Mutagenetix > Incidental Mutation

Incidental Mutation 'R9701:Vegfa'

729598

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

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R9701 (G1)

Quality Score

225.009

Status

Not validated

Chromosome

Chromosomal Location

46327919-46343295 bp(-) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

G to A at 46342713 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Proline to Leucine at position 35 (P35L)

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

probably benign
Transcript: ENSMUST00000024747

SMART Domains

Protein: ENSMUSP00000024747
Gene: ENSMUSG00000023951

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

Predicted Effect

probably damaging
Transcript: ENSMUST00000071648
AA Change: P35L

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)

SMART Domains

Protein: ENSMUSP00000071575
Gene: ENSMUSG00000023951
AA Change: P35L

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

probably benign
Transcript: ENSMUST00000113519

SMART Domains

Protein: ENSMUSP00000109147
Gene: ENSMUSG00000023951

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

SMART Domains

Protein: ENSMUSP00000109148
Gene: ENSMUSG00000023951

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: P35L

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)

SMART Domains

Protein: ENSMUSP00000115883
Gene: ENSMUSG00000023951
AA Change: P35L

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

probably damaging
Transcript: ENSMUST00000167860
AA Change: P35L

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)

SMART Domains

Protein: ENSMUSP00000131901
Gene: ENSMUSG00000023951
AA Change: P35L

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: P35L

PolyPhen 2 Score 0.958 (Sensitivity: 0.78; Specificity: 0.95)

Predicted Effect

probably damaging
Transcript: ENSMUST00000217017
AA Change: P35L

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)

