PRSS56

Chr 2AR

serine protease 56

Also known as: MCOP6

NCBI Gene: 646960 ENSG00000237412 UniProt: P0CW18 OMIM: 613858

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.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a protein that contains a peptidase S1 domain and possesses trypsin-like serine protease activity. The encoded protein may play a role in eye development, and mutations in this gene are a cause of autosomal recessive posterior microphthalmos. [provided by RefSeq, Dec 2011]

GeneReviews OMIM ResearchGenerating clinical summary…

LOFmechanismARLOEUF 0.701 OMIM phenotype

Clinical Summary— PRSS56

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Gene-Disease Validity (ClinGen)

isolated microphthalmia 6 · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)

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

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ClinVar Variants

24 unique Pathogenic / Likely Pathogenic· 137 VUS of 265 total submissions

Explore recent and relevant literature in Research Assistant →

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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

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.70LOEUF

pLI 0.000

Z-score 2.69

OE 0.41 (0.25–0.70)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

1.05Z-score

OE missense 0.83 (0.74–0.92)

241 obs / 291.6 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.41 (0.25–0.70)

0≤0.351.4

Missense OE?0.83 (0.74–0.92)

0≤0.61.4

Synonymous OE?0.94

0≤1.21.6

LoF obs/exp: 10 / 24.3Missense obs/exp: 241 / 291.6Syn Z: 0.54

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

definitivePRSS56-related microphthalmiaLOFAR

This gene — mechanism propensity

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

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

265 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic16

Likely Pathogenic8

VUS137

Likely Benign47

Benign38

Conflicting3

Pathogenic

Likely Pathogenic

137

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	11	5	0	0	16
Likely Pathogenic	2	6	0	0	8
VUS	0	135	2	0	137
Likely Benign	0	5	20	22	47
Benign	0	6	26	6	38
Conflicting	—				3
Total	13	157	48	28	249

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

View in ClinVar →

34 pathogenic / likely-pathogenic (of 43) ClinVar copy-number / structural variants overlap PRSS56 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →