Mutagenetix > Incidental Mutation

Incidental Mutation 'R1240:Fh1'

151910

Institutional Source

Beutler Lab

Gene Symbol

Fh1

Ensembl Gene

ENSMUSG00000026526

Gene Name

fumarate hydratase 1

Synonyms

fumarase

MMRRC Submission

039307-MU

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R1240 (G1)

Quality Score

225

Status

Not validated

Chromosome

Chromosomal Location

175428944-175453201 bp(-) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

A to T at 175431581 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Isoleucine to Asparagine at position 435 (I435N)

Ref Sequence

ENSEMBL: ENSMUSP00000027810 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000027810]

AlphaFold

P97807

Predicted Effect

probably damaging
Transcript: ENSMUST00000027810
AA Change: I435N

PolyPhen 2 Score 0.999 (Sensitivity: 0.14; Specificity: 0.99)

SMART Domains

Protein: ENSMUSP00000027810
Gene: ENSMUSG00000026526
AA Change: I435N

Domain	Start	End	E-Value	Type
low complexity region	3	16	N/A	INTRINSIC
Pfam:Lyase_1	55	386	1.8e-124	PFAM
Pfam:FumaraseC_C	452	505	2.5e-29	PFAM

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000130996

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000133218

Predicted Effect

unknown
Transcript: ENSMUST00000176740
AA Change: I94N

Coding Region Coverage

1x: 99.1%
3x: 98.3%
10x: 96.3%
20x: 92.8%

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 is an enzymatic component of the tricarboxylic acid (TCA) cycle, or Krebs cycle, and catalyzes the formation of L-malate from fumarate. It exists in both a cytosolic form and an N-terminal extended form, differing only in the translation start site used. The N-terminal extended form is targeted to the mitochondrion, where the removal of the extension generates the same form as in the cytoplasm. It is similar to some thermostable class II fumarases and functions as a homotetramer. Mutations in this gene can cause fumarase deficiency and lead to progressive encephalopathy. [provided by RefSeq, Jul 2008]
PHENOTYPE: Embryos homozygous for a knock-out allele fail to develop past the egg-cylinder stage and die at E6.0. [provided by MGI curators]

