CAPN1

calpain 1, the group of Calpains|EF-hand domain containing

Basic information

Region (hg38): 11:65180566-65212006

Links

ENSG00000014216 ∙ NCBI:823 ∙ OMIM:114220 ∙ HGNC:1476 ∙ Uniprot:P07384 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• autosomal recessive spastic paraplegia type 76 (Strong), mode of inheritance: AR
• autosomal recessive spastic paraplegia type 76 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Spastic paraplegia 76, autosomal recessive	AR	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	Neurologic	27153400

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CAPN1 gene.

• not_provided (225 variants)
• Inborn_genetic_diseases (88 variants)
• Autosomal_recessive_spastic_paraplegia_type_76 (35 variants)
• CAPN1-related_disorder (6 variants)
• not_specified (5 variants)
• Hereditary_spastic_paraplegia_11 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CAPN1 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000005186.4. 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	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				54	7	61
missense	4	1	137	10	1	153
nonsense	10	8				18
start loss						0
frameshift	9	2				11
splice donor/acceptor (+/-2bp)	5	5				10
Total	28	16	137	64	8

Highest pathogenic variant AF is 0.000105541556

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CAPN1	protein_coding	protein_coding	ENST00000527323	21	31441

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
5.86e-10	1.00	124649	0	71	124720	0.000285

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.68	369	472	0.782	0.0000315	4636
Missense in Polyphen		135	194.01	0.69583		1899
Synonymous	2.48	149	193	0.773	0.0000134	1354
Loss of Function	3.16	23	46.1	0.499	0.00000257	470

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00155	0.00154
Ashkenazi Jewish	0.000204	0.000199
East Asian	0.000112	0.000111
Finnish	0.000140	0.000139
European (Non-Finnish)	0.000214	0.000212
Middle Eastern	0.000112	0.000111
South Asian	0.000233	0.000229
Other	0.000165	0.000165

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Calcium-regulated non-lysosomal thiol-protease which catalyzes limited proteolysis of substrates involved in cytoskeletal remodeling and signal transduction. {ECO:0000269|PubMed:21531719, ECO:0000269|PubMed:2400579}.
• Disease: DISEASE: Spastic paraplegia 76, autosomal recessive (SPG76) [MIM:616907]: A form of spastic paraplegia, a neurodegenerative disorder characterized by a slow, gradual, progressive weakness and spasticity of the lower limbs. Rate of progression and the severity of symptoms are quite variable. Initial symptoms may include difficulty with balance, weakness and stiffness in the legs, muscle spasms, and dragging the toes when walking. In some forms of the disorder, bladder symptoms (such as incontinence) may appear, or the weakness and stiffness may spread to other parts of the body. {ECO:0000269|PubMed:27153400}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Protein processing in endoplasmic reticulum - Homo sapiens (human);Alzheimer,s disease - Homo sapiens (human);Necroptosis - Homo sapiens (human);Apoptosis - Homo sapiens (human);Cellular senescence - Homo sapiens (human);Integrin-mediated Cell Adhesion;Alzheimers Disease;Keratinization;Developmental Biology;Neutrophil degranulation;Deregulated CDK5 triggers multiple neurodegenerative pathways in Alzheimer,s disease models;Neurodegenerative Diseases;Disease;erk and pi-3 kinase are necessary for collagen binding in corneal epithelia;ucalpain and friends in cell spread;integrin signaling pathway;deregulation of cdk5 in alzheimers disease;mcalpain and friends in cell motility;Extracellular matrix organization;Innate Immune System;Immune System;Degradation of the extracellular matrix;Formation of the cornified envelope;Signaling events mediated by PTP1B (Consensus)

Recessive Scores

• pRec: 0.340

Intolerance Scores

• loftool: 0.500
• rvis_EVS: -0.33
• rvis_percentile_EVS: 30.82

Haploinsufficiency Scores

• pHI: 0.572
• hipred: Y
• hipred_score: 0.758
• ghis: 0.565

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.624

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Capn1
• 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); hematopoietic system 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); normal phenotype; embryo phenotype; immune system phenotype; homeostasis/metabolism phenotype; cellular phenotype

Zebrafish Information Network

• Gene name: capn1a
• Affected structure: neuron
• Phenotype tag: abnormal
• Phenotype quality: disorganized

Gene ontology

• Biological process: proteolysis;positive regulation of cell population proliferation;regulation of macroautophagy;receptor catabolic process;neutrophil degranulation;regulation of catalytic activity;mammary gland involution;cornification;self proteolysis;regulation of NMDA receptor activity
• Cellular component: extracellular region;cytoplasm;mitochondrion;lysosome;cytosol;plasma membrane;focal adhesion;membrane;extracellular exosome;ficolin-1-rich granule lumen
• Molecular function: endopeptidase activity;calcium-dependent cysteine-type endopeptidase activity;calcium ion binding;protein binding