PRSS16

Summary

PRSS16 (serine protease 16, HGNC:9480) is a protein-coding gene on chromosome 6p22.1, encoding Thymus-specific serine protease (Q9NQE7). Protease that may play a role in T-cell development.

This gene encodes a serine protease expressed exclusively in the thymus. It is thought to play a role in the alternative antigen presenting pathway used by cortical thymic epithelial cells during the positive selection of T cells. The gene is found in the large histone gene cluster on chromosome 6, near the major histocompatibility complex (MHC) class I region. A second transcript variant has been described, but its full length nature has not been determined.

Source: NCBI Gene 10279 — RefSeq curated summary.

At a glance

• GWAS associations: 31
• Clinical variants (ClinVar): 81 total
• MANE Select transcript: NM_005865

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9480
Approved symbol	PRSS16
Name	serine protease 16
Location	6p22.1
Locus type	gene with protein product
Status	Approved
Aliases	TSSP
Ensembl gene	ENSG00000112812
Ensembl biotype	protein_coding
OMIM	607169
Entrez	10279

Gene structure

Transcript identifiers

Ensembl transcripts: 21 — 6 protein_coding_CDS_not_defined, 6 retained_intron, 5 protein_coding, 4 nonsense_mediated_decay

ENST00000230582, ENST00000377456, ENST00000421826, ENST00000454665, ENST00000459736, ENST00000462664, ENST00000466364, ENST00000468138, ENST00000468930, ENST00000470870, ENST00000471463, ENST00000475106, ENST00000478690, ENST00000481125, ENST00000484493, ENST00000485603, ENST00000485993, ENST00000488649, ENST00000492575, ENST00000495683, ENST00000916331

RefSeq mRNA: 1 — MANE Select: NM_005865 NM_005865

CCDS: CCDS4623

Canonical transcript exons

ENST00000230582 — 12 exons

Exon	Start	End
ENSE00000703928	27247882	27248048
ENSE00000703930	27248847	27248946
ENSE00000703941	27251042	27251119
ENSE00000703945	27251217	27251264
ENSE00000848456	27250683	27250806
ENSE00001856508	27247701	27247807
ENSE00001866741	27255247	27256620
ENSE00003469703	27249100	27249229
ENSE00003485886	27251750	27252040
ENSE00003555995	27254693	27254872
ENSE00003557825	27254986	27255131
ENSE00003572095	27252808	27252949

Expression profiles

Bgee: expression breadth ubiquitous, 185 present calls, max score 98.97.

FANTOM5 (CAGE): breadth broad, TPM avg 2.5791 / max 747.2027, expressed in 574 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
66555	1.6022	530
66553	0.5940	9
66552	0.1877	4
66557	0.1760	94
66554	0.0192	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
thymus	UBERON:0002370	98.97	gold quality
body of pancreas	UBERON:0001150	93.86	gold quality
pancreas	UBERON:0001264	87.25	gold quality
mucosa of transverse colon	UBERON:0004991	86.65	gold quality
rectum	UBERON:0001052	85.18	gold quality
right lobe of thyroid gland	UBERON:0001119	85.10	gold quality
left lobe of thyroid gland	UBERON:0001120	84.93	gold quality
right uterine tube	UBERON:0001302	84.59	gold quality
thyroid gland	UBERON:0002046	84.58	gold quality
esophagus squamous epithelium	UBERON:0006920	84.11	gold quality
palpebral conjunctiva	UBERON:0001812	81.76	gold quality
duodenum	UBERON:0002114	80.76	gold quality
minor salivary gland	UBERON:0001830	80.69	gold quality
saliva-secreting gland	UBERON:0001044	80.68	gold quality
epithelium of esophagus	UBERON:0001976	80.49	gold quality
gall bladder	UBERON:0002110	79.86	gold quality
germinal epithelium of ovary	UBERON:0001304	79.54	silver quality
esophagus mucosa	UBERON:0002469	79.42	gold quality
hair follicle	UBERON:0002073	79.19	silver quality
secondary oocyte	CL:0000655	78.89	gold quality
islet of Langerhans	UBERON:0000006	78.40	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	78.39	gold quality
mouth mucosa	UBERON:0003729	78.08	gold quality
parotid gland	UBERON:0001831	77.47	silver quality
squamous epithelium	UBERON:0006914	77.04	gold quality
body of stomach	UBERON:0001161	77.03	gold quality
pituitary gland	UBERON:0000007	76.95	gold quality
transverse colon	UBERON:0001157	76.32	gold quality
upper lobe of left lung	UBERON:0008952	75.88	gold quality
skin of abdomen	UBERON:0001416	75.86	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-CURD-79	yes	2232.76
E-ANND-3	yes	6.32
E-CURD-10	no	75.58

