Mutagenetix > Incidental Mutation

Incidental Mutation 'R4968:Fhit'

384216

Institutional Source

Beutler Lab

Gene Symbol

Fhit

Ensembl Gene

ENSMUSG00000060579

Gene Name

fragile histidine triad gene

Synonyms

Fra14A2

MMRRC Submission

042564-MU

Accession Numbers

Essential gene?

Possibly essential (E-score: 0.650) question?

Stock #

R4968 (G1)

Quality Score

225

Status

Not validated

Chromosome

Chromosomal Location

11307738-12919681 bp(+) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

C to T at 10421522 bp (GRCm38)

Zygosity

Heterozygous

Amino Acid Change

Valine to Methionine at position 26 (V26M)

Ref Sequence

ENSEMBL: ENSMUSP00000136011 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000160340] [ENSMUST00000160956] [ENSMUST00000161302] [ENSMUST00000161895] [ENSMUST00000162278] [ENSMUST00000162817] [ENSMUST00000179394]

AlphaFold

O89106

Predicted Effect

probably damaging
Transcript: ENSMUST00000160340
AA Change: V89M

PolyPhen 2 Score 0.994 (Sensitivity: 0.69; Specificity: 0.97)

SMART Domains

Protein: ENSMUSP00000124017
Gene: ENSMUSG00000060579
AA Change: V89M

Domain	Start	End	E-Value	Type
Pfam:DcpS_C	60	170	2e-9	PFAM
Pfam:HIT	72	168	6.8e-28	PFAM

Predicted Effect

probably damaging
Transcript: ENSMUST00000160956
AA Change: V26M

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

SMART Domains

Protein: ENSMUSP00000123820
Gene: ENSMUSG00000060579
AA Change: V26M

Domain	Start	End	E-Value	Type
Pfam:HIT	9	57	6.5e-11	PFAM

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000161179

Predicted Effect

probably damaging
Transcript: ENSMUST00000161302
AA Change: V26M

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

SMART Domains

Protein: ENSMUSP00000123874
Gene: ENSMUSG00000060579
AA Change: V26M

Domain	Start	End	E-Value	Type
Pfam:DcpS_C	7	110	8.2e-10	PFAM
Pfam:HIT	9	105	4.9e-28	PFAM

Predicted Effect

probably damaging
Transcript: ENSMUST00000161895
AA Change: V26M

PolyPhen 2 Score 0.983 (Sensitivity: 0.75; Specificity: 0.96)

SMART Domains

Protein: ENSMUSP00000124957
Gene: ENSMUSG00000060579
AA Change: V26M

Domain	Start	End	E-Value	Type
Pfam:DcpS_C	6	110	4.3e-10	PFAM
Pfam:HIT	9	105	2e-28	PFAM

Predicted Effect

probably damaging
Transcript: ENSMUST00000162278
AA Change: V26M

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

SMART Domains

Protein: ENSMUSP00000124073
Gene: ENSMUSG00000060579
AA Change: V26M

Domain	Start	End	E-Value	Type
Pfam:DcpS_C	7	110	8.2e-10	PFAM
Pfam:HIT	9	105	4.9e-28	PFAM

Predicted Effect

probably damaging
Transcript: ENSMUST00000162817
AA Change: V26M

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

SMART Domains

Protein: ENSMUSP00000124500
Gene: ENSMUSG00000060579
AA Change: V26M

Domain	Start	End	E-Value	Type
Pfam:DcpS_C	5	100	2.3e-7	PFAM
Pfam:HIT	9	100	1.9e-24	PFAM

Predicted Effect

probably damaging
Transcript: ENSMUST00000179394
AA Change: V26M

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

SMART Domains

Protein: ENSMUSP00000136011
Gene: ENSMUSG00000060579
AA Change: V26M

Domain	Start	End	E-Value	Type
Pfam:DcpS_C	7	110	8.2e-10	PFAM
Pfam:HIT	9	105	4.9e-28	PFAM

Coding Region Coverage

1x: 99.1%
3x: 98.4%
10x: 96.7%
20x: 93.6%

Validation Efficiency

MGI Phenotype

FUNCTION: This gene encodes a member of the HIT family of proteins that are characterized by the presence of a histidine triad sequence. The encoded protein is a diadenosine triphosphate hydrolase enzyme that cleaves the P(1)-P(3)-bis(5'-adenosyl) triphosphate (Ap3A) to yield AMP and ADP. This locus is very fragile and has been found to be altered in different types of cancers. Mice lacking the encoded protein display increased susceptibility to spontaneous and induced tumors. Ectopic expression of the encoded protein in such knockout mice inhibits tumor development. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Apr 2015]
PHENOTYPE: Both homozygotes and heterozygotes for a targeted null mutation exhibit a similarly increased incidence of both spontaneous and nitrosomethylbenzalamine-induced tumors. [provided by MGI curators]

