Incidental Mutation 'IGL00489:Mcc'
| ID |
11928 |
| Institutional Source |
Australian Phenomics Network
(link to record)
|
| Gene Symbol |
Mcc
|
| Ensembl Gene |
ENSMUSG00000071856 |
| Gene Name |
mutated in colorectal cancers |
| Synonyms |
D18Ertd451e |
| Accession Numbers |
|
| Essential gene? |
Non essential
(E-score: 0.000)
|
| Stock # |
IGL00489
|
| Quality Score |
|
|
Status
|
|
| Chromosome |
18 |
| Chromosomal Location |
44558127-44945249 bp(-) (GRCm39) |
| Type of Mutation |
missense |
| DNA Base Change (assembly) |
T to C
at 44582283 bp (GRCm39)
|
| Zygosity |
Heterozygous |
| Amino Acid Change |
Methionine to Valine
at position 798
(M798V)
|
| Ref Sequence |
ENSEMBL: ENSMUSP00000087318
(fasta)
|
| Gene Model |
predicted gene model for transcript(s):
[ENSMUST00000089874]
[ENSMUST00000164666]
|
| AlphaFold |
E9PWI3 |
| Predicted Effect |
possibly damaging
Transcript: ENSMUST00000089874
AA Change: M798V
PolyPhen 2
Score 0.934 (Sensitivity: 0.80; Specificity: 0.94)
|
| SMART Domains |
Protein: ENSMUSP00000087318
Gene: ENSMUSG00000071856
AA Change: M798V
| Domain | Start | End | E-Value | Type |
|---|
|
low complexity region
|
9 |
23 |
N/A |
INTRINSIC |
|
EFh
|
24 |
52 |
1.36e-3 |
SMART |
|
EFh
|
57 |
85 |
7.36e0 |
SMART |
|
coiled coil region
|
196 |
308 |
N/A |
INTRINSIC |
|
coiled coil region
|
395 |
466 |
N/A |
INTRINSIC |
|
low complexity region
|
488 |
493 |
N/A |
INTRINSIC |
|
low complexity region
|
512 |
517 |
N/A |
INTRINSIC |
|
low complexity region
|
523 |
537 |
N/A |
INTRINSIC |
|
Pfam:MCC-bdg_PDZ
|
577 |
641 |
2.6e-32 |
PFAM |
|
low complexity region
|
715 |
731 |
N/A |
INTRINSIC |
|
coiled coil region
|
738 |
834 |
N/A |
INTRINSIC |
|
low complexity region
|
853 |
863 |
N/A |
INTRINSIC |
|
Pfam:MCC-bdg_PDZ
|
906 |
972 |
1.1e-21 |
PFAM |
|
| Predicted Effect |
probably benign
Transcript: ENSMUST00000164666
AA Change: M623V
PolyPhen 2
Score 0.388 (Sensitivity: 0.90; Specificity: 0.89)
|
| SMART Domains |
Protein: ENSMUSP00000128032
Gene: ENSMUSG00000071856
AA Change: M623V
| Domain | Start | End | E-Value | Type |
|---|
|
coiled coil region
|
21 |
133 |
N/A |
INTRINSIC |
|
Pfam:MCC-bdg_PDZ
|
233 |
289 |
1.2e-14 |
PFAM |
|
low complexity region
|
313 |
318 |
N/A |
INTRINSIC |
|
low complexity region
|
337 |
342 |
N/A |
INTRINSIC |
|
low complexity region
|
348 |
362 |
N/A |
INTRINSIC |
|
Pfam:MCC-bdg_PDZ
|
401 |
467 |
3.8e-32 |
PFAM |
|
low complexity region
|
540 |
556 |
N/A |
INTRINSIC |
|
coiled coil region
|
563 |
659 |
N/A |
INTRINSIC |
|
low complexity region
|
678 |
688 |
N/A |
INTRINSIC |
|
Pfam:MCC-bdg_PDZ
|
730 |
798 |
1.3e-27 |
PFAM |
|
| Coding Region Coverage |
|
| Validation Efficiency |
|
| MGI Phenotype |
FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene is a candidate colorectal tumor suppressor gene that is thought to negatively regulate cell cycle progression. The orthologous gene in the mouse expresses a phosphoprotein associated with the plasma membrane and membrane organelles, and overexpression of the mouse protein inhibits entry into S phase. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]
