Incidental Mutation 'D3080:Gab1'
ID |
126 |
Institutional Source |
Beutler Lab
|
Gene Symbol |
Gab1
|
Ensembl Gene |
ENSMUSG00000031714 |
Gene Name |
growth factor receptor bound protein 2-associated protein 1 |
Synonyms |
|
Accession Numbers |
|
Essential gene? |
Essential
(E-score: 1.000)
|
Stock # |
D3080
of strain
grasshopper
|
Quality Score |
|
Status
|
Validated
|
Chromosome |
8 |
Chromosomal Location |
81491067-81607148 bp(-) (GRCm39) |
Type of Mutation |
missense |
DNA Base Change (assembly) |
T to A
at 81493007 bp (GRCm39)
|
Zygosity |
Homozygous |
Amino Acid Change |
Aspartic acid to Valine
at position 710
(D710V)
|
Ref Sequence |
ENSEMBL: ENSMUSP00000147784
(fasta)
|
Gene Model |
predicted gene model for transcript(s):
[ENSMUST00000034150]
[ENSMUST00000210676]
|
AlphaFold |
Q9QYY0 |
Predicted Effect |
probably damaging
Transcript: ENSMUST00000034150
AA Change: D680V
PolyPhen 2
Score 0.999 (Sensitivity: 0.14; Specificity: 0.99)
|
SMART Domains |
Protein: ENSMUSP00000034150 Gene: ENSMUSG00000031714 AA Change: D680V
Domain | Start | End | E-Value | Type |
PH
|
6 |
118 |
1.16e-23 |
SMART |
low complexity region
|
336 |
354 |
N/A |
INTRINSIC |
low complexity region
|
572 |
586 |
N/A |
INTRINSIC |
|
Predicted Effect |
noncoding transcript
Transcript: ENSMUST00000210546
|
Predicted Effect |
probably damaging
Transcript: ENSMUST00000210676
AA Change: D710V
PolyPhen 2
Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)
|
Meta Mutation Damage Score |
0.4035 |
Coding Region Coverage |
|
Validation Efficiency |
82% (141/173) |
MGI Phenotype |
FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] The protein encoded by this gene is a member of the IRS1-like multisubstrate docking protein family. It is an important mediator of branching tubulogenesis and plays a central role in cellular growth response, transformation and apoptosis. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2008] PHENOTYPE: Homozygotes for targeted null mutations exhibit developmental defects in the placenta, heart, eye, muscle, and skin, and die between embryonic day 13.5 and 18.5. [provided by MGI curators]
|
Allele List at MGI |
All alleles(43) : Targeted, knock-out(1) Targeted, other(8) Gene trapped(34) |
Other mutations in this stock |
Total: 20 list
Gene | Ref | Var | Chr/Loc | Mutation | Predicted Effect | Zygosity |
2310003L06Rik |
C |
A |
5: 88,119,846 (GRCm39) |
P201Q |
possibly damaging |
Het |
Bdp1 |
A |
T |
13: 100,160,129 (GRCm39) |
S2417R |
probably benign |
Het |
Ccdc168 |
C |
A |
1: 44,106,495 (GRCm39) |
|
|
Het |
Dscaml1 |
A |
T |
9: 45,595,623 (GRCm39) |
H783L |
probably benign |
Het |
Fbxl5 |
A |
T |
5: 43,915,708 (GRCm39) |
M568K |
probably benign |
Het |
Gabrr2 |
T |
C |
4: 33,084,466 (GRCm39) |
F128S |
probably damaging |
Het |
Hyou1 |
T |
A |
