Mutagenetix > Incidental Mutation

Incidental Mutation 'R7284:Pfkfb4'

565877

Institutional Source

Beutler Lab

Gene Symbol

Pfkfb4

Ensembl Gene

ENSMUSG00000025648

Gene Name

6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 4

Synonyms

MMRRC Submission

045392-MU

Accession Numbers

Essential gene?

Non essential (E-score: 0.000) question?

Stock #

R7284 (G1)

Quality Score

225.009

Status

Validated

Chromosome

Chromosomal Location

108991778-109032228 bp(+) (GRCm38)

Type of Mutation

missense

DNA Base Change (assembly)

T to C at 109011240 bp (GRCm38)

Zygosity

Heterozygous

Amino Acid Change

Isoleucine to Threonine at position 308 (I308T)

Ref Sequence

ENSEMBL: ENSMUSP00000142378 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000051873] [ENSMUST00000196249] [ENSMUST00000198140] [ENSMUST00000199591]

AlphaFold

Q6DTY7

Predicted Effect

possibly damaging
Transcript: ENSMUST00000051873
AA Change: I292T

PolyPhen 2 Score 0.933 (Sensitivity: 0.80; Specificity: 0.94)

SMART Domains

Protein: ENSMUSP00000057197
Gene: ENSMUSG00000025648
AA Change: I292T

Domain	Start	End	E-Value	Type
Pfam:6PF2K	28	249	3.2e-105	PFAM
Pfam:AAA_33	41	199	2.3e-8	PFAM
PGAM	251	398	4.39e-16	SMART

Predicted Effect

probably benign
Transcript: ENSMUST00000196249

Predicted Effect

possibly damaging
Transcript: ENSMUST00000198140
AA Change: I308T

PolyPhen 2 Score 0.878 (Sensitivity: 0.82; Specificity: 0.94)

SMART Domains

Protein: ENSMUSP00000142378
Gene: ENSMUSG00000025648
AA Change: I308T

Domain	Start	End	E-Value	Type
Pfam:6PF2K	28	249	1.9e-105	PFAM
Pfam:AAA_33	41	198	8.5e-10	PFAM
PGAM	251	398	4.39e-16	SMART

Predicted Effect

probably damaging
Transcript: ENSMUST00000199591
AA Change: I308T

PolyPhen 2 Score 0.996 (Sensitivity: 0.55; Specificity: 0.98)

SMART Domains

Protein: ENSMUSP00000142992
Gene: ENSMUSG00000025648
AA Change: I308T

Domain	Start	End	E-Value	Type
Pfam:6PF2K	28	249	1.4e-105	PFAM
Pfam:AAA_33	41	198	6.6e-10	PFAM
PGAM	251	396	4.98e-6	SMART

Predicted Effect

probably damaging
Transcript: ENSMUST00000200015
AA Change: I18T

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

Meta Mutation Damage Score

0.7959

Coding Region Coverage

1x: 100.0%
3x: 99.9%
10x: 99.5%
20x: 98.3%

Validation Efficiency

99% (77/78)

MGI Phenotype

FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] The protein encoded by this gene is one of four bifunctional kinase/phosphatases that regulate the concentration of the glycolytic byproduct fructose-2,6-bisphosphate (F2,6BP). The encoded protein is highly expressed in cancer cells and is induced by hypoxia. This protein is essential to the survival of cancer cells under conditions of hypoxia, because it increases the amount of F2,6BP and ATP at a time when the cell cannot produce much of them. This finding suggests that this protein may be a good target for disruption in cancer cells, hopefully imperiling their survival. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2015]

