PRSS21

Summary

PRSS21 (serine protease 21, HGNC:9485) is a protein-coding gene on chromosome 16p13.3, encoding Testisin (Q9Y6M0). Could regulate proteolytic events associated with testicular germ cell maturation.

This gene encodes a cell-surface anchored serine protease, which is a member of the trypsin family of serine proteases. The encoded protein is predicted to be active on peptide linkages involving the carboxyl group of lysine or arginine. The encoded protein localizes to the cytoplasm and the plasma membrane of premeiotic testicular germ cells and may be involved in progression of testicular tumors of germ cell origin. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene.

Source: NCBI Gene 10942 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 64 total
• MANE Select transcript: NM_006799

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9485
Approved symbol	PRSS21
Name	serine protease 21
Location	16p13.3
Locus type	gene with protein product
Status	Approved
Aliases	ESP-1, TEST1
Ensembl gene	ENSG00000007038
Ensembl biotype	protein_coding
OMIM	608159
Entrez	10942

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 6 protein_coding, 3 retained_intron, 2 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000005995, ENST00000450020, ENST00000570594, ENST00000570629, ENST00000571141, ENST00000574265, ENST00000574813, ENST00000575199, ENST00000575739, ENST00000577043, ENST00000943033, ENST00000943034

RefSeq mRNA: 4 — MANE Select: NM_006799 NM_001270452, NM_006799, NM_144956, NM_144957

CCDS: CCDS10478, CCDS45388

Canonical transcript exons

ENST00000005995 — 6 exons

Exon	Start	End
ENSE00000664443	2820955	2821109
ENSE00000873872	2821366	2821719
ENSE00001854828	2817237	2817332
ENSE00003470635	2818677	2818969
ENSE00003628602	2817801	2817966
ENSE00003636758	2817430	2817456

Expression profiles

Bgee: expression breadth ubiquitous, 121 present calls, max score 97.84.

FANTOM5 (CAGE): breadth broad, TPM avg 1.4977 / max 56.7990, expressed in 230 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
152305	0.8179	173
152307	0.4767	125
152303	0.0818	42
152304	0.0701	40
152302	0.0512	26

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right testis	UBERON:0004534	97.84	gold quality
left testis	UBERON:0004533	97.17	gold quality
testis	UBERON:0000473	96.88	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	89.42	gold quality
granulocyte	CL:0000094	85.42	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	83.12	gold quality
bone marrow	UBERON:0002371	77.24	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	76.15	gold quality
monocyte	CL:0000576	75.79	gold quality
leukocyte	CL:0000738	75.71	gold quality
gall bladder	UBERON:0002110	75.07	gold quality
bone marrow cell	CL:0002092	74.30	gold quality
right uterine tube	UBERON:0001302	73.51	gold quality
saliva-secreting gland	UBERON:0001044	72.66	gold quality
minor salivary gland	UBERON:0001830	71.66	gold quality
blood	UBERON:0000178	71.57	gold quality
lymph node	UBERON:0000029	71.11	gold quality
fallopian tube	UBERON:0003889	71.11	gold quality
spleen	UBERON:0002106	70.25	gold quality
right lung	UBERON:0002167	69.89	gold quality
tonsil	UBERON:0002372	69.47	gold quality
prostate gland	UBERON:0002367	69.24	gold quality
vermiform appendix	UBERON:0001154	67.76	gold quality
esophagus mucosa	UBERON:0002469	66.86	gold quality
upper lobe of left lung	UBERON:0008952	66.50	gold quality
left uterine tube	UBERON:0001303	64.57	gold quality
body of pancreas	UBERON:0001150	63.81	gold quality
duodenum	UBERON:0002114	63.70	gold quality
vagina	UBERON:0000996	63.00	gold quality
lung	UBERON:0002048	62.37	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-MTAB-7249	yes	10.86
E-ANND-3	no	1.79

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

9 targeting PRSS21, 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-1-3P	99.93	72.35	1914
HSA-MIR-206	99.93	72.50	1893
HSA-MIR-613	99.91	71.50	1710
HSA-MIR-556-3P	99.74	68.75	1203
HSA-MIR-4708-3P	99.51	67.99	870
HSA-MIR-6128	99.33	67.83	1581
HSA-MIR-3173-5P	97.35	65.82	1282
HSA-MIR-6799-3P	97.35	65.60	1302
HSA-MIR-2861	95.24	65.47	1056

Literature-anchored findings (GeneRIF, showing 5)

