Incidental Mutation 'R6154:Mme'
ID 489430
Institutional Source Beutler Lab
Gene Symbol Mme
Ensembl Gene ENSMUSG00000027820
Gene Name membrane metallo endopeptidase
Synonyms neprilysin, 6030454K05Rik, neutral endopeptidase, NEP, CD10
MMRRC Submission 044301-MU
Accession Numbers
Essential gene? Non essential (E-score: 0.000) question?
Stock # R6154 (G1)
Quality Score 225.009
Status Validated
Chromosome 3
Chromosomal Location 63202632-63291134 bp(+) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) T to A at 63207674 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Isoleucine to Asparagine at position 40 (I40N)
Ref Sequence ENSEMBL: ENSMUSP00000141469 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000029400] [ENSMUST00000191633] [ENSMUST00000192002] [ENSMUST00000194134] [ENSMUST00000194150] [ENSMUST00000194324] [ENSMUST00000194836]
AlphaFold Q61391
Predicted Effect possibly damaging
Transcript: ENSMUST00000029400
AA Change: I40N

PolyPhen 2 Score 0.949 (Sensitivity: 0.79; Specificity: 0.95)
SMART Domains Protein: ENSMUSP00000029400
Gene: ENSMUSG00000027820
AA Change: I40N

DomainStartEndE-ValueType
PDB:2YVC|F 2 23 5e-7 PDB
transmembrane domain 29 51 N/A INTRINSIC
Pfam:Peptidase_M13_N 80 483 8.7e-103 PFAM
low complexity region 489 507 N/A INTRINSIC
low complexity region 515 526 N/A INTRINSIC
Pfam:Peptidase_M13 543 749 5.8e-75 PFAM
Predicted Effect probably damaging
Transcript: ENSMUST00000191633
AA Change: I40N

PolyPhen 2 Score 0.976 (Sensitivity: 0.76; Specificity: 0.96)
SMART Domains Protein: ENSMUSP00000141469
Gene: ENSMUSG00000027820
AA Change: I40N

DomainStartEndE-ValueType
Pfam:Peptidase_M13_N 14 130 3.3e-13 PFAM
Predicted Effect possibly damaging
Transcript: ENSMUST00000192002
AA Change: I40N

PolyPhen 2 Score 0.949 (Sensitivity: 0.79; Specificity: 0.95)
SMART Domains Protein: ENSMUSP00000141483
Gene: ENSMUSG00000027820
AA Change: I40N

DomainStartEndE-ValueType
PDB:2YVC|F 2 23 1e-7 PDB
transmembrane domain 29 51 N/A INTRINSIC
Pfam:Peptidase_M13_N 80 178 1.9e-32 PFAM
Predicted Effect noncoding transcript
Transcript: ENSMUST00000193805
Predicted Effect possibly damaging
Transcript: ENSMUST00000194134
AA Change: I40N

PolyPhen 2 Score 0.949 (Sensitivity: 0.79; Specificity: 0.95)
SMART Domains Protein: ENSMUSP00000142205
Gene: ENSMUSG00000027820
AA Change: I40N

DomainStartEndE-ValueType
PDB:2YVC|F 2 23 5e-7 PDB
transmembrane domain 29 51 N/A INTRINSIC
Pfam:Peptidase_M13_N 80 483 8.4e-134 PFAM
low complexity region 489 507 N/A INTRINSIC
low complexity region 515 526 N/A INTRINSIC
Pfam:Peptidase_M13 543 749 3.3e-67 PFAM
Predicted Effect possibly damaging
Transcript: ENSMUST00000194150
AA Change: I40N

PolyPhen 2 Score 0.949 (Sensitivity: 0.79; Specificity: 0.95)
SMART Domains Protein: ENSMUSP00000141544
Gene: ENSMUSG00000027820
AA Change: I40N

