PRSS35

Summary

PRSS35 (serine protease 35, HGNC:21387) is a protein-coding gene on chromosome 6q14.2, encoding Inactive serine protease 35 (Q8N3Z0).

Predicted to be located in extracellular region.

Source: NCBI Gene 167681 — RefSeq curated summary.

At a glance

• GWAS associations: 6
• Clinical variants (ClinVar): 56 total
• MANE Select transcript: NM_153362

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:21387
Approved symbol	PRSS35
Name	serine protease 35
Location	6q14.2
Locus type	gene with protein product
Status	Approved
Aliases	MGC46520, dJ223E3.1
Ensembl gene	ENSG00000146250
Ensembl biotype	protein_coding
Entrez	167681

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 3 protein_coding

ENST00000369700, ENST00000867649, ENST00000867650

RefSeq mRNA: 2 — MANE Select: NM_153362 NM_001170423, NM_153362

CCDS: CCDS4999

Canonical transcript exons

ENST00000369700 — 2 exons

Exon	Start	End
ENSE00001450674	83523422	83525704
ENSE00001450675	83512534	83512694

Expression profiles

Bgee: expression breadth ubiquitous, 170 present calls, max score 95.64.

FANTOM5 (CAGE): breadth broad, TPM avg 3.0246 / max 760.7019, expressed in 495 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
68777	2.6083	468
68776	0.3929	145
68779	0.0143	4
68778	0.0091	4

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
tibia	UBERON:0000979	95.64	gold quality
germinal epithelium of ovary	UBERON:0001304	86.87	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	84.94	gold quality
adrenal tissue	UBERON:0018303	82.24	gold quality
ventricular zone	UBERON:0003053	78.01	gold quality
descending thoracic aorta	UBERON:0002345	76.79	gold quality
dorsal root ganglion	UBERON:0000044	76.57	gold quality
thoracic aorta	UBERON:0001515	76.37	gold quality
ascending aorta	UBERON:0001496	76.21	gold quality
putamen	UBERON:0001874	75.95	gold quality
trigeminal ganglion	UBERON:0001675	75.58	gold quality
right coronary artery	UBERON:0001625	75.02	gold quality
caudate nucleus	UBERON:0001873	74.81	gold quality
ovary	UBERON:0000992	74.61	gold quality
nucleus accumbens	UBERON:0001882	74.53	gold quality
gall bladder	UBERON:0002110	73.38	gold quality
right atrium auricular region	UBERON:0006631	73.32	gold quality
cardiac atrium	UBERON:0002081	72.92	gold quality
aorta	UBERON:0000947	72.57	gold quality
cartilage tissue	UBERON:0002418	71.82	gold quality
left ovary	UBERON:0002119	71.65	gold quality
amygdala	UBERON:0001876	71.57	gold quality
parietal pleura	UBERON:0002400	70.94	gold quality
endothelial cell	CL:0000115	70.64	silver quality
cardiac muscle of right atrium	UBERON:0003379	70.59	silver quality
right ovary	UBERON:0002118	70.36	gold quality
metanephros	UBERON:0000081	70.02	gold quality
popliteal artery	UBERON:0002250	69.78	gold quality
tibial artery	UBERON:0007610	69.75	gold quality
right adrenal gland cortex	UBERON:0035827	69.46	gold quality

Single-cell (SCXA)

Detected in 6 experiment(s), a significant marker in 5.

