Incidental Mutation 'R8182:Tbc1d4'
ID 634697
Institutional Source Beutler Lab
Gene Symbol Tbc1d4
Ensembl Gene ENSMUSG00000033083
Gene Name TBC1 domain family, member 4
Synonyms AS160, 5930406J04Rik
MMRRC Submission 067606-MU
Accession Numbers
Essential gene? Non essential (E-score: 0.000) question?
Stock # R8182 (G1)
Quality Score 225.009
Status Validated
Chromosome 14
Chromosomal Location 101679796-101846627 bp(-) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) A to T at 101744990 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Valine to Glutamic Acid at position 212 (V212E)
Ref Sequence ENSEMBL: ENSMUSP00000097913 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000100340] [ENSMUST00000161991] [ENSMUST00000162617]
AlphaFold no structure available at present
Predicted Effect probably damaging
Transcript: ENSMUST00000100340
AA Change: V212E

PolyPhen 2 Score 0.999 (Sensitivity: 0.14; Specificity: 0.99)
SMART Domains Protein: ENSMUSP00000097913
Gene: ENSMUSG00000033083
AA Change: V212E

DomainStartEndE-ValueType
PTB 31 191 2.08e-29 SMART
PTB 197 457 3.16e-29 SMART
low complexity region 708 720 N/A INTRINSIC
Blast:TBC 773 834 3e-12 BLAST
Predicted Effect probably benign
Transcript: ENSMUST00000159951
SMART Domains Protein: ENSMUSP00000124511
Gene: ENSMUSG00000033083

DomainStartEndE-ValueType
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 probably damaging
Transcript: ENSMUST00000161991
AA Change: V212E

PolyPhen 2 Score 0.995 (Sensitivity: 0.68; Specificity: 0.97)
SMART Domains Protein: ENSMUSP00000125509
Gene: ENSMUSG00000033083
AA Change: V212E

DomainStartEndE-ValueType
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 damaging
Transcript: ENSMUST00000162617
AA Change: V212E

PolyPhen 2 Score 0.999 (Sensitivity: 0.14; Specificity: 0.99)
SMART Domains Protein: ENSMUSP00000124909
Gene: ENSMUSG00000033083
AA Change: V212E

DomainStartEndE-ValueType
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
  • 1x: 100.0%
  • 3x: 99.9%
  • 10x: 99.6%
  • 20x: 98.7%
Validation Efficiency 98% (48/49)
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: 48 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
Adprhl1 A G 8: 13,272,774 (GRCm39) V1328A probably benign Het
Akna T C 4: 63,313,034 (GRCm39) Y363C probably damaging Het
Aph1c A G 9: 66,740,549 (GRCm39) I59T possibly damaging Het
Bbs7 A T 3: 36,664,372 (GRCm39) F100I probably damaging Het
Cibar1 T C 4: 12,171,842 (GRCm39) H30R probably benign Het
Eef2k G A 7: 120,472,626 (GRCm39) R113Q probably damaging Het
Fam221b G A 4: 43,660,342 (GRCm39) R416C probably damaging Het
Fam98b C A 2: 117,080,302 (GRCm39) D18E probably damaging Het
Fat2 T A 11: 55,175,223 (GRCm39) Y1830F possibly damaging Het
Fbrsl1 T A 5: 110,526,861 (GRCm39) Q221L possibly damaging Het
Fbxo4 T C 15: 3,998,451 (GRCm39) R336G probably damaging Het
Fbxw15 A T 9: 109,384,778 (GRCm39) C341S probably benign Het
Fip1l1 T C 5: 74,748,813 (GRCm39) S398P probably damaging Het
Fsip2 A G 2: 82,806,951 (GRCm39) D1090G probably damaging Het
Fyb1 T A 15: 6,681,293 (GRCm39) M706K probably benign Het
Glg1 A T 8: 111,897,929 (GRCm39) F747I possibly damaging Het
Gm8257 A G 14: 44,887,623 (GRCm39) L254P probably benign Het
Hnf4g T C 3: 3,716,679 (GRCm39) Y283H possibly damaging Het
Irx6 C A 8: 93,403,642 (GRCm39) Y122* probably null Het
Jph4 C T 14: 55,347,213 (GRCm39) G445R possibly damaging Het
Kif16b G T 2: 142,554,819 (GRCm39) R660S possibly damaging Het
Kif21a C T 15: 90,819,964 (GRCm39) G1556D possibly damaging Het
Kif3a T A 11: 53,485,133 (GRCm39) Y531* probably null Het
Lrp2 T C 2: 69,319,673 (GRCm39) D1950G probably damaging Het
Med23 T G 10: 24,788,705 (GRCm39) S1371A probably benign Het
Mef2a T A 7: 66,917,875 (GRCm39) E112D probably benign Het
Mxra8 C G 4: 155,925,589 (GRCm39) Y99* probably null Het
Nbeal1 A G 1: 60,239,292 (GRCm39) T112A probably benign Het
Or8b49 G A 9: 38,505,840 (GRCm39) V108I probably benign Het
Pclo G A 5: 14,905,634 (GRCm39) E4955K unknown Het
Poc1b T C 10: 98,991,005 (GRCm39) probably null Het
Ptbp2 A G 3: 119,534,078 (GRCm39) Y264H probably damaging Het
Rhobtb2 A G 14: 70,034,070 (GRCm39) V385A probably benign Het
Rlf G A 4: 121,008,102 (GRCm39) P403S possibly damaging Het
Rnase9 T C 14: 51,276,537 (GRCm39) N147S probably benign Het
Serpinb9f A G 13: 33,518,603 (GRCm39) I368V probably benign Het
Slc1a1 A T 19: 28,878,848 (GRCm39) T196S probably benign Het
Smarca2 A G 19: 26,608,120 (GRCm39) S60G probably benign Het
Thap12 T A 7: 98,365,584 (GRCm39) I584N probably damaging Het
Ube3b T A 5: 114,530,199 (GRCm39) N195K possibly damaging Het
Upk3b T C 5: 136,067,982 (GRCm39) C58R probably damaging Het
Ush1c A G 7: 45,847,775 (GRCm39) probably null Het
Vmn1r60 T C 7: 5,547,876 (GRCm39) T75A Het
Vmn2r77 T A 7: 86,460,801 (GRCm39) L709H probably damaging Het
Wdcp T C 12: 4,901,850 (GRCm39) S569P probably damaging Het
Zfp418 A T 7: 7,184,658 (GRCm39) N207I probably benign Het
Zfp764l1 C T 7: 126,992,496 (GRCm39) C38Y probably null Het
Zfp808 G A 13: 62,319,521 (GRCm39) C250Y probably damaging Het
Other mutations in Tbc1d4
AlleleSourceChrCoordTypePredicted EffectPPH Score
IGL00087:Tbc1d4 APN 14 101,845,548 (GRCm39) missense probably damaging 1.00
IGL00864:Tbc1d4 APN 14 101,682,002 (GRCm39) missense probably benign 0.23
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
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
Predicted Primers PCR Primer
(F):5'- ATCCTCTCTGGGAAGCAAAC -3'
(R):5'- CGCCACTAAAATGAGGCCTTC -3'

Sequencing Primer
(F):5'- GGCTGTTGACTGTACCATCTGC -3'
(R):5'- GCCACTAAAATGAGGCCTTCAATTG -3'
Posted On 2020-07-13