DomainStartEndE-ValueType
PDB:2YVC|F 2 23 5e-7 PDB
transmembrane domain 29 51 N/A INTRINSIC
Pfam:Peptidase_M13_N 80 483 8.4e-134 PFAM
low complexity region 489 507 N/A INTRINSIC
low complexity region 515 526 N/A INTRINSIC
Pfam:Peptidase_M13 543 749 3.3e-67 PFAM
Predicted Effect possibly damaging
Transcript: ENSMUST00000194324
AA Change: I40N

PolyPhen 2 Score 0.789 (Sensitivity: 0.85; Specificity: 0.93)
SMART Domains Protein: ENSMUSP00000142259
Gene: ENSMUSG00000027820
AA Change: I40N

DomainStartEndE-ValueType
PDB:2YVC|F 2 23 5e-8 PDB
transmembrane domain 29 51 N/A INTRINSIC
Pfam:Peptidase_M13_N 80 131 2.3e-15 PFAM
Predicted Effect possibly damaging
Transcript: ENSMUST00000194836
AA Change: I40N

PolyPhen 2 Score 0.913 (Sensitivity: 0.81; Specificity: 0.94)
SMART Domains Protein: ENSMUSP00000141452
Gene: ENSMUSG00000027820
AA Change: I40N

DomainStartEndE-ValueType
PDB:2YVC|F 2 23 1e-7 PDB
transmembrane domain 29 51 N/A INTRINSIC
Pfam:Peptidase_M13_N 80 187 5.6e-33 PFAM
Meta Mutation Damage Score 0.3073 question?
Coding Region Coverage
  • 1x: 99.9%
  • 3x: 99.6%
  • 10x: 98.1%
  • 20x: 94.8%
Validation Efficiency 97% (70/72)
MGI Phenotype FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene encodes a common acute lymphocytic leukemia antigen that is an important cell surface marker in the diagnosis of human acute lymphocytic leukemia (ALL). This protein is present on leukemic cells of pre-B phenotype, which represent 85% of cases of ALL. This protein is not restricted to leukemic cells, however, and is found on a variety of normal tissues. It is a glycoprotein that is particularly abundant in kidney, where it is present on the brush border of proximal tubules and on glomerular epithelium. The protein is a neutral endopeptidase that cleaves peptides at the amino side of hydrophobic residues and inactivates several peptide hormones including glucagon, enkephalins, substance P, neurotensin, oxytocin, and bradykinin. This gene, which encodes a 100-kD type II transmembrane glycoprotein, exists in a single copy of greater than 45 kb. The 5' untranslated region of this gene is alternatively spliced, resulting in four separate mRNA transcripts. The coding region is not affected by alternative splicing. [provided by RefSeq, Jul 2008]
PHENOTYPE: Mice homozygous for a knock-out allele exhibit enhanced allergic contact dermatitis responses, diffuse hepatic necrosis after LPS shock or treatment with a combination of TNF and interleukin-1 beta, and increased brain and plasma amyloid beta peptide levels. [provided by MGI curators]
Allele List at MGI
Other mutations in this stock
Total: 72 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
Acss3 T G 10: 106,959,210 (GRCm39) I79L probably benign Het
Adam6a C T 12: 113,509,292 (GRCm39) T555I probably benign Het
Adap1 A G 5: 139,293,531 (GRCm39) V60A possibly damaging Het
Afg3l2 G T 18: 67,554,329 (GRCm39) L458M probably damaging Het
Angpt1 T C 15: 42,387,051 (GRCm39) E101G probably damaging Het
Asxl2 T C 12: 3,546,593 (GRCm39) V459A possibly damaging Het
Cabs1 C T 5: 88,127,613 (GRCm39) T88I possibly damaging Het
Camta2 G A 11: 70,569,211 (GRCm39) A578V probably damaging Het
Cdc16 A G 8: 13,818,609 (GRCm39) N316D possibly damaging Het
Chrm3 T A 13: 9,928,476 (GRCm39) M187L possibly damaging Het
Clcn4 T C 7: 7,294,481 (GRCm39) T367A probably benign Het
Clcn7 T C 17: 25,376,928 (GRCm39) S654P probably damaging Het
Col6a3 T A 1: 90,701,387 (GRCm39) T2510S unknown Het
Crisp4 T C 1: 18,193,012 (GRCm39) E192G possibly damaging Het
Dmbt1 T A 7: 130,711,370 (GRCm39) probably null Het
Dnah5 T G 15: 28,204,177 (GRCm39) L18R probably benign Het
Dnah9 T G 11: 65,746,164 (GRCm39) D3983A probably benign Het
Dock5 C A 14: 68,097,361 (GRCm39) V71L probably benign Het
Dync1h1 T C 12: 110,584,427 (GRCm39) V610A probably damaging Het
Dynlrb2 A G 8: 117,242,428 (GRCm39) Y86C probably benign Het
Ep400 T C 5: 110,903,799 (GRCm39) I267V probably damaging Het
Gaa A G 11: 119,169,178 (GRCm39) Y575C probably damaging Het
Gm8094 T A 14: 42,934,020 (GRCm39) D24V probably benign Het
Grina T C 15: 76,133,087 (GRCm39) I244T possibly damaging Het
Haus6 A G 4: 86,501,993 (GRCm39) L626P possibly damaging Het
Hexd A T 11: 121,112,097 (GRCm39) H439L probably benign Het
Ifna12 A T 4: 88,521,531 (GRCm39) C5* probably null Het
Igf2bp2 G T 16: 21,894,843 (GRCm39) S300* probably null Het
Ighv6-5 T C 12: 114,380,362 (GRCm39) R71G probably benign Het
Lrrc37 A G 11: 103,504,969 (GRCm39) V2333A probably benign Het
Lrrn4cl T C 19: 8,829,252 (GRCm39) S77P probably damaging Het
Mast4 A G 13: 102,923,929 (GRCm39) L302P probably damaging Het
Mink1 T C 11: 70,500,927 (GRCm39) V831A possibly damaging Het
Myh2 A G 11: 67,077,438 (GRCm39) T858A probably benign Het
Ncbp3 T A 11: 72,940,700 (GRCm39) Y67N probably damaging Het
Nedd1 T A 10: 92,534,104 (GRCm39) I349F possibly damaging Het
Nek11 A T 9: 105,200,368 (GRCm39) *81K probably null Het
Nrip1 A G 16: 76,090,718 (GRCm39) Y280H probably damaging Het
Obsl1 T C 1: 75,476,788 (GRCm39) D722G probably benign Het
Or10ag55-ps1 T G 2: 87,139,902 (GRCm39) S256R probably benign Het
Or2m12 A T 16: 19,105,181 (GRCm39) I104K probably damaging Het
Or4c29 A G 2: 88,740,734 (GRCm39) M1T probably null Het
Or5i1 A G 2: 87,613,100 (GRCm39) D72G possibly damaging Het
Or6c7 C T 10: 129,323,545 (GRCm39) T222I probably damaging Het
Pcdhb6 A G 18: 37,467,966 (GRCm39) I296V probably benign Het
Pcnx2 G T 8: 126,489,552 (GRCm39) L1681M probably damaging Het
Pdlim5 T C 3: 141,983,674 (GRCm39) R360G possibly damaging Het
Peli2 C T 14: 48,488,051 (GRCm39) Q81* probably null Het
Pitpnb C T 5: 111,486,263 (GRCm39) Q56* probably null Het
Ppp1r3a A G 6: 14,754,603 (GRCm39) S215P possibly damaging Het
