PRSS53

Summary

PRSS53 (serine protease 53, HGNC:34407) is a protein-coding gene on chromosome 16p11.2, encoding Serine protease 53 (Q2L4Q9). In vitro can degrade the fibrinogen alpha chain of as well as pro-urokinase-type plasminogen activator.

Predicted to enable serine-type endopeptidase activity. Predicted to be involved in proteolysis. Predicted to be located in extracellular region.

Source: NCBI Gene 339105 — RefSeq curated summary.

At a glance

• GWAS associations: 9
• Clinical variants (ClinVar): 111 total
• MANE Select transcript: NM_001039503

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:34407
Approved symbol	PRSS53
Name	serine protease 53
Location	16p11.2
Locus type	gene with protein product
Status	Approved
Aliases	POL3S
Ensembl gene	ENSG00000151006
Ensembl biotype	protein_coding
OMIM	610561
Entrez	339105

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 2 retained_intron, 1 protein_coding

ENST00000280606, ENST00000486499, ENST00000492427

RefSeq mRNA: 1 — MANE Select: NM_001039503 NM_001039503

CCDS: CCDS42153

Canonical transcript exons

ENST00000280606 — 11 exons

Exon	Start	End
ENSE00003507864	31084558	31084703
ENSE00003519279	31087537	31087699
ENSE00003528196	31086633	31086898
ENSE00003545557	31085110	31085260
ENSE00003562928	31085964	31086183
ENSE00003563208	31084780	31085024
ENSE00003582290	31086337	31086491
ENSE00003605692	31084119	31084335
ENSE00003656156	31087806	31087826
ENSE00003978296	31088752	31088943
ENSE00003978297	31083437	31083809

Expression profiles

Bgee: expression breadth ubiquitous, 128 present calls, max score 84.79.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right lobe of liver	UBERON:0001114	84.79	gold quality
right hemisphere of cerebellum	UBERON:0014890	79.81	gold quality
cerebellar hemisphere	UBERON:0002245	78.71	gold quality
cerebellar cortex	UBERON:0002129	78.54	gold quality
cerebellum	UBERON:0002037	78.50	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	78.12	silver quality
liver	UBERON:0002107	77.24	gold quality
ascending aorta	UBERON:0001496	75.82	gold quality
thoracic aorta	UBERON:0001515	75.71	gold quality
descending thoracic aorta	UBERON:0002345	75.56	gold quality
popliteal artery	UBERON:0002250	75.47	gold quality
tibial artery	UBERON:0007610	75.45	gold quality
mucosa of stomach	UBERON:0001199	74.44	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	74.00	gold quality
right coronary artery	UBERON:0001625	73.91	gold quality
granulocyte	CL:0000094	73.76	gold quality
pituitary gland	UBERON:0000007	73.18	gold quality
muscle layer of sigmoid colon	UBERON:0035805	72.98	gold quality
lower esophagus muscularis layer	UBERON:0035833	72.95	gold quality
lower esophagus	UBERON:0013473	72.92	gold quality
left coronary artery	UBERON:0001626	72.58	gold quality
right frontal lobe	UBERON:0002810	72.52	gold quality
myometrium	UBERON:0001296	71.96	gold quality
right ovary	UBERON:0002118	71.27	gold quality
adenohypophysis	UBERON:0002196	71.27	gold quality
body of uterus	UBERON:0009853	71.25	gold quality
skin of abdomen	UBERON:0001416	71.23	gold quality
stromal cell of endometrium	CL:0002255	71.16	gold quality
zone of skin	UBERON:0000014	70.93	gold quality
skin of leg	UBERON:0001511	70.89	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	2.09

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

31 targeting PRSS53, 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
MMU-MIR-709	100.00	67.75	1788
MMU-MIR-1961	100.00	73.21	1573
MMU-MIR-7116-3P	100.00	84.42	7037
MMU-MIR-6951-3P	100.00	83.23	6785
MMU-MIR-6954-5P	99.99	67.74	1337
MMU-LET-7A-5P	99.99	73.04	1183
MMU-LET-7B-5P	99.99	73.04	1187
MMU-LET-7C-5P	99.99	73.04	1183
MMU-LET-7E-5P	99.99	73.04	1183
MMU-LET-7F-5P	99.99	73.13	1184
MMU-LET-7G-5P	99.99	73.01	1188
MMU-LET-7I-5P	99.99	73.02	1191
MMU-LET-7K	99.99	73.04	1187
MMU-MIR-98-5P	99.99	73.06	1182
MMU-MIR-486A-3P	99.86	66.80	1099
MMU-MIR-486B-3P	99.86	66.80	1099
MMU-MIR-326-5P	99.85	66.50	1077
MMU-MIR-7673-5P	99.47	68.13	460
MMU-MIR-6986-3P	99.34	70.28	1481
MMU-MIR-149-5P	99.14	67.21	927
MMU-MIR-7049-5P	99.08	67.42	1094
MMU-MIR-6992-5P	98.95	66.94	715
MMU-MIR-3064-5P	98.76	66.47	1006
MMU-MIR-3085-3P	98.65	66.37	998
MMU-MIR-190B-3P	98.63	66.34	721
MMU-MIR-7652-3P	97.61	66.48	993
MMU-MIR-7688-3P	97.61	66.67	962
MMU-MIR-7052-3P	97.47	65.82	809
MMU-MIR-201-3P	96.94	68.54	860
MMU-MIR-7043-3P	96.39	66.59	705

