PRSS37

Summary

PRSS37 (serine protease 37, HGNC:29211) is a protein-coding gene on chromosome 7q34, encoding Probable inactive serine protease 37 (A4D1T9). Plays a role in male fertility.

Predicted to enable serine-type endopeptidase activity. Involved in positive regulation of acrosome reaction and regulation of protein processing. Located in acrosomal vesicle.

Source: NCBI Gene 136242 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 32 total
• MANE Select transcript: NM_001008270

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:29211
Approved symbol	PRSS37
Name	serine protease 37
Location	7q34
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000165076
Ensembl biotype	protein_coding
Entrez	136242

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 2 protein_coding, 2 nonsense_mediated_decay

ENST00000350549, ENST00000419085, ENST00000438520, ENST00000452758

RefSeq mRNA: 3 — MANE Select: NM_001008270 NM_001008270, NM_001171951, NM_001370403

CCDS: CCDS34764

Canonical transcript exons

ENST00000350549 — 5 exons

Exon	Start	End
ENSE00001152251	141836300	141836535
ENSE00001206685	141839338	141839479
ENSE00001393086	141841016	141841485
ENSE00003496773	141837860	141838113
ENSE00003502819	141837112	141837248

Expression profiles

Bgee: expression breadth ubiquitous, 101 present calls, max score 90.95.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0609 / max 62.2497, expressed in 3 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
86585	0.0609	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right testis	UBERON:0004534	90.95	gold quality
left testis	UBERON:0004533	90.90	gold quality
testis	UBERON:0000473	87.82	gold quality
sperm	CL:0000019	84.61	gold quality
adult organism	UBERON:0007023	80.54	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	79.94	gold quality
left ventricle myocardium	UBERON:0006566	78.35	gold quality
cardiac muscle of right atrium	UBERON:0003379	78.33	gold quality
kidney epithelium	UBERON:0004819	69.54	gold quality
epithelial cell of pancreas	CL:0000083	65.57	gold quality
myocardium	UBERON:0002349	63.04	gold quality
endothelial cell	CL:0000115	56.91	gold quality
nasal cavity epithelium	UBERON:0005384	55.87	gold quality
jejunal mucosa	UBERON:0000399	55.74	gold quality
gingival epithelium	UBERON:0001949	55.73	gold quality
tibialis anterior	UBERON:0001385	55.57	silver quality
pancreatic ductal cell	CL:0002079	55.35	silver quality
quadriceps femoris	UBERON:0001377	55.05	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	54.92	gold quality
calcaneal tendon	UBERON:0003701	54.80	gold quality
mucosa of paranasal sinus	UBERON:0005030	54.77	gold quality
vastus lateralis	UBERON:0001379	54.09	gold quality
upper arm skin	UBERON:0004263	53.52	gold quality
heart right ventricle	UBERON:0002080	52.39	gold quality
right uterine tube	UBERON:0001302	52.07	gold quality
deltoid	UBERON:0001476	51.83	gold quality
gingiva	UBERON:0001828	51.22	gold quality
cerebellar hemisphere	UBERON:0002245	50.83	gold quality
cerebellar cortex	UBERON:0002129	50.81	gold quality
right hemisphere of cerebellum	UBERON:0014890	50.75	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.93

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

17 targeting PRSS37, 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-4510	100.00	66.60	2050
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-579-3P	99.86	71.66	3628
HSA-MIR-221-3P	99.86	71.56	1329
HSA-MIR-222-3P	99.86	71.35	1337
HSA-MIR-664B-3P	99.84	71.65	3590
HSA-MIR-12131	99.48	68.72	1673
HSA-MIR-4686	98.77	66.87	964
HSA-MIR-2467-3P	98.65	67.18	1969
HSA-MIR-6873-5P	98.45	66.14	1417
HSA-MIR-5585-3P	98.25	67.41	941
HSA-MIR-1270	96.94	66.65	931
HSA-MIR-620	96.94	66.79	888

Literature-anchored findings (GeneRIF, showing 1)

• Sperm with low PRSS37 contents exhibit abnormal activation of the proacrosin/acrosin system and premature proteolysis of ADAM2, which may impair the functional competence of human sperm in vivo (PMID:27649891)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Prss37	ENSMUSG00000029909
rattus_norvegicus	Prss37	ENSRNOG00000012201

Paralogs (14): PRSS33 (ENSG00000103355), PLAT (ENSG00000104368), PLG (ENSG00000122194), PLGLB2 (ENSG00000125551), PRSS27 (ENSG00000172382), KLK15 (ENSG00000174562), PLGLB1 (ENSG00000183281), PRSS57 (ENSG00000185198), TMPRSS12 (ENSG00000186452), OVCH1 (ENSG00000187950), PRSS48 (ENSG00000189099), GZMM (ENSG00000197540), KLK9 (ENSG00000213022), PRSS50 (ENSG00000283706)

Protein

Protein identifiers

Probable inactive serine protease 37 — A4D1T9 (reviewed: A4D1T9)

Alternative names: Probable inactive trypsin-X2

All UniProt accessions (3): A4D1T9, F8WBF8, F8WDA6

UniProt curated annotations — full annotation on UniProt →

Function. Plays a role in male fertility. May have a role in sperm migration or binding to zona-intact eggs. Involved in the activation of the proacrosin/acrosin system.

