Mutagenetix > Incidental Mutation

Incidental Mutation 'YA93:Serpinf2'

Institutional Source

Beutler Lab

Gene Symbol

Serpinf2

Ensembl Gene

ENSMUSG00000038224

Gene Name

serine (or cysteine) peptidase inhibitor, clade F, member 2

Synonyms

Pli, alpha 2 antiplasmin

Accession Numbers

Essential gene?

Probably non essential (E-score: 0.105) question?

Stock #

YA93 of strain inept

Quality Score

Status

Validated

Chromosome

Chromosomal Location

75322562-75330327 bp(-) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

C to A at 75323510 bp (GRCm39)

Zygosity

Heterozygous

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]

AlphaFold

Q61247

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

Domain	Start	End	E-Value	Type
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

Domain	Start	End	E-Value	Type
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

Domain	Start	End	E-Value	Type
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

Domain	Start	End	E-Value	Type
signal peptide	1	21	N/A	INTRINSIC

Meta Mutation Damage Score

0.0898

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
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Arhgef4	C	T	1: 34,771,298 (GRCm39)	R1202W	probably benign	Het
B4galnt4	T	A	7: 140,647,324 (GRCm39)	I358K	possibly damaging	Homo
Ccdc168	A	G	1: 44,104,245 (GRCm39)		probably benign	Het
Chodl	A	G	16: 78,738,170 (GRCm39)	H46R	probably benign	Homo
Cubn	C	A	2: 13,388,803 (GRCm39)	R1468L	probably benign	Het
Dlg5	G	A	14: 24,205,201 (GRCm39)		probably benign	Het
Dntt	A	C	19: 41,041,626 (GRCm39)	M437L	probably benign	Het
Grsf1	G	A	5: 88,821,594 (GRCm39)	P157S	probably damaging	Het
Lct	C	T	1: 128,229,057 (GRCm39)	G812D	probably damaging	Het
Osbpl5	T	A	7: 143,247,607 (GRCm39)	I720F	probably benign	Homo
Pbld2	T	A	10: 62,890,224 (GRCm39)	Y211N	possibly damaging	Het
Peg3	T	A	7: 6,714,646 (GRCm39)	E192V	probably damaging	Het
Ptbp3	T	C	4: 59,524,413 (GRCm39)	T38A	possibly damaging	Het
Rpap3	T	A	15: 97,591,114 (GRCm39)	E241V	possibly damaging	Het
Scara3	C	A	14: 66,168,398 (GRCm39)	M406I	probably damaging	Het

Other mutations in Serpinf2

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL01019:Serpinf2	APN	11	75,327,333 (GRCm39)	missense	possibly damaging	0.58
IGL01367:Serpinf2	APN	11	75,328,871 (GRCm39)	missense	probably benign
IGL01382:Serpinf2	APN	11	75,328,863 (GRCm39)	unclassified	probably benign
R0122:Serpinf2	UTSW	11	75,327,372 (GRCm39)	missense	probably damaging	1.00
R0135:Serpinf2	UTSW	11	75,327,219 (GRCm39)	missense	probably damaging	1.00
R1864:Serpinf2	UTSW	11	75,328,309 (GRCm39)	missense	possibly damaging	0.74
R2202:Serpinf2	UTSW	11	75,327,588 (GRCm39)	missense	probably benign	0.07
R3082:Serpinf2	UTSW	11	75,328,354 (GRCm39)	missense	probably benign	0.19
R5117:Serpinf2	UTSW	11	75,323,326 (GRCm39)	missense	probably benign	0.28
R5487:Serpinf2	UTSW	11	75,324,031 (GRCm39)	missense	probably damaging	0.99
R5681:Serpinf2	UTSW	11	75,326,765 (GRCm39)	missense	probably damaging	0.99
R5764:Serpinf2	UTSW	11	75,328,230 (GRCm39)	missense	possibly damaging	0.94
R5868:Serpinf2	UTSW	11	75,324,065 (GRCm39)	missense	probably benign	0.00
R6349:Serpinf2	UTSW	11	75,323,257 (GRCm39)	missense	probably damaging	1.00
R6364:Serpinf2	UTSW	11	75,327,315 (GRCm39)	missense	probably damaging	1.00
R6488:Serpinf2	UTSW	11	75,328,329 (GRCm39)	missense	probably benign
R6701:Serpinf2	UTSW	11	75,323,269 (GRCm39)	missense	probably damaging	0.97
R7034:Serpinf2	UTSW	11	75,329,244 (GRCm39)	unclassified	probably benign
R7036:Serpinf2	UTSW	11	75,329,244 (GRCm39)	unclassified	probably benign
R9147:Serpinf2	UTSW	11	75,323,418 (GRCm39)	missense	probably damaging	1.00
R9148:Serpinf2	UTSW	11	75,323,418 (GRCm39)	missense	probably damaging	1.00
R9487:Serpinf2	UTSW	11	75,323,494 (GRCm39)	missense	probably damaging	0.97
R9509:Serpinf2	UTSW	11	75,328,895 (GRCm39)	missense	probably benign	0.01
R9578:Serpinf2	UTSW	11	75,327,615 (GRCm39)	missense	probably benign	0.07

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 On

2010-03-02