Mutagenetix > Incidental Mutations

Incidental Mutation 'R8031:Hk1'

617960

Institutional Source

Beutler Lab

Gene Symbol

Hk1

Ensembl Gene

ENSMUSG00000037012

Gene Name

hexokinase 1

Synonyms

mHk1-s, Hk-1, Hk1-s

MMRRC Submission

Accession Numbers

Is this an essential gene?

Possibly essential (E-score: 0.529) question?

Stock #

R8031 (G1)

Quality Score

225.009

Status

Validated

Chromosome

Chromosomal Location

62268855-62379908 bp(-) (GRCm38)

Type of Mutation

missense

DNA Base Change (assembly)

T to A at 62296699 bp (GRCm38)

Zygosity

Heterozygous

Amino Acid Change

Asparagine to Isoleucine at position 190 (N190I)

Ref Sequence

ENSEMBL: ENSMUSP00000097282 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000072357] [ENSMUST00000099691] [ENSMUST00000116238] [ENSMUST00000130422] [ENSMUST00000139228] [ENSMUST00000143179] [ENSMUST00000152761]

AlphaFold

no structure available at present

Predicted Effect

probably benign
Transcript: ENSMUST00000072357
AA Change: N194I

PolyPhen 2 Score 0.205 (Sensitivity: 0.92; Specificity: 0.88)

SMART Domains

Protein: ENSMUSP00000072195
Gene: ENSMUSG00000037012
AA Change: N194I

Domain	Start	End	E-Value	Type
Pfam:Hexokinase_1	25	224	1.2e-70	PFAM
Pfam:Hexokinase_2	229	486	8e-79	PFAM
Pfam:Hexokinase_1	496	695	7e-76	PFAM
Pfam:Hexokinase_2	700	934	4.2e-85	PFAM

Predicted Effect

probably benign
Transcript: ENSMUST00000099691
AA Change: N190I

PolyPhen 2 Score 0.149 (Sensitivity: 0.92; Specificity: 0.87)

SMART Domains

Protein: ENSMUSP00000097282
Gene: ENSMUSG00000037012
AA Change: N190I

Domain	Start	End	E-Value	Type
Pfam:Hexokinase_1	16	221	1.9e-86	PFAM
Pfam:Hexokinase_2	223	462	1e-102	PFAM
Pfam:Hexokinase_1	464	669	1.1e-90	PFAM
Pfam:Hexokinase_2	671	910	2.2e-109	PFAM

Predicted Effect

probably benign
Transcript: ENSMUST00000116238
AA Change: N194I

PolyPhen 2 Score 0.205 (Sensitivity: 0.92; Specificity: 0.88)

SMART Domains

Protein: ENSMUSP00000111946
Gene: ENSMUSG00000037012
AA Change: N194I

Domain	Start	End	E-Value	Type
Pfam:Hexokinase_1	21	225	1.3e-85	PFAM
Pfam:Hexokinase_2	227	357	3.6e-56	PFAM
Pfam:Hexokinase_2	362	489	9.3e-41	PFAM
Pfam:Hexokinase_1	491	696	2e-90	PFAM
Pfam:Hexokinase_2	698	937	3.8e-109	PFAM

Predicted Effect

probably benign
Transcript: ENSMUST00000130422
AA Change: N189I

PolyPhen 2 Score 0.263 (Sensitivity: 0.91; Specificity: 0.88)

SMART Domains

Protein: ENSMUSP00000118601
Gene: ENSMUSG00000037012
AA Change: N189I

Domain	Start	End	E-Value	Type
Pfam:Hexokinase_1	16	220	1.4e-85	PFAM
Pfam:Hexokinase_2	222	461	1e-102	PFAM
Pfam:Hexokinase_1	463	668	1.1e-90	PFAM
Pfam:Hexokinase_2	670	909	2.2e-109	PFAM

Predicted Effect

probably benign
Transcript: ENSMUST00000139228
AA Change: N176I

PolyPhen 2 Score 0.059 (Sensitivity: 0.94; Specificity: 0.84)

