Calpains are ubiquitous, well-conserved family of calcium-dependent, cysteine proteases. The calpain proteins are heterodimers consisting of an invariant small subunit and variable large subunits. The large subunit possesses a cysteine protease domain, and both subunits possess calcium-binding domains. Calpains have been implicated in neurodegenerative processes, as their activ... See more...

Aliases for CAPN6 Gene

Aliases for CAPN6 Gene

  • Calpain 6 2 3 5
  • CANPX 2 3 4
  • CalpM 2 3 4
  • Calpain-Like Protease X-Linked 3 4
  • Calpamodulin 3 4
  • Calpain-6 3 4
  • CAPNX 2 3
  • DJ914P14.1 3
  • EC 3.4.22 50
  • CAPN6 5
  • CALPM 4

External Ids for CAPN6 Gene

Previous GeneCards Identifiers for CAPN6 Gene

  • GC0XM105791
  • GC0XM107635
  • GC0XM108513
  • GC0XM109252
  • GC0XM110294
  • GC0XM110374
  • GC0XM110488
  • GC0XM100116

Summaries for CAPN6 Gene

Entrez Gene Summary for CAPN6 Gene

  • Calpains are ubiquitous, well-conserved family of calcium-dependent, cysteine proteases. The calpain proteins are heterodimers consisting of an invariant small subunit and variable large subunits. The large subunit possesses a cysteine protease domain, and both subunits possess calcium-binding domains. Calpains have been implicated in neurodegenerative processes, as their activation can be triggered by calcium influx and oxidative stress. The protein encoded by this gene is highly expressed in the placenta. Its C-terminal region lacks any homology to the calmodulin-like domain of other calpains. The protein lacks critical active site residues and thus is suggested to be proteolytically inactive. The protein may play a role in tumor formation by inhibiting apoptosis and promoting angiogenesis. [provided by RefSeq, Nov 2009]

GeneCards Summary for CAPN6 Gene

CAPN6 (Calpain 6) is a Protein Coding gene. Diseases associated with CAPN6 include Leiomyosarcoma and Leiomyoma. Among its related pathways are B Cell Receptor Signaling Pathway (sino) and Degradation of the extracellular matrix. Gene Ontology (GO) annotations related to this gene include microtubule binding and calcium-dependent cysteine-type endopeptidase activity. An important paralog of this gene is CAPN5.

UniProtKB/Swiss-Prot Summary for CAPN6 Gene

  • Microtubule-stabilizing protein that may be involved in the regulation of microtubule dynamics and cytoskeletal organization. May act as a regulator of RAC1 activity through interaction with ARHGEF2 to control lamellipodial formation and cell mobility. Does not seem to have protease activity as it has lost the active site residues (By similarity).

Tocris Summary for CAPN6 Gene

  • Calpains are a group of calcium-sensitive cysteine proteases that are ubiquitously expressed in mammals. Structurally, calpains contain two subunits; an 80 kDa catalytic subunit and a 28 kDa regulatory subunit that functions as a chaperone to stabilize the 80 kDa structure.

No data available for CIViC Summary , Gene Wiki entry , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for CAPN6 Gene

Genomics for CAPN6 Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for CAPN6 Gene
GeneHancer (GH) Identifier GH Type GH
Score
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH0XJ111268 Promoter/Enhancer 1.3 EPDnew Ensembl ENCODE CraniofacialAtlas 255.3 +1.5 1482 3.6 PRDM10 TAF1 CAPN6 5MWI_A-191 CHRDL1 lnc-PAK3-1 PAK3
GH0XJ112081 Promoter 0.7 Ensembl 3.6 -812.8 -812818 1.8 YY1 RXRA HNF4A RAD21 SP1 CTCF EZH2 RTL4 TRPC5 CAPN6 piR-39891-088 HSALNG0139559 LHFPL1
GH0XJ111282 Enhancer 0.2 ENCODE 4.1 -12.6 -12625 2.2 CHRDL1 CAPN6 HSALNG0139540 DCX
GH0XJ111220 Enhancer 0.2 Ensembl 4 +50.2 50182 0.2 CAPN6 piR-44878-076 FCF1P4 PAK3
GH0XJ111255 Enhancer 0.6 Ensembl ENCODE 0.4 +15.0 14986 0.2 MAFF ZNF316 MAFK MAFG FOS EMSY lnc-PAK3-1 5MWI_A-191 CAPN6 PAK3
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around CAPN6 on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for CAPN6