9: 44,295,774 (GRCm39) |
V343E |
probably damaging |
Het |
Nlrp4a |
A |
G |
7: 26,143,766 (GRCm39) |
T44A |
probably benign |
Het |
Nsd3 |
C |
A |
8: 26,203,572 (GRCm39) |
T1362N |
possibly damaging |
Homo |
Or6f2 |
G |
A |
7: 139,756,275 (GRCm39) |
V81M |
possibly damaging |
Het |
Pcm1 |
T |
A |
8: 41,728,976 (GRCm39) |
N649K |
probably damaging |
Homo |
Pde4dip |
T |
C |
3: 97,674,146 (GRCm39) |
K257E |
probably damaging |
Het |
Pfpl |
G |
A |
19: 12,406,196 (GRCm39) |
R149Q |
probably damaging |
Homo |
Pou2f2 |
G |
T |
7: 24,796,558 (GRCm39) |
|
probably benign |
Het |
Rptn |
A |
G |
3: 93,303,135 (GRCm39) |
D156G |
possibly damaging |
Het |
Sec31a |
T |
C |
5: 100,511,691 (GRCm39) |
D1107G |
probably damaging |
Het |
Smyd3 |
A |
G |
1: 178,913,987 (GRCm39) |
Y239H |
probably damaging |
Het |
Stoml3 |
T |
C |
3: 53,405,415 (GRCm39) |
F32S |
probably benign |
Het |
Tnnc1 |
C |
A |
14: 30,932,147 (GRCm39) |
D62E |
probably damaging |
Homo |
Vsig10 |
C |
T |
5: 117,481,884 (GRCm39) |
A358V |
probably damaging |
Het |
|
Other mutations in Gab1 |
Allele | Source | Chr | Coord | Type | Predicted Effect | PPH Score |
IGL01679:Gab1
|
APN |
8 |
81,518,178 (GRCm39) |
missense |
probably benign |
0.00 |
IGL02610:Gab1
|
APN |
8 |
81,526,728 (GRCm39) |
critical splice donor site |
probably null |
|
IGL02661:Gab1
|
APN |
8 |
81,515,566 (GRCm39) |
missense |
probably damaging |
1.00 |
IGL02716:Gab1
|
APN |
8 |
81,496,323 (GRCm39) |
missense |
probably damaging |
1.00 |
fallen_angel
|
UTSW |
8 |
81,606,161 (GRCm39) |
nonsense |
probably null |
|
fleabite
|
UTSW |
8 |
81,526,745 (GRCm39) |
missense |
probably damaging |
1.00 |
Welterweight
|
UTSW |
8 |
81,501,594 (GRCm39) |
nonsense |
probably null |
|
R0006:Gab1
|
UTSW |
8 |
81,496,359 (GRCm39) |
missense |
possibly damaging |
0.56 |
R0144:Gab1
|
UTSW |
8 |
81,511,830 (GRCm39) |
splice site |
probably benign |
|
R0173:Gab1
|
UTSW |
8 |
81,526,789 (GRCm39) |
missense |
possibly damaging |
0.68 |
R0414:Gab1
|
UTSW |
8 |
81,526,918 (GRCm39) |
missense |
probably damaging |
1.00 |
R0503:Gab1
|
UTSW |
8 |
81,526,771 (GRCm39) |
missense |
probably damaging |
1.00 |
R0675:Gab1
|
UTSW |
8 |
81,496,297 (GRCm39) |
missense |
probably damaging |
1.00 |
R0690:Gab1
|
UTSW |
8 |
81,526,745 (GRCm39) |
missense |
probably damaging |
1.00 |
R1068:Gab1
|
UTSW |
8 |
81,526,801 (GRCm39) |
missense |
possibly damaging |
0.95 |
R1175:Gab1
|
UTSW |
8 |
81,511,471 (GRCm39) |
missense |
probably damaging |
0.99 |
R1240:Gab1
|
UTSW |
8 |
81,515,159 (GRCm39) |
missense |
probably damaging |
1.00 |
R1430:Gab1
|
UTSW |
8 |
81,515,241 (GRCm39) |
missense |
probably benign |
0.34 |
R1656:Gab1
|
UTSW |
8 |
81,515,388 (GRCm39) |
missense |
probably damaging |
1.00 |
R1986:Gab1
|
UTSW |
8 |
81,493,010 (GRCm39) |
missense |
probably damaging |
1.00 |
R2860:Gab1
|
