Mutagenetix > Incidental Mutation

Incidental Mutation 'R8781:Fhit'

670272

Institutional Source

Beutler Lab

Gene Symbol

Fhit

Ensembl Gene

ENSMUSG00000060579

Gene Name

fragile histidine triad gene

Synonyms

Fra14A2

MMRRC Submission

068605-MU

Accession Numbers

Essential gene?

Possibly essential (E-score: 0.604) question?

Stock #

R8781 (G1)

Quality Score

225.009

Status

Validated

Chromosome

Chromosomal Location

11307738-12919681 bp(+) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

A to G at 10421503 bp (GRCm38)

Zygosity

Heterozygous

Amino Acid Change

Valine to Alanine at position 32 (V32A)

Ref Sequence

ENSEMBL: ENSMUSP00000123874 (fasta)

Gene Model

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

AlphaFold

O89106

Predicted Effect

possibly damaging
Transcript: ENSMUST00000160340
AA Change: V95A

PolyPhen 2 Score 0.859 (Sensitivity: 0.83; Specificity: 0.93)

SMART Domains

Protein: ENSMUSP00000124017
Gene: ENSMUSG00000060579
AA Change: V95A

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: V32A

PolyPhen 2 Score 0.988 (Sensitivity: 0.73; Specificity: 0.96)

SMART Domains

Protein: ENSMUSP00000123820
Gene: ENSMUSG00000060579
AA Change: V32A

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

Predicted Effect

probably damaging
Transcript: ENSMUST00000161302
AA Change: V32A

PolyPhen 2 Score 0.988 (Sensitivity: 0.73; Specificity: 0.96)

SMART Domains

Protein: ENSMUSP00000123874
Gene: ENSMUSG00000060579
AA Change: V32A

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: V32A

PolyPhen 2 Score 0.988 (Sensitivity: 0.73; Specificity: 0.96)

SMART Domains

Protein: ENSMUSP00000124957
Gene: ENSMUSG00000060579
AA Change: V32A

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: V32A

PolyPhen 2 Score 0.988 (Sensitivity: 0.73; Specificity: 0.96)

SMART Domains

Protein: ENSMUSP00000124073
Gene: ENSMUSG00000060579
AA Change: V32A

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: V32A

PolyPhen 2 Score 0.988 (Sensitivity: 0.73; Specificity: 0.96)

SMART Domains

Protein: ENSMUSP00000124500
Gene: ENSMUSG00000060579
AA Change: V32A

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: V32A

PolyPhen 2 Score 0.988 (Sensitivity: 0.73; Specificity: 0.96)

SMART Domains

Protein: ENSMUSP00000136011
Gene: ENSMUSG00000060579
AA Change: V32A

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: 100.0%
3x: 100.0%
10x: 99.8%
20x: 99.3%

Validation Efficiency

100% (59/59)