Top Transcription factor binding sites by QIAGEN in the CAPN6 gene promoter:
  • AREB6
  • Cart-1
  • GCNF
  • GCNF-1
  • GCNF-2
  • MyoD
  • MZF-1
  • Nkx2-5
  • SEF-1 (1)

Genomic Locations for CAPN6 Gene

Latest Assembly
chrX:111,245,099-111,270,483
(GRCh38/hg38)
Size:
25,385 bases
Orientation:
Minus strand

Previous Assembly
chrX:110,488,327-110,513,711
(GRCh37/hg19 by Entrez Gene)
Size:
25,385 bases
Orientation:
Minus strand

chrX:110,488,331-110,513,751
(GRCh37/hg19 by Ensembl)
Size:
25,421 bases
Orientation:
Minus strand

Genomic View for CAPN6 Gene

Genes around CAPN6 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
CAPN6 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for CAPN6 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for CAPN6 Gene

Proteins for CAPN6 Gene

  • Protein details for CAPN6 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q9Y6Q1-CAN6_HUMAN
    Recommended name:
    Calpain-6
    Protein Accession:
    Q9Y6Q1
    Secondary Accessions:
    • D3DUY7
    • Q9UEQ1
    • Q9UJA8

    Protein attributes for CAPN6 Gene

    Size:
    641 amino acids
    Molecular mass:
    74576 Da
    Quaternary structure:
    • Interacts (via domain III) with microtubules. Interacts (via domain II) with ARHGEF2 (via the N-terminal zinc finger).

neXtProt entry for CAPN6 Gene

Selected DME Specific Peptides for CAPN6 Gene

Q9Y6Q1:
  • YAGIFHF
  • LLEKAYAK

Post-translational modifications for CAPN6 Gene

  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

Other Protein References for CAPN6 Gene

ENSEMBL proteins:
REFSEQ proteins:

Antibodies for research

  • Boster Bio Antibodies for CAPN6

Domains & Families for CAPN6 Gene

Gene Families for CAPN6 Gene

HGNC:
Human Protein Atlas (HPA):
  • Cancer-related genes
  • Enzymes
  • Predicted intracellular proteins

Protein Domains for CAPN6 Gene

Suggested Antigen Peptide Sequences for CAPN6 Gene

GenScript: Design optimal peptide antigens:
  • Calpamodulin (CAN6_HUMAN)

Graphical View of Domain Structure for InterPro Entry

Q9Y6Q1

UniProtKB/Swiss-Prot:

CAN6_HUMAN :
  • Belongs to the peptidase C2 family.
Family:
  • Belongs to the peptidase C2 family.
genes like me logo Genes that share domains with CAPN6: view

Function for CAPN6 Gene

Molecular function for CAPN6 Gene

UniProtKB/Swiss-Prot Function:
Microtubule-stabilizing protein that may be involved in the regulation of microtubule dynamics and cytoskeletal organization. May act as a regulator of RAC1 activity through interaction with ARHGEF2 to control lamellipodial formation and cell mobility. Does not seem to have protease activity as it has lost the active site residues (By similarity).
GENATLAS Biochemistry:
calpain,class C,large polypeptide,likely lacking a protease activity,papain superfamily,nCL-3 type,expressed only in placenta,homolog to C elegans sex determination gene tra3

Enzyme Numbers (IUBMB) for CAPN6 Gene

Gene Ontology (GO) - Molecular Function for CAPN6 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0004198 NOT calcium-dependent cysteine-type endopeptidase activity TAS,IBA 21873635
GO:0005515 protein binding IPI 32296183
GO:0008017 microtubule binding IEA,ISS --
genes like me logo Genes that share ontologies with CAPN6: view
genes like me logo Genes that share phenotypes with CAPN6: view