Subcellular location. Cytoplasmic vesicle. Secretory vesicle. Acrosome. Secreted.

Tissue specificity. Testis-specific. Expressed in spermatids (at protein level).

Disease relevance. Patients with unexplained male infertility (UMI) show a decrease in the number of sperm cells compared to fertile men. Sperm exhibit also abnormal activation of the proacrosin/acrosin system and premature proteolysis of ADAM2.

Similarity. Belongs to the peptidase S1 family.

RefSeq proteins (3): NP_001008271, NP_001165422, NP_001357332 (=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 (7 total): disulfide bond 3, signal peptide 1, chain 1, domain 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-A4D1T9-F1	80.44	0.48

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): 40–56, 131–198, 163–177

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 63 (showing top): GOBP_SINGLE_FERTILIZATION, GOBP_POSITIVE_REGULATION_OF_REPRODUCTIVE_PROCESS, GOCC_SECRETORY_GRANULE, GOBP_PROTEIN_MATURATION, GOBP_SPERM_EGG_RECOGNITION, GOBP_REGULATION_OF_REPRODUCTIVE_PROCESS, GOBP_REGULATION_OF_PROTEIN_MATURATION, GOBP_REGULATION_OF_ACROSOME_REACTION, GOBP_ACROSOME_REACTION, GOBP_FERTILIZATION, GOBP_CELL_CELL_RECOGNITION, GOBP_REGULATION_OF_PROTEOLYSIS, GOBP_BINDING_OF_SPERM_TO_ZONA_PELLUCIDA, GOCC_SECRETORY_VESICLE, GOBP_PROTEOLYSIS

GO Biological Process (10): proteolysis (GO:0006508), binding of sperm to zona pellucida (GO:0007339), primordial germ cell migration (GO:0008354), cell migration (GO:0016477), protein maturation (GO:0051604), regulation of protein processing (GO:0070613), positive regulation of fertilization (GO:1905516), positive regulation of acrosome reaction (GO:2000344), single fertilization (GO:0007338), positive regulation of reproductive process (GO:2000243)

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

GO Cellular Component (6): acrosomal vesicle (GO:0001669), obsolete extracellular space (GO:0005615), nucleus (GO:0005634), extracellular region (GO:0005576), secretory granule (GO:0030141), cytoplasmic vesicle (GO:0031410)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein metabolic process	2
fertilization	2
positive regulation of reproductive process	2
sperm-egg recognition	1
gamete generation	1
cell migration	1
cell motility	1
gene expression	1
protein processing	1
regulation of proteolysis	1
regulation of protein maturation	1
regulation of fertilization	1
acrosome reaction	1
regulation of acrosome reaction	1
reproductive process	1
positive regulation of biological process	1
regulation of reproductive process	1
endopeptidase activity	1
serine-type peptidase activity	1
secretory granule	1
intracellular membrane-bounded organelle	1
cellular anatomical structure	1
endomembrane system	1
secretory vesicle	1
cytoplasm	1
intracellular vesicle	1

Protein interactions and networks

STRING

658 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PRSS37	PRSS55	Q6UWB4	686
PRSS37	PDILT	Q8N807	671
PRSS37	PRSS54	Q6PEW0	643
PRSS37	PRADC1	Q9BSG0	622
PRSS37	RNASE10	Q5GAN6	615
PRSS37	ADAM2	P78326	613
PRSS37	CALR3	Q96L12	595
PRSS37	PMIS2	A0A1W2PS18	544
PRSS37	CCDC18	Q5T9S5	509
PRSS37	TEX101	Q9BY14	502
PRSS37	UACA	Q9BZF9	502
PRSS37	SFXN4	Q6P4A7	492
PRSS37	TPST2	O60704	469
PRSS37	FAM170B	A6NMN3	456
PRSS37	ZNF490	Q9ULM2	447

IntAct

5 interactions, top by confidence:

A	B	Type	Score
PRSS37	MANBA	psi-mi:“MI:0914”(association)	0.530
GSK3A	PRSS37	psi-mi:“MI:0914”(association)	0.350
GSK3B	PRSS37	psi-mi:“MI:0914”(association)	0.350