Prrt3 A G 6: 113,471,989 (GRCm39) Y728H probably damaging Het
Rsf1 A AAGGCGACGG 7: 97,229,111 (GRCm39) probably null Het
Rsf1 GCG GCGACGGCGACG 7: 97,229,114 (GRCm39) probably benign Het
Sbno1 T C 5: 124,516,542 (GRCm39) H1277R possibly damaging Het
Siglecg C A 7: 43,061,441 (GRCm39) N481K possibly damaging Het
Sirt6 C T 10: 81,462,339 (GRCm39) G20D probably damaging Het
Sit1 C A 4: 43,482,981 (GRCm39) R89S probably benign Het
Slc7a12 A G 3: 14,546,094 (GRCm39) R80G probably damaging Het
Smok3c T A 5: 138,062,747 (GRCm39) M78K probably benign Het
Stk10 T A 11: 32,553,654 (GRCm39) probably null Het
Tada2b A G 5: 36,634,008 (GRCm39) V190A probably damaging Het
Tnk1 C T 11: 69,747,780 (GRCm39) V41I probably damaging Het
Tpr T A 1: 150,299,567 (GRCm39) V1146E probably benign Het
Trappc9 T C 15: 72,929,930 (GRCm39) D142G probably benign Het
Trpm3 T C 19: 22,965,178 (GRCm39) Y1558H probably damaging Het
Unc5c C A 3: 141,383,914 (GRCm39) S97R probably damaging Het
Vmn1r172 T C 7: 23,359,583 (GRCm39) I156T probably damaging Het
Vmn2r51 A T 7: 9,821,921 (GRCm39) M588K possibly damaging Het
Vps26a T G 10: 62,304,119 (GRCm39) E117D probably damaging Het
Zfp451 A T 1: 33,842,627 (GRCm39) probably benign Het
Zfp534 C A 4: 147,759,145 (GRCm39) R508I probably benign Het
Zp3r C T 1: 130,526,642 (GRCm39) C187Y probably damaging Het
Other mutations in Mme
AlleleSourceChrCoordTypePredicted EffectPPH Score
IGL00235:Mme APN 3 63,247,465 (GRCm39) missense possibly damaging 0.95
IGL00329:Mme APN 3 63,287,749 (GRCm39) nonsense probably null
IGL01013:Mme APN 3 63,235,281 (GRCm39) splice site probably null
IGL01316:Mme APN 3 63,247,580 (GRCm39) splice site probably benign
IGL01333:Mme APN 3 63,253,512 (GRCm39) missense probably damaging 1.00
IGL01392:Mme APN 3 63,269,467 (GRCm39) missense probably damaging 1.00
IGL01566:Mme APN 3 63,269,350 (GRCm39) splice site probably benign
IGL01739:Mme APN 3 63,247,534 (GRCm39) missense possibly damaging 0.78
IGL01996:Mme APN 3 63,250,970 (GRCm39) missense probably benign 0.11
IGL02125:Mme APN 3 63,256,070 (GRCm39) missense probably damaging 1.00
IGL02154:Mme APN 3 63,250,976 (GRCm39) missense probably benign
IGL03214:Mme APN 3 63,237,111 (GRCm39) missense possibly damaging 0.72
IGL03291:Mme APN 3 63,253,525 (GRCm39) missense probably benign 0.00
R0498:Mme UTSW 3 63,253,487 (GRCm39) missense probably damaging 1.00
R0595:Mme UTSW 3 63,235,602 (GRCm39) missense probably benign 0.27
R0980:Mme UTSW 3 63,247,550 (GRCm39) missense probably benign
R1210:Mme UTSW 3 63,251,027 (GRCm39) missense probably benign 0.01
R1600:Mme UTSW 3 63,272,479 (GRCm39) missense probably damaging 1.00
R1852:Mme UTSW 3 63,235,467 (GRCm39) missense probably benign 0.00
R1852:Mme UTSW 3 63,235,404 (GRCm39) missense probably benign 0.31
R2037:Mme UTSW 3 63,235,681 (GRCm39) missense probably null 1.00
R2177:Mme UTSW 3 63,208,426 (GRCm39) missense probably benign 0.02