Animal Models for CAPN6 Gene

MGI Knock Outs for CAPN6:

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for CAPN6

No data available for Phenotypes From GWAS Catalog , Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for CAPN6 Gene

Localization for CAPN6 Gene

Subcellular locations from UniProtKB/Swiss-Prot for CAPN6 Gene

Cytoplasm, perinuclear region. Cytoplasm, cytoskeleton, spindle. Note=During mitose associated with the mitotic spindle. At telophase colocalized to the midbody spindle.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for CAPN6 gene
Compartment Confidence
cytoskeleton 5
cytosol 4
nucleus 2
plasma membrane 1
extracellular 1
mitochondrion 1
endoplasmic reticulum 1
lysosome 1

Subcellular locations from the

Human Protein Atlas (HPA)
  • Cytosol (3)
  • Centriolar satellite (2)
  • Nucleoplasm (1)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for CAPN6 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005737 cytoplasm IBA 21873635
GO:0005819 spindle IEA --
GO:0005856 cytoskeleton IEA --
GO:0005874 microtubule IEA --
GO:0005876 spindle microtubule IDA 17210638
genes like me logo Genes that share ontologies with CAPN6: view

Pathways & Interactions for CAPN6 Gene

PathCards logo

SuperPathways for CAPN6 Gene

SuperPathway Contained pathways
1 DREAM Repression and Dynorphin Expression
.37
.36
.31
2 Degradation of the extracellular matrix
3 Apoptosis Pathway
4 B Cell Receptor Signaling Pathway (sino)
5 ERK Signaling
.61
genes like me logo Genes that share pathways with CAPN6: view

Pathways by source for CAPN6 Gene

1 Sino Biological pathway for CAPN6 Gene
1 BioSystems pathway for CAPN6 Gene
1 Tocris pathway for CAPN6 Gene
5 Qiagen pathways for CAPN6 Gene
  • Calpain Protease Regulates Cellular Mechanics
  • Caspase Cascade
  • ERK Signaling
  • FAK1 Signaling
  • nNOS Signaling in Skeletal Muscle

Gene Ontology (GO) - Biological Process for CAPN6 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0001578 microtubule bundle formation IEA,ISS --
GO:0006508 NOT proteolysis IEA,IBA 21873635
GO:0051493 regulation of cytoskeleton organization IEA,ISS --
genes like me logo Genes that share ontologies with CAPN6: view

No data available for SIGNOR curated interactions for CAPN6 Gene

Drugs & Compounds for CAPN6 Gene

(2) Drugs for CAPN6 Gene - From: Tocris

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Calpeptin Pharma Ca2+-dependent protease,calpain inhibitor, Calpain and cathepsin L inhibitor 0
MDL 28170 Pharma Calpain and cathepsin B inhibitor, selective, Potent, selective calpain and cathepsin B inhibitor 0

(2) Tocris Compounds for CAPN6 Gene

Compound Action Cas Number
Calpeptin Calpain and cathepsin L inhibitor 117591-20-5
MDL 28170 Potent, selective calpain and cathepsin B inhibitor 88191-84-8
genes like me logo Genes that share compounds with CAPN6: view

Transcripts for CAPN6 Gene

mRNA/cDNA for CAPN6 Gene

1 REFSEQ mRNAs :
8 NCBI additional mRNA sequence :
1 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for CAPN6

Alternative Splicing Database (ASD) splice patterns (SP) for CAPN6 Gene

ExUns: 1a · 1b ^ 2a · 2b ^ 3 ^ 4a · 4b · 4c ^ 5 ^ 6 ^ 7 ^ 8a · 8b ^ 9 ^ 10 ^ 11a · 11b ^ 12 ^ 13a · 13b
SP1: -
SP2: - - - -
SP3: - - - - -
SP4: -
SP5:

Relevant External Links for CAPN6 Gene

GeneLoc Exon Structure for
CAPN6

Expression for CAPN6 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for CAPN6 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for CAPN6 Gene

This gene is overexpressed in Uterus (x10.3).

