Incidental Mutation 'F6893:Mepe'
ID200
Institutional Source Beutler Lab
Gene Symbol Mepe
Ensembl Gene ENSMUSG00000053863
Gene Namematrix extracellular phosphoglycoprotein with ASARM motif (bone)
SynonymsOF45
Accession Numbers

Genbank: NM_053172; MGI: 2137384

Is this an essential gene? Probably non essential (E-score: 0.012) question?
Stock #F6893 (G3) of strain busy
Quality Score
Status Validated
Chromosome5
Chromosomal Location104325329-104338611 bp(+) (GRCm38)
Type of Mutationmissense
DNA Base Change (assembly) A to G at 104337376 bp
ZygosityHeterozygous
Amino Acid Change Isoleucine to Methionine at position 127 (I127M)
Ref Sequence ENSEMBL: ENSMUSP00000065200 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000066207]
Predicted Effect possibly damaging
Transcript: ENSMUST00000066207
AA Change: I127M

PolyPhen 2 Score 0.872 (Sensitivity: 0.83; Specificity: 0.93)
SMART Domains Protein: ENSMUSP00000065200
Gene: ENSMUSG00000053863
AA Change: I127M

DomainStartEndE-ValueType
signal peptide 1 24 N/A INTRINSIC
Pfam:Osteoregulin 29 192 4.2e-76 PFAM
low complexity region 257 272 N/A INTRINSIC
low complexity region 426 438 N/A INTRINSIC
Meta Mutation Damage Score 0.0492 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.] This gene encodes a secreted calcium-binding phosphoprotein that belongs to the small integrin-binding ligand, N-linked glycoprotein (SIBLING) family of proteins. Members of this family are components of the extracellular matrix of bone and dentin and regulate bone mineralization. Deficiency of a similar protein in mouse results in increased bone mass. Mice lacking this gene are resistant to aging-related trabecular bone loss. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2014]
PHENOTYPE: Mice homozygous for disruptions in this gene have increased amounts of trabecular bone in their skeleton and undergo less age related bone loss. Otherwise, they display a normal phenotype. [provided by MGI curators]
Allele List at MGI

All alleles(1) : Targeted, knock-out(1)

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
Mpi A T 9: 57,546,549 M230K probably benign Homo
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 Mepe
AlleleSourceChrCoordTypePredicted EffectPPH Score
IGL00335:Mepe APN 5 104337977 missense probably damaging 1.00
IGL01896:Mepe APN 5 104338269 missense possibly damaging 0.85
IGL01997:Mepe APN 5 104337600 missense probably damaging 1.00
IGL02311:Mepe APN 5 104337705 missense probably damaging 0.98
IGL02586:Mepe APN 5 104337450 missense probably benign 0.39
R1187:Mepe UTSW 5 104338248 missense probably damaging 0.98
R1218:Mepe UTSW 5 104327073 missense probably benign
R1633:Mepe UTSW 5 104337674 missense probably benign 0.25
R2024:Mepe UTSW 5 104327091 missense possibly damaging 0.72
R2026:Mepe UTSW 5 104327091 missense possibly damaging 0.72
R2027:Mepe UTSW 5 104327091 missense possibly damaging 0.72
R2393:Mepe UTSW 5 104337461 missense possibly damaging 0.95
R2920:Mepe UTSW 5 104338247 missense probably damaging 0.99
R3040:Mepe UTSW 5 104338122 missense probably damaging 0.99
R3716:Mepe UTSW 5 104337428 missense probably benign 0.25
R3973:Mepe UTSW 5 104337078 missense probably benign
R3976:Mepe UTSW 5 104337078 missense probably benign
R4894:Mepe UTSW 5 104325402 missense probably damaging 0.98
R5556:Mepe UTSW 5 104338212 missense probably damaging 1.00
R6256:Mepe UTSW 5 104337074 missense probably benign 0.01
R6788:Mepe UTSW 5 104338208 nonsense probably null
Nature of Mutation
DNA sequencing using the SOLiD technique identified an A to G transition at position 447 of the Mepe transcript in exon 3 of 3 total exons.  The mutated nucleotide causes an isoleucine to methionine substitution at amino acid 127 of the encoded protein. The mutation has been confirmed by DNA sequencing using the Sanger method (Figure 1).
Protein Function & Prediction
The Mepe gene encodes a 441 amino acid secreted matrix protein that negatively regulates bone mineralization (Uniprot Q924I1). Mice homozygous for disruptions in this gene have increased amounts of trabecular bone in their skeleton and undergo less age related bone loss. Otherwise, they display a normal phenotype.
 
The I127M change is predicted to be benign by the PolyPhen program.
Posted OnMay 03, 2010