UTSW |
8 |
81,511,382 (GRCm39) |
missense |
probably benign |
0.32 |
R2861:Gab1
|
UTSW |
8 |
81,511,382 (GRCm39) |
missense |
probably benign |
0.32 |
R4683:Gab1
|
UTSW |
8 |
81,515,261 (GRCm39) |
missense |
probably benign |
0.34 |
R4726:Gab1
|
UTSW |
8 |
81,515,682 (GRCm39) |
missense |
possibly damaging |
0.80 |
R5425:Gab1
|
UTSW |
8 |
81,527,018 (GRCm39) |
missense |
probably damaging |
1.00 |
R5684:Gab1
|
UTSW |
8 |
81,496,299 (GRCm39) |
missense |
probably damaging |
1.00 |
R6195:Gab1
|
UTSW |
8 |
81,606,161 (GRCm39) |
nonsense |
probably null |
|
R6217:Gab1
|
UTSW |
8 |
81,518,237 (GRCm39) |
missense |
possibly damaging |
0.48 |
R6233:Gab1
|
UTSW |
8 |
81,606,161 (GRCm39) |
nonsense |
probably null |
|
R6407:Gab1
|
UTSW |
8 |
81,515,226 (GRCm39) |
missense |
possibly damaging |
0.77 |
R6408:Gab1
|
UTSW |
8 |
81,515,226 (GRCm39) |
missense |
possibly damaging |
0.77 |
R6415:Gab1
|
UTSW |
8 |
81,515,226 (GRCm39) |
missense |
possibly damaging |
0.77 |
R6418:Gab1
|
UTSW |
8 |
81,515,226 (GRCm39) |
missense |
possibly damaging |
0.77 |
R6479:Gab1
|
UTSW |
8 |
81,515,226 (GRCm39) |
missense |
possibly damaging |
0.77 |
R7019:Gab1
|
UTSW |
8 |
81,511,446 (GRCm39) |
missense |
probably damaging |
0.99 |
R7291:Gab1
|
UTSW |
8 |
81,526,780 (GRCm39) |
missense |
probably damaging |
1.00 |
R7432:Gab1
|
UTSW |
8 |
81,515,298 (GRCm39) |
missense |
probably benign |
0.20 |
R7875:Gab1
|
UTSW |
8 |
81,515,395 (GRCm39) |
missense |
probably damaging |
1.00 |
R7893:Gab1
|
UTSW |
8 |
81,511,395 (GRCm39) |
missense |
possibly damaging |
0.47 |
R8405:Gab1
|
UTSW |
8 |
81,501,594 (GRCm39) |
nonsense |
probably null |
|
R9105:Gab1
|
UTSW |
8 |
81,515,589 (GRCm39) |
missense |
probably damaging |
1.00 |
R9485:Gab1
|
UTSW |
8 |
81,515,484 (GRCm39) |
missense |
probably damaging |
0.99 |
X0066:Gab1
|
UTSW |
8 |
81,606,193 (GRCm39) |
nonsense |
probably null |
|
|
Nature of Mutation |
DNA sequencing using the SOLiD technique identified an A to T transversion at position 2915 of the Gab1 transcript in exon 10 of 10 total exons. The mutated nucleotide causes an aspartic acid to valine substitution at amino acid 680 of the encoded protein. The mutation has been confirmed by DNA sequencing using the Sanger method (Figure 1).
|
Protein Function and Prediction |
The Gab1 gene encodes a 695 amino acid protein that is probably involved in EGF and insulin receptor signaling. GAB1 interacts with GRB2 and other SH2-containing proteins. It interacts with phosphorylated LAT2. GAB1 is phosphorylated on tyrosine residue(s) by the epidermal growth factor receptor (EGFR) and the insulin receptor (INSR), and contains one pleckstrin homology (PH) domain at amino acids 5-116 (Uniprot Q9QYY0).
The D680V change is predicted to be probably damaging by the PolyPhen program.
|
Posted On |
2010-03-12 |