Incidental Mutation 'R5276:Metap2'
ID 403959
Institutional Source Beutler Lab
Gene Symbol Metap2
Ensembl Gene ENSMUSG00000036112
Gene Name methionine aminopeptidase 2
Synonyms eIF-2-associated p67, 4930584B20Rik, A930035J23Rik, p67
MMRRC Submission 042863-MU
Accession Numbers
Essential gene? Essential (E-score: 1.000) question?
Stock # R5276 (G1)
Quality Score 225
Status Not validated
Chromosome 10
Chromosomal Location 93694351-93732952 bp(-) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) G to T at 93704784 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Proline to Histidine at position 281 (P281H)
Ref Sequence ENSEMBL: ENSMUSP00000138083 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000047910] [ENSMUST00000180688] [ENSMUST00000180840] [ENSMUST00000181091] [ENSMUST00000181217] [ENSMUST00000181470]
AlphaFold O08663
Predicted Effect possibly damaging
Transcript: ENSMUST00000047910
AA Change: P271H

PolyPhen 2 Score 0.510 (Sensitivity: 0.88; Specificity: 0.90)
SMART Domains Protein: ENSMUSP00000048285
Gene: ENSMUSG00000036112
AA Change: P271H

DomainStartEndE-ValueType
low complexity region 24 48 N/A INTRINSIC
low complexity region 77 108 N/A INTRINSIC
Pfam:Peptidase_M24 167 466 1.2e-47 PFAM
Predicted Effect probably benign
Transcript: ENSMUST00000180375
Predicted Effect unknown
Transcript: ENSMUST00000180392
AA Change: P128H
Predicted Effect probably benign
Transcript: ENSMUST00000180688
SMART Domains Protein: ENSMUSP00000137652
Gene: ENSMUSG00000036112

DomainStartEndE-ValueType
low complexity region 24 48 N/A INTRINSIC
low complexity region 76 107 N/A INTRINSIC
Pfam:Peptidase_M24 166 233 2e-14 PFAM
Predicted Effect possibly damaging
Transcript: ENSMUST00000180840
AA Change: P271H

PolyPhen 2 Score 0.510 (Sensitivity: 0.88; Specificity: 0.90)
SMART Domains Protein: ENSMUSP00000138006
Gene: ENSMUSG00000036112
AA Change: P271H

DomainStartEndE-ValueType
low complexity region 24 48 N/A INTRINSIC
low complexity region 77 108 N/A INTRINSIC
Pfam:Peptidase_M24 167 466 2.8e-50 PFAM
Predicted Effect noncoding transcript
Transcript: ENSMUST00000181009
Predicted Effect noncoding transcript
Transcript: ENSMUST00000181442
Predicted Effect possibly damaging
Transcript: ENSMUST00000181091
AA Change: P248H

PolyPhen 2 Score 0.853 (Sensitivity: 0.83; Specificity: 0.93)
SMART Domains Protein: ENSMUSP00000137904
Gene: ENSMUSG00000036112
AA Change: P248H

DomainStartEndE-ValueType
low complexity region 24 48 N/A INTRINSIC
low complexity region 77 108 N/A INTRINSIC
Pfam:Peptidase_M24 144 443 2.2e-50 PFAM
Predicted Effect possibly damaging
Transcript: ENSMUST00000181217
AA Change: P281H

PolyPhen 2 Score 0.925 (Sensitivity: 0.81; Specificity: 0.94)
SMART Domains Protein: ENSMUSP00000138083
Gene: ENSMUSG00000036112
AA Change: P281H

DomainStartEndE-ValueType
low complexity region 24 48 N/A INTRINSIC
low complexity region 77 108 N/A INTRINSIC
Pfam:Peptidase_M24 177 476 2.7e-50 PFAM
Predicted Effect noncoding transcript
Transcript: ENSMUST00000181894
Predicted Effect probably benign
Transcript: ENSMUST00000181470
SMART Domains Protein: ENSMUSP00000138050
Gene: ENSMUSG00000036112

