Mutagenetix > Incidental Mutation

Incidental Mutation 'R7762:F2'

597911

Institutional Source

Beutler Lab

Gene Symbol

Ensembl Gene

ENSMUSG00000027249

Gene Name

coagulation factor II

Synonyms

Cf-2, FII, prothrombin, Cf2, thrombin

MMRRC Submission

045818-MU

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R7762 (G1)

Quality Score

225.009

Status

Validated

Chromosome

Chromosomal Location

91455665-91466759 bp(-) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

T to C at 91459041 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Histidine to Arginine at position 476 (H476R)

Ref Sequence

ENSEMBL: ENSMUSP00000028681 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000028681] [ENSMUST00000111335]

AlphaFold

P19221

PDB Structure

Structural basis of Na+ activation mimicry in murine thrombin [X-RAY DIFFRACTION]
Crystal structure of murine thrombin in complex with the extracellular fragment of murine PAR3 [X-RAY DIFFRACTION]
Crystal structure of murine thrombin in complex with the extracellular fragment of murine PAR4 [X-RAY DIFFRACTION]
Crystal structure of the W215A/E217A mutant of murine thrombin [X-RAY DIFFRACTION]
Crystal structure of murine thrombin mutant W215A/E217A (one molecule in the asymmetric unit) [X-RAY DIFFRACTION]
Crystal structure of murine thrombin mutant W215A/E217A (two molecules in the asymmetric unit) [X-RAY DIFFRACTION]
Crystal structure of murine thrombin mutant W215A/E217A in complex with the extracellular fragment of human PAR1 [X-RAY DIFFRACTION]

Predicted Effect

possibly damaging
Transcript: ENSMUST00000028681
AA Change: H476R

PolyPhen 2 Score 0.614 (Sensitivity: 0.87; Specificity: 0.91)

SMART Domains

Protein: ENSMUSP00000028681
Gene: ENSMUSG00000027249
AA Change: H476R

Domain	Start	End	E-Value	Type
signal peptide	1	24	N/A	INTRINSIC
GLA	25	89	1.91e-30	SMART
KR	107	189	7.47e-37	SMART
KR	213	295	5.09e-30	SMART
Tryp_SPc	360	610	9.99e-84	SMART

Predicted Effect

possibly damaging
Transcript: ENSMUST00000111335
AA Change: H475R

PolyPhen 2 Score 0.614 (Sensitivity: 0.87; Specificity: 0.91)

SMART Domains

Protein: ENSMUSP00000106967
Gene: ENSMUSG00000027249
AA Change: H475R

Domain	Start	End	E-Value	Type
signal peptide	1	24	N/A	INTRINSIC
GLA	25	89	1.91e-30	SMART
KR	107	189	8.01e-37	SMART
KR	212	294	5.09e-30	SMART
Tryp_SPc	359	609	9.99e-84	SMART

Meta Mutation Damage Score

0.2893

Coding Region Coverage

1x: 100.0%
3x: 100.0%
10x: 99.8%
20x: 99.2%

Validation Efficiency

100% (79/79)

MGI Phenotype

FUNCTION: This gene encodes a vitamin K-dependent glycoprotein coagulation factor that plays an important role in the process of blood coagulation and hemostasis. The encoded protein is an inactive zymogen that undergoes enzymatic cleavage by the coagulation factor Xa to form an active serine protease that converts soluble fibrinogen to insoluble fibrin clot. Most of the mice lacking the encoded protein die at an embryonic stage due to defects in yolk sac vasculature, while the rare nenonates succumb to hemorrhage on the first postnatal day. [provided by RefSeq, Apr 2015]
PHENOTYPE: Homozygotes for targeted null mutations exhibit defects in yolk sac vasculature, internal bleeding, tissue necrosis, and die in mid- to late-gestation, or rarely, a few days after birth. [provided by MGI curators]

