Details for: PRSS12

Gene ID: 8492

Gene Type:  Protein-coding  - A gene that serves as a template for producing a messenger RNA (mRNA) molecule, which is then translated into a functional protein.

Symbol: PRSS12

Ensembl ID: ENSG00000164099

Description: serine protease 12

Cell Significance Landscape

Associated with

Significant Cells

Cell Significance Index (CSI) scores for the chosen context(s)

  • lung ciliated cell CL1000271
    CSI 6.19
    rCSI 7.16%
    PRS 79.08
  • epithelial cell of lower respiratory tract CL0002632
    CSI 4.99
    rCSI 3.87%
    PRS 88.92
  • neural cell CL0002319
    CSI 4.12
    rCSI 15.56%
    PRS 69.23
  • multi-ciliated epithelial cell CL0005012
    CSI 4.03
    rCSI 4.02%
    PRS 79.92
  • choroid plexus epithelial cell CL0000706
    CSI 3.09
    rCSI 5.06%
    PRS 76.71
  • brush cell of tracheobronchial tree CL0002075
    CSI 3.07
    rCSI 9.11%
    PRS 92.49
  • skin fibroblast CL0002620
    CSI 2.92
    rCSI 2.51%
    PRS 85.28
  • fibroblast of lung CL0002553
    CSI 2.84
    rCSI 2.64%
    PRS 86.59
  • cerebral cortex endothelial cell CL1001602
    CSI 2.39
    rCSI 4.14%
    PRS 78.64
  • ciliated epithelial cell CL0000067
    CSI 2.24
    rCSI 1.97%
    PRS 75.92
  • ependymal cell CL0000065
    CSI 2.17
    rCSI 4.4%
    PRS 66.01
  • lamp5 GABAergic cortical interneuron CL4023011
    CSI 2.14
    rCSI 3.6%
    PRS 69.77
  • VIP GABAergic cortical interneuron CL4023016
    CSI 2.08
    rCSI 2.49%
    PRS 69.91
  • stem cell CL0000034
    CSI 2.08
    rCSI 2%
    PRS 80.5
  • lung secretory cell CL1000272
    CSI 2.01
    rCSI 4.98%
    PRS 86.07
  • ciliated cell CL0000064
    CSI 1.94
    rCSI 3.14%
    PRS 80.38
  • squamous epithelial cell CL0000076
    CSI 1.88
    rCSI 4.46%
    PRS 84.42
  • colon epithelial cell CL0011108
    CSI 1.87
    rCSI 1.96%
    PRS 83.13
  • BEST4+ enteroycte CL4030026
    CSI 1.82
    rCSI 2.26%
    PRS 85.92
  • sst GABAergic cortical interneuron CL4023017
    CSI 1.78
    rCSI 2.3%
    PRS 70.92
  • M cell of gut CL0000682
    CSI 1.76
    rCSI 1.87%
    PRS 88.84
  • ciliated columnar cell of tracheobronchial tree CL0002145
    CSI 1.62
    rCSI 3.69%
    PRS 78.95
  • glutamatergic neuron CL0000679
    CSI 1.57
    rCSI 3.23%
    PRS 73.08
  • L4 intratelencephalic projecting glutamatergic neuron CL4030063
    CSI 1.41
    rCSI 3.37%
    PRS 73.57
  • near-projecting glutamatergic cortical neuron CL4023012
    CSI 1.36
    rCSI 5.12%
    PRS 70.1
  • placental villous trophoblast CL2000060
    CSI 1.22
    rCSI 1.89%
    PRS 84.41
  • L2/3-6 intratelencephalic projecting glutamatergic neuron CL4023040
    CSI 0.94
    rCSI 2.28%
    PRS 67.58

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this specific cell.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.
Network Configuration

Explore relationships of the current gene. Select an Interaction Source: 'ONTOLOGY' for shared pathways (GO/Reactome) or 'STRING' for protein-protein interactions. Further refine by selecting context genes and comparing Cell Significance Index (CSI) scores between baseline and target cell types and their specific contexts.