DomainStartEndE-ValueType
Pfam:Peptidase_M24 1 97 6.6e-15 PFAM
Predicted Effect noncoding transcript
Transcript: ENSMUST00000216232
Coding Region Coverage
  • 1x: 99.3%
  • 3x: 98.6%
  • 10x: 97.3%
  • 20x: 95.3%
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 a member of the methionyl aminopeptidase family. The encoded protein functions both by protecting the alpha subunit of eukaryotic initiation factor 2 from inhibitory phosphorylation and by removing the amino-terminal methionine residue from nascent proteins. Increased expression of this gene is associated with various forms of cancer, and the anti-cancer drugs fumagillin and ovalicin inhibit the protein by irreversibly binding to its active site. Inhibitors of this gene have also been shown to be effective for the treatment of obesity. A pseudogene of this gene is located on chromosome 2. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2015]
PHENOTYPE: Homozygous mutation of this gene results in embryonic lethality around E8.5, smaller size, failure to gastrulate, reduced cell proliferation and absence of a distinct mesoderm. [provided by MGI curators]
Allele List at MGI
Other mutations in this stock
Total: 63 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
Adam26a A G 8: 44,023,457 (GRCm39) F11S probably benign Het
Adipor2 T A 6: 119,334,182 (GRCm39) I343F probably damaging Het
Ahdc1 C T 4: 132,790,109 (GRCm39) P450L possibly damaging Het
Akna A C 4: 63,286,440 (GRCm39) V1353G possibly damaging Het
Baz2b G A 2: 59,792,958 (GRCm39) T390I probably benign Het
Btbd7 T C 12: 102,804,651 (GRCm39) K130E probably benign Het
Cdc42bpa A G 1: 179,965,415 (GRCm39) Y1101C probably damaging Het
Crlf2 T G 5: 109,705,501 (GRCm39) probably benign Het
Ddx59 A T 1: 136,347,186 (GRCm39) R281S probably damaging Het
Dgcr8 T G 16: 18,101,635 (GRCm39) T216P probably benign Het
Dsg4 A T 18: 20,579,896 (GRCm39) I34F probably benign Het
Enpp3 A G 10: 24,685,814 (GRCm39) S194P probably damaging Het
Entpd8 C T 2: 24,975,057 (GRCm39) R463W probably benign Het
Fam169a A G 13: 97,255,004 (GRCm39) T407A probably benign Het
Fam98b G T 2: 117,089,779 (GRCm39) V99F possibly damaging Het
Foxn3 T A 12: 99,162,687 (GRCm39) K405* probably null Het
Gsdmc T C 15: 63,673,806 (GRCm39) T160A probably benign Het
Hdac1 T C 4: 129,422,716 (GRCm39) probably null Het
Igfbp1 A C 11: 7,151,892 (GRCm39) T232P probably damaging Het
Lcor T A 19: 41,573,478 (GRCm39) H744Q probably damaging Het
Mertk G C 2: 128,643,234 (GRCm39) G878R possibly damaging Het
Mfn1 T C 3: 32,618,354 (GRCm39) V169A probably benign Het
Mms22l A G 4: 24,578,774 (GRCm39) D751G probably damaging Het
Mpl A G 4: 118,312,918 (GRCm39) V138A probably benign Het
Myef2 T A 2: 124,937,641 (GRCm39) K533N probably damaging Het
Mylk3 C T 8: 86,082,071 (GRCm39) G309E probably damaging Het
Nid1 T C 13: 13,643,157 (GRCm39) V365A probably damaging Het
Or4d2 A T 11: 87,784,018 (GRCm39) I244N probably damaging Het
Or5p57 A T 7: 107,665,423 (GRCm39) L164* probably null Het
Or7d10 C A 9: 19,831,917 (GRCm39) N137K possibly damaging Het
Or8g19 T C 9: 39,055,611 (GRCm39) C72R probably damaging Het
Pbrm1 A G 14: 30,828,141 (GRCm39) K1323E probably damaging Het
Pcdhga12 G A 18: 37,899,728 (GRCm39) D187N possibly damaging Het
Phrf1 T C 7: 140,839,196 (GRCm39) probably benign Het
Phtf2 A G 5: 20,977,195 (GRCm39) V608A probably benign Het
Plec G A 15: 76,057,638 (GRCm39) R4122W probably damaging Het
