Mutagenetix > Incidental Mutation

Incidental Mutation 'R7575:Tbc1d4'

586366

Institutional Source

Beutler Lab

Gene Symbol

Tbc1d4

Ensembl Gene

ENSMUSG00000033083

Gene Name

TBC1 domain family, member 4

Synonyms

AS160, 5930406J04Rik

MMRRC Submission

045632-MU

Accession Numbers

Essential gene?

Non essential (E-score: 0.000) question?

Stock #

R7575 (G1)

Quality Score

225.009

Status

Not validated

Chromosome

Chromosomal Location

101679796-101846627 bp(-) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

T to C at 101685025 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Lysine to Glutamic Acid at position 1209 (K1209E)

Ref Sequence

ENSEMBL: ENSMUSP00000124909 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000161991] [ENSMUST00000162617]

AlphaFold

no structure available at present

Predicted Effect

probably benign
Transcript: ENSMUST00000159951
AA Change: K859E

PolyPhen 2 Score 0.450 (Sensitivity: 0.89; Specificity: 0.90)

SMART Domains

Protein: ENSMUSP00000124511
Gene: ENSMUSG00000033083
AA Change: K859E

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

probably damaging
Transcript: ENSMUST00000161991
AA Change: K1146E

PolyPhen 2 Score 0.993 (Sensitivity: 0.70; Specificity: 0.97)

SMART Domains

Protein: ENSMUSP00000125509
Gene: ENSMUSG00000033083
AA Change: K1146E

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 damaging
Transcript: ENSMUST00000162617
AA Change: K1209E

PolyPhen 2 Score 0.999 (Sensitivity: 0.14; Specificity: 0.99)

