Mutagenetix > Incidental Mutation

Incidental Mutation 'R5481:Fen1'

434365

Institutional Source

Beutler Lab

Gene Symbol

Fen1

Ensembl Gene

ENSMUSG00000024742

Gene Name

flap structure specific endonuclease 1

Synonyms

MMRRC Submission

043042-MU

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R5481 (G1)

Quality Score

203

Status

Not validated

Chromosome

Chromosomal Location

10176496-10181533 bp(-) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

A to G at 10178022 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Cysteine to Arginine at position 141 (C141R)

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

Domain	Start	End	E-Value	Type
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: C141R

PolyPhen 2 Score 0.997 (Sensitivity: 0.41; Specificity: 0.98)

SMART Domains

Protein: ENSMUSP00000025651
Gene: ENSMUSG00000024742
AA Change: C141R

Domain	Start	End	E-Value	Type
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

Domain	Start	End	E-Value	Type
Pfam:UPF0197	3	79	3.3e-47	PFAM

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000081739

Predicted Effect

probably damaging
Transcript: ENSMUST00000116542
AA Change: C141R

PolyPhen 2 Score 0.997 (Sensitivity: 0.41; Specificity: 0.98)

SMART Domains

Protein: ENSMUSP00000112241
Gene: ENSMUSG00000024742
AA Change: C141R

Domain	Start	End	E-Value	Type
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

probably damaging
Transcript: ENSMUST00000142241
AA Change: C141R

PolyPhen 2 Score 0.997 (Sensitivity: 0.41; Specificity: 0.98)

SMART Domains

Protein: ENSMUSP00000119221
Gene: ENSMUSG00000024742
AA Change: C141R

Domain	Start	End	E-Value	Type
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

probably damaging
Transcript: ENSMUST00000156291
AA Change: C141R

PolyPhen 2 Score 0.997 (Sensitivity: 0.41; Specificity: 0.98)

SMART Domains

Protein: ENSMUSP00000117246
Gene: ENSMUSG00000024742
AA Change: C141R

Domain	Start	End	E-Value	Type
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: 97.6%
10x: 95.1%
20x: 90.0%