Comma-separated if multiple.
Comma-separated if multiple.
Legend:
  • Query Gene
  • Node Color (Target Cell CSI, relative to current network):
    • Very High
    • High
    • Medium
    • Low
    • Very Low
    • CSI N/A
  • Node Size: Proportional to Target Cell CSI magnitude
  • STRING PPI Edge
  • Shared Pathway Edge (ONTOLOGY)

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Other Information

This section provides additional information about the gene, including a description generated by an AI language model and details about associated proteins.

## Summary [PRSS12](/details-gene/8492), also known as neurotrypsin, is a protein-coding gene located on chromosome 4q26 that encodes a serine protease. Its primary molecular function is [serine-type endopeptidase activity](/details-cell/GO:0004252), and it is known to be localized to synaptic structures such as the [synaptic cleft](/details-cell/GO:0043083) and [presynapse](/details-cell/GO:0098793). Clinically, truncating loss-of-function mutations in [PRSS12](/details-gene/8492) are associated with a form of autosomal recessive nonsyndromic mental retardation ([OMIM:249500](https://omim.org/entry/249500)), underscoring its critical role in neural development or function ([Link](https://doi.org/10.1126/science.1076521)). Expression data reveals its highest significance not only in [neural cell](/details-cell/CL0002319)s, as expected, but also in respiratory cells, particularly [lung ciliated cell](/details-cell/CL1000271)s, suggesting a potentially uncharacterized but important function in the pulmonary system. ## Cellular Roles and Expression Landscape The expression profile of [PRSS12](/details-gene/8492) highlights a distinct dual-tissue significance in both the nervous and respiratory systems. **In the context of an **Overall** biological state**, [PRSS12](/details-gene/8492) shows its highest significance in cell types of the respiratory tract. It is a top marker for [lung ciliated cell](/details-cell/CL1000271) (CSI: 6.19), [epithelial cell of lower respiratory tract](/details-cell/CL0002632) (CSI: 4.99), and [multi-ciliated epithelial cell](/details-cell/CL0005012) (CSI: 4.03). Its high expression in these cells, along with [brush cell of tracheobronchial tree](/details-cell/CL0002075) and [lung secretory cell](/details-cell/CL1000272), suggests a functional role in airway physiology, potentially related to mucociliary clearance, host defense, or epithelial maintenance through its proteolytic activity. Consistent with its established role as neurotrypsin, [PRSS12](/details-gene/8492) is also highly significant in the central nervous system. It is a key marker for the broad category of [neural cell](/details-cell/CL0002319)s (CSI: 4.12) and shows specific enrichment in specialized cells such as [choroid plexus epithelial cell](/details-cell/CL0000706), [ependymal cell](/details-cell/CL0000065), and specific interneuron populations like [lamp5 GABAergic cortical interneuron](/details-cell/CL4023011) and [VIP GABAergic cortical interneuron](/details-cell/CL4023016). This expression pattern aligns with its known involvement in synaptic processes and its link to cognitive function. ## Pathways and Molecular Function The functional annotations for [PRSS12](/details-gene/8492) strongly support its identity as a secreted, active protease involved in synaptic regulation. Its molecular function is defined as [serine-type peptidase activity](/details-cell/GO:0008236), and it is implicated in biological processes such as [zymogen activation](/details-cell/GO:0031638), indicating it is likely synthesized as an inactive precursor before being proteolytically cleaved into its active form. Its localization is predominantly neuronal and synaptic. Cellular component annotations place the protein in the [axon](/details-cell/GO:0030424), [dendrite](/details-cell/GO:0030425), [synaptic cleft](/details-cell/GO:0043083), and specifically at the [glutamatergic synapse](/details-cell/GO:0098978). This precise localization suggests a role in modulating synaptic transmission, connectivity, or plasticity by cleaving specific substrates within the synaptic microenvironment. The association with [exocytosis](/details-cell/GO:0006887) and [cytoplasmic vesicle](/details-cell/GO:0031410)s is consistent with its secretion from presynaptic terminals into the synaptic cleft. ## Research Directions The dual-expression pattern of [PRSS12](/details-gene/8492) in the CNS and respiratory epithelium presents compelling avenues for future research, particularly regarding its largely uncharacterized role in the lung. **Proposed Hypotheses:** 1. Given its established role in the CNS and its localization to the [glutamatergic synapse](/details-cell/GO:0098978), [PRSS12](/details-gene/8492) likely regulates synaptic plasticity by cleaving key components of the extracellular matrix or cell adhesion molecules, such as agrin. Loss of this proteolytic activity could lead to aberrant synaptic stabilization and contribute to the cognitive deficits seen in patients with inactivating mutations. 2. The high significance of [PRSS12](/details-gene/8492) in [lung ciliated cell](/details-cell/CL1000271)s suggests it is secreted onto the airway surface to perform a proteolytic function. We hypothesize that [PRSS12](/details-gene/8492) modulates mucociliary clearance by cleaving mucin polymers to regulate mucus viscosity or by processing cell-surface receptors required for the coordinated beating of cilia. **Key Experimental Approach:** To test the second hypothesis regarding its role in the respiratory system, one could utilize an in vitro air-liquid interface (ALI) culture model of primary human bronchial epithelial cells, which differentiates to form a pseudostratified epithelium complete with ciliated and secretory cells. [PRSS12](/details-gene/8492) could be knocked down using lentiviral-delivered shRNA. The impact on ciliary function could be directly assessed by measuring ciliary beat frequency (CBF) with high-speed videomicroscopy. Furthermore, the protein composition and rheological properties of the secreted mucus could be analyzed using mass spectrometry and a rheometer, respectively, to determine if loss of [PRSS12](/details-gene/8492) alters the mucus layer and to identify its potential substrates. **Therapeutic Potential:** The clinical relevance of [PRSS12](/details-gene/8492) is currently linked to loss-of-function mutations causing a severe neurological disorder. This indicates that therapeutic strategies should focus on **activation or restoration of function**, rather than inhibition. For its neurological role, this presents a significant challenge. Potential long-term strategies could involve gene therapy to restore expression in affected neurons or the development of small-molecule chaperones or activators that could enhance the function of any residual or misfolded protein. However, its high expression in other critical tissues, such as the lung, would necessitate highly targeted delivery systems to avoid off-target effects.

