Incidental Mutation 'N/A:Glp1r'
| ID |
45 |
| Institutional Source |
Beutler Lab
|
| Gene Symbol |
Glp1r
|
| Ensembl Gene |
ENSMUSG00000024027 |
| Gene Name |
glucagon-like peptide 1 receptor |
| Synonyms |
GLP-1R, GLP1Rc |
| Accession Numbers |
|
| Essential gene? |
Non essential
(E-score: 0.000)
|
| Stock # |
N/A
of strain
294
|
| Quality Score |
|
|
Status
|
Validated
|
| Chromosome |
17 |
| Chromosomal Location |
31120841-31155484 bp(+) (GRCm39) |
| Type of Mutation |
missense |
| DNA Base Change (assembly) |
T to C
at 31150257 bp (GRCm39)
|
| Zygosity |
Homozygous |
| Amino Acid Change |
Phenylalanine to Serine
at position 393
(F393S)
|
| Ref Sequence |
ENSEMBL: ENSMUSP00000110221
(fasta)
|
| Gene Model |
predicted gene model for transcript(s):
[ENSMUST00000114574]
|
| AlphaFold |
O35659 |
| Predicted Effect |
probably damaging
Transcript: ENSMUST00000114574
AA Change: F393S
PolyPhen 2
Score 0.978 (Sensitivity: 0.76; Specificity: 0.96)
|
| SMART Domains |
Protein: ENSMUSP00000110221
Gene: ENSMUSG00000024027
AA Change: F393S
| Domain | Start | End | E-Value | Type |
|---|
|
signal peptide
|
1 |
21 |
N/A |
INTRINSIC |
|
HormR
|
58 |
135 |
9.88e-27 |
SMART |
|
Pfam:7tm_2
|
141 |
398 |
7.4e-82 |
PFAM |
|
low complexity region
|
440 |
456 |
N/A |
INTRINSIC |
|
| Meta Mutation Damage Score |
0.9155 |
| Coding Region Coverage |
|
| Validation Efficiency |
91% (106/116) |
| MGI Phenotype |
FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene encodes a 7-transmembrane protein that functions as a receptor for glucagon-like peptide 1 (GLP-1) hormone, which stimulates glucose-induced insulin secretion. This receptor, which functions at the cell surface, becomes internalized in response to GLP-1 and GLP-1 analogs, and it plays an important role in the signaling cascades leading to insulin secretion. It also displays neuroprotective effects in animal models. Polymorphisms in this gene are associated with diabetes. The protein is an important drug target for the treatment of type 2 diabetes and stroke. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Apr 2016]
PHENOTYPE: Glucose tolerance and pancreatic secretion is impaired in homozygous null mice. [provided by MGI curators]
|
| Allele List at MGI |
All alleles(1) : Targeted, knock-out(1) |
| Other mutations in this stock |
Total: 18 list
| Gene | Ref | Var | Chr/Loc | Mutation | Predicted Effect | Zygosity |
|---|
| 1700016P04Rik |
T |
A |
6: 13,415,772 (GRCm39) |
|
noncoding transcript |
Homo |
| Aif1 |
A |
G |
17: 35,391,496 (GRCm39) |
L7S |
possibly damaging |
Homo |
| Ankrd26 |
T |
C |
6: 118,506,535 (GRCm39) |
D646G |
probably benign |
Homo |
| Cacna1s |
A |
G |
1: 136,001,247 (GRCm39) |
I233V |
probably benign |
Homo |
| Cfap92 |
A |
T |
6: 87,667,773 (GRCm39) |
|
noncoding transcript |
Homo |
| Chchd4 |
T |
C |
6: 91,442,187 (GRCm39) |
Y77C |
probably damaging |
Homo |
| Crocc |
G |
A |
