Incidental Mutation 'R9370:Gck'
| ID |
709275 |
| Institutional Source |
Beutler Lab
|
| Gene Symbol |
Gck
|
| Ensembl Gene |
ENSMUSG00000041798 |
| Gene Name |
glucokinase |
| Synonyms |
Gls006, hexokinase 4, HK4, MODY2, Hlb62 |
| MMRRC Submission |
068964-MU
|
| Accession Numbers |
|
| Essential gene? |
Essential
(E-score: 1.000)
|
| Stock # |
R9370 (G1)
|
| Quality Score |
225.009 |
|
Status
|
Not validated
|
| Chromosome |
11 |
| Chromosomal Location |
5850820-5900081 bp(-) (GRCm39) |
| Type of Mutation |
missense |
| DNA Base Change (assembly) |
T to C
at 5852244 bp (GRCm39)
|
| Zygosity |
Heterozygous |
| Amino Acid Change |
Aspartic acid to Glycine
at position 365
(D365G)
|
| Ref Sequence |
ENSEMBL: ENSMUSP00000099984
(fasta)
|
| Gene Model |
predicted gene model for transcript(s):
[ENSMUST00000102920]
[ENSMUST00000102921]
[ENSMUST00000109822]
[ENSMUST00000109823]
|
| AlphaFold |
P52792 |
| Predicted Effect |
possibly damaging
Transcript: ENSMUST00000102920
AA Change: D365G
PolyPhen 2
Score 0.780 (Sensitivity: 0.85; Specificity: 0.93)
|
| SMART Domains |
Protein: ENSMUSP00000099984
Gene: ENSMUSG00000041798
AA Change: D365G
| Domain | Start | End | E-Value | Type |
|---|
|
Pfam:Hexokinase_1
|
10 |
217 |
4.3e-80 |
PFAM |
|
Pfam:Hexokinase_2
|
219 |
458 |
1.3e-100 |
PFAM |
|
| Predicted Effect |
probably benign
Transcript: ENSMUST00000102921
|
| SMART Domains |
Protein: ENSMUSP00000099985
Gene: ENSMUSG00000020469
| Domain | Start | End | E-Value | Type |
|---|
|
low complexity region
|
4 |
21 |
N/A |
INTRINSIC |
|
EFh
|
36 |
64 |
1.02e-2 |
SMART |
|
EFh
|
106 |
134 |
8.25e-3 |
SMART |
|
Blast:EFh
|
142 |
170 |
9e-12 |
BLAST |
|
| Predicted Effect |
possibly damaging
Transcript: ENSMUST00000109822
AA Change: D365G
PolyPhen 2
Score 0.861 (Sensitivity: 0.83; Specificity: 0.93)
|
| SMART Domains |
Protein: ENSMUSP00000105447
Gene: ENSMUSG00000041798
AA Change: D365G
| Domain | Start | End | E-Value | Type |
|---|
|
Pfam:Hexokinase_1
|
10 |
217 |
1e-79 |
PFAM |
|
Pfam:Hexokinase_2
|
219 |
458 |
7.8e-101 |
PFAM |
|
| Predicted Effect |
possibly damaging
Transcript: ENSMUST00000109823
AA Change: D365G
PolyPhen 2
Score 0.861 (Sensitivity: 0.83; Specificity: 0.93)
|
| SMART Domains |
Protein: ENSMUSP00000105448
Gene: ENSMUSG00000041798
AA Change: D365G
| Domain | Start | End | E-Value | Type |
|---|
|
Pfam:Hexokinase_1
|
15 |
216 |
1.9e-74 |
PFAM |
|
Pfam:Hexokinase_2
|
221 |
455 |
2.2e-79 |
PFAM |
|
| Predicted Effect |
probably benign
Transcript: ENSMUST00000125434
|
| SMART Domains |
Protein: ENSMUSP00000123016
Gene: ENSMUSG00000041798
| Domain | Start | End | E-Value | Type |
|---|
|
low complexity region
|
8 |
28 |
N/A |
INTRINSIC |
|
Pfam:Hexokinase_2
|
45 |
87 |
1.1e-8 |
PFAM |
|
| Coding Region Coverage |
- 1x: 100.0%
- 3x: 100.0%
- 10x: 99.8%
- 20x: 99.2%
|
| Validation Efficiency |
|
| MGI Phenotype |
FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] Hexokinases phosphorylate glucose to produce glucose-6-phosphate, the first step in most glucose metabolism pathways. Alternative splicing of this gene results in three tissue-specific forms of glucokinase, one found in pancreatic islet beta cells and two found in liver. The protein localizes to the outer membrane of mitochondria. In contrast to other forms of hexokinase, this enzyme is not inhibited by its product glucose-6-phosphate but remains active while glucose is abundant. Mutations in this gene have been associated with non-insulin dependent diabetes mellitus (NIDDM), maturity onset diabetes of the young, type 2 (MODY2) and persistent hyperinsulinemic hypoglycemia of infancy (PHHI). [provided by RefSeq, Apr 2009]
PHENOTYPE: Targeted disruption of this gene causes mild hyperglycemia in heterozygous mice and extreme hyperglycemia and embryonic to postnatal lethality in homozygous mice. Hyperglycemic knock-out or ENU-induced mutants may show reduced body weight and liver glycogen level, hepatic steatosis, and glucosuria. [provided by MGI curators]
|
| Allele List at MGI |
|
| Other mutations in this stock |
Total: 35 list
| Gene | Ref | Var | Chr/Loc | Mutation | Predicted Effect | Zygosity |
|---|
| Akr1d1 |
T |
A |
6: 37,544,099 (GRCm39) |
*326R |
probably null |
Het |
| Cntn5 |
T |
A |
9: 9,833,520 (GRCm39) |
I344F |
probably benign |
Het |
| Cyp2t4 |
G |
A |
7: 26,854,717 (GRCm39) |
V66M |
possibly damaging |
Het |
| Eln |
C |
T |
5: 134,741,476 (GRCm39) |
V563I |
unknown |
Het |
| Epb41l5 |
T |
C |
1: 119,561,312 (GRCm39) |
Y83C |
probably damaging |
Het |
| Epha8 |
T |
C |
4: 136,673,511 (GRCm39) |
D91G |
possibly damaging |
Het |
| Fscn3 |
T |
C |
6: 28,434,535 (GRCm39) |
V370A |
probably benign |
Het |
| Gcc2 |
A |
G |
10: 58,131,940 (GRCm39) |
N1550S |
probably benign |
Het |
| Hhatl |
C |
T |
9: 121,617,836 (GRCm39) |
G251E |
possibly damaging |
Het |
| Hspa12a |
A |
G |
19: 58,813,708 (GRCm39) |
F139S |
probably damaging |
Het |
| Ikzf2 |
T |
C |
1: 69,578,018 (GRCm39) |
D497G |
probably damaging |
Het |
| Ino80 |
A |
G |
2: 119,232,848 (GRCm39) |
S1157P |
probably damaging |
Het |
| Jmjd6 |
A |
G |
11: 116,729,952 (GRCm39) |
I315T |
probably benign |
Het |
| Jup |
C |
T |
11: 100,270,391 (GRCm39) |
C372Y |
probably damaging |
Het |
| Krt9 |
TCCACTTCCTCCTCCATAGCTGCCCCCACTTCCTCCTCCATAGCTGCCCCCACTTCCTCCTCCATAGCTGCCCCCACTTCCTCCTCCATAGCTGCC |
TCCACTTCCTCCTCCATAGCTGCCCCCACTTCCTCCTCCATAGCTGCCCCCACTTCCTCCTCCATAGCTGCC |
11: 100,079,903 (GRCm39) |
|
probably benign |
Het |
| Lyst |
C |
T |
13: 13,935,333 (GRCm39) |
H3601Y |
probably damaging |
Het |
| Mars2 |
T |
C |
1: 55,276,624 (GRCm39) |
S76P |
probably benign |
Het |
| Mtmr10 |
A |
G |
7: 63,969,249 (GRCm39) |
E337G |
probably benign |
Het |
| Myo5b |
A |
G |
18: 74,760,246 (GRCm39) |
D254G |
possibly damaging |
Het |
| Nell1 |
A |
T |
7: 49,770,292 (GRCm39) |
E117V |
probably damaging |
Het |
| Pcdhgb7 |
T |
C |
18: 37,884,937 (GRCm39) |
S36P |
possibly damaging |
Het |
| Rps6kc1 |
A |
C |
1: 190,531,222 (GRCm39) |
L927V |
probably damaging |
Het |
| Sacs |
T |
A |
14: 61,441,080 (GRCm39) |
I1042N |
probably damaging |
Het |
| Skint2 |
A |
G |
4: 112,481,259 (GRCm39) |
N41D |
possibly damaging |
Het |
| Slc5a11 |
A |
G |
7: 122,834,855 (GRCm39) |
T5A |
probably benign |
Het |
| Tbc1d22a |
C |
T |
15: 86,123,441 (GRCm39) |
T194I |
probably benign |
Het |
| Tmem234 |
T |
A |
4: 129,500,922 (GRCm39) |
V93D |
probably damaging |
Het |
| Trim43b |
T |
C |
9: 88,971,559 (GRCm39) |
E199G |
probably benign |
Het |
| Ttc24 |
A |
T |
