Mutagenetix > Incidental Mutation

Incidental Mutation 'R7863:Vegfa'

607690

Institutional Source

Beutler Lab

Gene Symbol

Vegfa

Ensembl Gene

ENSMUSG00000023951

Gene Name

vascular endothelial growth factor A

Synonyms

VEGF-A, VEGF120, VEGF188, VEGF164, VPF, Vegf

MMRRC Submission

045916-MU

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R7863 (G1)

Quality Score

225.009

Status

Not validated

Chromosome

Chromosomal Location

46327919-46343295 bp(-) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

A to G at 46336461 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Phenylalanine to Leucine at position 220 (F220L)

Ref Sequence

ENSEMBL: ENSMUSP00000115883 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000024747] [ENSMUST00000071648] [ENSMUST00000113519] [ENSMUST00000113520] [ENSMUST00000142351] [ENSMUST00000167860] [ENSMUST00000214739] [ENSMUST00000217017]

AlphaFold

no structure available at present

Predicted Effect

possibly damaging
Transcript: ENSMUST00000024747
AA Change: F42L

PolyPhen 2 Score 0.895 (Sensitivity: 0.82; Specificity: 0.94)

SMART Domains

Protein: ENSMUSP00000024747
Gene: ENSMUSG00000023951
AA Change: F42L

Domain	Start	End	E-Value	Type
PDGF	49	131	1.48e-49	SMART

Predicted Effect

probably damaging
Transcript: ENSMUST00000071648
AA Change: F220L

PolyPhen 2 Score 0.980 (Sensitivity: 0.75; Specificity: 0.96)

SMART Domains

Protein: ENSMUSP00000071575
Gene: ENSMUSG00000023951
AA Change: F220L

Domain	Start	End	E-Value	Type
low complexity region	31	51	N/A	INTRINSIC
low complexity region	60	71	N/A	INTRINSIC
low complexity region	87	105	N/A	INTRINSIC
low complexity region	121	143	N/A	INTRINSIC
low complexity region	158	176	N/A	INTRINSIC
PDGF	227	309	1.48e-49	SMART
Pfam:VEGF_C	312	368	2.3e-35	PFAM

Predicted Effect

possibly damaging
Transcript: ENSMUST00000113519
AA Change: F42L

PolyPhen 2 Score 0.904 (Sensitivity: 0.82; Specificity: 0.94)

SMART Domains

Protein: ENSMUSP00000109147
Gene: ENSMUSG00000023951
AA Change: F42L

Domain	Start	End	E-Value	Type
PDGF	49	131	1.48e-49	SMART
low complexity region	140	161	N/A	INTRINSIC

Predicted Effect

probably benign
Transcript: ENSMUST00000113520
AA Change: F42L

PolyPhen 2 Score 0.238 (Sensitivity: 0.91; Specificity: 0.88)

SMART Domains

Protein: ENSMUSP00000109148
Gene: ENSMUSG00000023951
AA Change: F42L

Domain	Start	End	E-Value	Type
PDGF	49	131	1.48e-49	SMART
Pfam:VEGF_C	154	208	9.5e-35	PFAM

Predicted Effect

probably damaging
Transcript: ENSMUST00000142351
AA Change: F220L

PolyPhen 2 Score 0.997 (Sensitivity: 0.41; Specificity: 0.98)

SMART Domains

Protein: ENSMUSP00000115883
Gene: ENSMUSG00000023951
AA Change: F220L

Domain	Start	End	E-Value	Type
low complexity region	31	51	N/A	INTRINSIC
low complexity region	60	71	N/A	INTRINSIC
low complexity region	87	105	N/A	INTRINSIC
low complexity region	121	143	N/A	INTRINSIC
low complexity region	158	176	N/A	INTRINSIC
PDGF	227	309	1.48e-49	SMART
Pfam:VEGF_C	339	392	1.9e-31	PFAM

Predicted Effect

possibly damaging
Transcript: ENSMUST00000167860
AA Change: F220L

PolyPhen 2 Score 0.895 (Sensitivity: 0.82; Specificity: 0.94)

