Mutagenetix > Incidental Mutation

Incidental Mutation 'R4849:Fh1'

373359

Institutional Source

Beutler Lab

Gene Symbol

Fh1

Ensembl Gene

ENSMUSG00000026526

Gene Name

fumarate hydratase 1

Synonyms

fumarase

MMRRC Submission

042461-MU

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R4849 (G1)

Quality Score

225

Status

Validated

Chromosome

Chromosomal Location

175428944-175453201 bp(-) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

A to G at 175448072 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Threonine to Alanine at position 25 (T25A)

Ref Sequence

ENSEMBL: ENSMUSP00000122943 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000027810] [ENSMUST00000140474] [ENSMUST00000154956]

AlphaFold

P97807

Predicted Effect

probably benign
Transcript: ENSMUST00000027810

SMART Domains

Protein: ENSMUSP00000027810
Gene: ENSMUSG00000026526

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: ENSMUST00000140474
AA Change: T25A

PolyPhen 2 Score 0.003 (Sensitivity: 0.98; Specificity: 0.44)

SMART Domains

Protein: ENSMUSP00000122943
Gene: ENSMUSG00000039783
AA Change: T25A

Domain	Start	End	E-Value	Type
Pfam:FAD_binding_3	44	240	2.9e-10	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

0.0898

Coding Region Coverage

1x: 99.2%
3x: 98.5%
10x: 96.9%
20x: 94.2%

Validation Efficiency

98% (90/92)