Protein differential expression in normal tissues from HIPED for CAPN6 Gene

This gene is overexpressed in Placenta (65.3).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB and MOPED for CAPN6 Gene



Transcriptomic regulation report from SPP (The Signaling Pathways Project) for CAPN6

SOURCE GeneReport for Unigene cluster for CAPN6 Gene:

Hs.496593

mRNA Expression by UniProt/SwissProt for CAPN6 Gene:

Q9Y6Q1-CAN6_HUMAN
Tissue specificity: Expressed only in placenta.

Evidence on tissue expression from TISSUES for CAPN6 Gene

  • Muscle(2.9)
  • Intestine(2.4)
genes like me logo Genes that share expression patterns with CAPN6: view

Primer products for research

No data available for Protein tissue co-expression partners and Phenotype-based relationships between genes and organs from Gene ORGANizer for CAPN6 Gene

Orthologs for CAPN6 Gene

This gene was present in the common ancestor of animals.

Orthologs for CAPN6 Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
Mammalia CAPN6 29 30
  • 99.32 (n)
OneToOne
Dog
(Canis familiaris)
Mammalia CAPN6 29 30
  • 92.98 (n)
OneToOne
Cow
(Bos Taurus)
Mammalia CAPN6 29 30
  • 91.63 (n)
OneToOne
Rat
(Rattus norvegicus)
Mammalia Capn6 29
  • 90.28 (n)
Mouse
(Mus musculus)
Mammalia Capn6 29 16 30
  • 90.12 (n)
OneToOne
Platypus
(Ornithorhynchus anatinus)
Mammalia CAPN6 30
  • 54 (a)
OneToOne
Oppossum
(Monodelphis domestica)
Mammalia CAPN6 30
  • 52 (a)
OneToOne
Chicken
(Gallus gallus)
Aves CAPN6 29 30
  • 62.25 (n)
OneToOne
Lizard
(Anolis carolinensis)
Reptilia CAPN6 30
  • 51 (a)
OneToOne
Zebrafish
(Danio rerio)
Actinopterygii CR847986.1 30
  • 40 (a)
ManyToMany
Worm
(Caenorhabditis elegans)
Secernentea tra-3 30 31
  • 35 (a)
OneToMany
Sea Squirt
(Ciona savignyi)
Ascidiacea CSA.3869 30
  • 26 (a)
OneToMany
Species where no ortholog for CAPN6 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • Alpha proteobacteria (Wolbachia pipientis)
  • Amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • Baker's yeast (Saccharomyces cerevisiae)
  • Barley (Hordeum vulgare)
  • Beta proteobacteria (Neisseria meningitidis)
  • Bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • Common water flea (Daphnia pulex)
  • Corn (Zea mays)
  • E. coli (Escherichia coli)
  • Filamentous fungi (Aspergillus nidulans)
  • Firmicute Bacteria (Streptococcus pneumoniae)
  • Fission Yeast (Schizosaccharomyces pombe)
  • Fruit Fly (Drosophila melanogaster)
  • Green Algae (Chlamydomonas reinhardtii)
  • Honey Bee (Apis mellifera)
  • K. Lactis Yeast (Kluyveromyces lactis)
  • Loblloly Pine (Pinus taeda)
  • Malaria Parasite (Plasmodium falciparum)
  • Medicago Trunc (Medicago Truncatula)
  • Moss (Physcomitrella patens)
  • Orangutan (Pongo pygmaeus)
  • Pig (Sus scrofa)
  • Rainbow Trout (Oncorhynchus mykiss)
  • Rice (Oryza sativa)
  • Rice Blast Fungus (Magnaporthe grisea)
  • Schistosome Parasite (Schistosoma mansoni)
  • Sea Anemone (Nematostella vectensis)
  • Sea Vase (Ciona intestinalis)
  • Sea Urchin (Strongylocentrotus purpuratus)
  • Sorghum (Sorghum bicolor)
  • Soybean (Glycine max)
  • Stem Rust Fungus (Puccinia graminis)
  • Sugarcane (Saccharum officinarum)
  • Thale Cress (Arabidopsis thaliana)
  • Tomato (Lycopersicon esculentum)
  • Toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • Tropical Clawed Frog (Silurana tropicalis)
  • Wheat (Triticum aestivum)

