Mutagenetix > Incidental Mutations

Incidental Mutation 'IGL00087:Tbc1d4'

940

Institutional Source

Australian Phenomics Network (link to record)

Gene Symbol

Tbc1d4

Ensembl Gene

ENSMUSG00000033083

Gene Name

TBC1 domain family, member 4

Synonyms

5930406J04Rik, AS160

Accession Numbers

Is this an essential gene?

Non essential (E-score: 0.000) question?

Stock #

IGL00087

Quality Score

Status

Chromosome

Chromosomal Location

101442360-101609191 bp(-) (GRCm38)

Type of Mutation

missense

DNA Base Change (assembly)

A to G at 101608112 bp

Zygosity

Heterozygous

Amino Acid Change

Phenylalanine to Leucine at position 117 (F117L)

Ref Sequence

ENSEMBL: ENSMUSP00000124909 (fasta)

Gene Model

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

Predicted Effect

possibly damaging
Transcript: ENSMUST00000100340
AA Change: F117L

PolyPhen 2 Score 0.654 (Sensitivity: 0.87; Specificity: 0.91)

SMART Domains

Protein: ENSMUSP00000097913
Gene: ENSMUSG00000033083
AA Change: F117L

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

noncoding transcript
Transcript: ENSMUST00000159668

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000160297

Predicted Effect

probably benign
Transcript: ENSMUST00000161991
AA Change: F117L

PolyPhen 2 Score 0.319 (Sensitivity: 0.90; Specificity: 0.89)

SMART Domains

Protein: ENSMUSP00000125509
Gene: ENSMUSG00000033083
AA Change: F117L

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: F117L

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)

SMART Domains

Protein: ENSMUSP00000124909
Gene: ENSMUSG00000033083
AA Change: F117L

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: 51 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
4930432M17Rik	C	A	3: 121,679,633		probably benign	Het
4930572O03Rik	C	A	5: 15,656,886		probably benign	Het
Actr2	C	A	11: 20,094,370	V79L	probably benign	Het
Ankrd36	A	C	11: 5,620,131	Y533S	probably benign	Het
Btnl1	A	T	17: 34,381,117	D198V	probably damaging	Het
Carmil2	T	A	8: 105,691,406	I684N	probably benign	Het
Ccdc129	T	A	6: 55,968,037	L581Q	possibly damaging	Het
Cdk17	T	A	10: 93,226,771	V257D	probably damaging	Het
Ctsj	T	G	13: 61,001,418	S271R	possibly damaging	Het
Cul9	T	A	17: 46,525,709	Q1130L	probably damaging	Het
Daam1	G	T	12: 71,942,219	S131I	unknown	Het
Dab1	G	A	4: 104,678,810	V139M	probably damaging	Het
Dab1	A	T	4: 104,678,753	I120F	possibly damaging	Het
Dnah2	A	G	11: 69,492,672	V1142A	possibly damaging	Het
Dsg1b	C	T	18: 20,396,476	T326I	probably damaging	Het
Eif3k	A	C	7: 28,974,676		probably benign	Het
Fam76b	T	C	9: 13,836,884	V3A	possibly damaging	Het
Fitm2	A	G	2: 163,469,792	V167A	probably benign	Het
Gfap	T	A	11: 102,888,718	I418F	possibly damaging	Het
Gm8857	C	T	5: 10,947,838		probably benign	Het
Grm5	T	C	7: 88,130,781	V1143A	probably benign	Het
Itpr2	A	G	6: 146,397,012	I317T	probably damaging	Het
Kcnn2	A	C	18: 45,592,236	R266S	probably damaging	Het
Kntc1	T	A	5: 123,790,159	S1240T	probably benign	Het
Lmnb2	T	C	10: 80,904,037	D490G	possibly damaging	Het
Muc4	G	A	16: 32,754,086	G1321R	probably benign	Het
Olfr401	A	T	11: 74,121,879	I197F	probably benign	Het
Pax9	A	G	12: 56,700,075	N232S	probably benign	Het
Pdcd6ip	A	G	9: 113,697,518	S108P	possibly damaging	Het
Pitpnc1	T	C	11: 107,212,643	E210G	possibly damaging	Het
Prdm10	T	C	9: 31,360,812		probably benign	Het
Prl4a1	G	A	13: 28,021,460	G136E	probably damaging	Het
Pstpip2	A	G	18: 77,874,294	S255G	probably benign	Het
Rimbp3	T	G	16: 17,209,743	S344A	probably benign	Het
Rint1	A	G	5: 23,794,431	T73A	probably benign	Het
Rnf145	T	C	11: 44,555,212	V291A	possibly damaging	Het
Rrm1	T	A	7: 102,454,507	L221*	probably null	Het
Scn11a	A	G	9: 119,770,506	L1114P	probably benign	Het
Slc44a4	A	G	17: 34,930,240		probably benign	Het
Sorl1	A	C	9: 41,974,094	N2070K	probably damaging	Het
Spaca7	C	T	8: 12,580,941		probably benign	Het
Srsf6	G	T	2: 162,931,707	V13F	probably damaging	Het
Stab1	G	T	14: 31,161,357	T336N	probably benign	Het
Strbp	A	G	2: 37,586,504		probably benign	Het
Tcf20	A	G	15: 82,854,895	V785A	probably damaging	Het
Ticrr	A	G	7: 79,677,283	K580E	probably damaging	Het
Ubr4	A	T	4: 139,465,322	E4225D	possibly damaging	Het
Uck1	A	T	2: 32,259,669	V66D	probably damaging	Het
Vmn2r25	A	G	6: 123,853,171	F7S	probably benign	Het
Zan	C	T	5: 137,387,820		probably null	Het
Zfp819	T	A	7: 43,611,979		probably benign	Het

