PRSS56

serine protease 56, the group of Serine proteases

Basic information

Region (hg38): 2:232520387-232525716

Links

ENSG00000237412 ∙ NCBI:646960 ∙ OMIM:613858 ∙ HGNC:39433 ∙ Uniprot:P0CW18 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• nanophthalmia (Supportive), mode of inheritance: AD
• isolated microphthalmia 6 (Definitive), mode of inheritance: AR
• isolated microphthalmia 6 (Strong), mode of inheritance: AR
• isolated microphthalmia 6 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Microphthalmia, isolated 6	AR	Ophthalmologic; Pharmacogenomic	Some individuals with angle-closure glaucoma have been described, and awareness of disease risk and surveillance may allow early treatment; Agents that may contribute to glaucoma should be avoided	Ophthalmologic	15823920; 19526372; 21397065; 21532570; 21850159; 23127749

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PRSS56 gene.

• Isolated microphthalmia 6 (75 variants)
• not provided (43 variants)
• Inborn genetic diseases (30 variants)
• not specified (1 variants)
• Lethal multiple pterygium syndrome (1 variants)
• PRSS56-related condition (1 variants)
• Nanophthalmia (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PRSS56 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			1	12	5	18
missense		1	55	2	5	63
nonsense	2					2
start loss						0
frameshift	3	2				5
inframe indel			2			2
splice donor/acceptor (+/-2bp)						0
splice region			1	1	2	4
non coding				14	20	34
Total	5	3	58	28	30

Highest pathogenic variant AF is 0.0000657

Variants in PRSS56

This is a list of pathogenic ClinVar variants found in the PRSS56 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
2-232520492-C-T			Benign (Jun 26, 2018)
2-232520611-G-A		Isolated microphthalmia 6	Benign (Nov 29, 2023)
2-232520629-C-T		Inborn genetic diseases	Uncertain significance (Feb 22, 2023)
2-232520651-A-G		Isolated microphthalmia 6	Uncertain significance (Sep 01, 2022)
2-232520652-C-T		Isolated microphthalmia 6	Likely benign (Jun 14, 2022)
2-232520672-G-A		Inborn genetic diseases	Uncertain significance (May 23, 2023)
2-232520676-GCCC-G		Isolated microphthalmia 6	Uncertain significance (Oct 24, 2022)
2-232520686-G-A		Isolated microphthalmia 6	Benign (Jan 31, 2024)
2-232520691-GC-G		Isolated microphthalmia 6	Likely pathogenic (Jun 23, 2019)
2-232520713-C-T		Isolated microphthalmia 6	Benign (Jun 21, 2023)
2-232520722-C-T			Benign (Jul 10, 2018)
2-232521178-C-T			Benign (Jun 26, 2018)
2-232521258-C-T			Benign (Jun 26, 2018)
2-232521279-C-G			Benign (Jul 06, 2018)
2-232521329-G-A		Inborn genetic diseases	Uncertain significance (Mar 06, 2023)
2-232521331-C-T		Isolated microphthalmia 6	Likely benign (Sep 10, 2023)
2-232521346-G-A		Isolated microphthalmia 6	Likely benign (Oct 11, 2023)
2-232521367-C-T		Isolated microphthalmia 6	Likely benign (Mar 31, 2023)
2-232521368-G-A		Isolated microphthalmia 6	Uncertain significance (Sep 01, 2021)
2-232521387-G-A		Inborn genetic diseases	Uncertain significance (Mar 13, 2023)
2-232521393-C-T		Isolated microphthalmia 6 • Inborn genetic diseases	Uncertain significance (Dec 21, 2023)
2-232521414-C-T		Inborn genetic diseases	Likely benign (Jan 03, 2024)
2-232521419-G-A		Inborn genetic diseases	Uncertain significance (Jun 21, 2022)
2-232521425-C-G		Inborn genetic diseases	Uncertain significance (Jun 30, 2023)
2-232521438-C-G		Isolated microphthalmia 6 • PRSS56-related disorder	Benign (Jan 26, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PRSS56	protein_coding	protein_coding	ENST00000449534	13	5250

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.000341	0.998	0	0	0	0	0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.05	241	292	0.826	0.0000159	3693
Missense in Polyphen		61	88.623	0.68831		1211
Synonymous	0.536	129	137	0.942	0.00000790	1379
Loss of Function	2.69	10	24.3	0.411	0.00000129	281

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.00	0.00
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Serine protease required during eye development. {ECO:0000269|PubMed:21397065}.
• Disease: DISEASE: Microphthalmia, isolated, 6 (MCOP6) [MIM:613517]: A developmental ocular disorder characterized by small malformed eyes. Clinical features are extreme hyperopia due to short axial length with essentially normal anterior segment, steep corneal curvatures, shallow anterior chamber, thick lenses, and thickened scleral wall. Palpebral fissures appear narrow because of relatively deep-set eyes, visual acuity is mildly to moderately reduced, and anisometropic or strabismic amblyopia is common. The fundus of the eye shows crowded optical disks, tortuous vessels, and an abnormal foveal avascular zone. {ECO:0000269|PubMed:21397065, ECO:0000269|PubMed:21532570, ECO:0000269|PubMed:21850159}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Essentials

• essential_gene_CRISPR2: N

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Prss56
• Phenotype: hematopoietic system phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); vision/eye phenotype; immune system phenotype

Gene ontology

• Biological process: proteolysis;camera-type eye development
• Cellular component: extracellular space;endoplasmic reticulum
• Molecular function: serine-type endopeptidase activity