CAPN5

calpain 5, the group of Calpains|C2 domain containing

Basic information

Region (hg38): 11:77066960-77126155

Previous symbols: [ "VRNI" ]

Links

ENSG00000149260 ∙ NCBI:726 ∙ OMIM:602537 ∙ HGNC:1482 ∙ Uniprot:O15484 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• autosomal dominant neovascular inflammatory vitreoretinopathy (Moderate), mode of inheritance: AD
• autosomal dominant neovascular inflammatory vitreoretinopathy (Supportive), mode of inheritance: AD
• CAPN5-related vitreoretinopathy (Definitive), mode of inheritance: AD
• CAPN5-related vitreoretinopathy (Strong), mode of inheritance: AD
• CAPN5-related vitreoretinopathy (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Vitreoretinopathy, neovascular inflammatory	AD	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Ophthalmologic	23055945

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CAPN5 gene.

• not provided (524 variants)
• Inborn genetic diseases (50 variants)
• not specified (6 variants)
• Proliferative vitreoretinopathy (5 variants)
• Retinal dystrophy (2 variants)
• Autosomal dominant neovascular inflammatory vitreoretinopathy (1 variants)
• Occult macular dystrophy (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CAPN5 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			4	113	15	132
missense	3		241	16	6	266
nonsense			12			12
start loss						0
frameshift			14	1		15
inframe indel			5			5
splice donor/acceptor (+/-2bp)			4			4
splice region			13	10	6	29
non coding			10	52	11	73
Total	3	0	290	182	32

Variants in CAPN5

This is a list of pathogenic ClinVar variants found in the CAPN5 region.

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

Position	Type	Phenotype	Significance	ClinVar
11-77084894-C-T			Uncertain significance (Jul 07, 2023)
11-77084895-G-A			Likely benign (Dec 11, 2023)
11-77084899-G-A			Uncertain significance (Aug 19, 2023)
11-77084904-G-A			Likely benign (Apr 04, 2022)
11-77084907-C-G		CAPN5-related disorder	Benign/Likely benign (Jan 23, 2024)
11-77084909-A-G			Uncertain significance (Nov 19, 2023)
11-77084914-G-A			Uncertain significance (Jun 04, 2022)
11-77084914-G-T		Inborn genetic diseases	Uncertain significance (Sep 25, 2023)
11-77084915-A-G			Uncertain significance (Mar 31, 2022)
11-77084916-C-G		not specified	Benign (Jan 31, 2024)
11-77084916-C-T			Likely benign (Dec 30, 2021)
11-77084922-C-T			Likely benign (Oct 22, 2019)
11-77084937-G-A			Likely benign (Aug 22, 2022)
11-77084938-C-T		not specified	Likely benign (Dec 11, 2023)
11-77084939-G-A			Benign (Dec 22, 2023)
11-77084942-A-AC			Uncertain significance (Oct 03, 2023)
11-77084943-C-T			Likely benign (Aug 16, 2022)
11-77084947-C-T		Inborn genetic diseases	Uncertain significance (Oct 13, 2023)
11-77084950-C-T		Inborn genetic diseases	Uncertain significance (Sep 04, 2023)
11-77084951-G-A			Uncertain significance (Apr 30, 2023)
11-77084953-A-T			Uncertain significance (Nov 30, 2020)
11-77084956-A-G			Uncertain significance (Jan 08, 2024)
11-77084960-T-C			Uncertain significance (Dec 28, 2020)
11-77084962-C-T			Uncertain significance (Jan 06, 2023)
11-77084964-C-T			Likely benign (Nov 01, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CAPN5	protein_coding	protein_coding	ENST00000278559	12	59223

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
2.52e-8	0.995	125624	0	124	125748	0.000493

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.534	394	425	0.927	0.0000295	4179
Missense in Polyphen		158	188.81	0.83684		1866
Synonymous	0.0735	177	178	0.993	0.0000129	1250
Loss of Function	2.56	18	34.1	0.527	0.00000190	345

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00118	0.00117
Ashkenazi Jewish	0.00129	0.00129
East Asian	0.000763	0.000761
Finnish	0.0000464	0.0000462
European (Non-Finnish)	0.000541	0.000536
Middle Eastern	0.000763	0.000761
South Asian	0.000263	0.000261
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Calcium-regulated non-lysosomal thiol-protease. {ECO:0000250}.
• Disease: DISEASE: Vitreoretinopathy, neovascular inflammatory (VRNI) [MIM:193235]: An autoimmune condition of the eye that sequentially mimics uveitis, retinitis pigmentosa, and proliferative diabetic retinopathy as it progresses to complete blindness. Patients present during the second or third decade of life with posterior uveitis and reduction of the electroretinogram b-wave. They become more symptomatic when cataracts, cystoid macular edema, and disk edema diminish visual acuity during the second stage. Severe vision loss begins during the third stage when proliferative retinal neovascularization and epiretinal membranes appear. There is an ongoing pigmentary retinal degeneration and peripheral visual field loss during all stages. In the fourth stage, proliferative vitreoretinopathy causes tractional retinal detachments at the macula and vitreous base. The fifth or end- stage disease is marked by phthisis. {ECO:0000269|PubMed:23055945}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Integrin-mediated Cell Adhesion;Extracellular matrix organization;Degradation of the extracellular matrix (Consensus)

Recessive Scores

• pRec: 0.116

Intolerance Scores

• loftool: 0.214
• rvis_EVS: -0.9
• rvis_percentile_EVS: 10.14

Haploinsufficiency Scores

• pHI: 0.238
• hipred: N
• hipred_score: 0.289
• ghis: 0.467

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.392

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Capn5
• Phenotype: growth/size/body region phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span)

Gene ontology

• Biological process: proteolysis;signal transduction
• Cellular component: cytoplasm;focal adhesion;cell surface;extracellular exosome
• Molecular function: calcium-dependent cysteine-type endopeptidase activity