Mutagenetix > Incidental Mutation

Incidental Mutation 'R0729:Fh1'

67358

Institutional Source

Beutler Lab

Gene Symbol

Fh1

Ensembl Gene

ENSMUSG00000026526

Gene Name

fumarate hydratase 1

Synonyms

fumarase

MMRRC Submission

038910-MU

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R0729 (G1)

Quality Score

225

Status

Validated

Chromosome

Chromosomal Location

175428944-175453201 bp(-) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

T to G at 175442383 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Asparagine to Histidine at position 156 (N156H)

Ref Sequence

ENSEMBL: ENSMUSP00000027810 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000027810] [ENSMUST00000154956]

AlphaFold

P97807

Predicted Effect

probably damaging
Transcript: ENSMUST00000027810
AA Change: N156H

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)

SMART Domains

Protein: ENSMUSP00000027810
Gene: ENSMUSG00000026526
AA Change: N156H

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

probably benign
Transcript: ENSMUST00000154956

SMART Domains

Protein: ENSMUSP00000135140
Gene: ENSMUSG00000026526

Domain	Start	End	E-Value	Type
low complexity region	3	16	N/A	INTRINSIC

Meta Mutation Damage Score

0.9735

Coding Region Coverage

1x: 99.4%
3x: 98.9%
10x: 97.8%
20x: 96.0%

Validation Efficiency

97% (74/76)

