CAPN5

Chr 11AD

calpain 5

Also known as: ADNIV, HTRA3, VRNI, nCL-3

NCBI Gene: 726 ENSG00000149260 UniProt: O15484 OMIM: 602537

Calpains are calcium-dependent cysteine proteases involved in signal transduction in a variety of cellular processes. A functional calpain protein consists of an invariant small subunit and 1 of a family of large subunits. CAPN5 is one of the large subunits. Unlike some of the calpains, CAPN5 and CAPN6 lack a calmodulin-like domain IV. Because of the significant similarity to Caenorhabditis elegans sex determination gene tra-3, CAPN5 is also called as HTRA3. [provided by RefSeq, Jul 2008]

OMIM Research

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Vitreoretinopathy, neovascular inflammatoryMIM #193235

Clinical highlights

Gene–disease validity (ClinGen)

Definitive · CAPN5-related vitreoretinopathy · AD · ClinGen 2021

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

—

LOEUF

Multiple*

Mechanism· predicted

Some data sources returned errors (1)

gnomad: Error: gnomAD API error: 400

Population Genetics & Constraint

gnomAD

Constraint data not available from gnomAD.

Background carrier burden — how many people carry a rare variant somewhere in CAPN5?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 42

882 rare PASS variants

Rare truncating (LoF)

1 in 510

148 rare PASS variants

Rare synonymous (reference)

1 in 93

370 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for CAPN5. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 65	1 in 600
South Asian	~43k	1 in 32	1 in 750
Remaining (unassigned)	~30k	1 in 40	1 in 820
European (Finnish)	~27k	1 in 170	1 in 2,300
Admixed American	~22k	1 in 41	1 in 1,200
African / African American	~21k	1 in 46	1 in 420
East Asian	~20k	1 in 60	1 in 490
Ashkenazi Jewish	~13k	1 in 96	≈ 1 in 6,500
Middle Eastern	~2,884	1 in 33	≈ 1 in 690

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 12 coding exons well covered in gnomAD exomes and genomes.? see exons ↓