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

92 targeting PRSS16, 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-1252-5P	100.00	69.80	2774
HSA-MIR-4425	100.00	67.59	1049
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-6758-5P	100.00	66.21	1470
HSA-MIR-6856-5P	100.00	65.47	1298
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-4455	100.00	65.48	1587
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-6759-5P	99.99	66.54	785
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-6835-3P	99.93	70.49	2904
HSA-MIR-539-5P	99.93	70.30	2855
HSA-MIR-3143	99.93	71.96	3104
HSA-MIR-5680	99.91	69.83	3421
HSA-MIR-10523-5P	99.91	69.22	2038
HSA-MIR-6783-3P	99.89	67.92	2059
HSA-MIR-1343-3P	99.89	66.78	1815
HSA-MIR-9902	99.89	69.15	2250
HSA-MIR-3919	99.87	69.45	2489
HSA-MIR-6124	99.87	69.78	3551
HSA-MIR-137-3P	99.87	74.74	2401
HSA-MIR-3121-3P	99.82	71.96	3630
HSA-MIR-6739-5P	99.80	67.87	2806
HSA-MIR-4659A-3P	99.80	72.62	4248
HSA-MIR-4659B-3P	99.80	72.62	4248
HSA-MIR-4668-5P	99.79	70.58	3782

Literature-anchored findings (GeneRIF, showing 6)

• The gene encoding thymus-specific serine protease (PRSS16) maps to the extended HLA complex, which harbours several genes predisposing for autoimmune diseases. (PMID:12140752)
• data suggest that it is unlikely that polymorphisms within the PRSS16 gene are involved in the predisposition to diabetes type 1 (PMID:17584581)
• our results identify PRSS16 and BTN3A2, two genes thought to play important roles in regulating the immune response, as potentially novel susceptibility genes for Type I diabetes. (PMID:19295542)
• ZNF804a regulates expression of the schizophrenia-associated genes PRSS16, COMT, PDE4B, and DRD2 (PMID:22384243)
• The genes HIST1H2BJ, PRSS16, and PGBD1 were not associated with Japanese patients with schizophrenia. (PMID:22488895)
• the level of TSSP expression by thymic dendritic cells may modify the risk factors for multiple sclerosis conferred by some MHC class II haplotypes (PMID:29061767)

Cross-species orthologs

11 orthologs

Organism	Symbol	Gene ID
mus_musculus	Prss16	ENSMUSG00000006179
rattus_norvegicus	Prss16	ENSRNOG00000057865
drosophila_melanogaster	CG3734	FBGN0038700
drosophila_melanogaster	CG18493	FBGN0038701
drosophila_melanogaster	CG3739	FBGN0038702
drosophila_melanogaster	CG11626	FBGN0038705
caenorhabditis_elegans		WBGENE00003957
caenorhabditis_elegans		WBGENE00003958
caenorhabditis_elegans		WBGENE00003959
caenorhabditis_elegans		WBGENE00017592
caenorhabditis_elegans		WBGENE00017594

Paralogs (2): PRCP (ENSG00000137509), DPP7 (ENSG00000176978)

Protein

Protein identifiers

Thymus-specific serine protease — Q9NQE7 (reviewed: Q9NQE7)

Alternative names: Serine protease 16

All UniProt accessions (8): B4DZV2, C9JDN6, Q9NQE7, F2Z2N5, F8WBG5, F8WF25, H0Y893, H0Y8B9

UniProt curated annotations — full annotation on UniProt →

Function. Protease that may play a role in T-cell development.

