Incidental Mutation 'R4245:Fen1'
ID 320402
Institutional Source Beutler Lab
Gene Symbol Fen1
Ensembl Gene ENSMUSG00000024742
Gene Name flap structure specific endonuclease 1
Synonyms
MMRRC Submission 041061-MU
Accession Numbers
Essential gene? Essential (E-score: 1.000) question?
Stock # R4245 (G1)
Quality Score 225
Status Validated
Chromosome 19
Chromosomal Location 10176496-10181533 bp(-) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) T to A at 10177731 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Isoleucine to Phenylalanine at position 238 (I238F)
Ref Sequence ENSEMBL: ENSMUSP00000117246 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000010807] [ENSMUST00000025651] [ENSMUST00000040372] [ENSMUST00000116542] [ENSMUST00000142241] [ENSMUST00000156291]
AlphaFold no structure available at present
Predicted Effect probably benign
Transcript: ENSMUST00000010807
SMART Domains Protein: ENSMUSP00000010807
Gene: ENSMUSG00000010663

DomainStartEndE-ValueType
Cyt-b5 22 97 1.32e-19 SMART
transmembrane domain 134 156 N/A INTRINSIC
Pfam:FA_desaturase 158 421 7.4e-35 PFAM
Predicted Effect probably damaging
Transcript: ENSMUST00000025651
AA Change: I238F

PolyPhen 2 Score 0.993 (Sensitivity: 0.70; Specificity: 0.97)
SMART Domains Protein: ENSMUSP00000025651
Gene: ENSMUSG00000024742
AA Change: I238F

DomainStartEndE-ValueType
XPGN 1 107 2.5e-60 SMART
XPGI 146 218 2.22e-34 SMART
HhH2 220 253 1.41e-13 SMART
low complexity region 354 380 N/A INTRINSIC
Predicted Effect probably benign
Transcript: ENSMUST00000040372
SMART Domains Protein: ENSMUSP00000044751
Gene: ENSMUSG00000036372

DomainStartEndE-ValueType
Pfam:UPF0197 3 79 3.3e-47 PFAM
Predicted Effect noncoding transcript
Transcript: ENSMUST00000081739
Predicted Effect probably damaging
Transcript: ENSMUST00000116542
AA Change: I238F

PolyPhen 2 Score 0.993 (Sensitivity: 0.70; Specificity: 0.97)
SMART Domains Protein: ENSMUSP00000112241
Gene: ENSMUSG00000024742
AA Change: I238F

DomainStartEndE-ValueType
XPGN 1 107 2.5e-60 SMART
XPGI 146 218 2.22e-34 SMART
HhH2 220 253 1.41e-13 SMART
low complexity region 354 380 N/A INTRINSIC
Predicted Effect noncoding transcript
Transcript: ENSMUST00000127878
Predicted Effect noncoding transcript
Transcript: ENSMUST00000150038
Predicted Effect probably damaging
Transcript: ENSMUST00000142241
AA Change: I238F

PolyPhen 2 Score 0.993 (Sensitivity: 0.70; Specificity: 0.97)
SMART Domains Protein: ENSMUSP00000119221
Gene: ENSMUSG00000024742
AA Change: I238F

DomainStartEndE-ValueType
XPGN 1 107 2.5e-60 SMART
XPGI 146 218 2.22e-34 SMART
HhH2 220 253 1.41e-13 SMART
low complexity region 354 380 N/A INTRINSIC
Predicted Effect probably damaging
Transcript: ENSMUST00000156291
AA Change: I238F

PolyPhen 2 Score 0.993 (Sensitivity: 0.70; Specificity: 0.97)
SMART Domains Protein: ENSMUSP00000117246
Gene: ENSMUSG00000024742
AA Change: I238F

