Incidental Mutation 'R0054:Brms1'
| ID |
16248 |
| Institutional Source |
Beutler Lab
|
| Gene Symbol |
Brms1
|
| Ensembl Gene |
ENSMUSG00000080268 |
| Gene Name |
breast cancer metastasis-suppressor 1 |
| Synonyms |
|
| MMRRC Submission |
038348-MU
|
| Accession Numbers |
|
| Essential gene? |
Probably essential
(E-score: 0.818)
|
| Stock # |
R0054 (G1)
|
| Quality Score |
|
|
Status
|
Validated
|
| Chromosome |
19 |
| Chromosomal Location |
5091391-5099940 bp(+) (GRCm39) |
| Type of Mutation |
nonsense |
| DNA Base Change (assembly) |
T to A
at 5096727 bp (GRCm39)
|
| Zygosity |
Heterozygous |
| Amino Acid Change |
Cysteine to Stop codon
at position 136
(C136*)
|
| Ref Sequence |
ENSEMBL: ENSMUSP00000112266
(fasta)
|
| Gene Model |
predicted gene model for transcript(s):
[ENSMUST00000025818]
[ENSMUST00000116567]
[ENSMUST00000224178]
[ENSMUST00000224288]
[ENSMUST00000224363]
[ENSMUST00000225799]
[ENSMUST00000225427]
|
| AlphaFold |
Q99N20 |
| Predicted Effect |
probably benign
Transcript: ENSMUST00000025818
|
| SMART Domains |
Protein: ENSMUSP00000025818
Gene: ENSMUSG00000024883
| Domain | Start | End | E-Value | Type |
|---|
|
SH2
|
66 |
153 |
2.16e-5 |
SMART |
|
low complexity region
|
241 |
264 |
N/A |
INTRINSIC |
|
low complexity region
|
286 |
300 |
N/A |
INTRINSIC |
|
low complexity region
|
307 |
341 |
N/A |
INTRINSIC |
|
low complexity region
|
405 |
422 |
N/A |
INTRINSIC |
|
low complexity region
|
432 |
454 |
N/A |
INTRINSIC |
|
VPS9
|
478 |
596 |
2.29e-64 |
SMART |
|
RA
|
613 |
694 |
1.14e-12 |
SMART |
|
| Predicted Effect |
probably null
Transcript: ENSMUST00000116567
AA Change: C136*
|
| SMART Domains |
Protein: ENSMUSP00000112266
Gene: ENSMUSG00000080268
AA Change: C136*
| Domain | Start | End | E-Value | Type |
|---|
|
low complexity region
|
29 |
59 |
N/A |
INTRINSIC |
|
Pfam:Sds3
|
60 |
209 |
5.3e-23 |
PFAM |
|
| Predicted Effect |
probably benign
Transcript: ENSMUST00000224178
|
| Predicted Effect |
noncoding transcript
Transcript: ENSMUST00000224254
|
| Predicted Effect |
probably benign
Transcript: ENSMUST00000224288
|
| Predicted Effect |
probably benign
Transcript: ENSMUST00000224363
|
| Predicted Effect |
noncoding transcript
Transcript: ENSMUST00000225203
|
| Predicted Effect |
probably benign
Transcript: ENSMUST00000225799
|
| Predicted Effect |
probably benign
Transcript: ENSMUST00000225427
|
| Meta Mutation Damage Score |
0.9755 |
| Coding Region Coverage |
- 1x: 88.8%
- 3x: 85.6%
- 10x: 76.3%
- 20x: 59.9%
|
| Validation Efficiency |
96% (91/95) |
| MGI Phenotype |
FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene reduces the metastatic potential, but not the tumorogenicity, of human breast cancer and melanoma cell lines. The protein encoded by this gene localizes primarily to the nucleus and is a component of the mSin3a family of histone deacetylase complexes (HDAC). The protein contains two coiled-coil motifs and several imperfect leucine zipper motifs. Alternative splicing results in two transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]
|
| Allele List at MGI |
All alleles(12) : Targeted(2) Gene trapped(10)
|
| Other mutations in this stock |
Total: 57 list
| Gene | Ref | Var | Chr/Loc | Mutation | Predicted Effect | Zygosity |
|---|
| Abcc9 |
A |
G |
6: 142,547,500 (GRCm39) |
|
probably null |
Het |
| Apoa4 |
A |
G |
9: 46,153,822 (GRCm39) |
D141G |
probably benign |
Het |
| Atg9a |
T |
C |
1: 75,161,143 (GRCm39) |
Y701C |
probably damaging |
Het |
| Baz2b |
C |
T |
2: 59,762,510 (GRCm39) |
R922Q |
probably damaging |
Het |
| Bmal2 |
T |
G |
6: 146,731,216 (GRCm39) |
V507G |