Allele List at MGI

Other mutations in this stock

Total: 69 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
2810021J22Rik	A	T	11: 58,769,616 (GRCm39)	K53*	probably null	Het
4921513D11Rik	T	C	17: 79,935,651 (GRCm39)	S255P	probably benign	Het
Ace	A	G	11: 105,872,679 (GRCm39)	N367S	possibly damaging	Het
Agl	A	T	3: 116,582,175 (GRCm39)	N282K	probably benign	Het
Ahnak	C	A	19: 8,992,464 (GRCm39)	P4583T	probably damaging	Het
Alpi	T	C	1: 87,029,247 (GRCm39)	D4G	probably benign	Het
Anks6	C	T	4: 47,030,795 (GRCm39)	G601S	probably damaging	Het
Aplnr	T	C	2: 84,967,289 (GRCm39)	Y105H	probably damaging	Het
Arhgap9	G	A	10: 127,162,875 (GRCm39)	R395K	possibly damaging	Het
Asah1	A	G	8: 41,807,067 (GRCm39)	M119T		Het
Atp5f1b	T	C	10: 127,919,856 (GRCm39)	F75L	probably damaging	Het
B4galt6	G	T	18: 20,861,026 (GRCm39)	N75K	possibly damaging	Het
Bco1	A	T	8: 117,857,833 (GRCm39)	H486L	probably benign	Het
Btaf1	T	A	19: 36,947,351 (GRCm39)	L480Q	probably null	Het
Ccdc34	G	T	2: 109,871,078 (GRCm39)		probably null	Het
Cdh19	T	C	1: 110,852,958 (GRCm39)	S326G	probably benign	Het
Cep89	A	G	7: 35,109,055 (GRCm39)	D178G	possibly damaging	Het
Cyp11b2	A	T	15: 74,725,854 (GRCm39)		probably null	Het
Cyp21a1	A	G	17: 35,022,383 (GRCm39)	I157T	possibly damaging	Het
Dcbld2	A	G	16: 58,245,074 (GRCm39)	D116G	probably damaging	Het
Ddx5	T	C	11: 106,674,953 (GRCm39)	Q377R	probably damaging	Het
Deup1	T	C	9: 15,503,724 (GRCm39)	D279G	probably damaging	Het
F11	G	A	8: 45,698,770 (GRCm39)	A458V	probably benign	Het
Fhad1	C	A	4: 141,645,618 (GRCm39)	G326W	probably damaging	Het
Gjb5	A	T	4: 127,250,015 (GRCm39)	V43E	probably damaging	Het
Grtp1	A	T	8: 13,242,184 (GRCm39)	I75N	probably damaging	Het
Hmcn1	A	G	1: 150,533,221 (GRCm39)	I3022T	possibly damaging	Het
Hsp90ab1	T	C	17: 45,881,962 (GRCm39)	T166A	probably benign	Het
Ift70b	T	C	2: 75,768,391 (GRCm39)	I121V	probably benign	Het
Iho1	C	T	9: 108,289,713 (GRCm39)	V170M	probably benign	Het
Ikbke	GCC	G	1: 131,203,004 (GRCm39)		probably null	Het
Kcnk10	T	C	12: 98,401,161 (GRCm39)	I491V	probably benign	Het
Kcp	A	T	6: 29,497,628 (GRCm39)	C519*	probably null	Het
Lcmt2	T	C	2: 120,970,217 (GRCm39)	T69A	probably benign	Het
Lmf1	A	G	17: 25,804,592 (GRCm39)	Y90C	probably damaging	Het
Lpp	A	G	16: 24,798,064 (GRCm39)	D612G	probably damaging	Het
Lrfn5	C	A	12: 61,886,461 (GRCm39)	S83Y	probably damaging	Het
Lrp1b	T	C	2: 40,592,719 (GRCm39)		probably null	Het
Lrp1b	C	T	2: 41,679,074 (GRCm39)	C6Y	probably damaging	Het
Lrrc8c	A	G	5: 105,754,993 (GRCm39)	D256G	probably damaging	Het
Mphosph10	A	G	7: 64,032,656 (GRCm39)	Y478H	probably damaging	Het
Mpp2	T	C	11: 101,955,124 (GRCm39)	H167R	probably benign	Het
Mtss1	A	G	15: 58,815,767 (GRCm39)	S598P	probably damaging	Het
Myh10	A	G	11: 68,684,049 (GRCm39)	E1154G	probably damaging	Het
Myo10	T	C	15: 25,808,270 (GRCm39)	V1218A	probably damaging	Het
Myo19	A	G	11: 84,792,328 (GRCm39)	K599R	probably damaging	Het
Neurl4	T	C	11: 69,798,134 (GRCm39)	M771T	probably damaging	Het
Nlrc4	A	G	17: 74,753,936 (GRCm39)	V149A	probably benign	Het
Nup133	A	T	8: 124,641,935 (GRCm39)	S843T	probably benign	Het
Or2y1c	T	C	11: 49,361,358 (GRCm39)	C127R	probably damaging	Het
Or51k1	T	C	7: 103,661,777 (GRCm39)	N44S	probably damaging	Het
P3h2	A	G	16: 25,811,412 (GRCm39)		probably null	Het
Piezo2	A	T	18: 63,278,042 (GRCm39)	Y287*	probably null	Het
Prob1	T	C	18: 35,785,605 (GRCm39)	Y883C	probably damaging	Het
Pxdn	T	A	12: 30,050,011 (GRCm39)	H506Q	probably benign	Het
Ripor3	T	C	2: 167,827,037 (GRCm39)	D658G	probably benign	Het
Rufy1	T	A	11: 50,301,434 (GRCm39)	I333L	probably benign	Het
Selenok	T	A	14: 29,692,064 (GRCm39)	V34E	probably benign	Het
Selplg	T	C	5: 113,957,787 (GRCm39)	E173G	possibly damaging	Het
Septin10	A	G	10: 59,016,943 (GRCm39)	F194L	probably damaging	Het
Sptbn2	A	T	19: 4,779,230 (GRCm39)		probably null	Het
St6galnac6	C	T	2: 32,498,098 (GRCm39)	P6S	probably benign	Het
Syngr2	T	C	11: 117,704,296 (GRCm39)	Y194H	probably damaging	Het
Thbs4	A	G	13: 92,894,576 (GRCm39)	I649T	possibly damaging	Het
Triobp	T	A	15: 78,850,816 (GRCm39)	N323K	probably benign	Het
Tuba8	T	A	6: 121,197,548 (GRCm39)	L70Q	probably damaging	Het
Vmn2r61	A	G	7: 41,949,478 (GRCm39)	T633A	probably benign	Het
Zfp280b	G	T	10: 75,875,188 (GRCm39)	V356L	probably damaging	Het
Zswim4	A	T	8: 84,944,001 (GRCm39)	V746D	probably benign	Het