Allele List at MGI

Other mutations in this stock

Total: 60 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Abcb9	T	G	5: 124,227,984 (GRCm39)	I86L	probably benign	Het
Ankfn1	A	G	11: 89,282,960 (GRCm39)	L229P	probably damaging	Het
Aoc1	T	C	6: 48,882,549 (GRCm39)	S164P	probably benign	Het
Arhgef28	C	T	13: 98,066,000 (GRCm39)	V1618I	probably benign	Het
Arpc3	T	C	5: 122,542,242 (GRCm39)	F88S	probably damaging	Het
Asgr2	G	T	11: 69,987,676 (GRCm39)	R58L	possibly damaging	Het
Bach2	T	C	4: 32,563,198 (GRCm39)	F432S	probably damaging	Het
Brms1l	C	A	12: 55,891,293 (GRCm39)	R116S	probably damaging	Het
Casp2	T	A	6: 42,245,879 (GRCm39)	C179S	probably damaging	Het
Ccdc73	A	T	2: 104,821,906 (GRCm39)	E618D	probably benign	Het
Cdh6	T	A	15: 13,057,541 (GRCm39)	D260V	possibly damaging	Het
Cenpc1	G	T	5: 86,183,369 (GRCm39)	N473K	probably benign	Het
Chst2	T	C	9: 95,287,536 (GRCm39)	E270G	possibly damaging	Het
Chst9	C	T	18: 15,586,231 (GRCm39)	E111K	probably benign	Het
Cyp3a44	T	G	5: 145,711,250 (GRCm39)	I474L	probably benign	Het
Dbr1	G	T	9: 99,466,073 (GRCm39)	E550D	probably benign	Het
Dph6	T	C	2: 114,475,199 (GRCm39)		probably null	Het
Fam227b	T	A	2: 125,966,505 (GRCm39)	I136L	possibly damaging	Het
Fcgbp	A	G	7: 27,819,950 (GRCm39)	N2559S	probably damaging	Het
Gab1	A	C	8: 81,515,159 (GRCm39)	S386R	probably damaging	Het
Gkn1	T	A	6: 87,326,098 (GRCm39)	N31Y	probably damaging	Het
Grk2	A	G	19: 4,340,707 (GRCm39)	C251R	probably damaging	Het
H2-DMa	G	T	17: 34,357,380 (GRCm39)		probably null	Het
Hp1bp3	T	C	4: 137,957,009 (GRCm39)	S63P	probably damaging	Het
Ift74	A	G	4: 94,581,174 (GRCm39)		probably null	Het
Inf2	G	A	12: 112,577,210 (GRCm39)	R1018Q	unknown	Het
Kat2b	A	G	17: 53,931,425 (GRCm39)	D141G	probably benign	Het
Klhl30	T	C	1: 91,288,737 (GRCm39)	S499P	probably benign	Het
Lama2	A	C	10: 26,917,120 (GRCm39)	D2268E	probably damaging	Het
Lsmem1	GTACATACATACATACATACATACATACA	GTACATACATACATACATACATACATACATACA	12: 40,235,260 (GRCm39)		probably null	Het
Marf1	T	C	16: 13,964,626 (GRCm39)	N258S	possibly damaging	Het
Mc1r	T	A	8: 124,134,999 (GRCm39)	C251S	probably damaging	Het
Myo15b	C	A	11: 115,771,327 (GRCm39)	Q257K	possibly damaging	Het
Nbeal2	A	G	9: 110,456,176 (GRCm39)	F2431S	probably damaging	Het
Neb	T	A	2: 52,186,321 (GRCm39)	H917L	possibly damaging	Het
Nlrp1a	A	G	11: 71,004,292 (GRCm39)		probably null	Het
Nr1d2	A	T	14: 18,211,891 (GRCm38)	M404K	probably benign	Het
Or4b1d	T	G	2: 89,969,157 (GRCm39)	I109L	possibly damaging	Het
Or8u8	T	G	2: 86,012,453 (GRCm39)	M1L	possibly damaging	Het
Otoa	T	C	7: 120,755,713 (GRCm39)	S1040P	probably benign	Het
Pctp	T	C	11: 89,893,640 (GRCm39)	D10G	probably benign	Het
Pja2	G	T	17: 64,616,613 (GRCm39)	T94K	probably benign	Het
Plxna1	C	T	6: 89,298,032 (GRCm39)	V1749M	probably damaging	Het
Prdm15	C	T	16: 97,638,800 (GRCm39)	E87K	probably damaging	Het
Rgsl1	A	G	1: 153,660,937 (GRCm39)	F1028L	probably benign	Het
Sepsecs	T	C	5: 52,818,021 (GRCm39)	N252S	probably damaging	Het
Skint5	A	T	4: 113,574,304 (GRCm39)	L749Q	unknown	Het
Slc22a22	G	A	15: 57,114,268 (GRCm39)	S353F	probably benign	Het
Slc49a4	A	G	16: 35,518,379 (GRCm39)	F445L	probably benign	Het
Slc7a13	A	T	4: 19,819,212 (GRCm39)	K137N	probably damaging	Het
Snx13	G	T	12: 35,141,405 (GRCm39)	V163L	probably damaging	Het
Synrg	A	T	11: 83,914,182 (GRCm39)	T1115S	probably damaging	Het
Tenm3	A	G	8: 48,740,928 (GRCm39)	V1185A	possibly damaging	Het
Tent5b	T	C	4: 133,213,815 (GRCm39)	F229L	probably benign	Het
Tg	T	A	15: 66,700,397 (GRCm39)	N118K	probably benign	Het
Top1mt	T	C	15: 75,541,916 (GRCm39)	K153E	probably damaging	Het
Trmt11	T	C	10: 30,466,821 (GRCm39)		probably benign	Het
Unc80	A	G	1: 66,675,061 (GRCm39)	D1953G	possibly damaging	Het
Vmn2r25	T	A	6: 123,828,864 (GRCm39)	S137C	probably damaging	Het
Vwf	C	A	6: 125,580,271 (GRCm39)		probably null	Het

