Incidental Mutation 'R2163:Fh1'
ID 235253
Institutional Source Beutler Lab
Gene Symbol Fh1
Ensembl Gene ENSMUSG00000026526
Gene Name fumarate hydratase 1
Synonyms fumarase
MMRRC Submission 040166-MU
Accession Numbers
Essential gene? Essential (E-score: 1.000) question?
Stock # R2163 (G1)
Quality Score 225
Status Validated
Chromosome 1
Chromosomal Location 175428944-175453201 bp(-) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) A to G at 175442406 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Methionine to Threonine at position 148 (M148T)
Ref Sequence ENSEMBL: ENSMUSP00000027810 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000027810] [ENSMUST00000154956]
AlphaFold P97807
Predicted Effect possibly damaging
Transcript: ENSMUST00000027810
AA Change: M148T

PolyPhen 2 Score 0.803 (Sensitivity: 0.84; Specificity: 0.93)
SMART Domains Protein: ENSMUSP00000027810
Gene: ENSMUSG00000026526
AA Change: M148T

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 probably benign
Transcript: ENSMUST00000154956
SMART Domains Protein: ENSMUSP00000135140
Gene: ENSMUSG00000026526

DomainStartEndE-ValueType
low complexity region 3 16 N/A INTRINSIC
Meta Mutation Damage Score 0.9747 question?
Coding Region Coverage
  • 1x: 99.3%
  • 3x: 98.7%
  • 10x: 97.6%
  • 20x: 95.9%
Validation Efficiency 97% (76/78)
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: 77 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
4930578I07Rik C A 14: 67,175,997 (GRCm39) T64K unknown Het
Ablim2 T C 5: 35,959,697 (GRCm39) probably benign Het
Acp4 T C 7: 43,905,400 (GRCm39) D107G probably damaging Het
Adamts2 T A 11: 50,679,632 (GRCm39) C871S probably benign Het
Adamts3 A G 5: 89,856,577 (GRCm39) V332A probably damaging Het
Alkal1 C T 1: 6,459,736 (GRCm39) T104M probably benign Het
Astn1 A G 1: 158,329,720 (GRCm39) S192G probably damaging Het
Axdnd1 A C 1: 156,219,573 (GRCm39) V337G probably damaging Het
Baiap2l2 T C 15: 79,143,395 (GRCm39) D481G possibly damaging Het
Cacna2d1 C T 5: 16,567,317 (GRCm39) T964I probably damaging Het
Carf T C 1: 60,186,645 (GRCm39) probably benign Het
Catsper2 T C 2: 121,230,656 (GRCm39) D295G probably damaging Het
Cdh1 A G 8: 107,375,713 (GRCm39) T84A probably benign Het
Chd8 T A 14: 52,436,275 (GRCm39) H2508L possibly damaging Het
Chl1 A T 6: 103,688,192 (GRCm39) T284S probably damaging Het
Chtop A T 3: 90,409,518 (GRCm39) M125K probably benign Het
Col14a1 T A 15: 55,308,041 (GRCm39) probably benign Het
Cplane1 T A 15: 8,232,735 (GRCm39) probably null Het
Cyp2b10 A T 7: 25,624,810 (GRCm39) probably benign Het
Cyp2c70 G A 19: 40,149,163 (GRCm39) H328Y possibly damaging Het
Dcbld1 A G 10: 52,162,452 (GRCm39) T77A probably damaging Het
Dnah6 A T 6: 73,066,729 (GRCm39) probably null Het
Efhd1 A T 1: 87,217,195 (GRCm39) D104V probably damaging Het
Eif5b A T 1: 38,087,875 (GRCm39) D957V probably benign Het
Eps15 T A 4: 109,227,866 (GRCm39) S549R probably damaging Het
Fbxo3 C A 2: 103,885,330 (GRCm39) H400N probably benign Het
Fcer1a A G 1: 173,050,264 (GRCm39) V86A probably damaging Het
Foxc1 C A 13: 31,992,586 (GRCm39) H466N unknown Het
Gadl1 T A 9: 115,778,626 (GRCm39) I180N possibly damaging Het
