Incidental Mutation 'D4043:Mael'
| ID |
265 |
| Institutional Source |
Beutler Lab
|
| Gene Symbol |
Mael
|
| Ensembl Gene |
ENSMUSG00000040629 |
| Gene Name |
maelstrom spermatogenic transposon silencer |
| Synonyms |
4933405K18Rik |
| Accession Numbers |
|
| Essential gene? |
Possibly non essential
(E-score: 0.468)
|
| Stock # |
D4043 (G3)
of strain
483
|
| Quality Score |
|
|
Status
|
Validated
|
| Chromosome |
1 |
| Chromosomal Location |
166028954-166066313 bp(-) (GRCm39) |
| Type of Mutation |
missense |
| DNA Base Change (assembly) |
T to C
at 166064455 bp (GRCm39)
|
| Zygosity |
Homozygous |
| 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]
|
| AlphaFold |
Q8BVN9 |
| 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
| Domain | Start | End | E-Value | Type |
|---|
|
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
| Domain | Start | End | E-Value | Type |
|---|
|
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 |
0.0898 |
| Coding Region Coverage |
|
| 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
| Gene | Ref | Var | Chr/Loc | Mutation | Predicted Effect | Zygosity |
|---|
| Adam29 |
A |
T |
8: 56,325,496 (GRCm39) |
C319* |
probably null |
Het |
| Adgrg1 |
T |
C |
8: 95,731,857 (GRCm39) |
|
probably null |
Homo |
| Ago3 |
A |
T |
4: 126,244,796 (GRCm39) |
V630E |
probably damaging |
Het |
| Armc8 |
G |
T |
9: 99,366,029 (GRCm39) |
N628K |
probably benign |
Het |
| Cfap96 |
A |
G |
8: 46,409,440 (GRCm39) |
V293A |
probably damaging |
Het |
| Chd7 |
A |
G |
4: 8,862,650 (GRCm39) |
D2579G |
probably damaging |
Het |
| Duox1 |
G |
A |
2: 122,175,276 (GRCm39) |
C1358Y |
probably benign |
Het |
| Ftsj3 |
C |
A |
11: 106,145,634 (GRCm39) |
M66I |
possibly damaging |
Homo |
| Iqub |
C |
T |
6: 24,505,750 (GRCm39) |
E53K |
possibly damaging |
Het |
| Kirrel1 |
T |
A |
3: 86,990,510 (GRCm39) |
T771S |
probably benign |
Het |
| Lrrc66 |
A |
T |
5: 73,764,869 (GRCm39) |
S725T |
probably benign |
Het |
| Mkks |
C |
T |
2: 136,716,530 (GRCm39) |
V457I |
probably benign |
Het |
| Nadk2 |
T |
A |
15: 9,103,473 (GRCm39) |
|
probably benign |
Homo |
| Npas1 |
T |
C |
7: 16,197,169 (GRCm39) |
|
probably null |
Het |
| Ocrl |
T |
C |
X: 47,025,200 (GRCm39) |
V359A |
probably benign |
Homo |
| Or8k27 |
G |
A |
2: 86,275,564 (GRCm39) |
T254M |
probably damaging |
Het |
| Pde6b |
C |
T |
5: 108,573,222 (GRCm39) |
R531* |
probably null |
Het |
| Polr1a |
G |
A |
6: 71,918,401 (GRCm39) |
C653Y |
possibly damaging |
Het |
| Rbm26 |
A |
G |
14: 105,389,976 (GRCm39) |
V216A |
possibly damaging |
Het |
| Rin2 |
C |
A |
2: 145,664,283 (GRCm39) |
H52Q |
possibly damaging |
Het |
| Ssc5d |
C |
T |
7: 4,946,982 (GRCm39) |
T1112I |
possibly damaging |
Het |
| Sv2c |
C |
T |
13: 96,224,989 (GRCm39) |
V107M |
probably benign |
Het |
| Tasor |
A |
G |
14: 27,193,949 (GRCm39) |
I1050V |
probably benign |
Het |
| Tulp3 |
G |
A |
6: 128,301,113 (GRCm39) |
S366L |
probably benign |
Het |
| Zfp831 |
T |
A |
2: 174,487,059 (GRCm39) |
V578E |
probably benign |
Homo |
|
| Other mutations in Mael |
| Allele | Source | Chr | Coord | Type | Predicted Effect | PPH Score |
|---|
|
IGL00907:Mael
|
APN |
1 |
166,032,418 (GRCm39) |
missense |
probably damaging |
1.00 |
|
IGL01153:Mael
|
APN |
1 |
166,029,919 (GRCm39) |
missense |
possibly damaging |
0.89 |
|
R0218:Mael
|
UTSW |
1 |
166,066,159 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R0811:Mael
|
UTSW |
1 |
166,062,968 (GRCm39) |
critical splice donor site |
probably null |
|
|
R0812:Mael
|
UTSW |
1 |
166,062,968 (GRCm39) |
critical splice donor site |
probably null |
|
|
R1544:Mael
|
UTSW |
1 |
166,029,859 (GRCm39) |
missense |
probably benign |
0.28 |
|
R2096:Mael
|
UTSW |
1 |
166,053,244 (GRCm39) |
missense |
probably benign |
0.41 |
|
R2914:Mael
|
UTSW |
1 |
166,054,179 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R3031:Mael
|
UTSW |
1 |
166,032,375 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R3709:Mael
|
UTSW |
1 |
166,066,135 (GRCm39) |
missense |
probably damaging |
0.99 |
|
R3710:Mael
|
UTSW |
1 |
166,066,135 (GRCm39) |
missense |
probably damaging |
0.99 |
|
R3880:Mael
|
UTSW |
1 |
166,064,437 (GRCm39) |
splice site |
probably benign |
|
|
R4594:Mael
|
UTSW |
1 |
166,063,056 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R4669:Mael
|
UTSW |
1 |
166,063,077 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R7382:Mael
|
UTSW |
1 |
166,029,167 (GRCm39) |
missense |
probably benign |
0.00 |
|
R8024:Mael
|
UTSW |
1 |
166,054,196 (GRCm39) |
missense |
probably damaging |
0.99 |
|
R8519:Mael
|
UTSW |
1 |
166,063,127 (GRCm39) |
critical splice acceptor site |
probably null |
|
|
R8793:Mael
|
UTSW |
1 |
166,029,257 (GRCm39) |
missense |
probably benign |
0.41 |
|
R9090:Mael
|
UTSW |
1 |
166,032,424 (GRCm39) |
missense |
probably benign |
0.01 |
|
R9147:Mael
|
UTSW |
1 |
166,029,259 (GRCm39) |
missense |
probably benign |
0.08 |
|
R9148:Mael
|
UTSW |
1 |
166,029,259 (GRCm39) |
missense |
probably benign |
0.08 |
|
R9271:Mael
|
UTSW |
1 |
166,032,424 (GRCm39) |
missense |
probably benign |
0.01 |
|
R9382:Mael
|
UTSW |
1 |
166,053,282 (GRCm39) |
missense |
probably damaging |
0.97 |
|
X0018:Mael
|
UTSW |
1 |
166,029,137 (GRCm39) |
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 On |
2010-08-09 |
Incidental Mutation