R2200:Mme UTSW 3 63,287,713 (GRCm39) missense possibly damaging 0.87
R2306:Mme UTSW 3 63,207,673 (GRCm39) missense probably benign 0.00
R2847:Mme UTSW 3 63,252,620 (GRCm39) missense possibly damaging 0.91
R3008:Mme UTSW 3 63,266,378 (GRCm39) missense probably damaging 1.00
R3749:Mme UTSW 3 63,250,961 (GRCm39) missense probably damaging 1.00
R3876:Mme UTSW 3 63,269,480 (GRCm39) splice site probably benign
R3961:Mme UTSW 3 63,252,613 (GRCm39) missense probably damaging 1.00
R3981:Mme UTSW 3 63,235,485 (GRCm39) missense probably damaging 1.00
R3982:Mme UTSW 3 63,235,485 (GRCm39) missense probably damaging 1.00
R3983:Mme UTSW 3 63,235,485 (GRCm39) missense probably damaging 1.00
R4494:Mme UTSW 3 63,254,613 (GRCm39) missense probably benign
R4589:Mme UTSW 3 63,287,693 (GRCm39) missense probably benign
R4706:Mme UTSW 3 63,256,133 (GRCm39) missense possibly damaging 0.92
R4871:Mme UTSW 3 63,247,453 (GRCm39) missense probably benign 0.01
R4957:Mme UTSW 3 63,250,910 (GRCm39) splice site probably benign
R5053:Mme UTSW 3 63,272,270 (GRCm39) missense probably damaging 1.00
R5316:Mme UTSW 3 63,276,375 (GRCm39) missense probably damaging 1.00
R5502:Mme UTSW 3 63,207,702 (GRCm39) nonsense probably null
R5579:Mme UTSW 3 63,256,066 (GRCm39) missense probably damaging 1.00
R6007:Mme UTSW 3 63,250,929 (GRCm39) nonsense probably null
R6022:Mme UTSW 3 63,272,218 (GRCm39) missense probably damaging 1.00
R6143:Mme UTSW 3 63,207,532 (GRCm39) splice site probably null
R6333:Mme UTSW 3 63,249,382 (GRCm39) missense probably benign 0.00
R6476:Mme UTSW 3 63,251,056 (GRCm39) critical splice donor site probably null
R6514:Mme UTSW 3 63,272,265 (GRCm39) nonsense probably null
R6711:Mme UTSW 3 63,249,339 (GRCm39) missense possibly damaging 0.93
R6842:Mme UTSW 3 63,269,465 (GRCm39) missense probably damaging 1.00
R6996:Mme UTSW 3 63,253,523 (GRCm39) missense possibly damaging 0.63
R7040:Mme UTSW 3 63,276,344 (GRCm39) missense probably damaging 1.00
R7043:Mme UTSW 3 63,252,638 (GRCm39) nonsense probably null
R7084:Mme UTSW 3 63,235,638 (GRCm39) missense probably damaging 0.98
R7126:Mme UTSW 3 63,276,322 (GRCm39) missense probably damaging 0.97
R7783:Mme UTSW 3 63,272,288 (GRCm39) missense probably damaging 1.00
R8501:Mme UTSW 3 63,234,156 (GRCm39) missense probably damaging 1.00
R8857:Mme UTSW 3 63,256,070 (GRCm39) missense probably damaging 1.00
R9453:Mme UTSW 3 63,272,306 (GRCm39) missense possibly damaging 0.90
R9556:Mme UTSW 3 63,272,225 (GRCm39) missense probably damaging 0.97
R9648:Mme UTSW 3 63,208,426 (GRCm39) missense probably benign 0.02
X0058:Mme UTSW 3 63,272,442 (GRCm39) missense probably damaging 1.00
Predicted Primers PCR Primer
(F):5'- GGGACCAATCAGATTCAGATGTGTG -3'
(R):5'- CACTTTAACATATGGATGCGGATC -3'

Sequencing Primer
(F):5'- CACAGATGTGCTTTTTATGAAATGC -3'
(R):5'- GGATGCGGATCTTCTAAATGAATCC -3'
Posted On 2017-10-10