4: 140,749,057 (GRCm39) |
R1419C |
probably damaging |
Homo |
| Cyp4f39 |
A |
C |
17: 32,687,655 (GRCm39) |
M74L |
probably benign |
Homo |
| Fgf9 |
C |
A |
14: 58,327,421 (GRCm39) |
|
probably benign |
Homo |
| Gimap6 |
T |
C |
6: 48,679,349 (GRCm39) |
D229G |
probably damaging |
Homo |
| Lrrc7 |
T |
G |
3: 157,865,977 (GRCm39) |
I1255L |
probably benign |
Homo |
| Mtrr |
C |
A |
13: 68,723,516 (GRCm39) |
|
probably benign |
Homo |
| Pde6b |
A |
T |
5: 108,576,969 (GRCm39) |
|
probably benign |
Homo |
| Rbm19 |
A |
T |
5: 120,282,162 (GRCm39) |
I840F |
probably damaging |
Homo |
| Serpina3c |
A |
C |
12: 104,115,864 (GRCm39) |
S227A |
probably benign |
Homo |
| Spag17 |
G |
A |
3: 99,889,570 (GRCm39) |
|
probably benign |
Homo |
| Spmip3 |
G |
A |
1: 177,561,100 (GRCm39) |
R13H |
probably damaging |
Homo |
| Zbtb8b |
T |
C |
4: 129,326,361 (GRCm39) |
D268G |
probably benign |
Homo |
|
| Other mutations in Glp1r |
| Allele | Source | Chr | Coord | Type | Predicted Effect | PPH Score |
|---|
|
IGL00158:Glp1r
|
APN |
17 |
31,120,891 (GRCm39) |
missense |
possibly damaging |
0.96 |
|
IGL00516:Glp1r
|
APN |
17 |
31,144,532 (GRCm39) |
missense |
probably damaging |
1.00 |
|
IGL00653:Glp1r
|
APN |
17 |
31,149,734 (GRCm39) |
missense |
probably damaging |
1.00 |
|
IGL00917:Glp1r
|
APN |
17 |
31,138,443 (GRCm39) |
splice site |
probably benign |
|
|
IGL02005:Glp1r
|
APN |
17 |
31,143,585 (GRCm39) |
missense |
probably benign |
0.03 |
|
IGL02411:Glp1r
|
APN |
17 |
31,143,485 (GRCm39) |
missense |
probably damaging |
1.00 |
|
IGL02889:Glp1r
|
APN |
17 |
31,150,118 (GRCm39) |
splice site |
probably benign |
|
|
IGL02928:Glp1r
|
APN |
17 |
31,137,911 (GRCm39) |
missense |
probably benign |
0.00 |
|
R0135:Glp1r
|
UTSW |
17 |
31,143,551 (GRCm39) |
missense |
probably benign |
0.00 |
|
R0395:Glp1r
|
UTSW |
17 |
31,155,312 (GRCm39) |
missense |
probably benign |
0.34 |
|
R0481:Glp1r
|
UTSW |
17 |
31,150,191 (GRCm39) |
missense |
probably benign |
0.03 |
|
R0602:Glp1r
|
UTSW |
17 |
31,128,201 (GRCm39) |
missense |
probably benign |
0.12 |
|
R0841:Glp1r
|
UTSW |
17 |
31,138,406 (GRCm39) |
missense |
probably benign |
0.01 |
|
R1145:Glp1r
|
UTSW |
17 |
31,138,406 (GRCm39) |
missense |
probably benign |
0.01 |
|
R1145:Glp1r
|
UTSW |
17 |
31,138,406 (GRCm39) |
missense |
probably benign |
0.01 |
|
R1232:Glp1r
|
UTSW |
17 |
31,137,905 (GRCm39) |
missense |
probably benign |
|
|
R1804:Glp1r
|
UTSW |
17 |
31,149,687 (GRCm39) |
splice site |
probably null |
|
|
R1846:Glp1r
|
UTSW |
17 |
31,148,909 (GRCm39) |
critical splice acceptor site |
probably null |
|
|
R1982:Glp1r
|
UTSW |
17 |
31,144,601 (GRCm39) |
nonsense |
probably null |
|
|
R1990:Glp1r
|
UTSW |
17 |
31,149,722 (GRCm39) |
missense |
possibly damaging |
0.53 |
|
R2091:Glp1r
|
UTSW |
17 |
31,144,523 (GRCm39) |
missense |
probably damaging |
0.97 |
|
R3432:Glp1r
|
UTSW |
17 |
31,143,531 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R4456:Glp1r
