Incidental Mutation 'R6223:Mmel1'
ID 504134
Institutional Source Beutler Lab
Gene Symbol Mmel1
Ensembl Gene ENSMUSG00000058183
Gene Name membrane metallo-endopeptidase-like 1
Synonyms NEPLP alpha, NEPLP beta, Mell1, SEP, Nep2, Nl1, NEPLP gamma
MMRRC Submission 044354-MU
Accession Numbers
Essential gene? Probably non essential (E-score: 0.151) question?
Stock # R6223 (G1)
Quality Score 225.009
Status Not validated
Chromosome 4
Chromosomal Location 154954042-154979985 bp(+) (GRCm39)
Type of Mutation splice site (4577 bp from exon)
DNA Base Change (assembly) A to G at 154956159 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change
Ref Sequence ENSEMBL: ENSMUSP00000146409 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000050220] [ENSMUST00000079269] [ENSMUST00000080559] [ENSMUST00000105634] [ENSMUST00000105635] [ENSMUST00000163732] [ENSMUST00000207854]
AlphaFold no structure available at present
Predicted Effect probably null
Transcript: ENSMUST00000050220
SMART Domains Protein: ENSMUSP00000051782
Gene: ENSMUSG00000046637

DomainStartEndE-ValueType
Blast:TPR 38 68 4e-6 BLAST
low complexity region 69 85 N/A INTRINSIC
TPR 166 199 2.66e0 SMART
TPR 200 233 4.45e-2 SMART
TPR 294 327 9e1 SMART
Blast:TPR 328 361 2e-7 BLAST
TPR 412 445 8.77e1 SMART
TPR 452 485 1.78e-1 SMART
Blast:TPR 500 533 9e-8 BLAST
Predicted Effect possibly damaging
Transcript: ENSMUST00000079269
AA Change: E17G

PolyPhen 2 Score 0.725 (Sensitivity: 0.86; Specificity: 0.92)
SMART Domains Protein: ENSMUSP00000078252
Gene: ENSMUSG00000058183
AA Change: E17G

DomainStartEndE-ValueType
transmembrane domain 20 42 N/A INTRINSIC
Pfam:Peptidase_M13_N 99 498 1.7e-135 PFAM
Pfam:Peptidase_M13 559 767 1.2e-68 PFAM
Predicted Effect probably benign
Transcript: ENSMUST00000080559
AA Change: E17G

PolyPhen 2 Score 0.399 (Sensitivity: 0.89; Specificity: 0.89)
SMART Domains Protein: ENSMUSP00000079399
Gene: ENSMUSG00000058183
AA Change: E17G

DomainStartEndE-ValueType
transmembrane domain 20 42 N/A INTRINSIC
Pfam:Peptidase_M13_N 76 512 4.8e-131 PFAM
Pfam:Peptidase_M13 573 779 3.4e-71 PFAM
Predicted Effect probably benign
Transcript: ENSMUST00000105634
AA Change: E17G

PolyPhen 2 Score 0.399 (Sensitivity: 0.89; Specificity: 0.89)
SMART Domains Protein: ENSMUSP00000101259
Gene: ENSMUSG00000058183
AA Change: E17G

DomainStartEndE-ValueType
transmembrane domain 20 42 N/A INTRINSIC
Pfam:Peptidase_M13_N 76 512 1.4e-105 PFAM
Pfam:Peptidase_M13 573 781 4e-74 PFAM
Predicted Effect probably benign
Transcript: ENSMUST00000105635
AA Change: E17G

PolyPhen 2 Score 0.399 (Sensitivity: 0.89; Specificity: 0.89)
SMART Domains Protein: ENSMUSP00000101260
Gene: ENSMUSG00000058183
AA Change: E17G

DomainStartEndE-ValueType
transmembrane domain 20 42 N/A INTRINSIC
Pfam:Peptidase_M13_N 76 475 1.6e-135 PFAM
Pfam:Peptidase_M13 536 744 1.2e-68 PFAM
Predicted Effect noncoding transcript
Transcript: ENSMUST00000138795
Predicted Effect possibly damaging
Transcript: ENSMUST00000163732
AA Change: E17G

PolyPhen 2 Score 0.950 (Sensitivity: 0.79; Specificity: 0.95)
SMART Domains Protein: ENSMUSP00000131753
Gene: ENSMUSG00000058183
AA Change: E17G