Experiment	Marker?	Max mean expression
E-MTAB-7008	yes	307.66
E-HCAD-10	yes	33.93
E-MTAB-7316	yes	33.79
E-GEOD-137537	yes	33.39
E-CURD-112	yes	5.76
E-ANND-3	no	2.62

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CTCF

miRNA regulators (miRDB)

77 targeting PRSS35, 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-5692A	100.00	74.40	6850
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-4673	100.00	66.64	1490
HSA-MIR-485-3P	99.98	70.68	1585
HSA-MIR-539-3P	99.98	70.74	1616
HSA-MIR-6888-3P	99.97	65.95	1170
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-23A-3P	99.95	74.24	3163
HSA-MIR-23B-3P	99.95	74.24	3163
HSA-MIR-23C	99.95	73.92	3192
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-548AQ-3P	99.93	72.66	4867
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-374A-5P	99.90	71.34	2923
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-605-3P	99.88	69.22	1833
HSA-MIR-3919	99.87	69.45	2489
HSA-MIR-548D-3P	99.87	70.67	4362
HSA-MIR-548BB-3P	99.86	70.58	4354
HSA-MIR-629-3P	99.85	67.99	1875
HSA-MIR-369-3P	99.85	70.52	2264
HSA-MIR-548AC	99.84	70.77	4351
HSA-MIR-548H-3P	99.84	70.80	4349
HSA-MIR-548Z	99.84	70.80	4349

Literature-anchored findings (GeneRIF, showing 2)

• Mouse ortholog of human PRSS35 is an ovary-selectively expressed gene. (PMID:16870946)
• We provide further evidence of the involvement of chromosome 6q in cleft lip/palate and suggest PRSS35 as a novel candidate gene. (PMID:20511563)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	PRSS35	ENSDARG00000059081
danio_rerio	prss35	ENSDARG00000100691
mus_musculus	Prss35	ENSMUSG00000033491
rattus_norvegicus	Prss35	ENSRNOG00000025184

Paralogs (1): PRSS23 (ENSG00000150687)

Protein

Protein identifiers

Inactive serine protease 35 — Q8N3Z0 (reviewed: Q8N3Z0)

All UniProt accessions (1): Q8N3Z0

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Secreted.

Similarity. Belongs to the peptidase S1 family.

RefSeq proteins (2): NP_001163894, NP_699193* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001254	Trypsin_dom	Domain
IPR009003	Peptidase_S1_PA	Homologous_superfamily
IPR018114	TRYPSIN_HIS	Active_site
IPR043504
IPR050966	Glutamyl_endopeptidase	Family

Pfam: PF00089

UniProt features (10 total): compositionally biased region 3, signal peptide 1, chain 1, domain 1, region of interest 1, glycosylation site 1, disulfide bond 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8N3Z0-F1	79.60	0.53

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 (1): 154–170

Glycosylation sites (1): 90

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 79 (showing top): RRAGTTGT_UNKNOWN, STAEGE_EWING_FAMILY_TUMOR, GOZGIT_ESR1_TARGETS_DN, AML_Q6, AACTTT_UNKNOWN, AFFAR_YY1_TARGETS_UP, SENESE_HDAC1_TARGETS_UP, PIT1_Q6, RIGGI_EWING_SARCOMA_PROGENITOR_UP, WANG_SMARCE1_TARGETS_UP, chr6q14, TGATTTRY_GFI1_01, MIKKELSEN_ES_ICP_WITH_H3K4ME3, CHICAS_RB1_TARGETS_CONFLUENT, QI_HYPOXIA_TARGETS_OF_HIF1A_AND_FOXA2

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

GO Molecular Function (2): serine-type endopeptidase activity (GO:0004252), protein binding (GO:0005515)

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
cellular anatomical structure	1

Protein interactions and networks

STRING

580 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PRSS35	WFDC2	Q14508	605
PRSS35	DHRS13	Q6UX07	564
PRSS35	MDGA2	Q7Z553	458
PRSS35	RGS17	Q9UGC6	449
PRSS35	ADAMTS9	Q9P2N4	446
PRSS35	SNAP91	O60641	443
PRSS35	KCNQ3	O43525	416
PRSS35	RANBP3L	Q86VV4	396
PRSS35	CCL26	Q9Y258	393
PRSS35	KDF1	Q8NAX2	385
PRSS35	TMEM54	Q969K7	349
PRSS35	SLC46A2	Q9BY10	336
PRSS35	SIGLEC15	Q6ZMC9	313
PRSS35	PRSS54	Q6PEW0	307
PRSS35	COL6A2	P12110	306