Other mutations in Fh1

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL01723:Fh1	APN	1	175,429,108 (GRCm39)	missense	probably damaging	1.00
IGL02637:Fh1	APN	1	175,437,332 (GRCm39)	missense	probably benign	0.00
IGL02954:Fh1	APN	1	175,437,301 (GRCm39)	missense	probably damaging	1.00
IGL03056:Fh1	APN	1	175,433,728 (GRCm39)	missense	probably damaging	1.00
IGL03309:Fh1	APN	1	175,431,609 (GRCm39)	missense	probably benign	0.01
R0729:Fh1	UTSW	1	175,442,383 (GRCm39)	missense	probably damaging	1.00
R1327:Fh1	UTSW	1	175,437,310 (GRCm39)	missense	probably benign	0.32
R1576:Fh1	UTSW	1	175,435,385 (GRCm39)	missense	probably null	1.00
R1779:Fh1	UTSW	1	175,428,990 (GRCm39)	makesense	probably null
R1823:Fh1	UTSW	1	175,444,114 (GRCm39)	missense	probably damaging	1.00
R1851:Fh1	UTSW	1	175,435,452 (GRCm39)	missense	probably damaging	1.00
R1943:Fh1	UTSW	1	175,437,344 (GRCm39)	missense	probably benign
R2163:Fh1	UTSW	1	175,442,406 (GRCm39)	missense	possibly damaging	0.80
R3766:Fh1	UTSW	1	175,442,316 (GRCm39)	missense	probably damaging	1.00
R4193:Fh1	UTSW	1	175,442,407 (GRCm39)	missense	possibly damaging	0.51
R4672:Fh1	UTSW	1	175,431,617 (GRCm39)	missense	probably benign	0.07
R4812:Fh1	UTSW	1	175,429,025 (GRCm39)	missense	probably damaging	0.99
R4849:Fh1	UTSW	1	175,448,072 (GRCm39)	missense	probably benign	0.00
R4905:Fh1	UTSW	1	175,446,639 (GRCm39)	missense	probably damaging	1.00
R4978:Fh1	UTSW	1	175,431,533 (GRCm39)	missense	probably damaging	1.00
R6645:Fh1	UTSW	1	175,442,442 (GRCm39)	missense	possibly damaging	0.94
R6681:Fh1	UTSW	1	175,446,690 (GRCm39)	missense	probably null	0.71
R7075:Fh1	UTSW	1	175,435,421 (GRCm39)	missense	probably benign	0.00
R7646:Fh1	UTSW	1	175,442,479 (GRCm39)	missense	probably benign	0.03
R7783:Fh1	UTSW	1	175,439,744 (GRCm39)	missense	probably damaging	1.00
R7862:Fh1	UTSW	1	175,442,400 (GRCm39)	missense	probably damaging	0.97
R7991:Fh1	UTSW	1	175,437,337 (GRCm39)	missense	probably damaging	1.00
R8694:Fh1	UTSW	1	175,448,126 (GRCm39)	missense	probably benign	0.00
R8765:Fh1	UTSW	1	175,435,378 (GRCm39)	intron	probably benign
R8882:Fh1	UTSW	1	175,437,353 (GRCm39)	missense	possibly damaging	0.85

Predicted Primers

PCR Primer
(F):5'- TAAACACCAGCATCCGAGGTCCTG -3'
(R):5'- CCAAGGGCTGTCTTGTGTTAATTGC -3'

Sequencing Primer
(F):5'- agacagacagacagacacac -3'
(R):5'- TACATGTCCAGTATGGAACAGC -3'

Posted On

2014-01-29