SMART Domains

Protein: ENSMUSP00000124909
Gene: ENSMUSG00000033083
AA Change: K1209E

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

1x: 100.0%
3x: 99.9%
10x: 99.7%
20x: 99.0%

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: 91 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
3425401B19Rik	C	T	14: 32,384,589 (GRCm39)	V459I	probably benign	Het
4921539E11Rik	T	C	4: 103,088,192 (GRCm39)	D439G	probably damaging	Het
Adam18	T	C	8: 25,115,873 (GRCm39)	N607S	possibly damaging	Het
Adamtsl3	A	T	7: 82,223,756 (GRCm39)	N1179I	possibly damaging	Het
Adarb1	A	G	10: 77,139,129 (GRCm39)	F552S	probably damaging	Het
Ago1	T	C	4: 126,347,701 (GRCm39)	E394G	probably benign	Het
Alb	G	A	5: 90,613,788 (GRCm39)	C224Y	probably damaging	Het
Alms1	T	A	6: 85,599,141 (GRCm39)	H1322Q	possibly damaging	Het
Arhgef18	T	G	8: 3,501,635 (GRCm39)	V643G	probably damaging	Het
Asah2	T	C	19: 31,994,103 (GRCm39)	Q414R	probably benign	Het
Atpsckmt	C	T	15: 31,606,186 (GRCm39)	A48V	probably damaging	Het
Bbc3	G	A	7: 16,046,292 (GRCm39)	R76H	possibly damaging	Het
Bub1b	T	A	2: 118,471,639 (GRCm39)	S1000T	possibly damaging	Het
Bud23	A	T	5: 135,089,982 (GRCm39)	Y70*	probably null	Het
C1d	A	G	11: 17,212,694 (GRCm39)	E13G	probably damaging	Het
Camk1	T	A	6: 113,315,325 (GRCm39)	I158F	probably damaging	Het
Ccr2	A	C	9: 123,905,843 (GRCm39)	D41A	probably benign	Het
Cdh18	G	T	15: 23,400,683 (GRCm39)	E348*	probably null	Het
Col6a3	A	G	1: 90,738,321 (GRCm39)	L1066P	possibly damaging	Het
Cyp11b1	T	A	15: 74,711,162 (GRCm39)	D172V	probably benign	Het
Cyp2j8	A	G	4: 96,358,785 (GRCm39)	I378T	possibly damaging	Het
Cys1	T	A	12: 24,718,647 (GRCm39)	K69*	probably null	Het
Dip2c	A	G	13: 9,678,048 (GRCm39)	K1165E	probably damaging	Het
Drd3	A	T	16: 43,637,496 (GRCm39)	I232F	probably benign	Het
Dusp7	T	C	9: 106,250,876 (GRCm39)	C334R	probably damaging	Het
Eppk1	A	G	15: 75,995,442 (GRCm39)	S480P	not run	Het
Erc1	G	T	6: 119,801,721 (GRCm39)	P99T	possibly damaging	Het
Fam170b	C	T	14: 32,558,155 (GRCm39)	P330L	unknown	Het
Fasn	G	T	11: 120,703,513 (GRCm39)	T1573K	possibly damaging	Het
Fras1	A	T	5: 96,691,173 (GRCm39)	T130S	probably benign	Het
Fzd4	A	G	7: 89,056,918 (GRCm39)	I322V	possibly damaging	Het
Gbp10	G	A	5: 105,384,015 (GRCm39)		probably benign	Het
Gdpd4	A	T	7: 97,647,448 (GRCm39)	H365L	probably benign	Het
Gfy	A	G	7: 44,827,524 (GRCm39)	S191P	probably benign	Het
Ghr	A	T	15: 3,349,994 (GRCm39)	S395T	probably damaging	Het
Git2	C	T	5: 114,904,550 (GRCm39)	R123H	probably damaging	Het
Htt	A	G	5: 35,062,987 (GRCm39)	D2873G	probably damaging	Het
Idua	A	T	5: 108,829,565 (GRCm39)	D476V	probably damaging	Het
Inppl1	G	A	7: 101,477,689 (GRCm39)	R683W	probably damaging	Het
Ipp	T	C	4: 116,389,841 (GRCm39)	S466P	probably benign	Het
Iqgap2	A	G	13: 95,798,131 (GRCm39)	V1058A	probably damaging	Het
Jmy	A	T	13: 93,601,103 (GRCm39)	Y434*	probably null	Het
Kmt2d	CTGCTGCTG	CTGCTGCTGATGCTGCTG	15: 98,747,492 (GRCm39)		probably benign	Het
Mogs	T	G	6: 83,092,816 (GRCm39)	S85R	probably damaging	Het
Mroh2b	A	T	15: 4,964,087 (GRCm39)	D863V	probably damaging	Het
Mtmr10	A	T	7: 63,947,213 (GRCm39)	I43F	probably damaging	Het
Mtr	T	C	13: 12,213,963 (GRCm39)	D903G	probably benign	Het
Ncor1	A	G	11: 62,274,082 (GRCm39)	V186A	probably benign	Het