Gm10801 G C 2: 98,494,352 (GRCm39) R143T possibly damaging Het
Gm21718 T C 14: 51,555,223 (GRCm39) noncoding transcript Het
Hivep2 T A 10: 14,003,970 (GRCm39) Y189* probably null Het
Hoxd13 T A 2: 74,499,413 (GRCm39) S254T possibly damaging Het
Hspd1 A G 1: 55,117,697 (GRCm39) probably benign Het
Il1r1 A G 1: 40,334,023 (GRCm39) M198V probably benign Het
Katnal1 T A 5: 148,825,746 (GRCm39) I362F probably damaging Het
Muc2 CGTG CGTGTG 7: 141,699,185 (GRCm38) probably null Het
Mybpc1 T C 10: 88,376,804 (GRCm39) probably benign Het
Mycbp2 A G 14: 103,407,291 (GRCm39) probably null Het
Nell2 G T 15: 95,327,859 (GRCm39) N301K probably damaging Het
Nenf T A 1: 191,042,132 (GRCm39) D108V probably damaging Het
Nfkbiz T C 16: 55,638,581 (GRCm39) N293S probably benign Het
Nipbl T C 15: 8,366,403 (GRCm39) K1229E probably damaging Het
Nlrp4a T C 7: 26,152,822 (GRCm39) F631L probably benign Het
Nrp1 T A 8: 129,224,352 (GRCm39) V705E probably damaging Het
Nsf G C 11: 103,754,159 (GRCm39) A459G possibly damaging Het
Or1af1 A G 2: 37,110,089 (GRCm39) E196G probably damaging Het
Or5w10 A G 2: 87,375,238 (GRCm39) S217P probably damaging Het
Pdia4 C T 6: 47,775,341 (GRCm39) D490N possibly damaging Het
Pinlyp T A 7: 24,241,226 (GRCm39) Y192F probably benign Het
Pkd2 T C 5: 104,603,543 (GRCm39) probably benign Het
Ppara A G 15: 85,685,247 (GRCm39) K399E probably benign Het
Ppp4r2 C A 6: 100,842,047 (GRCm39) N169K probably damaging Het
Prom1 T A 5: 44,171,505 (GRCm39) E632V possibly damaging Het
Rpap3 T A 15: 97,578,229 (GRCm39) Y562F possibly damaging Het
Rsph14 T A 10: 74,793,611 (GRCm39) K263N probably damaging Het
Sanbr T C 11: 23,526,826 (GRCm39) probably benign Het
Scn11a T G 9: 119,584,091 (GRCm39) D1508A probably damaging Het
Scn7a T C 2: 66,506,300 (GRCm39) T1530A probably damaging Het
Sec14l1 T A 11: 117,034,108 (GRCm39) probably null Het
Slc4a4 A G 5: 89,362,435 (GRCm39) I840V probably damaging Het
Slco1a8 G A 6: 141,926,664 (GRCm39) T554I possibly damaging Het
Slco1c1 T A 6: 141,505,478 (GRCm39) V419D probably benign Het
Sltm T A 9: 70,498,964 (GRCm39) F1013I probably damaging Het
Spam1 A G 6: 24,796,846 (GRCm39) K266E probably benign Het
Syt15 A G 14: 33,948,073 (GRCm39) E306G probably benign Het
Tap1 A T 17: 34,408,447 (GRCm39) probably null Het
Tbc1d16 G C 11: 119,045,904 (GRCm39) probably benign Het
Tex47 T C 5: 7,355,022 (GRCm39) Y68H probably damaging Het
Ttn T C 2: 76,642,845 (GRCm39) T13264A probably damaging Het
Ttn A T 2: 76,641,587 (GRCm39) L5176Q possibly damaging Het
Ubxn2a A T 12: 4,935,757 (GRCm39) F131Y probably damaging Het
Usp40 T C 1: 87,923,580 (GRCm39) probably benign Het
Vmn1r170 T C 7: 23,306,462 (GRCm39) L288P probably damaging Het
Vmn1r175 A G 7: 23,508,352 (GRCm39) Y92H probably benign Het
Wdpcp G T 11: 21,835,015 (GRCm39) E673* probably null Het
Zfr T A 15: 12,162,309 (GRCm39) L820I probably 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
R1943:Fh1 UTSW 1 175,437,344 (GRCm39) missense probably benign
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'- CTGGACTTACGAGCACAGTCTC -3'
(R):5'- GCCATTAGCAAGCCACTTAGC -3'

Sequencing Primer
(F):5'- GAGCACAGTCTCCCCTACG -3'
(R):5'- CATTAGCAAGCCACTTAGCGTGTG -3'
Posted On 2014-10-01