SMART Domains

Protein: ENSMUSP00000131901
Gene: ENSMUSG00000023951
AA Change: F220L

Domain	Start	End	E-Value	Type
low complexity region	31	51	N/A	INTRINSIC
low complexity region	60	71	N/A	INTRINSIC
low complexity region	87	105	N/A	INTRINSIC
low complexity region	121	143	N/A	INTRINSIC
low complexity region	158	176	N/A	INTRINSIC
PDGF	227	309	1.48e-49	SMART

Predicted Effect

probably damaging
Transcript: ENSMUST00000214739
AA Change: F220L

PolyPhen 2 Score 0.995 (Sensitivity: 0.68; Specificity: 0.97)

Predicted Effect

probably damaging
Transcript: ENSMUST00000217017
AA Change: F220L

PolyPhen 2 Score 0.998 (Sensitivity: 0.27; Specificity: 0.99)

Coding Region Coverage

1x: 100.0%
3x: 99.9%
10x: 99.6%
20x: 98.7%

Validation Efficiency

MGI Phenotype

FUNCTION: This gene is a member of the PDGF/VEGF growth factor family. It encodes a heparin-binding protein, which exists as a disulfide-linked homodimer. This growth factor induces proliferation and migration of vascular endothelial cells, and is essential for both physiological and pathological angiogenesis. Disruption of this gene in mice resulted in abnormal embryonic blood vessel formation. This gene is upregulated in many known tumors and its expression is correlated with tumor stage and progression. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. There is also evidence for alternative translation initiation from upstream non-AUG (CUG) codons resulting in additional isoforms. A recent study showed that a C-terminally extended isoform is produced by use of an alternative in-frame translation termination codon via a stop codon readthrough mechanism, and that this isoform is antiangiogenic. Expression of some isoforms derived from the AUG start codon is regulated by a small upstream open reading frame, which is located within an internal ribosome entry site.[provided by RefSeq, Nov 2015]
PHENOTYPE: Hetero- or homozygous null mutants show embryonic lethality with impaired angiogenesis and blood-island formation. Mutants selectively expressing isoform 120 or 188 exhibit vascular outgrowth/patterning defects or impaired arterial development, respectively. [provided by MGI curators]

