Incidental Mutation 'R3545:Fhit'
ID 268179
Institutional Source Beutler Lab
Gene Symbol Fhit
Ensembl Gene ENSMUSG00000060579
Gene Name fragile histidine triad gene
Synonyms Fra14A2
Accession Numbers
Essential gene? Possibly essential (E-score: 0.650) question?
Stock # R3545 (G1)
Quality Score 225
Status Not validated
Chromosome 14
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

DomainStartEndE-ValueType
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

DomainStartEndE-ValueType
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

DomainStartEndE-ValueType
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

DomainStartEndE-ValueType
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

DomainStartEndE-ValueType
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

DomainStartEndE-ValueType
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

DomainStartEndE-ValueType
Pfam:DcpS_C 7 110 8.2e-10 PFAM
Pfam:HIT 9 105 4.9e-28 PFAM
Meta Mutation Damage Score 0.0750 question?
Coding Region Coverage
  • 1x: 99.2%
  • 3x: 98.5%
  • 10x: 97.1%
  • 20x: 94.7%
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: 34 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
Ankrd28 A G 14: 31,437,217 (GRCm39) L646S probably benign Het
Clip1 A G 5: 123,769,141 (GRCm39) L532P probably damaging Het
Efl1 A T 7: 82,412,018 (GRCm39) E802D probably benign Het
F11r T C 1: 171,288,829 (GRCm39) V149A probably damaging Het
Fmn2 A G 1: 174,330,192 (GRCm39) D194G unknown Het
Gdi1 T A X: 73,351,414 (GRCm39) F175L possibly damaging Het
Herc3 T C 6: 58,833,670 (GRCm39) S186P probably damaging Het
Hexa A G 9: 59,464,581 (GRCm39) N157S probably damaging Het
Kdm1b C T 13: 47,216,553 (GRCm39) R308W probably damaging Het
Lig1 T A 7: 13,026,089 (GRCm39) N281K possibly damaging Het
Lrp1b A T 2: 40,490,300 (GRCm39) L287H probably damaging Het
Mcf2 T C X: 59,180,806 (GRCm39) K74R probably damaging Het
Nat1 A G 8: 67,943,684 (GRCm39) D23G possibly damaging Het
Nbeal1 T C 1: 60,317,939 (GRCm39) F1959L probably damaging Het
Ncf1 T A 5: 134,255,463 (GRCm39) K143* probably null Het
Nid2 T A 14: 19,813,779 (GRCm39) Y195N probably damaging Het
Nlrp9a T C 7: 26,256,757 (GRCm39) I125T probably benign Het
Nme7 T C 1: 164,213,351 (GRCm39) F343S probably damaging Het
Otud4 A G 8: 80,391,684 (GRCm39) E443G probably damaging Het
Palld G T 8: 62,003,112 (GRCm39) A329E possibly damaging Het
Pask A T 1: 93,244,837 (GRCm39) V1095D probably damaging Het
Pdzd2 C T 15: 12,375,557 (GRCm39) R1526Q probably benign Het
Prkcq A G 2: 11,288,627 (GRCm39) K527E probably benign Het
Ramac T A 7: 81,418,270 (GRCm39) probably null Het
Reln A G 5: 22,432,598 (GRCm39) V134A possibly damaging Het
Rufy4 T C 1: 74,186,822 (GRCm39) C537R probably damaging Het
Septin9 T C 11: 117,243,499 (GRCm39) I350T probably damaging Het
Slc16a7 T A 10: 125,130,569 (GRCm39) K39* probably null Het
Spata32 T C 11: 103,101,570 (GRCm39) E21G possibly damaging Het
Tbc1d1 G A 5: 64,443,350 (GRCm39) R523Q probably damaging Het
Thnsl1 T G 2: 21,217,438 (GRCm39) D397E probably benign Het
Tubal3 T G 13: 3,983,560 (GRCm39) *447G probably null Het
Uprt T A X: 103,526,934 (GRCm39) L123H probably damaging Het
Usp9x T C X: 12,994,629 (GRCm39) L940P probably benign Het
Other mutations in Fhit
AlleleSourceChrCoordTypePredicted EffectPPH 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
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
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'- AGTCTGCAAGATTCCAGGCC -3'

Sequencing Primer
(F):5'- TGCAGACCACAAAAACCATTTCTCTG -3'
(R):5'- CCCAAGTCAATGGAACTCGGG -3'
Posted On 2015-02-19