IntAct

6 interactions, top by confidence:

A	B	Type	Score
PRSS35	C1QBP	psi-mi:“MI:0915”(physical association)	0.500
PRSS35	C1QBP	psi-mi:“MI:0914”(association)	0.500
PRSS35	H2BC9	psi-mi:“MI:0915”(physical association)	0.400
PRSS35	NDUFAB1	psi-mi:“MI:0914”(association)	0.350

BioGRID (8): PRSS35 (Affinity Capture-MS), OXCT1 (Affinity Capture-MS), MTFMT (Affinity Capture-MS), C1QBP (Affinity Capture-MS), ECH1 (Affinity Capture-MS), HIST1H2BH (Proximity Label-MS), PRSS35 (Affinity Capture-MS), PRSS35 (Affinity Capture-MS)

ESM2 similar proteins: A4VCL2, O19112, O62589, O73797, O75072, O75339, O95084, P13721, P18292, P19221, P30432, P79701, Q08629, Q09101, Q0VBN2, Q0WQD2, Q1LZE9, Q1WK23, Q1WK24, Q4G148, Q5E9X7, Q5K027, Q5R212, Q5R537, Q5XIL2, Q5XV99, Q60HG0, Q62288, Q66K08, Q6AY61, Q701R0, Q701R1, Q701R2, Q8C0F9, Q8CBQ5, Q8GWW4, Q8GZ81, Q8IZU8, Q8N3Z0, Q8R507

Diamond homologs: O19045, O46644, O95084, Q1LZE9, Q1WK23, Q1WK24, Q5E9X7, Q5R212, Q63207, Q6AY61, Q8C0F9, Q8N3Z0, Q9D6X6, P08217

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	48
Likely benign	4
Benign	3

Top pathogenic / likely-pathogenic (0)

SpliceAI

305 predictions. Top by Δscore:

Variant	Effect	Δscore
6:83521294:GTT:G	donor_gain	1.0000
6:83523420:A:G	acceptor_gain	1.0000
6:83521292:GAGTT:G	donor_gain	0.9900
6:83523418:TAAG:T	acceptor_loss	0.9900
6:83523419:A:AG	acceptor_gain	0.9900
6:83523419:AAG:A	acceptor_gain	0.9900
6:83523420:A:AT	acceptor_loss	0.9900
6:83523421:G:GG	acceptor_gain	0.9900
6:83523421:G:GT	acceptor_loss	0.9900
6:83512692:C:T	donor_gain	0.9800
6:83521297:G:GG	donor_gain	0.9800
6:83512692:CAGG:C	donor_loss	0.9700
6:83512693:AGGT:A	donor_loss	0.9700
6:83512694:GGTAA:G	donor_loss	0.9700
6:83512695:G:GA	donor_loss	0.9700
6:83512696:T:G	donor_loss	0.9700
6:83521286:GTTAC:G	donor_gain	0.9700
6:83521287:TTACT:T	donor_gain	0.9700
6:83521295:T:TA	donor_gain	0.9600
6:83515293:G:GA	donor_gain	0.9500
6:83521287:T:G	donor_gain	0.9500
6:83521295:T:G	donor_gain	0.9500
6:83523421:GGACA:G	acceptor_gain	0.9500
6:83523420:AG:A	acceptor_gain	0.9400
6:83523421:GG:G	acceptor_gain	0.9400
6:83523421:GGA:G	acceptor_gain	0.9400
6:83521375:C:CG	donor_gain	0.9200
6:83523426:A:G	acceptor_gain	0.9200
6:83521290:C:CG	donor_gain	0.9000
6:83523421:GGAC:G	acceptor_gain	0.9000