Allele List at MGI

Other mutations in this stock

Total: 81 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
9930111J21Rik1	A	G	11: 48,838,101 (GRCm39)	S829P	probably benign	Het
Abca1	A	T	4: 53,107,179 (GRCm39)	F183I	probably benign	Het
Abca12	A	T	1: 71,332,656 (GRCm39)	M1235K	probably damaging	Het
Abca7	A	G	10: 79,844,655 (GRCm39)	D1488G	probably damaging	Het
Adgrl3	A	G	5: 81,660,596 (GRCm39)	Y387C	probably damaging	Het
Adnp	T	C	2: 168,031,270 (GRCm39)	K14E	possibly damaging	Het
Ago3	T	C	4: 126,243,990 (GRCm39)	R721G	possibly damaging	Het
Aldh3b3	T	A	19: 4,015,322 (GRCm39)	Y196*	probably null	Het
Alox12b	T	C	11: 69,057,753 (GRCm39)	W506R	probably damaging	Het
Arid4b	A	G	13: 14,338,734 (GRCm39)	I402V	probably benign	Het
Cep55	C	T	19: 38,046,247 (GRCm39)		probably benign	Het
Chl1	A	G	6: 103,683,475 (GRCm39)	N767S	possibly damaging	Het
Cldn6	A	G	17: 23,900,096 (GRCm39)	N20S	probably benign	Het
Col23a1	A	T	11: 51,463,597 (GRCm39)	I420F	probably damaging	Het
Cxcr6	G	A	9: 123,639,914 (GRCm39)	R312Q	probably damaging	Het
Cyp4a10	T	C	4: 115,375,622 (GRCm39)	V35A	probably benign	Het
Def6	A	G	17: 28,446,841 (GRCm39)	N548D	possibly damaging	Het
Dock6	A	G	9: 21,757,954 (GRCm39)	V50A	possibly damaging	Het
Epha8	T	A	4: 136,660,966 (GRCm39)	I639F	probably damaging	Het
Ephx2	T	A	14: 66,344,692 (GRCm39)	R211*	probably null	Het
Espn	C	T	4: 152,236,616 (GRCm39)	V17M	probably damaging	Het
Ezr	A	G	17: 7,008,863 (GRCm39)	L403P	probably damaging	Het
Fan1	T	A	7: 64,022,234 (GRCm39)	N340Y	probably damaging	Het
Golm1	T	C	13: 59,797,383 (GRCm39)	Y154C	probably damaging	Het
Gpam	A	G	19: 55,059,388 (GRCm39)	Y820H	probably damaging	Het
Gpr12	T	C	5: 146,520,370 (GRCm39)	D184G	possibly damaging	Het
Gpr87	C	T	3: 59,087,317 (GRCm39)	A63T	probably damaging	Het
Hmx2	G	T	7: 131,156,082 (GRCm39)	G16V	probably benign	Het
Hspg2	T	C	4: 137,292,135 (GRCm39)	V4009A	probably benign	Het
Iglc3	T	C	16: 18,884,248 (GRCm39)	D61G	not run	Het
Ikzf2	G	T	1: 69,609,796 (GRCm39)	Q144K	possibly damaging	Het
Il1rap	C	T	16: 26,495,461 (GRCm39)	R23C	probably damaging	Het
Kctd9	T	A	14: 67,967,166 (GRCm39)	D161E	possibly damaging	Het
Klhl8	T	C	5: 104,019,968 (GRCm39)	N351S	probably benign	Het
Krt28	G	A	11: 99,255,999 (GRCm39)	T420I	possibly damaging	Het
Marchf7	T	A	2: 60,071,366 (GRCm39)	H623Q	probably benign	Het
Max	A	G	12: 76,986,848 (GRCm39)	I63T	probably damaging	Het
Mrpl28	T	A	17: 26,343,615 (GRCm39)	V125E	possibly damaging	Het
Mtmr10	T	A	7: 63,969,205 (GRCm39)	D322E	probably benign	Het
Mtrex	T	C	13: 113,045,435 (GRCm39)	T366A	probably benign	Het
Nlrp4f	A	T	13: 65,342,059 (GRCm39)	Y529N	possibly damaging	Het
Nlrx1	A	G	9: 44,176,509 (GRCm39)	I31T	probably benign	Het
Oaz2	G	A	9: 65,596,449 (GRCm39)	R171Q	possibly damaging	Het
Or4c121	T	G	2: 89,024,295 (GRCm39)	I28L	probably benign	Het
Or5a1	T	G	19: 12,097,974 (GRCm39)	D34A	possibly damaging	Het
Or5t16	T	G	2: 86,819,424 (GRCm39)	Y32S	probably damaging	Het
Pcdhgc4	T	A	18: 37,951,027 (GRCm39)	Y814*	probably null	Het
Pcm1	T	A	8: 41,714,163 (GRCm39)	I243K	probably damaging	Het
Pdcd11	A	T	19: 47,085,403 (GRCm39)	N171I	probably damaging	Het
Phf20l1	T	A	15: 66,487,084 (GRCm39)	V400E	possibly damaging	Het
Pira13	C	T	7: 3,827,801 (GRCm39)		probably null	Het
Psg28	T	A	7: 18,162,042 (GRCm39)	T154S	possibly damaging	Het
Ptgs2	T	A	1: 149,977,090 (GRCm39)	M99K	probably damaging	Het
Ptprh	T	A	7: 4,606,097 (GRCm39)	M1L	probably benign	Het
Rbp4	T	C	19: 38,112,546 (GRCm39)	T140A	possibly damaging	Het
Rhbdd3	G	A	11: 5,053,236 (GRCm39)	R12Q	probably benign	Het
Saal1	T	C	7: 46,342,327 (GRCm39)	N372S	probably benign	Het
Satb1	T	C	17: 52,112,350 (GRCm39)	E88G	possibly damaging	Het
Shfl	G	A	9: 20,782,672 (GRCm39)	A79T	possibly damaging	Het
Slc49a3	A	T	5: 108,593,400 (GRCm39)	L146Q	probably damaging	Het
Slc6a9	G	T	4: 117,721,207 (GRCm39)	C319F	probably damaging	Het
Smc6	T	G	12: 11,339,130 (GRCm39)	V322G	probably benign	Het
Snrnp200	T	A	2: 127,073,609 (GRCm39)	F1336I	probably damaging	Het
Spg7	T	A	8: 123,815,788 (GRCm39)		probably null	Het
Stab2	G	A	10: 86,808,745 (GRCm39)	T188I	probably benign	Het
Tbata	A	G	10: 61,011,521 (GRCm39)	E19G	probably benign	Het
Tcof1	G	C	18: 60,962,123 (GRCm39)	A702G	possibly damaging	Het
Ticrr	T	C	7: 79,331,760 (GRCm39)	V757A	possibly damaging	Het
Tle1	T	C	4: 72,059,529 (GRCm39)	S261G	probably null	Het
Tlr3	T	A	8: 45,850,774 (GRCm39)	I708L	probably benign	Het
Tph2	A	C	10: 114,915,906 (GRCm39)	S422R	probably damaging	Het
Trim26	A	G	17: 37,161,664 (GRCm39)	T28A	probably damaging	Het
Trmt10c	A	G	16: 55,855,554 (GRCm39)	L27S	probably benign	Het
Tubb6	T	C	18: 67,534,790 (GRCm39)	S230P	probably damaging	Het
Usf1	C	T	1: 171,245,385 (GRCm39)	Q266*	probably null	Het
Vmn2r105	C	T	17: 20,428,937 (GRCm39)	C713Y	probably benign	Het
Vmn2r17	T	A	5: 109,568,035 (GRCm39)	S53T	probably benign	Het
Xirp2	A	T	2: 67,343,074 (GRCm39)	T1772S	probably benign	Het
Zfp462	T	C	4: 55,007,747 (GRCm39)	I62T	probably benign	Het
Zfp516	T	A	18: 83,019,453 (GRCm39)	I1157N	probably benign	Het
Zfp819	C	A	7: 43,267,316 (GRCm39)	Q600K	probably benign	Het

