Incidental Mutation 'N/A:Mtrr'
| ID |
37 |
| Institutional Source |
Beutler Lab
|
| Gene Symbol |
Mtrr
|
| Ensembl Gene |
ENSMUSG00000034617 |
| Gene Name |
5-methyltetrahydrofolate-homocysteine methyltransferase reductase |
| Synonyms |
|
| Accession Numbers |
|
| Essential gene? |
Non essential
(E-score: 0.000)
|
| Stock # |
N/A
of strain
294
|
| Quality Score |
|
|
Status
|
Validated
|
| Chromosome |
13 |
| Chromosomal Location |
68708899-68730268 bp(-) (GRCm39) |
| Type of Mutation |
splice site |
| DNA Base Change (assembly) |
C to A
at 68723516 bp (GRCm39)
|
| Zygosity |
Homozygous |
| Amino Acid Change |
|
| Ref Sequence |
ENSEMBL: ENSMUSP00000152387
(fasta)
|
| Gene Model |
predicted gene model for transcript(s):
[ENSMUST00000045827]
[ENSMUST00000220973]
[ENSMUST00000221259]
[ENSMUST00000222107]
[ENSMUST00000223101]
[ENSMUST00000223398]
|
| AlphaFold |
no structure available at present |
| Predicted Effect |
probably benign
Transcript: ENSMUST00000045827
|
| SMART Domains |
Protein: ENSMUSP00000039810
Gene: ENSMUSG00000034617
| Domain | Start | End | E-Value | Type |
|---|
|
Pfam:Flavodoxin_5
|
5 |
126 |
2.7e-9 |
PFAM |
|
Pfam:Flavodoxin_1
|
6 |
142 |
4.3e-32 |
PFAM |
|
Pfam:FAD_binding_1
|
267 |
490 |
2.6e-51 |
PFAM |
|
Pfam:NAD_binding_1
|
540 |
660 |
5.4e-21 |
PFAM |
|
| Predicted Effect |
probably benign
Transcript: ENSMUST00000220973
|
| Predicted Effect |
probably benign
Transcript: ENSMUST00000221259
|
| Predicted Effect |
noncoding transcript
Transcript: ENSMUST00000221800
|
| Predicted Effect |
probably benign
Transcript: ENSMUST00000222107
|
| Predicted Effect |
noncoding transcript
Transcript: ENSMUST00000223055
|
| Predicted Effect |
probably benign
Transcript: ENSMUST00000223101
|
| Predicted Effect |
probably benign
Transcript: ENSMUST00000223398
|
| Coding Region Coverage |
|
| Validation Efficiency |
91% (106/116) |
| MGI Phenotype |
FUNCTION: Methionine is an essential amino acid required for protein synthesis and one-carbon metabolism. Its synthesis is catalyzed by the enzyme methionine synthase. Methionine synthase eventually becomes inactive due to the oxidation of its cob(I)alamin cofactor. The protein encoded by this gene regenerates a functional methionine synthase via reductive methylation. It is a member of the ferredoxin-NADP(+) reductase (FNR) family of electron transferases. Mutations in a similar gene in human have been associated with cblE complementation type homocystinuria-megaloblastic anemia and susceptibility to folate-sensitive neural tube defects. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, May 2015]
PHENOTYPE: Mice homozygous for a hypomorphic gene trap allele are viable and display a male-specific reduction in postnatal weight gain as well as hyperhomocysteinemia, hypomethionemia, increased tissue methyltetrahydrofolate, and AdoMet/AdoHcy ratios that range from high to slightly below normal. [provided by MGI curators]
|
| Allele List at MGI |
All alleles(46) : Gene trapped(46) |
| Other mutations in this stock |