Coding Region Coverage

1x: 100.0%
3x: 99.9%
10x: 99.7%
20x: 98.9%

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: 62 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Abcc8	T	C	7: 45,786,054 (GRCm39)	D673G	probably benign	Het
Alg8	T	A	7: 97,027,486 (GRCm39)	V118E	possibly damaging	Het
Ap4e1	T	C	2: 126,875,563 (GRCm39)	V218A	probably benign	Het
Armc12	A	T	17: 28,751,375 (GRCm39)	D123V	probably damaging	Het
Bltp3b	G	A	10: 89,615,755 (GRCm39)	V133I	probably benign	Het
Bms1	T	A	6: 118,368,147 (GRCm39)	K1039I	probably damaging	Het
Col4a2	A	G	8: 11,493,104 (GRCm39)	N1299S	probably benign	Het
Cux1	T	C	5: 136,343,169 (GRCm39)	D405G	probably damaging	Het
Cwf19l2	A	T	9: 3,430,454 (GRCm39)	Q262L	probably damaging	Het
Dclk3	A	G	9: 111,298,244 (GRCm39)	D596G	probably damaging	Het
Dnah7a	A	T	1: 53,561,388 (GRCm39)	C2090S	probably benign	Het
Dock7	T	C	4: 98,846,384 (GRCm39)	D1749G	unknown	Het
Dock9	A	T	14: 121,876,983 (GRCm39)	C463S	probably benign	Het
Dyrk1b	G	A	7: 27,885,838 (GRCm39)	R548Q	probably damaging	Het
Egr1	T	C	18: 34,995,674 (GRCm39)	F152S	probably damaging	Het
Eln	C	A	5: 134,744,559 (GRCm39)	A479S	unknown	Het
Gm973	T	A	1: 59,566,032 (GRCm39)	W84R	possibly damaging	Het
Gnpat	A	G	8: 125,613,678 (GRCm39)	K642E	probably benign	Het
Gpr180	G	A	14: 118,391,302 (GRCm39)	G235R	probably damaging	Het
Gpx6	A	T	13: 21,501,777 (GRCm39)	Q133L	probably benign	Het
Gzmn	T	C	14: 56,405,310 (GRCm39)	Y58C	probably benign	Het
Hcfc2	G	T	10: 82,574,269 (GRCm39)	G148*	probably null	Het
Hspa5	C	T	2: 34,664,649 (GRCm39)	R368*	probably null	Het
Igkv3-10	T	C	6: 70,550,001 (GRCm39)	V49A	probably damaging	Het
Inpp5f	A	C	7: 128,278,515 (GRCm39)	D435A	possibly damaging	Het
Jmjd1c	A	T	10: 67,060,745 (GRCm39)	I852F	possibly damaging	Het
Lhx5	T	A	5: 120,572,663 (GRCm39)	V94E	possibly damaging	Het
Map1s	C	T	8: 71,369,712 (GRCm39)	T928I	possibly damaging	Het
Mib1	T	A	18: 10,798,494 (GRCm39)	L785H	probably damaging	Het
Mrgpra6	C	T	7: 46,835,533 (GRCm39)	R296K	probably benign	Het
Mrpl9	A	G	3: 94,351,892 (GRCm39)		probably null	Het
Mutyh	A	G	4: 116,676,485 (GRCm39)	S486G	probably benign	Het
Naa15	T	A	3: 51,349,370 (GRCm39)	Y96*	probably null	Het
Nlrp1a	T	C	11: 70,987,946 (GRCm39)	S1175G	probably benign	Het
Nup153	A	T	13: 46,840,211 (GRCm39)	D1132E	probably benign	Het
Nxf1	G	A	19: 8,739,772 (GRCm39)	G42D	probably damaging	Het
Or13j1	C	A	4: 43,705,793 (GRCm39)	M258I	probably benign	Het
Plekhg6	C	T	6: 125,347,602 (GRCm39)	V451I	probably benign	Het
Prkab1	T	C	5: 116,162,274 (GRCm39)	E12G	probably benign	Het
Ptprd	A	G	4: 75,916,896 (GRCm39)	Y752H	probably damaging	Het
Rbm12	A	G	2: 155,938,166 (GRCm39)	I702T	probably benign	Het
Rnf212	A	G	5: 108,922,738 (GRCm39)		probably null	Het
Sall3	C	A	18: 81,017,443 (GRCm39)	A162S	probably benign	Het
Sec24d	T	C	3: 123,063,321 (GRCm39)	S13P	probably damaging	Het
Serpina16	T	C	12: 103,638,873 (GRCm39)	Q238R	probably benign	Het
Shank1	G	A	7: 43,962,342 (GRCm39)	S71N	unknown	Het
Skint3	T	A	4: 112,111,094 (GRCm39)	V73E	probably damaging	Het
Slc6a20a	T	A	9: 123,489,585 (GRCm39)	T153S	probably damaging	Het
Slc6a6	T	C	6: 91,700,478 (GRCm39)	Y69H	probably damaging	Het
Sorl1	A	G	9: 42,003,766 (GRCm39)	Y177H	probably damaging	Het
Srbd1	T	C	17: 86,433,559 (GRCm39)	Y346C	probably damaging	Het
Syne2	A	G	12: 76,037,197 (GRCm39)	E3792G	probably damaging	Het
Tg	C	G	15: 66,637,991 (GRCm39)	T2268S	probably benign	Het
Thbs1	A	G	2: 117,950,716 (GRCm39)	N721S	probably benign	Het
Treh	A	G	9: 44,594,648 (GRCm39)	Y275C	probably damaging	Het
Trpv5	G	T	6: 41,651,594 (GRCm39)	H195N	possibly damaging	Het
Tshz1	A	G	18: 84,032,579 (GRCm39)	S610P	possibly damaging	Het
Ttll4	A	G	1: 74,720,482 (GRCm39)	N499S	probably benign	Het
Ttn	G	T	2: 76,748,927 (GRCm39)	H4041N	probably benign	Het
Ubtf	A	G	11: 102,199,718 (GRCm39)		probably null	Het
Urod	C	T	4: 116,849,778 (GRCm39)	V207M	probably damaging	Het
Zc3h7b	C	T	15: 81,676,505 (GRCm39)	P749L	probably damaging	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
R7863:Vegfa	UTSW	17	46,336,461 (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
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'- AAAGTTCATGGTTTCGGAGGCC -3'
(R):5'- AAGTGACTGACCTGCTTTTGGG -3'

Sequencing Primer
(F):5'- TCTCCCTTCTGGAACCGAGG -3'
(R):5'- ACCTGCTTTTGGGGGTGAC -3'

Posted On

2022-10-06