DomainStartEndE-ValueType
transmembrane domain 20 42 N/A INTRINSIC
Pfam:Peptidase_M13_N 99 498 1.7e-135 PFAM
Pfam:Peptidase_M13 559 765 3.3e-71 PFAM
Predicted Effect probably null
Transcript: ENSMUST00000207854
Predicted Effect noncoding transcript
Transcript: ENSMUST00000151696
Coding Region Coverage
  • 1x: 99.9%
  • 3x: 99.7%
  • 10x: 98.4%
  • 20x: 95.6%
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 neutral endopeptidase (NEP) or membrane metallo-endopeptidase (MME) family. Family members play important roles in pain perception, arterial pressure regulation, phosphate metabolism and homeostasis. This protein is a type II transmembrane protein and is thought to be expressed as a secreted protein. This gene is expressed mainly in testis with weak expression in the brain, kidney, and heart. [provided by RefSeq, Jul 2008]
PHENOTYPE: Homozygous null mice display impaired male fertility. Female fertility is not affected. [provided by MGI curators]
Allele List at MGI
Other mutations in this stock
Total: 60 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
6820408C15Rik A C 2: 152,269,873 (GRCm39) R8S probably benign Het
Abca8b A G 11: 109,868,672 (GRCm39) V164A probably benign Het
Acadm C A 3: 153,644,186 (GRCm39) probably null Het
Ap3b2 G A 7: 81,123,210 (GRCm39) R435* probably null Het
Art2b A G 7: 101,229,158 (GRCm39) F247S possibly damaging Het
C1rb T A 6: 124,551,539 (GRCm39) D216E probably benign Het
Casz1 C A 4: 149,017,840 (GRCm39) D90E probably damaging Het
Ccdc13 A G 9: 121,627,975 (GRCm39) probably benign Het
Cdc25a C A 9: 109,718,842 (GRCm39) P409T possibly damaging Het
Cidea A C 18: 67,491,809 (GRCm39) K23T possibly damaging Het
Clspn T A 4: 126,479,961 (GRCm39) D1101E probably damaging Het
Col10a1 A T 10: 34,271,183 (GRCm39) D385V probably damaging Het
Crat C T 2: 30,297,042 (GRCm39) V304I probably benign Het
Cyp2d26 A T 15: 82,675,918 (GRCm39) W265R probably benign Het
Dock8 A T 19: 25,138,416 (GRCm39) Y1247F probably benign Het
Dync2i1 T C 12: 116,221,078 (GRCm39) D11G possibly damaging Het
Eed A G 7: 89,605,495 (GRCm39) Y365H probably damaging Het
Fabp5 T A 3: 10,080,170 (GRCm39) F73L probably benign Het
Fbn1 C T 2: 125,254,591 (GRCm39) C224Y possibly damaging Het
Ggcx T C 6: 72,406,588 (GRCm39) F684L probably damaging Het
Glrp1 G A 1: 88,431,164 (GRCm39) Q69* probably null Het
Gm29797 T C 2: 181,300,850 (GRCm39) V115A possibly damaging Het
Gtf3c1 C T 7: 125,275,797 (GRCm39) R543K probably benign Het
Ifih1 T C 2: 62,428,603 (GRCm39) I891V probably benign Het
Ifnar2 C T 16: 91,184,876 (GRCm39) T89M probably damaging Het
Kat6a C A 8: 23,430,442 (GRCm39) N1932K unknown Het
Mgat5 A T 1: 127,310,716 (GRCm39) D210V possibly damaging Het
Myh3 G T 11: 66,988,843 (GRCm39) V1499L probably benign Het
Ncan A C 8: 70,562,604 (GRCm39) D551E probably benign Het
Nol11 G T 11: 107,062,442 (GRCm39) T598K possibly damaging Het
Olfml3 G A 3: 103,643,776 (GRCm39) R202W probably damaging Het
Or2w4 G A 13: 21,795,536 (GRCm39) T201I probably benign Het
Or4e2 A G 14: 52,688,136 (GRCm39) R89G probably benign Het
Pcdh9 T C 14: 93,253,169 (GRCm39) K1131E probably benign Het
Pcolce A G 5: 137,603,561 (GRCm39) M424T probably damaging Het
Pi16 C A 17: 29,546,413 (GRCm39) S397* probably null Het
Pi4ka A T 16: 17,175,435 (GRCm39) Y464* probably null Het
Pik3c2b T A 1: 132,998,095 (GRCm39) L324M probably damaging Het
Prdm2 T C 4: 142,868,777 (GRCm39) N179S probably benign Het
Prss56 C T 1: 87,113,134 (GRCm39) P183S probably benign Het
Prx T G 7: 27,216,261 (GRCm39) M393R probably damaging Het
Qpctl T C 7: 18,877,134 (GRCm39) D328G probably damaging Het
Qser1 A G 2: 104,617,993 (GRCm39) S940P probably benign Het
Rchy1 G A 5: 92,105,826 (GRCm39) R41W probably damaging Het
Scp2d1 T C 2: 144,665,868 (GRCm39) I69T possibly damaging Het
Sirpb1a A G 3: 15,444,086 (GRCm39) V388A probably benign Het