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: 62 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
1810055G02Rik	A	G	19: 3,767,538 (GRCm39)	D375G	possibly damaging	Het
Abi3bp	C	T	16: 56,426,512 (GRCm39)	T509I	probably damaging	Het
Atp13a2	T	A	4: 140,723,691 (GRCm39)	C257S	probably benign	Het
Ccdc183	T	A	2: 25,502,208 (GRCm39)		probably benign	Het
Cd109	C	T	9: 78,543,929 (GRCm39)	P158S	probably damaging	Het
Cdh23	C	T	10: 60,167,567 (GRCm39)	E1810K	probably damaging	Het
Cog5	T	A	12: 31,883,249 (GRCm39)	W393R	probably damaging	Het
Cyth1	C	T	11: 118,073,069 (GRCm39)	R277Q	probably damaging	Het
Ddx54	G	T	5: 120,751,217 (GRCm39)	R6L	probably benign	Het
Dnah8	T	A	17: 30,944,078 (GRCm39)	I1765N	probably damaging	Het
Erp27	G	A	6: 136,886,458 (GRCm39)	Q192*	probably null	Het
Fam81a	T	A	9: 70,032,381 (GRCm39)	H37L	probably damaging	Het
Fbn2	A	G	18: 58,194,719 (GRCm39)	S1481P	possibly damaging	Het
Fbp1	T	G	13: 63,016,831 (GRCm39)	I224L	probably benign	Het
Gapvd1	T	A	2: 34,610,698 (GRCm39)	H495L	probably benign	Het
Gas2l3	T	C	10: 89,266,841 (GRCm39)	D33G	probably damaging	Het
Heatr5b	A	T	17: 79,102,738 (GRCm39)	D1213E	probably benign	Het
Hsf2bp	C	G	17: 32,252,241 (GRCm39)	E65Q	possibly damaging	Het
Kif28	G	T	1: 179,525,481 (GRCm39)	T937K	probably benign	Het
Klf6	T	A	13: 5,915,071 (GRCm39)	V170D	probably benign	Het
Kri1	A	T	9: 21,191,748 (GRCm39)	S283T		Het
Lcor	C	T	19: 41,573,698 (GRCm39)	R818W	probably damaging	Het
Lct	A	G	1: 128,215,261 (GRCm39)	Y1772H	probably damaging	Het
Lrrc37	T	A	11: 103,508,958 (GRCm39)	E1003D	unknown	Het
Naip5	T	A	13: 100,356,338 (GRCm39)	E1092D	probably benign	Het
Or2b2b	A	G	13: 21,859,013 (GRCm39)	S34P	probably damaging	Het
Or52j3	T	A	7: 102,836,082 (GRCm39)	D91E	probably benign	Het
Or8c14-ps1	T	G	9: 38,101,385 (GRCm39)	D121E	probably damaging	Het
Parg	T	A	14: 31,936,400 (GRCm39)	D518E	probably benign	Het
Pcx	G	A	19: 4,670,980 (GRCm39)	A1095T	probably damaging	Het
Pde1b	G	A	15: 103,433,727 (GRCm39)	V342M	probably damaging	Het
Pik3r2	C	T	8: 71,222,046 (GRCm39)	G579D	possibly damaging	Het
Pknox1	G	A	17: 31,821,837 (GRCm39)		probably benign	Het
Pla2g3	C	A	11: 3,438,530 (GRCm39)	T60K	probably benign	Het
Ppfia3	C	T	7: 44,997,953 (GRCm39)	E725K	possibly damaging	Het
Ppl	C	T	16: 4,915,800 (GRCm39)	V588I	possibly damaging	Het
Sardh	T	A	2: 27,086,715 (GRCm39)	E815V	possibly damaging	Het
Scn7a	T	C	2: 66,567,775 (GRCm39)	E273G	probably benign	Het
Slc7a8	A	T	14: 54,996,996 (GRCm39)		probably benign	Het
Smg8	G	A	11: 86,971,147 (GRCm39)	P875S	possibly damaging	Het
Sncaip	T	C	18: 53,039,614 (GRCm39)	S603P	probably benign	Het
Speg	G	A	1: 75,383,665 (GRCm39)	G1218S	probably damaging	Het
Stk31	A	T	6: 49,383,709 (GRCm39)	D92V	probably damaging	Het
Suco	A	G	1: 161,645,951 (GRCm39)	V1250A	probably damaging	Het
Tas2r138	A	G	6: 40,589,850 (GRCm39)	V132A	probably benign	Het
Tcp1	T	C	17: 13,143,263 (GRCm39)	I524T	probably damaging	Het
Tenm3	CTGCTGTGAAATG	C	8: 48,795,484 (GRCm39)		probably null	Het
Tln2	C	A	9: 67,163,233 (GRCm39)	V1105L	probably damaging	Het
Tmem19	T	C	10: 115,195,563 (GRCm39)		probably benign	Het
Tmprss4	T	C	9: 45,087,740 (GRCm39)	Y283C	possibly damaging	Het
Trim29	T	A	9: 43,222,615 (GRCm39)	V148D	probably benign	Het
Trip10	C	T	17: 57,562,313 (GRCm39)	A277V	probably benign	Het
Usp12	C	A	5: 146,700,172 (GRCm39)	R61L	probably benign	Het
Vmn1r58	T	G	7: 5,413,482 (GRCm39)	L249F	probably benign	Het
Vmn2r31	C	T	7: 7,387,400 (GRCm39)	V724I	possibly damaging	Het
Vmn2r66	C	T	7: 84,644,355 (GRCm39)	W685*	probably null	Het
Vmn2r8	A	G	5: 108,945,597 (GRCm39)	I670T	possibly damaging	Het
Vmn2r91	T	A	17: 18,305,323 (GRCm39)	M2K	possibly damaging	Het
Wdr12	A	G	1: 60,126,300 (GRCm39)	W172R	probably damaging	Het
Yipf5	A	T	18: 40,340,752 (GRCm39)	V200E	possibly damaging	Het
Zfp608	T	C	18: 55,031,801 (GRCm39)	K713R	probably damaging	Het
Zfp768	A	G	7: 126,942,476 (GRCm39)	S554P	probably damaging	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
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
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'- AAGCAACCCTCCTTAGAAGTTC -3'
(R):5'- ACGTGCTACATGAACTTCATTG -3'

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

Posted On

2021-04-30