Mutagenetix > Incidental Mutation

Incidental Mutation 'R4685:Fhit'

353637

Institutional Source

Beutler Lab

Gene Symbol

Fhit

Ensembl Gene

ENSMUSG00000060579

Gene Name

fragile histidine triad gene

Synonyms

Fra14A2

MMRRC Submission

041936-MU

Accession Numbers

Essential gene?

Possibly essential (E-score: 0.650) question?

Stock #

R4685 (G1)

Quality Score

225

Status

Validated

Chromosome

Chromosomal Location

11307738-12919681 bp(+) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

T to A at 9870091 bp (GRCm38)

Zygosity

Heterozygous

Amino Acid Change

Glutamine to Leucine at position 63 (Q63L)

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: Q126L

PolyPhen 2 Score 0.980 (Sensitivity: 0.75; Specificity: 0.96)

SMART Domains

Protein: ENSMUSP00000124017
Gene: ENSMUSG00000060579
AA Change: Q126L

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 benign
Transcript: ENSMUST00000160956

SMART Domains

Protein: ENSMUSP00000123820
Gene: ENSMUSG00000060579

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: Q63L

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

SMART Domains

Protein: ENSMUSP00000123874
Gene: ENSMUSG00000060579
AA Change: Q63L

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: Q63L

PolyPhen 2 Score 0.995 (Sensitivity: 0.68; Specificity: 0.97)

SMART Domains

Protein: ENSMUSP00000124957
Gene: ENSMUSG00000060579
AA Change: Q63L

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: Q63L

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

SMART Domains

Protein: ENSMUSP00000124073
Gene: ENSMUSG00000060579
AA Change: Q63L

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: Q63L

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

SMART Domains

Protein: ENSMUSP00000124500
Gene: ENSMUSG00000060579
AA Change: Q63L

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: Q63L

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

SMART Domains

Protein: ENSMUSP00000136011
Gene: ENSMUSG00000060579
AA Change: Q63L

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

Meta Mutation Damage Score

0.4291

Coding Region Coverage

1x: 99.2%
3x: 98.6%
10x: 97.1%
20x: 95.0%

Validation Efficiency

97% (71/73)

