PRSS12

Chr 4AR

serine protease 12

Also known as: BSSP-3, BSSP3, MRT1

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.

Summary from RefSeq, OMIM, UniProt
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Primary Disease Associations & Inheritance

Intellectual developmental disorder, autosomal recessive 1MIM #249500
AR
0
Active trials
3
Pubs (1 yr)
0
P/LP submissions
P/LP missense
1.24
LOEUF
LOF
Mechanism· G2P
Clinical SummaryPRSS12
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Gene-Disease Validity (ClinGen)
non-syndromic intellectual disability · ARLimited

Limited evidence — not for standalone diagnostic reporting

Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.24LOEUF
pLI 0.000
Z-score 0.22
OE 0.96 (0.761.24)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.39Z-score
OE missense 0.95 (0.881.03)
460 obs / 483.9 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.96 (0.761.24)
00.351.4
Missense OE0.95 (0.881.03)
00.61.4
Synonymous OE0.96
01.21.6
LoF obs/exp: 44 / 45.6Missense obs/exp: 460 / 483.9Syn Z: 0.40

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

PRSS12 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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