Mutagenetix > Incidental Mutation

Incidental Mutation 'R4664:Tbc1d4'

353133

Institutional Source

Beutler Lab

Gene Symbol

Tbc1d4

Ensembl Gene

ENSMUSG00000033083

Gene Name

TBC1 domain family, member 4

Synonyms

AS160, 5930406J04Rik

MMRRC Submission

041922-MU

Accession Numbers

Essential gene?

Non essential (E-score: 0.000) question?

Stock #

R4664 (G1)

Quality Score

225

Status

Validated

Chromosome

Chromosomal Location

101679796-101846627 bp(-) (GRCm39)

Type of Mutation

intron

DNA Base Change (assembly)

A to G at 101700263 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Ref Sequence

ENSEMBL: ENSMUSP00000124909 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000100340] [ENSMUST00000162617] [ENSMUST00000161991]

AlphaFold

no structure available at present

Predicted Effect

probably benign
Transcript: ENSMUST00000100340

SMART Domains

Protein: ENSMUSP00000097913
Gene: ENSMUSG00000033083

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
Blast:TBC	773	834	3e-12	BLAST

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000159484

Predicted Effect

probably benign
Transcript: ENSMUST00000159664

SMART Domains

Protein: ENSMUSP00000124734
Gene: ENSMUSG00000033083

Domain	Start	End	E-Value	Type
SCOP:d1ddma_	2	48	1e-6	SMART
Blast:PTB	2	58	3e-35	BLAST

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000159668

Predicted Effect

probably benign
Transcript: ENSMUST00000159951

SMART Domains

Protein: ENSMUSP00000124511
Gene: ENSMUSG00000033083

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: ENSMUST00000160297

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000161304

Predicted Effect

probably benign
Transcript: ENSMUST00000162617

SMART Domains

Protein: ENSMUSP00000124909
Gene: ENSMUSG00000033083

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

Predicted Effect

probably benign
Transcript: ENSMUST00000161991

SMART Domains

Protein: ENSMUSP00000125509
Gene: ENSMUSG00000033083

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

Meta Mutation Damage Score

0.0898

Coding Region Coverage

1x: 99.2%
3x: 98.6%
10x: 97.2%
20x: 95.2%

Validation Efficiency

96% (110/115)