Subcellular location. Cytoplasmic vesicle.

Tissue specificity. Expressed predominantly in cortical thymic epithelial cells.

Similarity. Belongs to the peptidase S28 family.

RefSeq proteins (1): NP_005856* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR008758	Peptidase_S28	Family
IPR029058	AB_hydrolase_fold	Homologous_superfamily
IPR042269	Ser_carbopepase_S28_SKS	Homologous_superfamily

Pfam: PF05577

UniProt features (10 total): active site 3, glycosylation site 3, sequence variant 2, signal peptide 1, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NQE7-F1	90.00	0.81

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): 185 (charge relay system); 447 (charge relay system); 472 (charge relay system)

Glycosylation sites (3): 70, 172, 321

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 148 (showing top): GSE45365_NK_CELL_VS_CD8A_DC_MCMV_INFECTION_DN, MORF_RAGE, MORF_FLT1, CAR_TNFRSF25, YAGI_AML_WITH_INV_16_TRANSLOCATION, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, IVANOVA_HEMATOPOIESIS_LATE_PROGENITOR, MORF_ESR1, MODULE_205, CAR_MLANA, MODULE_88, MORF_PML, WHN_B, GOBP_PROTEIN_CATABOLIC_PROCESS, MODULE_104

GO Biological Process (2): proteolysis (GO:0006508), protein catabolic process (GO:0030163)

GO Molecular Function (5): serine-type peptidase activity (GO:0008236), dipeptidyl-peptidase activity (GO:0008239), serine-type exopeptidase activity (GO:0070008), peptidase activity (GO:0008233), hydrolase activity (GO:0016787)

GO Cellular Component (4): lysosome (GO:0005764), endosome (GO:0005768), membrane (GO:0016020), cytoplasmic vesicle (GO:0031410)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein metabolic process	2
exopeptidase activity	2
macromolecule catabolic process	1
peptidase activity	1
serine hydrolase activity	1
serine-type peptidase activity	1
hydrolase activity	1
catalytic activity, acting on a protein	1
catalytic activity	1
lytic vacuole	1
endomembrane system	1
cytoplasmic vesicle	1
cellular anatomical structure	1
cytoplasm	1
intracellular vesicle	1

Protein interactions and networks

STRING

616 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PRSS16	PSMB11	A5LHX3	809
PRSS16	PREP	P48147	783
PRSS16	POM121L2	Q96KW2	614
PRSS16	TBATA	Q96M53	596
PRSS16	ZNF804A	Q7Z570	572
PRSS16	FOXN1	O15353	566
PRSS16	PGBD1	Q96JS3	526
PRSS16	CTSL	P07711	524
PRSS16	SYNGR1	O43759	486
PRSS16	AIRE	O43918	466
PRSS16	LY75	O60449	461
PRSS16	ZNF184	Q99676	432
PRSS16	MFSD12	Q6NUT3	426
PRSS16	COMT	P21964	417
PRSS16	CCL25	O15444	411

IntAct

4 interactions, top by confidence:

A	B	Type	Score
PRSS16	CHRM5	psi-mi:“MI:0915”(physical association)	0.370
PRSS16	KLK10	psi-mi:“MI:0914”(association)	0.350
MTCL3	PRKCB	psi-mi:“MI:0914”(association)	0.350

BioGRID (46): ACADSB (Co-fractionation), PRSS16 (Affinity Capture-MS), PRSS16 (Affinity Capture-MS), PRSS16 (Two-hybrid), CASP14 (Affinity Capture-MS), GSDMA (Affinity Capture-MS), FLG2 (Affinity Capture-MS), DSG1 (Affinity Capture-MS), KLK7 (Affinity Capture-MS), ACPP (Affinity Capture-MS), IL37 (Affinity Capture-MS), KLK5 (Affinity Capture-MS), CST6 (Affinity Capture-MS), PLBD1 (Affinity Capture-MS), TGM3 (Affinity Capture-MS)