Other mutations in Tbc1d4

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL00864:Tbc1d4	APN	14	101444566	missense	probably benign	0.23
IGL01065:Tbc1d4	APN	14	101449193	splice site	probably benign
IGL01144:Tbc1d4	APN	14	101444663	missense	probably damaging	0.99
IGL01153:Tbc1d4	APN	14	101608015	missense	possibly damaging	0.52
IGL01472:Tbc1d4	APN	14	101489864	nonsense	probably null
IGL02177:Tbc1d4	APN	14	101454939	missense	possibly damaging	0.90
IGL02259:Tbc1d4	APN	14	101465730	missense	probably damaging	1.00
IGL02938:Tbc1d4	APN	14	101501100	missense	probably damaging	1.00
IGL02975:Tbc1d4	APN	14	101458113	missense	probably damaging	1.00
R0396:Tbc1d4	UTSW	14	101458063	splice site	probably null
R0787:Tbc1d4	UTSW	14	101449209	missense	probably damaging	1.00
R0944:Tbc1d4	UTSW	14	101479220	splice site	probably benign
R1167:Tbc1d4	UTSW	14	101608019	missense	probably damaging	1.00
R1456:Tbc1d4	UTSW	14	101507106	missense	probably damaging	1.00
R1465:Tbc1d4	UTSW	14	101447688	missense	possibly damaging	0.87
R1465:Tbc1d4	UTSW	14	101447688	missense	possibly damaging	0.87
R1672:Tbc1d4	UTSW	14	101475215	missense	possibly damaging	0.92
R1762:Tbc1d4	UTSW	14	101507138	missense	possibly damaging	0.95
R2057:Tbc1d4	UTSW	14	101477155	missense	probably damaging	0.97
R2260:Tbc1d4	UTSW	14	101494411	missense	probably damaging	1.00
R2762:Tbc1d4	UTSW	14	101494361	missense	probably damaging	1.00
R3814:Tbc1d4	UTSW	14	101458755	missense	possibly damaging	0.94
R3983:Tbc1d4	UTSW	14	101507213	missense	probably benign	0.00
R4498:Tbc1d4	UTSW	14	101608336	missense	probably damaging	1.00
R4580:Tbc1d4	UTSW	14	101458783	missense	probably benign	0.00
R4664:Tbc1d4	UTSW	14	101462827	intron	probably benign
R4872:Tbc1d4	UTSW	14	101444708	missense	probably benign	0.06
R4940:Tbc1d4	UTSW	14	101507231	missense	probably benign	0.27
R4964:Tbc1d4	UTSW	14	101458174	missense	probably damaging	1.00
R4966:Tbc1d4	UTSW	14	101458174	missense	probably damaging	1.00
R5103:Tbc1d4	UTSW	14	101458882	nonsense	probably null
R5180:Tbc1d4	UTSW	14	101507572	missense	probably damaging	1.00
R5366:Tbc1d4	UTSW	14	101607976	missense	possibly damaging	0.67
R5673:Tbc1d4	UTSW	14	101455008	missense	probably damaging	1.00
R6057:Tbc1d4	UTSW	14	101489917	missense	probably damaging	0.99
R6180:Tbc1d4	UTSW	14	101458770	missense	probably benign	0.01
R6361:Tbc1d4	UTSW	14	101507174	missense	probably damaging	0.97
R6509:Tbc1d4	UTSW	14	101608318	missense	possibly damaging	0.92
R6791:Tbc1d4	UTSW	14	101608259	missense	probably damaging	0.98
R7001:Tbc1d4	UTSW	14	101458749	missense	probably benign	0.43
R7016:Tbc1d4	UTSW	14	101487441	missense	probably damaging	1.00
R7575:Tbc1d4	UTSW	14	101447589	missense	probably damaging	1.00
R7691:Tbc1d4	UTSW	14	101507641	missense	probably damaging	1.00
Z1088:Tbc1d4	UTSW	14	101452423	missense	probably damaging	1.00

Posted On

2011-07-12