Total: 18 list
| Gene | Ref | Var | Chr/Loc | Mutation | Predicted Effect | Zygosity |
|---|
| 1700016P04Rik |
T |
A |
6: 13,415,772 (GRCm39) |
|
noncoding transcript |
Homo |
| Aif1 |
A |
G |
17: 35,391,496 (GRCm39) |
L7S |
possibly damaging |
Homo |
| Ankrd26 |
T |
C |
6: 118,506,535 (GRCm39) |
D646G |
probably benign |
Homo |
| Cacna1s |
A |
G |
1: 136,001,247 (GRCm39) |
I233V |
probably benign |
Homo |
| Cfap92 |
A |
T |
6: 87,667,773 (GRCm39) |
|
noncoding transcript |
Homo |
| Chchd4 |
T |
C |
6: 91,442,187 (GRCm39) |
Y77C |
probably damaging |
Homo |
| Crocc |
G |
A |
4: 140,749,057 (GRCm39) |
R1419C |
probably damaging |
Homo |
| Cyp4f39 |
A |
C |
17: 32,687,655 (GRCm39) |
M74L |
probably benign |
Homo |
| Fgf9 |
C |
A |
14: 58,327,421 (GRCm39) |
|
probably benign |
Homo |
| Gimap6 |
T |
C |
6: 48,679,349 (GRCm39) |
D229G |
probably damaging |
Homo |
| Glp1r |
T |
C |
17: 31,150,257 (GRCm39) |
F393S |
probably damaging |
Homo |
| Lrrc7 |
T |
G |
3: 157,865,977 (GRCm39) |
I1255L |
probably benign |
Homo |
| Pde6b |
A |
T |
5: 108,576,969 (GRCm39) |
|
probably benign |
Homo |
| Rbm19 |
A |
T |
5: 120,282,162 (GRCm39) |
I840F |
probably damaging |
Homo |
| Serpina3c |
A |
C |
12: 104,115,864 (GRCm39) |
S227A |
probably benign |
Homo |
| Spag17 |
G |
A |
3: 99,889,570 (GRCm39) |
|
probably benign |
Homo |
| Spmip3 |
G |
A |
1: 177,561,100 (GRCm39) |
R13H |
probably damaging |
Homo |
| Zbtb8b |
T |
C |
4: 129,326,361 (GRCm39) |
D268G |
probably benign |
Homo |
|
| Other mutations in Mtrr |
| Allele | Source | Chr | Coord | Type | Predicted Effect | PPH Score |
|---|
|
IGL01787:Mtrr
|
APN |
13 |
68,719,266 (GRCm39) |
missense |
probably damaging |
1.00 |
|
IGL01806:Mtrr
|
APN |
13 |
68,728,719 (GRCm39) |
missense |
possibly damaging |
0.92 |
|
IGL01808:Mtrr
|
APN |
13 |
68,714,212 (GRCm39) |
missense |
probably benign |
0.00 |
|
IGL01875:Mtrr
|
APN |
13 |
68,720,728 (GRCm39) |
missense |
probably damaging |
1.00 |
|
IGL02137:Mtrr
|
APN |
13 |
68,716,920 (GRCm39) |
missense |
possibly damaging |
0.75 |
|
IGL02186:Mtrr
|
APN |
13 |
68,712,476 (GRCm39) |
missense |
probably benign |
|
|
IGL03114:Mtrr
|
APN |
13 |
68,712,441 (GRCm39) |
nonsense |
probably null |
|
|
3-1:Mtrr
|
UTSW |
13 |
68,723,135 (GRCm39) |
critical splice donor site |
probably null |
|
|
H8562:Mtrr
|
UTSW |
13 |
68,712,496 (GRCm39) |
missense |
probably damaging |
0.97 |
|
R0007:Mtrr
|
UTSW |
13 |
68,723,449 (GRCm39) |
missense |
probably benign |
0.02 |
|
R0741:Mtrr
|
UTSW |
13 |
68,727,658 (GRCm39) |
splice site |
probably null |
|
|
R2140:Mtrr
|
UTSW |
13 |
68,717,059 (GRCm39) |
missense |
possibly damaging |
0.47 |
|
R2513:Mtrr
|
UTSW |
13 |
68,715,092 (GRCm39) |
nonsense |
probably null |
|
|
R4604:Mtrr
|
UTSW |
13 |
68,712,631 (GRCm39) |
splice site |
probably null |
|
|
R5501:Mtrr
|
UTSW |
13 |
68,727,766 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R5658:Mtrr
|
UTSW |
13 |
68,717,034 (GRCm39) |
missense |
possibly damaging |
0.67 |
|
R6477:Mtrr
|
UTSW |
13 |