PHENOTYPE: Mice homozygous for hypomorphic or null mutations are viable and fertile with no gross abnormalities. [provided by MGI curators]
|
| Allele List at MGI |
All alleles(29) : Targeted(2) Gene trapped(27)
|
| Other mutations in this stock |
Total: 29 list
| Gene | Ref | Var | Chr/Loc | Mutation | Predicted Effect | Zygosity |
|---|
| Adgrg6 |
T |
C |
10: 14,316,147 (GRCm39) |
|
probably null |
Het |
| Alcam |
T |
A |
16: 52,115,380 (GRCm39) |
|
probably benign |
Het |
| Aspm |
C |
A |
1: 139,406,429 (GRCm39) |
A1772E |
probably damaging |
Het |
| Bag6 |
T |
A |
17: 35,363,627 (GRCm39) |
D770E |
probably damaging |
Het |
| Baz2b |
A |
T |
2: 59,788,019 (GRCm39) |
Y724* |
probably null |
Het |
| Ccdc178 |
A |
T |
18: 21,977,968 (GRCm39) |
I833N |
probably benign |
Het |
| Ccdc28a |
C |
A |
10: 18,106,261 (GRCm39) |
V22F |
possibly damaging |
Het |
| Cmya5 |
T |
C |
13: 93,229,628 (GRCm39) |
N1820S |
probably benign |
Het |
| Fancm |
T |
G |
12: 65,152,967 (GRCm39) |
I1141S |
probably benign |
Het |
| Fgfrl1 |
G |
A |
5: 108,853,753 (GRCm39) |
G287S |
probably damaging |
Het |
| Galntl6 |
G |
A |
8: 58,310,574 (GRCm39) |
P376S |
probably damaging |
Het |
| Gm21985 |
A |
G |
2: 112,168,342 (GRCm39) |
|
probably benign |
Het |
| Hck |
A |
G |
2: 152,992,939 (GRCm39) |
E482G |
possibly damaging |
Het |
| Kcna3 |
C |
T |
3: 106,944,472 (GRCm39) |
S245L |
probably benign |
Het |
| Nlrp9c |
T |
C |
7: 26,084,013 (GRCm39) |
Y522C |
probably benign |
Het |
| Ofcc1 |
C |
A |
13: 40,433,967 (GRCm39) |
S46I |
probably damaging |
Het |
| Pdgfra |
A |
G |
5: 75,324,340 (GRCm39) |
D65G |
probably benign |
Het |
| Phf24 |
A |
C |
4: 42,933,905 (GRCm39) |
T59P |
possibly damaging |
Het |
| Pik3cg |
A |
G |
12: 32,255,148 (GRCm39) |
Y280H |
probably damaging |
Het |
| Pkd1l1 |
C |
A |
11: 8,784,773 (GRCm39) |
|
probably null |
Het |
| Plcd4 |
C |
A |
1: 74,591,274 (GRCm39) |
T223N |
probably damaging |
Het |
| Polr1b |
G |
A |
2: 128,967,829 (GRCm39) |
G1074D |
probably damaging |
Het |
| Pou2f3 |
T |
C |
9: 43,040,188 (GRCm39) |
T367A |
probably damaging |
Het |
| Prkdc |
T |
A |
16: 15,617,790 (GRCm39) |
M3207K |
possibly damaging |
Het |
| Rb1cc1 |
T |
C |
1: 6,319,730 (GRCm39) |
S1050P |
probably damaging |
Het |
| Sf3b3 |
G |
A |
8: 111,540,383 (GRCm39) |
R1013* |
probably null |
Het |
| Svep1 |
T |
C |
4: 58,068,988 (GRCm39) |
T2933A |
possibly damaging |
Het |
| Vwf |
A |
G |
6: 125,635,835 (GRCm39) |
R289G |
unknown |
Het |
| Zfp263 |
T |
C |
16: 3,563,710 (GRCm39) |
S155P |
probably benign |
Het |
|
| Other mutations in Mcc |
| Allele | Source | Chr | Coord | Type | Predicted Effect | PPH Score |
|---|
|
IGL00981:Mcc
|
APN |
18 |
44,582,416 (GRCm39) |
missense |
probably damaging |
0.99 |
|
IGL00985:Mcc
|
APN |
18 |
44,624,306 (GRCm39) |
missense |
probably damaging |
1.00 |
|
IGL01674:Mcc
|
APN |
18 |
44,624,223 (GRCm39) |
missense |
probably benign |
0.10 |
|
IGL01862:Mcc
|
APN |
18 |
44,892,363 (GRCm39) |
missense |
probably benign |
0.00 |
|
IGL01935:Mcc
|
APN |
18 |
44,652,583 (GRCm39) |
critical splice donor site |
probably null |