DomainStartEndE-ValueType
XPGN 1 107 2.5e-60 SMART
XPGI 146 218 2.22e-34 SMART
HhH2 220 253 1.41e-13 SMART
low complexity region 354 380 N/A INTRINSIC
Predicted Effect noncoding transcript
Transcript: ENSMUST00000153854
Meta Mutation Damage Score 0.7603 question?
Coding Region Coverage
  • 1x: 99.2%
  • 3x: 98.7%
  • 10x: 97.4%
  • 20x: 95.5%
Validation Efficiency 98% (47/48)
MGI Phenotype FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] The protein encoded by this gene removes 5' overhanging flaps in DNA repair and processes the 5' ends of Okazaki fragments in lagging strand DNA synthesis. Direct physical interaction between this protein and AP endonuclease 1 during long-patch base excision repair provides coordinated loading of the proteins onto the substrate, thus passing the substrate from one enzyme to another. The protein is a member of the XPG/RAD2 endonuclease family and is one of ten proteins essential for cell-free DNA replication. DNA secondary structure can inhibit flap processing at certain trinucleotide repeats in a length-dependent manner by concealing the 5' end of the flap that is necessary for both binding and cleavage by the protein encoded by this gene. Therefore, secondary structure can deter the protective function of this protein, leading to site-specific trinucleotide expansions. [provided by RefSeq, Jul 2008]
PHENOTYPE: Homozygous null mutants do not form an inner cell mass, lack DNA synthesis in blastocyst giant cells and die by embryonic day 9.5. Embryonic day 3.5 blastocysts are hypersensitive to irradiation. Heterozygotes show enhanced adenocarcinoma susceptibility. [provided by MGI curators]
Allele List at MGI
Other mutations in this stock
Total: 41 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
4930449A18Rik T A 3: 59,733,203 (GRCm39) noncoding transcript Het
Acacb A T 5: 114,368,845 (GRCm39) T1688S probably damaging Het
Actr1b T C 1: 36,740,911 (GRCm39) Y171C possibly damaging Het
C8a A G 4: 104,733,543 (GRCm39) V4A probably benign Het
Ccdc171 A G 4: 83,473,045 (GRCm39) D158G probably damaging Het
Ccdc184 T A 15: 98,066,750 (GRCm39) probably null Het
Cdc23 T C 18: 34,770,100 (GRCm39) probably benign Het
Dnah5 A G 15: 28,219,335 (GRCm39) N51S probably benign Het
Dock10 T A 1: 80,544,472 (GRCm39) E905V probably benign Het
Eepd1 T C 9: 25,505,920 (GRCm39) I460T probably benign Het
Fhdc1 C A 3: 84,352,133 (GRCm39) V1031F probably benign Het
Gm5493 A G 17: 22,966,199 (GRCm39) E28G probably benign Het
Jakmip2 A G 18: 43,710,501 (GRCm39) V234A probably benign Het
Map3k6 T C 4: 132,979,258 (GRCm39) Y1204H possibly damaging Het
Mpeg1 C A 19: 12,440,272 (GRCm39) Q577K probably damaging Het
Mthfd1 T C 12: 76,348,047 (GRCm39) S564P probably damaging Het
Mtmr11 T A 3: 96,075,393 (GRCm39) C358S probably damaging Het
Muc4 T C 16: 32,753,802 (GRCm38) I1226T probably benign Het
Myo18b G A 5: 112,840,261 (GRCm39) H2511Y possibly damaging Het
Ndufs6 A T 13: 73,468,512 (GRCm39) D62E probably damaging Het
Or5af2 T C 11: 58,708,604 (GRCm39) Y257H probably damaging Het
Or7e178 T C 9: 20,225,629 (GRCm39) I196V possibly damaging Het
Pcdhga1 T A 18: 37,796,605 (GRCm39) D536E probably damaging Het
Phactr3 G A 2: 177,924,982 (GRCm39) probably null Het
Ptgir A G 7: 16,640,794 (GRCm39) M29V possibly damaging Het
Ptk2 C T 15: 73,103,825 (GRCm39) G749D probably benign Het
Rab3il1 A T 19: 10,007,518 (GRCm39) D222V probably damaging Het
Radil T C 5: 142,529,546 (GRCm39) D50G probably damaging Het
Rfx7 A G 9: 72,499,051 (GRCm39) T72A possibly damaging Het
Scn7a T C 2: 66,572,345 (GRCm39) I209V probably benign Het
Sf3a1 C T 11: 4,117,774 (GRCm39) R179C probably damaging Het
Spata31e2 T C 1: 26,721,161 (GRCm39) N1340D probably benign Het
Styxl2 T C 1: 165,928,685 (GRCm39) E309G probably damaging Het
Tg T C 15: 66,568,318 (GRCm39) V1335A possibly damaging Het
Thnsl1 A G 2: 21,217,059 (GRCm39) E271G probably benign Het
Vill T A 9: 118,900,359 (GRCm39) probably benign Het
Vmn2r79 A G 7: 86,651,624 (GRCm39) D341G possibly damaging Het
Wdr59 T C 8: 112,216,996 (GRCm39) N272D possibly damaging Het
Zar1 T C 5: 72,737,736 (GRCm39) E121G possibly damaging Het
Zfp985 A G 4: 147,667,396 (GRCm39) K88R probably damaging Het
Zscan29 C T 2: 120,995,275 (GRCm39) probably null Het
Other mutations in Fen1
AlleleSourceChrCoordTypePredicted EffectPPH Score
IGL02991:Fen1 UTSW 19 10,178,026 (GRCm39) missense probably benign
R3161:Fen1 UTSW 19 10,177,655 (GRCm39) missense probably damaging 0.96
R5481:Fen1 UTSW 19 10,178,022 (GRCm39) missense probably damaging 1.00
R5553:Fen1 UTSW 19 10,177,787 (GRCm39) missense probably benign
R5733:Fen1 UTSW 19 10,178,022 (GRCm39) missense possibly damaging 0.86
R5783:Fen1 UTSW 19 10,178,194 (GRCm39) nonsense probably null
R6244:Fen1 UTSW 19 10,178,051 (GRCm39) missense probably damaging 1.00
R6498:Fen1 UTSW 19 10,177,479 (GRCm39) missense probably damaging 0.96
R6797:Fen1 UTSW 19 10,178,067 (GRCm39) missense probably benign 0.37
R7988:Fen1 UTSW 19 10,177,674 (GRCm39) missense possibly damaging 0.94
R8374:Fen1 UTSW 19 10,177,824 (GRCm39) missense probably benign 0.26
R9016:Fen1 UTSW 19 10,178,306 (GRCm39) missense probably damaging 1.00
R9719:Fen1 UTSW 19 10,178,016 (GRCm39) missense probably benign 0.16
Predicted Primers PCR Primer
(F):5'- CAGACTCTGGGTCCAGTACTTC -3'
(R):5'- CCTTACCTTGATGCACCCAG -3'

Sequencing Primer
(F):5'- AGTACTTCTGGCTCCAGGAAG -3'
(R):5'- GCTGGCAAAGTCTATGCTGC -3'
Posted On 2015-06-12