Incidental Mutation 'R5733:Fen1'
ID 451562
Institutional Source Beutler Lab
Gene Symbol Fen1
Ensembl Gene ENSMUSG00000024742
Gene Name flap structure specific endonuclease 1
Synonyms
MMRRC Submission 043193-MU
Accession Numbers
Essential gene? Essential (E-score: 1.000) question?
Stock # R5733 (G1)
Quality Score 225
Status Not validated
Chromosome 19
Chromosomal Location 10176496-10181533 bp(-) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) A to T at 10178022 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Cysteine to Serine at position 141 (C141S)
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 possibly damaging
Transcript: ENSMUST00000025651
AA Change: C141S

PolyPhen 2 Score 0.864 (Sensitivity: 0.83; Specificity: 0.93)
SMART Domains Protein: ENSMUSP00000025651
Gene: ENSMUSG00000024742
AA Change: C141S

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 possibly damaging
Transcript: ENSMUST00000116542
AA Change: C141S

PolyPhen 2 Score 0.864 (Sensitivity: 0.83; Specificity: 0.93)
SMART Domains Protein: ENSMUSP00000112241
Gene: ENSMUSG00000024742
AA Change: C141S

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 possibly damaging
Transcript: ENSMUST00000142241
AA Change: C141S

PolyPhen 2 Score 0.864 (Sensitivity: 0.83; Specificity: 0.93)
SMART Domains Protein: ENSMUSP00000119221
Gene: ENSMUSG00000024742
AA Change: C141S

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: ENSMUST00000150038
Predicted Effect possibly damaging
Transcript: ENSMUST00000156291
AA Change: C141S

PolyPhen 2 Score 0.864 (Sensitivity: 0.83; Specificity: 0.93)
SMART Domains Protein: ENSMUSP00000117246
Gene: ENSMUSG00000024742
AA Change: C141S

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
Coding Region Coverage
  • 1x: 99.1%
  • 3x: 98.4%
  • 10x: 97.0%
  • 20x: 95.0%
Validation Efficiency
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: 43 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
Acox3 T A 5: 35,762,543 (GRCm39) probably null Het
Ahnak2 A T 12: 112,742,100 (GRCm39) Y657* probably null Het
Anxa3 T A 5: 96,968,331 (GRCm39) I128N probably damaging Het
Bsnd T C 4: 106,345,198 (GRCm39) T83A probably benign Het
Capn10 A G 1: 92,871,635 (GRCm39) Y411C probably benign Het
Capn3 G A 2: 120,315,075 (GRCm39) W201* probably null Het
Crtap T C 9: 114,207,164 (GRCm39) T365A probably benign Het
Daam1 A G 12: 71,992,272 (GRCm39) D329G unknown Het
Dmxl2 A T 9: 54,283,550 (GRCm39) L2761Q possibly damaging Het
Fcho2 A C 13: 98,926,310 (GRCm39) V91G probably damaging Het
Fkbp15 G C 4: 62,225,166 (GRCm39) A831G probably benign Het
Frmd4a A T 2: 4,305,768 (GRCm39) R14S possibly damaging Het
Fzr1 A G 10: 81,206,160 (GRCm39) F176L possibly damaging Het
Garem2 A G 5: 30,321,336 (GRCm39) D565G probably damaging Het
Garre1 A T 7: 33,944,505 (GRCm39) S76T probably damaging Het
Iqca1 G T 1: 89,998,257 (GRCm39) T549K probably damaging Het
Itgax T A 7: 127,739,647 (GRCm39) S686R probably damaging Het
Knop1 C A 7: 118,445,305 (GRCm39) G220C probably damaging Het
Lyzl1 T A 18: 4,169,142 (GRCm39) C49S probably damaging Het
Mpzl1 A T 1: 165,433,180 (GRCm39) I157K probably benign Het
Mrgprb2 T C 7: 48,202,261 (GRCm39) I155V probably benign Het
Mucl3 T C 17: 35,949,102 (GRCm39) M166V probably benign Het
Mvb12b T C 2: 33,717,728 (GRCm39) T167A probably benign Het
Myh3 A G 11: 66,979,445 (GRCm39) N491S probably benign Het
Myo5b A G 18: 74,787,128 (GRCm39) D511G possibly damaging Het
Or10ak8 C T 4: 118,774,035 (GRCm39) V210I probably benign Het
Or11h4 T C 14: 50,974,509 (GRCm39) T37A probably benign Het
Or6b1 C T 6: 42,815,180 (GRCm39) R122C probably damaging Het
Or8k21 T G 2: 86,145,558 (GRCm39) Q24P probably damaging Het
Ptcd1 A G 5: 145,091,671 (GRCm39) M476T probably damaging Het
Pum3 A G 19: 27,398,695 (GRCm39) probably null Het
Ranbp2 G A 10: 58,321,658 (GRCm39) D2652N probably damaging Het
Rassf1 T C 9: 107,435,213 (GRCm39) V166A probably damaging Het
Rictor A G 15: 6,812,585 (GRCm39) H907R probably benign Het
Rorb T C 19: 18,965,471 (GRCm39) E6G probably damaging Het
Serpina3f A T 12: 104,183,182 (GRCm39) T15S possibly damaging Het
Sorbs2 T C 8: 46,212,226 (GRCm39) L100P probably damaging Het
Sprr2k T C 3: 92,340,655 (GRCm39) probably benign Het
Srrm2 T A 17: 24,040,360 (GRCm39) S2431T probably damaging Het
Stox2 T A 8: 47,866,172 (GRCm39) K57* probably null Het
Ttc21a G A 9: 119,770,327 (GRCm39) V133I probably benign Het
Vasn T C 16: 4,468,026 (GRCm39) Y658H possibly damaging Het
Zfp251 A G 15: 76,754,527 (GRCm39) Y35H probably damaging 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
R4245:Fen1 UTSW 19 10,177,731 (GRCm39) missense probably damaging 0.99
R5481:Fen1 UTSW 19 10,178,022 (GRCm39) missense probably damaging 1.00
R5553:Fen1 UTSW 19 10,177,787 (GRCm39) missense probably benign
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'- TCACTGGCAGTTAAGTGTCG -3'
(R):5'- TGGGCATGTTCTACCGTACC -3'

Sequencing Primer
(F):5'- CAGTTAAGTGTCGCATTAGCACG -3'
(R):5'- GCATCAAGCCTGTGTACGTC -3'
Posted On 2017-01-03