• Loss of Testisin is caused, at least in part, by DNA hypermethylation and histone deacetylation, and suggest a tumour suppressor role for Testisin in testicular tumorigenesis. (PMID:15685234)
• The results demonstrate for the first time that aberrant methylation of specific CpG sites near the transcription initiation site is an important factor in testisin gene silencing in TGCT. (PMID:16810501)
• These data suggest that aberrant regulation of PRSS21 may underlie certain secondary male infertility syndromes, such as “easily decapitated” spermatozoa in humans. (PMID:19571264)
• Testisin may promote carcinogenesis by inhibiting tumor suppressor activity of maspin. (PMID:20211623)
• Testisin activates PAR-2, inducing PAR-2 loss from the cell surface, internalization, and cellular signaling. (PMID:25519908)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
mus_musculus	Prss21	ENSMUSG00000024116
rattus_norvegicus	Prss21	ENSRNOG00000047969
drosophila_melanogaster	Sb	FBGN0003319
drosophila_melanogaster	CG17242	FBGN0250841

Paralogs (17): PRSS22 (ENSG00000005001), TMPRSS11E (ENSG00000087128), HPN (ENSG00000105707), TMPRSS13 (ENSG00000137747), ST14 (ENSG00000149418), TMPRSS11D (ENSG00000153802), TMPRSS15 (ENSG00000154646), TMPRSS3 (ENSG00000160183), TMPRSS5 (ENSG00000166682), TMPRSS7 (ENSG00000176040), TMPRSS9 (ENSG00000178297), TMPRSS2 (ENSG00000184012), TMPRSS11B (ENSG00000185873), TMPRSS6 (ENSG00000187045), TMPRSS11A (ENSG00000187054), TMPRSS11F (ENSG00000198092), PRSS41 (ENSG00000215148)

Protein

Protein identifiers

Testisin — Q9Y6M0 (reviewed: Q9Y6M0)

Alternative names: Eosinophil serine protease 1, Serine protease 21

All UniProt accessions (5): Q9Y6M0, I3L0U2, I3L2G7, I3L3C7, I3L3F7

UniProt curated annotations — full annotation on UniProt →

Function. Could regulate proteolytic events associated with testicular germ cell maturation.

Subcellular location. Cell membrane.

Tissue specificity. Expressed predominantly in premeiotic testicular germ cells, mostly late pachytene and diplotene spermatocytes.

Similarity. Belongs to the peptidase S1 family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q9Y6M0-1	1, L	yes
Q9Y6M0-2	2, S
Q9Y6M0-3	3

RefSeq proteins (4): NP_001257381, NP_006790, NP_659205, NP_659206 (=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 (20 total): disulfide bond 5, glycosylation site 3, active site 3, propeptide 2, splice variant 2, signal peptide 1, sequence variant 1, chain 1, domain 1, lipid moiety-binding region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9Y6M0-F1	85.01	0.71

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): 82 (charge relay system); 137 (charge relay system); 238 (charge relay system)

Post-translational modifications (1): 288

Disulfide bonds (5): 33–157, 67–83, 171–244, 204–223, 234–262

Glycosylation sites (3): 200, 273, 167

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-163125	Post-translational modification: synthesis of GPI-anchored proteins
R-HSA-392499	Metabolism of proteins
R-HSA-597592	Post-translational protein modification

MSigDB gene sets: 47 (showing top): RIZKI_TUMOR_INVASIVENESS_3D_DN, GOBP_MALE_GAMETE_GENERATION, GOBP_DEVELOPMENTAL_PROCESS_INVOLVED_IN_REPRODUCTION, GOCC_SIDE_OF_MEMBRANE, GOBP_PROTEOLYSIS, NIKOLSKY_BREAST_CANCER_16P13_AMPLICON, GOMF_PEPTIDASE_ACTIVITY, REACTOME_POST_TRANSLATIONAL_PROTEIN_MODIFICATION, FORTSCHEGGER_PHF8_TARGETS_DN, ZWANG_TRANSIENTLY_UP_BY_2ND_EGF_PULSE_ONLY, ATM_DN.V1_DN, REACTOME_POST_TRANSLATIONAL_MODIFICATION_SYNTHESIS_OF_GPI_ANCHORED_PROTEINS, BRCA1_DN.V1_UP, STK33_NOMO_DN, KRAS.KIDNEY_UP.V1_DN

GO Biological Process (2): proteolysis (GO:0006508), spermatogenesis (GO:0007283)

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

GO Cellular Component (6): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615), cytoplasm (GO:0005737), plasma membrane (GO:0005886), membrane (GO:0016020), side of membrane (GO:0098552)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Post-translational protein modification	1
Metabolism of proteins	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
membrane	2
protein metabolic process	1
developmental process involved in reproduction	1
male gamete generation	1
endopeptidase activity	1
serine-type peptidase activity	1
peptidase activity	1
serine hydrolase activity	1
binding	1
hydrolase activity	1
catalytic activity, acting on a protein	1
catalytic activity	1
intracellular anatomical structure	1
cell periphery	1
leaflet of membrane bilayer	1

