Mutagenetix > Incidental Mutation

Incidental Mutation 'IGL01144:Tbc1d4'

52733

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) question?

Stock #

IGL01144

Quality Score

Status

Chromosome

Chromosomal Location

101679796-101846627 bp(-) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

A to T at 101682099 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Tyrosine to Asparagine at position 1266 (Y1266N)

Ref Sequence

ENSEMBL: ENSMUSP00000124909 (fasta)

Gene Model

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

AlphaFold

no structure available at present

Predicted Effect

unknown
Transcript: ENSMUST00000159951
AA Change: Y916N

SMART Domains

Protein: ENSMUSP00000124511
Gene: ENSMUSG00000033083
AA Change: Y916N

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 damaging
Transcript: ENSMUST00000161991
AA Change: Y1203N

PolyPhen 2 Score 0.988 (Sensitivity: 0.73; Specificity: 0.96)

SMART Domains

Protein: ENSMUSP00000125509
Gene: ENSMUSG00000033083
AA Change: Y1203N

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: Y1266N

PolyPhen 2 Score 0.994 (Sensitivity: 0.69; Specificity: 0.97)

SMART Domains

Protein: ENSMUSP00000124909
Gene: ENSMUSG00000033083
AA Change: Y1266N

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: 19 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Cox19	T	C	5: 139,330,881 (GRCm39)	K10E	probably damaging	Het
Ddx21	T	A	10: 62,434,329 (GRCm39)	K143N	unknown	Het
Dnajb13	T	C	7: 100,152,431 (GRCm39)	D295G	possibly damaging	Het
Gm14496	A	G	2: 181,636,814 (GRCm39)	N91D	probably damaging	Het
Kidins220	T	C	12: 25,060,925 (GRCm39)	I801T	probably damaging	Het
Nexmif	A	G	X: 103,127,559 (GRCm39)	S1453P	possibly damaging	Het
Nobox	A	G	6: 43,280,935 (GRCm39)	V513A	possibly damaging	Het
Phactr1	G	A	13: 43,191,000 (GRCm39)	D157N	possibly damaging	Het
Plod1	G	T	4: 148,017,211 (GRCm39)	Q49K	probably benign	Het
Ppp1r10	C	T	17: 36,237,456 (GRCm39)	R209C	probably benign	Het
Prr12	T	C	7: 44,696,882 (GRCm39)	E1011G	unknown	Het
Rab27a	G	A	9: 72,982,850 (GRCm39)		probably null	Het
Rbbp6	T	A	7: 122,575,169 (GRCm39)	D59E	possibly damaging	Het
Sbf2	G	T	7: 109,929,110 (GRCm39)	T1432K	probably damaging	Het
Sorbs3	A	C	14: 70,429,017 (GRCm39)	S383A	probably benign	Het
Spta1	T	A	1: 174,014,829 (GRCm39)	D436E	probably benign	Het
Ttn	A	T	2: 76,551,173 (GRCm39)	Y29660*	probably null	Het
Ubr2	A	G	17: 47,268,247 (GRCm39)	I989T	probably damaging	Het
Zkscan14	G	T	5: 145,132,806 (GRCm39)	R242S	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
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

2013-06-21