Literature-anchored findings (GeneRIF, showing 1)

• Comparative analysis of polyserase-3 with the two human polyserases described to date, revealed that this novel polyprotein is more closely related to polyserase-2 than to polyserase-1. (PMID:16566820)

Cross-species orthologs

31 orthologs

Organism	Symbol	Gene ID
mus_musculus	Prss53	ENSMUSG00000044139
rattus_norvegicus	Prss53	ENSRNOG00000026040
drosophila_melanogaster	alphaTry	FBGN0003863
drosophila_melanogaster	betaTry	FBGN0010357
drosophila_melanogaster	deltaTry	FBGN0010358
drosophila_melanogaster	gammaTry	FBGN0010359
drosophila_melanogaster	epsilonTry	FBGN0010425
drosophila_melanogaster	thetaTry	FBGN0011555
drosophila_melanogaster	zetaTry	FBGN0011556
drosophila_melanogaster	Ser12	FBGN0011832
drosophila_melanogaster	iotaTry	FBGN0015001
drosophila_melanogaster	Try29F	FBGN0015316
drosophila_melanogaster	Ser8	FBGN0019928
drosophila_melanogaster	Send1	FBGN0031406
drosophila_melanogaster	CG8299	FBGN0034052
drosophila_melanogaster	CG11192	FBGN0034507
drosophila_melanogaster	CG13430	FBGN0034518
drosophila_melanogaster	CG10405	FBGN0038431
drosophila_melanogaster	CG7829	FBGN0039703
drosophila_melanogaster	CG17239	FBGN0042186
drosophila_melanogaster	CG17234	FBGN0042187
drosophila_melanogaster	lambdaTry	FBGN0043470
drosophila_melanogaster	kappaTry	FBGN0043471
drosophila_melanogaster	CG30025	FBGN0050025
drosophila_melanogaster	CG30031	FBGN0050031
drosophila_melanogaster	CG31265	FBGN0051265
drosophila_melanogaster	CG31681	FBGN0051681
drosophila_melanogaster	CG31954	FBGN0051954
drosophila_melanogaster	CG32374	FBGN0052374
drosophila_melanogaster	CG34458	FBGN0085487
drosophila_melanogaster	CG17571	FBGN0259998

Paralogs (1): PRSS36 (ENSG00000178226)

Protein

Protein identifiers

Serine protease 53 — Q2L4Q9 (reviewed: Q2L4Q9)

Alternative names: Polyserine protease 3

All UniProt accessions (1): Q2L4Q9

UniProt curated annotations — full annotation on UniProt →

Function. In vitro can degrade the fibrinogen alpha chain of as well as pro-urokinase-type plasminogen activator.

Subcellular location. Secreted.

Tissue specificity. Predominantly detected in testis, liver, heart and ovary, as well as in several tumor cell lines.

Similarity. Belongs to the peptidase S1 family.

RefSeq proteins (1): NP_001034592* (*=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 (18 total): disulfide bond 7, active site 6, domain 2, signal peptide 1, chain 1, region of interest 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q2L4Q9-F1	85.77	0.60

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 (6): 478 (charge relay system); 77 (charge relay system); 128 (charge relay system); 224 (charge relay system); 341 (charge relay system); 382 (charge relay system)

Disulfide bonds (7): 62–78, 158–230, 187–209, 220–249, 326–342, 444–464, 474–502

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 37 (showing top): BASSO_B_LYMPHOCYTE_NETWORK, chr16p11, RAMASWAMY_METASTASIS_DN, GOBP_PROTEOLYSIS, GOMF_PEPTIDASE_ACTIVITY, BOYAULT_LIVER_CANCER_SUBCLASS_G1_DN, MARTENS_TRETINOIN_RESPONSE_DN, PILON_KLF1_TARGETS_UP, NFE2L2.V2, SUPT16H_TARGET_GENES, ZNF768_TARGET_GENES, MIR6825_5P, GSE10240_IL22_VS_IL22_AND_IL17_STIM_PRIMARY_BRONCHIAL_EPITHELIAL_CELLS_DN, GSE12845_NAIVE_VS_DARKZONE_GC_TONSIL_BCELL_UP, GSE13484_12H_VS_3H_YF17D_VACCINE_STIM_PBMC_DN