SMART Domains

Protein: ENSMUSP00000118166
Gene: ENSMUSG00000037012
AA Change: N176I

Domain	Start	End	E-Value	Type
Pfam:Hexokinase_1	3	184	1.4e-74	PFAM

Predicted Effect

probably benign
Transcript: ENSMUST00000143179

SMART Domains

Protein: ENSMUSP00000120151
Gene: ENSMUSG00000037012

Domain	Start	End	E-Value	Type
Pfam:Hexokinase_1	5	80	5e-29	PFAM

Predicted Effect

probably benign
Transcript: ENSMUST00000152761
AA Change: N174I

PolyPhen 2 Score 0.095 (Sensitivity: 0.93; Specificity: 0.85)

SMART Domains

Protein: ENSMUSP00000117752
Gene: ENSMUSG00000037012
AA Change: N174I

Domain	Start	End	E-Value	Type
Pfam:Hexokinase_1	2	205	5.6e-88	PFAM

Meta Mutation Damage Score

0.1049

Coding Region Coverage

1x: 100.0%
3x: 100.0%
10x: 99.7%
20x: 99.0%

Validation Efficiency

100% (60/60)

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. This gene encodes a ubiquitous form of hexokinase which localizes to the outer membrane of mitochondria. Mutations in this gene have been associated with hemolytic anemia due to hexokinase deficiency. Alternative splicing of this gene results in several transcript variants which encode different isoforms, some of which are tissue-specific. [provided by RefSeq, Apr 2016]
PHENOTYPE: Homozygous mutant mice exhibit hemolytic anemia with extensive tissue iron deposition and reticulocytosis and female infertility. [provided by MGI curators]

Allele List at MGI

Other mutations in this stock

Total: 61 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Ace3	T	C	11: 105,998,098		probably null	Het
Arhgdib	A	G	6: 136,924,276	Y152H	probably benign	Het
Atxn10	T	G	15: 85,393,393	S354A	probably benign	Het
Cacng6	T	C	7: 3,424,885	V75A	possibly damaging	Het
Cdc23	A	G	18: 34,651,688	V7A	unknown	Het
Cdc40	T	A	10: 40,852,516	E157D	probably benign	Het
Defa25	T	A	8: 21,085,237	N77K	probably benign	Het
Dsc2	C	T	18: 20,032,274	G881R	possibly damaging	Het
Efcab6	T	C	15: 83,983,498	K260E	possibly damaging	Het
Eif4a3	T	C	11: 119,288,905	Y352C	probably damaging	Het
Erc2	A	T	14: 28,011,692	K566N	probably damaging	Het
Fam3b	A	C	16: 97,481,852	Y74*	probably null	Het
Flg2	T	A	3: 93,220,214	S2144R	unknown	Het
Fmo4	G	T	1: 162,798,852	S375*	probably null	Het
Fsip2	A	G	2: 82,986,891	T4323A	probably benign	Het
Gm11639	T	C	11: 104,881,469	V2659A	possibly damaging	Het
