Incidental Mutation 'E7848:Capn2'
ID54
Institutional Source Beutler Lab
Gene Symbol Capn2
Ensembl Gene ENSMUSG00000026509
Gene Namecalpain 2
SynonymsCapa-2, Capa2, m-calpain
Accession Numbers

Genbank: NM_009794 ; MGI: 88264

Is this an essential gene? Essential (E-score: 1.000) question?
Stock #E7848 of strain Klein-zschocher
Quality Score
Status Validated
Chromosome1
Chromosomal Location182467260-182517608 bp(-) (GRCm38)
Type of Mutationmissense
DNA Base Change (assembly) T to A at 182486594 bp
ZygosityHeterozygous
Amino Acid Change Aspartic acid to Valine at position 362 (D362V)
Ref Sequence ENSEMBL: ENSMUSP00000068895 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000068505]
Predicted Effect possibly damaging
Transcript: ENSMUST00000068505
AA Change: D362V

PolyPhen 2 Score 0.666 (Sensitivity: 0.86; Specificity: 0.91)
SMART Domains Protein: ENSMUSP00000068895
Gene: ENSMUSG00000026509
AA Change: D362V

DomainStartEndE-ValueType
CysPc 27 352 1.62e-186 SMART
calpain_III 355 510 3.47e-90 SMART
low complexity region 513 532 N/A INTRINSIC
EFh 576 604 5.86e0 SMART
EFh 606 634 3.21e0 SMART
Predicted Effect noncoding transcript
Transcript: ENSMUST00000192230
Predicted Effect noncoding transcript
Transcript: ENSMUST00000192483
Predicted Effect noncoding transcript
Transcript: ENSMUST00000192568
Predicted Effect noncoding transcript
Transcript: ENSMUST00000195868
Meta Mutation Damage Score 0.1796 question?
Coding Region Coverage
  • 1x: 86.1%
  • 3x: 63.4%
Validation Efficiency 94% (82/87)
MGI Phenotype FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] The calpains, calcium-activated neutral proteases, are nonlysosomal, intracellular cysteine proteases. The mammalian calpains include ubiquitous, stomach-specific, and muscle-specific proteins. The ubiquitous enzymes consist of heterodimers with distinct large, catalytic subunits associated with a common small, regulatory subunit. This gene encodes the large subunit of the ubiquitous enzyme, calpain 2. Multiple heterogeneous transcriptional start sites in the 5' UTR have been reported. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2009]
PHENOTYPE: Homozygous inactivation of this gene leads to complete prenatal lethality. Mice homozygous for one null allele display placental dysfunction, thin ventricular walls, and peripheral vessel failure. [provided by MGI curators]
Allele List at MGI

All alleles(1) : Targeted, knock-out(1)

Other mutations in this stock
Total: 5 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
Cdsn T C 17: 35,556,107 V511A probably benign Homo
Cyp2j11 T A 4: 96,319,365 I238L probably benign Het
Nat8f5 T G 6: 85,817,619 T120P probably damaging Homo
Sybu A T 15: 44,673,422 S375T probably benign Homo
Trappc8 T C 18: 20,850,918 H680R probably damaging Het
Other mutations in Capn2
AlleleSourceChrCoordTypePredicted EffectPPH Score
IGL02049:Capn2 APN 1 182473954 splice site probably benign
IGL02589:Capn2 APN 1 182484348 missense probably damaging 1.00
IGL02679:Capn2 APN 1 182472584 missense probably benign
IGL03207:Capn2 APN 1 182489013 missense possibly damaging 0.92
R0070:Capn2 UTSW 1 182473869 splice site probably benign
R0070:Capn2 UTSW 1 182473869 splice site probably benign
R0540:Capn2 UTSW 1 182492184 nonsense probably null
R0571:Capn2 UTSW 1 182470760 missense probably benign 0.01
R1620:Capn2 UTSW 1 182517137 missense probably damaging 1.00
R1818:Capn2 UTSW 1 182472597 missense probably benign 0.00
R1819:Capn2 UTSW 1 182472597 missense probably benign 0.00
R1822:Capn2 UTSW 1 182472960 missense possibly damaging 0.95
R1880:Capn2 UTSW 1 182489016 missense probably damaging 1.00
R2174:Capn2 UTSW 1 182479725 missense probably benign 0.22
R2391:Capn2 UTSW 1 182478609 missense probably benign 0.01
R2860:Capn2 UTSW 1 182472920 splice site probably benign
R2861:Capn2 UTSW 1 182472920 splice site probably benign
R2878:Capn2 UTSW 1 182517233 missense probably benign 0.00
R3052:Capn2 UTSW 1 182487772 missense probably benign 0.06
R4463:Capn2 UTSW 1 182479764 intron probably benign
R4669:Capn2 UTSW 1 182470780 missense probably benign 0.00
R5077:Capn2 UTSW 1 182472573 missense possibly damaging 0.71
R5397:Capn2 UTSW 1 182470706 missense probably damaging 1.00
R5696:Capn2 UTSW 1 182478600 missense possibly damaging 0.79
R6777:Capn2 UTSW 1 182470177 critical splice donor site probably null
R6800:Capn2 UTSW 1 182481480 missense probably damaging 0.99
R7741:Capn2 UTSW 1 182479723 nonsense probably null
R7814:Capn2 UTSW 1 182492146 missense probably damaging 1.00
R7995:Capn2 UTSW 1 182478546 critical splice donor site probably null
Nature of Mutation
Two transcripts of Capn2 are displayed on Ensembl. DNA sequencing using the SOLiD technique identified an A to T transversion at position 1214 of the first Capn2 transcript, in exon 9 of 21 total exons. The mutated nucleotide causes an aspartic acid to valine substitution at amino acid 362. In the second Capn2 transcript, the mutation is located within intron 9, nine nucleotides downstream from the previous exon 9. The second Capn2 transcript contains 19 exons. The mutation has been confirmed by DNA sequencing using the Sanger method (Figure 1).
Protein Function and Prediction
The Capn2 gene encodes the 700 amino acid Calpain-2 catalytic subunit, also known as M-calpain (Uniprot O08529). Calpains are a family of calcium-dependent cysteine proteases constituting the peptidase C2 family. M-calpain has broad endopeptidase specificity and is likely to be involved in multiple biological processes including cytoskeletal remodeling and signal transduction. M-calpain contains a small propeptide at amino acids 2-19 that anchors to its regulatory subunit, a calpain catalytic domain at amino acids 45-344, a calpain III domain located at residues 345-514, and 2 EF-hand domains that bind calcium between amino acids 572-637 (also known as the calpain IV domain). M-calpain is necessary for preimplantation embryonic development in mice.
 
The D362A change is located in the calpain III domain, and is predicted to be probably damaging by the PolyPhen program.
Posted On2009-11-13