Incidental Mutation 'F6893:Mpi'
ID194
Institutional Source Beutler Lab
Gene Symbol Mpi
Ensembl Gene ENSMUSG00000032306
Gene Namemannose phosphate isomerase
Synonyms1110002E17Rik, Mpi-1, Mpi1
Accession Numbers

Genbank: NM_025837; MGI: 97075

Is this an essential gene? Essential (E-score: 1.000) question?
Stock #F6893 (G3) of strain busy
Quality Score
Status Validated
Chromosome9
Chromosomal Location57544256-57552763 bp(-) (GRCm38)
Type of Mutationmissense
DNA Base Change (assembly) A to T at 57546549 bp
ZygosityHomozygous
Amino Acid Change Methionine to Lysine at position 230 (M230K)
Ref Sequence ENSEMBL: ENSMUSP00000034856 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000034856] [ENSMUST00000093833] [ENSMUST00000114200]
Predicted Effect probably benign
Transcript: ENSMUST00000034856
AA Change: M230K

PolyPhen 2 Score 0.115 (Sensitivity: 0.93; Specificity: 0.86)
SMART Domains Protein: ENSMUSP00000034856
Gene: ENSMUSG00000032306
AA Change: M230K

DomainStartEndE-ValueType
Pfam:PMI_typeI 6 384 4.3e-145 PFAM
Predicted Effect probably benign
Transcript: ENSMUST00000093833
SMART Domains Protein: ENSMUSP00000091353
Gene: ENSMUSG00000032305

DomainStartEndE-ValueType
Pfam:FAM219A 72 128 4.2e-18 PFAM
Predicted Effect probably benign
Transcript: ENSMUST00000114200
SMART Domains Protein: ENSMUSP00000109838
Gene: ENSMUSG00000032305

DomainStartEndE-ValueType
Pfam:FAM219A 72 197 1.6e-62 PFAM
Predicted Effect noncoding transcript
Transcript: ENSMUST00000124593
Predicted Effect noncoding transcript
Transcript: ENSMUST00000140671
Predicted Effect noncoding transcript
Transcript: ENSMUST00000145543
Predicted Effect probably benign
Transcript: ENSMUST00000156428
SMART Domains Protein: ENSMUSP00000119342
Gene: ENSMUSG00000032306

DomainStartEndE-ValueType
Pfam:PMI_typeI 3 119 3.1e-45 PFAM
Meta Mutation Damage Score 0.102 question?
Coding Region Coverage
  • 1x: 88.7%
  • 3x: 74.0%
Validation Efficiency 88% (165/188)
MGI Phenotype FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] Phosphomannose isomerase catalyzes the interconversion of fructose-6-phosphate and mannose-6-phosphate and plays a critical role in maintaining the supply of D-mannose derivatives, which are required for most glycosylation reactions. Mutations in the MPI gene were found in patients with carbohydrate-deficient glycoprotein syndrome, type Ib. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2014]
PHENOTYPE: Homozygous null mice display embryonic lethality during organogenesis, variable abnormalities of the yolk sac and embryonic vasculature, and partial penetrance of abnormal chorioallantoic fusion, placental defects, impaired emrbyo turning, increased apoptosis, and posterior axial truncations. [provided by MGI curators]
Allele List at MGI

All alleles(6) : Targeted, other(2) Gene trapped(4)

