold quality
right coronary artery	UBERON:0001625	58.58	gold quality
thoracic mammary gland	UBERON:0005200	58.11	gold quality
ascending aorta	UBERON:0001496	58.06	gold quality
thoracic aorta	UBERON:0001515	58.00	gold quality
right hemisphere of cerebellum	UBERON:0014890	57.90	gold quality
cortex of kidney	UBERON:0001225	57.68	gold quality
brain	UBERON:0000955	57.04	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	56.96	gold quality
pancreas	UBERON:0001264	56.85	gold quality
body of stomach	UBERON:0001161	56.59	gold quality
right uterine tube	UBERON:0001302	56.55	gold quality
substantia nigra	UBERON:0002038	56.15	gold quality
liver	UBERON:0002107	55.92	gold quality
Ammon’s horn	UBERON:0001954	55.88	gold quality
anterior cingulate cortex	UBERON:0009835	55.39	gold quality
monocyte	CL:0000576	55.38	gold quality
temporal lobe	UBERON:0001871	55.05	gold quality
right lung	UBERON:0002167	55.04	gold quality
amygdala	UBERON:0001876	55.00	gold quality
anatomical system	UBERON:0000467	54.87	gold quality
material anatomical entity	UBERON:0000465	54.84	gold quality
multicellular organism	UBERON:0000468	54.84	gold quality
right frontal lobe	UBERON:0002810	54.73	gold quality
esophagus	UBERON:0001043	54.05	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	54.04	gold quality
cerebral cortex	UBERON:0000956	54.03	gold quality
left coronary artery	UBERON:0001626	53.93	gold quality
leukocyte	CL:0000738	53.66	gold quality
nucleus accumbens	UBERON:0001882	53.41	gold quality
stomach	UBERON:0000945	52.98	gold quality
frontal cortex	UBERON:0001870	52.82	gold quality
Brodmann (1909) area 9	UBERON:0013540	52.33	gold quality
caudate nucleus	UBERON:0001873	52.10	gold quality
prefrontal cortex	UBERON:0000451	52.06	gold quality
urinary bladder	UBERON:0001255	51.97	gold quality
omental fat pad	UBERON:0010414	51.80	gold quality
colon	UBERON:0001155	51.69	gold quality
gastrocnemius	UBERON:0001388	51.64	gold quality
smooth muscle tissue	UBERON:0001135	51.30	gold quality
putamen	UBERON:0001874	50.88	gold quality
muscle of leg	UBERON:0001383	50.80	gold quality
superior frontal gyrus	UBERON:0002661	50.19	gold quality
tibial nerve	UBERON:0001323	49.61	gold quality
muscle tissue	UBERON:0002385	49.58	gold quality
right adrenal gland	UBERON:0001233	49.52	gold quality
intestine	UBERON:0000160	48.93	gold quality
adipose tissue	UBERON:0001013	48.78	gold quality
upper lobe of left lung	UBERON:0008952	48.73	gold quality
left adrenal gland	UBERON:0001234	48.43	gold quality
left adrenal gland cortex	UBERON:0035825	48.40	gold quality
esophagus mucosa	UBERON:0002469	48.07	gold quality
adrenal gland	UBERON:0002369	48.05	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