Evolution for CAPN6 Gene

ENSEMBL:
Gene Tree for CAPN6 (if available)
TreeFam:
Gene Tree for CAPN6 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for CAPN6: view image
Alliance of Genome Resources:
Additional Orthologs for CAPN6

Paralogs for CAPN6 Gene

(7) SIMAP similar genes for CAPN6 Gene using alignment to 2 proteins:

  • CAN6_HUMAN
  • F5GWQ6_HUMAN
genes like me logo Genes that share paralogs with CAPN6: view

Variants for CAPN6 Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for CAPN6 Gene

SNP ID Clinical significance and condition Chr 0X pos Variation AA Info Type
rs17879776 Benign: not provided 111,248,637(-) G/A
NM_014289.4(CAPN6):c.1416C>T (p.Thr472=)
SYNONYMOUS
rs193921059 Uncertain Significance: Malignant tumor of prostate 111,246,746(-) C/T
NM_014289.4(CAPN6):c.1757G>A (p.Arg586Gln)
MISSENSE
VAR_036048 A colorectal cancer sample p.Gly358Arg
rs12013711 -- p.Val277Leu
rs12851517 -- p.Thr518Ile

dbSNP identifiers (rs#s) for variants without ClinVar clinical significance for CAPN6 Gene

All consequence types are included: molecular consequences (e.g. missense, synonymous), and location-based (e.g. intron, upstream).

Structural Variations from Database of Genomic Variants (DGV) for CAPN6 Gene

Variant ID Type Subtype PubMed ID
esv3361732 OTHER inversion 20981092

Variation tolerance for CAPN6 Gene

Residual Variation Intolerance Score: 10.2% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 6.40; 77.07% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for CAPN6 Gene

SNPedia medical, phenotypic, and genealogical associations of SNPs for
CAPN6
Leiden Open Variation Database (LOVD)
CAPN6

SNP Genotyping and Copy Number Assays for research

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for CAPN6 Gene

Disorders for CAPN6 Gene

MalaCards: The human disease database

(7) MalaCards diseases for CAPN6 Gene - From: COP and GCD

Disorder Aliases PubMed IDs
leiomyosarcoma
  • leiomyosarcomas
leiomyoma
  • leiomyomatous neoplasm
corneal dystrophy, endothelial, x-linked
  • xecd
coffin-siris syndrome 1
  • css1
corneal dystrophy, posterior polymorphous, 1
  • ppcd1
- elite association - COSMIC cancer census association via MalaCards
Search CAPN6 in MalaCards View complete list of genes associated with diseases

Additional Disease Information for CAPN6

Human Genome Epidemiology Navigator
(HuGE)
Atlas
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
Open Targets Platform
Open Targets Platform
genes like me logo Genes that share disorders with CAPN6: view

No data available for UniProtKB/Swiss-Prot and Genatlas for CAPN6 Gene

Publications for CAPN6 Gene

  1. A new subfamily of vertebrate calpains lacking a calmodulin-like domain: implications for calpain regulation and evolution. (PMID: 9339374) Dear N … Boehm T (Genomics 1997) 2 3 4 22
  2. Calpain 6 is involved in microtubule stabilization and cytoskeletal organization. (PMID: 17210638) Tonami K … Kurihara H (Molecular and cellular biology 2007) 3 4 22
  3. Genomic organization of mouse Capn5 and Capn6 genes confirms that they are a distinct calpain subfamily. (PMID: 9503024) Matena K … Dear N (Genomics 1998) 2 3 22
  4. Variation at the NFATC2 locus increases the risk of thiazolidinedione-induced edema in the Diabetes REduction Assessment with ramipril and rosiglitazone Medication (DREAM) study. (PMID: 20628086) Bailey SD … DREAM investigators (Diabetes care 2010) 3 40
  5. Family-based association study for bipolar affective disorder. (PMID: 20414141) Secolin R … Lopes-Cendes I (Psychiatric genetics 2010) 3 40

Products for CAPN6 Gene

Sources for CAPN6 Gene