68,718,192 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R6694:Mtrr
|
UTSW |
13 |
68,712,452 (GRCm39) |
missense |
probably benign |
|
|
R6979:Mtrr
|
UTSW |
13 |
68,718,122 (GRCm39) |
critical splice donor site |
probably null |
|
|
R7094:Mtrr
|
UTSW |
13 |
68,727,803 (GRCm39) |
missense |
possibly damaging |
0.83 |
|
R7296:Mtrr
|
UTSW |
13 |
68,716,979 (GRCm39) |
nonsense |
probably null |
|
|
R7354:Mtrr
|
UTSW |
13 |
68,714,326 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R7378:Mtrr
|
UTSW |
13 |
68,712,521 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R7546:Mtrr
|
UTSW |
13 |
68,730,268 (GRCm39) |
unclassified |
probably benign |
|
|
R7562:Mtrr
|
UTSW |
13 |
68,714,336 (GRCm39) |
missense |
probably damaging |
0.96 |
|
R7759:Mtrr
|
UTSW |
13 |
68,718,146 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R7975:Mtrr
|
UTSW |
13 |
68,727,666 (GRCm39) |
splice site |
probably null |
|
|
R8101:Mtrr
|
UTSW |
13 |
68,725,740 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R8168:Mtrr
|
UTSW |
13 |
68,720,732 (GRCm39) |
missense |
probably benign |
0.00 |
|
R9097:Mtrr
|
UTSW |
13 |
68,723,441 (GRCm39) |
missense |
probably benign |
0.28 |
|
R9260:Mtrr
|
UTSW |
13 |
68,728,674 (GRCm39) |
missense |
possibly damaging |
0.70 |
|
R9295:Mtrr
|
UTSW |
13 |
68,719,258 (GRCm39) |
missense |
possibly damaging |
0.94 |
|
R9516:Mtrr
|
UTSW |
13 |
68,720,755 (GRCm39) |
missense |
probably benign |
0.00 |
|
R9517:Mtrr
|
UTSW |
13 |
68,728,730 (GRCm39) |
missense |
probably benign |
0.06 |
|
R9627:Mtrr
|
UTSW |
13 |
68,725,756 (GRCm39) |
missense |
probably damaging |
1.00 |
|
| Nature of Mutation |
 DNA sequencing using the SOLiD technique identified a G to T transversion at position 68714274 in the Genbank genomic region NC_000079 for the Mtrr gene on chromosome 13 (TCCGTACCAG ->TCCTTACCAG). The mutation is located within intron 4, seven nucleotides upstream from the start of exon 5, and may impair the acceptor splice site of intron 4. Mtrr contains 15 exons. The mutation has been confirmed by DNA sequencing using the Sanger method (Figure 1).
|
| Protein Function and Prediction |
Mtrr encodes the 696 amino acid methionine synthase reductase or MTRR. This enzyme belongs to the family of oxidoreductases that oxidize metal ions using nicotinamide adenine dinucleotide (NAD+) or nicotinamide adenine dinucleotide phosphate (NADP+) as an acceptor. MTRR uses flavoproteins (flavin adenine nucleotide or flavin mononucleotide) as cofactors. MTRR catalyzes reductive methylation of methionine synthase (MTR), the enzyme necessary for remethylation of methionine, thus enabling MTR activity. S-adenosylmethionine (SAM) is used as a methyl donor in this reaction. MTRR contains an N-terminal flavodoxin domain, followed by a flavin adenine nucleotide (FAD) binding domain, and an NAD+ binding domain. Mutations in the human MTRR gene cause megaloblastic anemia, developmental delay, hyperhomocysteinemia, and hypomethioninemia (OMIM #236270).
|
| Posted On |
2009-11-11 |
Incidental Mutation