|
UTSW |
17 |
31,137,949 (GRCm39) |
nonsense |
probably null |
|
|
R4488:Glp1r
|
UTSW |
17 |
31,137,905 (GRCm39) |
missense |
probably benign |
|
|
R4610:Glp1r
|
UTSW |
17 |
31,150,221 (GRCm39) |
missense |
probably benign |
0.03 |
|
R4884:Glp1r
|
UTSW |
17 |
31,155,240 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R5055:Glp1r
|
UTSW |
17 |
31,137,861 (GRCm39) |
missense |
probably benign |
|
|
R6358:Glp1r
|
UTSW |
17 |
31,151,618 (GRCm39) |
missense |
probably benign |
0.07 |
|
R6359:Glp1r
|
UTSW |
17 |
31,148,946 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R6490:Glp1r
|
UTSW |
17 |
31,143,546 (GRCm39) |
missense |
probably damaging |
0.98 |
|
R6698:Glp1r
|
UTSW |
17 |
31,155,375 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R7063:Glp1r
|
UTSW |
17 |
31,144,532 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R7165:Glp1r
|
UTSW |
17 |
31,128,297 (GRCm39) |
missense |
probably benign |
0.23 |
|
R7293:Glp1r
|
UTSW |
17 |
31,143,599 (GRCm39) |
missense |
probably benign |
0.00 |
|
R7646:Glp1r
|
UTSW |
17 |
31,155,257 (GRCm39) |
missense |
probably benign |
0.38 |
|
R7655:Glp1r
|
UTSW |
17 |
31,149,572 (GRCm39) |
critical splice donor site |
probably null |
|
|
R7656:Glp1r
|
UTSW |
17 |
31,149,572 (GRCm39) |
critical splice donor site |
probably null |
|
|
R7686:Glp1r
|
UTSW |
17 |
31,144,633 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R8531:Glp1r
|
UTSW |
17 |
31,143,531 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R9050:Glp1r
|
UTSW |
17 |
31,137,892 (GRCm39) |
missense |
probably damaging |
1.00 |
|
X0064:Glp1r
|
UTSW |
17 |
31,138,437 (GRCm39) |
critical splice donor site |
probably null |
|
|
| Nature of Mutation |
 DNA sequencing using the SOLiD technique identified a T to C transition at position 1453 of the Glp1r transcript, in exon 13 of 13 total exons. The mutated nucleotide causes a phenylalanine to serine substitution at amino acid 393. The mutation has been confirmed by DNA sequencing using the Sanger method (Figure 1).
|
| Protein Function and Prediction |
The Glp1r gene encodes the 489 amino acid long Glucagon-like peptide 1 receptor (GLP-1R). This is a G-protein coupled receptor (GPCR) for glucagon-like peptide 1 (GLP-1). The GLP-1R protein contains a signal peptide at amino acids 1-21, seven transmembrane domains, and shares homology with other GPCRs. Conserved disulfide bonds are likely to be located between residues 46 and 71, 62 and 104, and 85 and 126 (Uniprot O35659). Glucose tolerance and secretion of pancreatic hormones is impaired in homozygous knockout mice. Learning and memory, regulation of heart contraction, normal stress responses, and bone resorption are also impaired in these animals.
The F1453S change occurs in the seventh transmembrane domain of GLP-1R, and is predicted to be possibly damaging by the PolyPhen program. |
| Posted On |
2009-11-10 |
Incidental Mutation