Incidental Mutation 'IGL00864:Tbc1d4'
| ID |
14386 |
| Institutional Source |
Australian Phenomics Network
(link to record)
|
| Gene Symbol |
Tbc1d4
|
| Ensembl Gene |
ENSMUSG00000033083 |
| Gene Name |
TBC1 domain family, member 4 |
| Synonyms |
AS160, 5930406J04Rik |
| Accession Numbers |
|
| Essential gene? |
Non essential
(E-score: 0.000)
|
| Stock # |
IGL00864
|
| Quality Score |
|
|
Status
|
|
| Chromosome |
14 |
| Chromosomal Location |
101679796-101846627 bp(-) (GRCm39) |
| Type of Mutation |
missense |
| DNA Base Change (assembly) |
T to A
at 101682002 bp (GRCm39)
|
| Zygosity |
Heterozygous |
| Amino Acid Change |
Aspartic acid to Valine
at position 1235
(D1235V)
|
| Ref Sequence |
ENSEMBL: ENSMUSP00000125509
(fasta)
|
| Gene Model |
predicted gene model for transcript(s):
[ENSMUST00000161991]
[ENSMUST00000162617]
|
| AlphaFold |
no structure available at present |
| Predicted Effect |
unknown
Transcript: ENSMUST00000159951
AA Change: D948V
|
| SMART Domains |
Protein: ENSMUSP00000124511
Gene: ENSMUSG00000033083
AA Change: D948V
| Domain | Start | End | E-Value | Type |
|---|
|
PTB
|
28 |
170 |
8.6e-22 |
SMART |
|
Pfam:DUF3350
|
459 |
522 |
2.3e-31 |
PFAM |
|
TBC
|
574 |
794 |
5.2e-77 |
SMART |
|
Blast:TBC
|
819 |
877 |
7e-24 |
BLAST |
|
Blast:TBC
|
882 |
936 |
1e-20 |
BLAST |
|
| Predicted Effect |
noncoding transcript
Transcript: ENSMUST00000161304
|
| Predicted Effect |
probably benign
Transcript: ENSMUST00000161991
AA Change: D1235V
PolyPhen 2
Score 0.233 (Sensitivity: 0.91; Specificity: 0.88)
|
| SMART Domains |
Protein: ENSMUSP00000125509
Gene: ENSMUSG00000033083
AA Change: D1235V
| Domain | Start | End | E-Value | Type |
|---|
|
PTB
|
31 |
191 |
2.08e-29 |
SMART |
|
PTB
|
197 |
457 |
3.16e-29 |
SMART |
|
Pfam:DUF3350
|
746 |
809 |
1.2e-27 |
PFAM |
|
TBC
|
860 |
1080 |
5.2e-77 |
SMART |
|
Blast:TBC
|
1105 |
1163 |
1e-23 |
BLAST |
|
Blast:TBC
|
1168 |
1222 |
1e-20 |
BLAST |
|
| Predicted Effect |
probably benign
Transcript: ENSMUST00000162617
AA Change: D1298V
PolyPhen 2
Score 0.061 (Sensitivity: 0.94; Specificity: 0.84)
|
| SMART Domains |
Protein: ENSMUSP00000124909
Gene: ENSMUSG00000033083
AA Change: D1298V
| Domain | Start | End | E-Value | Type |
|---|
|
PTB
|
31 |
191 |
2.08e-29 |
SMART |
|
PTB
|
197 |
457 |
3.16e-29 |
SMART |
|
low complexity region
|
708 |
720 |
N/A |
INTRINSIC |
|
Pfam:DUF3350
|
809 |
872 |
3.3e-31 |
PFAM |
|
TBC
|
923 |
1143 |
5.2e-77 |
SMART |
|
Blast:TBC
|
1168 |
1226 |
2e-23 |
BLAST |
|
Blast:TBC
|
1231 |
1285 |
1e-20 |
BLAST |
|
| Coding Region Coverage |
|
| Validation Efficiency |
|
| MGI Phenotype |
FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene is a member of the Tre-2/BUB2/CDC16 domain family. The protein encoded by this gene is a Rab-GTPase-activating protein, and contains two phopshotyrosine-binding domains (PTB1 and PTB2), a calmodulin-binding domain (CBD), a Rab-GTPase domain, and multiple AKT phosphomotifs. This protein is thought to play an important role in glucose homeostasis by regulating the insulin-dependent trafficking of the glucose transporter 4 (GLUT4), important for removing glucose from the bloodstream into skeletal muscle and fat tissues. Reduced expression of this gene results in an increase in GLUT4 levels at the plasma membrane, suggesting that this protein is important in intracellular retention of GLUT4 under basal conditions. When exposed to insulin, this protein is phosphorylated, dissociates from GLUT4 vesicles, resulting in increased GLUT4 at the cell surface, and enhanced glucose transport. Phosphorylation of this protein by AKT is required for proper translocation of GLUT4 to the cell surface. Individuals homozygous for a mutation in this gene are at higher risk for type 2 diabetes and have higher levels of circulating glucose and insulin levels after glucose ingestion. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Aug 2015]