Allele List at MGI

Other mutations in this stock

Total: 77 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
2310035C23Rik	T	A	1: 105,734,583	H942Q	probably benign	Het
2900092C05Rik	G	T	7: 12,512,678	E34*	probably null	Het
4933421I07Rik	C	T	7: 42,447,980	R30H	probably damaging	Het
AB124611	C	A	9: 21,539,104	Q158K	probably benign	Het
Abcc3	C	T	11: 94,357,047	A1207T	probably benign	Het
Abcc9	A	T	6: 142,682,917	L367Q	probably damaging	Het
Aftph	T	C	11: 20,726,812	K266E	probably benign	Het
Akap9	T	A	5: 3,956,246	D190E	probably damaging	Het
Angel1	G	T	12: 86,720,524	D359E	probably damaging	Het
Ano6	T	C	15: 95,948,303	I474T	probably damaging	Het
Atp2c1	A	T	9: 105,520,809		probably null	Het
Best1	T	C	19: 9,986,373		probably null	Het
Bhlha9	A	G	11: 76,672,666	S40G	probably benign	Het
Cabin1	G	A	10: 75,694,834	R178C		Het
Ccnb1ip1	A	G	14: 50,792,279	Y109H	probably damaging	Het
Col14a1	T	C	15: 55,518,319	S1763P	probably damaging	Het
Dars	T	C	1: 128,372,267	T327A	probably benign	Het
Dhx8	T	C	11: 101,754,822	Y889H	probably damaging	Het
Dlg4	T	A	11: 70,042,082	Y523*	probably null	Het
Dnah10	A	T	5: 124,832,598	D4484V	probably benign	Het
Dnah9	A	T	11: 65,990,476	M2591K	probably damaging	Het
Dock2	T	C	11: 34,230,672	E1715G	probably benign	Het
Dym	A	G	18: 75,119,171	Y336C	possibly damaging	Het
Ezh2	A	G	6: 47,544,519	M439T	probably benign	Het
Folr1	T	G	7: 101,859,470	N83H	possibly damaging	Het
Ganab	T	C	19: 8,912,540	L656P	probably damaging	Het
Gmnc	T	C	16: 26,960,792	H161R	probably benign	Het
Gria4	A	G	9: 4,472,017	Y491H	probably damaging	Het
Heatr3	T	A	8: 88,156,774	C412S	possibly damaging	Het
Hmgcr	A	C	13: 96,652,665	V716G	probably damaging	Het
Igsf9	A	G	1: 172,496,912	D799G	probably damaging	Het
Ikbkb	T	C	8: 22,668,960	T501A	probably benign	Het
Kbtbd3	C	T	9: 4,330,690	R355*	probably null	Het
Kcna7	T	A	7: 45,409,228	I313N	probably damaging	Het
Kirrel	A	C	3: 87,083,387	D709E	probably benign	Het
Klb	T	A	5: 65,383,478	S971R	probably benign	Het
Krtap4-13	A	T	11: 99,809,412	C140*	probably null	Het
Lacc1	A	T	14: 77,030,869	L334Q	probably damaging	Het
Map6d1	T	A	16: 20,241,025	R97*	probably null	Het
Mgat5b	T	C	11: 116,944,920	S129P	probably damaging	Het
Mmp1a	TG	TGG	9: 7,465,083		probably null	Het
Myh9	G	A	15: 77,787,596	R432C	probably damaging	Het
Ncf4	A	G	15: 78,260,702	T236A	probably benign	Het
Neb	T	C	2: 52,258,792	D2581G	probably damaging	Het
Nid1	T	A	13: 13,489,090	M778K	probably benign	Het
Npas2	A	G	1: 39,324,467	D209G	probably benign	Het
Nploc4	C	T	11: 120,416,370	V181I	possibly damaging	Het
Nrcam	A	T	12: 44,564,034	I506F	probably damaging	Het
Olfr197	A	G	16: 59,185,968	*172Q	probably null	Het
Olfr692	T	A	7: 105,368,545	M73K	probably damaging	Het
Olfr803	T	C	10: 129,691,351	N230S	probably benign	Het
Pask	T	A	1: 93,320,669	Q970L	probably benign	Het
Pla2g4d	A	T	2: 120,284,136	L38Q	probably damaging	Het
Pld1	A	G	3: 28,131,733	T1036A	possibly damaging	Het
Pom121l2	A	G	13: 21,982,605	T349A	probably damaging	Het
Ppp1r13b	A	G	12: 111,834,966	I551T	possibly damaging	Het
Prps1l1	A	G	12: 34,985,318	N144S	possibly damaging	Het
Prss56	A	G	1: 87,185,401	N179S	probably null	Het
Prune2	T	C	19: 17,119,886	L918P	probably damaging	Het
Ptprz1	C	T	6: 23,000,098	T729I	probably damaging	Het
Rrp7a	T	C	15: 83,121,870	T60A	probably damaging	Het
Snx27	A	G	3: 94,524,191	Y299H	probably damaging	Het
Spaca3	G	T	11: 80,864,021	R96L	possibly damaging	Het
Stat1	A	G	1: 52,148,922	N495S	probably benign	Het
Tas2r130	T	C	6: 131,630,307	N175S	probably benign	Het
Tcaf2	A	G	6: 42,629,538	L494P	probably damaging	Het
Tdrd12	C	A	7: 35,480,136		probably null	Het
Thbs1	A	G	2: 118,119,356	N604S	probably damaging	Het
Togaram1	T	C	12: 65,008,680	F1482L	probably benign	Het
Trhr2	A	T	8: 122,360,375	S109T	probably damaging	Het
Trpc3	A	T	3: 36,624,413	M841K	probably damaging	Het
Tubgcp5	C	T	7: 55,823,567	R798C	probably benign	Het
Xirp2	T	A	2: 67,516,829	M3138K	probably benign	Het
Zdhhc4	G	A	5: 143,321,891	T125I	probably benign	Het
Zfp239	T	A	6: 117,871,755	C151*	probably null	Het
Zfp473	C	T	7: 44,733,203	E569K	not run	Het
Zzef1	T	A	11: 72,886,690	D1782E	probably damaging	Het