GO Biological Process (1): proteolysis (GO:0006508)

GO Molecular Function (5): serine-type endopeptidase activity (GO:0004252), protein binding (GO:0005515), peptidase activity (GO:0008233), serine-type peptidase activity (GO:0008236), hydrolase activity (GO:0016787)

GO Cellular Component (1): extracellular region (GO:0005576)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein metabolic process	1
endopeptidase activity	1
serine-type peptidase activity	1
binding	1
hydrolase activity	1
catalytic activity, acting on a protein	1
peptidase activity	1
serine hydrolase activity	1
catalytic activity	1
cellular anatomical structure	1

Protein interactions and networks

STRING

788 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PRSS53	FGA	P02671	650
PRSS53	HOXD13	P35453	605
PRSS53	FBXL19	Q6PCT2	526
PRSS53	PRR14	Q9BWN1	503
PRSS53	CFAP119	A1A4V9	477
PRSS53	STARD9	Q9P2P6	446
PRSS53	SLC45A1	Q9Y2W3	443
PRSS53	VKORC1	Q9BQB6	442
PRSS53	TMEM229B	Q8NBD8	424
PRSS53	TCHHL1	Q5QJ38	422
PRSS53	CSDC2	Q9Y534	421
PRSS53	IQCJ-SCHIP1	B3KU38	416
PRSS53	ZNF713	Q8N859	413
PRSS53	UBE2D2	P51669	411
PRSS53	EDAR	Q9UNE0	400

IntAct

5 interactions, top by confidence:

A	B	Type	Score
PRSS53	UBAP2	psi-mi:“MI:0915”(physical association)	0.560
LMLN	PRSS53	psi-mi:“MI:0914”(association)	0.350
PRSS53	UBAP2	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (2): PRSS53 (Two-hybrid), PRSS53 (Affinity Capture-MS)

ESM2 similar proteins: A0A1B0GVH4, A1L453, A2VE36, A6NIE9, A8MTI9, E5RG02, O35453, O43240, O70169, O97507, P00748, P83748, P98140, Q04962, Q14B25, Q14BX2, Q16651, Q2L4Q9, Q2UVH8, Q3UKY7, Q3V0Q7, Q402U7, Q571E5, Q5K2P8, Q5K2P9, Q5K4E3, Q5M8S2, Q6BEA2, Q6IE62, Q6IE63, Q6UWB4, Q76HL1, Q7RTY3, Q7RTY5, Q7Z5A4, Q8BJR6, Q8BLH5, Q8IU80, Q8K4I7, Q8VIF2

Diamond homologs: A0A1B0GVH4, A1L453, A2VE36, E5RG02, F2YMG0, O35205, O35453, O60235, O97370, P03952, P05981, P06868, P08001, P08709, P10323, P14272, P19236, P20231, P22457, P23578, P26262, P29293, P29786, P35035, P35036, P35038, P35039, P35040, P35041, P39675, P49275, P49864, P50342, P69526, P70375, P83748, P98139, Q05511, Q14B25, Q14BX2

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	95
Likely benign	7
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

1647 predictions. Top by Δscore:

Variant	Effect	Δscore
16:31084117:A:AC	donor_gain	1.0000
16:31084118:C:CC	donor_gain	1.0000
16:31085257:CAGG:C	acceptor_gain	1.0000
16:31085259:GG:G	acceptor_gain	1.0000
16:31085261:C:CC	acceptor_gain	1.0000
16:31085967:CACAG:C	donor_gain	1.0000
16:31086377:AGCAT:A	donor_gain	1.0000
16:31086378:G:C	donor_gain	1.0000
16:31087535:A:AC	donor_gain	1.0000
16:31087536:C:CC	donor_gain	1.0000
16:31088750:AC:A	donor_gain	1.0000
16:31088751:CC:C	donor_gain	1.0000
16:31084121:A:AC	donor_gain	0.9900
16:31084122:T:C	donor_gain	0.9900
16:31084138:T:TA	donor_gain	0.9900
16:31085102:AGACT:A	donor_loss	0.9900
16:31085103:GACTC:G	donor_loss	0.9900
16:31085104:ACTCA:A	donor_loss	0.9900
16:31085105:CT:C	donor_loss	0.9900
16:31085106:TCACC:T	donor_loss	0.9900
16:31085107:CA:C	donor_loss	0.9900
16:31085108:A:AT	donor_loss	0.9900
16:31085108:AC:A	donor_gain	0.9900
16:31085109:CC:C	donor_gain	0.9900
16:31085256:ACAGG:A	acceptor_gain	0.9900
16:31085257:CAGGC:C	acceptor_gain	0.9900
16:31085258:AGG:A	acceptor_gain	0.9900
16:31085260:GC:G	acceptor_loss	0.9900
16:31085262:T:C	acceptor_loss	0.9900
16:31085987:ATCT:A	donor_gain	0.9900