Allele List at MGI

Other mutations in this stock

Total: 83 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Acod1	T	G	14: 103,288,776 (GRCm39)	D95E	probably damaging	Het
Agpat4	A	G	17: 12,429,209 (GRCm39)	T154A	possibly damaging	Het
Ahnak2	A	T	12: 112,742,114 (GRCm39)	S653T	probably benign	Het
Aoc1l2	G	A	6: 48,909,620 (GRCm39)	V622I	probably benign	Het
Aox1	C	T	1: 58,388,263 (GRCm39)	P1124S	probably damaging	Het
Armh3	A	G	19: 45,928,882 (GRCm39)		probably null	Het
Atp4a	T	C	7: 30,419,461 (GRCm39)	I637T	probably damaging	Het
Atxn7	T	A	14: 14,100,467 (GRCm38)	C718S	probably damaging	Het
Btbd2	T	A	10: 80,479,390 (GRCm39)	I516F	probably damaging	Het
Card6	A	G	15: 5,134,820 (GRCm39)	S128P	probably benign	Het
Cat	T	C	2: 103,287,203 (GRCm39)	K476E	probably benign	Het
Ccr9	A	T	9: 123,609,022 (GRCm39)	T235S	probably benign	Het
Cep55	T	G	19: 38,057,517 (GRCm39)		probably null	Het
Clec2e	A	G	6: 129,072,091 (GRCm39)	F96S	possibly damaging	Het
Clk2	G	A	3: 89,074,498 (GRCm39)	V53I	probably benign	Het
Clnk	T	C	5: 38,925,484 (GRCm39)	M106V	probably benign	Het
Col6a5	T	C	9: 105,808,523 (GRCm39)	I842V	unknown	Het
Csf1r	A	T	18: 61,243,572 (GRCm39)	N196I	probably benign	Het
D5Ertd579e	A	T	5: 36,770,725 (GRCm39)	N116K		Het
Dnaja4	A	G	9: 54,616,494 (GRCm39)	I166V	probably benign	Het
Dqx1	A	G	6: 83,038,013 (GRCm39)	E467G	probably damaging	Het
Dync2h1	T	C	9: 7,129,719 (GRCm39)	T1760A	probably benign	Het
Eea1	T	C	10: 95,864,301 (GRCm39)	V940A	probably benign	Het
Egr1	T	A	18: 34,996,598 (GRCm39)	V460E	probably damaging	Het
Eral1	A	G	11: 77,965,359 (GRCm39)	I352T	possibly damaging	Het
Fam83b	A	G	9: 76,399,714 (GRCm39)	V463A	possibly damaging	Het
Fat1	T	A	8: 45,490,374 (GRCm39)	L3762H	probably damaging	Het
Fat1	T	C	8: 45,476,359 (GRCm39)	S1802P	probably damaging	Het
Fibp	A	T	19: 5,514,202 (GRCm39)	N296Y	probably benign	Het
Figla	A	G	6: 85,994,308 (GRCm39)	M28V	probably benign	Het
Foxd3	C	A	4: 99,545,362 (GRCm39)	Y167*	probably null	Het
Gm17019	T	A	5: 15,081,006 (GRCm39)	H145L	probably benign	Het
Gm48552	C	T	10: 81,226,269 (GRCm39)	P18L	probably damaging	Het
H2-Q6	A	G	17: 35,647,077 (GRCm39)	N283S	probably benign	Het
Hrh2	T	A	13: 54,368,058 (GRCm39)	C11*	probably null	Het
Hrnr	G	T	3: 93,239,506 (GRCm39)	G3248V	unknown	Het
Iapp	C	A	6: 142,249,122 (GRCm39)	N58K	possibly damaging	Het
Itga5	T	C	15: 103,258,184 (GRCm39)	N837S	probably benign	Het
Klhl35	C	A	7: 99,117,647 (GRCm39)	H64N	probably benign	Het
Lcor	T	C	19: 41,572,106 (GRCm39)	L287S	probably benign	Het
Lrba	T	A	3: 86,439,508 (GRCm39)	V2015E	probably damaging	Het
