PRSS54

Summary

PRSS54 (serine protease 54, HGNC:26336) is a protein-coding gene on chromosome 16q21, encoding Inactive serine protease 54 (Q6PEW0).

This gene encodes a putative serine-type endopeptidase containing the peptidase S1 domain. Alternative splicing of this gene results in multiple transcript variants.

Source: NCBI Gene 221191 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 35 total
• MANE Select transcript: NM_001305173

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:26336
Approved symbol	PRSS54
Name	serine protease 54
Location	16q21
Locus type	gene with protein product
Status	Approved
Aliases	FLJ25339, KLKBL4, CT67
Ensembl gene	ENSG00000103023
Ensembl biotype	protein_coding
Entrez	221191

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 5 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000219301, ENST00000543437, ENST00000563336, ENST00000567164, ENST00000569079, ENST00000569727

RefSeq mRNA: 3 — MANE Select: NM_001305173 NM_001080492, NM_001305173, NM_001305174

CCDS: CCDS32463, CCDS76882

Canonical transcript exons

ENST00000567164 — 7 exons

Exon	Start	End
ENSE00000686751	58284590	58284721
ENSE00001298781	58279997	58280757
ENSE00001504118	58290959	58291136
ENSE00002579515	58293985	58294209
ENSE00002620499	58294887	58295025
ENSE00003498476	58285937	58286195
ENSE00003542823	58293732	58293822

Expression profiles

Bgee: expression breadth broad, 80 present calls, max score 91.11.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0565 / max 54.1302, expressed in 4 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
157614	0.0379	3
157615	0.0086	3
207902	0.0059	4
157613	0.0042	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
left testis	UBERON:0004533	91.11	gold quality
sperm	CL:0000019	90.83	gold quality
right testis	UBERON:0004534	90.82	gold quality
testis	UBERON:0000473	88.52	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	81.64	silver quality
adult organism	UBERON:0007023	72.64	gold quality
buccal mucosa cell	CL:0002336	65.57	gold quality
medial globus pallidus	UBERON:0002477	61.55	silver quality
oviduct epithelium	UBERON:0004804	61.46	silver quality
tibia	UBERON:0000979	58.70	silver quality
globus pallidus	UBERON:0001875	57.02	silver quality
cartilage tissue	UBERON:0002418	55.66	gold quality
tendon of biceps brachii	UBERON:0008188	55.06	gold quality
cardiac muscle of right atrium	UBERON:0003379	54.34	gold quality
left ventricle myocardium	UBERON:0006566	54.23	gold quality
kidney epithelium	UBERON:0004819	53.93	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	53.76	gold quality
epithelial cell of pancreas	CL:0000083	53.59	gold quality
upper arm skin	UBERON:0004263	53.52	gold quality
tibialis anterior	UBERON:0001385	51.71	silver quality
ileal mucosa	UBERON:0000331	51.26	silver quality
pancreatic ductal cell	CL:0002079	51.23	silver quality
myocardium	UBERON:0002349	50.25	gold quality
deltoid	UBERON:0001476	50.12	gold quality
nasal cavity epithelium	UBERON:0005384	47.03	gold quality
quadriceps femoris	UBERON:0001377	46.59	gold quality
fallopian tube	UBERON:0003889	46.03	gold quality
prefrontal cortex	UBERON:0000451	45.61	gold quality
vastus lateralis	UBERON:0001379	45.40	gold quality
upper leg skin	UBERON:0004262	45.25	silver quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	2.13

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

17 targeting PRSS54, 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-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-1323	99.83	69.89	2471
HSA-MIR-92A-2-5P	99.75	67.01	2164
HSA-MIR-3913-3P	99.74	66.53	938
HSA-MIR-7157-5P	99.66	69.33	1829
HSA-MIR-4310	99.59	68.84	2527
HSA-MIR-4328	99.57	71.06	4094
HSA-MIR-6731-5P	99.28	67.42	2375
HSA-MIR-8085	99.28	67.56	2362
HSA-MIR-6873-5P	98.45	66.14	1417
HSA-MIR-338-3P	98.14	67.38	1137
HSA-MIR-4797-3P	97.48	67.14	989
HSA-MIR-5000-5P	97.40	66.11	1055
HSA-MIR-514A-3P	96.43	67.77	1048
HSA-MIR-514B-3P	96.43	67.77	1048
HSA-MIR-6858-3P	96.37	64.41	771
HSA-MIR-4264	96.35	64.76	1480