Other mutations in this stock
Total: 35 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
Abca14 G A 7: 120,325,038 V1638M probably damaging Het
Agrn C T 4: 156,174,179 R972Q probably benign Het
Anxa3 T C 5: 96,824,994 probably benign Het
Bpifa6 G T 2: 153,987,158 D202Y probably damaging Het
Ccdc15 G A 9: 37,315,640 T346I probably damaging Homo
Celsr3 G A 9: 108,835,067 R1731H probably benign Het
Ces4a A G 8: 105,147,227 R443G possibly damaging Het
Chd2 T C 7: 73,507,872 Q175R possibly damaging Het
Dpyd T A 3: 118,804,134 probably null Het
Dscam G T 16: 97,056,460 H117N possibly damaging Het
F13a1 A G 13: 36,972,025 Y205H probably damaging Het
Fat3 A C 9: 16,006,789 L1446R probably damaging Homo
Golga4 T C 9: 118,553,457 L515S probably damaging Het
Hoxb1 A T 11: 96,365,902 T26S probably benign Het
Igsf10 T G 3: 59,331,060 T567P probably damaging Het
Lamb2 T C 9: 108,482,556 V365A probably benign Het
Mepe A G 5: 104,337,376 I127M possibly damaging Het
Myh4 A G 11: 67,255,457 D1447G probably null Homo
Olfr161 A G 16: 3,593,163 I256V possibly damaging Het
Olfr350 A G 2: 36,850,807 T254A probably benign Het
Panx2 T C 15: 89,068,010 Y235H probably damaging Homo
Pdzd7 A G 19: 45,036,734 W441R probably damaging Het
Poldip2 A G 11: 78,519,194 I267M probably damaging Homo
Pros1 T A 16: 62,924,639 V539E probably damaging Het
Sacs T C 14: 61,212,976 M4157T probably benign Het
Slc45a3 A G 1: 131,981,337 E424G probably benign Homo
Slc9a1 A G 4: 133,422,146 E761G probably benign Homo
Stab2 G A 10: 86,855,171 P2178L probably damaging Het
Syt4 C T 18: 31,444,221 V27I possibly damaging Homo
Thumpd1 T A 7: 119,720,576 K56* probably null Het
Tpr A G 1: 150,393,562 K19E possibly damaging Homo
Ttll10 A G 4: 156,048,318 I74T probably benign Het
Txnrd1 C T 10: 82,866,989 Q95* probably null Homo
Zc3h7b A G 15: 81,778,671 E421G possibly damaging Homo
Zc3hc1 G T 6: 30,387,526 D51E probably benign Homo
Other mutations in Mpi
AlleleSourceChrCoordTypePredicted EffectPPH Score
IGL00921:Mpi APN 9 57552266 missense probably damaging 1.00
IGL01071:Mpi APN 9 57550592 missense probably damaging 1.00
IGL01604:Mpi APN 9 57550742 missense possibly damaging 0.85
IGL02090:Mpi APN 9 57550653 missense probably benign 0.00
benadryl UTSW 9 57550757 missense probably damaging 1.00
R0751:Mpi UTSW 9 57550614 missense probably damaging 1.00
R1146:Mpi UTSW 9 57545189 splice donor site probably benign
R3727:Mpi UTSW 9 57544849 missense possibly damaging 0.69
R3944:Mpi UTSW 9 57545253 missense probably damaging 1.00
R4645:Mpi UTSW 9 57550757 missense probably damaging 1.00
R4772:Mpi UTSW 9 57544898 missense probably damaging 1.00
R4856:Mpi UTSW 9 57545307 missense probably damaging 1.00
R5088:Mpi UTSW 9 57550604 missense probably damaging 0.97
R5504:Mpi UTSW 9 57545217 missense probably damaging 1.00
R5886:Mpi UTSW 9 57548462 intron probably benign
Nature of Mutation
DNA sequencing using the SOLiD technique identified a T to A transversion at position 722 of the Mpi transcript in exon 6 of 8 total exons.  Multiple transcripts of the Mpi gene are displayed on Ensembl. The mutated nucleotide causes a methione to lysine substitution at amino acid 230 of the encoded protein. The mutation has been confirmed by DNA sequencing using the Sanger method (Figure 1).
 
Protein Function and Prediction
The Mpi gene encodes a 423 amino acid zinc-binding protein that is involved in the synthesis of the GDP-mannose and dolichol-phosphate-mannose required for a number of critical mannosyl transfer reactions (Uniprot Q924M7). Homozygous null mice display embryonic lethality during organogenesis, variable abnormalities of the yolk sac and embryonic vasculature, and partial penetrance of abnormal chorioallantoic fusion, placental defects, impaired emrbyo turning, increased apoptosis, and posterior axial truncations.
 
The M230K change is predicted to be benign by the PolyPhen program.
Posted On2010-05-03