PRSS12

Chr 4AR

serine protease 12

Also known as: BSSP-3, BSSP3, MRT1

NCBI Gene: 8492 ENSG00000164099 UniProt: P56730 OMIM: 606709

The protein is a secreted serine protease (neurotrypsin) that cleaves agrin in the synaptic cleft to regulate excitatory synapse formation and maintenance, contributing to neuronal plasticity and learning/memory processes. Mutations cause autosomal recessive intellectual developmental disorder (MRT1). The gene shows very low constraint against loss-of-function variants (pLI near zero), which is consistent with its recessive inheritance pattern.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a member of the trypsin family of serine proteases and contains a signal peptide, a proline-rich region, a Kringle domain, four scavenger receptor cysteine-rich domains, and a trypsin-like serine protease domain. The protein, sometimes referred to as neurotrypsin or motopsin, is secreted from neuronal cells and localizes to the synaptic cleft. Studies in mice show that this protein cleaves a protein, agrin, that is important for the formation and maintenance of exitatory synapses. Defects in this gene cause a form of autosomal recessive cognitive impairment (MRT1). [provided by RefSeq, Jul 2017]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Intellectual developmental disorder, autosomal recessive 1MIM #249500

Clinical highlights

Gene-disease validity (ClinGen)

non-syndromic intellectual disability · ARLimitednot for standalone diagnostic reporting

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

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P/LP submissions

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P/LP missense

1.24

LOEUF

LOF

Mechanism· G2P