Mutagenetix > Incidental Mutation

Incidental Mutation 'R7034:Gck'

546550

Institutional Source

Beutler Lab

Gene Symbol

Gck

Ensembl Gene

ENSMUSG00000041798

Gene Name

glucokinase

Synonyms

Gls006, hexokinase 4, HK4, MODY2, Hlb62

MMRRC Submission

045135-MU

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R7034 (G1)

Quality Score

225.009

Status

Not validated

Chromosome

Chromosomal Location

5850820-5900081 bp(-) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

A to G at 5851747 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Serine to Proline at position 441 (S441P)

Ref Sequence

ENSEMBL: ENSMUSP00000105448 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000102920] [ENSMUST00000102921] [ENSMUST00000109822] [ENSMUST00000109823]

AlphaFold

P52792

Predicted Effect

probably damaging
Transcript: ENSMUST00000102920
AA Change: S441P

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

SMART Domains

Protein: ENSMUSP00000099984
Gene: ENSMUSG00000041798
AA Change: S441P

Domain	Start	End	E-Value	Type
Pfam:Hexokinase_1	10	217	4.3e-80	PFAM
Pfam:Hexokinase_2	219	458	1.3e-100	PFAM

Predicted Effect

probably benign
Transcript: ENSMUST00000102921

SMART Domains

Protein: ENSMUSP00000099985
Gene: ENSMUSG00000020469

Domain	Start	End	E-Value	Type
low complexity region	4	21	N/A	INTRINSIC
EFh	36	64	1.02e-2	SMART
EFh	106	134	8.25e-3	SMART
Blast:EFh	142	170	9e-12	BLAST

Predicted Effect

probably damaging
Transcript: ENSMUST00000109822
AA Change: S441P

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

SMART Domains

Protein: ENSMUSP00000105447
Gene: ENSMUSG00000041798
AA Change: S441P

Domain	Start	End	E-Value	Type
Pfam:Hexokinase_1	10	217	1e-79	PFAM
Pfam:Hexokinase_2	219	458	7.8e-101	PFAM

Predicted Effect

probably damaging
Transcript: ENSMUST00000109823
AA Change: S441P

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

SMART Domains

Protein: ENSMUSP00000105448
Gene: ENSMUSG00000041798
AA Change: S441P

Domain	Start	End	E-Value	Type
Pfam:Hexokinase_1	15	216	1.9e-74	PFAM
Pfam:Hexokinase_2	221	455	2.2e-79	PFAM

Predicted Effect

SMART Domains

Protein: ENSMUSP00000123016
Gene: ENSMUSG00000041798
AA Change: S72P

Domain	Start	End	E-Value	Type
low complexity region	8	28	N/A	INTRINSIC
Pfam:Hexokinase_2	45	87	1.1e-8	PFAM

Coding Region Coverage

1x: 100.0%
3x: 100.0%
10x: 99.7%
20x: 99.1%

Validation Efficiency

MGI Phenotype

FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] Hexokinases phosphorylate glucose to produce glucose-6-phosphate, the first step in most glucose metabolism pathways. Alternative splicing of this gene results in three tissue-specific forms of glucokinase, one found in pancreatic islet beta cells and two found in liver. The protein localizes to the outer membrane of mitochondria. In contrast to other forms of hexokinase, this enzyme is not inhibited by its product glucose-6-phosphate but remains active while glucose is abundant. Mutations in this gene have been associated with non-insulin dependent diabetes mellitus (NIDDM), maturity onset diabetes of the young, type 2 (MODY2) and persistent hyperinsulinemic hypoglycemia of infancy (PHHI). [provided by RefSeq, Apr 2009]
PHENOTYPE: Targeted disruption of this gene causes mild hyperglycemia in heterozygous mice and extreme hyperglycemia and embryonic to postnatal lethality in homozygous mice. Hyperglycemic knock-out or ENU-induced mutants may show reduced body weight and liver glycogen level, hepatic steatosis, and glucosuria. [provided by MGI curators]