Other mutations in Fhit

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL01411:Fhit	APN	14	9,573,483 (GRCm38)	missense	probably benign	0.19
IGL01412:Fhit	APN	14	9,870,065 (GRCm38)	missense	probably damaging	1.00
IGL02831:Fhit	APN	14	9,870,080 (GRCm38)	missense	probably benign	0.00
IGL03025:Fhit	APN	14	10,421,534 (GRCm38)	missense	probably damaging	1.00
overtax	UTSW	14	10,421,534 (GRCm38)	missense	probably damaging	1.00
R0464:Fhit	UTSW	14	10,991,567 (GRCm38)	start gained	probably benign
R0544:Fhit	UTSW	14	9,870,172 (GRCm38)	missense	probably damaging	1.00
R3545:Fhit	UTSW	14	9,870,095 (GRCm38)	missense	probably benign	0.03
R3547:Fhit	UTSW	14	9,870,095 (GRCm38)	missense	probably benign	0.03
R3548:Fhit	UTSW	14	9,870,095 (GRCm38)	missense	probably benign	0.03
R4033:Fhit	UTSW	14	10,751,671 (GRCm38)	intron	probably benign
R4685:Fhit	UTSW	14	9,870,091 (GRCm38)	missense	probably damaging	1.00
R5624:Fhit	UTSW	14	10,421,534 (GRCm38)	missense	probably damaging	1.00
R6011:Fhit	UTSW	14	9,870,068 (GRCm38)	missense	probably benign	0.16
R6061:Fhit	UTSW	14	9,573,435 (GRCm38)	missense	probably benign	0.00
R6208:Fhit	UTSW	14	9,573,435 (GRCm38)	missense	probably benign	0.00
R6846:Fhit	UTSW	14	9,763,762 (GRCm38)	missense	possibly damaging	0.73
R7288:Fhit	UTSW	14	9,763,784 (GRCm38)	missense	probably damaging	1.00
R7625:Fhit	UTSW	14	9,870,177 (GRCm38)	critical splice acceptor site	probably null
R8094:Fhit	UTSW	14	10,751,666 (GRCm38)	missense	unknown
R8482:Fhit	UTSW	14	10,751,616 (GRCm38)	missense	probably benign	0.09
R8781:Fhit	UTSW	14	10,421,503 (GRCm38)	missense	probably damaging	0.99
R9246:Fhit	UTSW	14	10,421,494 (GRCm38)	critical splice donor site	probably null
Z1177:Fhit	UTSW	14	9,870,128 (GRCm38)	missense	probably benign	0.00

Predicted Primers

PCR Primer
(F):5'- GCAACCCTCCTTAGAAGTTCTAC -3'
(R):5'- GGGATCCCATTCTATCAAAGAGTC -3'

Sequencing Primer
(F):5'- ATATTGCGGGTGCCACCAAC -3'
(R):5'- AGAGTCTTTACTAATGGAATTTGCC -3'

Posted On

2016-04-27