HPA expression

RNA tissue specificity: Group enriched

showing 60 of 62 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Testis	tissue	20.2	high
Pituitary gland	tissue	18.2
Midbrain	tissue	2.9
Epididymis	tissue	2.8	not detected
Cerebellum	tissue	2.8	not detected
Spinal cord	tissue	2.5
Vagina	tissue	2.2	not detected
Thalamus	tissue	2.2
Seminal vesicle	tissue	2.0	not detected
Medulla oblongata	tissue	1.9
Thyroid gland	tissue	1.9	not detected
Salivary gland	tissue	1.8	not detected
Substantia nigra	tissue	1.8
Locus coeruleus	tissue	1.7
Superior colliculi	tissue	1.6
Hypothalamus	tissue	1.4
Parathyroid gland	tissue	1.3	not detected
Hippocampus	tissue	1.3	not detected
Pons	tissue	1.2
Pancreas	tissue	1.2	not detected
Choroid plexus	tissue	1.1
Adrenal gland	tissue	1.1	not detected
Periaqueductal gray	tissue	0.9
Postcentral gyrus	tissue	0.8
Septum	tissue	0.8
Frontal cortex	tissue	0.7
Caudate putamen	tissue	0.7
Amygdala	tissue	0.6
Hippocampal formation	tissue	0.6
Nucleus accumbens	tissue	0.5
Prostate	tissue	0.5	not detected
Fallopian tube	tissue	0.5	not detected
Cervix	tissue	0.4	not detected
Breast	tissue	0.4	not detected
Cerebral cortex	tissue	0.4	not detected
Ovary	tissue	0.4	not detected
Temporal cortex	tissue	0.4
Prefrontal cortex	tissue	0.3
Endometrium 1	tissue	0.3	not detected
Motor cortex	tissue	0.3
Corpus callosum	tissue	0.3
Insular cortex	tissue	0.3
Retina	tissue	0.2
Smooth muscle	tissue	0.2	not detected
Liver	tissue	0.2	not detected
Kidney	tissue	0.2	not detected
Thymus	tissue	0.2
Entorhinal cortex	tissue	0.2
Ventral forebrain	tissue	0.2
Retrosplenial and cingulate cortex	tissue	0.2
Olfactory bulb	tissue	0.2
Retrosplenial cortex	tissue	0.2
Skin 1	tissue	0.1	not detected
Adipose tissue	tissue	0.1	not detected
Urinary bladder	tissue	0.1	not detected
Placenta	tissue	0.1	not detected
Lung	tissue	0.1	not detected
Spleen	tissue	0.1	not detected
Gallbladder	tissue	0.1	not detected
Bone marrow	tissue	0.1	not detected

Brain sub-regions (HPA Brain Atlas): detected in 189; highest nTPM — Vermis (4.0), Flocculonodular lobe (3.2), Cerebellar cortex (2.7), Ventral spinal cord (2.5), Dorsal spinal cord (2.4).

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CEBPB, CEBPG, NKX3-1, SP1, TP53

miRNA regulators (miRDB)

Targeting PRSS50 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

5 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-6124	99.87	69.78	3551
HSA-MIR-33A-3P	99.70	70.27	3362
HSA-MIR-939-3P	98.97	65.07	2347

Functional genomics

gnomAD constraint: pLI 2.69e-06, LOEUF 1.01, missense Z 0.5 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000315170 — one region, missense o/e 0.94.

Literature-anchored findings (GeneRIF, showing 21)