Allele List at MGI

Other mutations in this stock

Total: 84 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
1700017N19Rik	T	A	10: 100,445,118 (GRCm39)		probably null	Het
Adamts1	T	A	16: 85,599,634 (GRCm39)		probably benign	Het
Aff4	A	G	11: 53,299,236 (GRCm39)	K979E	probably damaging	Het
Aftph	A	T	11: 20,642,498 (GRCm39)	M845K	probably damaging	Het
Akt2	T	C	7: 27,336,437 (GRCm39)		probably null	Het
Aldh1a7	A	T	19: 20,685,542 (GRCm39)	L336Q	possibly damaging	Het
Ank3	C	T	10: 69,835,209 (GRCm39)	T680M	probably damaging	Het
Apeh	T	C	9: 107,971,470 (GRCm39)	E59G	possibly damaging	Het
Armc8	C	T	9: 99,366,018 (GRCm39)		probably null	Het
Armh3	A	G	19: 45,953,688 (GRCm39)	I195T	probably damaging	Het
Atp2b1	C	T	10: 98,823,172 (GRCm39)	T244I	probably damaging	Het
Btaf1	C	A	19: 36,981,869 (GRCm39)	T1633K	probably benign	Het
Cacng8	A	G	7: 3,463,819 (GRCm39)	S324G	probably benign	Het
Calcr	T	A	6: 3,692,543 (GRCm39)	Q400L	probably damaging	Het
Caprin2	G	A	6: 148,749,703 (GRCm39)	P536S	possibly damaging	Het
Ccdc54	A	T	16: 50,410,951 (GRCm39)	M105K	probably benign	Het
Ccna1	T	C	3: 54,953,460 (GRCm39)	E381G	possibly damaging	Het
Cd2ap	A	T	17: 43,109,490 (GRCm39)	L623Q	probably damaging	Het
Cdkl3	A	G	11: 51,918,042 (GRCm39)	E415G	probably benign	Het
Chd5	C	A	4: 152,445,398 (GRCm39)	L430I	possibly damaging	Het
Clspn	G	A	4: 126,474,775 (GRCm39)	E975K	possibly damaging	Het
Cobl	C	A	11: 12,204,177 (GRCm39)	V835F	probably damaging	Het
D430041D05Rik	C	A	2: 104,022,883 (GRCm39)	R1037L	probably damaging	Het
Derl1	A	G	15: 57,742,443 (GRCm39)		probably null	Het
Dhrs9	T	G	2: 69,223,520 (GRCm39)	N89K	probably benign	Het
Erich1	A	G	8: 14,114,330 (GRCm39)	I60T	probably benign	Het
Fam184a	A	T	10: 53,570,910 (GRCm39)	S408T	possibly damaging	Het
Fcgr4	T	A	1: 170,847,657 (GRCm39)	M85K	probably benign	Het
Foxj3	A	G	4: 119,476,497 (GRCm39)	E259G	probably damaging	Het
Galnt11	T	C	5: 25,463,811 (GRCm39)	I361T	probably damaging	Het
Gdap1l1	G	T	2: 163,288,065 (GRCm39)	V98F	probably damaging	Het
Gramd1a	A	G	7: 30,832,181 (GRCm39)		probably null	Het
H2ac21	C	T	3: 96,127,304 (GRCm39)	Q25*	probably null	Het
Herc3	A	T	6: 58,853,840 (GRCm39)	M629L	probably benign	Het
Hoxc12	G	A	15: 102,846,795 (GRCm39)	G229D	probably damaging	Het
Hycc2	T	A	1: 58,574,696 (GRCm39)	M282L	probably benign	Het
Itga9	T	C	9: 118,527,433 (GRCm39)	L528P	probably benign	Het
Krt39	A	C	11: 99,412,062 (GRCm39)	V8G	probably benign	Het
Krt71	A	G	15: 101,646,772 (GRCm39)	I312T	probably benign	Het
Lrrc37	T	A	11: 103,506,638 (GRCm39)		probably benign	Het
Mllt11	A	G	3: 95,127,744 (GRCm39)	Y9H	probably damaging	Het