AlphaMissense

2734 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:83524409:G:C	R323P	0.998
6:83524415:G:A	C325Y	0.998
6:83524416:C:G	C325W	0.998
6:83524457:G:A	C339Y	0.998
6:83523830:G:T	R130M	0.997
6:83523832:T:C	F131L	0.997
6:83523834:C:A	F131L	0.997
6:83523834:C:G	F131L	0.997
6:83523932:T:A	V164D	0.997
6:83524414:T:C	C325R	0.997
6:83524456:T:C	C339R	0.997
6:83523871:T:C	F144L	0.996
6:83523873:C:A	F144L	0.996
6:83523873:C:G	F144L	0.996
6:83524411:T:C	F324L	0.996
6:83524413:T:A	F324L	0.996
6:83524413:T:G	F324L	0.996
6:83524414:T:A	C325S	0.996
6:83524415:G:C	C325S	0.996
6:83524456:T:A	C339S	0.996
6:83524457:G:C	C339S	0.996
6:83524458:C:G	C339W	0.996
6:83524543:G:C	A368P	0.996
6:83523904:A:C	S155R	0.995
6:83523906:T:A	S155R	0.995
6:83523906:T:G	S155R	0.995
6:83523908:G:A	G156D	0.995
6:83524194:G:C	W251C	0.995
6:83524194:G:T	W251C	0.995
6:83524457:G:T	C339F	0.995

dbSNP variants (sampled 300 via entrez): RS1000011463 (6:83511255 A>G), RS1000294285 (6:83524272 T>C,G), RS1000501772 (6:83511999 T>C), RS1000870455 (6:83522504 C>A), RS1000914063 (6:83511760 C>A,G), RS1000915286 (6:83517561 C>A,G), RS1000965783 (6:83517860 G>C), RS1001566057 (6:83511722 A>G), RS1001852155 (6:83526033 A>G), RS1001907950 (6:83513204 G>A), RS1001968087 (6:83519350 A>G), RS1002186496 (6:83510925 A>G), RS1002904427 (6:83521886 T>C), RS1003130609 (6:83515682 A>G), RS1003246333 (6:83520318 A>G,T)

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

6 associations (top):

Study	Trait	p-value
GCST001715_1	Bipolar disorder with mood-incongruent psychosis	1.000000e-07
GCST002951_7	Response to zileuton treatment in asthma (FEV1 change interaction)	8.000000e-07
GCST004521_292	Autism spectrum disorder or schizophrenia	5.000000e-08
GCST009309_13	Face memory	9.000000e-06
GCST009600_69	Anorexia nervosa, attention-deficit/hyperactivity disorder, autism spectrum disorder, bipolar disorder, major depression, obsessive-compulsive disorder, schizophrenia, or Tourette syndrome (pleiotropy)	8.000000e-11
GCST010002_328	Refractive error	2.000000e-26

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0005921	FEV change measurement
EFO:0004874	memory performance

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

36 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression	7
aristolochic acid I	increases expression	1
fluorene-9-bisphenol	decreases expression	1
methylmercuric chloride	decreases expression	1
propionaldehyde	increases expression	1
pirinixic acid	affects binding, increases activity, increases expression	1
trichostatin A	increases expression	1
sodium arsenite	increases expression	1
S-(1,2-dichlorovinyl)cysteine	affects cotreatment, increases expression	1
pentabromodiphenyl ether	decreases expression	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
2,2’,4,4’,5-brominated diphenyl ether	decreases expression	1
abrine	decreases expression	1
quinocetone	increases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
dorsomorphin	affects cotreatment, increases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	increases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Temozolomide	increases expression	1
Sunitinib	decreases expression	1
Zoledronic Acid	increases expression	1
Air Pollutants	decreases expression, increases abundance	1
Benzo(a)pyrene	affects methylation, increases methylation	1
Camptothecin	increases expression	1
Cytarabine	decreases expression	1
Dichlorodiphenyl Dichloroethylene	decreases expression	1
Estradiol	affects expression	1
Lipopolysaccharides	affects cotreatment, increases expression	1
Plant Extracts	affects cotreatment, decreases expression	1

Clinical trials (associated diseases)

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