probably benign |
Het |
| Ccdc180 |
T |
A |
4: 45,890,900 (GRCm39) |
V24E |
probably benign |
Het |
| Clec4f |
C |
T |
6: 83,629,911 (GRCm39) |
V216M |
probably benign |
Het |
| Cpd |
C |
G |
11: 76,681,664 (GRCm39) |
G1160R |
probably damaging |
Het |
| Creb5 |
A |
G |
6: 53,424,642 (GRCm39) |
M128V |
probably benign |
Het |
| Ddb2 |
G |
T |
2: 91,065,165 (GRCm39) |
Q87K |
probably benign |
Het |
| Defb41 |
A |
G |
1: 18,321,471 (GRCm39) |
Y48H |
probably damaging |
Het |
| Dido1 |
T |
C |
2: 180,303,267 (GRCm39) |
N1546D |
probably benign |
Het |
| Dmac1 |
A |
G |
4: 75,196,337 (GRCm39) |
V51A |
possibly damaging |
Het |
| Dnajb11 |
C |
T |
16: 22,681,369 (GRCm39) |
A49V |
probably damaging |
Het |
| Dnajc14 |
G |
A |
10: 128,643,448 (GRCm39) |
D457N |
probably damaging |
Het |
| Eif3a |
C |
A |
19: 60,755,264 (GRCm39) |
D973Y |
unknown |
Het |
| Farsb |
T |
A |
1: 78,439,011 (GRCm39) |
K395* |
probably null |
Het |
| Fem1b |
A |
G |
9: 62,704,082 (GRCm39) |
S393P |
probably damaging |
Het |
| Fsip2 |
A |
C |
2: 82,817,299 (GRCm39) |
N4344T |
possibly damaging |
Het |
| Gphn |
A |
G |
12: 78,684,277 (GRCm39) |
S558G |
probably damaging |
Het |
| Gpr142 |
C |
A |
11: 114,689,755 (GRCm39) |
H2Q |
probably benign |
Het |
| Grhpr |
T |
C |
4: 44,988,915 (GRCm39) |
|
probably benign |
Het |
| Grik3 |
C |
A |
4: 125,517,368 (GRCm39) |
N70K |
probably damaging |
Het |
| Gsap |
T |
A |
5: 21,455,933 (GRCm39) |
|
probably benign |
Het |
| Iars1 |
T |
A |
13: 49,846,611 (GRCm39) |
C237S |
probably damaging |
Het |
| Ighv1-9 |
A |
T |
12: 114,547,602 (GRCm39) |
F7L |
probably benign |
Het |
| Ints8 |
A |
G |
4: 11,204,595 (GRCm39) |
|
probably benign |
Het |
| Kcnj16 |
G |
T |
11: 110,915,549 (GRCm39) |
W70C |
probably damaging |
Het |
| Kpna6 |
T |
C |
4: 129,551,251 (GRCm39) |
M85V |
probably benign |
Het |
| Kri1 |
G |
A |
9: 21,186,661 (GRCm39) |
S447L |
probably damaging |
Het |
| Lrp1b |
A |
G |
2: 40,632,829 (GRCm39) |
V3528A |
probably benign |
Het |
| Lrrc46 |
A |
T |
11: 96,929,605 (GRCm39) |
L77Q |
probably damaging |
Het |
| Mrpl44 |
T |
C |
1: 79,757,212 (GRCm39) |
L219S |
probably damaging |
Het |
| Ms4a14 |
T |
C |
19: 11,281,303 (GRCm39) |
I418M |
probably benign |
Het |
| Myo7a |
T |
C |
7: 97,714,905 (GRCm39) |
D112G |
probably damaging |
Het |
| Ncoa3 |
A |
G |
2: 165,897,098 (GRCm39) |
T630A |
possibly damaging |
Het |
| Nsl1 |
T |
C |
1: 190,814,381 (GRCm39) |
L194P |
probably damaging |
Het |
| Or5ac23 |
T |
C |
16: 59,149,428 (GRCm39) |
Y148C |
possibly damaging |
Het |
| Or8u10 |
T |
C |
2: 85,915,705 (GRCm39) |
K139E |
probably benign |
Het |
| Pde4d |
A |
G |
13: 109,876,955 (GRCm39) |
S159G |
probably benign |
Het |
| Pi4ka |
T |
C |
16: 17,142,978 (GRCm39) |
R845G |
probably null |
Het |
| Pld1 |
A |
G |
3: 28,150,033 (GRCm39) |
|
probably benign |
Het |
| Psd |
T |
A |
19: 46,311,781 (GRCm39) |
I300F |
probably damaging |
Het |
| Ptprz1 |
T |
A |
6: 22,986,195 (GRCm39) |
W332R |
probably damaging |
Het |
| Rnf212 |
T |
A |
5: 108,893,530 (GRCm39) |
M70L |
possibly damaging |
Het |
| Sema4f |
A |
G |
6: 82,896,674 (GRCm39) |
|
probably benign |
Het |
| Sez6 |
C |
A |
11: 77,844,699 (GRCm39) |
T7K |
possibly damaging |
Het |
| Skint2 |
T |
C |
4: 112,502,660 (GRCm39) |
I290T |
probably benign |
Het |
| Slc5a3 |
T |
A |
16: 91,874,522 (GRCm39) |
I193N |
probably damaging |
Het |
| Snip1 |
T |
A |
4: 124,966,633 (GRCm39) |
Y354* |
probably null |
Het |
| Tmco5 |
A |
G |
2: 116,717,768 (GRCm39) |
Y200C |
probably damaging |
Het |
| Tmem87b |
T |
A |
2: 128,673,361 (GRCm39) |
|
probably benign |
Het |
| Trim60 |