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: 82 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Acp7	G	T	7: 28,314,877 (GRCm39)	R239S	possibly damaging	Het
Angptl1	C	A	1: 156,684,735 (GRCm39)	N301K	probably benign	Het
Ankrd26	T	A	6: 118,509,257 (GRCm39)	T603S	probably benign	Het
App	T	C	16: 84,853,322 (GRCm39)	D252G	unknown	Het
Atxn3	A	G	12: 101,900,627 (GRCm39)	S219P	probably benign	Het
Birc6	T	C	17: 74,954,383 (GRCm39)	S3397P	probably damaging	Het
Bivm	A	G	1: 44,182,033 (GRCm39)	I414V	possibly damaging	Het
Cemip	A	G	7: 83,584,945 (GRCm39)	F1324L	possibly damaging	Het
Ckap5	T	A	2: 91,445,616 (GRCm39)	N1724K	probably damaging	Het
Corin	T	A	5: 72,460,178 (GRCm39)	M1035L	probably damaging	Het
Ctnna3	T	C	10: 64,709,094 (GRCm39)	I711T	probably damaging	Het
Cts6	A	T	13: 61,349,415 (GRCm39)	W98R	probably null	Het
Dip2a	A	G	10: 76,130,367 (GRCm39)	S580P	probably damaging	Het
Dock6	A	G	9: 21,723,068 (GRCm39)		probably null	Het
Dusp15	T	A	2: 152,791,002 (GRCm39)	T32S	probably damaging	Het
Eogt	T	A	6: 97,093,016 (GRCm39)	N387I	probably damaging	Het
Evx2	T	C	2: 74,489,675 (GRCm39)	D29G	probably benign	Het
Fat1	A	G	8: 45,466,007 (GRCm39)	N1422S	probably benign	Het
Fat2	T	C	11: 55,201,463 (GRCm39)	D537G	probably damaging	Het
Fat3	A	C	9: 16,289,244 (GRCm39)	I93S	probably benign	Het
Fem1b	T	C	9: 62,704,576 (GRCm39)	E228G	probably damaging	Het
Fndc3b	A	G	3: 27,514,097 (GRCm39)	W695R	probably damaging	Het
Gaa	G	A	11: 119,163,813 (GRCm39)	V222I	possibly damaging	Het
Ggnbp1	T	C	17: 27,251,947 (GRCm39)		probably null	Het
Gipc1	A	G	8: 84,388,756 (GRCm39)	Y154C	probably benign	Het
Gm5356	G	T	8: 89,913,670 (GRCm39)		noncoding transcript	Het
Gnl1	T	A	17: 36,298,603 (GRCm39)		probably null	Het
Gpcpd1	C	T	2: 132,376,019 (GRCm39)	G605R	probably damaging	Het
Guca1a	T	C	17: 47,705,662 (GRCm39)	T177A	possibly damaging	Het
Ifit1bl1	T	C	19: 34,572,076 (GRCm39)	E127G	probably damaging	Het
Ift81	A	T	5: 122,729,282 (GRCm39)	I350N	probably damaging	Het
Ikbke	GCC	G	1: 131,203,004 (GRCm39)		probably null	Het
Ing4	A	G	6: 125,020,946 (GRCm39)	R23G	probably damaging	Het
Ins1	A	G	19: 52,253,384 (GRCm39)	N108S	probably damaging	Het
Iqce	A	T	5: 140,679,214 (GRCm39)	M72K	possibly damaging	Het
Itga3	C	A	11: 94,967,097 (GRCm39)	M22I	probably benign	Het
Kctd18	T	C	1: 58,001,152 (GRCm39)	E201G	probably damaging	Het
Klc1	A	G	12: 111,748,129 (GRCm39)	N344S	probably damaging	Het
Klrb1f	A	T	6: 129,033,347 (GRCm39)	I192F	probably damaging	Het
Klrg2	A	T	6: 38,607,214 (GRCm39)		probably null	Het
Kntc1	A	C	5: 123,897,128 (GRCm39)	I164L	probably benign	Het
Ltf	T	A	9: 110,855,058 (GRCm39)	I357K	probably benign	Het
Mr1	T	C	1: 155,006,436 (GRCm39)	T304A	probably benign	Het
Msh6	C	T	17: 88,290,947 (GRCm39)	R178C	possibly damaging	Het
Mtch1	T	C	17: 29,566,565 (GRCm39)	D66G	probably benign	Het
Mtmr7	A	G	8: 41,062,040 (GRCm39)	V15A	probably benign	Het
Mtss2	A	T	8: 111,452,875 (GRCm39)	H40L	possibly damaging	Het
Mxra8	A	G	4: 155,925,331 (GRCm39)		probably benign	Het
Myo3b	T	C	2: 70,075,253 (GRCm39)	L535P	probably damaging	Het
Neurl2	T	A	2: 164,674,739 (GRCm39)		probably null	Het
Nfia	A	C	4: 97,970,048 (GRCm39)	T503P	probably damaging	Het
Noa1	T	C	5: 77,454,179 (GRCm39)	E487G	possibly damaging	Het
Nuak1	A	T	10: 84,211,143 (GRCm39)	V315D	probably damaging	Het
Nup205	A	G	6: 35,207,505 (GRCm39)	N1519S	possibly damaging	Het
Or10x1	T	A	1: 174,196,966 (GRCm39)	I161K	probably damaging	Het
Or1l4b	T	C	2: 37,036,266 (GRCm39)	L14P	probably damaging	Het
Or1o1	T	C	17: 37,716,589 (GRCm39)	V50A	probably benign	Het
Or51f1e	A	G	7: 102,747,526 (GRCm39)	I193V	possibly damaging	Het
Or6b13	G	T	7: 139,782,340 (GRCm39)	C114*	probably null	Het
Or9s18	G	A	13: 65,300,493 (GRCm39)	V152M	possibly damaging	Het
Peli1	T	A	11: 21,098,528 (GRCm39)		probably benign	Het
Ppp6r1	A	G	7: 4,646,206 (GRCm39)	L175P	probably damaging	Het
Prkcd	A	G	14: 30,321,700 (GRCm39)	L498P	probably damaging	Het
Prss30	T	A	17: 24,191,769 (GRCm39)	I251F	probably benign	Het
Psme3	A	T	11: 101,207,907 (GRCm39)	N21Y	probably benign	Het
Ptpra	T	C	2: 130,374,081 (GRCm39)	Y271H	probably damaging	Het
Ralgapa1	T	A	12: 55,745,588 (GRCm39)	N1303Y	probably damaging	Het
Rims4	T	C	2: 163,707,463 (GRCm39)	I121V	probably benign	Het
Rnf123	A	T	9: 107,933,290 (GRCm39)	L1149Q	probably damaging	Het
Ryr3	T	A	2: 112,738,807 (GRCm39)	L593F	probably damaging	Het
Sec23b	T	C	2: 144,427,519 (GRCm39)	F582S	probably damaging	Het
Sgpl1	T	C	10: 60,940,297 (GRCm39)	K335R	probably benign	Het
Sirpa	C	T	2: 129,451,163 (GRCm39)	T141I	probably damaging	Het
Slit1	G	T	19: 41,637,983 (GRCm39)	A270E	probably benign	Het
Snap91	T	C	9: 86,674,613 (GRCm39)	T533A	possibly damaging	Het
Sphkap	T	G	1: 83,255,105 (GRCm39)	E881D	probably benign	Het
Sptan1	C	A	2: 29,901,054 (GRCm39)	R1407S	probably damaging	Het
Tfdp1	A	G	8: 13,423,895 (GRCm39)	T353A	probably benign	Het
Ttyh1	A	G	7: 4,125,533 (GRCm39)	I62V	possibly damaging	Het
Vwde	A	T	6: 13,196,047 (GRCm39)	V326D	possibly damaging	Het
Zfp398	T	C	6: 47,836,446 (GRCm39)	I82T	possibly damaging	Het
Zp1	A	G	19: 10,896,198 (GRCm39)	Y176H	possibly damaging	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
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
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'- TTTCCTCACAATGCAGATAGGATC -3'
(R):5'- TTTTGGCTCCTGAGTCTCAAAG -3'

Sequencing Primer
(F):5'- TAGGATCTGCGGCAAAGAACCTTC -3'
(R):5'- GTCTCAAAGACCAGCATGCGTG -3'

Posted On

2016-03-01