Incidental Mutation 'IGL02991:Fen1'
ID 452954
Institutional Source Beutler Lab
Gene Symbol Fen1
Ensembl Gene ENSMUSG00000024742
Gene Name flap structure specific endonuclease 1
Synonyms
Accession Numbers
Essential gene? Essential (E-score: 1.000) question?
Stock # IGL02991 (G1)
Quality Score 225
Status Validated
Chromosome 19
Chromosomal Location 10176496-10181533 bp(-) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) A to T at 10178026 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Aspartic acid to Glutamic Acid at position 139 (D139E)
Ref Sequence ENSEMBL: ENSMUSP00000117246 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000010807] [ENSMUST00000025651] [ENSMUST00000040372] [ENSMUST00000116542] [ENSMUST00000156291] [ENSMUST00000142241]
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: D139E

PolyPhen 2 Score 0.000 (Sensitivity: 1.00; Specificity: 0.00)
SMART Domains Protein: ENSMUSP00000025651
Gene: ENSMUSG00000024742
AA Change: D139E

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 benign
Transcript: ENSMUST00000116542
AA Change: D139E

PolyPhen 2 Score 0.000 (Sensitivity: 1.00; Specificity: 0.00)
SMART Domains Protein: ENSMUSP00000112241
Gene: ENSMUSG00000024742
AA Change: D139E

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 benign
Transcript: ENSMUST00000156291
AA Change: D139E

PolyPhen 2 Score 0.000 (Sensitivity: 1.00; Specificity: 0.00)
SMART Domains Protein: ENSMUSP00000117246
Gene: ENSMUSG00000024742
AA Change: D139E

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: D139E

PolyPhen 2 Score 0.000 (Sensitivity: 1.00; Specificity: 0.00)
SMART Domains Protein: ENSMUSP00000119221
Gene: ENSMUSG00000024742
AA Change: D139E

