Mutagenetix > Incidental Mutation

Incidental Mutation 'F6893:Pros1'

182

Institutional Source

Beutler Lab

Gene Symbol

Pros1

Ensembl Gene

ENSMUSG00000022912

Gene Name

protein S (alpha)

Synonyms

protein S

Accession Numbers

Genbank: NM_011173; MGI: 1095733

Is this an essential gene?

Essential (E-score: 1.000) question?

Stock #

F6893 (G3) of strain busy

Quality Score

Status

Validated

Chromosome

Chromosomal Location

62854307-62929346 bp(+) (GRCm38)

Type of Mutation

missense

DNA Base Change (assembly)

T to A at 62924639 bp (GRCm38)

Zygosity

Heterozygous

Amino Acid Change

Valine to Glutamic Acid at position 539 (V539E)

Ref Sequence

ENSEMBL: ENSMUSP00000023629 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000023629]

AlphaFold

Q08761

Predicted Effect

probably damaging
Transcript: ENSMUST00000023629
AA Change: V539E

PolyPhen 2 Score 0.979 (Sensitivity: 0.75; Specificity: 0.96)

SMART Domains

Protein: ENSMUSP00000023629
Gene: ENSMUSG00000022912
AA Change: V539E

Domain	Start	End	E-Value	Type
GLA	23	86	3.63e-31	SMART
EGF	120	155	4.39e-2	SMART
EGF_CA	157	200	6.91e-9	SMART
EGF_CA	201	242	5.23e-9	SMART
EGF_CA	243	283	1.1e-7	SMART
LamG	321	458	8.55e-22	SMART
LamG	506	646	1.57e-1	SMART

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000127502

Meta Mutation Damage Score

0.2485

Coding Region Coverage

1x: 88.7%
3x: 74.0%

Validation Efficiency

88% (165/188)

MGI Phenotype

FUNCTION: This gene encodes a vitamin K-dependent protein with key roles in multiple biological processes including coagulation, apoptosis and vasculogenesis. The encoded protein undergoes proteolytic processing to generate a mature protein which is secreted into the plasma. Mice lacking the encoded protein die in utero from a fulminant coagulopathy and associated hemorrhages. [provided by RefSeq, Oct 2015]
PHENOTYPE: Mice homozygous for a knock-out allele exhibit neonatal lethality associated with thrombosis, hemorrhage, and thrombocytopenia. [provided by MGI curators]

Allele List at MGI

All alleles(5) : Targeted, knock-out(1) Targeted, other(2) Gene trapped(2)

Other mutations in this stock

Total: 35 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Abca14	G	A	7: 120,325,038	V1638M	probably damaging	Het
Agrn	C	T	4: 156,174,179	R972Q	probably benign	Het
Anxa3	T	C	5: 96,824,994		probably benign	Het
Bpifa6	G	T	2: 153,987,158	D202Y	probably damaging	Het
Ccdc15	G	A	9: 37,315,640	T346I	probably damaging	Homo
Celsr3	G	A	9: 108,835,067	R1731H	probably benign	Het
Ces4a	A	G	8: 105,147,227	R443G	possibly damaging	Het
Chd2	T	C	7: 73,507,872	Q175R	possibly damaging	Het
Dpyd	T	A	3: 118,804,134		probably null	Het
Dscam	G	T	16: 97,056,460	H117N	possibly damaging	Het
F13a1	A	G	13: 36,972,025	Y205H	probably damaging	Het
Fat3	A	C	9: 16,006,789	L1446R	probably damaging	Homo
Golga4	T	C	9: 118,553,457	L515S	probably damaging	Het
Hoxb1	A	T	11: 96,365,902	T26S	probably benign	Het
Igsf10	T	G	3: 59,331,060	T567P	probably damaging	Het
Lamb2	T	C	9: 108,482,556	V365A	probably benign	Het
Mepe	A	G	5: 104,337,376	I127M	possibly damaging	Het
Mpi	A	T	9: 57,546,549	M230K	probably benign	Homo
Myh4	A	G	11: 67,255,457	D1447G	probably null	Homo
Olfr161	A	G	16: 3,593,163	I256V	possibly damaging	Het
Olfr350	A	G	2: 36,850,807	T254A	probably benign	Het
Panx2	T	C	15: 89,068,010	Y227H	probably damaging	Homo
Pdzd7	A	G	19: 45,036,734	W441R	probably damaging	Het
Poldip2	A	G	11: 78,519,194	I267M	probably damaging	Homo
Sacs	T	C	14: 61,212,976	M4157T	probably benign	Het
Slc45a3	A	G	1: 131,981,337	E424G	probably benign	Homo
Slc9a1	A	G	4: 133,422,146	E761G	probably benign	Homo
Stab2	G	A	10: 86,855,171	P2178L	probably damaging	Het
Syt4	C	T	18: 31,444,221	V27I	possibly damaging	Homo
Thumpd1	T	A	7: 119,720,576	K56*	probably null	Het
Tpr	A	G	1: 150,393,562	K19E	possibly damaging	Homo
Ttll10	A	G	4: 156,048,318	I74T	probably benign	Het
Txnrd1	C	T	10: 82,866,989	Q95*	probably null	Homo
Zc3h7b	A	G	15: 81,778,671	E421G	possibly damaging	Homo
Zc3hc1	G	T	6: 30,387,526	D51E	probably benign	Homo

