Incidental Mutation 'I2289:Rraga'
| ID |
608 |
| Institutional Source |
Beutler Lab
|
| Gene Symbol |
Rraga
|
| Ensembl Gene |
ENSMUSG00000070934 |
| Gene Name |
Ras-related GTP binding A |
| Synonyms |
FIP-1, 1300010C19Rik |
| Accession Numbers |
|
| Essential gene? |
Essential
(E-score: 1.000)
|
| Stock # |
I2289 (G3)
of strain
633
|
| Quality Score |
|
|
Status
|
Validated
|
| Chromosome |
4 |
| Chromosomal Location |
86493910-86495522 bp(+) (GRCm39) |
| Type of Mutation |
missense |
| DNA Base Change (assembly) |
T to C
at 86494522 bp (GRCm39)
|
| Zygosity |
Heterozygous |
| Amino Acid Change |
Phenylalanine to Leucine
at position 123
(F123L)
|
| Ref Sequence |
ENSEMBL: ENSMUSP00000088591
(fasta)
|
| Gene Model |
predicted gene model for transcript(s):
[ENSMUST00000070607]
[ENSMUST00000091064]
|
| AlphaFold |
Q80X95 |
| Predicted Effect |
probably benign
Transcript: ENSMUST00000070607
|
| SMART Domains |
Protein: ENSMUSP00000070504
Gene: ENSMUSG00000038047
| Domain | Start | End | E-Value | Type |
|---|
|
Pfam:HAUS6_N
|
14 |
238 |
1.1e-77 |
PFAM |
|
low complexity region
|
613 |
624 |
N/A |
INTRINSIC |
|
low complexity region
|
771 |
785 |
N/A |
INTRINSIC |
|
low complexity region
|
915 |
927 |
N/A |
INTRINSIC |
|
| Predicted Effect |
probably damaging
Transcript: ENSMUST00000091064
AA Change: F123L
PolyPhen 2
Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)
|
| SMART Domains |
Protein: ENSMUSP00000088591
Gene: ENSMUSG00000070934
AA Change: F123L
| Domain | Start | End | E-Value | Type |
|---|
|
Pfam:Arf
|
1 |
176 |
6.3e-10 |
PFAM |
|
Pfam:MMR_HSR1
|
9 |
130 |
1e-7 |
PFAM |
|
Pfam:Roc
|
9 |
131 |
3.9e-10 |
PFAM |
|
Pfam:Ras
|
9 |
177 |
3.2e-10 |
PFAM |
|
Pfam:Gtr1_RagA
|
9 |
235 |
2.5e-111 |
PFAM |
|
| Meta Mutation Damage Score |
0.5579 |
| Coding Region Coverage |
|
| Het Detection Efficiency |
55.8% |
| Validation Efficiency |
88% (46/52) |
| MGI Phenotype |
PHENOTYPE: Mice homozygous for a constitutively active knock-in allele exhibit neonatal lethality associated with impaired hepatic gluconeogenesis and impaired autophagy. [provided by MGI curators]
|
| Allele List at MGI |
All alleles(1) : Gene trapped(1)
|
| Other mutations in this stock |
Total: 21 list
| Gene | Ref | Var | Chr/Loc | Mutation | Predicted Effect | Zygosity |
|---|
| Adamts12 |
T |
A |
15: 11,071,894 (GRCm39) |
L146Q |
probably benign |
Homo |
| Adgrv1 |
A |
G |
13: 81,585,643 (GRCm39) |
L4607P |
probably damaging |
Het |
| Amelx |
A |
G |
X: 167,961,009 (GRCm39) |
|
probably null |
Homo |
| Ankfy1 |
A |
G |
11: 72,621,311 (GRCm39) |
K199R |
probably benign |
Het |
| Arfgef1 |
T |
C |
1: 10,243,478 (GRCm39) |
K1024E |
probably damaging |
Het |
| Bank1 |
T |
A |
3: 135,760,179 (GRCm39) |
D782V |
probably damaging |
Homo |
| Csmd1 |
A |
T |
8: 15,962,381 (GRCm39) |
I3271K |
probably benign |
Homo |
| Fat1 |
A |
G |
8: 45,478,033 (GRCm39) |
I2360V |
probably benign |
Homo |
| Gldc |
G |
A |
19: 30,124,576 (GRCm39) |
R241* |
probably null |
Het |
| Golgb1 |
A |
G |
16: 36,718,904 (GRCm39) |
H270R |
probably benign |
Het |
| Heg1 |
T |
C |
16: 33,583,829 (GRCm39) |
I1212T |
probably damaging |