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 0.0822 question?
Coding Region Coverage
  • 1x: 0.0%
  • 3x: 0.0%
  • 10x: 0.0%
  • 20x: 0.0%
Validation Efficiency 95% (73/77)
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: 64 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
4933416I08Rik TCC TCCC X: 52,692,862 (GRCm39) noncoding transcript Het
Adam23 T C 1: 63,586,978 (GRCm39) probably null Het
Aptx C A 4: 40,686,687 (GRCm39) G199C probably damaging Het
Asap2 T C 12: 21,299,294 (GRCm39) probably benign Het
Atp11b A G 3: 35,881,140 (GRCm39) T566A probably benign Het
Bcas3 C T 11: 85,348,713 (GRCm39) Q202* probably null Het
Cacna1h C A 17: 25,610,286 (GRCm39) R740L possibly damaging Het
Casp8 T A 1: 58,866,438 (GRCm39) N146K probably benign Het
Ccdc63 T C 5: 122,246,275 (GRCm39) M549V probably benign Het
Cdc45 C T 16: 18,617,479 (GRCm39) M200I probably benign Het
Cdh20 T C 1: 104,861,972 (GRCm39) S51P probably benign Het
Chd7 T C 4: 8,828,398 (GRCm39) M1113T possibly damaging Het
Cilp TGGG TGG 9: 65,187,412 (GRCm39) probably null Het
Crb1 ACC AC 1: 139,164,822 (GRCm39) probably null Het
Crb1 CG C 1: 139,164,824 (GRCm39) probably null Het
Cxcl11 C T 5: 92,509,169 (GRCm39) R28H probably damaging Het
Defb40 C T 8: 19,025,119 (GRCm39) C29Y probably damaging Het
Fcna G C 2: 25,520,693 (GRCm39) probably benign Het
Frem3 A G 8: 81,395,511 (GRCm39) E1846G probably damaging Het
Gria2 T A 3: 80,615,116 (GRCm39) K455* probably null Het
Hmcn1 A T 1: 150,614,409 (GRCm39) N1332K possibly damaging Het
Htr5b C T 1: 121,455,756 (GRCm39) V55M probably benign Het
Ighv6-5 A T 12: 114,380,315 (GRCm39) N86K probably benign Het
Il4ra T C 7: 125,174,833 (GRCm39) V347A possibly damaging Het
Itih5 A G 2: 10,256,162 (GRCm39) E876G probably benign Het
Itpkb A T 1: 180,155,279 (GRCm39) probably benign Het
Lbr T C 1: 181,649,117 (GRCm39) Y334C probably damaging Het
Lrfn2 T C 17: 49,377,732 (GRCm39) L271P probably damaging Het
Lss T A 10: 76,379,745 (GRCm39) probably benign Het
Map1a T C 2: 121,132,091 (GRCm39) V731A probably damaging Het
Mmp1a TG TGG 9: 7,465,083 (GRCm38) probably null Het
Mob3b T A 4: 35,083,805 (GRCm39) Q128L probably benign Het
Mog T C 17: 37,334,091 (GRCm39) M1V probably null Het
Mrpl4 A G 9: 20,919,901 (GRCm39) Y284C probably damaging Het
Mtus2 T G 5: 148,250,310 (GRCm39) V310G probably damaging Het
Mup11 ACAGCAGCAGCAGCAGCA ACAGCAGCAGCAGCA 4: 60,618,275 (GRCm39) probably benign Het
Odad4 A G 11: 100,444,698 (GRCm39) S285G probably benign Het
Or10g9 T C 9: 39,911,698 (GRCm39) Y275C probably damaging Het
Or8g55 T A 9: 39,785,362 (GRCm39) S264T probably benign Het
Orc3 T G 4: 34,593,083 (GRCm39) Q328P probably damaging Het
Otulinl T C 15: 27,658,388 (GRCm39) S211G possibly damaging Het
Pcdhb20 G T 18: 37,639,264 (GRCm39) G597C probably damaging Het
Pdxdc1 A G 16: 13,675,260 (GRCm39) I334T probably damaging Het
Ppef2 C T 5: 92,383,759 (GRCm39) W450* probably null Het
Proz G A 8: 13,123,490 (GRCm39) E254K probably benign Het
Psma6 T C 12: 55,454,357 (GRCm39) probably benign Het
Rbm12 C T 2: 155,937,480 (GRCm39) probably benign Het
Ryr2 A G 13: 11,776,192 (GRCm39) V1115A probably damaging Het
Sfxn5 G T 6: 85,266,190 (GRCm39) N102K possibly damaging Het
Sgo2a G T 1: 58,054,514 (GRCm39) probably benign Het
Slc14a2 A T 18: 78,249,049 (GRCm39) M1K probably null Het
Spag5 T A 11: 78,205,077 (GRCm39) L621M probably damaging Het
Spata31 A G 13: 65,068,533 (GRCm39) Y227C probably benign Het
Speer4c1 A C 5: 15,919,214 (GRCm39) probably benign Het
Supt6 T C 11: 78,116,179 (GRCm39) E728G probably damaging Het
Sympk T A 7: 18,764,502 (GRCm39) L69Q probably damaging Het
Timd4 T A 11: 46,732,974 (GRCm39) probably benign Het
Trh G A 6: 92,220,719 (GRCm39) R48W probably damaging Het
Trip12 C A 1: 84,716,536 (GRCm39) D383Y probably damaging Het
Tspo2 T A 17: 48,757,014 (GRCm39) I23F possibly damaging Het
Tspyl5 A G 15: 33,686,989 (GRCm39) S319P probably damaging Het
Txlnb A G 10: 17,717,201 (GRCm39) K403E probably damaging Het
Vmn2r34 C A 7: 7,675,720 (GRCm39) C556F probably damaging Het
Vps13c C A 9: 67,821,159 (GRCm39) A1223E probably damaging Het
Other mutations in Fen1
AlleleSourceChrCoordTypePredicted EffectPPH Score
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
R9719:Fen1 UTSW 19 10,178,016 (GRCm39) missense probably benign 0.16
Predicted Primers PCR Primer
(F):5'- CACTGGCAGTTAAGTGTCGC -3'
(R):5'- ATGGGCATGTTCTACCGTACC -3'

Sequencing Primer
(F):5'- CAGTTAAGTGTCGCATTAGCACG -3'
(R):5'- GCATCAAGCCTGTGTACGTC -3'
Posted On 2017-01-24