Other mutations in Pros1

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL00937:Pros1	APN	16	62910045	missense	probably damaging	0.99
IGL01300:Pros1	APN	16	62913811	missense	possibly damaging	0.85
IGL02709:Pros1	APN	16	62898945	missense	probably damaging	0.99
IGL03080:Pros1	APN	16	62918143	missense	probably damaging	0.98
IGL03095:Pros1	APN	16	62907769	nonsense	probably null
R0124:Pros1	UTSW	16	62913946	missense	possibly damaging	0.95
R0517:Pros1	UTSW	16	62903518	missense	probably benign	0.03
R1113:Pros1	UTSW	16	62913865	missense	probably damaging	0.99
R1308:Pros1	UTSW	16	62913865	missense	probably damaging	0.99
R1355:Pros1	UTSW	16	62919558	missense	probably benign	0.23
R1370:Pros1	UTSW	16	62919558	missense	probably benign	0.23
R1517:Pros1	UTSW	16	62885512	missense	probably damaging	0.98
R1866:Pros1	UTSW	16	62928135	missense	possibly damaging	0.86
R1876:Pros1	UTSW	16	62903518	missense	probably damaging	0.96
R2255:Pros1	UTSW	16	62903572	missense	possibly damaging	0.86
R2364:Pros1	UTSW	16	62913848	missense	probably damaging	0.99
R2369:Pros1	UTSW	16	62928069	missense	probably damaging	1.00
R2979:Pros1	UTSW	16	62913866	missense	probably damaging	0.99
R3724:Pros1	UTSW	16	62900329	missense	possibly damaging	0.86
R4056:Pros1	UTSW	16	62900645	nonsense	probably null
R4556:Pros1	UTSW	16	62900673	missense	possibly damaging	0.95
R4688:Pros1	UTSW	16	62889007	critical splice donor site	probably null
R4850:Pros1	UTSW	16	62885524	missense	probably damaging	0.98
R4923:Pros1	UTSW	16	62903572	missense	possibly damaging	0.86
R5008:Pros1	UTSW	16	62928185	missense	possibly damaging	0.53
R5370:Pros1	UTSW	16	62913976	missense	probably benign	0.01
R5580:Pros1	UTSW	16	62926326	critical splice acceptor site	probably null
R5930:Pros1	UTSW	16	62928061	missense	probably damaging	0.96
R5974:Pros1	UTSW	16	62900667	missense	probably damaging	0.98
R6233:Pros1	UTSW	16	62898921	missense	possibly damaging	0.47
R6949:Pros1	UTSW	16	62924575	missense	probably benign	0.01
R7055:Pros1	UTSW	16	62928102	missense	possibly damaging	0.85
R7347:Pros1	UTSW	16	62919523	missense	probably damaging	0.97
R7375:Pros1	UTSW	16	62924550	missense	probably damaging	0.96
R7419:Pros1	UTSW	16	62928070	nonsense	probably null
R7980:Pros1	UTSW	16	62928153	missense	possibly damaging	0.86
R8234:Pros1	UTSW	16	62928177	missense	possibly damaging	0.73
R8479:Pros1	UTSW	16	62907739	missense	probably damaging	1.00
R8514:Pros1	UTSW	16	62910109	missense	probably benign	0.03
R8827:Pros1	UTSW	16	62926464	missense	probably benign	0.13
R9131:Pros1	UTSW	16	62928034	missense	probably damaging	0.96
R9484:Pros1	UTSW	16	62924524	missense	possibly damaging	0.91

Nature of Mutation

DNA sequencing using the SOLiD technique identified a T to A transversion at position 1711 of the Pros1 transcript in exon 13 of 15 total exons. Three transcripts of the Pros1 gene are displayed on Ensembl. The mutated nucleotide causes a valine to glutamic acid substitution at amino acid 539 of the encoded protein. The mutation has been confirmed by DNA sequencing using the Sanger method (Figure 1)..

Protein Function and Prediction

The Pros1 gene encodes a 675 amino acid protein that is a cofactor to activated protein C in the degradation of coagulation factors Va and VIIIa. It helps to prevent coagulation and stimulating fibrinolysis. Protein S contains four EGF-like domains, one gamma-carboxyglutamate domain and two laminin G-like domains (Uniprot Q08761). Mice homozygous for a knock-out allele exhibit neonatal lethality associated with thrombosis, hemorrhage, and thrombocytopenia.

The V539E change occurs in the second laminin G-like domain, and is predicted to be probably damaging by the PolyPhen program.

Posted On

2010-05-03