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: 106 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Ano2	A	G	6: 125,840,501 (GRCm39)	I391V	probably benign	Het
Apc	T	A	18: 34,431,647 (GRCm39)	L349M	probably damaging	Het
Atmin	A	G	8: 117,684,698 (GRCm39)	D786G	probably damaging	Het
Atp8a1	T	A	5: 67,919,929 (GRCm39)	D379V	possibly damaging	Het
Aurkb	A	G	11: 68,939,435 (GRCm39)	K173E	probably damaging	Het
Bak1	T	C	17: 27,241,510 (GRCm39)	I83V	possibly damaging	Het
Btbd17	A	C	11: 114,684,832 (GRCm39)	V69G	probably damaging	Het
Cacna1a	T	A	8: 85,328,396 (GRCm39)	Y1597*	probably null	Het
Camk2a	C	A	18: 61,088,696 (GRCm39)	Q167K	possibly damaging	Het
Capn1	A	T	19: 6,061,045 (GRCm39)	N253K	probably benign	Het
Ccer2	A	G	7: 28,455,928 (GRCm39)	E40G	probably benign	Het
Cdc42bpa	A	G	1: 179,972,130 (GRCm39)	T527A	probably damaging	Het
Cdkl2	T	C	5: 92,185,124 (GRCm39)	D89G	probably damaging	Het
Cep128	G	T	12: 91,263,027 (GRCm39)	R291S	probably damaging	Het
Cert1	T	C	13: 96,735,965 (GRCm39)	V175A	probably benign	Het
Chd4	A	G	6: 125,078,465 (GRCm39)	M203V	possibly damaging	Het
Chrna4	A	G	2: 180,679,286 (GRCm39)	S54P	probably damaging	Het
Cic	TGTTGCCCTC	T	7: 24,990,099 (GRCm39)		probably benign	Het
Cntn5	T	A	9: 10,144,214 (GRCm39)	I152L	possibly damaging	Het
Cntn6	A	G	6: 104,705,245 (GRCm39)	E154G	probably benign	Het
Col16a1	A	C	4: 129,955,883 (GRCm39)		probably benign	Het
Cpvl	C	T	6: 53,908,918 (GRCm39)	E282K	probably benign	Het
Cyth2	T	C	7: 45,460,143 (GRCm39)	D183G	probably damaging	Het
Ddx47	A	T	6: 134,989,319 (GRCm39)	T48S	possibly damaging	Het
Dgkk	A	G	X: 6,794,751 (GRCm39)	D685G	probably benign	Het
Dis3l	C	T	9: 64,238,080 (GRCm39)	S29N	unknown	Het
Dlg5	T	C	14: 24,187,249 (GRCm39)	H1834R	possibly damaging	Het
Dnah10	T	C	5: 124,905,536 (GRCm39)	M4060T	possibly damaging	Het
Dock3	T	A	9: 106,870,743 (GRCm39)	N557I	possibly damaging	Het
Dync2i1	T	C	12: 116,219,831 (GRCm39)	E37G	probably damaging	Het
Eprs1	A	T	1: 185,105,273 (GRCm39)		probably benign	Het
Faim2	C	A	15: 99,422,581 (GRCm39)		probably null	Het
Faim2	T	G	15: 99,422,582 (GRCm39)	S72R	probably benign	Het
Fanca	T	C	8: 123,995,711 (GRCm39)	T1364A	probably damaging	Het
Fance	T	C	17: 28,534,636 (GRCm39)		probably benign	Het
Farsb	A	T	1: 78,420,402 (GRCm39)	H496Q	possibly damaging	Het
Fryl	C	T	5: 73,248,022 (GRCm39)	E1032K	possibly damaging	Het
Galnt14	A	T	17: 73,814,808 (GRCm39)		probably benign	Het
Gba2	A	T	4: 43,568,619 (GRCm39)		probably benign	Het
Gjb4	C	A	4: 127,245,571 (GRCm39)	K123N	probably damaging	Het
Gmcl1	G	A	6: 86,709,980 (GRCm39)	T56I	probably benign	Het
Gtf2ird1	T	A	5: 134,412,756 (GRCm39)	E55V	probably damaging	Het
Gtpbp2	T	C	17: 46,472,080 (GRCm39)	V5A	probably benign	Het
Hnrnpr	A	G	4: 136,044,486 (GRCm39)		probably benign	Het
Homer3	G	A	8: 70,742,793 (GRCm39)		probably null	Het
Hsd3b3	T	C	3: 98,649,532 (GRCm39)	S264G	probably damaging	Het
Ints8	T	C	4: 11,227,152 (GRCm39)	M574V	probably benign	Het
Kif4-ps	G	A	12: 101,115,477 (GRCm39)		noncoding transcript	Het
Klhl14	A	T	18: 21,687,765 (GRCm39)	N552K	probably benign	Het
Klhl40	A	G	9: 121,609,799 (GRCm39)	E528G	probably damaging	Het
Lactb2	T	C	1: 13,717,624 (GRCm39)	E133G	probably damaging	Het
Lratd2	A	T	15: 60,695,478 (GRCm39)	D89E	probably benign	Het
Lrrtm2	T	C	18: 35,347,310 (GRCm39)		probably null	Het
Mab21l2	T	A	3: 86,454,811 (GRCm39)	Y63F	probably benign	Het
Mbd1	T	A	18: 74,402,597 (GRCm39)	I33N	possibly damaging	Het
