Incidental Mutation 'R8235:Vegfa'
| ID |
637331 |
| 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 |
067667-MU
|
| Accession Numbers |
|
| Essential gene? |
Essential
(E-score: 1.000)
|
| Stock # |
R8235 (G1)
|
| Quality Score |
225.009 |
|
Status
|
Validated
|
| Chromosome |
17 |
| Chromosomal Location |
46327919-46343295 bp(-) (GRCm39) |
| Type of Mutation |
missense |
| DNA Base Change (assembly) |
A to T
at 46342236 bp (GRCm39)
|
| Zygosity |
Heterozygous |
| Amino Acid Change |
Leucine to Glutamine
at position 194
(L194Q)
|
| Ref Sequence |
ENSEMBL: ENSMUSP00000115883
(fasta)
|
| Gene Model |
predicted gene model for transcript(s):
[ENSMUST00000024747]
[ENSMUST00000071648]
[ENSMUST00000113519]
[ENSMUST00000113520]
[ENSMUST00000142351]
[ENSMUST00000167860]
|
| AlphaFold |
no structure available at present |
| Predicted Effect |
probably damaging
Transcript: ENSMUST00000024747
AA Change: L16Q
PolyPhen 2
Score 0.994 (Sensitivity: 0.69; Specificity: 0.97)
|
| SMART Domains |
Protein: ENSMUSP00000024747
Gene: ENSMUSG00000023951
AA Change: L16Q
| Domain | Start | End | E-Value | Type |
|---|
|
PDGF
|
49 |
131 |
1.48e-49 |
SMART |
|
| Predicted Effect |
probably damaging
Transcript: ENSMUST00000071648
AA Change: L194Q
PolyPhen 2
Score 0.993 (Sensitivity: 0.70; Specificity: 0.97)
|
| SMART Domains |
Protein: ENSMUSP00000071575
Gene: ENSMUSG00000023951
AA Change: L194Q
| 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 damaging
Transcript: ENSMUST00000113519
AA Change: L16Q
PolyPhen 2
Score 0.999 (Sensitivity: 0.14; Specificity: 0.99)
|
| SMART Domains |
Protein: ENSMUSP00000109147
Gene: ENSMUSG00000023951
AA Change: L16Q
| 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: L16Q
PolyPhen 2
Score 0.244 (Sensitivity: 0.91; Specificity: 0.88)
|
| SMART Domains |
Protein: ENSMUSP00000109148
Gene: ENSMUSG00000023951
AA Change: L16Q
| Domain | Start | End | E-Value | Type |
|---|
|
PDGF
|
49 |
131 |
1.48e-49 |
SMART |
|
Pfam:VEGF_C
|
154 |
208 |
9.5e-35 |
PFAM |
|
| Predicted Effect |
possibly damaging
Transcript: ENSMUST00000142351
AA Change: L194Q
PolyPhen 2
Score 0.910 (Sensitivity: 0.81; Specificity: 0.94)
|
| SMART Domains |
Protein: ENSMUSP00000115883
Gene: ENSMUSG00000023951
AA Change: L194Q
| 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: L194Q
PolyPhen 2
Score 0.994 (Sensitivity: 0.69; Specificity: 0.97)
|
| SMART Domains |
Protein: ENSMUSP00000131901
Gene: ENSMUSG00000023951
AA Change: L194Q
| 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 |
|
| Coding Region Coverage |
- 1x: 99.9%
- 3x: 99.8%
- 10x: 99.5%
- 20x: 98.8%
|
| Validation Efficiency |
98% (44/45) |
| 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: 43 list
| Gene | Ref | Var | Chr/Loc | Mutation | Predicted Effect | Zygosity |
|---|
| Abca13 |
A |
C |
11: 9,212,077 (GRCm39) |
Q279H |
probably damaging |
Het |
| Abhd13 |
G |
A |
8: 10,037,394 (GRCm39) |
|
probably benign |
Het |
| Atp8b3 |
T |
C |
10: 80,365,650 (GRCm39) |
N368S |
probably damaging |
Het |
| Bptf |
A |
G |
11: 106,967,458 (GRCm39) |
M1089T |
probably benign |
Het |
| Cbll1 |
C |
T |
12: 31,541,570 (GRCm39) |
D103N |
probably benign |
Het |
| Ccnd2 |
T |