Ssu2 G T 6: 112,353,409 (GRCm39) C238* probably null Het
Stub1 C T 17: 26,051,787 (GRCm39) G14D probably damaging Het
Tab1 T A 15: 80,032,464 (GRCm39) C24S probably damaging Het
Tdrd1 T C 19: 56,854,282 (GRCm39) V1076A probably damaging Het
Tex10 T C 4: 48,468,525 (GRCm39) R134G probably damaging Het
Tg T A 15: 66,579,771 (GRCm39) N1525K probably benign Het
Tll2 G A 19: 41,124,391 (GRCm39) T208I possibly damaging Het
Tmem232 T C 17: 65,807,191 (GRCm39) M1V probably null Het
Ttc7b A G 12: 100,353,368 (GRCm39) probably null Het
Ubb A G 11: 62,443,351 (GRCm39) E127G possibly damaging Het
Ulk2 A T 11: 61,678,330 (GRCm39) Y796* probably null Het
Vdac2 G A 14: 21,895,246 (GRCm39) G265R possibly damaging Het
Vmn2r45 A T 7: 8,486,301 (GRCm39) V329E probably benign Het
Zbtb47 G A 9: 121,592,853 (GRCm39) R391Q possibly damaging Het
Other mutations in Mmel1
AlleleSourceChrCoordTypePredicted EffectPPH Score
IGL00971:Mmel1 APN 4 154,972,289 (GRCm39) splice site probably benign
IGL01560:Mmel1 APN 4 154,976,967 (GRCm39) missense probably null 1.00
IGL01734:Mmel1 APN 4 154,976,408 (GRCm39) missense probably benign 0.00
IGL02933:Mmel1 APN 4 154,968,087 (GRCm39) missense probably damaging 1.00
IGL03178:Mmel1 APN 4 154,975,311 (GRCm39) missense possibly damaging 0.75
R1161:Mmel1 UTSW 4 154,979,671 (GRCm39) missense probably damaging 1.00
R1522:Mmel1 UTSW 4 154,979,443 (GRCm39) missense probably damaging 1.00
R1566:Mmel1 UTSW 4 154,968,110 (GRCm39) missense probably damaging 1.00
R1885:Mmel1 UTSW 4 154,975,333 (GRCm39) missense possibly damaging 0.76
R2177:Mmel1 UTSW 4 154,978,560 (GRCm39) missense probably damaging 1.00
R3413:Mmel1 UTSW 4 154,974,043 (GRCm39) missense probably damaging 1.00
R3432:Mmel1 UTSW 4 154,969,955 (GRCm39) splice site probably benign
R3870:Mmel1 UTSW 4 154,968,095 (GRCm39) missense probably benign 0.01
R4197:Mmel1 UTSW 4 154,977,761 (GRCm39) missense probably damaging 1.00
R4822:Mmel1 UTSW 4 154,972,354 (GRCm39) missense probably benign 0.00
R4998:Mmel1 UTSW 4 154,969,967 (GRCm39) missense probably benign 0.00
R5135:Mmel1 UTSW 4 154,966,781 (GRCm39) missense probably benign 0.20
R5225:Mmel1 UTSW 4 154,976,456 (GRCm39) missense probably damaging 0.96
R5821:Mmel1 UTSW 4 154,970,044 (GRCm39) missense possibly damaging 0.82
R6131:Mmel1 UTSW 4 154,979,475 (GRCm39) missense probably damaging 1.00
R6132:Mmel1 UTSW 4 154,979,475 (GRCm39) missense probably damaging 1.00
R6133:Mmel1 UTSW 4 154,979,475 (GRCm39) missense probably damaging 1.00
R6194:Mmel1 UTSW 4 154,967,673 (GRCm39) nonsense probably null
R6786:Mmel1 UTSW 4 154,976,885 (GRCm39) nonsense probably null
R6921:Mmel1 UTSW 4 154,966,134 (GRCm39) missense probably damaging 0.97
R7272:Mmel1 UTSW 4 154,978,547 (GRCm39) missense probably damaging 1.00
R7373:Mmel1 UTSW 4 154,973,665 (GRCm39) missense not run
R7685:Mmel1 UTSW 4 154,956,111 (GRCm39) start codon destroyed probably null 0.28
R7996:Mmel1 UTSW 4 154,976,912 (GRCm39) missense probably benign 0.03
R8683:Mmel1 UTSW 4 154,973,985 (GRCm39) missense probably benign 0.13
R8856:Mmel1 UTSW 4 154,969,478 (GRCm39) missense possibly damaging 0.84
R8924:Mmel1 UTSW 4 154,974,091 (GRCm39) missense probably damaging 1.00
R9364:Mmel1 UTSW 4 154,976,967 (GRCm39) missense probably null 1.00
R9594:Mmel1 UTSW 4 154,978,592 (GRCm39) missense probably benign 0.15
R9683:Mmel1 UTSW 4 154,977,285 (GRCm39) missense probably damaging 1.00
X0025:Mmel1 UTSW 4 154,979,142 (GRCm39) missense probably benign 0.06
Z1176:Mmel1 UTSW 4 154,979,665 (GRCm39) nonsense probably null
Z1177:Mmel1 UTSW 4 154,978,531 (GRCm39) critical splice acceptor site probably null
Predicted Primers PCR Primer
(F):5'- AGTGTGTCCTAGGCATCCGATC -3'
(R):5'- GACAGAGCTTTCTGGATGGG -3'

Sequencing Primer
(F):5'- ATCCGGGCTCCAGCTGC -3'
(R):5'- ACCTCTGGAGTCAGCAGTGTG -3'
Posted On 2018-02-28