Genular Protein ID: 2077857894

Symbol: NETR_HUMAN

Name: Neurotrypsin

UniProtKB Accession Codes:

P56730 Q9UP16

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CDD 1 CTD 1 ChEMBL 1 ChiTaRS 1 DMDM 1 DNASU 1 DisGeNET 1 EC 1 EMBL 3 Ensembl 1 GO 12 Gene3D 3 GeneCards 1 GeneTree 1 GenomeRNAi 1 GlyCosmos 1 GlyGen 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 14 KEGG 1 MANE-Select 1 MEROPS 1 MIM 3 MalaCards 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 Orphanet 1 OrthoDB 1 PANTHER 2 PRINTS 2 PRO 1 PROSITE 7 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 3 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 1 RNAct 1 RefSeq 1 SMART 3 SMR 1 STRING 1 SUPFAM 3 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 neXtProt 1

Citations:

PubMed ID: 9540828

Title: Cloning and sequencing of the cDNA encoding human neurotrypsin.

PubMed ID: 9540828

DOI: 10.1016/s0167-4781(97)00205-4

PubMed ID: 15815621

Title: Generation and annotation of the DNA sequences of human chromosomes 2 and 4.

PubMed ID: 15815621

DOI: 10.1038/nature03466

PubMed ID: 10103056

Title: Cloning and structural analysis of leydin, a novel human serine protease expressed by the Leydig cells of the testis.

PubMed ID: 10103056

DOI: 10.1046/j.1432-1327.1999.00266.x

PubMed ID: 12459588

Title: Truncating neurotrypsin mutation in autosomal recessive nonsyndromic mental retardation.

