Mutagenetix > Incidental Mutation

Incidental Mutation 'R9102:Gck'

691767

Institutional Source

Beutler Lab

Gene Symbol

Gck

Ensembl Gene

ENSMUSG00000041798

Gene Name

glucokinase

Synonyms

Gls006, hexokinase 4, HK4, MODY2, Hlb62

MMRRC Submission

068916-MU

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R9102 (G1)

Quality Score

225.009

Status

Validated

Chromosome

Chromosomal Location

5850820-5900081 bp(-) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

A to G at 5856516 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Tyrosine to Histidine at position 214 (Y214H)

Ref Sequence

ENSEMBL: ENSMUSP00000099984 (fasta)

Gene Model

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

AlphaFold

P52792

Predicted Effect

probably damaging
Transcript: ENSMUST00000102920
AA Change: Y214H

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

SMART Domains

Protein: ENSMUSP00000099984
Gene: ENSMUSG00000041798
AA Change: Y214H

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 damaging
Transcript: ENSMUST00000109822
AA Change: Y214H

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

SMART Domains

Protein: ENSMUSP00000105447
Gene: ENSMUSG00000041798
AA Change: Y214H

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: Y214H

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

SMART Domains

Protein: ENSMUSP00000105448
Gene: ENSMUSG00000041798
AA Change: Y214H

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

probably benign
Transcript: ENSMUST00000125434

SMART Domains

Protein: ENSMUSP00000123016
Gene: ENSMUSG00000041798

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

Meta Mutation Damage Score

0.8003

Coding Region Coverage

1x: 100.0%
3x: 100.0%
10x: 99.8%
20x: 99.3%

Validation Efficiency

97% (62/64)