Other mutations in Pfkfb4

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL01653:Pfkfb4	APN	9	108999134	missense	probably damaging	1.00
IGL01978:Pfkfb4	APN	9	109028942	missense	probably damaging	1.00
IGL02119:Pfkfb4	APN	9	109025110	missense	probably damaging	1.00
IGL02121:Pfkfb4	APN	9	109025110	missense	probably damaging	1.00
IGL02122:Pfkfb4	APN	9	109025110	missense	probably damaging	1.00
IGL02123:Pfkfb4	APN	9	109025110	missense	probably damaging	1.00
IGL02125:Pfkfb4	APN	9	109025110	missense	probably damaging	1.00
IGL02126:Pfkfb4	APN	9	109025110	missense	probably damaging	1.00
IGL02506:Pfkfb4	APN	9	109030336	missense	probably benign	0.00
IGL02881:Pfkfb4	APN	9	109007296	missense	probably null	1.00
PIT4466001:Pfkfb4	UTSW	9	108999154	missense	probably benign	0.12
PIT4472001:Pfkfb4	UTSW	9	108999154	missense	probably benign	0.12
R0087:Pfkfb4	UTSW	9	109007701	missense	probably damaging	1.00
R0101:Pfkfb4	UTSW	9	109010643	missense	probably benign	0.03
R0109:Pfkfb4	UTSW	9	108998889	missense	probably benign	0.27
R0109:Pfkfb4	UTSW	9	108998889	missense	probably benign	0.27
R0379:Pfkfb4	UTSW	9	109027742	splice site	probably benign
R0511:Pfkfb4	UTSW	9	109027757	missense	probably damaging	1.00
R1146:Pfkfb4	UTSW	9	109007726	missense	probably benign	0.00
R1146:Pfkfb4	UTSW	9	109007726	missense	probably benign	0.00
R1490:Pfkfb4	UTSW	9	109027620	missense	probably damaging	1.00
R1521:Pfkfb4	UTSW	9	109007305	missense	probably damaging	1.00
R1932:Pfkfb4	UTSW	9	108999169	missense	probably damaging	1.00
R2214:Pfkfb4	UTSW	9	109005609	missense	probably benign	0.17
R3112:Pfkfb4	UTSW	9	109025042	splice site	probably benign
R5470:Pfkfb4	UTSW	9	109027593	missense	probably damaging	1.00
R5646:Pfkfb4	UTSW	9	109008421	missense	probably damaging	1.00
R5930:Pfkfb4	UTSW	9	109030394	unclassified	probably benign
R6139:Pfkfb4	UTSW	9	109027757	missense	probably damaging	1.00
R6632:Pfkfb4	UTSW	9	109009562	splice site	probably null
R6873:Pfkfb4	UTSW	9	109010335	splice site	probably null
R6958:Pfkfb4	UTSW	9	109010547	missense	probably damaging	1.00
R7098:Pfkfb4	UTSW	9	108999154	missense	probably benign	0.05
R7131:Pfkfb4	UTSW	9	109007302	missense	probably benign	0.21
R7148:Pfkfb4	UTSW	9	109027608	missense	probably damaging	0.99
R7903:Pfkfb4	UTSW	9	108998951	missense	probably damaging	1.00
R7973:Pfkfb4	UTSW	9	109025111	missense	probably damaging	1.00
R8506:Pfkfb4	UTSW	9	109005599	missense	possibly damaging	0.80

Predicted Primers

PCR Primer
(F):5'- GGATGTGTACACCATTGGGAAG -3'
(R):5'- ATGACTACCCTACATTATTCTCCAG -3'

Sequencing Primer
(F):5'- TACACCATTGGGAAGTTAGTGTGAC -3'
(R):5'- ATTATTCTCCAGACCATACTGAGC -3'

Posted On

2019-06-26