Mutagenetix > Incidental Mutation

Incidental Mutation 'R1442:Vegfa'

161575

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

039497-MU

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R1442 (G1)

Quality Score

225

Status

Validated

Chromosome

Chromosomal Location

46327919-46343295 bp(-) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

G to A at 46336418 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Threonine to Isoleucine at position 56 (T56I)

Ref Sequence

ENSEMBL: ENSMUSP00000109147 (fasta)

Gene Model

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

AlphaFold

no structure available at present

Predicted Effect

probably benign
Transcript: ENSMUST00000024747
AA Change: T56I

PolyPhen 2 Score 0.058 (Sensitivity: 0.94; Specificity: 0.84)

SMART Domains

Protein: ENSMUSP00000024747
Gene: ENSMUSG00000023951
AA Change: T56I

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

Predicted Effect

possibly damaging
Transcript: ENSMUST00000071648
AA Change: T234I

PolyPhen 2 Score 0.487 (Sensitivity: 0.88; Specificity: 0.90)

SMART Domains

Protein: ENSMUSP00000071575
Gene: ENSMUSG00000023951
AA Change: T234I

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: T56I

PolyPhen 2 Score 0.845 (Sensitivity: 0.83; Specificity: 0.93)

SMART Domains

Protein: ENSMUSP00000109147
Gene: ENSMUSG00000023951
AA Change: T56I

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: T56I

PolyPhen 2 Score 0.033 (Sensitivity: 0.95; Specificity: 0.82)

SMART Domains

Protein: ENSMUSP00000109148
Gene: ENSMUSG00000023951
AA Change: T56I

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

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000133605

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000142321

Predicted Effect

possibly damaging
Transcript: ENSMUST00000142351
AA Change: T234I

PolyPhen 2 Score 0.817 (Sensitivity: 0.84; Specificity: 0.93)

SMART Domains

Protein: ENSMUSP00000115883
Gene: ENSMUSG00000023951
AA Change: T234I

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 benign
Transcript: ENSMUST00000167860
AA Change: T234I

PolyPhen 2 Score 0.447 (Sensitivity: 0.89; Specificity: 0.90)

SMART Domains

Protein: ENSMUSP00000131901
Gene: ENSMUSG00000023951
AA Change: T234I

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

noncoding transcript
Transcript: ENSMUST00000146149

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000143985

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000150327

Predicted Effect

possibly damaging
Transcript: ENSMUST00000217017
AA Change: T234I

PolyPhen 2 Score 0.781 (Sensitivity: 0.85; Specificity: 0.93)

Predicted Effect

possibly damaging
Transcript: ENSMUST00000214739
AA Change: T234I

PolyPhen 2 Score 0.601 (Sensitivity: 0.87; Specificity: 0.91)

Meta Mutation Damage Score

0.0892

Coding Region Coverage

1x: 98.9%
3x: 97.9%
10x: 95.0%
20x: 88.4%

Validation Efficiency

100% (71/71)