ESM2 similar proteins: A0JND9, E1BPW0, O14773, O18956, O35795, O55026, O75173, O75355, O75356, O75578, O89023, O93295, P08514, P08648, P11688, P17405, P49961, P55772, P56201, P79784, P97687, Q04519, Q0VD19, Q12794, Q32M88, Q49HH9, Q49KI5, Q5DRK1, Q5IS74, Q5MY95, Q5RFL1, Q5RFQ8, Q60HH1, Q6P3E7, Q6P6S9, Q717C1, Q717C2, Q7RTX0, Q8BFW6, Q8BNJ2

Diamond homologs: P34528, P90893, Q9NQE7, Q9QXE5, D4AYS6, P34610, P34676, P42785, Q1PF50, Q2TA14, Q5RBU7, Q7TMR0, Q9EPB1, Q9ET22, Q9UHL4

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	64
Likely benign	1
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

1501 predictions. Top by Δscore:

Variant	Effect	Δscore
6:27255242:CACA:C	acceptor_loss	1.0000
6:27255243:ACAG:A	acceptor_loss	1.0000
6:27255245:A:AG	acceptor_gain	1.0000
6:27255246:G:GG	acceptor_gain	1.0000
6:27255246:GAAC:G	acceptor_gain	1.0000
6:27248834:T:G	acceptor_gain	0.9900
6:27249228:GC:G	donor_gain	0.9900
6:27249230:G:GG	donor_gain	0.9900
6:27249240:G:GT	donor_gain	0.9900
6:27251040:A:AG	acceptor_gain	0.9900
6:27251041:G:GG	acceptor_gain	0.9900
6:27251120:G:GG	donor_gain	0.9900
6:27252950:G:GG	donor_gain	0.9900
6:27254124:T:TA	acceptor_gain	0.9900
6:27254980:TTCCA:T	acceptor_loss	0.9900
6:27254981:TCCA:T	acceptor_loss	0.9900
6:27254984:A:AG	acceptor_gain	0.9900
6:27254984:AG:A	acceptor_gain	0.9900
6:27254984:AGG:A	acceptor_gain	0.9900
6:27254985:G:GG	acceptor_gain	0.9900
6:27254985:GG:G	acceptor_gain	0.9900
6:27254985:GGG:G	acceptor_gain	0.9900
6:27255132:GTAAG:G	donor_loss	0.9900
6:27255133:T:G	donor_loss	0.9900
6:27255246:GA:G	acceptor_gain	0.9900
6:27255246:GAA:G	acceptor_gain	0.9900
6:27248047:AGG:A	donor_loss	0.9800
6:27248049:GT:G	donor_loss	0.9800
6:27248839:C:G	acceptor_gain	0.9800
6:27249166:GCC:G	donor_gain	0.9800

AlphaMissense

3255 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:27249171:A:C	S137R	0.992
6:27249173:T:A	S137R	0.992
6:27249173:T:G	S137R	0.992
6:27249159:T:C	F133L	0.991
6:27249161:T:A	F133L	0.991
6:27249161:T:G	F133L	0.991
6:27248850:T:G	Y81D	0.987
6:27249151:A:T	E130V	0.985
6:27249219:A:C	S153R	0.985
6:27249221:C:A	S153R	0.985
6:27249221:C:G	S153R	0.985
6:27254761:T:A	C407S	0.980
6:27254762:G:C	C407S	0.980
6:27255012:A:C	S453R	0.977
6:27255014:T:A	S453R	0.977
6:27255014:T:G	S453R	0.977
6:27254773:T:C	F411L	0.975
6:27254775:T:A	F411L	0.975
6:27254775:T:G	F411L	0.975
6:27252918:G:C	W373C	0.974
6:27252918:G:T	W373C	0.974
6:27249152:A:C	E130D	0.973
6:27249152:A:T	E130D	0.973
6:27249157:G:T	R132I	0.973
6:27249172:G:T	S137I	0.973
6:27249157:G:C	R132T	0.972
6:27248040:T:C	F77L	0.971
6:27248042:C:A	F77L	0.971
6:27248042:C:G	F77L	0.971
6:27248896:T:C	F96S	0.971

dbSNP variants (sampled 300 via entrez): RS1000427791 (6:27248647 A>G), RS1000673604 (6:27256539 T>G), RS1000898514 (6:27250874 T>C), RS1001431196 (6:27250411 A>C), RS1001817675 (6:27252211 T>C), RS1002438397 (6:27252207 G>A), RS1002549219 (6:27256225 A>C,G), RS1003065120 (6:27246777 T>C), RS1003115687 (6:27248495 T>C), RS1003442101 (6:27254296 T>C), RS1003493593 (6:27254255 T>A), RS1004434522 (6:27246613 C>G), RS1004923678 (6:27253723 C>G), RS1004975454 (6:27246991 C>A,T), RS1005385695 (6:27254265 G>T)