Protein interactions and networks

STRING

932 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PRSS21	OAZ3	Q9UMX2	578
PRSS21	ODF1	Q14990	501
PRSS21	STEEP1	Q9H5V9	476
PRSS21	PRSS37	A4D1T9	421
PRSS21	CCDC42	Q96M95	408
PRSS21	SPATC1L	Q9H0A9	400
PRSS21	ERLIN2	O94905	393
PRSS21	PAQR4	Q8N4S7	384
PRSS21	EIF1	P41567	377
PRSS21	HNRNPA1L2	Q32P51	377
PRSS21	FUNDC2	Q9BWH2	371
PRSS21	PPP1CC	P36873	368
PRSS21	PLD5	Q8N7P1	364
PRSS21	SPATA6	Q9NWH7	358
PRSS21	PTTG1	O95997	353
PRSS21	TACSTD2	P09758	353

IntAct

15 interactions, top by confidence:

A	B	Type	Score
SERPINB5	PRSS21	psi-mi:“MI:0915”(physical association)	0.640
PRSS21	SERPINB5	psi-mi:“MI:0915”(physical association)	0.640
SERPINB5	PRSS21	psi-mi:“MI:0407”(direct interaction)	0.640
PRSS21	SERPINB5	psi-mi:“MI:0403”(colocalization)	0.640
PARP2	PRSS21	psi-mi:“MI:0557”(adp ribosylation reaction)	0.440
SECTM1	BCLAF1	psi-mi:“MI:0914”(association)	0.350
BST1	GXYLT2	psi-mi:“MI:0914”(association)	0.350
PRSS21	HSPA5	psi-mi:“MI:0914”(association)	0.350
OR14J1	BST1	psi-mi:“MI:0914”(association)	0.350
AFG2A	ESYT2	psi-mi:“MI:0914”(association)	0.350
POLD3	ESYT2	psi-mi:“MI:0914”(association)	0.350
AFG2B	MMP24OS	psi-mi:“MI:0914”(association)	0.350

BioGRID (35): PRSS21 (Affinity Capture-MS), PRSS21 (Affinity Capture-MS), PRSS21 (Affinity Capture-MS), PRSS21 (Affinity Capture-MS), PRSS21 (Affinity Capture-MS), PRSS21 (Affinity Capture-MS), PRSS21 (Affinity Capture-MS), PRSS21 (Affinity Capture-MS), PRSS21 (Affinity Capture-MS), PRSS21 (Affinity Capture-MS), PRSS21 (Affinity Capture-MS), PRSS21 (Affinity Capture-MS), PRSS21 (Affinity Capture-MS), PRSS21 (Affinity Capture-MS), PRSS21 (Affinity Capture-RNA)

ESM2 similar proteins: A1L453, A2VE36, A6NIE9, A8MTI9, E5RG02, O35453, O70169, P08709, P20231, P21845, P50343, P83748, Q14B25, Q14BX2, Q15661, Q16651, Q2F9P2, Q2F9P4, Q2UVH8, Q3UKY7, Q3V0Q7, Q402U7, Q571E5, Q5FBW1, Q5FBW2, Q5M8S2, Q6AXZ6, Q6BEA2, Q6IE62, Q6IE63, Q6UWB4, Q76HL1, Q7RTY5, Q7Z410, Q7Z5A4, Q8BJR6, Q8K4I7, Q8VIF2, Q920S2, Q99MS4

Diamond homologs: A0A1S4GMJ4, A6NIE9, A8JUP7, G3V801, O08762, O42207, O60235, P00741, P00745, P00762, P00765, P03951, P05049, P07477, P07478, P0CW18, P15120, P16292, P16295, P19799, P29786, P29787, P35030, P35039, P69525, P79953, Q14B25, Q14BX2, Q14C59, Q1JRP2, Q27081, Q28278, Q28315, Q28412, Q29463, Q2KJ63, Q2VG86, Q5G265, Q5U405, Q6BEA2

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
PRSS21	up-regulates	RAD21	cleavage

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	50
Likely benign	8
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1416 predictions. Top by Δscore:

Variant	Effect	Δscore
16:2817325:G:GT	donor_gain	1.0000
16:2818963:G:GT	donor_gain	1.0000
16:2818968:GG:G	donor_gain	1.0000
16:2818969:GG:G	donor_gain	1.0000
16:2817328:GCCGG:G	donor_gain	0.9900
16:2817330:CGGG:C	donor_loss	0.9900
16:2817331:GG:G	donor_gain	0.9900
16:2817332:GG:G	donor_gain	0.9900
16:2817332:GGT:G	donor_loss	0.9900
16:2817333:G:GC	donor_loss	0.9900
16:2817334:T:A	donor_loss	0.9900
16:2817967:G:GG	donor_gain	0.9900
16:2818907:T:G	donor_gain	0.9900
16:2818911:G:GG	donor_gain	0.9900
16:2818932:C:G	donor_gain	0.9900
16:2820939:A:AG	acceptor_gain	0.9900
16:2820940:C:G	acceptor_gain	0.9900
16:2820943:T:G	acceptor_gain	0.9900
16:2820980:GGAA:G	acceptor_gain	0.9900
16:2821105:GCTTC:G	donor_gain	0.9900
16:2821110:G:GG	donor_gain	0.9900
16:2821141:G:GT	donor_gain	0.9900
16:2821142:A:T	donor_gain	0.9900
16:2817333:G:GG	donor_gain	0.9800
16:2817335:GAGC:G	donor_loss	0.9800
16:2817962:GAAAC:G	donor_gain	0.9800
16:2818675:A:AG	acceptor_gain	0.9800
16:2818676:G:GA	acceptor_gain	0.9800
16:2818676:GCT:G	acceptor_gain	0.9800
16:2818907:T:TG	donor_gain	0.9800

AlphaMissense

2032 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:2817874:G:C	W55C	0.998
16:2817874:G:T	W55C	0.998
16:2818947:G:C	W176C	0.998
16:2818947:G:T	W176C	0.998
16:2821014:T:A	C204S	0.998
16:2821015:G:C	C204S	0.998
16:2821071:T:A	C223S	0.998
16:2821072:G:C	C223S	0.998
16:2817872:T:A	W55R	0.997
16:2817872:T:C	W55R	0.997
16:2817917:A:C	S70R	0.997
16:2817919:C:A	S70R	0.997
16:2817919:C:G	S70R	0.997
16:2817958:C:G	C83W	0.997
16:2818834:G:C	A139P	0.997
16:2818835:C:A	A139D	0.997
16:2818829:A:T	D137V	0.996
16:2818945:T:A	W176R	0.996
16:2818945:T:C	W176R	0.996
16:2821015:G:A	C204Y	0.996
16:2821071:T:C	C223R	0.996
16:2821072:G:A	C223Y	0.996
16:2821429:A:C	S257R	0.996
16:2821431:C:A	S257R	0.996
16:2821431:C:G	S257R	0.996
16:2817878:G:T	G57W	0.995
16:2817957:G:A	C83Y	0.995
16:2818932:C:G	C171W	0.995
16:2821016:C:G	C204W	0.995
16:2821073:T:G	C223W	0.995

dbSNP variants (sampled 300 via entrez): RS1000507369 (16:2820072 A>G), RS1000968942 (16:2818001 G>A,C,T), RS1001195163 (16:2816839 G>A,C), RS1001349126 (16:2820643 G>A), RS1002683412 (16:2820302 C>T), RS1003165474 (16:2816616 T>C), RS1003273772 (16:2815428 C>G,T), RS1003502740 (16:2817663 A>G), RS1003803085 (16:2819365 C>A,T), RS1004438407 (16:2819664 G>T), RS1005477675 (16:2820365 G>C), RS1005631667 (16:2820657 C>A,G,T), RS1005806844 (16:2821498 T>A), RS1006372088 (16:2817017 G>A,C), RS1007128468 (16:2821164 C>T)

Disease associations

OMIM: gene MIM:608159 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

14 total (human), top 14 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, affects cotreatment, increases abundance, increases expression	3
fluorene-9-bisphenol	decreases expression	1
bisphenol A	decreases methylation, affects cotreatment	1
arsenite	increases methylation	1
2-amino-3,8-dimethylimidazo(4,5-f)quinoxaline	decreases expression	1
bisphenol S	decreases methylation	1
Fulvestrant	affects cotreatment, decreases methylation	1
Acetaminophen	decreases expression	1
Air Pollutants	increases expression, increases abundance	1
Arsenic	affects cotreatment, decreases expression, increases abundance	1
Benzo(a)pyrene	increases methylation	1
Valproic Acid	increases methylation	1
Cadmium Chloride	decreases expression	1
Particulate Matter	increases abundance, increases expression	1

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B2C9	Abcam HeLa PRSS21 KO	Cancer cell line	Female

Clinical trials (associated diseases)

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