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: 67 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
5031439G07Rik	A	T	15: 84,839,833 (GRCm39)		probably benign	Het
Adamts7	T	A	9: 90,070,823 (GRCm39)	I648N	probably damaging	Het
Akap13	T	A	7: 75,385,526 (GRCm39)	F2252I	probably damaging	Het
Akr1c6	A	T	13: 4,507,159 (GRCm39)	H314L	probably damaging	Het
Anxa3	T	A	5: 96,976,549 (GRCm39)		probably null	Het
Apob	T	G	12: 8,036,165 (GRCm39)	F298V	probably benign	Het
Atp8a2	A	C	14: 60,097,772 (GRCm39)		probably benign	Het
Atp8b5	A	T	4: 43,334,313 (GRCm39)	T360S	probably damaging	Het
BC051665	A	T	13: 60,932,555 (GRCm39)	N43K	probably benign	Het
Bicral	T	A	17: 47,112,650 (GRCm39)	H850L	probably benign	Het
C1qtnf1	A	G	11: 118,339,011 (GRCm39)	D227G	probably damaging	Het
C8a	T	A	4: 104,685,275 (GRCm39)	T323S	possibly damaging	Het
Cep89	T	C	7: 35,117,636 (GRCm39)		probably benign	Het
Cercam	G	T	2: 29,770,652 (GRCm39)	V408L	probably benign	Het
CN725425	G	A	15: 91,123,158 (GRCm39)	V76M	possibly damaging	Het
Cops7b	T	A	1: 86,532,835 (GRCm39)	M231K	probably benign	Het
Cpa2	T	A	6: 30,544,865 (GRCm39)		probably null	Het
Dab2ip	A	T	2: 35,600,268 (GRCm39)	I287F	probably damaging	Het
Defb10	A	T	8: 22,348,944 (GRCm39)	M1L	probably benign	Het
Dscam	C	A	16: 96,409,274 (GRCm39)	R1883L	possibly damaging	Het
Dsg4	T	A	18: 20,595,717 (GRCm39)	I640N	possibly damaging	Het
Duox2	G	C	2: 122,112,232 (GRCm39)	P1318R	probably benign	Het
Dzip3	T	C	16: 48,765,985 (GRCm39)	D466G	probably benign	Het
E230025N22Rik	T	A	18: 36,824,462 (GRCm39)		probably null	Het
E2f3	A	G	13: 30,102,652 (GRCm39)	L80P	probably damaging	Het
Eif2b2	T	C	12: 85,266,360 (GRCm39)	S9P	probably benign	Het
Etaa1	A	T	11: 17,897,201 (GRCm39)	D305E	probably benign	Het
Fads6	C	A	11: 115,188,235 (GRCm39)	R23L	probably benign	Het
Flrt2	T	C	12: 95,746,979 (GRCm39)	V439A	probably damaging	Het
Galm	A	C	17: 80,452,614 (GRCm39)	Q184P	probably damaging	Het
Gtse1	C	T	15: 85,744,303 (GRCm39)		probably benign	Het
Irf7	T	C	7: 140,843,935 (GRCm39)	T246A	probably damaging	Het
Kif28	A	G	1: 179,532,697 (GRCm39)	V639A	possibly damaging	Het
Klhdc8a	G	A	1: 132,230,385 (GRCm39)	A167T	possibly damaging	Het
Lrfn3	T	C	7: 30,059,469 (GRCm39)	H252R	probably benign	Het
Lzts1	G	T	8: 69,591,638 (GRCm39)	A170E	probably damaging	Het
Mphosph9	T	A	5: 124,403,461 (GRCm39)	I856F	possibly damaging	Het
Mroh2a	C	T	1: 88,160,075 (GRCm39)		probably benign	Het
Mroh2a	C	A	1: 88,170,142 (GRCm39)	A685D	possibly damaging	Het
Myh3	A	G	11: 66,978,103 (GRCm39)	N392D	possibly damaging	Het
Naalad2	T	C	9: 18,262,328 (GRCm39)		probably benign	Het
Npc1	T	A	18: 12,328,106 (GRCm39)	M1068L	probably benign	Het
Nup58	T	A	14: 60,469,992 (GRCm39)		probably benign	Het
Or10c1	T	C	17: 37,522,595 (GRCm39)	T50A	probably benign	Het
Or4k40	A	T	2: 111,250,438 (GRCm39)	I286N	probably damaging	Het
Or8b1	A	T	9: 38,399,939 (GRCm39)	I205F	probably benign	Het
Or8s16	T	C	15: 98,211,068 (GRCm39)	Y121C	probably damaging	Het
Parp2	T	G	14: 51,056,732 (GRCm39)		probably null	Het
Ppp4r4	T	C	12: 103,564,504 (GRCm39)	V9A	probably damaging	Het
Ptprc	T	A	1: 138,000,050 (GRCm39)	D856V	probably damaging	Het
Ptpru	T	A	4: 131,535,580 (GRCm39)	T466S	probably benign	Het
Rhob	A	G	12: 8,549,325 (GRCm39)	V103A	possibly damaging	Het
Sec23ip	A	C	7: 128,378,510 (GRCm39)	S775R	probably benign	Het
Slit2	T	G	5: 48,395,725 (GRCm39)	D709E	probably damaging	Het
Smok2b	C	G	17: 13,454,390 (GRCm39)	I183M	probably damaging	Het
Smtnl1	T	A	2: 84,648,780 (GRCm39)	D158V	probably damaging	Het
Syne2	T	C	12: 75,993,489 (GRCm39)	I2087T	probably damaging	Het
Tada1	G	A	1: 166,214,319 (GRCm39)	R106H	possibly damaging	Het
Tecta	T	A	9: 42,243,778 (GRCm39)	I2025F	probably damaging	Het
Themis	T	C	10: 28,658,131 (GRCm39)	V386A	probably damaging	Het
Ubr5	G	A	15: 38,015,168 (GRCm39)		probably benign	Het
Vcl	T	A	14: 21,033,446 (GRCm39)	I134N	probably damaging	Het
Vmn2r108	T	A	17: 20,692,623 (GRCm39)	K78*	probably null	Het
Vmn2r82	A	T	10: 79,215,201 (GRCm39)	T395S	probably benign	Het
Wbp2nl	T	C	15: 82,198,407 (GRCm39)	S315P	probably benign	Het
Zfp566	T	C	7: 29,777,344 (GRCm39)	Y279C	probably damaging	Het
Zmym2	T	C	14: 57,180,784 (GRCm39)	Y899H	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
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
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'- GAGGCCCAGACAACCTTCTAATGC -3'
(R):5'- TGTACCCAGACTCAGGCTGTCATC -3'

Sequencing Primer
(F):5'- GACAACCTTCTAATGCCCCTC -3'
(R):5'- ACTCAGGCTGTCATCTGGAG -3'

Posted On

2014-03-14