Incidental Mutation 'P0016:Mbd1'
| ID |
7569 |
| Institutional Source |
Beutler Lab
|
| Gene Symbol |
Mbd1
|
| Ensembl Gene |
ENSMUSG00000024561 |
| Gene Name |
methyl-CpG binding domain protein 1 |
| Synonyms |
PCM1, Cxxc3 |
| MMRRC Submission |
038269-MU
|
| Accession Numbers |
|
| Essential gene? |
Non essential
(E-score: 0.000)
|
| Stock # |
P0016 (G1)
|
| Quality Score |
|
|
Status
|
Validated
|
| Chromosome |
18 |
| Chromosomal Location |
74400676-74415803 bp(+) (GRCm39) |
| Type of Mutation |
nonsense |
| DNA Base Change (assembly) |
C to T
at 74407609 bp (GRCm39)
|
| Zygosity |
Heterozygous |
| Amino Acid Change |
Arginine to Stop codon
at position 130
(R130*)
|
| Ref Sequence |
ENSEMBL: ENSMUSP00000153085
(fasta)
|
| Gene Model |
predicted gene model for transcript(s):
[ENSMUST00000097530]
[ENSMUST00000224047]
[ENSMUST00000224332]
|
| AlphaFold |
no structure available at present |
| Predicted Effect |
probably null
Transcript: ENSMUST00000097530
AA Change: R240*
|
| SMART Domains |
Protein: ENSMUSP00000095137
Gene: ENSMUSG00000024561
AA Change: R240*
| Domain | Start | End | E-Value | Type |
|---|
|
MBD
|
3 |
76 |
3.94e-27 |
SMART |
|
low complexity region
|
82 |
97 |
N/A |
INTRINSIC |
|
low complexity region
|
123 |
153 |
N/A |
INTRINSIC |
|
Pfam:zf-CXXC
|
194 |
241 |
1.9e-13 |
PFAM |
|
Pfam:zf-CXXC
|
243 |
288 |
1.2e-13 |
PFAM |
|
low complexity region
|
358 |
368 |
N/A |
INTRINSIC |
|
low complexity region
|
513 |
527 |
N/A |
INTRINSIC |
|
| Predicted Effect |
probably null
Transcript: ENSMUST00000224047
AA Change: R240*
|
| Predicted Effect |
noncoding transcript
Transcript: ENSMUST00000224159
|
| Predicted Effect |
probably null
Transcript: ENSMUST00000224332
AA Change: R130*
|
| Predicted Effect |
noncoding transcript
Transcript: ENSMUST00000224907
|
| Meta Mutation Damage Score |
0.9755 |
| Coding Region Coverage |
- 1x: 85.6%
- 3x: 81.0%
- 10x: 66.8%
- 20x: 50.1%
|
| Validation Efficiency |
96% (97/101) |
| 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 a family of nuclear proteins related by the presence of a methyl-CpG binding domain (MBD). These proteins are capable of binding specifically to methylated DNA, and some members can also repress transcription from methylated gene promoters. This protein contains multiple domains: MBD at the N-terminus that functions both in binding to methylated DNA and in protein interactions; several CXXC-type zinc finger domains that mediate binding to non-methylated CpG dinucleotides; transcriptional repression domain (TRD) at the C-terminus that is involved in transcription repression and in protein interactions. Numerous alternatively spliced transcript variants encoding different isoforms have been noted for this gene.[provided by RefSeq, Feb 2011]
PHENOTYPE: Homozygous null exhibited defects in adult hippocampal neurogenesis and function. Spatial learning was also impaired in mutant mice. [provided by MGI curators]
|
| Allele List at MGI |
All alleles(3) : Targeted(2) Gene trapped(1)
|
| Other mutations in this stock |
Total: 18 list
| Gene | Ref | Var | Chr/Loc | Mutation | Predicted Effect | Zygosity |
|---|
| 1700123K08Rik |
A |
T |
5: 138,561,200 (GRCm39) |
L154* |
probably null |
Het |
| 4930432E11Rik |
T |
C |
7: 29,262,537 (GRCm39) |
|
noncoding transcript |
Het |
| Arap3 |
T |
A |
18: 38,117,401 (GRCm39) |
T892S |
probably benign |
Het |
| Ctnnd2 |
G |
A |
15: 30,967,084 (GRCm39) |
V987I |
probably benign |
Het |
| Dennd6b |
T |
C |
