CAPNS1

calpain small subunit 1, the group of EF-hand domain containing

Basic information

Region (hg38): 19:36139953-36150353

Previous symbols: [ "CAPN4" ]

Links

ENSG00000126247

∙ NCBI:826 ∙ OMIM:114170 ∙ HGNC:1481 ∙ Uniprot:P04632 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Pulmonary hypertension, primary, 6	AR	Cardiovascular; Pulmonary	The condition can involve severe, early-onset pulmonary hypertension, with related cardiovascular sequelae, and awareness may allow early identification and management	Cardiovascular; Pulmonary	38230350

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CAPNS1 gene.

not_specified (31 variants)
not_provided (2 variants)
Pulmonary_hypertension,_primary,_6 (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CAPNS1 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000001749.4. Only rare variants are included in the table.

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.

Effect	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous				2 clinvar		2
missense			31 clinvar			31
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)	2 clinvar					2
Total	2	0	31	2	0

Highest pathogenic variant AF is 0.0000150330725

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CAPNS1	protein_coding	protein_coding	ENST00000246533	10	10779

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
7.11e-7	0.724	125699	0	49	125748	0.000195

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.592	124	144	0.861	0.00000834	1745
Missense in Polyphen		37	54.776	0.67548		697
Synonymous	-1.13	62	51.6	1.20	0.00000280	504
Loss of Function	1.21	12	17.5	0.687	0.00000124	177

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000867	0.0000867
Ashkenazi Jewish	0.000298	0.000298
East Asian	0.0000589	0.0000544
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.000302	0.000299
Middle Eastern	0.0000589	0.0000544
South Asian	0.000196	0.000196
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

Function: FUNCTION: Regulatory subunit of the calcium-regulated non- lysosomal thiol-protease which catalyzes limited proteolysis of substrates involved in cytoskeletal remodeling and signal transduction.;
Pathway: Apoptosis Modulation and Signaling;Integrin-mediated Cell Adhesion;Keratinization;Developmental Biology;Deregulated CDK5 triggers multiple neurodegenerative pathways in Alzheimer,s disease models;Neurodegenerative Diseases;Disease;ucalpain and friends in cell spread;role of mef2d in t-cell apoptosis;mcalpain and friends in cell motility;Extracellular matrix organization;Degradation of the extracellular matrix;Formation of the cornified envelope (Consensus)

Recessive Scores

pRec: 0.341

Intolerance Scores

loftool: 0.656
rvis_EVS: -0.27
rvis_percentile_EVS: 33.97

Haploinsufficiency Scores

pHI: 0.0837
hipred: N
hipred_score: 0.489
ghis: 0.550

Essentials

essential_gene_CRISPR: N
essential_gene_CRISPR2: N
essential_gene_gene_trap: E
gene_indispensability_pred: E
gene_indispensability_score: 0.828

Gene Damage Prediction

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

Mouse Genome Informatics

Gene name: Capns1
Phenotype: respiratory system phenotype; embryo 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); hematopoietic system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); muscle phenotype; cellular phenotype; homeostasis/metabolism phenotype;

Gene ontology

Biological process: proteolysis;positive regulation of cell population proliferation;regulation of macroautophagy;cornification
Cellular component: cytosol;plasma membrane;membrane;extracellular exosome
Molecular function: endopeptidase activity;calcium-dependent cysteine-type endopeptidase activity;calcium ion binding;protein binding