Mertk	G	A	2: 128,643,132 (GRCm39)	V844M	probably benign	Het
Myh11	T	C	16: 14,044,448 (GRCm39)	T652A	possibly damaging	Het
Nlrp4a	C	A	7: 26,148,943 (GRCm39)	Y183*	probably null	Het
Noa1	T	A	5: 77,447,600 (GRCm39)	T558S	probably benign	Het
Nol11	A	T	11: 107,071,826 (GRCm39)	S256T	possibly damaging	Het
Nr1d1	G	T	11: 98,662,086 (GRCm39)	R183S	possibly damaging	Het
Nrg2	G	T	18: 36,185,948 (GRCm39)	Q264K	possibly damaging	Het
Nsd3	T	A	8: 26,188,894 (GRCm39)	F1027I	probably damaging	Het
Ntrk3	T	A	7: 78,110,847 (GRCm39)	I285F	probably damaging	Het
Obox8	T	C	7: 14,066,771 (GRCm39)	N91S	possibly damaging	Het
Oga	T	C	19: 45,760,384 (GRCm39)	E258G	probably benign	Het
Orc5	C	T	5: 22,751,520 (GRCm39)	S63N	probably benign	Het
Osbpl6	C	T	2: 76,398,552 (GRCm39)	T412I	probably benign	Het
P2ry14	C	T	3: 59,022,563 (GRCm39)	C308Y	probably damaging	Het
Pacsin1	T	C	17: 27,926,038 (GRCm39)	F127L	probably damaging	Het
Pex11b	T	C	3: 96,551,151 (GRCm39)	L198P	possibly damaging	Het
Pla2g4e	A	T	2: 120,001,669 (GRCm39)	V660E	probably damaging	Het
Plxna4	C	A	6: 32,493,885 (GRCm39)	V244F	possibly damaging	Het
Polr3b	A	G	10: 84,550,233 (GRCm39)	Y981C	probably damaging	Het
Popdc2	T	A	16: 38,194,649 (GRCm39)	S357T	probably damaging	Het
Prr29	A	G	11: 106,267,159 (GRCm39)	H58R	probably damaging	Het
Pyy	T	A	11: 101,998,178 (GRCm39)	M1L	possibly damaging	Het
Rasd2	T	C	8: 75,948,556 (GRCm39)	S161P	possibly damaging	Het
Ryr3	C	T	2: 112,826,900 (GRCm39)		probably benign	Het
Sectm1a	G	A	11: 120,960,552 (GRCm39)	R88C	possibly damaging	Het
Serpinb13	C	T	1: 106,910,574 (GRCm39)	S66L	probably damaging	Het
Siglecf	A	T	7: 43,005,837 (GRCm39)	I465F	possibly damaging	Het
Sorl1	A	T	9: 41,915,347 (GRCm39)	M1294K	probably damaging	Het
Spam1	A	T	6: 24,796,661 (GRCm39)	H204L	probably benign	Het
Sspo	A	T	6: 48,450,468 (GRCm39)	N2586Y	possibly damaging	Het
Tceanc2	A	T	4: 107,022,757 (GRCm39)	S77T	probably damaging	Het
Tedc2	A	G	17: 24,439,114 (GRCm39)		probably benign	Het
Tgm6	A	G	2: 129,979,314 (GRCm39)	D148G	probably benign	Het
Tgm6	A	T	2: 129,983,128 (GRCm39)	Q239L	probably benign	Het
Thsd7a	T	A	6: 12,337,313 (GRCm39)	T1235S	possibly damaging	Het
Thsd7a	T	A	6: 12,504,012 (GRCm39)	I381F	possibly damaging	Het
Tmc4	T	C	7: 3,674,270 (GRCm39)		probably null	Het
Tmem54	A	T	4: 129,004,704 (GRCm39)	E186D	possibly damaging	Het
Tpk1	A	T	6: 43,588,269 (GRCm39)	F32I	probably benign	Het
Trpc4ap	A	G	2: 155,514,917 (GRCm39)	I97T	probably benign	Het
Tut7	G	A	13: 59,948,413 (GRCm39)	T636I	possibly damaging	Het
Txlnb	A	G	10: 17,718,942 (GRCm39)	E591G	probably damaging	Het
Tyk2	C	T	9: 21,025,503 (GRCm39)	A741T	probably damaging	Het
Ubr4	G	A	4: 139,133,829 (GRCm39)	E742K	possibly damaging	Het
Uckl1	A	T	2: 181,216,661 (GRCm39)	S95T	possibly damaging	Het
Uevld	T	A	7: 46,587,734 (GRCm39)	D322V	probably damaging	Het
Ugt1a1	CAGAGAGAGAGAGA	CAGAGAGAGAGA	1: 88,139,706 (GRCm39)		probably benign	Het
Vmn1r238	G	T	18: 3,123,300 (GRCm39)	T38K	probably damaging	Het
Vps8	T	A	16: 21,262,938 (GRCm39)		probably null	Het
Wdr83	T	C	8: 85,806,680 (GRCm39)		probably benign	Het
Zfp619	A	G	7: 39,183,559 (GRCm39)	T51A	probably benign	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
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

Predicted Primers

PCR Primer
(F):5'- CAGGGATCTACATTCTTCGTTACTC -3'
(R):5'- TAGACAGGACTGAGCTGCTC -3'

Sequencing Primer
(F):5'- CTTCGTTACTCAAAAGGCTACTG -3'
(R):5'- CTTGTCTGGTGACGAGGACACAG -3'

Posted On

2015-10-08