PHENOTYPE: Mice homozygous for a null allele exhibit reduced blood glucose levels under both fasted and fed conditions, insulin resistance in both muscle and liver, decreased energy expenditure and oxygen consumption, abnormal adipocyte and muscle cell glucose uptake, and increased hepatic gluconeogenesis. [provided by MGI curators]
|
| Allele List at MGI |
|
| Other mutations in this stock |
Total: 21 list
| Gene | Ref | Var | Chr/Loc | Mutation | Predicted Effect | Zygosity |
|---|
| 4921539E11Rik |
T |
C |
4: 103,092,895 (GRCm39) |
D142G |
probably damaging |
Het |
| Ap2b1 |
A |
C |
11: 83,223,984 (GRCm39) |
D195A |
probably damaging |
Het |
| Asxl3 |
T |
A |
18: 22,655,503 (GRCm39) |
I1171K |
probably benign |
Het |
| Atm |
T |
C |
9: 53,445,233 (GRCm39) |
S2G |
probably damaging |
Het |
| Crygd |
C |
T |
1: 65,101,250 (GRCm39) |
R115Q |
probably benign |
Het |
| Ephx1 |
A |
G |
1: 180,818,016 (GRCm39) |
S356P |
probably damaging |
Het |
| H1f8 |
A |
G |
6: 115,925,587 (GRCm39) |
K128R |
probably damaging |
Het |
| Il12rb2 |
A |
G |
6: 67,313,738 (GRCm39) |
I6T |
probably benign |
Het |
| Itm2b |
T |
C |
14: 73,600,575 (GRCm39) |
K242E |
probably damaging |
Het |
| Kcnq5 |
T |
A |
1: 21,575,987 (GRCm39) |
Q239L |
probably damaging |
Het |
| Lmbrd2 |
T |
C |
15: 9,175,297 (GRCm39) |
S403P |
probably damaging |
Het |
| Ola1 |
A |
T |
2: 72,987,241 (GRCm39) |
D130E |
probably benign |
Het |
| Opcml |
G |
A |
9: 28,812,886 (GRCm39) |
E193K |
probably damaging |
Het |
| Opcml |
A |
C |
9: 28,812,887 (GRCm39) |
E193A |
probably damaging |
Het |
| Rab44 |
T |
C |
17: 29,358,711 (GRCm39) |
S300P |
probably benign |
Het |
| Sergef |
C |
A |
7: 46,165,087 (GRCm39) |
|
probably null |
Het |
| Slc6a2 |
T |
C |
8: 93,722,622 (GRCm39) |
F540L |
probably benign |
Het |
| Spag6l |
A |
G |
16: 16,598,597 (GRCm39) |
V298A |
probably benign |
Het |
| Svep1 |
G |
T |
4: 58,068,533 (GRCm39) |
Y3084* |
probably null |
Het |
| Tlr9 |
T |
C |
9: 106,102,206 (GRCm39) |
L499P |
probably damaging |
Het |
| Ttn |
G |
A |
2: 76,544,178 (GRCm39) |
S24609F |
probably damaging |
Het |
|
| Other mutations in Tbc1d4 |
| Allele | Source | Chr | Coord | Type | Predicted Effect | PPH Score |
|---|
|
IGL00087:Tbc1d4
|
APN |
14 |
101,845,548 (GRCm39) |
missense |
probably damaging |
1.00 |
|
IGL01065:Tbc1d4
|
APN |
14 |
101,686,629 (GRCm39) |
splice site |
probably benign |
|
|
IGL01144:Tbc1d4
|
APN |
14 |
101,682,099 (GRCm39) |
missense |
probably damaging |
0.99 |
|
IGL01153:Tbc1d4
|
APN |
14 |
101,845,451 (GRCm39) |
missense |
possibly damaging |
0.52 |
|
IGL01472:Tbc1d4
|
APN |
14 |
101,727,300 (GRCm39) |
nonsense |
probably null |
|
|
IGL02177:Tbc1d4
|
APN |
14 |
101,692,375 (GRCm39) |
missense |
possibly damaging |
0.90 |
|
IGL02259:Tbc1d4
|
APN |
14 |
101,703,166 (GRCm39) |
missense |
probably damaging |
1.00 |
|
IGL02938:Tbc1d4
|
APN |
14 |
101,738,536 (GRCm39) |
missense |
probably damaging |
1.00 |
|
IGL02975:Tbc1d4
|
APN |
14 |
101,695,549 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R0396:Tbc1d4
|
UTSW |
14 |
101,695,499 (GRCm39) |
splice site |
probably null |
|
|
R0787:Tbc1d4
|
UTSW |
14 |
101,686,645 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R0944:Tbc1d4
|
UTSW |
14 |
101,716,656 (GRCm39) |
splice site |
probably benign |
|
|
R1167:Tbc1d4
|
UTSW |
14 |
101,845,455 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R1456:Tbc1d4
|
UTSW |
14 |
101,744,542 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R1465:Tbc1d4
|
UTSW |
14 |
101,685,124 (GRCm39) |
missense |
possibly damaging |
0.87 |
|
R1465:Tbc1d4
|
UTSW |
14 |
101,685,124 (GRCm39) |
missense |
possibly damaging |
0.87 |
|
R1672:Tbc1d4
|
UTSW |
14 |
101,712,651 (GRCm39) |
