Mutagenetix > Incidental Mutation

Incidental Mutation 'R3161:Fen1'

258192

Institutional Source

Beutler Lab

Gene Symbol

Fen1

Ensembl Gene

ENSMUSG00000024742

Gene Name

flap structure specific endonuclease 1

Synonyms

MMRRC Submission

040612-MU

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R3161 (G1)

Quality Score

225

Status

Validated

Chromosome

Chromosomal Location

10176496-10181533 bp(-) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

A to G at 10177655 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Leucine to Proline at position 263 (L263P)

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: L263P

PolyPhen 2 Score 0.959 (Sensitivity: 0.78; Specificity: 0.95)

SMART Domains

Protein: ENSMUSP00000025651
Gene: ENSMUSG00000024742
AA Change: L263P

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: L263P

PolyPhen 2 Score 0.959 (Sensitivity: 0.78; Specificity: 0.95)

SMART Domains

Protein: ENSMUSP00000112241
Gene: ENSMUSG00000024742
AA Change: L263P

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: L263P

PolyPhen 2 Score 0.959 (Sensitivity: 0.78; Specificity: 0.95)

SMART Domains

Protein: ENSMUSP00000119221
Gene: ENSMUSG00000024742
AA Change: L263P

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 damaging
Transcript: ENSMUST00000156291
AA Change: L263P

PolyPhen 2 Score 0.959 (Sensitivity: 0.78; Specificity: 0.95)

SMART Domains

Protein: ENSMUSP00000117246
Gene: ENSMUSG00000024742
AA Change: L263P

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

noncoding transcript
Transcript: ENSMUST00000153854

Meta Mutation Damage Score

0.4562

Coding Region Coverage

1x: 99.1%
3x: 98.5%
10x: 97.1%
20x: 94.3%

Validation Efficiency

98% (54/55)

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: 52 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
0610040J01Rik	T	C	5: 64,053,833 (GRCm39)		probably benign	Het
1700066M21Rik	T	A	1: 57,422,234 (GRCm39)	N203K	probably benign	Het
Adcy9	A	G	16: 4,129,452 (GRCm39)	L715P	probably damaging	Het
Adgrl2	G	A	3: 148,523,187 (GRCm39)	L1354F	probably damaging	Het
Amer2	A	G	14: 60,616,000 (GRCm39)	D65G	probably damaging	Het
Aox1	G	T	1: 58,343,597 (GRCm39)	V427L	possibly damaging	Het
Atad2b	C	A	12: 4,989,689 (GRCm39)	N133K	possibly damaging	Het
Bptf	A	T	11: 106,965,302 (GRCm39)	D1182E	probably damaging	Het
Camk1g	T	C	1: 193,042,115 (GRCm39)	T45A	possibly damaging	Het
Caps2	C	A	10: 112,018,391 (GRCm39)	Y180*	probably null	Het
Cfap54	T	A	10: 92,881,140 (GRCm39)	K349N	probably damaging	Het
Chct1	A	G	11: 85,064,110 (GRCm39)	S84G	probably damaging	Het
Ciz1	A	G	2: 32,260,075 (GRCm39)	D207G	probably benign	Het
Copa	T	A	1: 171,918,800 (GRCm39)	C127S	probably damaging	Het
Crabp2	A	T	3: 87,859,484 (GRCm39)	K45*	probably null	Het
Daam1	C	A	12: 71,993,872 (GRCm39)	T425K	unknown	Het
Dapk2	T	G	9: 66,161,893 (GRCm39)	V267G	probably damaging	Het
Disp1	T	C	1: 182,868,806 (GRCm39)	K1205E	probably benign	Het
Dlg4	G	C	11: 69,908,051 (GRCm39)	R4T	probably damaging	Het
Fbf1	A	G	11: 116,039,046 (GRCm39)	I743T	probably damaging	Het
G6pc2	A	G	2: 69,050,456 (GRCm39)	N27S	probably damaging	Het
Garnl3	A	T	2: 32,924,723 (GRCm39)	N246K	probably damaging	Het
Gm7337	A	C	5: 87,999,416 (GRCm39)		noncoding transcript	Het
Gpr152	A	G	19: 4,192,713 (GRCm39)	T85A	probably benign	Het
Hnrnpu	T	C	1: 178,158,690 (GRCm39)		probably benign	Het
Ighv1-81	C	G	12: 115,883,949 (GRCm39)	E101Q	probably benign	Het
Ipo9	T	C	1: 135,337,214 (GRCm39)	T174A	probably benign	Het
Myo9a	C	T	9: 59,739,598 (GRCm39)		probably benign	Het
Nup155	G	T	15: 8,177,867 (GRCm39)	R1083S	possibly damaging	Het
Or11g24	T	A	14: 50,662,488 (GRCm39)	C171S	probably damaging	Het
Or5an1c	T	C	19: 12,218,860 (GRCm39)	H55R	probably benign	Het
Or6d13	C	T	6: 116,517,807 (GRCm39)	A131V	probably damaging	Het
Or7a35	C	A	10: 78,853,438 (GRCm39)	T94N	probably benign	Het
Phyh	T	A	2: 4,942,482 (GRCm39)		probably benign	Het
Pkp4	G	T	2: 59,138,449 (GRCm39)	R233M	probably damaging	Het
Plcb1	A	T	2: 135,177,402 (GRCm39)	Q578L	probably benign	Het
Ppil3	A	T	1: 58,473,573 (GRCm39)	N92K	probably benign	Het
Prokr1	C	T	6: 87,565,413 (GRCm39)	R144H	probably damaging	Het
Psap	T	C	10: 60,113,575 (GRCm39)	L4P	possibly damaging	Het
Rai14	T	C	15: 10,633,250 (GRCm39)	T47A	possibly damaging	Het
Rps2	G	T	17: 24,939,952 (GRCm39)	A129S	probably benign	Het
Sult2a4	T	C	7: 13,723,396 (GRCm39)	T40A	probably benign	Het
Tacr2	A	G	10: 62,101,024 (GRCm39)	D378G	probably benign	Het
Topaz1	T	C	9: 122,578,446 (GRCm39)	I452T	probably benign	Het
Ttn	A	G	2: 76,663,581 (GRCm39)		probably benign	Het
Vmn2r115	T	A	17: 23,575,998 (GRCm39)	M532K	possibly damaging	Het
Vmn2r117	A	G	17: 23,679,352 (GRCm39)	L624P	probably damaging	Het
Vstm5	T	G	9: 15,168,594 (GRCm39)	S53A	probably benign	Het
Wipf1	C	T	2: 73,265,293 (GRCm39)	E437K	probably damaging	Het
Wls	G	T	3: 159,603,073 (GRCm39)	C162F	probably damaging	Het
Yeats2	T	C	16: 20,012,395 (GRCm39)	V531A	probably damaging	Het
Zfp868	A	G	8: 70,064,736 (GRCm39)	S200P	probably benign	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
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'- TTGACCCCACTGCGAATTC -3'
(R):5'- TGCGACACTTAACTGCCAGTG -3'

Sequencing Primer
(F):5'- GAATTCGCTCTTCAGAAAACTGC -3'
(R):5'- GCTGCCCATCCAAGAGTTC -3'

Posted On

2015-01-23