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: 62 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
4930522H14Rik	A	G	4: 109,362,759 (GRCm39)	S187P	probably damaging	Het
Aass	C	A	6: 23,113,475 (GRCm39)	V282L	probably benign	Het
Adh6a	G	T	3: 138,031,719 (GRCm39)	V204F	probably damaging	Het
Adrm1b	A	G	3: 92,336,658 (GRCm39)	S15P	possibly damaging	Het
Aspm	A	G	1: 139,384,799 (GRCm39)	K148E	possibly damaging	Het
Atp12a	A	T	14: 56,610,846 (GRCm39)	D330V	possibly damaging	Het
Barhl1	A	G	2: 28,805,352 (GRCm39)	Y114H	probably damaging	Het
BC106179	T	A	16: 23,042,918 (GRCm39)		probably benign	Het
Cabin1	A	G	10: 75,570,900 (GRCm39)	L792P	probably benign	Het
Calcoco2	A	G	11: 95,998,369 (GRCm39)	V18A	probably damaging	Het
Chpf2	A	T	5: 24,794,340 (GRCm39)	H170L	probably damaging	Het
Chrna1	T	A	2: 73,397,270 (GRCm39)	I340F	possibly damaging	Het
Ckap5	A	T	2: 91,402,792 (GRCm39)	I690F	possibly damaging	Het
Col10a1	A	G	10: 34,271,660 (GRCm39)	H544R	probably benign	Het
Cyp2b19	A	C	7: 26,466,246 (GRCm39)	T350P	probably damaging	Het
Dgkq	A	G	5: 108,796,676 (GRCm39)		probably null	Het
Dnah1	A	G	14: 31,030,828 (GRCm39)	V443A	possibly damaging	Het
Erbb3	T	C	10: 128,408,349 (GRCm39)	D855G	probably damaging	Het
Fam3c	T	C	6: 22,321,357 (GRCm39)	D138G	probably benign	Het
Flnc	G	A	6: 29,441,216 (GRCm39)	G390D	probably damaging	Het
Fnip1	C	A	11: 54,393,470 (GRCm39)	D635E	probably benign	Het
Fry	A	T	5: 150,183,784 (GRCm39)	L17F	probably benign	Het
Fsip2	T	C	2: 82,810,230 (GRCm39)	I2183T	probably benign	Het
Gfpt1	T	A	6: 87,027,951 (GRCm39)	I19N	probably damaging	Het
Hus1b	T	C	13: 31,130,942 (GRCm39)	D239G	probably benign	Het
Kif1a	T	C	1: 92,987,966 (GRCm39)	K546R	probably benign	Het
Kmt2d	A	G	15: 98,759,886 (GRCm39)	V1124A	unknown	Het
Krtap16-1	A	G	11: 99,876,153 (GRCm39)	I417T	probably damaging	Het
Manba	A	T	3: 135,230,317 (GRCm39)	N297Y	possibly damaging	Het
Mblac1	A	G	5: 138,193,078 (GRCm39)	D140G	probably damaging	Het
Mlh1	T	C	9: 111,058,905 (GRCm39)		probably null	Het
Morc1	T	A	16: 48,381,848 (GRCm39)		probably null	Het
Morc3	C	A	16: 93,659,543 (GRCm39)	P449Q	probably damaging	Het
Mtr	T	C	13: 12,203,041 (GRCm39)		probably null	Het
Mylk	T	A	16: 34,741,974 (GRCm39)	C829S	probably benign	Het
Myo1d	A	G	11: 80,553,921 (GRCm39)	I520T	possibly damaging	Het
Ncam2	C	T	16: 81,231,766 (GRCm39)	R77*	probably null	Het
Nos1	A	T	5: 118,005,819 (GRCm39)	I180F	probably benign	Het
Ntsr1	C	T	2: 180,183,313 (GRCm39)	T341M	possibly damaging	Het
Or8b51	A	T	9: 38,568,916 (GRCm39)	F257L	probably benign	Het
P2rx7	A	G	5: 122,818,883 (GRCm39)	D435G	possibly damaging	Het
Peli2	C	A	14: 48,490,090 (GRCm39)	N136K	probably damaging	Het
Pigt	C	A	2: 164,348,342 (GRCm39)	P429H	probably damaging	Het
Pik3r2	T	C	8: 71,222,408 (GRCm39)	I515V	probably benign	Het
Pkhd1l1	A	G	15: 44,422,042 (GRCm39)	Y3104C	probably damaging	Het
Ppp1r16a	A	C	15: 76,575,221 (GRCm39)	E43A	probably damaging	Het
Ptpn18	T	C	1: 34,510,744 (GRCm39)	L260P	possibly damaging	Het
Scaf11	A	T	15: 96,318,498 (GRCm39)	S355R	probably damaging	Het
Sema4a	A	T	3: 88,360,347 (GRCm39)	Y77*	probably null	Het
Serpinb9b	T	C	13: 33,222,076 (GRCm39)	V230A	possibly damaging	Het
Sfswap	T	A	5: 129,591,882 (GRCm39)	S300T	probably damaging	Het
Slc22a30	T	C	19: 8,314,201 (GRCm39)	N495S	probably benign	Het
Srcap	G	A	7: 127,131,369 (GRCm39)	G836D	probably damaging	Het
Stard4	A	C	18: 33,338,298 (GRCm39)	C137W	probably benign	Het
Stat6	A	G	10: 127,483,695 (GRCm39)		probably null	Het
Steap3	T	C	1: 120,169,454 (GRCm39)	D243G	probably benign	Het
Taf1c	A	G	8: 120,325,979 (GRCm39)	S628P	probably damaging	Het
Unkl	C	T	17: 25,420,146 (GRCm39)	Q13*	probably null	Het
Usp38	A	G	8: 81,719,952 (GRCm39)	S426P	possibly damaging	Het
Vmn2r8	T	C	5: 108,949,636 (GRCm39)	T404A	probably benign	Het
Washc1	T	C	17: 66,425,860 (GRCm39)	V425A	probably benign	Het
Zfyve9	A	G	4: 108,501,546 (GRCm39)	I590T	probably damaging	Het

Other mutations in Fen1

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH 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
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'- ACTGGCAGTTAAGTGTCGC -3'
(R):5'- TGATGGGCATGTTCTACCGTAC -3'

Sequencing Primer
(F):5'- CAGTTAAGTGTCGCATTAGCACG -3'
(R):5'- GCATCAAGCCTGTGTACGTC -3'

Posted On

2016-10-06