Mutagenetix > Incidental Mutation

Incidental Mutation 'R8891:Gck'

677702

Institutional Source

Beutler Lab

Gene Symbol

Gck

Ensembl Gene

ENSMUSG00000041798

Gene Name

glucokinase

Synonyms

Gls006, hexokinase 4, HK4, MODY2, Hlb62

MMRRC Submission

068753-MU

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R8891 (G1)

Quality Score

225.009

Status

Not validated

Chromosome

Chromosomal Location

5850820-5900081 bp(-) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

G to T at 5851733 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Serine to Arginine at position 445 (S445R)

Ref Sequence

ENSEMBL: ENSMUSP00000099984 (fasta)

Gene Model

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

AlphaFold

P52792

Predicted Effect

probably damaging
Transcript: ENSMUST00000102920
AA Change: S445R

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

SMART Domains

Protein: ENSMUSP00000099984
Gene: ENSMUSG00000041798
AA Change: S445R

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: S445R

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

SMART Domains

Protein: ENSMUSP00000105447
Gene: ENSMUSG00000041798
AA Change: S445R

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: S445R

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

SMART Domains

Protein: ENSMUSP00000105448
Gene: ENSMUSG00000041798
AA Change: S445R

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: S76R

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: 99.8%
20x: 99.4%

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: 62 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
1110002E22Rik	A	T	3: 137,772,520 (GRCm39)	K570*	probably null	Het
Abi1	T	C	2: 22,861,262 (GRCm39)	I99V	probably damaging	Het
Abtb3	G	A	10: 85,223,958 (GRCm39)	G256R	unknown	Het
Adgrg7	T	A	16: 56,572,762 (GRCm39)	E351D	probably benign	Het
Ankrd34c	T	G	9: 89,612,143 (GRCm39)	K66T	probably damaging	Het
Asap2	C	T	12: 21,162,144 (GRCm39)	R34W	probably damaging	Het
Atr	A	G	9: 95,787,813 (GRCm39)	T1469A	probably benign	Het
Ccdc168	T	C	1: 44,096,284 (GRCm39)	I1605V	probably benign	Het
Celsr1	G	T	15: 85,822,194 (GRCm39)	R1708S	probably benign	Het
Chmp2a	T	A	7: 12,767,840 (GRCm39)	E28D	probably benign	Het
Cldn24	A	T	8: 48,275,281 (GRCm39)	N35I	probably benign	Het
Coa6	G	C	8: 127,149,570 (GRCm39)		probably null	Het
Copa	C	T	1: 171,946,818 (GRCm39)	R1009C	probably damaging	Het
Crybb2	G	A	5: 113,209,913 (GRCm39)	T150M	possibly damaging	Het
Ctnnd2	A	T	15: 30,620,076 (GRCm39)	T143S	probably benign	Het
Eid3	A	G	10: 82,702,992 (GRCm39)	N151S	probably damaging	Het
Fbxo17	G	T	7: 28,434,733 (GRCm39)	V173L	possibly damaging	Het
Fmn2	CCCTCCTCTCCCTGGAATGGGAATACCTCCCCCACCTCCTCTCCCTGGAATGGGAATACCTCCCCCACCTCCTCTCCCTGGAATGGGAATATCTCCCCTACCTCCTCTCCCTGGAATGGGAATACCTCC	CCCTCCTCTCCCTGGAATGGGAATACCTCCCCCACCTCCTCTCCCTGGAATGGGAATATCTCCCCTACCTCCTCTCCCTGGAATGGGAATACCTCC	1: 174,436,769 (GRCm39)		probably benign	Het
