Incidental Mutation 'A2778:Capn9'
ID 23
Institutional Source Beutler Lab
Gene Symbol Capn9
Ensembl Gene ENSMUSG00000031981
Gene Name calpain 9
Synonyms GC36, nCL-4
Accession Numbers
Essential gene? Possibly non essential (E-score: 0.394) question?
Stock # A2778 of strain phoebus
Quality Score
Status Validated
Chromosome 8
Chromosomal Location 125302850-125345470 bp(+) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) T to C at 125332217 bp (GRCm39)
Zygosity Homozygous
Amino Acid Change Phenylalanine to Serine at position 396 (F396S)
Ref Sequence ENSEMBL: ENSMUSP00000090717 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000093033]
AlphaFold Q9D805
Predicted Effect possibly damaging
Transcript: ENSMUST00000093033
AA Change: F396S

PolyPhen 2 Score 0.953 (Sensitivity: 0.79; Specificity: 0.95)
SMART Domains Protein: ENSMUSP00000090717
Gene: ENSMUSG00000031981
AA Change: F396S

DomainStartEndE-ValueType
CysPc 24 345 1.53e-196 SMART
calpain_III 348 494 1.91e-87 SMART
low complexity region 504 522 N/A INTRINSIC
EFh 565 593 1.25e-2 SMART
EFh 595 623 2.64e-1 SMART
Meta Mutation Damage Score 0.6907 question?
Coding Region Coverage
  • 1x: 78.0%
  • 3x: 41.9%
Validation Efficiency 85% (57/67)
MGI Phenotype FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] 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 expressed predominantly in stomach and small intestine and may have specialized functions in the digestive tract. This gene is thought to be associated with gastric cancer. Multiple alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]
PHENOTYPE: Mice homozygous for a knock-out allele exhibit increased sensitivity to ethanol-induced gastric mucosa injury. [provided by MGI curators]
Allele List at MGI

All alleles(1) : Gene trapped(1)

