Incidental Mutation 'YA93:Serpinf2'
ID89
Institutional Source Beutler Lab
Gene Symbol Serpinf2
Ensembl Gene ENSMUSG00000038224
Gene Nameserine (or cysteine) peptidase inhibitor, clade F, member 2
Synonymsalpha 2 antiplasmin, Pli
Accession Numbers

Genbank: NM_008878; MGI: 107173

Is this an essential gene? Probably non essential (E-score: 0.107) question?
Stock #YA93 of strain inept
Quality Score
Status Validated
Chromosome11
Chromosomal Location75431732-75439591 bp(-) (GRCm38)
Type of Mutationmissense
DNA Base Change (assembly) C to A at 75432684 bp
ZygosityHeterozygous
Amino Acid Change Valine to Leucine at position 399 (V399L)
Ref Sequence ENSEMBL: ENSMUSP00000104076 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000043696] [ENSMUST00000108437] [ENSMUST00000128330] [ENSMUST00000142094]
Predicted Effect probably benign
Transcript: ENSMUST00000043696
AA Change: V399L

PolyPhen 2 Score 0.004 (Sensitivity: 0.98; Specificity: 0.59)
SMART Domains Protein: ENSMUSP00000048704
Gene: ENSMUSG00000038224
AA Change: V399L

DomainStartEndE-ValueType
signal peptide 1 21 N/A INTRINSIC
SERPIN 91 436 1.5e-137 SMART
Predicted Effect probably benign
Transcript: ENSMUST00000108437
AA Change: V399L

PolyPhen 2 Score 0.004 (Sensitivity: 0.98; Specificity: 0.59)
SMART Domains Protein: ENSMUSP00000104076
Gene: ENSMUSG00000038224
AA Change: V399L

DomainStartEndE-ValueType
signal peptide 1 21 N/A INTRINSIC
SERPIN 91 436 1.5e-137 SMART
Predicted Effect noncoding transcript
Transcript: ENSMUST00000119634
Predicted Effect probably benign
Transcript: ENSMUST00000128330
SMART Domains Protein: ENSMUSP00000114450
Gene: ENSMUSG00000038224

DomainStartEndE-ValueType
signal peptide 1 21 N/A INTRINSIC
SERPIN 91 280 1.07e-8 SMART
Predicted Effect probably benign
Transcript: ENSMUST00000142094
SMART Domains Protein: ENSMUSP00000120812
Gene: ENSMUSG00000038224

DomainStartEndE-ValueType
signal peptide 1 21 N/A INTRINSIC
Meta Mutation Damage Score 0.0898 question?
Coding Region Coverage
  • 1x: 90.4%
  • 3x: 81.3%
Validation Efficiency 88% (101/115)
MGI Phenotype FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene encodes a member of the serpin family of serine protease inhibitors. The protein is a major inhibitor of plasmin, which degrades fibrin and various other proteins. Consequently, the proper function of this gene has a major role in regulating the blood clotting pathway. Mutations in this gene result in alpha-2-plasmin inhibitor deficiency, which is characterized by severe hemorrhagic diathesis. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2009]
PHENOTYPE: Mice homozygous for disruptions in this gene have an essentially normal phenotype. Spontaneous lysis of blood clots occurs more readily but bleeding times are unaffected. [provided by MGI curators]
Allele List at MGI

All alleles(2) : Targeted, knock-out(2)

Other mutations in this stock
Total: 15 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
Arhgef4 C T 1: 34,732,217 R1202W probably benign Het
B4galnt4 T A 7: 141,067,411 I358K possibly damaging Homo
Chodl A G 16: 78,941,282 H46R probably benign Homo
Cubn C A 2: 13,383,992 R1468L probably benign Het
Dlg5 G A 14: 24,155,133 probably benign Het
Dntt A C 19: 41,053,187 M437L probably benign Het
Gm8251 A G 1: 44,065,085 probably benign Het
Grsf1 G A 5: 88,673,735 P157S probably damaging Het
Lct C T 1: 128,301,320 G812D probably damaging Het
Osbpl5 T A 7: 143,693,870 I720F probably benign Homo
Pbld2 T A 10: 63,054,445 Y211N possibly damaging Het
Peg3 T A 7: 6,711,647 E192V probably damaging Het
Ptbp3 T C 4: 59,524,413 T38A possibly damaging Het
Rpap3 T A 15: 97,693,233 E241V possibly damaging Het
Scara3 C A 14: 65,930,949 M406I probably damaging Het
Other mutations in Serpinf2
AlleleSourceChrCoordTypePredicted EffectPPH Score
IGL01019:Serpinf2 APN 11 75436507 missense possibly damaging 0.58
IGL01367:Serpinf2 APN 11 75438045 missense probably benign
IGL01382:Serpinf2 APN 11 75438037 unclassified probably benign
R0122:Serpinf2 UTSW 11 75436546 missense probably damaging 1.00
R0135:Serpinf2 UTSW 11 75436393 missense probably damaging 1.00
R1864:Serpinf2 UTSW 11 75437483 missense possibly damaging 0.74
R2202:Serpinf2 UTSW 11 75436762 missense probably benign 0.07
R3082:Serpinf2 UTSW 11 75437528 missense probably benign 0.19
R5117:Serpinf2 UTSW 11 75432500 missense probably benign 0.28
R5487:Serpinf2 UTSW 11 75433205 missense probably damaging 0.99
R5681:Serpinf2 UTSW 11 75435939 missense probably damaging 0.99
R5764:Serpinf2 UTSW 11 75437404 missense possibly damaging 0.94
R5868:Serpinf2 UTSW 11 75433239 missense probably benign 0.00
R6349:Serpinf2 UTSW 11 75432431 missense probably damaging 1.00
R6364:Serpinf2 UTSW 11 75436489 missense probably damaging 1.00
R6488:Serpinf2 UTSW 11 75437503 missense probably benign
R6701:Serpinf2 UTSW 11 75432443 missense probably damaging 0.97
R7034:Serpinf2 UTSW 11 75438418 unclassified probably benign
R7036:Serpinf2 UTSW 11 75438418 unclassified probably benign
Nature of Mutation
DNA sequencing using the SOLiD technique identified a G to T transversion at position 1231 of the Serpinf2 transcript in exon 10 of 12 total exons. Two transcripts of the Serpinf2 gene are displayed on Ensembl. The mutated nucleotide causes a valine to leucine substitution at amino acid 399 of the encoded protein. The mutation has been confirmed by DNA sequencing using the Sanger method (Figure 1).
Protein Function and Prediction
The Serpinf2 gene encodes a 491 amino acid protein that belongs to the serpin family and is known as the alpha-2 antiplasmin protein (Alpha-2-AP). Alpha-2-AP is a secreted protein whose major function is to inactivate plasmin and trypsin. Alpha-2-AP can also inactivate chymotrypsin.  (Uniprot Q61247). Mice homozygous for disruptions in this gene have an essentially normal phenotype. Spontaneous lysis of blood clots occurs more readily, but bleeding times are unaffected.
 
The V399L change is predicted to be benign by the PolyPhen program.
Posted On2010-03-02