Mrgpra3	G	T	7: 47,239,838 (GRCm39)	N29K	possibly damaging	Het
Mug1	A	G	6: 121,850,603 (GRCm39)	T700A	probably benign	Het
Myl1	T	C	1: 66,969,395 (GRCm39)	N79S	probably damaging	Het
Myo18b	G	A	5: 112,871,770 (GRCm39)	Q2104*	probably null	Het
Nalf1	G	A	8: 9,820,589 (GRCm39)	P144S	possibly damaging	Het
Ndufs2	T	C	1: 171,065,877 (GRCm39)	D256G	probably benign	Het
Nek5	T	C	8: 22,597,739 (GRCm39)	N280S	probably benign	Het
Nwd2	A	T	5: 63,962,258 (GRCm39)	N614I	probably damaging	Het
Or6c88	G	A	10: 129,406,941 (GRCm39)	C139Y	possibly damaging	Het
Parp1	G	T	1: 180,425,817 (GRCm39)	K849N	possibly damaging	Het
Pcnx2	T	C	8: 126,512,041 (GRCm39)	T1422A	probably damaging	Het
Plce1	A	G	19: 38,727,801 (GRCm39)	N1520S	probably damaging	Het
Ppcdc	T	C	9: 57,322,453 (GRCm39)	T149A	probably damaging	Het
Ppl	A	G	16: 4,905,366 (GRCm39)	V1643A	probably benign	Het
Pramel23	A	T	4: 143,423,898 (GRCm39)	I297N	probably damaging	Het
Prrx1	T	A	1: 163,075,907 (GRCm39)	M220L	probably benign	Het
Pspc1	A	C	14: 56,996,085 (GRCm39)		probably null	Het
Ptpn20	A	G	14: 33,336,392 (GRCm39)	*44W	probably null	Het
Qars1	T	A	9: 108,391,976 (GRCm39)	V83E	probably damaging	Het
Rbm33	T	C	5: 28,599,496 (GRCm39)	M956T	unknown	Het
Sash1	C	A	10: 8,605,847 (GRCm39)	E848*	probably null	Het
Scai	T	A	2: 39,011,147 (GRCm39)	Y163F	probably damaging	Het
Serpinf2	A	T	11: 75,329,244 (GRCm39)		probably benign	Het
Sgo2b	T	A	8: 64,379,868 (GRCm39)	H988L	probably benign	Het
Sh2b2	G	A	5: 136,247,739 (GRCm39)	T604I	probably benign	Het
Skint4	A	T	4: 112,015,281 (GRCm39)	I449F	possibly damaging	Het
Slc30a2	A	G	4: 134,074,653 (GRCm39)	I88V	possibly damaging	Het
Smug1	A	G	15: 103,064,369 (GRCm39)	L184P	probably damaging	Het
Spatc1	A	G	15: 76,168,080 (GRCm39)	T180A	probably benign	Het
Ssr1	A	T	13: 38,178,001 (GRCm39)	L20Q	probably null	Het
Supt4a	A	G	11: 87,634,084 (GRCm39)	E100G	probably damaging	Het
Teddm2	T	C	1: 153,726,320 (GRCm39)	I132V	probably benign	Het
Tmem131	C	T	1: 36,832,054 (GRCm39)	G1861E	possibly damaging	Het
Tpr	A	T	1: 150,299,358 (GRCm39)	H1186L	probably benign	Het
Trim34b	A	T	7: 103,978,743 (GRCm39)		probably benign	Het
Trpm2	T	C	10: 77,748,426 (GRCm39)	M1415V	probably benign	Het
Ttll12	A	G	15: 83,471,086 (GRCm39)	F264S	probably benign	Het
Vmn2r59	T	C	7: 41,695,644 (GRCm39)	E256G	probably benign	Het
Vmn2r93	A	T	17: 18,546,672 (GRCm39)	H848L	probably benign	Het
Vps35l	T	C	7: 118,372,315 (GRCm39)	S290P	probably damaging	Het
Wdfy3	G	A	5: 102,055,384 (GRCm39)	T1562I	probably damaging	Het
Ybey	T	C	10: 76,304,197 (GRCm39)	S2G	possibly damaging	Het
Zfp346	A	T	13: 55,280,200 (GRCm39)	Q308L	probably benign	Het

