PRSS56

Chr 2AR

serine protease 56

Also known as: MCOP6

This gene encodes a serine protease with trypsin-like activity that is required for normal eye development. Mutations cause autosomal recessive isolated microphthalmia (microphthalmia 6), presenting as congenital underdevelopment of one or both eyes. The gene is not highly constrained against loss-of-function variants in the general population.

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

Microphthalmia, isolated 6MIM #613517
AR
0
Active trials
7
Pubs (1 yr)
82
P/LP submissions
19%
P/LP missense
0.70
LOEUF
LOF
Mechanism· G2P
Clinical SummaryPRSS56
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
57 unique Pathogenic / Likely Pathogenic· 143 VUS of 305 total submissions
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GeneReview available — PRSS56
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.70LOEUF
pLI 0.000
Z-score 2.69
OE 0.41 (0.250.70)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
1.05Z-score
OE missense 0.83 (0.740.92)
241 obs / 291.6 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.41 (0.250.70)
00.351.4
Missense OE0.83 (0.740.92)
00.61.4
Synonymous OE0.94
01.21.6
LoF obs/exp: 10 / 24.3Missense obs/exp: 241 / 291.6Syn Z: 0.54
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitivePRSS56-related microphthalmiaLOFAR

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.6259th %ile
GOF
0.6833th %ile
LOF
0.3746th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

305 submitted variants in ClinVar

Classification Summary

Pathogenic48
Likely Pathogenic9
VUS143
Likely Benign47
Benign39
Conflicting3
48
Pathogenic
9
Likely Pathogenic
143
VUS
47
Likely Benign
39
Benign
3
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
8
5
35
0
48
Likely Pathogenic
2
6
1
0
9
VUS
0
131
12
0
143
Likely Benign
0
5
20
22
47
Benign
0
6
27
6
39
Conflicting
3
Total101539528289

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

PRSS56 · 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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