Gm16503	A	T	4: 147,541,310	H87L	unknown	Het
Hes7	C	T	11: 69,122,765	A150V	probably damaging	Het
Il17rc	A	G	6: 113,482,821	D576G	probably damaging	Het
Inhba	T	A	13: 16,026,275	S141T	possibly damaging	Het
Itga8	G	T	2: 12,155,486	D840E	probably benign	Het
Kazn	T	C	4: 142,154,551	E126G		Het
Kcnk13	A	G	12: 99,966,179	Y78C	probably damaging	Het
Kcnt1	C	A	2: 25,908,042		probably benign	Het
Krt42	G	C	11: 100,265,039	R294G	possibly damaging	Het
Myo9a	A	G	9: 59,780,091	K160E	probably benign	Het
Nlrp1b	T	C	11: 71,216,921	R585G	probably benign	Het
Ntrk2	T	C	13: 58,874,379	I416T	probably benign	Het
Olfr1080	G	A	2: 86,554,103	T7I	probably damaging	Het
Olfr1217	A	T	2: 89,023,628	I125N	probably damaging	Het
Olfr177	T	C	16: 58,872,691	N153S	probably benign	Het
Olfr652	T	A	7: 104,565,109	I296N	probably damaging	Het
P4ha3	A	G	7: 100,292,698	E106G	probably damaging	Het
Pcif1	A	G	2: 164,886,522	N233S	probably damaging	Het
Pgm2l1	C	A	7: 100,272,418	R619S	probably damaging	Het
Pkhd1l1	A	G	15: 44,512,834	Q964R	probably damaging	Het
Pla2g4a	T	A	1: 149,901,213	I89F	possibly damaging	Het
Ppp1cc	G	A	5: 122,174,088	A306T	probably benign	Het
Psmd4	T	C	3: 95,035,892	D67G	probably damaging	Het
Ptprt	G	A	2: 162,135,457	T307I	probably damaging	Het
Rnf213	C	A	11: 119,430,281	C1188*	probably null	Het
Ror2	C	T	13: 53,113,157	C426Y	probably damaging	Het
Sacs	C	T	14: 61,204,191	H1229Y	probably damaging	Het
Slc25a25	A	T	2: 32,421,505	L118Q	probably damaging	Het
Slc38a6	G	A	12: 73,350,603	A340T	probably benign	Het
Smarca5	A	T	8: 80,704,682	Y969N	probably damaging	Het
Sorbs1	C	A	19: 40,326,489	M626I	probably benign	Het
Spink5	T	A	18: 44,010,236	D753E	probably benign	Het
Taf1d	T	G	9: 15,310,399	I226S	probably damaging	Het
Tmem225	A	G	9: 40,149,393	I83V	possibly damaging	Het
Top2b	A	G	14: 16,412,986	D965G	probably damaging	Het
Traf3ip1	A	G	1: 91,501,419	K303E	probably damaging	Het
Ube2n	C	T	10: 95,541,382	R70C	probably benign	Het
Ubl7	C	T	9: 57,923,206	P312S	probably damaging	Het
Vmn1r34	A	T	6: 66,637,181	M191K	probably damaging	Het
Vmn2r103	C	T	17: 19,793,497	H184Y	probably benign	Het
Vmn2r104	T	C	17: 20,042,786	I138V	probably benign	Het
Vmn2r49	T	C	7: 9,986,481	E361G	possibly damaging	Het
Vmn2r78	T	C	7: 86,954,867	L751P	probably damaging	Het
Zc3h13	T	A	14: 75,330,630	I1121N	not run	Het
Zfp235	T	A	7: 24,141,689	V511E	probably benign	Het