T |
C |
8: 65,453,973 (GRCm39) |
E92G |
probably benign |
Het |
| Ttn |
A |
T |
2: 76,626,804 (GRCm39) |
D13067E |
possibly damaging |
Het |
| Ufl1 |
A |
T |
4: 25,269,087 (GRCm39) |
I168N |
probably damaging |
Het |
| Zfp385c |
G |
A |
11: 100,520,782 (GRCm39) |
P293S |
probably benign |
Het |
| Zfp473 |
T |
A |
7: 44,383,899 (GRCm39) |
S144C |
probably damaging |
Het |
|
| Other mutations in Brms1 |
| Allele | Source | Chr | Coord | Type | Predicted Effect | PPH Score |
|---|
|
IGL00485:Brms1
|
APN |
19 |
5,099,070 (GRCm39) |
unclassified |
probably benign |
|
|
IGL01391:Brms1
|
APN |
19 |
5,096,723 (GRCm39) |
missense |
possibly damaging |
0.79 |
|
IGL02583:Brms1
|
APN |
19 |
5,096,206 (GRCm39) |
missense |
probably damaging |
0.99 |
|
PIT4576001:Brms1
|
UTSW |
19 |
5,096,229 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R0054:Brms1
|
UTSW |
19 |
5,096,727 (GRCm39) |
nonsense |
probably null |
|
|
R0670:Brms1
|
UTSW |
19 |
5,095,999 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R1757:Brms1
|
UTSW |
19 |
5,096,435 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R1962:Brms1
|
UTSW |
19 |
5,096,027 (GRCm39) |
missense |
probably damaging |
0.97 |
|
R6963:Brms1
|
UTSW |
19 |
5,096,681 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R7096:Brms1
|
UTSW |
19 |
5,096,708 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R8241:Brms1
|
UTSW |
19 |
5,096,007 (GRCm39) |
missense |
probably benign |
0.00 |
|
R8444:Brms1
|
UTSW |
19 |
5,091,520 (GRCm39) |
critical splice donor site |
probably null |
|
|
| Protein Function and Prediction |
Brms1 encodes BRMS1, a breast carcinoma metastasis suppressor gene that functions to suppress the spread of a primary tumor to a discontinuous site (1). BRMS1 domains include a glutamine-rich domain at the N-terminus, followed by two coiled-coil domains, and two C-terminal nuclear localization signals (2). Studies on the murine homolog of BRMS1 determined that it can suppress the metastatic capability of primary tumors, similar to the human protein (3). Further studies determined that one of the mechansims of BRMS1-dependent suppression of tumor metastasis involves inhibition of NF-κB activity and subsequent suppression of uPA expression in cancer cells (4).
|
| Expression/Localization |
Northern blot analysis determined that BRMS1 is ubiquitously expressed (5). Mouse Brms1 is highly expressed in testis, liver, kidney and heart; spleen and lungs showed moderate expression; and skeletal muscles showed minimal expression (3).
|
| References |
2. Hurst, D. R., Xie, Y., Vaidya, K. S., Mehta, A., Moore, B. P., Accavitti-Loper, M. A., Samant, R. S., Saxena, R., Silveira, A. C., and Welch, D. R. (2008) Alterations of BRMS1-ARID4A Interaction Modify Gene Expression but Still Suppress Metastasis in Human Breast Cancer Cells. J Biol Chem. 283, 7438-7444.
3. Samant, R. S., Debies, M. T., Shevde, L. A., Verderame, M. F., and Welch, D. R. (2002) Identification and Characterization of the Murine Ortholog (brms1) of Breast-Cancer Metastasis Suppressor 1 (BRMS1). Int J Cancer. 97, 15-20.
4. Cicek, M., Fukuyama, R., Welch, D. R., Sizemore, N., and Casey, G. (2005) Breast Cancer Metastasis Suppressor 1 Inhibits Gene Expression by Targeting Nuclear Factor-kappaB Activity. Cancer Res. 65, 3586-3595.
5. Seraj, M. J., Samant, R. S., Verderame, M. F., and Welch, D. R. (2000) Functional Evidence for a Novel Human Breast Carcinoma Metastasis Suppressor, BRMS1, Encoded at Chromosome 11q13. Cancer Res. 60, 2764-2769. |
| Posted On |
2013-01-20 |
| Science Writer |
Anne Murray |
Incidental Mutation