Incidental Mutation 'R1943:Fh1'
ID 216342
Institutional Source Beutler Lab
Gene Symbol Fh1
Ensembl Gene ENSMUSG00000026526
Gene Name fumarate hydratase 1
Synonyms fumarase
MMRRC Submission 039961-MU
Accession Numbers
Essential gene? Essential (E-score: 1.000) question?
Stock # R1943 (G1)
Quality Score 225
Status Not validated
Chromosome 1
Chromosomal Location 175428944-175453201 bp(-) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) C to T at 175437344 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Valine to Isoleucine at position 252 (V252I)
Ref Sequence ENSEMBL: ENSMUSP00000027810 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000027810] [ENSMUST00000154956]
AlphaFold P97807
Predicted Effect probably benign
Transcript: ENSMUST00000027810
AA Change: V252I

PolyPhen 2 Score 0.000 (Sensitivity: 1.00; Specificity: 0.00)
SMART Domains Protein: ENSMUSP00000027810
Gene: ENSMUSG00000026526
AA Change: V252I

DomainStartEndE-ValueType
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: ENSMUST00000133218
Predicted Effect probably benign
Transcript: ENSMUST00000154956
SMART Domains Protein: ENSMUSP00000135140
Gene: ENSMUSG00000026526

DomainStartEndE-ValueType
low complexity region 3 16 N/A INTRINSIC
Predicted Effect probably benign
Transcript: ENSMUST00000176740
Coding Region Coverage
  • 1x: 99.2%
  • 3x: 98.5%
  • 10x: 96.8%
  • 20x: 94.3%
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: 62 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
A2m A G 6: 121,645,506 (GRCm39) N1017S possibly damaging Het
Abca8a T C 11: 109,960,689 (GRCm39) I610V probably benign Het
Acp5 C T 9: 22,040,900 (GRCm39) V108M probably damaging Het
Adam23 T C 1: 63,516,916 (GRCm39) probably null Het
Adam34 T A 8: 44,103,864 (GRCm39) T594S possibly damaging Het
Adam34 A T 8: 44,104,852 (GRCm39) N264K probably damaging Het
Arsa G A 15: 89,357,742 (GRCm39) T407I probably damaging Het
Bicc1 A G 10: 70,995,353 (GRCm39) S32P probably damaging Het
Cacna1i T A 15: 80,279,245 (GRCm39) D1995E probably benign Het
Cemip2 G A 19: 21,825,404 (GRCm39) probably null Het
Chst15 A T 7: 131,864,579 (GRCm39) probably null Het
Cntnap4 T A 8: 113,542,128 (GRCm39) F754I probably benign Het
Cpz C T 5: 35,669,772 (GRCm39) E302K probably damaging Het
Daw1 A T 1: 83,186,987 (GRCm39) I371F possibly damaging Het
Dennd1b C A 1: 139,096,690 (GRCm39) probably benign Het
Dhtkd1 T G 2: 5,937,293 (GRCm39) Q73P probably benign Het
Dmgdh T C 13: 93,847,878 (GRCm39) I525T probably benign Het
Dst C A 1: 34,267,450 (GRCm39) T4964K possibly damaging Het
Ercc3 A G 18: 32,379,663 (GRCm39) Y290C probably damaging Het
Gm13199 C T 2: 5,867,517 (GRCm39) probably benign Het
Il1rn T C 2: 24,238,611 (GRCm39) S82P possibly damaging Het
Lama4 T C 10: 38,973,134 (GRCm39) V1567A possibly damaging Het
Lamtor4 A G 5: 138,254,054 (GRCm39) probably null Het
Llgl1 A G 11: 60,596,842 (GRCm39) N148D probably benign Het
Lmo7 G T 14: 102,139,738 (GRCm39) G774V probably damaging Het
Luzp2 A T 7: 54,914,050 (GRCm39) K293M possibly damaging Het
Mknk1 T C 4: 115,720,223 (GRCm39) V83A probably damaging Het
Mug2 T C 6: 122,056,598 (GRCm39) V1181A probably benign Het
Myo16 G A 8: 10,644,905 (GRCm39) D1746N possibly damaging Het
Or1ad8 A G 11: 50,898,502 (GRCm39) I234M probably benign Het
Or2aj4 A T 16: 19,385,187 (GRCm39) W149R probably benign Het
Osbpl3 A G 6: 50,297,054 (GRCm39) I548T probably benign Het
Parp14 A G 16: 35,656,499 (GRCm39) Y1676H probably damaging Het
Phtf1 A T 3: 103,901,198 (GRCm39) K416* probably null Het
Pmp2 T C 3: 10,247,570 (GRCm39) T40A probably benign Het
Ptpra T C 2: 130,386,024 (GRCm39) M541T probably damaging Het
Rapgef6 A G 11: 54,548,089 (GRCm39) I753V possibly damaging Het
Rdh14 T C 12: 10,441,162 (GRCm39) V108A probably benign Het
Rnf38 A T 4: 44,138,748 (GRCm39) H248Q probably damaging Het
Rsph6a A C 7: 18,808,001 (GRCm39) Y388S probably damaging Het
Ryr2 T C 13: 11,746,609 (GRCm39) D1981G probably benign Het
Sf3a3 A G 4: 124,609,694 (GRCm39) K97E possibly damaging Het
Shisa9 A G 16: 12,085,620 (GRCm39) T394A probably benign Het
Slc43a2 T A 11: 75,436,567 (GRCm39) probably null Het
Slc45a1 A G 4: 150,728,734 (GRCm39) F23S probably benign Het
Slc7a10 T A 7: 34,899,723 (GRCm39) V435E probably benign Het
Snx15 A G 19: 6,178,096 (GRCm39) Y28H probably damaging Het
Spef2 T G 15: 9,663,280 (GRCm39) K834Q possibly damaging Het
Tdpoz2 G T 3: 93,559,230 (GRCm39) Y247* probably null Het
Tedc2 G A 17: 24,436,923 (GRCm39) R271W possibly damaging Het
Tfr2 C A 5: 137,577,183 (GRCm39) H378Q probably benign Het
Tigit T A 16: 43,469,581 (GRCm39) H170L probably benign Het
Tmem62 A T 2: 120,817,107 (GRCm39) Q91L probably benign Het
Tmtc1 G T 6: 148,327,416 (GRCm39) C32* probably null Het
Txndc12 G A 4: 108,713,407 (GRCm39) V90I probably benign Het
Vmn2r93 C A 17: 18,546,063 (GRCm39) T645K probably benign Het
Vmn2r96 C T 17: 18,806,664 (GRCm39) T345I probably benign Het
Vps13d A T 4: 144,882,427 (GRCm39) D1055E probably benign Het
Xirp2 A G 2: 67,342,959 (GRCm39) I1733M probably benign Het
Zfp512b T C 2: 181,230,208 (GRCm39) H516R probably damaging Het
Zfp606 T C 7: 12,227,615 (GRCm39) S521P probably damaging Het
Zfp715 A T 7: 42,949,054 (GRCm39) V302E possibly damaging Het
Other mutations in Fh1
AlleleSourceChrCoordTypePredicted EffectPPH 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
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'- TGAGTAGCAATGCATGTGGTC -3'
(R):5'- AGCAATAGTTCAGTGTAGTGGAGC -3'

Sequencing Primer
(F):5'- ATGCATGTGGTCCCCAAC -3'
(R):5'- GGGACGTTTGGTTATAAACTAAGC -3'
Posted On 2014-08-01