Other mutations in Capn9
AlleleSourceChrCoordTypePredicted EffectPPH Score
IGL01743:Capn9 APN 8 125,318,508 (GRCm39) missense probably benign
IGL01987:Capn9 APN 8 125,302,965 (GRCm39) missense probably benign 0.01
IGL02150:Capn9 APN 8 125,340,582 (GRCm39) missense probably benign 0.01
IGL02348:Capn9 APN 8 125,321,416 (GRCm39) missense probably damaging 1.00
IGL02720:Capn9 APN 8 125,327,236 (GRCm39) splice site probably benign
IGL02723:Capn9 APN 8 125,335,922 (GRCm39) splice site probably benign
IGL03065:Capn9 APN 8 125,332,298 (GRCm39) missense probably damaging 1.00
IGL03169:Capn9 APN 8 125,332,616 (GRCm39) missense probably damaging 1.00
R0288:Capn9 UTSW 8 125,327,230 (GRCm39) splice site probably benign
R1353:Capn9 UTSW 8 125,332,305 (GRCm39) splice site probably null
R1611:Capn9 UTSW 8 125,338,251 (GRCm39) missense possibly damaging 0.90
R1672:Capn9 UTSW 8 125,340,570 (GRCm39) missense probably benign 0.03
R1682:Capn9 UTSW 8 125,338,304 (GRCm39) splice site probably null
R1729:Capn9 UTSW 8 125,332,450 (GRCm39) missense possibly damaging 0.90
R1739:Capn9 UTSW 8 125,332,450 (GRCm39) missense possibly damaging 0.90
R1762:Capn9 UTSW 8 125,332,450 (GRCm39) missense possibly damaging 0.90
R1783:Capn9 UTSW 8 125,332,450 (GRCm39) missense possibly damaging 0.90
R1784:Capn9 UTSW 8 125,332,450 (GRCm39) missense possibly damaging 0.90
R1785:Capn9 UTSW 8 125,332,450 (GRCm39) missense possibly damaging 0.90
R1836:Capn9 UTSW 8 125,332,304 (GRCm39) critical splice donor site probably null
R1883:Capn9 UTSW 8 125,338,297 (GRCm39) missense probably benign
R1924:Capn9 UTSW 8 125,302,965 (GRCm39) missense probably benign 0.01
R2008:Capn9 UTSW 8 125,318,424 (GRCm39) missense probably damaging 1.00
R2049:Capn9 UTSW 8 125,332,450 (GRCm39) missense possibly damaging 0.90
R2069:Capn9 UTSW 8 125,332,450 (GRCm39) missense possibly damaging 0.90
R2131:Capn9 UTSW 8 125,332,450 (GRCm39) missense possibly damaging 0.90
R2141:Capn9 UTSW 8 125,332,450 (GRCm39) missense possibly damaging 0.90
R2219:Capn9 UTSW 8 125,335,898 (GRCm39) nonsense probably null
R4193:Capn9 UTSW 8 125,327,225 (GRCm39) missense probably null 0.00
R4707:Capn9 UTSW 8 125,340,195 (GRCm39) missense possibly damaging 0.82
R5092:Capn9 UTSW 8 125,324,264 (GRCm39) missense probably damaging 1.00
R5386:Capn9 UTSW 8 125,332,279 (GRCm39) missense possibly damaging 0.83
R5697:Capn9 UTSW 8 125,315,810 (GRCm39) missense unknown
R5734:Capn9 UTSW 8 125,332,583 (GRCm39) missense probably damaging 1.00
R5999:Capn9 UTSW 8 125,315,817 (GRCm39) missense probably damaging 1.00
R6026:Capn9 UTSW 8 125,332,601 (GRCm39) missense probably damaging 1.00
R6298:Capn9 UTSW 8 125,344,193 (GRCm39) missense probably benign
R6787:Capn9 UTSW 8 125,342,924 (GRCm39) missense probably benign 0.00
R6856:Capn9 UTSW 8 125,324,308 (GRCm39) missense probably damaging 1.00
R7131:Capn9 UTSW 8 125,303,017 (GRCm39) missense probably damaging 1.00
R7149:Capn9 UTSW 8 125,332,448 (GRCm39) missense probably benign 0.00
R7975:Capn9 UTSW 8 125,325,515 (GRCm39) missense probably damaging 1.00
R8086:Capn9 UTSW 8 125,334,692 (GRCm39) critical splice acceptor site probably null
R9197:Capn9 UTSW 8 125,340,600 (GRCm39) missense probably damaging 0.98
R9366:Capn9 UTSW 8 125,332,280 (GRCm39) missense probably benign 0.24
R9415:Capn9 UTSW 8 125,332,449 (GRCm39) missense probably benign 0.00
R9472:Capn9 UTSW 8 125,325,534 (GRCm39) critical splice donor site probably null
RF015:Capn9 UTSW 8 125,345,221 (GRCm39) missense probably benign 0.00
Nature of Mutation
DNA sequencing using the SOLiD technique identified a T to C transition at position 1221 of the Capn9 transcript, in exon 10 of 20 total exons. The mutated nucleotide causes a phenylalanine to serine substitution at amino acid 396. The mutation has been confirmed by DNA sequencing using the Sanger method (Figure 1).
 
 
Protein Function and Prediction
The Capn9 gene encodes a 690 amino acid protein, Calpain-9, with evidence at the transcript level (Uniprot Q9D805). Capn9 mRNA is predominantly expressed in stomach and small intestine. Calpains are a family of calcium-dependent cysteine proteases constituting the peptidase C2 family. Calpain-9 contains a calpain catalytic domain at amino acids 42-337, a calpain III domain located at residues 338-521, and 3 EF-hand domains that bind calcium between amino acids 518 and 626 (also known as the calpain IV domain).  The F396S mutation is located in the calpain III domain, and is predicted to be possibly damaging by the PolyPhen program.
Posted On 2009-11-09