Disease associations

OMIM: gene MIM:607169 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

31 associations (top):

Study	Trait	p-value
GCST000433_1	Schizophrenia	1.000000e-08
GCST000435_5	Schizophrenia	1.000000e-12
GCST004521_113	Autism spectrum disorder or schizophrenia	3.000000e-19
GCST004521_116	Autism spectrum disorder or schizophrenia	3.000000e-16
GCST004521_166	Autism spectrum disorder or schizophrenia	4.000000e-24
GCST004521_208	Autism spectrum disorder or schizophrenia	5.000000e-17
GCST004521_215	Autism spectrum disorder or schizophrenia	5.000000e-13
GCST004521_57	Autism spectrum disorder or schizophrenia	1.000000e-20
GCST004521_69	Autism spectrum disorder or schizophrenia	8.000000e-24
GCST004571_11	Iron status biomarkers (total iron binding capacity)	5.000000e-08
GCST004571_31	Iron status biomarkers (total iron binding capacity)	1.000000e-07
GCST004572_20	Iron status biomarkers (transferrin saturation)	1.000000e-07
GCST004572_23	Iron status biomarkers (transferrin saturation)	5.000000e-08
GCST004748_86	Lung cancer	5.000000e-09
GCST004749_68	Lung cancer in ever smokers	1.000000e-07
GCST004750_84	Squamous cell lung carcinoma	9.000000e-10
GCST008921_9	Asthma and major depressive disorder	3.000000e-08
GCST009107_20	Body mass index variance	8.000000e-17
GCST009121_20	Body mass index	4.000000e-08
GCST010002_50	Refractive error	4.000000e-34
GCST010142_16	Fish- and plant-related diet	2.000000e-10
GCST010142_19	Fish- and plant-related diet	4.000000e-10
GCST010142_34	Fish- and plant-related diet	7.000000e-09
GCST010142_35	Fish- and plant-related diet	8.000000e-09
GCST010142_42	Fish- and plant-related diet	1.000000e-08
GCST010142_7	Fish- and plant-related diet	3.000000e-12
GCST010204_194	Low density lipoprotein cholesterol levels	1.000000e-18
GCST012226_447	Waist circumference adjusted for body mass index	6.000000e-10
GCST012338_22	Gout	5.000000e-09
GCST90020028_831	Hip circumference adjusted for BMI	7.000000e-09

EFO canonical traits (6, from GWAS)

EFO ID	Trait name
EFO:0006334	total iron binding capacity
EFO:0004340	body mass index
EFO:0008111	diet measurement
EFO:0004611	low density lipoprotein cholesterol measurement
EFO:0007789	BMI-adjusted waist circumference
EFO:0008039	BMI-adjusted hip circumference

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

20 total (human), top 20 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression	5
sodium arsenite	decreases expression	2
Estradiol	affects cotreatment, decreases expression	2
methylmercuric chloride	increases expression	1
bisphenol A	decreases methylation	1
beta-lapachone	increases expression	1
perfluorooctane sulfonic acid	increases expression	1
entinostat	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
abrine	decreases expression	1
dorsomorphin	increases expression, affects cotreatment	1
jinfukang	increases expression	1
Dichlorodiphenyl Dichloroethylene	decreases expression	1
Silicon Dioxide	decreases expression	1
Smoke	decreases expression	1
Testosterone	decreases expression	1
Tobacco Smoke Pollution	affects expression	1
Tunicamycin	increases expression	1
Asbestos, Crocidolite	decreases expression	1
Cadmium Chloride	decreases expression	1

Clinical trials (associated diseases)

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