Mdn1	T	C	4: 32,734,421 (GRCm39)	I3276T	probably benign	Het
Mlh3	G	T	12: 85,315,058 (GRCm39)	T376K	possibly damaging	Het
Muc21	G	A	17: 35,932,977 (GRCm39)	T403I	unknown	Het
Nbea	A	T	3: 55,557,126 (GRCm39)	H2550Q	probably damaging	Het
Nid1	G	A	13: 13,663,630 (GRCm39)	G763D	probably damaging	Het
Ntf5	C	A	7: 45,065,243 (GRCm39)	A125E	probably damaging	Het
Obsl1	A	T	1: 75,480,167 (GRCm39)	C460S	probably benign	Het
Or1j19	A	T	2: 36,677,022 (GRCm39)	I162F	probably benign	Het
Or1s2	A	T	19: 13,758,650 (GRCm39)	R223W	probably damaging	Het
Or2g7	G	A	17: 38,378,566 (GRCm39)	C168Y	probably damaging	Het
Or2y10	T	A	11: 49,455,588 (GRCm39)	I280N	possibly damaging	Het
Or4b1b	T	A	2: 90,126,975 (GRCm39)	K77*	probably null	Het
Or6c33	A	G	10: 129,853,050 (GRCm39)		probably benign	Het
Or8d1b	G	A	9: 38,887,490 (GRCm39)	V173I	probably benign	Het
Orai3	G	A	7: 127,372,743 (GRCm39)	G130S	unknown	Het
Pcdhb12	T	G	18: 37,568,977 (GRCm39)	V41G	probably damaging	Het
Plec	A	T	15: 76,067,823 (GRCm39)	L1194Q	unknown	Het
Pml	C	A	9: 58,127,456 (GRCm39)	C763F	probably damaging	Het
Prdm15	T	A	16: 97,619,473 (GRCm39)	I318F	probably benign	Het
Rcbtb2	C	A	14: 73,415,906 (GRCm39)	T473N	probably benign	Het
Sbno1	T	A	5: 124,512,729 (GRCm39)	I1347F	probably benign	Het
Secisbp2l	C	T	2: 125,610,113 (GRCm39)	D269N	probably damaging	Het
Serpina9	A	T	12: 103,967,575 (GRCm39)	F273L	probably damaging	Het
Sgms2	T	A	3: 131,116,898 (GRCm39)	Y319F	probably benign	Het
Sgo2b	A	T	8: 64,379,531 (GRCm39)	H1100Q	probably benign	Het
Sh3bp5l	A	T	11: 58,236,754 (GRCm39)		probably null	Het
Shh	T	G	5: 28,671,664 (GRCm39)	K33T	probably benign	Het
Slc5a9	A	G	4: 111,747,371 (GRCm39)	Y339H	probably damaging	Het
Spice1	T	A	16: 44,190,864 (GRCm39)		probably null	Het
Tbx2	A	G	11: 85,726,727 (GRCm39)	E257G	probably damaging	Het
Tenm2	G	A	11: 35,914,133 (GRCm39)	T2468I	possibly damaging	Het
Tmeff2	A	T	1: 51,018,575 (GRCm39)	N186Y	probably benign	Het
Tmem132c	T	C	5: 127,631,760 (GRCm39)	V673A	possibly damaging	Het
Trappc11	G	T	8: 47,975,411 (GRCm39)	T269K	probably damaging	Het
Trpc6	T	C	9: 8,653,150 (GRCm39)	F652S	possibly damaging	Het
Trpv1	G	T	11: 73,145,048 (GRCm39)	K711N	probably benign	Het
Vcan	G	T	13: 89,841,056 (GRCm39)	P1496Q	probably damaging	Het
Vmn1r192	G	T	13: 22,371,845 (GRCm39)	A125E	probably damaging	Het
Vti1b	A	T	12: 79,211,720 (GRCm39)		probably null	Het
Vwa3b	A	C	1: 37,163,126 (GRCm39)	D583A	probably damaging	Het
Zfp638	T	C	6: 83,953,254 (GRCm39)	S1120P	probably damaging	Het
Zfyve26	A	T	12: 79,315,409 (GRCm39)	F1356I	probably benign	Het

