Neurotrypsin

PRSS12
Identifiers
Aliases	PRSS12, BSSP-3, BSSP3, MRT1, protease, serine 12, serine protease 12, motopsin, leydin
External IDs	OMIM: 606709; MGI: 1100881; GeneCards: PRSS12
Gene location (Human)
Chr.	Chromosome 4 (human)
End	118,353,003 bp
Gene location (Mouse)
Chr.	Chromosome 3 (mouse)
End	123,300,246 bp
RNA expression pattern
	Top expressed in
	bronchial epithelial cell; ; stromal cell of endometrium; ; olfactory zone of nasal mucosa; ; right uterine tube; ; mucosa of paranasal sinus; ; gonad; ; gallbladder; ; epithelium of nasopharynx; ; vulva; ; nasal epithelium;
	Top expressed in
	sciatic nerve; ; morula; ; trigeminal ganglion; ; facial motor nucleus; ; fossa; ; cartilage tissue; ; ankle joint; ; primary oocyte; ; prefrontal cortex; ; motor neuron;
	More reference expression data
	n/a
Gene ontology
Molecular function	scavenger receptor activity; peptidase activity; serine-type peptidase activity; serine-type endopeptidase activity; hydrolase activity;
Cellular component	extracellular region; axon; terminal bouton; plasma membrane; dendrite; synapse; synaptic cleft; cytoplasmic vesicle; membrane;
Biological process	zymogen activation; receptor-mediated endocytosis; proteolysis; exocytosis; endocytosis;
	Sources:Amigo / QuickGO
Orthologs
Databases	NCBI: entry; OMA: entry
	8492
	19142
	ENSG00000164099
	ENSMUSG00000027978
	P56730
	O08762
	NM_003619
	NM_008939
	NP_003610
	NP_032965
	Wikidata
View/Edit Human	View/Edit Mouse

Neurotrypsin, also called motopsin, is an enzyme that in humans is encoded by the gene PRSS12 (protease, serine 12). This enzyme specifically cleaves the protein agrin, and is particularly important during brain development.

Function

Neurotrypsin is activated by NMDA receptors, leading to the cleavage of agrin in the neural synapses. The cleaved agrin subsequently binds to and inhibits the α3 subunit of the sodium-potassium pump, which causes more frequent neuron firing. In the hippocampus, the cleaving of agrin appears to be important for the formation of dendritic filopodia.

Medical Significance

Pathogenic mutations in PRSS12 are associated with moderate to severe intellectual disability. This form of disability is called autosomal recessive intellectual developmental disorder-1, and denoted MRT1 (based on a previous historical name).

References

1 2 3 GRCh38: Ensembl release 89: ENSG00000164099 – Ensembl, May 2017
1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000027978 – Ensembl, May 2017
↑ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
↑ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
↑ "Neurotrypsin". uniprot.org. UniProt consortium. Retrieved 2026-10-20.
1 2 Wang Y, Luo W, Reiser G (January 2008). "Trypsin and trypsin-like proteases in the brain: proteolysis and cellular functions" (PDF). Cellular and Molecular Life Sciences. 65 (2): 237–52. doi:10.1007/s00018-007-7288-3.
1 2 3 Kaufman L, Ayub M, Vincent JB (December 2010). "The genetic basis of non-syndromic intellectual disability: a review". Journal of neurodevelopmental disorders. 2 (4): 182–209. doi:10.1007/s11689-010-9055-2.
↑ McKusick VA, Tiller GE (2024-03-29). "INTELLECTUAL DEVELOPMENTAL DISORDER, AUTOSOMAL RECESSIVE 1; MRT1". OMIM. Johns Hopkins university. Retrieved 2026-10-20.

This article on a gene on human chromosome 4 is a stub. You can help Wikipedia by adding missing information.

[refGRCh38Ensembl-1] 1 2 3 GRCh38: Ensembl release 89: ENSG00000164099 – Ensembl, May 2017

[refGRCm38Ensembl-2] 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000027978 – Ensembl, May 2017

[3] "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[4] "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[uniprot-5] "Neurotrypsin". uniprot.org. UniProt consortium. Retrieved 2026-10-20.

[Wang2008-6] 1 2 Wang Y, Luo W, Reiser G (January 2008). "Trypsin and trypsin-like proteases in the brain: proteolysis and cellular functions" (PDF). Cellular and Molecular Life Sciences. 65 (2): 237–52. doi:10.1007/s00018-007-7288-3.

[Kaufman2010-7] 1 2 3 Kaufman L, Ayub M, Vincent JB (December 2010). "The genetic basis of non-syndromic intellectual disability: a review". Journal of neurodevelopmental disorders. 2 (4): 182–209. doi:10.1007/s11689-010-9055-2.

[8] McKusick VA, Tiller GE (2024-03-29). "INTELLECTUAL DEVELOPMENTAL DISORDER, AUTOSOMAL RECESSIVE 1; MRT1". OMIM. Johns Hopkins university. Retrieved 2026-10-20.