• TSP50, a possible protease in human testes, is activated in breast cancer epithelial cells. (PMID:11782390)
• TSP50 was largely downregulated in all testicular germ cell tumors. It may function in mammalian spermatogenesis. Its linear catalytic structure is similar to many serine proteases, except for a Thr-for-Ser residual catalytic site substitution. (PMID:15491742)
• Overexpression of Sp1 and C/EBPbeta transcriptional factors upregulated the activities of the TSP50 promoter. (PMID:18462069)
• These findings suggested that DNA methylation might regulate the TSP50 and mTSP50 gene expressions in different types of tissues and spermatic cells. (PMID:18662669)
• Results strongly suggest that bFGF mediates TSP50 downregulation by ERK1/2 activation, leading to the phosphorylation of Sp1 in this process. (PMID:20506264)
• TSP50 is a potential effective indicator of poor survival for colorectal carcinoma patients, especially for those with early-stage tumors. (PMID:21765952)
• the importance of threonine 310, the most critical protease catalytic site in TSP50, to TSP50-induced cell proliferation and tumor formation (PMID:22574111)
• The mutations in the catalytic triad of TSP50 could significantly depressed TSP50-mediated cell proliferation and tumor formation. (PMID:25049081)
• High TSP50 expression is associated with laryngocarcinoma. (PMID:25077921)
• TSP50’s threonine protease activity is crucial for its effects on tumor formation. (PMID:25312478)
• Results show that TSP50 is up-regulated in laryngocarcinoma tumour tissues and its down-regulation inhibits cell proliferation, reduces cell migration and induces cell apoptosis of laryngocarcinoma in NF-KB mediated pathway. (PMID:25399078)
• we found that some breast cancer diagnosis-associated features such as tumor size, tumor grade, estrogen receptors (ER) and progesterone receptors (PR) levels, were correlated well with TSP50/p65 and TSP50/MMP9 expression status (PMID:25811800)
• Results suggest that 7P3A, which consists of 70 % 25-methoxyl-dammarane-3beta, 12beta, 20-triol and 30 % artemisinin, exhibits anti-cancer effects, in part, through downregulation of testes-specific protease 50 (TSP50) expression. (PMID:27039397)
• TSP50 plays a significant role in NSCLC cell proliferation and may act as a novel oncogene in the development and progression of NSCLC. (PMID:27109614)
• In patients with Colon cancer, the expression of TSP50 gene was associated with a poor prognosis. (PMID:28631709)
• human epidermal growth factor receptor 2 (HER-2) levels, were correlated well with TSP50/p-Samd2/3 and TSP50/p27 expression status. Thus, our studies revealed a novel regulatory mechanism underlying TSP50-induced cell proliferation and provided a new favorable intervention target for the treatment of breast cancer (PMID:28650473)
• TSP50 promotes the proliferation, migration and invasion of gastric cancer cells involving NF-kappaB dependent EMT activation. Targeting TSP50 may provide a novel therapeutic strategy for the management of gastric cancer (PMID:29361914)
• TSP50 promotes hepatocyte proliferation and tumour formation by activating glucose-6-phosphate dehydrogenase (G6PD). (PMID:33630390)
• miR-4709-3p Inhibits Cell Proliferation by Downregulating TSP50 Expression in Breast Cancer Cells. (PMID:33956530)
• TSP50 promotes the Warburg effect and hepatocyte proliferation via regulating PKM2 acetylation. (PMID:34016961)
• Expression of TSP50, SERCA2 and IL-8 in Colorectal Adenoma and Carcinoma: Correlation to Clinicopathological Factors. (PMID:34744521)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Prss50	ENSMUSG00000048752
rattus_norvegicus	Prss50	ENSRNOG00000037175

Paralogs (14): PRSS33 (ENSG00000103355), PLAT (ENSG00000104368), PLG (ENSG00000122194), PLGLB2 (ENSG00000125551), PRSS37 (ENSG00000165076), PRSS27 (ENSG00000172382), KLK15 (ENSG00000174562), PLGLB1 (ENSG00000183281), PRSS57 (ENSG00000185198), TMPRSS12 (ENSG00000186452), OVCH1 (ENSG00000187950), PRSS48 (ENSG00000189099), GZMM (ENSG00000197540), KLK9 (ENSG00000213022)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:2447303) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 20 distinct phenotype terms.

Mouse phenotype (MP)	Records
decreased bone mineral density	1
reduced male fertility	1
male infertility	1
decreased litter size	1
abnormal seminiferous tubule morphology	1
asthenozoospermia	1
abnormal bone mineralization	1
decreased T cell number	1
teratozoospermia	1
abnormal spermatid morphology	1
decreased CD8-positive, alpha-beta T cell number	1
absent sperm flagellum	1
decreased hyperactivated sperm motility	1
absent sperm mitochondrial sheath	1
abnormal sperm annulus morphology	1
abnormal sperm axoneme morphology	1
multiflagellated sperm	1
decreased sperm progressive motility	1
immotile sperm	1
multi-headed sperm	1

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Bos taurus	A2VE36	80.0%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
TMIE	protein-coding	259236
FAM240A	protein-coding	100132146
ALS2CL	protein-coding	259173
CRIPTO	protein-coding	6997

Protein

Protein identifiers

Probable threonine protease PRSS50 — Q9UI38 (reviewed: Q9UI38)

Alternative names: Cancer/testis antigen 20, Serine protease 50, Testis-specific protease-like protein 50

All UniProt accessions (2): A0A140VJY3, Q9UI38

UniProt curated annotations — full annotation on UniProt →

Function. May be involved in proteolysis through its threonine endopeptidase activity.