missense |
possibly damaging |
0.92 |
|
R1762:Tbc1d4
|
UTSW |
14 |
101,744,574 (GRCm39) |
missense |
possibly damaging |
0.95 |
|
R2057:Tbc1d4
|
UTSW |
14 |
101,714,591 (GRCm39) |
missense |
probably damaging |
0.97 |
|
R2260:Tbc1d4
|
UTSW |
14 |
101,731,847 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R2762:Tbc1d4
|
UTSW |
14 |
101,731,797 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R3814:Tbc1d4
|
UTSW |
14 |
101,696,191 (GRCm39) |
missense |
possibly damaging |
0.94 |
|
R3983:Tbc1d4
|
UTSW |
14 |
101,744,649 (GRCm39) |
missense |
probably benign |
0.00 |
|
R4498:Tbc1d4
|
UTSW |
14 |
101,845,772 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R4580:Tbc1d4
|
UTSW |
14 |
101,696,219 (GRCm39) |
missense |
probably benign |
0.00 |
|
R4664:Tbc1d4
|
UTSW |
14 |
101,700,263 (GRCm39) |
intron |
probably benign |
|
|
R4872:Tbc1d4
|
UTSW |
14 |
101,682,144 (GRCm39) |
missense |
probably benign |
0.06 |
|
R4940:Tbc1d4
|
UTSW |
14 |
101,744,667 (GRCm39) |
missense |
probably benign |
0.27 |
|
R4964:Tbc1d4
|
UTSW |
14 |
101,695,610 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R4966:Tbc1d4
|
UTSW |
14 |
101,695,610 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R5103:Tbc1d4
|
UTSW |
14 |
101,696,318 (GRCm39) |
nonsense |
probably null |
|
|
R5180:Tbc1d4
|
UTSW |
14 |
101,745,008 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R5366:Tbc1d4
|
UTSW |
14 |
101,845,412 (GRCm39) |
missense |
possibly damaging |
0.67 |
|
R5673:Tbc1d4
|
UTSW |
14 |
101,692,444 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R6057:Tbc1d4
|
UTSW |
14 |
101,727,353 (GRCm39) |
missense |
probably damaging |
0.99 |
|
R6180:Tbc1d4
|
UTSW |
14 |
101,696,206 (GRCm39) |
missense |
probably benign |
0.01 |
|
R6361:Tbc1d4
|
UTSW |
14 |
101,744,610 (GRCm39) |
missense |
probably damaging |
0.97 |
|
R6509:Tbc1d4
|
UTSW |
14 |
101,845,754 (GRCm39) |
missense |
possibly damaging |
0.92 |
|
R6791:Tbc1d4
|
UTSW |
14 |
101,845,695 (GRCm39) |
missense |
probably damaging |
0.98 |
|
R7001:Tbc1d4
|
UTSW |
14 |
101,696,185 (GRCm39) |
missense |
probably benign |
0.43 |
|
R7016:Tbc1d4
|
UTSW |
14 |
101,724,877 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R7575:Tbc1d4
|
UTSW |
14 |
101,685,025 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R7691:Tbc1d4
|
UTSW |
14 |
101,745,077 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R7936:Tbc1d4
|
UTSW |
14 |
101,703,190 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R7991:Tbc1d4
|
UTSW |
14 |
101,845,715 (GRCm39) |
missense |
probably damaging |
0.98 |
|
R8182:Tbc1d4
|
UTSW |
14 |
101,744,990 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R8540:Tbc1d4
|
UTSW |
14 |
101,845,712 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R9126:Tbc1d4
|
UTSW |
14 |
101,724,952 (GRCm39) |
missense |
probably benign |
0.01 |
|
R9282:Tbc1d4
|
UTSW |
14 |
101,845,616 (GRCm39) |
missense |
possibly damaging |
0.93 |
|
R9288:Tbc1d4
|
UTSW |
14 |
101,692,308 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R9385:Tbc1d4
|
UTSW |
14 |
101,700,356 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R9424:Tbc1d4
|
UTSW |
14 |
101,703,096 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R9494:Tbc1d4
|
UTSW |
14 |
101,845,895 (GRCm39) |
start codon destroyed |
probably null |
0.90 |
|
R9655:Tbc1d4
|
UTSW |
14 |
101,744,567 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R9658:Tbc1d4
|
UTSW |
14 |
101,845,856 (GRCm39) |
missense |
probably damaging |
0.98 |
|
R9712:Tbc1d4
|
UTSW |
14 |
101,744,846 (GRCm39) |
missense |
probably benign |
|
|
Z1088:Tbc1d4
|
UTSW |
14 |
101,689,859 (GRCm39) |
missense |
probably damaging |
1.00 |
|
Z1176:Tbc1d4
|
UTSW |
14 |
101,744,523 (GRCm39) |
critical splice donor site |
probably null |
|
|
| Posted On |
2012-12-06 |
Incidental Mutation