Incidental Mutation 'D4043:Mael'
ID265
Institutional Source Beutler Lab
Gene Symbol Mael
Ensembl Gene ENSMUSG00000040629
Gene Namemaelstrom spermatogenic transposon silencer
Synonyms4933405K18Rik
Accession Numbers

Genbank: NM_175296; MGI: 2138453

Is this an essential gene? Possibly non essential (E-score: 0.401) question?
Stock #D4043 (G3) of strain 483
Quality Score
Status Validated
Chromosome1
Chromosomal Location166201201-166238747 bp(-) (GRCm38)
Type of Mutationmissense
DNA Base Change (assembly) T to C at 166236886 bp
ZygosityHomozygous
Amino Acid Change Isoleucine to Methionine at position 104 (I104M)
Ref Sequence ENSEMBL: ENSMUSP00000141652 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000038782] [ENSMUST00000194057]
Predicted Effect probably benign
Transcript: ENSMUST00000038782
AA Change: I104M

PolyPhen 2 Score 0.001 (Sensitivity: 0.99; Specificity: 0.15)
SMART Domains Protein: ENSMUSP00000045828
Gene: ENSMUSG00000040629
AA Change: I104M

DomainStartEndE-ValueType
Pfam:HMG_box_2 2 73 4.4e-27 PFAM
Pfam:Maelstrom 128 329 1.6e-58 PFAM
low complexity region 399 407 N/A INTRINSIC
Predicted Effect probably benign
Transcript: ENSMUST00000194057
AA Change: I104M

PolyPhen 2 Score 0.002 (Sensitivity: 0.99; Specificity: 0.30)
SMART Domains Protein: ENSMUSP00000141652
Gene: ENSMUSG00000040629
AA Change: I104M

DomainStartEndE-ValueType
Pfam:HMG_box_2 2 73 1.6e-24 PFAM
Pfam:Maelstrom 128 314 2.6e-43 PFAM
low complexity region 385 393 N/A INTRINSIC
Meta Mutation Damage Score 0.1132 question?
Coding Region Coverage
  • 1x: 88.8%
  • 3x: 72.5%
Validation Efficiency 88% (220/249)
MGI Phenotype PHENOTYPE: Male mice homozygous for a null allele are infertile and display small testes, a complete block of spermatogenesis due to apoptosis during meiotic prophase I, defects in homologous chromosome synapsis, DNA damage, reduced DNA methylation, and derepression of L1 retrotransposons in the adult testis. [provided by MGI curators]
Allele List at MGI

All alleles(2) : Targeted, other(2)

Other mutations in this stock
Total: 25 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
1110020G09Rik T A 15: 9,103,385 probably benign Homo
1700029J07Rik A G 8: 45,956,403 V293A probably damaging Het
Adam29 A T 8: 55,872,461 C319* probably null Het
Adgrg1 T C 8: 95,005,229 probably null Homo
Ago3 A T 4: 126,351,003 V630E probably damaging Het
Armc8 G T 9: 99,483,976 N628K probably benign Het
Chd7 A G 4: 8,862,650 D2579G probably damaging Het
Duox1 G A 2: 122,344,795 C1358Y probably benign Het
Fam208a A G 14: 27,471,992 I1050V probably benign Het
Ftsj3 C A 11: 106,254,808 M66I possibly damaging Homo
Iqub C T 6: 24,505,751 E53K possibly damaging Het
Kirrel T A 3: 87,083,203 T771S probably benign Het
Lrrc66 A T 5: 73,607,526 S725T probably benign Het
Mkks C T 2: 136,874,610 V457I probably benign Het
Npas1 T C 7: 16,463,244 probably null Het
Ocrl T C X: 47,936,323 V359A probably benign Homo
Olfr1065 G A 2: 86,445,220 T254M probably damaging Het
Pde6b C T 5: 108,425,356 R531* probably null Het
Polr1a G A 6: 71,941,417 C653Y possibly damaging Het
Rbm26 A G 14: 105,152,540 V216A possibly damaging Het
Rin2 C A 2: 145,822,363 H52Q possibly damaging Het
Ssc5d C T 7: 4,943,983 T1112I possibly damaging Het
Sv2c C T 13: 96,088,481 V107M probably benign Het
Tulp3 G A 6: 128,324,150 S366L probably benign Het
Zfp831 T A 2: 174,645,266 V578E probably benign Homo
Other mutations in Mael
AlleleSourceChrCoordTypePredicted EffectPPH Score
IGL00907:Mael APN 1 166204849 missense probably damaging 1.00
IGL01153:Mael APN 1 166202350 missense possibly damaging 0.89
R0218:Mael UTSW 1 166238590 missense probably damaging 1.00
R0811:Mael UTSW 1 166235399 critical splice donor site probably null
R0812:Mael UTSW 1 166235399 critical splice donor site probably null
R1544:Mael UTSW 1 166202290 missense probably benign 0.28
R2096:Mael UTSW 1 166225675 missense probably benign 0.41
R2914:Mael UTSW 1 166226610 missense probably damaging 1.00
R3031:Mael UTSW 1 166204806 missense probably damaging 1.00
R3709:Mael UTSW 1 166238566 missense probably damaging 0.99
R3710:Mael UTSW 1 166238566 missense probably damaging 0.99
R3880:Mael UTSW 1 166236868 splice site probably benign
R4594:Mael UTSW 1 166235487 missense probably damaging 1.00
R4669:Mael UTSW 1 166235508 missense probably damaging 1.00
X0018:Mael UTSW 1 166201568 missense probably benign
Nature of Mutation
DNA sequencing using the SOLiD technique identified an A to G transition at position 390 of the Mael transcript in exon 3 of 12 total exons. The mutated nucleotide causes an isoleucine to methionine substitution at amino acid 104 of the encoded protein. The mutation has been confirmed by DNA sequencing using the Sanger method (Figure 1).
Protein Function and Prediction
The Mael gene encodes a 434 amino acid protein that is a homologue of the Drosophila melanogaster maelstrom protein that is a component of the meiotic nuage, a germ-cell-specific organelle required to repress transposon activity during meiosis. The protein is testis-specific, and prevents transposon mobilization by forming complexes composed of piRNAs and Piwi proteins and governing the methylation and subsequent repression of transposons.  The MAEL protein contains one HMG box DNA-binding domain at amino acids 4-73 (Uniprot Q8BVN9).  Mice lacking the Mael gene are viable, but show a profound defect in synapsis of homologous chromosomes in male meiosis, piRNA production defects, and increased transposon expression.
 
The I104M change is predicted to be benign by the PolyPhen program.

 

Posted On2010-08-09