Mutagenetix > Incidental Mutation

Incidental Mutation 'R4279:Vegfa'

322822

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

041079-MU

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R4279 (G1)

Quality Score

Status

Validated

Chromosome

Chromosomal Location

46327919-46343295 bp(-) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

A to G at 46342392 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Valine to Alanine at position 142 (V142A)

Ref Sequence

ENSEMBL: ENSMUSP00000151185 (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 benign
Transcript: ENSMUST00000071648
AA Change: V142A

PolyPhen 2 Score 0.000 (Sensitivity: 1.00; Specificity: 0.00)

SMART Domains

Protein: ENSMUSP00000071575
Gene: ENSMUSG00000023951
AA Change: V142A

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 benign
Transcript: ENSMUST00000142351
AA Change: V142A

PolyPhen 2 Score 0.000 (Sensitivity: 1.00; Specificity: 0.00)

SMART Domains

Protein: ENSMUSP00000115883
Gene: ENSMUSG00000023951
AA Change: V142A

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

noncoding transcript
Transcript: ENSMUST00000146149

Predicted Effect

probably benign
Transcript: ENSMUST00000167860
AA Change: V142A

PolyPhen 2 Score 0.000 (Sensitivity: 1.00; Specificity: 0.00)

SMART Domains

Protein: ENSMUSP00000131901
Gene: ENSMUSG00000023951
AA Change: V142A

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 benign
Transcript: ENSMUST00000214739
AA Change: V142A

PolyPhen 2 Score 0.000 (Sensitivity: 1.00; Specificity: 0.00)

Predicted Effect

probably benign
Transcript: ENSMUST00000217017
AA Change: V142A

PolyPhen 2 Score 0.000 (Sensitivity: 1.00; Specificity: 0.00)

Meta Mutation Damage Score

0.0898

Coding Region Coverage

1x: 99.3%
3x: 98.8%
10x: 97.6%
20x: 96.0%

Validation Efficiency

98% (40/41)

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: 37 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Arid2	T	A	15: 96,269,637 (GRCm39)	L1250Q	probably damaging	Het
Ccdc73	A	T	2: 104,815,355 (GRCm39)	N364Y	possibly damaging	Het
Ccl25	T	A	8: 4,399,829 (GRCm39)	L56Q	probably damaging	Het
Ctnnd2	C	A	15: 30,905,966 (GRCm39)	A871E	probably damaging	Het
Cyp2b23	C	T	7: 26,365,452 (GRCm39)	S461N	possibly damaging	Het
Dgat2	C	A	7: 98,813,912 (GRCm39)	G120V	probably damaging	Het
Dsp	A	T	13: 38,369,207 (GRCm39)	I768F	probably damaging	Het
Dzank1	T	C	2: 144,333,765 (GRCm39)	E356G	probably benign	Het
Fam120a	A	T	13: 49,042,734 (GRCm39)	V889D	probably benign	Het
Fxyd5	C	A	7: 30,734,811 (GRCm39)	D139Y	probably null	Het
Gcnt2	T	C	13: 41,041,666 (GRCm39)	V275A	probably benign	Het
Gimap4	A	G	6: 48,667,511 (GRCm39)	I89V	probably benign	Het
Gm6578	G	A	6: 12,100,187 (GRCm39)		noncoding transcript	Het
Jmjd8	A	G	17: 26,048,787 (GRCm39)		probably benign	Het
Jmy	G	C	13: 93,635,390 (GRCm39)	P142R	probably damaging	Het
Jmy	C	A	13: 93,635,781 (GRCm39)	D12Y	probably damaging	Het
Kif13b	G	T	14: 65,016,805 (GRCm39)	A1324S	probably damaging	Het
Klhl31	T	C	9: 77,563,121 (GRCm39)	S629P	unknown	Het
Lpar1	A	G	4: 58,487,115 (GRCm39)	V52A	possibly damaging	Het
Lrp5	A	G	19: 3,641,778 (GRCm39)	S1395P	possibly damaging	Het
Mogs	T	C	6: 83,093,048 (GRCm39)	L132P	probably damaging	Het
Ncam1	C	A	9: 49,418,259 (GRCm39)		probably benign	Het
Ndufs8	A	T	19: 3,961,014 (GRCm39)	F88I	probably damaging	Het
Nos2	T	A	11: 78,820,602 (GRCm39)	L69Q	probably benign	Het
Or51a6	T	A	7: 102,604,292 (GRCm39)	Q179L	probably benign	Het
Pls3	A	T	X: 74,846,138 (GRCm39)	I192N	probably benign	Het
Psmd6	T	C	14: 14,112,297 (GRCm38)	N388S	possibly damaging	Het
Rrbp1	T	C	2: 143,805,028 (GRCm39)	T1046A	probably benign	Het
Scn11a	T	C	9: 119,583,428 (GRCm39)	E1729G	probably benign	Het
Slc6a3	A	G	13: 73,692,953 (GRCm39)	D191G	possibly damaging	Het
Slc9a1	T	C	4: 133,139,400 (GRCm39)	F206S	probably benign	Het
Tmc5	A	G	7: 118,273,886 (GRCm39)	*968W	probably null	Het
Ttn	T	A	2: 76,585,168 (GRCm39)	I22042F	probably damaging	Het
Unc13a	T	C	8: 72,119,311 (GRCm39)	K9R	probably damaging	Het
Vmn1r119	T	A	7: 20,745,786 (GRCm39)	M199L	probably benign	Het
Vnn1	A	T	10: 23,774,410 (GRCm39)	D151V	possibly damaging	Het
Zfp365	A	T	10: 67,733,431 (GRCm39)	F254I	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
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'- CTTACCTTGGCATGGTGGAG -3'
(R):5'- GGAAACTTTTCGTCCAACTTCTGG -3'

Sequencing Primer
(F):5'- CCTTGGCATGGTGGAGGTACAG -3'
(R):5'- CTGGGAGAAGTGCTAGCTCG -3'

Posted On

2015-06-20