15: 89,071,180 (GRCm39) |
I351V |
probably benign |
Het |
| Kif27 |
G |
A |
13: 58,451,266 (GRCm39) |
Q1021* |
probably null |
Het |
| Klb |
G |
A |
5: 65,537,266 (GRCm39) |
W865* |
probably null |
Het |
| Mroh7 |
T |
A |
4: 106,565,054 (GRCm39) |
|
probably null |
Het |
| Myo16 |
C |
T |
8: 10,450,596 (GRCm39) |
|
probably benign |
Het |
| Rbm22 |
T |
A |
18: 60,703,842 (GRCm39) |
|
probably benign |
Het |
| Rnaseh2a |
C |
G |
8: 85,686,429 (GRCm39) |
D206H |
probably damaging |
Het |
| Slain1 |
A |
G |
14: 103,923,110 (GRCm39) |
T187A |
probably benign |
Het |
| Slamf6 |
A |
G |
1: 171,764,068 (GRCm39) |
T154A |
probably damaging |
Het |
| Traip |
A |
G |
9: 107,845,855 (GRCm39) |
D316G |
possibly damaging |
Het |
| Ttn |
T |
C |
2: 76,641,527 (GRCm39) |
D5196G |
probably damaging |
Het |
| Ubr5 |
C |
T |
15: 38,000,822 (GRCm39) |
V1569M |
probably damaging |
Het |
| Zfp750 |
T |
A |
11: 121,404,804 (GRCm39) |
K24* |
probably null |
Het |
| Zfp799 |
T |
C |
17: 33,038,331 (GRCm39) |
E645G |
possibly damaging |
Het |
|
| Other mutations in Mbd1 |
| Allele | Source | Chr | Coord | Type | Predicted Effect | PPH Score |
|---|
|
IGL00902:Mbd1
|
APN |
18 |
74,408,310 (GRCm39) |
missense |
possibly damaging |
0.72 |
|
IGL01551:Mbd1
|
APN |
18 |
74,402,614 (GRCm39) |
unclassified |
probably benign |
|
|
IGL02213:Mbd1
|
APN |
18 |
74,408,453 (GRCm39) |
missense |
probably damaging |
1.00 |
|
IGL02562:Mbd1
|
APN |
18 |
74,409,993 (GRCm39) |
missense |
probably benign |
0.00 |
|
IGL02596:Mbd1
|
APN |
18 |
74,409,868 (GRCm39) |
splice site |
probably benign |
|
|
IGL02944:Mbd1
|
APN |
18 |
74,410,481 (GRCm39) |
missense |
probably damaging |
1.00 |
|
IGL02973:Mbd1
|
APN |
18 |
74,408,498 (GRCm39) |
splice site |
probably benign |
|
|
IGL03200:Mbd1
|
APN |
18 |
74,409,502 (GRCm39) |
missense |
probably benign |
0.02 |
|
IGL03247:Mbd1
|
APN |
18 |
74,407,825 (GRCm39) |
nonsense |
probably null |
|
|
IGL03340:Mbd1
|
APN |
18 |
74,407,553 (GRCm39) |
missense |
probably benign |
0.00 |
|
Shortbread
|
UTSW |
18 |
74,407,128 (GRCm39) |
critical splice donor site |
probably null |
|
|
FR4737:Mbd1
|
UTSW |
18 |
74,406,644 (GRCm39) |
small deletion |
probably benign |
|
|
R0385:Mbd1
|
UTSW |
18 |
74,406,312 (GRCm39) |
frame shift |
probably null |
|
|
R0630:Mbd1
|
UTSW |
18 |
74,409,798 (GRCm39) |
splice site |
probably benign |
|
|
R0717:Mbd1
|
UTSW |
18 |
74,406,668 (GRCm39) |
missense |
possibly damaging |
0.89 |
|
R1084:Mbd1
|
UTSW |
18 |
74,402,603 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R1290:Mbd1
|
UTSW |
18 |
74,402,557 (GRCm39) |
missense |
possibly damaging |
0.59 |
|
R1575:Mbd1
|
UTSW |
18 |
74,408,490 (GRCm39) |
critical splice donor site |
probably null |
|
|
R2065:Mbd1
|
UTSW |
18 |
74,409,955 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R2192:Mbd1
|
UTSW |
18 |
74,410,449 (GRCm39) |
missense |
probably damaging |
0.99 |
|
R2308:Mbd1
|
UTSW |
18 |
74,409,548 (GRCm39) |
missense |
probably benign |
0.42 |
|
R2697:Mbd1
|
UTSW |
18 |
74,406,688 (GRCm39) |
missense |
possibly damaging |
0.95 |
|
R3407:Mbd1
|
UTSW |
18 |
74,410,438 (GRCm39) |
missense |
possibly damaging |
0.94 |
|
R4348:Mbd1
|
UTSW |
18 |
74,407,487 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R4664:Mbd1
|
UTSW |
18 |
74,402,597 (GRCm39) |
missense |
possibly damaging |
0.86 |
|
R5460:Mbd1
|
UTSW |
18 |
74,402,581 (GRCm39) |
missense |
probably benign |
0.03 |
|
R5860:Mbd1
|
UTSW |
18 |
74,409,768 (GRCm39) |
nonsense |
probably null |