AlphaMissense

3540 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:31086440:C:T	C187Y	0.994
16:31086440:C:G	C187S	0.992
16:31086441:A:T	C187S	0.992
16:31086374:C:G	C209S	0.991
16:31086375:A:T	C209S	0.991
16:31085003:C:A	W352C	0.990
16:31085003:C:G	W352C	0.990
16:31086115:G:C	S244R	0.990
16:31086115:G:T	S244R	0.990
16:31086117:T:G	S244R	0.990
16:31086440:C:A	C187F	0.990
16:31086439:A:C	C187W	0.989
16:31086652:C:A	W163C	0.989
16:31086652:C:G	W163C	0.989
16:31087635:C:A	W48C	0.985
16:31087635:C:G	W48C	0.985
16:31085005:A:G	W352R	0.984
16:31085005:A:T	W352R	0.984
16:31085202:C:A	W314C	0.984
16:31085202:C:G	W314C	0.984
16:31086374:C:T	C209Y	0.984
16:31087545:G:C	C78W	0.980
16:31087564:A:T	V72D	0.980
16:31087594:C:G	C62S	0.980
16:31087595:A:T	C62S	0.980
16:31084201:C:A	W520C	0.979
16:31084201:C:G	W520C	0.979
16:31086375:A:G	C209R	0.979
16:31086441:A:G	C187R	0.978
16:31087546:C:G	C78S	0.978

dbSNP variants (sampled 300 via entrez): RS1000027766 (16:31088543 C>T), RS1000094700 (16:31086975 G>A), RS1000449091 (16:31088122 G>C,T), RS1000718213 (16:31083157 A>C), RS1000874236 (16:31088835 G>C), RS1001269622 (16:31089291 G>A), RS1001544186 (16:31086255 C>G), RS1002459057 (16:31090195 G>A,C), RS1002532650 (16:31090024 C>T), RS1003372856 (16:31085570 G>A), RS1003813371 (16:31085250 G>A), RS1003946947 (16:31088523 A>G), RS1003999430 (16:31088300 T>C), RS1004016466 (16:31090763 C>A,G), RS1004282501 (16:31084565 C>G,T)

Disease associations

OMIM: gene MIM:610561 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

9 associations (top):

Study	Trait	p-value
GCST000834_4	Psoriasis	9.000000e-10
GCST001430_15	Parkinson’s disease	4.000000e-07
GCST003268_13	Psoriasis vulgaris	5.000000e-11
GCST003270_11	Psoriatic arthritis	9.000000e-06
GCST003474_3	Scalp hair shape	7.000000e-09
GCST005527_17	Psoriasis	1.000000e-16
GCST007293_141	Body fat distribution (arm fat ratio)	4.000000e-15
GCST007293_82	Body fat distribution (arm fat ratio)	3.000000e-15
GCST007293_99	Body fat distribution (arm fat ratio)	1.000000e-14

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:1001494	psoriasis vulgaris
EFO:0004341	body fat distribution

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

PharmGKB clinical annotations

1 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs17886199	Dosage	3	warfarin

PharmGKB variants

9 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs7294	PRSS53, VKORC1	1B	43.25	3	acenocoumarol;acenocoumarol;phenprocoumon;warfarin
rs2359612	PRSS53, VKORC1	1B	38.25	1	warfarin
rs7200749	PRSS53, VKORC1	3	3.00	2	acenocoumarol;warfarin
rs9923231	BCKDK, PRSS53, VKORC1	1A	484.38	9	warfarin;acenocoumarol;phenprocoumon
rs9934438	PRSS53, VKORC1	1B	109.62	6	warfarin;fluindione;acenocoumarol;phenprocoumon
rs11150606	PRSS53, VKORC1	3	2.00	1	warfarin
rs17886199	PRSS53, VKORC1	3	2.00	1	warfarin
rs61742245	PRSS53, VKORC1	2A	7.25	2	acenocoumarol;warfarin
rs104894542	PRSS53, VKORC1	3	0.25	1	warfarin

CTD chemical–gene interactions

13 total (human), top 13 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sotorasib	affects cotreatment, decreases expression	1
bisphenol A	decreases expression	1
sodium arsenite	decreases expression	1
bisphenol S	decreases expression	1
trametinib	decreases expression, affects cotreatment	1
NVP-BKM120	affects cotreatment, decreases expression	1
Air Pollutants, Occupational	affects expression	1
Benzo(a)pyrene	decreases expression	1
Lead	decreases expression	1
Nickel	increases expression	1
Smoke	decreases expression	1
Warfarin	affects response to substance	1
Okadaic Acid	decreases expression	1

Clinical trials (associated diseases)

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