C |
6: 127,107,305 (GRCm39) |
D288G |
probably benign |
Het |
| Chek1 |
T |
A |
9: 36,630,870 (GRCm39) |
R181S |
probably benign |
Het |
| Chrna7 |
T |
C |
7: 62,861,972 (GRCm39) |
R27G |
probably damaging |
Het |
| Crybb1 |
A |
G |
5: 112,405,266 (GRCm39) |
K6R |
probably damaging |
Het |
| Ehbp1 |
G |
A |
11: 22,189,153 (GRCm39) |
T83M |
probably damaging |
Het |
| Entpd7 |
G |
A |
19: 43,705,984 (GRCm39) |
E269K |
probably damaging |
Het |
| Eps8 |
A |
G |
6: 137,460,576 (GRCm39) |
V729A |
possibly damaging |
Het |
| Farsa |
A |
G |
8: 85,595,545 (GRCm39) |
H480R |
probably damaging |
Het |
| Gm10110 |
C |
T |
14: 90,135,677 (GRCm39) |
V76M |
noncoding transcript |
Het |
| Hpn |
T |
C |
7: 30,802,208 (GRCm39) |
T228A |
possibly damaging |
Het |
| Lyst |
T |
A |
13: 13,935,323 (GRCm39) |
H3597Q |
possibly damaging |
Het |
| Map3k4 |
A |
T |
17: 12,458,968 (GRCm39) |
|
probably null |
Het |
| Msto1 |
A |
T |
3: 88,820,228 (GRCm39) |
L89Q |
probably damaging |
Het |
| Mycbp2 |
T |
C |
14: 103,436,110 (GRCm39) |
E2185G |
probably damaging |
Het |
| Myh2 |
A |
G |
11: 67,083,824 (GRCm39) |
E1534G |
probably damaging |
Het |
| Nfkbia |
T |
C |
12: 55,537,608 (GRCm39) |
Y195C |
probably damaging |
Het |
| Npr2 |
T |
A |
4: 43,641,603 (GRCm39) |
M469K |
probably benign |
Het |
| Nwd1 |
TCATCC |
TCATCCATCC |
8: 73,438,314 (GRCm39) |
|
probably null |
Het |
| Or8i2 |
T |
C |
2: 86,852,226 (GRCm39) |
I221V |
probably benign |
Het |
| Potefam3e |
C |
A |
8: 19,799,476 (GRCm39) |
T308N |
probably benign |
Het |
| Prdm2 |
G |
A |
4: 142,859,037 (GRCm39) |
Q1418* |
probably null |
Het |
| Ptk2 |
T |
C |
15: 73,215,140 (GRCm39) |
T13A |
probably benign |
Het |
| Ptprk |
T |
A |
10: 28,465,037 (GRCm39) |
N1292K |
possibly damaging |
Het |
| Ptprq |
A |
C |
10: 107,418,402 (GRCm39) |
V1658G |
probably damaging |
Het |
| Ptprq |
A |
T |
10: 107,541,351 (GRCm39) |
F392I |
probably benign |
Het |
| Rbm46 |
C |
T |
3: 82,772,775 (GRCm39) |
R119Q |
probably benign |
Het |
| Rsf1 |
T |
C |
7: 97,325,461 (GRCm39) |
|
probably benign |
Het |
| Samd4b |
C |
T |
7: 28,106,031 (GRCm39) |
V396I |
probably benign |
Het |
| Spta1 |
T |
A |
1: 174,029,952 (GRCm39) |
L906Q |
probably damaging |
Het |
| Sytl1 |
T |
C |
4: 132,988,257 (GRCm39) |
D33G |
probably damaging |
Het |
| Trmt10c |
T |
C |
16: 55,854,939 (GRCm39) |
N232S |
probably benign |
Het |
| Trpc4 |
G |
A |
3: 54,209,669 (GRCm39) |
C678Y |
probably benign |
Het |
| Tulp3 |
T |
C |
6: 128,304,640 (GRCm39) |
N205D |
probably benign |
Het |
| Ufl1 |
T |
C |
4: 25,278,656 (GRCm39) |
I100V |
probably benign |
Het |
| Unc45b |
A |
G |
11: 82,810,681 (GRCm39) |
I314V |
probably benign |
Het |
| Vps13c |
T |
C |
9: 67,834,678 (GRCm39) |
F1669S |
probably damaging |
Het |
| Vps13c |
T |
A |
9: 67,863,063 (GRCm39) |
H3026Q |
probably benign |
Het |
| Zfp184 |
T |
G |
13: 22,144,053 (GRCm39) |
I586M |
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 |
|
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'- CTCCACGTACGACGACAGAG -3'
(R):5'- TGGGAGAAGTGCTAGCTCGG -3'
Sequencing Primer
(F):5'- ACAGAGGGGGACGCCTC -3'
(R):5'- TAGCTCGGGCCTGGAGAAG -3'
|
| Posted On |
2020-07-13 |
Incidental Mutation