3: 87,980,136 (GRCm39) |
V148E |
probably benign |
Het |
| Utp15 |
A |
G |
13: 98,387,119 (GRCm39) |
F434L |
probably damaging |
Het |
| Vmn2r81 |
A |
G |
10: 79,104,424 (GRCm39) |
Y349C |
probably damaging |
Het |
| Xpo5 |
T |
A |
17: 46,546,844 (GRCm39) |
V865E |
probably damaging |
Het |
| Zfhx3 |
C |
T |
8: 109,521,340 (GRCm39) |
R821C |
probably damaging |
Het |
| Zfp90 |
A |
G |
8: 107,145,791 (GRCm39) |
D41G |
probably damaging |
Het |
| Zzef1 |
T |
A |
11: 72,744,148 (GRCm39) |
C835S |
probably damaging |
Het |
|
| Other mutations in Gck |
| Allele | Source | Chr | Coord | Type | Predicted Effect | PPH Score |
|---|
|
IGL01624:Gck
|
APN |
11 |
5,853,106 (GRCm39) |
missense |
possibly damaging |
0.67 |
|
IGL01647:Gck
|
APN |
11 |
5,854,472 (GRCm39) |
missense |
probably damaging |
0.97 |
|
IGL03145:Gck
|
APN |
11 |
5,859,093 (GRCm39) |
missense |
probably damaging |
0.99 |
|
Grahamcracker
|
UTSW |
11 |
5,852,165 (GRCm39) |
missense |
probably damaging |
1.00 |
|
Tootsie
|
UTSW |
11 |
5,859,150 (GRCm39) |
missense |
possibly damaging |
0.63 |
|
R0139:Gck
|
UTSW |
11 |
5,860,370 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R0139:Gck
|
UTSW |
11 |
5,859,139 (GRCm39) |
nonsense |
probably null |
|
|
R0691:Gck
|
UTSW |
11 |
5,856,691 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R1829:Gck
|
UTSW |
11 |
5,860,984 (GRCm39) |
missense |
probably damaging |
0.97 |
|
R1866:Gck
|
UTSW |
11 |
5,853,253 (GRCm39) |
missense |
probably benign |
0.02 |
|
R1868:Gck
|
UTSW |
11 |
5,852,165 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R1992:Gck
|
UTSW |
11 |
5,856,515 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R3885:Gck
|
UTSW |
11 |
5,860,318 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R4179:Gck
|
UTSW |
11 |
5,860,295 (GRCm39) |
missense |
probably benign |
0.43 |
|
R4888:Gck
|
UTSW |
11 |
5,859,150 (GRCm39) |
missense |
possibly damaging |
0.63 |
|
R7034:Gck
|
UTSW |
11 |
5,851,747 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R7155:Gck
|
UTSW |
11 |
5,899,705 (GRCm39) |
start gained |
probably benign |
|
|
R7548:Gck
|
UTSW |
11 |
5,852,040 (GRCm39) |
missense |
|
|
|
R8039:Gck
|
UTSW |
11 |
5,860,301 (GRCm39) |
missense |
probably benign |
0.12 |
|
R8891:Gck
|
UTSW |
11 |
5,851,733 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R9100:Gck
|
UTSW |
11 |
5,856,516 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R9101:Gck
|
UTSW |
11 |
5,856,516 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R9102:Gck
|
UTSW |
11 |
5,856,516 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R9116:Gck
|
UTSW |
11 |
5,854,377 (GRCm39) |
missense |
possibly damaging |
0.71 |
|
R9420:Gck
|
UTSW |
11 |
5,899,553 (GRCm39) |
critical splice donor site |
probably null |
|
|
R9536:Gck
|
UTSW |
11 |
5,852,307 (GRCm39) |
missense |
possibly damaging |
0.92 |
|
Z1176:Gck
|
UTSW |
11 |
5,856,526 (GRCm39) |
missense |
probably damaging |
1.00 |
|
Z1177:Gck
|
UTSW |
11 |
5,860,958 (GRCm39) |
missense |
possibly damaging |
0.81 |
|
| Predicted Primers |
PCR Primer
(F):5'- AAGCCTGGAGTTGAAAGCCG -3'
(R):5'- GTGGCATTGTCATCCTCACGAC -3'
Sequencing Primer
(F):5'- TTGAAAGCCGCGCCCTTG -3'
(R):5'- TTGTCATCCTCACGACAGAGAAAAC -3'
|
| Posted On |
2022-04-18 |
Incidental Mutation