|
|
IGL02168:Mcc
|
APN |
18 |
44,582,366 (GRCm39) |
missense |
probably damaging |
0.97 |
|
IGL02449:Mcc
|
APN |
18 |
44,593,025 (GRCm39) |
missense |
probably benign |
0.10 |
|
IGL02613:Mcc
|
APN |
18 |
44,563,021 (GRCm39) |
missense |
probably damaging |
1.00 |
|
IGL02709:Mcc
|
APN |
18 |
44,578,877 (GRCm39) |
missense |
possibly damaging |
0.73 |
|
R0009:Mcc
|
UTSW |
18 |
44,579,000 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R0009:Mcc
|
UTSW |
18 |
44,579,000 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R0021:Mcc
|
UTSW |
18 |
44,652,583 (GRCm39) |
critical splice donor site |
probably benign |
|
|
R0022:Mcc
|
UTSW |
18 |
44,652,583 (GRCm39) |
critical splice donor site |
probably benign |
|
|
R0062:Mcc
|
UTSW |
18 |
44,652,583 (GRCm39) |
critical splice donor site |
probably benign |
|
|
R0062:Mcc
|
UTSW |
18 |
44,652,583 (GRCm39) |
critical splice donor site |
probably benign |
|
|
R0063:Mcc
|
UTSW |
18 |
44,652,583 (GRCm39) |
critical splice donor site |
probably benign |
|
|
R0064:Mcc
|
UTSW |
18 |
44,652,583 (GRCm39) |
critical splice donor site |
probably benign |
|
|
R0217:Mcc
|
UTSW |
18 |
44,652,583 (GRCm39) |
critical splice donor site |
probably benign |
|
|
R0218:Mcc
|
UTSW |
18 |
44,652,583 (GRCm39) |
critical splice donor site |
probably benign |
|
|
R0243:Mcc
|
UTSW |
18 |
44,892,366 (GRCm39) |
missense |
probably benign |
|
|
R0373:Mcc
|
UTSW |
18 |
44,608,289 (GRCm39) |
missense |
probably benign |
0.01 |
|
R0564:Mcc
|
UTSW |
18 |
44,601,574 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R0604:Mcc
|
UTSW |
18 |
44,606,823 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R0691:Mcc
|
UTSW |
18 |
44,578,927 (GRCm39) |
missense |
possibly damaging |
0.67 |
|
R0965:Mcc
|
UTSW |
18 |
44,857,593 (GRCm39) |
missense |
probably benign |
0.41 |
|
R1015:Mcc
|
UTSW |
18 |
44,857,736 (GRCm39) |
missense |
probably benign |
|
|
R1186:Mcc
|
UTSW |
18 |
44,892,470 (GRCm39) |
missense |
probably benign |
|
|
R1215:Mcc
|
UTSW |
18 |
44,601,561 (GRCm39) |
missense |
possibly damaging |
0.93 |
|
R1878:Mcc
|
UTSW |
18 |
44,601,467 (GRCm39) |
missense |
possibly damaging |
0.69 |
|
R1990:Mcc
|
UTSW |
18 |
44,624,382 (GRCm39) |
nonsense |
probably null |
|
|
R1991:Mcc
|
UTSW |
18 |
44,624,382 (GRCm39) |
nonsense |
probably null |
|
|
R1992:Mcc
|
UTSW |
18 |
44,624,382 (GRCm39) |
nonsense |
probably null |
|
|
R2186:Mcc
|
UTSW |
18 |
44,945,145 (GRCm39) |
missense |
possibly damaging |
0.71 |
|
R2189:Mcc
|
UTSW |
18 |
44,667,297 (GRCm39) |
missense |
possibly damaging |
0.93 |
|
R2258:Mcc
|
UTSW |
18 |
44,608,203 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R2267:Mcc
|
UTSW |
18 |
44,652,608 (GRCm39) |
missense |
probably damaging |
0.99 |
|
R2310:Mcc
|
UTSW |
18 |
44,564,433 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R2343:Mcc
|
UTSW |
18 |
44,592,864 (GRCm39) |
critical splice donor site |
probably null |
|
|
R2377:Mcc
|
UTSW |
18 |
44,652,616 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R3110:Mcc
|
UTSW |
18 |
44,582,330 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R3112:Mcc