Other mutations in Vegfa

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL01355:Vegfa	APN	17	46,336,347 (GRCm39)	missense	possibly damaging	0.88
IGL02859:Vegfa	APN	17	46,335,421 (GRCm39)	missense	probably benign	0.43
R1442:Vegfa	UTSW	17	46,336,418 (GRCm39)	missense	possibly damaging	0.85
R1760:Vegfa	UTSW	17	46,336,395 (GRCm39)	missense	probably damaging	1.00
R1982:Vegfa	UTSW	17	46,329,786 (GRCm39)	makesense	probably null
R2012:Vegfa	UTSW	17	46,336,284 (GRCm39)	missense	probably benign	0.21
R3729:Vegfa	UTSW	17	46,335,446 (GRCm39)	missense	possibly damaging	0.80
R4276:Vegfa	UTSW	17	46,342,392 (GRCm39)	missense	probably benign
R4277:Vegfa	UTSW	17	46,342,392 (GRCm39)	missense	probably benign
R4279:Vegfa	UTSW	17	46,342,392 (GRCm39)	missense	probably benign
R4654:Vegfa	UTSW	17	46,336,176 (GRCm39)	intron	probably benign
R4696:Vegfa	UTSW	17	46,339,272 (GRCm39)	splice site	probably null
R7798:Vegfa	UTSW	17	46,342,761 (GRCm39)	missense	probably damaging	1.00
R7946:Vegfa	UTSW	17	46,336,377 (GRCm39)	missense	probably damaging	0.96
R8235:Vegfa	UTSW	17	46,342,236 (GRCm39)	missense	possibly damaging	0.91
R8683:Vegfa	UTSW	17	46,342,396 (GRCm39)	missense	probably benign	0.35
R8756:Vegfa	UTSW	17	46,342,465 (GRCm39)	missense	probably damaging	1.00
R9700:Vegfa	UTSW	17	46,342,713 (GRCm39)	missense	probably damaging	1.00
R9701:Vegfa	UTSW	17	46,342,713 (GRCm39)	missense	probably damaging	1.00
R9733:Vegfa	UTSW	17	46,335,401 (GRCm39)	missense	probably damaging	1.00
X0026:Vegfa	UTSW	17	46,336,452 (GRCm39)	missense	probably damaging	1.00

Predicted Primers

PCR Primer
(F):5'- CCTGCATGGTGATGTTGCTC -3'
(R):5'- GCCATAGTTGGTAGGAACTTGC -3'

Sequencing Primer
(F):5'- TTGCTCTCTGACGTGGGCAC -3'
(R):5'- CTTGCTGTGACAATGAGGAATG -3'

Posted On

2019-12-20