Subcellular location. Endoplasmic reticulum.

Tissue specificity. Testis specific. Differentially expressed in some breast cancer tissues.

Miscellaneous. DNA hypomethylation is accompanied by the expression of the gene in the testis.

Similarity. Belongs to the peptidase S1 family.

RefSeq proteins (1): NP_037402* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001254	Trypsin_dom	Domain
IPR001314	Peptidase_S1A	Family
IPR009003	Peptidase_S1_PA	Homologous_superfamily
IPR043504

Pfam: PF00089

UniProt features (15 total): disulfide bond 4, active site 3, sequence variant 2, glycosylation site 2, signal peptide 1, chain 1, mutagenesis site 1, domain 1

Structure

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UI38-F1	75.38	0.54

Human Protein Atlas

Protein class: Enzymes, Peptidases, Serine-type peptidases, Predicted intracellular proteins

Protein evidence: Evidence at protein level

Antibody reliability (HPA): IH supported

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)

Position	Role
153	charge relay system
206	charge relay system
310	charge relay system

Disulfide bonds (4)

Type	Positions
Disulfide bond	273–296, 306–334, 138–154, 240–316

Glycosylation sites (2)

Type	Positions
N-linked (glcnac…) asparagine	133, 279

Mutagenesis-validated functional residues (1)

Position	Phenotype
310	loss of catalytic activity.

Function

Pathways and Gene Ontology

Reactome pathways

0 curated (TAS) of 0; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

MSigDB gene sets: 56 (showing top): LFA1_Q6, GOBP_PROTEIN_MATURATION, WEBER_METHYLATED_HCP_IN_SPERM_UP, WEBER_METHYLATED_HCP_IN_FIBROBLAST_DN, GOBP_PROTEOLYSIS, GOMF_PEPTIDASE_ACTIVITY, GOMF_THREONINE_TYPE_PEPTIDASE_ACTIVITY, MEISSNER_NPC_HCP_WITH_H3_UNMETHYLATED, MEISSNER_BRAIN_HCP_WITH_H3K27ME3, HATADA_METHYLATED_IN_LUNG_CANCER_UP, MIKKELSEN_MEF_HCP_WITH_H3K27ME3, MARTENS_TRETINOIN_RESPONSE_UP, GOBP_PROTEIN_PROCESSING, TORCHIA_TARGETS_OF_EWSR1_FLI1_FUSION_DN, ZWANG_TRANSIENTLY_UP_BY_2ND_EGF_PULSE_ONLY

GO Biological Process (2): proteolysis (GO:0006508), protein processing (GO:0016485)

GO Molecular Function (5): serine-type endopeptidase activity (GO:0004252), threonine-type endopeptidase activity (GO:0004298), serine-type peptidase activity (GO:0008236), peptidase activity (GO:0008233), hydrolase activity (GO:0016787)

GO Cellular Component (2): cytoplasm (GO:0005737), endoplasmic reticulum (GO:0005783)

GO top-level categories

16 GO namespaces:

Category	Terms
endopeptidase activity	2
protein metabolic process	1
proteolysis	1
protein maturation	1
serine-type peptidase activity	1
threonine-type peptidase activity	1
peptidase activity	1
serine hydrolase activity	1
hydrolase activity	1
catalytic activity, acting on a protein	1
catalytic activity	1
intracellular anatomical structure	1
cellular anatomical structure	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 4 of 9 annotations. The rest are phylogenetic / computational / electronic (IEA).