Other mutations in F2

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL02334:F2	APN	2	91,463,439 (GRCm39)	missense	probably benign	0.16
IGL02390:F2	APN	2	91,463,332 (GRCm39)	missense	possibly damaging	0.81
IGL02859:F2	APN	2	91,456,087 (GRCm39)	missense	probably damaging	1.00
IGL02970:F2	APN	2	91,455,896 (GRCm39)	missense	possibly damaging	0.95
IGL03278:F2	APN	2	91,465,527 (GRCm39)	missense	probably benign	0.01
Sarode	UTSW	2	91,465,539 (GRCm39)	missense	probably benign	0.35
R0007:F2	UTSW	2	91,460,952 (GRCm39)	missense	probably benign	0.00
R0015:F2	UTSW	2	91,460,952 (GRCm39)	missense	probably benign	0.00
R0137:F2	UTSW	2	91,456,075 (GRCm39)	missense	probably damaging	1.00
R0211:F2	UTSW	2	91,460,503 (GRCm39)	missense	probably damaging	1.00
R0304:F2	UTSW	2	91,463,578 (GRCm39)	missense	probably damaging	0.99
R0601:F2	UTSW	2	91,463,656 (GRCm39)	splice site	probably null
R0830:F2	UTSW	2	91,460,545 (GRCm39)	missense	probably benign	0.34
R1693:F2	UTSW	2	91,459,524 (GRCm39)	missense	probably damaging	1.00
R1720:F2	UTSW	2	91,459,175 (GRCm39)	nonsense	probably null
R1763:F2	UTSW	2	91,465,251 (GRCm39)	missense	probably damaging	1.00
R1865:F2	UTSW	2	91,465,539 (GRCm39)	missense	probably benign	0.35
R1955:F2	UTSW	2	91,463,440 (GRCm39)	missense	probably benign	0.01
R2055:F2	UTSW	2	91,458,787 (GRCm39)	missense	probably benign	0.00
R2168:F2	UTSW	2	91,458,693 (GRCm39)	missense	probably damaging	0.98
R2230:F2	UTSW	2	91,456,102 (GRCm39)	missense	probably benign	0.01
R3916:F2	UTSW	2	91,455,833 (GRCm39)	missense	probably damaging	1.00
R4004:F2	UTSW	2	91,458,741 (GRCm39)	missense	possibly damaging	0.88
R4134:F2	UTSW	2	91,459,553 (GRCm39)	missense	possibly damaging	0.93
R4298:F2	UTSW	2	91,459,665 (GRCm39)	critical splice acceptor site	probably null
R4626:F2	UTSW	2	91,461,015 (GRCm39)	missense	probably benign	0.07
R4902:F2	UTSW	2	91,465,316 (GRCm39)	intron	probably benign
R5093:F2	UTSW	2	91,465,302 (GRCm39)	splice site	probably benign
R5095:F2	UTSW	2	91,465,302 (GRCm39)	splice site	probably benign
R5140:F2	UTSW	2	91,465,302 (GRCm39)	splice site	probably benign
R5229:F2	UTSW	2	91,460,586 (GRCm39)	nonsense	probably null
R5271:F2	UTSW	2	91,465,466 (GRCm39)	intron	probably benign
R5335:F2	UTSW	2	91,465,277 (GRCm39)	missense	possibly damaging	0.68
R7650:F2	UTSW	2	91,458,741 (GRCm39)	missense	possibly damaging	0.88
R8178:F2	UTSW	2	91,460,618 (GRCm39)	splice site	probably null
R8976:F2	UTSW	2	91,466,738 (GRCm39)	missense	probably benign
R9458:F2	UTSW	2	91,461,113 (GRCm39)	missense	probably benign

Predicted Primers

PCR Primer
(F):5'- CCTTTATAACCAGCCCGGAG -3'
(R):5'- AGCTGAGGATCTCATGAGTGG -3'

Sequencing Primer
(F):5'- GCCCGGAGCAAGCTTTAG -3'
(R):5'- AGGATCTCATGAGTGGTTCTTCTC -3'

Posted On

2019-11-26