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: 63 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Abcb9	T	C	5: 124,228,176 (GRCm39)	T22A	possibly damaging	Het
Adam33	T	C	2: 130,897,737 (GRCm39)	Q227R	probably benign	Het
Adgrb2	G	A	4: 129,912,802 (GRCm39)	G1276D	probably benign	Het
Adra1b	A	G	11: 43,667,056 (GRCm39)	S394P	possibly damaging	Het
Arap2	T	A	5: 62,906,341 (GRCm39)	H226L	probably benign	Het
Bckdk	A	G	7: 127,506,658 (GRCm39)	D297G	probably null	Het
Brwd1	T	C	16: 95,869,725 (GRCm39)	T101A	probably benign	Het
Ciita	A	G	16: 10,324,565 (GRCm39)	R166G	probably benign	Het
Cnksr1	A	G	4: 133,956,323 (GRCm39)	F587S	probably damaging	Het
Col4a1	A	T	8: 11,253,007 (GRCm39)	C1548S	possibly damaging	Het
Cxcl15	G	T	5: 90,949,154 (GRCm39)	M106I		Het
Dennd6a	T	C	14: 26,350,689 (GRCm39)	I598T	probably damaging	Het
Dlg5	G	A	14: 24,199,567 (GRCm39)	P1446S	probably damaging	Het
Dnah6	A	T	6: 73,044,469 (GRCm39)	I3214N	probably benign	Het
Dnmt3b	T	C	2: 153,518,703 (GRCm39)	V622A	probably damaging	Het
Fam170b	T	A	14: 32,557,404 (GRCm39)	S80T	probably damaging	Het
Fbxl13	G	T	5: 21,837,801 (GRCm39)	H45Q	probably benign	Het
Fbxo39	T	C	11: 72,208,316 (GRCm39)	F223L	possibly damaging	Het
Fndc3b	C	A	3: 27,523,014 (GRCm39)		probably null	Het
Gbp3	G	C	3: 142,273,586 (GRCm39)	V378L	probably benign	Het
Gc	C	T	5: 89,591,444 (GRCm39)	S98N	probably benign	Het
Gpr158	A	T	2: 21,830,078 (GRCm39)	S708C	probably damaging	Het
Hmcn1	A	T	1: 150,573,331 (GRCm39)	M2106K	probably benign	Het
Hoxd11	T	A	2: 74,513,274 (GRCm39)	Y180N	possibly damaging	Het
Hydin	A	G	8: 111,235,546 (GRCm39)	I1844V	probably benign	Het
Knl1	T	C	2: 118,917,973 (GRCm39)	I1777T	probably benign	Het
Krt33b	A	C	11: 99,915,846 (GRCm39)	L300R	probably damaging	Het
Madd	C	T	2: 90,988,404 (GRCm39)	A1208T	probably benign	Het
Meis2	T	A	2: 115,694,760 (GRCm39)	N461I	probably benign	Het
Mgat1	T	A	11: 49,152,165 (GRCm39)	V216E	probably damaging	Het
Nox4	G	A	7: 87,025,448 (GRCm39)	R525Q	probably benign	Het
Npc1l1	C	T	11: 6,164,684 (GRCm39)	V1122M	possibly damaging	Het
Nrsn1	A	G	13: 25,437,517 (GRCm39)	M137T	probably benign	Het
Nrxn3	T	C	12: 90,298,924 (GRCm39)	S1015P	probably benign	Het
Nudt22	T	A	19: 6,972,119 (GRCm39)	I166F	probably benign	Het
Or10d1b	A	C	9: 39,613,984 (GRCm39)	V27G	probably benign	Het
Or5j1	C	T	2: 86,879,171 (GRCm39)	M136I	possibly damaging	Het
Or6k4	A	T	1: 173,964,322 (GRCm39)	N4I		Het
Or6n2	T	A	1: 173,897,176 (GRCm39)	F104Y	probably damaging	Het
Or8b4	T	A	9: 37,829,992 (GRCm39)	I13N	probably damaging	Het
Or8g31-ps1	C	T	9: 39,276,388 (GRCm39)	P178S	unknown	Het
Pcdha4	T	A	18: 37,087,630 (GRCm39)	N604K	probably damaging	Het
Plxnc1	C	T	10: 94,663,107 (GRCm39)	V1181M	probably damaging	Het
Pms1	G	C	1: 53,307,021 (GRCm39)	H128Q	probably benign	Het
Prkar2b	G	A	12: 32,013,025 (GRCm39)	H364Y	probably benign	Het
Pus7	A	T	5: 23,957,380 (GRCm39)	I357K	possibly damaging	Het
Rsf1	GCGGC	GCGGCGGCGCCGGC	7: 97,229,138 (GRCm39)		probably benign	Het
Ryr3	T	C	2: 112,508,906 (GRCm39)		probably benign	Het
Siglec1	T	C	2: 130,915,389 (GRCm39)	I1401V	probably benign	Het
Slc6a6	G	T	6: 91,731,940 (GRCm39)	V590L	probably benign	Het
Slc9b1	C	T	3: 135,100,725 (GRCm39)	P490L	probably damaging	Het
Sprn	T	C	7: 139,733,278 (GRCm39)	D98G	possibly damaging	Het
Srrm4	T	C	5: 116,620,563 (GRCm39)	D55G	unknown	Het
Sugct	A	G	13: 17,497,833 (GRCm39)	V280A	probably benign	Het
Tbx6	A	G	7: 126,381,014 (GRCm39)	E83G	possibly damaging	Het
Tmem120a	T	C	5: 135,765,455 (GRCm39)	T209A	probably benign	Het
Top3a	T	C	11: 60,647,155 (GRCm39)	R255G	probably damaging	Het
Trav6-1	T	A	14: 52,876,008 (GRCm39)	F13I	probably benign	Het
Tsnaxip1	A	G	8: 106,568,622 (GRCm39)	E410G	probably benign	Het
Ubr5	A	G	15: 38,018,596 (GRCm39)	V842A		Het
Ubtf	A	G	11: 102,201,015 (GRCm39)		probably null	Het
Vwa3b	G	A	1: 37,174,593 (GRCm39)	M1I	probably null	Het
Zfp518b	T	C	5: 38,831,181 (GRCm39)	T275A	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
R7034:Gck	UTSW	11	5,851,747 (GRCm39)	missense	probably damaging	1.00
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
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'- ACAAGCCACATGAATGGTGC -3'
(R):5'- CTCCGAGATGCTATCAAGAGGAG -3'

Sequencing Primer
(F):5'- AGCCACATGAATGGTGCCATTTTG -3'
(R):5'- AGAGGGGTGAGCATAGCTTTGC -3'

Posted On

2021-12-30