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: 71 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
4933427D14Rik	C	A	11: 72,050,281 (GRCm39)	A828S	probably benign	Het
Acsm3	T	C	7: 119,383,207 (GRCm39)		probably benign	Het
Adamts12	G	A	15: 11,255,769 (GRCm39)	R446H	possibly damaging	Het
Adgrb1	A	G	15: 74,420,398 (GRCm39)	N849S	probably damaging	Het
Ankra2	A	G	13: 98,408,235 (GRCm39)	D228G	probably damaging	Het
Bicd1	T	C	6: 149,414,412 (GRCm39)	V375A	probably damaging	Het
Blvrb	A	G	7: 27,147,555 (GRCm39)	K5E	possibly damaging	Het
Cacna2d2	A	G	9: 107,394,456 (GRCm39)	N573D	probably benign	Het
Calhm2	C	A	19: 47,121,356 (GRCm39)	G271V	possibly damaging	Het
Capn13	C	T	17: 73,629,064 (GRCm39)	G581E	probably damaging	Het
Capzb	T	C	4: 139,016,288 (GRCm39)		probably benign	Het
Casd1	T	C	6: 4,619,753 (GRCm39)		probably benign	Het
Clca4b	A	G	3: 144,634,111 (GRCm39)		probably benign	Het
Col1a2	G	A	6: 4,518,822 (GRCm39)		probably benign	Het
Crx	A	G	7: 15,605,058 (GRCm39)		probably benign	Het
Cyp2c68	T	C	19: 39,727,994 (GRCm39)		probably benign	Het
Dcaf8	T	A	1: 172,000,221 (GRCm39)	D126E	probably benign	Het
Ddx31	T	C	2: 28,764,186 (GRCm39)	I464T	probably damaging	Het
Dhx32	G	A	7: 133,339,150 (GRCm39)	T155I	probably benign	Het
Elac2	C	A	11: 64,889,349 (GRCm39)	P567T	possibly damaging	Het
Fat4	A	G	3: 39,054,444 (GRCm39)		probably benign	Het
Gm10064	T	C	5: 122,835,584 (GRCm39)		noncoding transcript	Het
Gm14137	A	G	2: 119,005,834 (GRCm39)	E131G	probably benign	Het
Gpr22	T	A	12: 31,759,312 (GRCm39)	K233M	probably damaging	Het
Gpr63	A	G	4: 25,007,480 (GRCm39)	N68S	probably benign	Het
Gypa	C	T	8: 81,223,421 (GRCm39)	P66S	unknown	Het
Htr2a	A	T	14: 74,879,587 (GRCm39)	Q72L	probably benign	Het
Klhdc7b	C	T	15: 89,271,598 (GRCm39)	R827*	probably null	Het
Leo1	G	A	9: 75,364,420 (GRCm39)	R520Q	possibly damaging	Het
Lrrc66	T	C	5: 73,765,757 (GRCm39)	M429V	probably benign	Het
Lrrc74a	C	T	12: 86,792,353 (GRCm39)	Q225*	probably null	Het
Mamdc4	T	A	2: 25,460,048 (GRCm39)	N68Y	probably damaging	Het
Map3k10	G	A	7: 27,360,992 (GRCm39)	P507L	probably damaging	Het
Methig1	T	A	15: 100,272,870 (GRCm39)	C68S	probably benign	Het
Metrn	C	T	17: 26,015,202 (GRCm39)		probably benign	Het
Mmp12	C	T	9: 7,358,290 (GRCm39)	T392I	possibly damaging	Het
Mss51	A	T	14: 20,533,160 (GRCm39)	I437N	probably damaging	Het
Mtus2	A	G	5: 148,014,097 (GRCm39)	T297A	probably benign	Het
Myo10	T	C	15: 25,722,243 (GRCm39)		probably benign	Het
Ncoa7	G	A	10: 30,567,575 (GRCm39)	P319S	probably benign	Het
Nlrp4d	A	T	7: 10,111,612 (GRCm39)		probably benign	Het
Obscn	A	G	11: 58,923,535 (GRCm39)	S6455P	probably damaging	Het
Or5b97	T	C	19: 12,878,259 (GRCm39)	N295S	probably damaging	Het
Or8b37	G	T	9: 37,959,123 (GRCm39)	V202L	probably benign	Het
Pcdh12	A	G	18: 38,415,517 (GRCm39)	I536T	probably benign	Het
Pex5l	G	T	3: 33,008,685 (GRCm39)		probably benign	Het
Pla2g2e	A	C	4: 138,608,046 (GRCm39)	K43Q	possibly damaging	Het
Rasa4	T	C	5: 136,130,924 (GRCm39)		probably benign	Het
Rsf1	C	T	7: 97,328,234 (GRCm39)	R1079W	probably damaging	Het
Sez6	A	G	11: 77,867,411 (GRCm39)	T803A	probably benign	Het
Shcbp1	T	A	8: 4,786,297 (GRCm39)	N602Y	probably benign	Het
Slc16a13	G	A	11: 70,109,857 (GRCm39)	P215S	probably damaging	Het
Slc39a6	T	C	18: 24,734,527 (GRCm39)	Q54R	probably benign	Het
Smg1	C	A	7: 117,745,512 (GRCm39)		probably benign	Het
Spg7	A	G	8: 123,797,156 (GRCm39)	N110D	probably damaging	Het
Sptbn1	A	T	11: 30,060,902 (GRCm39)	S2010T	probably damaging	Het
Sun1	T	A	5: 139,223,619 (GRCm39)		probably benign	Het
Sytl5	A	G	X: 9,860,736 (GRCm39)	E717G	probably damaging	Het
Tle1	A	T	4: 72,044,679 (GRCm39)		probably benign	Het
Tm9sf4	T	A	2: 153,033,065 (GRCm39)	V290E	probably damaging	Het
Tmem63b	A	G	17: 45,985,060 (GRCm39)	S179P	probably damaging	Het
Trpm3	T	A	19: 22,965,153 (GRCm39)	F1549L	probably benign	Het
Ubr4	A	T	4: 139,212,631 (GRCm39)	Y5063F	possibly damaging	Het
Uroc1	T	A	6: 90,313,937 (GRCm39)	Y75N	probably damaging	Het
Vmn2r70	T	C	7: 85,215,112 (GRCm39)	T141A	probably benign	Het
Vps13c	A	G	9: 67,868,931 (GRCm39)	K3128E	probably damaging	Het
Wdr26	T	C	1: 181,013,470 (GRCm39)		probably null	Het
Wrn	T	A	8: 33,738,946 (GRCm39)		probably null	Het
Zfp106	C	T	2: 120,385,729 (GRCm39)	V13M	probably damaging	Het
Zfp456	G	A	13: 67,514,663 (GRCm39)	H348Y	probably damaging	Het
Zfpm1	G	A	8: 123,063,398 (GRCm39)	R819H	probably benign	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
R1240:Fh1	UTSW	1	175,431,581 (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'- GCAGGCATGATCCCTAAGTCTTCTC -3'
(R):5'- AGCCATTAGCAAGCCACTTAGCG -3'

Sequencing Primer
(F):5'- CTAAGTCTTCTCTAGCGGAGCAG -3'
(R):5'- CACTTAGCGTGTGGAACAAC -3'

Posted On

2013-09-03