|
UTSW |
18 |
44,582,330 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R4135:Mcc
|
UTSW |
18 |
44,857,707 (GRCm39) |
missense |
probably benign |
0.03 |
|
R4404:Mcc
|
UTSW |
18 |
44,892,365 (GRCm39) |
missense |
probably benign |
|
|
R4600:Mcc
|
UTSW |
18 |
44,652,587 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R4606:Mcc
|
UTSW |
18 |
44,601,488 (GRCm39) |
missense |
probably damaging |
0.96 |
|
R4721:Mcc
|
UTSW |
18 |
44,652,623 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R5858:Mcc
|
UTSW |
18 |
44,643,208 (GRCm39) |
missense |
probably damaging |
0.98 |
|
R5997:Mcc
|
UTSW |
18 |
44,582,388 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R6482:Mcc
|
UTSW |
18 |
44,578,931 (GRCm39) |
missense |
possibly damaging |
0.94 |
|
R6502:Mcc
|
UTSW |
18 |
44,601,458 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R6502:Mcc
|
UTSW |
18 |
44,601,457 (GRCm39) |
nonsense |
probably null |
|
|
R6518:Mcc
|
UTSW |
18 |
44,794,878 (GRCm39) |
start gained |
probably benign |
|
|
R6796:Mcc
|
UTSW |
18 |
44,857,627 (GRCm39) |
missense |
probably benign |
|
|
R6846:Mcc
|
UTSW |
18 |
44,606,707 (GRCm39) |
missense |
possibly damaging |
0.63 |
|
R6879:Mcc
|
UTSW |
18 |
44,945,179 (GRCm39) |
missense |
unknown |
|
|
R7147:Mcc
|
UTSW |
18 |
44,626,580 (GRCm39) |
missense |
probably damaging |
0.99 |
|
R7475:Mcc
|
UTSW |
18 |
44,609,303 (GRCm39) |
missense |
probably damaging |
0.98 |
|
R7515:Mcc
|
UTSW |
18 |
44,626,499 (GRCm39) |
missense |
probably benign |
0.02 |
|
R7608:Mcc
|
UTSW |
18 |
44,624,294 (GRCm39) |
missense |
possibly damaging |
0.83 |
|
R8092:Mcc
|
UTSW |
18 |
44,892,299 (GRCm39) |
missense |
probably benign |
0.00 |
|
R8119:Mcc
|
UTSW |
18 |
44,601,500 (GRCm39) |
missense |
possibly damaging |
0.95 |
|
R8162:Mcc
|
UTSW |
18 |
44,582,508 (GRCm39) |
critical splice acceptor site |
probably null |
|
|
R8187:Mcc
|
UTSW |
18 |
44,667,327 (GRCm39) |
missense |
possibly damaging |
0.53 |
|
R8716:Mcc
|
UTSW |
18 |
44,582,403 (GRCm39) |
missense |
possibly damaging |
0.92 |
|
R8744:Mcc
|
UTSW |
18 |
44,857,639 (GRCm39) |
missense |
probably benign |
|
|
R9383:Mcc
|
UTSW |
18 |
44,575,985 (GRCm39) |
missense |
probably benign |
0.24 |
|
R9517:Mcc
|
UTSW |
18 |
44,794,794 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R9570:Mcc
|
UTSW |
18 |
44,578,925 (GRCm39) |
missense |
probably damaging |
0.97 |
|
R9590:Mcc
|
UTSW |
18 |
44,592,977 (GRCm39) |
missense |
possibly damaging |
0.93 |
|
X0010:Mcc
|
UTSW |
18 |
44,563,024 (GRCm39) |
missense |
possibly damaging |
0.94 |
|
Z1177:Mcc
|
UTSW |
18 |
44,624,313 (GRCm39) |
missense |
probably benign |
0.04 |
|
| Protein Function and Prediction |
MCC is a PSD-95/Dlg/ZO-1 (PDZ) domain-containing protein involved in the pathogenesis of human colon cancer (1). MCC negatively regulates the cell cycle and its phosphorylation is necessary in response to DNA damage caused by single-strand DNA breaks (2;3). MCC modulates the nuclear factor kappa B (NFκB) signaling pathway by interacting with inhibitor of kappa B (IκB) (3;4). MCC has also been shown to affect Wnt signaling (5).