Notch3	C	T	17: 32,373,793 (GRCm39)	D472N	possibly damaging	Het
Or4k44	A	T	2: 111,368,597 (GRCm39)	F12L	probably damaging	Het
Or6c68	T	C	10: 129,157,728 (GRCm39)	F79L	probably damaging	Het
Or8j3c	A	G	2: 86,253,582 (GRCm39)	F146S	probably benign	Het
Or9i1	T	C	19: 13,839,381 (GRCm39)	S75P	probably damaging	Het
Oxr1	T	G	15: 41,686,758 (GRCm39)	L547V	possibly damaging	Het
Pappa2	A	T	1: 158,642,100 (GRCm39)	C1319S	probably damaging	Het
Papss1	A	C	3: 131,348,857 (GRCm39)	K623N	probably damaging	Het
Parp4	T	C	14: 56,875,375 (GRCm39)	F1198S	probably benign	Het
Pcare	T	A	17: 72,057,850 (GRCm39)	Q609L	probably damaging	Het
Pcnt	A	T	10: 76,225,086 (GRCm39)	V1806D	probably benign	Het
Pitx2	A	T	3: 129,009,375 (GRCm39)	H98L	probably damaging	Het
Polq	C	A	16: 36,911,496 (GRCm39)	D2410E	probably benign	Het
Prdm9	C	T	17: 15,764,890 (GRCm39)	C630Y	probably damaging	Het
Preb	A	T	5: 31,115,839 (GRCm39)	D201E	probably damaging	Het
Rasa3	A	T	8: 13,645,887 (GRCm39)	I151N	possibly damaging	Het
Rasgrp2	T	A	19: 6,454,397 (GRCm39)	S147T	probably damaging	Het
Rev3l	A	G	10: 39,697,441 (GRCm39)	D646G	possibly damaging	Het
Sdc1	A	G	12: 8,840,619 (GRCm39)	E128G	probably damaging	Het
Slamf7	A	C	1: 171,466,762 (GRCm39)	C148G	probably damaging	Het
Slc19a2	T	C	1: 164,084,691 (GRCm39)	S194P	probably damaging	Het
Spata31	C	T	13: 65,070,726 (GRCm39)	P958L	unknown	Het
Sprr2b	CTGAGCCTTGTCCTCCTCCAAAGTGCCCTGAGCCTTGTCCTCCCCCAGTATGCTGTGAGCCTTGTCCTCCTCCAAAGTGCCCTGAGCCTTGTCCTCCCCCAGTATGCTGTGAGCCTTGTCCTCC	CTGAGCCTTGTCCTCCTCCAAAGTGCCCTGAGCCTTGTCCTCCCCCAGTATGCTGTGAGCCTTGTCCTCC	3: 92,224,826 (GRCm39)		probably benign	Het
Stradb	A	G	1: 59,027,739 (GRCm39)	I90V	probably benign	Het
Tas2r134	A	G	2: 51,518,166 (GRCm39)	D215G	probably damaging	Het
Thbs1	A	G	2: 117,953,409 (GRCm39)	D942G	probably damaging	Het
Tmem107	C	T	11: 68,963,633 (GRCm39)	P139S	probably benign	Het
Tmem216	A	T	19: 10,529,266 (GRCm39)	M40K	probably benign	Het
Tpte	A	G	8: 22,845,498 (GRCm39)	Y516C	probably damaging	Het
Trim54	G	A	5: 31,291,431 (GRCm39)	G184D	possibly damaging	Het
Try5	A	T	6: 41,288,748 (GRCm39)	L157Q	probably benign	Het
Ubqlnl	G	A	7: 103,797,697 (GRCm39)	A600V	probably damaging	Het
Uhrf2	C	A	19: 30,048,768 (GRCm39)	P258Q	probably damaging	Het
Ush2a	A	T	1: 188,554,885 (GRCm39)	E3554D	possibly damaging	Het
Usp40	A	C	1: 87,877,682 (GRCm39)	L1158W	probably damaging	Het
Vmn1r121	T	A	7: 20,832,198 (GRCm39)	R81*	probably null	Het
Vmn1r203	C	A	13: 22,708,588 (GRCm39)	T123K	probably benign	Het
Vmn2r101	T	C	17: 19,831,654 (GRCm39)	V550A	probably benign	Het
Wdr49	A	T	3: 75,358,193 (GRCm39)	M184K	probably damaging	Het
Wipi2	A	G	5: 142,643,987 (GRCm39)	N123S	probably damaging	Het
Zbtb14	T	C	17: 69,694,442 (GRCm39)	F47L	probably damaging	Het
Zc3h7b	C	A	15: 81,662,086 (GRCm39)	S385*	probably null	Het
Zhx2	T	A	15: 57,686,658 (GRCm39)	F676I	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
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
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

Predicted Primers

PCR Primer
(F):5'- CCAAGGCTCTTCATCTTCAGTGG -3'
(R):5'- TCCATTAGCACTGGGAAGTAAACAG -3'

Sequencing Primer
(F):5'- AGGCTCTTCATCTTCAGTGGTTTAAC -3'
(R):5'- GCAGTATATACCACTTGTATCATGG -3'

Posted On

2019-10-24