BioGRID (22): LRP5 (Affinity Capture-MS), CD109 (Affinity Capture-MS), FUT11 (Affinity Capture-MS), MANBA (Affinity Capture-MS), LRP6 (Affinity Capture-MS), AKAP1 (Affinity Capture-MS), ARSK (Affinity Capture-MS), GPR98 (Affinity Capture-MS), PCDH20 (Affinity Capture-MS), UBR5 (Affinity Capture-MS), FAT4 (Affinity Capture-MS), PRSS37 (Affinity Capture-MS), PRSS37 (Affinity Capture-MS), GPR98 (Affinity Capture-MS), MANBA (Affinity Capture-MS)

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: 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

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	26
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

634 predictions. Top by Δscore:

Variant	Effect	Δscore
7:141836547:CA:C	acceptor_gain	1.0000
7:141837132:CTT:C	donor_gain	1.0000
7:141837133:TTT:T	donor_gain	1.0000
7:141837134:TTC:T	donor_gain	1.0000
7:141837135:T:A	donor_gain	1.0000
7:141837159:T:A	donor_gain	1.0000
7:141837172:T:A	donor_gain	1.0000
7:141839335:A:AC	donor_gain	1.0000
7:141839336:A:C	donor_gain	1.0000
7:141839370:G:C	donor_gain	1.0000
7:141836548:A:AC	acceptor_gain	0.9900
7:141836548:A:C	acceptor_gain	0.9900
7:141836551:C:CT	acceptor_gain	0.9900
7:141836552:A:T	acceptor_gain	0.9900
7:141837106:GATTA:G	donor_loss	0.9900
7:141837107:ATTAC:A	donor_loss	0.9900
7:141837108:TTACC:T	donor_loss	0.9900
7:141837109:TA:T	donor_loss	0.9900
7:141837110:ACC:A	donor_gain	0.9900
7:141837110:ACCCC:A	donor_loss	0.9900
7:141837111:CCC:C	donor_gain	0.9900
7:141837859:CCA:C	donor_gain	0.9900
7:141837972:AG:A	donor_gain	0.9900
7:141837973:G:C	donor_gain	0.9900
7:141837997:T:TA	donor_gain	0.9900
7:141838112:TT:T	acceptor_gain	0.9900
7:141841012:ATACC:A	donor_loss	0.9900
7:141841014:A:AC	donor_gain	0.9900
7:141841015:C:CC	donor_gain	0.9900
7:141841015:C:T	donor_loss	0.9900

AlphaMissense

1549 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:141836422:C:A	W227C	0.997
7:141836422:C:G	W227C	0.997
7:141837191:C:G	C163S	0.997
7:141837192:A:T	C163S	0.997
7:141837897:A:C	C131W	0.997
7:141837898:C:G	C131S	0.997
7:141837899:A:T	C131S	0.997
7:141837149:C:G	C177S	0.996
7:141837150:A:T	C177S	0.996
7:141837899:A:G	C131R	0.996
7:141839347:C:G	C56S	0.995
7:141839348:A:T	C56S	0.995
7:141837898:C:T	C131Y	0.994
7:141837985:A:G	L102P	0.994
7:141836510:C:G	C198S	0.993
7:141836511:A:T	C198S	0.993
7:141839346:G:C	C56W	0.993
7:141839347:C:T	C56Y	0.993
7:141839348:A:G	C56R	0.993
7:141839395:C:T	C40Y	0.993
7:141836424:A:G	W227R	0.992
7:141836424:A:T	W227R	0.992
7:141839394:A:C	C40W	0.992
7:141839395:C:G	C40S	0.992
7:141839396:A:T	C40S	0.992
7:141837991:A:G	L100P	0.991
7:141838093:C:A	G66V	0.991
7:141839396:A:G	C40R	0.991
7:141837876:C:A	W138C	0.990
7:141837876:C:G	W138C	0.990

dbSNP variants (sampled 300 via entrez): RS1000087368 (7:141837773 C>T), RS1000107818 (7:141842696 G>A), RS1000189128 (7:141843087 C>CT), RS1001376947 (7:141838611 A>G), RS1003213694 (7:141840646 T>C), RS1003455030 (7:141840012 C>A), RS1004172344 (7:141840101 T>A), RS1004631908 (7:141840341 A>G), RS1004669132 (7:141835979 G>A), RS1006133736 (7:141842821 A>G), RS1006254653 (7:141841373 T>C), RS1006648064 (7:141843238 C>G,T), RS1006706653 (7:141839971 T>G), RS1007065146 (7:141840253 T>C), RS1007132499 (7:141842469 A>G)

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
GCST007880_7	Emotional lability in attention deficit hyperactivity disorder	8.000000e-06
GCST008017_3	Bitter taste perception (6-n-propylthiouracil) in obesity with metabolic syndrome	8.000000e-07

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0008475	mood instability measurement

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
Benzo(a)pyrene	increases methylation	1
Diethylhexyl Phthalate	decreases expression	1
Folic Acid	decreases expression	1
Silicon Dioxide	decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Valproic Acid	decreases methylation	1

Clinical trials (associated diseases)

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