|
| Expression/Localization |
Mcc is expressed in the posterior primitive streak during gastrulation and in diverse tissues of both mesodermal and endodermal origin (1). Mcc transcripts localize to the posterior neural tube (1). In the developing nervous system, Mcc transcripts label several cranial ganglia and nerves and two parallel tracts of motor neurons (1). The MCC protein is localized to the surface epithelium of the colon and villi of the small intestine as well as diverse other adult tissues including the cerebellar cortex, kidney, pancreas, and liver (6;7). MCC is differentially phosphorylated during the cell cycle (6).
|
| Background |
Mutations in MCC are linked to colorectal cancer (8).
MccGt(D062B07)Wrst/Gt(D062B07)Wrst; MGI:3889488
involves: 129S2/SvPas * C57BL/6
Mice homozygous for hypomorphic or null mutations are viable and fertile with no gross abnormalities (1).
MccGt(W197F04)Wrst/ Gt(W197F04)Wrst; MGI:4335844
involves: 129S2/SvPas * C57BL/6
Mice homozygous for hypomorphic or null mutations are viable and fertile with no gross abnormalities (1).
|
| References |
1. Young, T., Poobalan, Y., Ali, Y., Siew Tein, W., Sadasivam, A., Ee Kim, T., Erica Tay, P., and Dunn, N. R. (2011) Mutated in Colorectal Cancer (Mcc), a Candidate Tumor Suppressor, is Dynamically Expressed during Mouse Embryogenesis. Dev Dyn. 240, 2166-2174.
2. Pangon, L., Sigglekow, N. D., Larance, M., Al-Sohaily, S., Mladenova, D. N., Selinger, C. I., Musgrove, E. A., and Kohonen-Corish, M. R. (2010) The "Mutated in Colorectal Cancer" Protein is a Novel Target of the UV-Induced DNA Damage Checkpoint. Genes Cancer. 1, 917-926.
3. Sigglekow, N. D., Pangon, L., Brummer, T., Molloy, M., Hawkins, N. J., Ward, R. L., Musgrove, E. A., and Kohonen-Corish, M. R. (2012) Mutated in Colorectal Cancer Protein Modulates the NFkappaB Pathway. Anticancer Res. 32, 73-79.
4. Bouwmeester, T., Bauch, A., Ruffner, H., Angrand, P. O., Bergamini, G., Croughton, K., Cruciat, C., Eberhard, D., Gagneur, J., Ghidelli, S., Hopf, C., Huhse, B., Mangano, R., Michon, A. M., Schirle, M., Schlegl, J., Schwab, M., Stein, M. A., Bauer, A., Casari, G., Drewes, G., Gavin, A. C., Jackson, D. B., Joberty, G., Neubauer, G., Rick, J., Kuster, B., and Superti-Furga, G. (2004) A Physical and Functional Map of the Human TNF-alpha/NF-Kappa B Signal Transduction Pathway. Nat Cell Biol. 6, 97-105.
5. Fukuyama, R., Niculaita, R., Ng, K. P., Obusez, E., Sanchez, J., Kalady, M., Aung, P. P., Casey, G., and Sizemore, N. (2008) Mutated in Colorectal Cancer, a Putative Tumor Suppressor for Serrated Colorectal Cancer, Selectively Represses Beta-Catenin-Dependent Transcription. Oncogene. 27, 6044-6055.
6. Matsumine, A., Senda, T., Baeg, G. H., Roy, B. C., Nakamura, Y., Noda, M., Toyoshima, K., and Akiyama, T. (1996) MCC, a Cytoplasmic Protein that Blocks Cell Cycle Progression from the G0/G1 to S Phase. J Biol Chem. 271, 10341-10346.
8. Kinzler, K. W., Nilbert, M. C., Vogelstein, B., Bryan, T. M., Levy, D. B., Smith, K. J., Preisinger, A. C., Hamilton, S. R., Hedge, P., and Markham, A. (1991) Identification of a Gene Located at Chromosome 5q21 that is Mutated in Colorectal Cancers. Science. 251, 1366-1370. |
| Posted On |
2012-12-06 |
| Science Writer |
Anne Murray |
Incidental Mutation