Other mutations in Hk1

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL00493:Hk1	APN	10	62286348	nonsense	probably null
IGL01108:Hk1	APN	10	62296708	missense	probably benign	0.00
IGL01810:Hk1	APN	10	62353105	missense	probably benign	0.13
IGL01950:Hk1	APN	10	62315394	missense	probably damaging	0.99
IGL02165:Hk1	APN	10	62281888	missense	probably damaging	1.00
IGL02227:Hk1	APN	10	62281140	splice site	probably benign
IGL02257:Hk1	APN	10	62271643	missense	probably benign	0.07
IGL02341:Hk1	APN	10	62284380	missense	possibly damaging	0.54
IGL02553:Hk1	APN	10	62295773	missense	possibly damaging	0.71
IGL02623:Hk1	APN	10	62292359	missense	probably benign	0.21
IGL02700:Hk1	APN	10	62284811	missense	probably damaging	1.00
IGL02863:Hk1	APN	10	62295755	missense	possibly damaging	0.83
IGL03002:Hk1	APN	10	62271799	missense	probably damaging	1.00
BB009:Hk1	UTSW	10	62315520	missense	probably damaging	1.00
BB019:Hk1	UTSW	10	62315520	missense	probably damaging	1.00
R0029:Hk1	UTSW	10	62315394	missense	probably damaging	0.99
R0436:Hk1	UTSW	10	62299275	splice site	probably benign
R0853:Hk1	UTSW	10	62271716	nonsense	probably null
R1422:Hk1	UTSW	10	62296094	missense	probably null	0.98
R1531:Hk1	UTSW	10	62284784	missense	probably damaging	1.00
R1760:Hk1	UTSW	10	62281899	missense	probably damaging	1.00
R2064:Hk1	UTSW	10	62286536	missense	probably benign	0.03
R3236:Hk1	UTSW	10	62296019	splice site	probably null
R3788:Hk1	UTSW	10	62275688	missense	possibly damaging	0.85
R3977:Hk1	UTSW	10	62290319	missense	probably benign	0.10
R4373:Hk1	UTSW	10	62315540	missense	probably damaging	0.98
R4374:Hk1	UTSW	10	62315540	missense	probably damaging	0.98
R4377:Hk1	UTSW	10	62315540	missense	probably damaging	0.98
R4435:Hk1	UTSW	10	62275844	missense	probably damaging	1.00
R4609:Hk1	UTSW	10	62358415	utr 5 prime	probably benign
R4648:Hk1	UTSW	10	62304779	missense	probably benign	0.00
R4864:Hk1	UTSW	10	62342539	missense	probably benign	0.00
R4934:Hk1	UTSW	10	62358386	utr 5 prime	probably benign
R5110:Hk1	UTSW	10	62286651	missense	probably damaging	1.00
R5352:Hk1	UTSW	10	62304770	missense	probably damaging	0.97
R5569:Hk1	UTSW	10	62286441	missense	probably benign	0.35
R5609:Hk1	UTSW	10	62342551	missense	probably benign	0.30
R5647:Hk1	UTSW	10	62275744	missense	probably damaging	0.99
R5750:Hk1	UTSW	10	62274466	missense	possibly damaging	0.86
R5770:Hk1	UTSW	10	62286449	missense	probably benign
R5832:Hk1	UTSW	10	62292365	missense	probably benign	0.17
R5905:Hk1	UTSW	10	62353058	missense	probably null	0.82
R5933:Hk1	UTSW	10	62269994	missense	probably damaging	1.00
R6028:Hk1	UTSW	10	62353058	missense	probably null	0.82
R6196:Hk1	UTSW	10	62299259	missense	probably damaging	1.00
R6314:Hk1	UTSW	10	62292444	missense	possibly damaging	0.93
R6372:Hk1	UTSW	10	62291978	missense	probably benign
R6801:Hk1	UTSW	10	62281131	missense	probably damaging	0.97
R6838:Hk1	UTSW	10	62271658	missense	probably damaging	0.98
R7045:Hk1	UTSW	10	62286570	missense	probably damaging	1.00
R7420:Hk1	UTSW	10	62269982	missense	probably damaging	1.00
R7491:Hk1	UTSW	10	62295745	missense	probably damaging	1.00
R7527:Hk1	UTSW	10	62304782	missense	probably damaging	0.99
R7561:Hk1	UTSW	10	62281028	splice site	probably null
R7932:Hk1	UTSW	10	62315520	missense	probably damaging	1.00
R8128:Hk1	UTSW	10	62281843	missense	probably benign
R8204:Hk1	UTSW	10	62296744	missense	probably damaging	1.00
R8294:Hk1	UTSW	10	62295845	missense	probably benign	0.00
R8685:Hk1	UTSW	10	62296674	splice site	probably benign
R8865:Hk1	UTSW	10	62315515	missense	probably benign	0.00
R9015:Hk1	UTSW	10	62292339	missense	possibly damaging	0.95
R9022:Hk1	UTSW	10	62269989	missense	probably damaging	1.00
R9063:Hk1	UTSW	10	62286650	missense	probably damaging	1.00
R9404:Hk1	UTSW	10	62296080	missense	possibly damaging	0.76
X0018:Hk1	UTSW	10	62275706	missense	probably benign	0.02
X0063:Hk1	UTSW	10	62275704	nonsense	probably null

Predicted Primers

PCR Primer
(F):5'- GATGGCATTTCGGAGAGCTC -3'
(R):5'- CCCTTTAAGTGGACAGACAGACAG -3'

Sequencing Primer
(F):5'- ATTTCGGAGAGCTCACATCTGAC -3'
(R):5'- GACAGACAGATCCGGCTCTATCTTC -3'

Posted On

2020-01-23