|
|
R6431:Mbd1
|
UTSW |
18 |
74,406,762 (GRCm39) |
splice site |
probably null |
|
|
R6734:Mbd1
|
UTSW |
18 |
74,409,114 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R6861:Mbd1
|
UTSW |
18 |
74,406,645 (GRCm39) |
|
|
|
|
R7363:Mbd1
|
UTSW |
18 |
74,406,357 (GRCm39) |
missense |
probably damaging |
0.97 |
|
R7543:Mbd1
|
UTSW |
18 |
74,407,520 (GRCm39) |
missense |
probably damaging |
0.97 |
|
R7657:Mbd1
|
UTSW |
18 |
74,407,804 (GRCm39) |
missense |
probably damaging |
0.99 |
|
R7871:Mbd1
|
UTSW |
18 |
74,407,128 (GRCm39) |
critical splice donor site |
probably null |
|
|
R8960:Mbd1
|
UTSW |
18 |
74,406,890 (GRCm39) |
critical splice donor site |
probably null |
|
|
R9161:Mbd1
|
UTSW |
18 |
74,407,792 (GRCm39) |
missense |
probably benign |
0.01 |
|
R9774:Mbd1
|
UTSW |
18 |
74,408,274 (GRCm39) |
missense |
probably benign |
|
|
RF005:Mbd1
|
UTSW |
18 |
74,406,644 (GRCm39) |
small deletion |
probably benign |
|
|
RF011:Mbd1
|
UTSW |
18 |
74,406,681 (GRCm39) |
small deletion |
probably benign |
|
|
RF024:Mbd1
|
UTSW |
18 |
74,406,681 (GRCm39) |
small deletion |
probably benign |
|
|
RF024:Mbd1
|
UTSW |
18 |
74,406,644 (GRCm39) |
small deletion |
probably benign |
|
|
RF058:Mbd1
|
UTSW |
18 |
74,406,680 (GRCm39) |
frame shift |
probably null |
|
|
Z1177:Mbd1
|
UTSW |
18 |
74,410,010 (GRCm39) |
missense |
probably null |
0.72 |
|
| Protein Function and Prediction |
Mbd1 is a factor in DNA methylation-mediated epigenetic gene regulation (1;2). Mbd1 expression is important in brain development and cognitive functions (1). Mbd proteins bind to methyl-CpG pairs to repress transcription (2).
|
| Expression/Localization |
Mbd1 is expressed in both neural progenitors and neurons (3).
|
| Background |
Mbd1tm1Fhg/tm1Fhg; MGI:2664084
129S4/SvJae-Mbd1tm1Fhg
Homozygous null animals exhibit abnormal neuron differentiation, reductions in hippocampal neurogenesis, decreased brain weight, and reduced hippocampal function (3). Adult homozygotes are healthy and display no significant deficits in motor coordination or locomotor activity, although spatial learning is impaired (3). Homozygous animals also have aneuploidy, chromosomal instability, and chromosomal breakage; no chromosomal translocation was detected (3).
Mbd1tm1Fhg/tm1Fhg; MGI:2664084
129S4 x C57BL/6
Homozygous mice exhibit no gross abnormality and have nearly normal lifespan (1). However, they exhibit several core deficits frequently associated with autism, including reduced social interaction, learning deficits, anxiety, defective sensory motor gating, depression and abnormal brain serotonin activity (1).
|
| References |
1. Allan, A. M., Liang, X., Luo, Y., Pak, C., Li, X., Szulwach, K. E., Chen, D., Jin, P., and Zhao, X. (2008) The Loss of Methyl-CpG Binding Protein 1 Leads to Autism-Like Behavioral Deficits. Hum Mol Genet. 17, 2047-2057.
2. Nakao, M., Matsui, S., Yamamoto, S., Okumura, K., Shirakawa, M., and Fujita, N. (2001) Regulation of Transcription and Chromatin by Methyl-CpG Binding Protein MBD1. Brain Dev. 23 Suppl 1, S174-6.
3. Zhao, X., Ueba, T., Christie, B. R., Barkho, B., McConnell, M. J., Nakashima, K., Lein, E. S., Eadie, B. D., Willhoite, A. R., Muotri, A. R., Summers, R. G., Chun, J., Lee, K. F., and Gage, F. H. (2003) Mice Lacking Methyl-CpG Binding Protein 1 have Deficits in Adult Neurogenesis and Hippocampal Function. Proc Natl Acad Sci U S A. 100, 6777-6782. |
| Posted On |
2012-10-05 |
| Science Writer |
Anne Murray |
Incidental Mutation