PubMed ID: 12459588

DOI: 10.1126/science.1076521

Sequence Information:

  • Length: 875
  • Mass: 97067
  • Checksum: EB357047C39371BC
  • Sequence:
    • MTLARFVLAL MLGALPEVVG FDSVLNDSLH HSHRHSPPAG PHYPYYLPTQ QRPPRTRPPP 
PLPRFPRPPR ALPAQRPHAL QAGHTPRPHP WGCPAGEPWV SVTDFGAPCL RWAEVPPFLE 
RSPPASWAQL RGQRHNFCRS PDGAGRPWCF YGDARGKVDW GYCDCRHGSV RLRGGKNEFE 
GTVEVYASGV WGTVCSSHWD DSDASVICHQ LQLGGKGIAK QTPFSGLGLI PIYWSNVRCR 
GDEENILLCE KDIWQGGVCP QKMAAAVTCS FSHGPTFPII RLAGGSSVHE GRVELYHAGQ 
WGTVCDDQWD DADAEVICRQ LGLSGIAKAW HQAYFGEGSG PVMLDEVRCT GNELSIEQCP 
KSSWGEHNCG HKEDAGVSCT PLTDGVIRLA GGKGSHEGRL EVYYRGQWGT VCDDGWTELN 
TYVVCRQLGF KYGKQASANH FEESTGPIWL DDVSCSGKET RFLQCSRRQW GRHDCSHRED 
VSIACYPGGE GHRLSLGFPV RLMDGENKKE GRVEVFINGQ WGTICDDGWT DKDAAVICRQ 
LGYKGPARAR TMAYFGEGKG PIHVDNVKCT GNERSLADCI KQDIGRHNCR HSEDAGVICD 
YFGKKASGNS NKESLSSVCG LRLLHRRQKR IIGGKNSLRG GWPWQVSLRL KSSHGDGRLL 
CGATLLSSCW VLTAAHCFKR YGNSTRSYAV RVGDYHTLVP EEFEEEIGVQ QIVIHREYRP 
DRSDYDIALV RLQGPEEQCA RFSSHVLPAC LPLWRERPQK TASNCYITGW GDTGRAYSRT 
LQQAAIPLLP KRFCEERYKG RFTGRMLCAG NLHEHKRVDS CQGDSGGPLM CERPGESWVV 
YGVTSWGYGC GVKDSPGVYT KVSAFVPWIK SVTKL

Genular Protein ID: 1852013819

Symbol: Q96I80_HUMAN

Name: N/A

UniProtKB Accession Codes:

Q96I80

Database IDs:

ARBA 3 AlphaFoldDB 1 BioGRID-ORCS 1 CTD 1 DNASU 1 DisGeNET 1 EMBL 2 GO 4 Gene3D 2 InterPro 8 KEGG 1 MEROPS 1 NCBI Taxonomy 1 OrthoDB 1 PANTHER 2 PRINTS 1 PROSITE 6 PROSITE-ProRule 2 PeptideAtlas 1 Pfam 2 PharmGKB 1 RefSeq 1 SAM 2 SMART 2 SMR 1 SUPFAM 2

Citations:

PubMed ID: 15489334

Title: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).

PubMed ID: 15489334

DOI: 10.1101/gr.2596504

Sequence Information:

  • Length: 505
  • Mass: 55659
  • Checksum: 7FF863A6246226BD
  • Sequence:
    • MTLARFVLAL MLGALPEVVG FDSVLNDSLH HSHRHSPPAG PHYPYYLPTQ QRPPTTRPPP 
PLPRFPRPPR ALPAQRPHAL QAGHTPRPHP WGCPAGEPWV SVTDFGAPCL RWAEVPPFLE 
RSPPASWAQL RGQRHNFCRS PDGAGRPWCF YGDARGKVDW GYCDCRHGSV RLRGGKNEFE 
GTVEVYASGV WGTVCSSHWD DSDASVICHQ LQLGGKGIAK QTPFSGLGLI PIYWSNVRCR 
GDEENILLCE KDIWQGGVCP QKMAAAVTCS FSHGPTFPII RLAGGSSVHE GRVELYHAGQ 
WGTVCDDQWD DADAEVICRQ LGLSGIAKAW HQAYFGEGSG PVMLDEVRCT GNELSIEQCP 
KSSWGEHNCG HKEDAGVSCT PLTDGVIRLA GGKGSHEGRL EVYYRGQWGT VCDDGWTELN 
TYVVCRQLGF KYGKQASANH FEESTGPIWL DDVSCSGKET RFLQCSRRQW GRHDCSHRED 
VSIACYPGGE GHRLSLGFPV RLMDG