Incidental Mutation 'R9719:Fen1'
ID 730691
Institutional Source Beutler Lab
Gene Symbol Fen1
Ensembl Gene ENSMUSG00000024742
Gene Name flap structure specific endonuclease 1
Synonyms
MMRRC Submission
Accession Numbers
Essential gene? Essential (E-score: 1.000) question?
Stock # R9719 (G1)
Quality Score 225.009
Status Not validated
Chromosome 19
Chromosomal Location 10176496-10181533 bp(-) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) G to A at 10178016 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Histidine to Tyrosine at position 143 (H143Y)
Ref Sequence ENSEMBL: ENSMUSP00000025651 (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 benign
Transcript: ENSMUST00000025651
AA Change: H143Y

PolyPhen 2 Score 0.155 (Sensitivity: 0.92; Specificity: 0.87)
SMART Domains Protein: ENSMUSP00000025651
Gene: ENSMUSG00000024742
AA Change: H143Y

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 probably benign
Transcript: ENSMUST00000116542
AA Change: H143Y

PolyPhen 2 Score 0.155 (Sensitivity: 0.92; Specificity: 0.87)
SMART Domains Protein: ENSMUSP00000112241
Gene: ENSMUSG00000024742
AA Change: H143Y

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: ENSMUST00000142241
AA Change: H143Y

PolyPhen 2 Score 0.155 (Sensitivity: 0.92; Specificity: 0.87)
SMART Domains Protein: ENSMUSP00000119221
Gene: ENSMUSG00000024742
AA Change: H143Y

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: ENSMUST00000156291
AA Change: H143Y

PolyPhen 2 Score 0.155 (Sensitivity: 0.92; Specificity: 0.87)
SMART Domains Protein: ENSMUSP00000117246
Gene: ENSMUSG00000024742
AA Change: H143Y

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
Coding Region Coverage
  • 1x: 100.0%
  • 3x: 99.9%
  • 10x: 99.7%
  • 20x: 99.1%
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: 48 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
Alppl2 T A 1: 87,016,136 (GRCm39) Q241L probably benign Het
Apob T A 12: 8,065,464 (GRCm39) N4144K probably benign Het
B4gat1 A G 19: 5,090,516 (GRCm39) H413R probably benign Het
Ccdc179 T C 7: 51,664,612 (GRCm39) T28A probably benign Het
Ceacam5 A C 7: 17,491,835 (GRCm39) D735A probably damaging Het
Col18a1 C T 10: 76,949,432 (GRCm39) D27N unknown Het
Colgalt1 A G 8: 72,073,456 (GRCm39) E359G probably benign Het
Crybg2 T A 4: 133,793,148 (GRCm39) I261N probably benign Het
Cyyr1 A T 16: 85,219,203 (GRCm39) L68Q unknown Het
Dgkz T A 2: 91,768,911 (GRCm39) probably null Het
Efcab3 A T 11: 104,867,912 (GRCm39) E3947V unknown Het
Eif2ak2 C A 17: 79,162,783 (GRCm39) D472Y probably damaging Het
Elp2 A G 18: 24,755,539 (GRCm39) T429A possibly damaging Het
Gm10518 C A 1: 179,631,113 (GRCm39) R58S unknown Het
Hspa1b T C 17: 35,176,467 (GRCm39) D506G probably damaging Het
Inhca G T 9: 103,132,014 (GRCm39) P569H probably benign Het
Kcna7 A G 7: 45,056,390 (GRCm39) D202G probably benign Het
Krt9 TCCACTTCCTCCTCCATAGCTGCCCCCACTTCCTCCTCCATAGCTGCCCCCACTTCCTCCTCCATAGCTGCCCCCACTTCCTCCTCCATAGCTGCC TCCACTTCCTCCTCCATAGCTGCCCCCACTTCCTCCTCCATAGCTGCCCCCACTTCCTCCTCCATAGCTGCC 11: 100,079,903 (GRCm39) probably benign Het
Mal C T 2: 127,498,025 (GRCm39) S10N possibly damaging Het
Mgat2 T A 12: 69,232,115 (GRCm39) W230R probably damaging Het
Myo3a A T 2: 22,436,493 (GRCm39) T883S probably benign Het
Ncaph2 T C 15: 89,249,526 (GRCm39) S277P probably benign Het
Olfm3 G A 3: 114,916,091 (GRCm39) W341* probably null Het
Or13c7e-ps1 A C 4: 43,781,454 (GRCm39) M292R probably damaging Het
Or1p1 A C 11: 74,180,146 (GRCm39) I225L probably damaging Het
Or5b119 A G 19: 13,457,368 (GRCm39) S65P probably damaging Het
Or5d46 T A 2: 88,169,928 (GRCm39) N6K Het
Or5g26 T A 2: 85,494,608 (GRCm39) I57F probably benign Het
Or6z1 C A 7: 6,504,999 (GRCm39) M75I probably benign Het
Pcnx4 T C 12: 72,603,039 (GRCm39) Y434H probably damaging Het
Ptpn14 T A 1: 189,583,484 (GRCm39) M777K probably benign Het
Rasef A G 4: 73,688,102 (GRCm39) I17T possibly damaging Het
Rptor A T 11: 119,781,940 (GRCm39) D1089V probably benign Het
Scel A T 14: 103,809,442 (GRCm39) probably null Het
Scfd2 A T 5: 74,386,004 (GRCm39) L605Q probably damaging Het
Son A G 16: 91,456,440 (GRCm39) E1729G probably damaging Het
Spata31e2 C G 1: 26,722,820 (GRCm39) E787Q probably benign Het
Spout1 A G 2: 30,065,813 (GRCm39) Y243H probably benign Het
Syne1 A G 10: 5,276,601 (GRCm39) F1765S possibly damaging Het
Tet2 A T 3: 133,191,803 (GRCm39) V877E possibly damaging Het
Txn2 T C 15: 77,812,289 (GRCm39) probably benign Het
Vmn1r158 T C 7: 22,489,331 (GRCm39) I293V possibly damaging Het
Vmn1r81 G A 7: 11,994,449 (GRCm39) T53I probably damaging Het
Vps18 T C 2: 119,127,553 (GRCm39) F792S probably damaging Het
Vps25 A G 11: 101,146,853 (GRCm39) D91G probably null Het
Wdr26 G A 1: 181,015,224 (GRCm39) L396F possibly damaging Het
Zfp1005 T A 2: 150,111,304 (GRCm39) C665S possibly damaging Het
Zfp26 T C 9: 20,347,861 (GRCm39) E901G possibly 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
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
Predicted Primers PCR Primer
(F):5'- CTCACTGGCAGTTAAGTGTCG -3'
(R):5'- ATGGGCATGTTCTACCGTAC -3'

Sequencing Primer
(F):5'- CAGTTAAGTGTCGCATTAGCACG -3'
(R):5'- GTACGTCTTTGATGGCAAACC -3'
Posted On 2022-10-06