Polm A G 11: 5,779,393 (GRCm39) S441P probably benign Het
Prrc2b T A 2: 32,104,734 (GRCm39) V1404E probably benign Het
Ptger1 T G 8: 84,395,974 (GRCm39) S344A possibly damaging Het
Rasef A T 4: 73,654,004 (GRCm39) D401E probably null Het
Rbfox3 T C 11: 118,387,178 (GRCm39) Y312C probably damaging Het
Rbm48 A G 5: 3,634,759 (GRCm39) C402R probably benign Het
Rhbdl3 G A 11: 80,210,492 (GRCm39) A82T probably benign Het
Rnf123 AT ATT 9: 107,941,202 (GRCm39) probably null Het
Sfi1 A ATCTTCCCAAAGCCAGTGC 11: 3,103,384 (GRCm39) probably benign Homo
Sidt2 T A 9: 45,866,075 (GRCm39) N44Y probably damaging Het
Slf2 T A 19: 44,923,600 (GRCm39) L138Q possibly damaging Het
Spag16 T C 1: 69,935,742 (GRCm39) probably null Het
Sspo C T 6: 48,467,401 (GRCm39) P4188S probably damaging Het
Synm C T 7: 67,384,437 (GRCm39) S1075N probably benign Het
Tacc2 G T 7: 130,331,047 (GRCm39) D2151Y probably damaging Het
Tbc1d32 C A 10: 56,027,914 (GRCm39) L729F probably damaging Het
Tnfsf4 A G 1: 161,244,584 (GRCm39) N91S possibly damaging Het
Trim63 G A 4: 134,050,444 (GRCm39) E243K probably benign Het
Trim72 T G 7: 127,603,714 (GRCm39) L20R probably damaging Het
Tubb1 A G 2: 174,299,217 (GRCm39) M300V probably damaging Het
Ubfd1 C T 7: 121,668,091 (GRCm39) A207V probably damaging Het
Usp16 T A 16: 87,267,339 (GRCm39) probably null Het
Vmn2r23 A G 6: 123,689,936 (GRCm39) T271A possibly damaging Het
Vmn2r72 T A 7: 85,387,462 (GRCm39) I701F possibly damaging Het
Wdfy4 A G 14: 32,769,232 (GRCm39) Y2078H probably damaging Het
Wdr41 T C 13: 95,153,958 (GRCm39) probably null Het
Zfp955b A G 17: 33,522,031 (GRCm39) Y500C probably damaging Het
Other mutations in Metap2
AlleleSourceChrCoordTypePredicted EffectPPH Score
IGL01671:Metap2 APN 10 93,707,340 (GRCm39) splice site probably benign
IGL02553:Metap2 APN 10 93,701,311 (GRCm39) missense probably damaging 1.00
R0212:Metap2 UTSW 10 93,697,242 (GRCm39) missense probably damaging 1.00
R0749:Metap2 UTSW 10 93,715,429 (GRCm39) missense probably benign 0.43
R1183:Metap2 UTSW 10 93,706,046 (GRCm39) missense probably damaging 1.00
R1459:Metap2 UTSW 10 93,704,811 (GRCm39) missense probably damaging 1.00
R1468:Metap2 UTSW 10 93,707,345 (GRCm39) splice site probably null
R1468:Metap2 UTSW 10 93,707,345 (GRCm39) splice site probably null
R1646:Metap2 UTSW 10 93,706,059 (GRCm39) missense probably damaging 1.00
R3810:Metap2 UTSW 10 93,706,026 (GRCm39) nonsense probably null
R3811:Metap2 UTSW 10 93,706,026 (GRCm39) nonsense probably null
R3812:Metap2 UTSW 10 93,706,026 (GRCm39) nonsense probably null
R4174:Metap2 UTSW 10 93,715,427 (GRCm39) missense possibly damaging 0.68
R4801:Metap2 UTSW 10 93,704,757 (GRCm39) missense probably damaging 1.00
R4802:Metap2 UTSW 10 93,704,757 (GRCm39) missense probably damaging 1.00
R4983:Metap2 UTSW 10 93,725,462 (GRCm39) missense possibly damaging 0.86
R5030:Metap2 UTSW 10 93,715,539 (GRCm39) splice site probably null
R5276:Metap2 UTSW 10 93,704,794 (GRCm39) missense probably benign 0.02
R8191:Metap2 UTSW 10 93,701,267 (GRCm39) critical splice donor site probably null
R8311:Metap2 UTSW 10 93,697,384 (GRCm39) missense possibly damaging 0.71
R9622:Metap2 UTSW 10 93,707,366 (GRCm39) missense probably benign 0.02
Predicted Primers PCR Primer
(F):5'- TTTGTCGGAAACACCAGCCG -3'
(R):5'- TGGGGACTTGAAATACTGCCTTC -3'

Sequencing Primer
(F):5'- CACCAGCCGTGACAAGTTTGTATG -3'
(R):5'- GACTTGAAATACTGCCTTCCTGTGAG -3'
Posted On 2016-07-22