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: 67 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
2410004P03Rik	T	C	12: 17,057,185 (GRCm39)	D104G	probably damaging	Het
2810021J22Rik	T	C	11: 58,771,750 (GRCm39)	S411P	probably damaging	Het
Adcy2	T	C	13: 68,876,024 (GRCm39)	R493G	probably benign	Het
Adcy8	A	G	15: 64,609,287 (GRCm39)	I874T	probably benign	Het
Ano2	G	T	6: 125,957,087 (GRCm39)	E619*	probably null	Het
Apob	A	G	12: 8,056,456 (GRCm39)	K1613R	probably benign	Het
Arhgef10	T	A	8: 15,006,963 (GRCm39)	F476Y	probably damaging	Het
Bmf	G	A	2: 118,377,283 (GRCm39)	A74V	probably damaging	Het
Cadps	T	C	14: 12,467,139 (GRCm38)	E925G	possibly damaging	Het
Ccdc162	T	C	10: 41,557,682 (GRCm39)	D181G	possibly damaging	Het
Ccdc85c	A	T	12: 108,173,434 (GRCm39)	C387S	probably benign	Het
Cntnap5a	T	C	1: 116,374,410 (GRCm39)	V974A	possibly damaging	Het
Cplx3	T	A	9: 57,516,483 (GRCm39)	I407F	probably damaging	Het
Dnah7b	T	C	1: 46,250,488 (GRCm39)	F1703S	probably damaging	Het
Dsg3	C	A	18: 20,672,793 (GRCm39)	D821E	probably benign	Het
Ecel1	G	T	1: 87,080,668 (GRCm39)		probably null	Het
Edn1	A	T	13: 42,458,729 (GRCm39)		probably null	Het
Egfr	G	A	11: 16,808,980 (GRCm39)	C58Y	probably damaging	Het
Fam184a	T	C	10: 53,574,596 (GRCm39)	N282D	probably benign	Het
Gabarapl2	T	C	8: 112,669,150 (GRCm39)	V36A	probably benign	Het
Glis1	T	C	4: 107,424,842 (GRCm39)	V151A	probably benign	Het
Gm12695	A	G	4: 96,650,217 (GRCm39)	S210P	probably damaging	Het
Gpat4	TAGAAGA	TAGA	8: 23,672,865 (GRCm39)		probably benign	Het
H2-M10.4	G	A	17: 36,772,688 (GRCm39)	A98V	probably benign	Het
Hhat	C	A	1: 192,277,362 (GRCm39)	G366C	probably damaging	Het
Hydin	C	A	8: 111,189,154 (GRCm39)	A1186E	probably damaging	Het
Itgb2	T	A	10: 77,385,937 (GRCm39)		probably null	Het
Kank1	C	T	19: 25,387,398 (GRCm39)	A329V	possibly damaging	Het
Kdm4b	T	A	17: 56,708,675 (GRCm39)	S1070T	probably benign	Het
Kyat1	A	G	2: 30,078,277 (GRCm39)	Y101H	probably damaging	Het
Map4k5	T	C	12: 69,858,140 (GRCm39)	K679R	probably benign	Het
Mill1	A	T	7: 17,989,853 (GRCm39)	D45V	probably damaging	Het
Myo3a	T	A	2: 22,412,233 (GRCm39)	Y743N	probably damaging	Het
Nox4	C	G	7: 86,946,716 (GRCm39)	I137M	probably benign	Het
Odf4	A	G	11: 68,813,665 (GRCm39)		probably null	Het
Ostf1	A	T	19: 18,558,652 (GRCm39)	D210E	probably damaging	Het
Paxip1	A	T	5: 27,966,675 (GRCm39)		probably null	Het
Pitrm1	A	G	13: 6,606,578 (GRCm39)	T211A	probably benign	Het
Pla2g4f	A	G	2: 120,135,496 (GRCm39)	S393P	probably damaging	Het
Plppr3	T	C	10: 79,703,359 (GRCm39)	T42A	probably damaging	Het
Plxna4	C	A	6: 32,142,779 (GRCm39)	G1559W	probably damaging	Het
Ppp1r13l	T	C	7: 19,109,308 (GRCm39)		probably null	Het
Prex1	C	T	2: 166,480,252 (GRCm39)	V163M	probably damaging	Het
Prl6a1	A	G	13: 27,500,307 (GRCm39)	T93A	probably benign	Het
Psg16	T	C	7: 16,824,459 (GRCm39)	V81A	probably benign	Het
Rbm33	A	T	5: 28,613,280 (GRCm39)		probably benign	Het
Rest	C	T	5: 77,423,090 (GRCm39)	P298L	possibly damaging	Het
Rhobtb3	G	A	13: 76,027,051 (GRCm39)	R441*	probably null	Het
Rims4	T	A	2: 163,706,914 (GRCm39)	K155*	probably null	Het
Rps6kb1	C	T	11: 86,410,713 (GRCm39)		probably null	Het
Ryr2	T	C	13: 11,707,532 (GRCm39)	D2835G	probably damaging	Het
Sc5d	C	T	9: 42,169,946 (GRCm39)	V92I	probably benign	Het
Sell	A	T	1: 163,893,829 (GRCm39)	I175F	probably damaging	Het
Serpinb6d	A	G	13: 33,855,211 (GRCm39)	D295G	probably damaging	Het
Sphk1	A	G	11: 116,426,106 (GRCm39)	D96G	probably damaging	Het
Spns3	A	T	11: 72,428,096 (GRCm39)	V228D	probably damaging	Het
Sspo	A	G	6: 48,469,828 (GRCm39)	S4500G	probably damaging	Het
Syt9	T	A	7: 107,035,678 (GRCm39)	C232S	possibly damaging	Het
Terf1	A	G	1: 15,889,185 (GRCm39)	I176V	possibly damaging	Het
Tln2	C	T	9: 67,209,854 (GRCm39)	A428T	probably damaging	Het
Tmprss7	T	C	16: 45,499,711 (GRCm39)	N321S	probably benign	Het
Tomm40	A	G	7: 19,435,761 (GRCm39)	I323T	probably benign	Het
Try5	T	A	6: 41,288,233 (GRCm39)	Q240L	possibly damaging	Het
Vmn1r213	A	T	13: 23,195,800 (GRCm39)	I128L	probably benign	Het
Vmn2r80	T	C	10: 79,030,162 (GRCm39)	F663L	possibly damaging	Het
Znfx1	T	A	2: 166,880,950 (GRCm39)	Y278F	probably damaging	Het
Zpbp2	A	G	11: 98,442,117 (GRCm39)		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
R4968:Fhit	UTSW	14	10,421,522 (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'- CACTTATGGGCCATGGACAG -3'
(R):5'- CCCCAAGTCAATGGAACTCG -3'

Sequencing Primer
(F):5'- CTGCTGTTATATAAATGCAGACCAC -3'
(R):5'- TCGGGGCTTCATGTACAAAC -3'

Posted On

2015-10-21