Other mutations in Gck

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL01624:Gck	APN	11	5,853,106 (GRCm39)	missense	possibly damaging	0.67
IGL01647:Gck	APN	11	5,854,472 (GRCm39)	missense	probably damaging	0.97
IGL03145:Gck	APN	11	5,859,093 (GRCm39)	missense	probably damaging	0.99
Grahamcracker	UTSW	11	5,852,165 (GRCm39)	missense	probably damaging	1.00
Tootsie	UTSW	11	5,859,150 (GRCm39)	missense	possibly damaging	0.63
R0139:Gck	UTSW	11	5,860,370 (GRCm39)	missense	probably damaging	1.00
R0139:Gck	UTSW	11	5,859,139 (GRCm39)	nonsense	probably null
R0691:Gck	UTSW	11	5,856,691 (GRCm39)	missense	probably damaging	1.00
R1829:Gck	UTSW	11	5,860,984 (GRCm39)	missense	probably damaging	0.97
R1866:Gck	UTSW	11	5,853,253 (GRCm39)	missense	probably benign	0.02
R1868:Gck	UTSW	11	5,852,165 (GRCm39)	missense	probably damaging	1.00
R1992:Gck	UTSW	11	5,856,515 (GRCm39)	missense	probably damaging	1.00
R3885:Gck	UTSW	11	5,860,318 (GRCm39)	missense	probably damaging	1.00
R4179:Gck	UTSW	11	5,860,295 (GRCm39)	missense	probably benign	0.43
R4888:Gck	UTSW	11	5,859,150 (GRCm39)	missense	possibly damaging	0.63
R7155:Gck	UTSW	11	5,899,705 (GRCm39)	start gained	probably benign
R7548:Gck	UTSW	11	5,852,040 (GRCm39)	missense
R8039:Gck	UTSW	11	5,860,301 (GRCm39)	missense	probably benign	0.12
R8891:Gck	UTSW	11	5,851,733 (GRCm39)	missense	probably damaging	1.00
R9100:Gck	UTSW	11	5,856,516 (GRCm39)	missense	probably damaging	1.00
R9101:Gck	UTSW	11	5,856,516 (GRCm39)	missense	probably damaging	1.00
R9102:Gck	UTSW	11	5,856,516 (GRCm39)	missense	probably damaging	1.00
R9116:Gck	UTSW	11	5,854,377 (GRCm39)	missense	possibly damaging	0.71
R9370:Gck	UTSW	11	5,852,244 (GRCm39)	missense	possibly damaging	0.78
R9420:Gck	UTSW	11	5,899,553 (GRCm39)	critical splice donor site	probably null
R9536:Gck	UTSW	11	5,852,307 (GRCm39)	missense	possibly damaging	0.92
Z1176:Gck	UTSW	11	5,856,526 (GRCm39)	missense	probably damaging	1.00
Z1177:Gck	UTSW	11	5,860,958 (GRCm39)	missense	possibly damaging	0.81

Predicted Primers

PCR Primer
(F):5'- CAGCAGAATAGGTCTCCTGC -3'
(R):5'- ATTCTCCCTGGGCCTGGAATAC -3'

Sequencing Primer
(F):5'- AGAATAGGTCTCCTGCCCTAGTG -3'
(R):5'- ACTGAATATATACTGCAGTCTGGGG -3'

Posted On

2019-05-13