4 experimentally-supported GO terms:

GO term	NS	Evidence
proteolysis	BP	direct assay
cytoplasm	CC	direct assay
endoplasmic reticulum	CC	direct assay
threonine-type endopeptidase activity	MF	mutant phenotype

Protein interactions and networks

STRING

showing 16 of 668 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PRSS50	PAGE5	Q96GU1	800
PRSS50	SAGE1	Q9NXZ1	717
PRSS50	SPA17	Q15506	638
PRSS50	MAGEC2	Q9UBF1	637
PRSS50	ADAM2	P78326	631
PRSS50	LIPI	Q6XZB0	608
PRSS50	PER2	O15055	509
PRSS50	ACRBP	Q8NEB7	494
PRSS50	BMAL1	O00327	470
PRSS50	ADAM30	Q9UKF2	438
PRSS50	CRY1	Q16526	421
PRSS50	NR1D1	P20393	419
PRSS50	MYOZ3	Q8TDC0	414
PRSS50	MAGEC1	O60732	400
PRSS50	CLOCK	O15516	400
PRSS50	CAGE1	Q8TC20	400

IntAct

Human interaction partners of PRSS50 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

8 partners by confidence:

Partner	Interaction type	MIscore	Records
CASP8	physical association	0.370	1
ESR2	physical association	0.370	1
HRAS	physical association	0.370	1
STK11	physical association	0.370	1
TGFB1	physical association	0.370	1
TSG101	physical association	0.370	1
PRSS46P	association	0.350	1
TUBB	association	0.350	1

BioGRID (67 interactions; top human partners by supporting records): ACVR2A (Affinity Capture-Western; 3 records), ADAMTS1 (Affinity Capture-MS; 3 records), CBWD3 (Affinity Capture-MS; 3 records), FKBP14 (Affinity Capture-MS; 3 records), HSPA5 (Affinity Capture-MS; 3 records), PIGS (Affinity Capture-MS; 3 records), PRSS46 (Affinity Capture-MS; 3 records), TUBB1 (Affinity Capture-MS; 3 records), ZYG11B (Affinity Capture-MS; 3 records), FOXF1 (Affinity Capture-MS; 2 records), GPAA1 (Affinity Capture-MS; 2 records), PIGT (Affinity Capture-MS; 2 records), SPCS2 (Affinity Capture-MS; 2 records), TOR3A (Affinity Capture-MS; 2 records), ACAD10 (Affinity Capture-MS)

Disease & clinical

Genetic variants

Variant evidence for PRSS50: 74 ClinVar records (0 pathogenic / likely pathogenic); 1 GWAS association.

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	63
Likely benign	5
Benign	2

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 26 predictions of 432):

Position(s)	Effect	Δscore	Sites
3:46712899–46712900	donor_loss	1.0000	4
3:46712904	donor_gain	1.0000
3:46713068	acceptor_loss	1.0000	2
3:46714216–46714217	donor_loss	1.0000	5
3:46715533–46715534	donor_loss	1.0000	5
3:46717717–46717718	donor_loss	1.0000	5
3:46712900	donor_loss	0.9900
3:46712909	donor_gain	0.9900
3:46712915	donor_gain	0.9900
3:46713069	acceptor_loss	0.9900

AlphaMissense

384 missense substitutions predicted likely pathogenic (of 2,489 scored), across 122 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
C240	7	0.927	0.971
W245	7	0.921	0.986
C273	7	0.905	0.965
C138	7	0.902	0.944
C154	7	0.897	0.946
C296	7	0.895	0.954
W126	7	0.887	0.975
C226	7	0.876	0.918
C306	7	0.862	0.903
W147	7	0.850	0.958
C316	7	0.849	0.901
C334	7	0.844	0.928
W124	7	0.809	0.928
W352	7	0.803	0.967
C104	7	0.777	0.856
S129	6	0.919	0.977
G167	6	0.852	0.926
P125	6	0.796	0.879
F305	5	0.870	0.945
W330	5	0.759	0.911

HPA cancer prognostics

RNA cancer specificity: Cancer enhanced (Ovary Serous Cystadenocarcinoma)

Disease associations

OMIM: gene MIM:607950 | disease phenotypes:

GWAS associations

1 associations:

Study	Trait	p-value
GCST006630_78	Diastolic blood pressure	3e-10

EFO canonical traits (from GWAS)

1 canonical traits:

EFO ID	Trait name
EFO:0006336	diastolic blood pressure

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (CPIC guideline: no)

CTD chemical–gene interactions

3 total (human), top 3 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
alantolactone	decreases expression	1
Sunitinib	increases expression	1
Benzo(a)pyrene	affects methylation	1

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.