Mutagenetix > Incidental Mutation

Incidental Mutation 'R3548:Fhit'

268314

Institutional Source

Beutler Lab

Gene Symbol

Fhit

Ensembl Gene

ENSMUSG00000060579

Gene Name

fragile histidine triad gene

Synonyms

Fra14A2

MMRRC Submission

040667-MU

Accession Numbers

Essential gene?

Possibly essential (E-score: 0.604) question?

Stock #

R3548 (G1)

Quality Score

225

Status

Validated

Chromosome

Chromosomal Location

11307738-12919681 bp(+) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

T to C at 9870095 bp (GRCm38)

Zygosity

Heterozygous

Amino Acid Change

Threonine to Alanine at position 125 (T125A)

Ref Sequence

ENSEMBL: ENSMUSP00000124017 (fasta)

Gene Model

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

AlphaFold

O89106

Predicted Effect

probably benign
Transcript: ENSMUST00000160340
AA Change: T125A

PolyPhen 2 Score 0.027 (Sensitivity: 0.95; Specificity: 0.81)

SMART Domains

Protein: ENSMUSP00000124017
Gene: ENSMUSG00000060579
AA Change: T125A

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 benign
Transcript: ENSMUST00000161302
AA Change: T62A

PolyPhen 2 Score 0.002 (Sensitivity: 0.99; Specificity: 0.30)

SMART Domains

Protein: ENSMUSP00000123874
Gene: ENSMUSG00000060579
AA Change: T62A

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 benign
Transcript: ENSMUST00000161895
AA Change: T62A

PolyPhen 2 Score 0.005 (Sensitivity: 0.97; Specificity: 0.74)

SMART Domains

Protein: ENSMUSP00000124957
Gene: ENSMUSG00000060579
AA Change: T62A

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 benign
Transcript: ENSMUST00000162278
AA Change: T62A

PolyPhen 2 Score 0.002 (Sensitivity: 0.99; Specificity: 0.30)

SMART Domains

Protein: ENSMUSP00000124073
Gene: ENSMUSG00000060579
AA Change: T62A

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 benign
Transcript: ENSMUST00000162817
AA Change: T62A

PolyPhen 2 Score 0.002 (Sensitivity: 0.99; Specificity: 0.30)

SMART Domains

Protein: ENSMUSP00000124500
Gene: ENSMUSG00000060579
AA Change: T62A

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 benign
Transcript: ENSMUST00000179394
AA Change: T62A

PolyPhen 2 Score 0.002 (Sensitivity: 0.99; Specificity: 0.30)

SMART Domains

Protein: ENSMUSP00000136011
Gene: ENSMUSG00000060579
AA Change: T62A

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

0.0750

Coding Region Coverage

1x: 99.1%
3x: 98.4%
10x: 96.6%
20x: 92.8%

Validation Efficiency

97% (35/36)

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: 31 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Amph	C	A	13: 19,287,129 (GRCm39)	H279Q	probably damaging	Het
Ankrd28	A	G	14: 31,437,217 (GRCm39)	L646S	probably benign	Het
Bmal1	A	T	7: 112,912,752 (GRCm39)	I610F	probably damaging	Het
Celf3	T	G	3: 94,395,845 (GRCm39)	C304G	probably damaging	Het
Chrnb2	T	A	3: 89,668,898 (GRCm39)	Y139F	probably benign	Het
Clcc1	T	A	3: 108,575,429 (GRCm39)	C169S	probably benign	Het
Clip1	A	G	5: 123,769,141 (GRCm39)	L532P	probably damaging	Het
Cr2	A	T	1: 194,838,196 (GRCm39)	C1089*	probably null	Het
Dnah10	A	T	5: 124,824,694 (GRCm39)	I617F	possibly damaging	Het
F12	T	C	13: 55,565,950 (GRCm39)	N132D	probably benign	Het
Frs3	T	G	17: 48,014,561 (GRCm39)	I418S	probably damaging	Het
Gpr149	A	T	3: 62,502,549 (GRCm39)	C436S	probably benign	Het
Igsf10	C	A	3: 59,243,935 (GRCm39)	R133L	probably damaging	Het
Il17rb	A	G	14: 29,730,729 (GRCm39)		probably null	Het
Kdm1b	C	T	13: 47,216,553 (GRCm39)	R308W	probably damaging	Het
Khdc4	A	G	3: 88,600,443 (GRCm39)		probably benign	Het
Mtus2	C	A	5: 148,232,316 (GRCm39)	H120Q	probably damaging	Het
Muc6	G	A	7: 141,218,313 (GRCm39)	S2120F	possibly damaging	Het
Ncf1	T	A	5: 134,255,463 (GRCm39)	K143*	probably null	Het
Nes	C	A	3: 87,880,429 (GRCm39)		probably benign	Het
Nid2	T	A	14: 19,813,779 (GRCm39)	Y195N	probably damaging	Het
Nlrp9c	A	T	7: 26,070,876 (GRCm39)	C790S	probably damaging	Het
Or5b12	A	T	19: 12,897,031 (GRCm39)	I214N	probably benign	Het
Phf24	T	G	4: 42,937,879 (GRCm39)	Y85*	probably null	Het
Pycr1	T	C	11: 120,533,072 (GRCm39)	S33G	probably benign	Het
Rufy4	T	C	1: 74,186,822 (GRCm39)	C537R	probably damaging	Het
Sirt2	A	G	7: 28,467,096 (GRCm39)	E19G	probably damaging	Het
Sort1	T	C	3: 108,245,225 (GRCm39)	V359A	possibly damaging	Het
Tnni1	A	G	1: 135,732,791 (GRCm39)		probably null	Het
Ube2q1	T	A	3: 89,688,383 (GRCm39)	M183K	probably damaging	Het
Vmn1r50	T	A	6: 90,084,476 (GRCm39)	F74I	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
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
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'- CTGCTGTTATATAAATGCAGACCAC -3'
(R):5'- TAGTCTGCAAGATTCCAGGCC -3'

Sequencing Primer
(F):5'- TGCAGACCACAAAAACCATTTCTCTG -3'
(R):5'- CCCAAGTCAATGGAACTCGGG -3'

Posted On

2015-02-19