Literature-anchored findings (GeneRIF, showing 1)

• Testis-specific serine protease PRSS54 regulates acrosomal granule localization and sperm head morphogenesis in micedagger. (PMID:35863763)

Cross-species orthologs

13 orthologs

Organism	Symbol	Gene ID
mus_musculus	Prss54	ENSMUSG00000048400
rattus_norvegicus	Prss54	ENSRNOG00000023092
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): KLK14 (ENSG00000129437), KLK8 (ENSG00000129455), TMPRSS4 (ENSG00000137648), KLK3 (ENSG00000142515), KLK1 (ENSG00000167748), KLK4 (ENSG00000167749), KLK2 (ENSG00000167751), KLK5 (ENSG00000167754), KLK11 (ENSG00000167757), KLK7 (ENSG00000169035), KLK12 (ENSG00000186474), PRSS58 (ENSG00000258223)

Protein

Protein identifiers

Inactive serine protease 54 — Q6PEW0 (reviewed: Q6PEW0)

Alternative names: Cancer/testis antigen 67, Plasma kallikrein-like protein 4

All UniProt accessions (5): Q6PEW0, A0A140VKC3, F5H6C6, H3BNY0, H3BQS7

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Secreted.

Similarity. Belongs to the peptidase S1 family. Plasma kallikrein subfamily.

RefSeq proteins (3): NP_001073961, NP_001292102, NP_001292103 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001254	Trypsin_dom	Domain
IPR009003	Peptidase_S1_PA	Homologous_superfamily
IPR043504

Pfam: PF00089

UniProt features (13 total): sequence variant 3, disulfide bond 3, glycosylation site 2, signal peptide 1, chain 1, domain 1, region of interest 1, compositionally biased region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6PEW0-F1	67.53	0.34

Functional residue map

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

Disulfide bonds (3): 164–227, 195–205, 217–248

Glycosylation sites (2): 123, 327

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 24 (showing top): chr16q21, GOBP_PROTEOLYSIS, GOMF_PEPTIDASE_ACTIVITY, ROYLANCE_BREAST_CANCER_16Q_COPY_NUMBER_UP, MIR4310, MIR6858_3P, DESCARTES_MAIN_FETAL_CILIATED_EPITHELIAL_CELLS, DESCARTES_FETAL_LUNG_CILIATED_EPITHELIAL_CELLS, GSE18791_CTRL_VS_NEWCASTLE_VIRUS_DC_1H_UP, GOMF_SERINE_HYDROLASE_ACTIVITY, GSE36392_TYPE_2_MYELOID_VS_EOSINOPHIL_IL25_TREATED_LUNG_UP, GSE7460_TREG_VS_TCONV_ACT_DN, GSE7460_CTRL_VS_TGFB_TREATED_ACT_TCONV_UP, GOMF_ENDOPEPTIDASE_ACTIVITY, GSE5589_WT_VS_IL10_KO_LPS_AND_IL6_STIM_MACROPHAGE_45MIN_DN

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

GO Molecular Function (1): serine-type endopeptidase activity (GO:0004252)

GO Cellular Component (2): obsolete extracellular space (GO:0005615), 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
cellular anatomical structure	1

Protein interactions and networks

STRING

340 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PRSS54	PRSS37	A4D1T9	643
PRSS54	TEX55	Q96M34	643
PRSS54	OR5C1	Q8NGR4	598
PRSS54	SPMAP2	Q9P2T0	571
PRSS54	CT62	P0C5K7	541
PRSS54	SPATA46	Q5T0L3	507
PRSS54	C1orf167	Q5SNV9	479
PRSS54	CPXCR1	Q8N123	479
PRSS54	SPMIP9	Q96LM6	479
PRSS54	OR4X1	Q8NH49	452
PRSS54	PASD1	Q8IV76	447
PRSS54	RBM46	Q8TBY0	418
PRSS54	GPR25	O00155	414
PRSS54	OR7C2	O60412	400
PRSS54	ADAM29	Q9UKF5	397

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: Q6AY28, Q6PEW0, Q6UWB4, Q7M756, Q2KJ63, E5AJX2, P03951, P03952, Q5NTB3, Q91Y47

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	28
Likely benign	4
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

1247 predictions. Top by Δscore:

Variant	Effect	Δscore
16:58284728:CA:C	acceptor_gain	1.0000
16:58284729:A:AC	acceptor_gain	1.0000
16:58284729:A:C	acceptor_gain	1.0000
16:58285935:A:C	donor_gain	1.0000
16:58293626:C:A	donor_gain	1.0000
16:58280754:CCCC:C	acceptor_gain	0.9900
16:58280755:CCC:C	acceptor_gain	0.9900
16:58280755:CCCC:C	acceptor_gain	0.9900
16:58280756:CC:C	acceptor_gain	0.9900
16:58280756:CCC:C	acceptor_gain	0.9900
16:58280756:CCCTG:C	acceptor_loss	0.9900
16:58280757:CC:C	acceptor_gain	0.9900
16:58280758:C:CC	acceptor_gain	0.9900
16:58280759:T:C	acceptor_loss	0.9900
16:58284566:G:C	donor_gain	0.9900
16:58284727:CCA:C	acceptor_gain	0.9900
16:58285955:T:TA	donor_gain	0.9900
16:58293730:A:AC	donor_gain	0.9900
16:58293731:C:CC	donor_gain	0.9900
16:58280753:TCCCC:T	acceptor_gain	0.9800
16:58280754:CCCCC:C	acceptor_gain	0.9800
16:58284718:CTGT:C	acceptor_gain	0.9800
16:58284729:A:T	acceptor_gain	0.9800
16:58294798:CAGAG:C	donor_gain	0.9800
16:58294799:A:AC	donor_gain	0.9800
16:58294799:AGAGA:A	donor_gain	0.9800
16:58294800:G:C	donor_gain	0.9800
16:58294898:CATG:C	donor_gain	0.9800
16:58294899:ATGA:A	donor_gain	0.9800
16:58280760:G:GC	acceptor_gain	0.9700

AlphaMissense

2612 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:58290982:G:C	S80R	0.997
16:58290982:G:T	S80R	0.997
16:58290984:T:G	S80R	0.997
16:58285952:C:A	W169C	0.996
16:58285952:C:G	W169C	0.996
16:58280623:C:A	W263C	0.994
16:58280623:C:G	W263C	0.994
16:58286068:C:G	A131P	0.993
16:58285954:A:G	W169R	0.992
16:58285954:A:T	W169R	0.992
16:58291050:A:G	S58P	0.992
16:58286061:A:G	L133P	0.991
16:58286096:A:C	F121L	0.991
16:58286096:A:T	F121L	0.991
16:58286098:A:G	F121L	0.991
16:58286067:G:T	A131D	0.990
16:58280625:A:G	W263R	0.989
16:58280625:A:T	W263R	0.989
16:58286064:A:G	L132P	0.989
16:58280732:C:G	C227S	0.988
16:58280733:A:T	C227S	0.988
16:58286072:G:C	N129K	0.987
16:58286072:G:T	N129K	0.987
16:58291059:A:G	W55R	0.987
16:58291059:A:T	W55R	0.987
16:58285967:G:C	C164W	0.985
16:58291013:C:T	G70D	0.985
16:58291043:T:G	Q60P	0.985
16:58280733:A:G	C227R	0.983
16:58285968:C:G	C164S	0.982

dbSNP variants (sampled 300 via entrez): RS1000003641 (16:58280355 G>A), RS1000032484 (16:58295691 C>T), RS1000075756 (16:58280128 G>A,T), RS1000156624 (16:58290058 T>A), RS1000294649 (16:58293043 A>G,T), RS1000451091 (16:58286932 A>G), RS1000829508 (16:58287173 T>A), RS1001054161 (16:58281865 C>G), RS1001190895 (16:58294403 T>G), RS1001321074 (16:58286468 T>C), RS1001422959 (16:58293747 G>A), RS1002056437 (16:58283439 A>G), RS1002209588 (16:58295337 A>G), RS1002314647 (16:58289319 G>A), RS1002459544 (16:58289581 T>TTC)

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

2 associations (top):

Study	Trait	p-value
GCST003121_9	Alcohol dependence	5.000000e-06
GCST003155_34	Systemic lupus erythematosus	4.000000e-06

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

6 total (human), top 6 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
FR900359	affects phosphorylation	1
bisphenol A	increases expression	1
CGP 52608	affects binding, increases reaction	1
Resveratrol	affects cotreatment, decreases expression	1
Plant Extracts	affects cotreatment, decreases expression	1
Valproic Acid	increases methylation	1

Clinical trials (associated diseases)

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