Het |
| Hes1 |
T |
A |
16: 29,884,699 (GRCm39) |
S53R |
probably damaging |
Het |
| Ibsp |
G |
A |
5: 104,450,353 (GRCm39) |
R57Q |
possibly damaging |
Homo |
| Lrp1b |
A |
T |
2: 41,012,944 (GRCm39) |
I2001K |
probably damaging |
Het |
| Nf1 |
G |
A |
11: 79,438,602 (GRCm39) |
R2181H |
probably damaging |
Het |
| Nrcam |
C |
A |
12: 44,611,098 (GRCm39) |
H567Q |
probably benign |
Homo |
| Or51a10 |
T |
C |
7: 103,698,961 (GRCm39) |
Y200C |
probably damaging |
Homo |
| Or5bw2 |
A |
T |
7: 6,573,818 (GRCm39) |
Y276F |
probably damaging |
Het |
| Spam1 |
A |
G |
6: 24,796,477 (GRCm39) |
I143V |
probably benign |
Het |
| Synj2 |
A |
G |
17: 6,072,542 (GRCm39) |
|
probably benign |
Homo |
| T |
A |
T |
17: 8,657,474 (GRCm39) |
T112S |
probably benign |
Homo |
|
| Other mutations in Rraga |
| Allele | Source | Chr | Coord | Type | Predicted Effect | PPH Score |
|---|
|
IGL03197:Rraga
|
APN |
4 |
86,494,513 (GRCm39) |
missense |
probably damaging |
0.98 |
|
workings
|
UTSW |
4 |
86,494,796 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R0612:Rraga
|
UTSW |
4 |
86,494,564 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R0624:Rraga
|
UTSW |
4 |
86,494,454 (GRCm39) |
missense |
probably benign |
0.00 |
|
R1477:Rraga
|
UTSW |
4 |
86,494,996 (GRCm39) |
missense |
probably benign |
|
|
R1804:Rraga
|
UTSW |
4 |
86,494,681 (GRCm39) |
missense |
probably damaging |
0.99 |
|
R4167:Rraga
|
UTSW |
4 |
86,494,304 (GRCm39) |
missense |
possibly damaging |
0.95 |
|
R6488:Rraga
|
UTSW |
4 |
86,494,565 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R7153:Rraga
|
UTSW |
4 |
86,494,253 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R8039:Rraga
|
UTSW |
4 |
86,494,217 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R8686:Rraga
|
UTSW |
4 |
86,495,048 (GRCm39) |
missense |
probably damaging |
0.96 |
|
R9007:Rraga
|
UTSW |
4 |
86,494,675 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R9144:Rraga
|
UTSW |
4 |
86,494,796 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R9666:Rraga
|
UTSW |
4 |
86,494,574 (GRCm39) |
missense |
possibly damaging |
0.93 |
|
| Nature of Mutation |
 DNA sequencing using the SOLiD technique identified a T to C transition at position 613 of the Rraga transcript using Genbank record NM_178376.3. The mutated nucleotide causes a phenylalanine to leucine substitution at amino acid 123 of the encoded protein. The mutation has been confirmed by DNA sequencing using the Sanger method.
|
| Protein Function and Prediction |
The Rraga gene encodes a 313 amino acid Ras related GTP binding protein. However, RAGA lacks intrinsic GTPase activity. The protein is required for the amino acid-induced relocalization of mTORC1 to the lysosomes and its subsequent activation by the GTPase RHEB. This is a crucial step in the activation of the TOR signaling cascade by amino acids. RAGA is also involved in the RCC1/Ran-GTPase pathway, and may play a direct role in a TNF-alpha signaling pathway leading to induction of cell death. Nucleotide binding occurs at residues 14-21, 62-66, and 127-130 (Uniprot Q80X95).
|
| Posted On |
2011-03-03 |
Incidental Mutation