Galntl6	T	C	8: 58,415,433 (GRCm39)	N240S	probably damaging	Het
Gm5114	C	A	7: 39,057,718 (GRCm39)	V634F	probably benign	Het
Gnat2	G	A	3: 108,005,634 (GRCm39)	D200N		Het
H13	A	G	2: 152,546,049 (GRCm39)	N390S	probably benign	Het
Helz	T	A	11: 107,552,842 (GRCm39)	M1206K	probably damaging	Het
Itpr3	G	A	17: 27,337,651 (GRCm39)		probably benign	Het
Kank1	G	A	19: 25,387,439 (GRCm39)	G371R	probably benign	Het
Kif13b	A	G	14: 64,982,326 (GRCm39)	T513A	probably damaging	Het
L3mbtl4	T	C	17: 68,762,781 (GRCm39)	S105P	possibly damaging	Het
Lpo	T	A	11: 87,697,848 (GRCm39)	E653V	probably benign	Het
Lyst	A	G	13: 13,887,435 (GRCm39)	D3088G	possibly damaging	Het
Man2b1	C	A	8: 85,811,084 (GRCm39)	H72N	probably damaging	Het
Mast3	A	T	8: 71,233,801 (GRCm39)	H981Q	probably damaging	Het
Meioc	T	A	11: 102,559,246 (GRCm39)	I56N	probably benign	Het
Mul1	A	C	4: 138,162,164 (GRCm39)	K32Q	probably benign	Het
Oas1c	C	T	5: 120,946,126 (GRCm39)	S124N	probably benign	Het
Omg	T	A	11: 79,393,829 (GRCm39)	K10*	probably null	Het
Or2a52	A	G	6: 43,144,750 (GRCm39)	I253V	probably benign	Het
Or4k52	A	T	2: 111,611,186 (GRCm39)	I174F	probably damaging	Het
Or6c88	A	G	10: 129,407,046 (GRCm39)	H174R	probably damaging	Het
Pcdhb14	T	A	18: 37,582,692 (GRCm39)	N599K	probably damaging	Het
Pcdhb18	C	A	18: 37,623,700 (GRCm39)	N343K	probably damaging	Het
Phf7	C	A	14: 30,971,613 (GRCm39)		probably benign	Het
Pramel15	C	T	4: 144,099,397 (GRCm39)	C456Y	probably damaging	Het
Qdpr	T	C	5: 45,604,982 (GRCm39)	N42S	probably damaging	Het
Rbm44	T	A	1: 91,090,136 (GRCm39)	D716E	probably benign	Het
Rprd2	A	C	3: 95,671,367 (GRCm39)	H1345Q	possibly damaging	Het
Rsf1	G	GACGGCGGCT	7: 97,229,116 (GRCm39)		probably benign	Het
Ryr2	G	A	13: 11,814,768 (GRCm39)	A668V	probably damaging	Het
Sag	T	A	1: 87,759,683 (GRCm39)	L307Q	probably damaging	Het
Sash1	G	A	10: 8,603,734 (GRCm39)	P1106L	probably damaging	Het
Sec16b	T	A	1: 157,382,409 (GRCm39)	I615N	probably damaging	Het
Sfi1	A	ATCTTCCCAAAGCCAGTGC	11: 3,103,384 (GRCm39)		probably benign	Het
Slco1b2	T	C	6: 141,628,993 (GRCm39)	V600A	probably benign	Het
Sucnr1	A	G	3: 59,994,263 (GRCm39)	T264A	probably benign	Het
Tbx3	A	G	5: 119,809,983 (GRCm39)		probably benign	Het
Tigd5	T	C	15: 75,783,069 (GRCm39)	V477A	possibly damaging	Het
Tle7	T	A	8: 110,836,763 (GRCm39)	S216R	possibly damaging	Het
Ttc17	G	A	2: 94,192,764 (GRCm39)	A89V	probably damaging	Het
Twsg1	A	G	17: 66,255,657 (GRCm39)	I39T		Het
Zfp184	T	C	13: 22,143,512 (GRCm39)	F406S	probably damaging	Het
Zfp429	A	T	13: 67,538,830 (GRCm39)	C205S	probably damaging	Het
Zfp59	T	A	7: 27,554,313 (GRCm39)	D588E	probably benign	Het
Zfp64	A	T	2: 168,797,083 (GRCm39)	M1K	probably null	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
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'- CATTTTCCAGGGGTAGCAGC -3'
(R):5'- GGCCTGGAATACTGAATATATACTGC -3'

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

Posted On

2021-08-02