Incidental Mutation 'R0022:Mcc'
ID 15209
Institutional Source Beutler Lab
Gene Symbol Mcc
Ensembl Gene ENSMUSG00000071856
Gene Name mutated in colorectal cancers
Synonyms D18Ertd451e
MMRRC Submission 038317-MU
Accession Numbers
Essential gene? Non essential (E-score: 0.000) question?
Stock # R0022 (G1)
Quality Score
Status Validated
Chromosome 18
Chromosomal Location 44558127-44945249 bp(-) (GRCm39)
Type of Mutation critical splice donor site
DNA Base Change (assembly) C to G at 44652583 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change
Ref Sequence ENSEMBL: ENSMUSP00000128032 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000089874] [ENSMUST00000089874] [ENSMUST00000164666] [ENSMUST00000164666]
AlphaFold E9PWI3
Predicted Effect probably benign
Transcript: ENSMUST00000089874
SMART Domains Protein: ENSMUSP00000087318
Gene: ENSMUSG00000071856

DomainStartEndE-ValueType
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: ENSMUST00000089874
SMART Domains Protein: ENSMUSP00000087318
Gene: ENSMUSG00000071856

DomainStartEndE-ValueType
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
SMART Domains Protein: ENSMUSP00000128032
Gene: ENSMUSG00000071856

DomainStartEndE-ValueType
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
Predicted Effect probably benign
Transcript: ENSMUST00000164666
SMART Domains Protein: ENSMUSP00000128032
Gene: ENSMUSG00000071856

DomainStartEndE-ValueType
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
Predicted Effect noncoding transcript
Transcript: ENSMUST00000202090
Meta Mutation Damage Score 0.1325 question?
Coding Region Coverage
  • 1x: 82.0%
  • 3x: 74.9%
  • 10x: 56.1%
  • 20x: 37.0%
Validation Efficiency 97% (90/93)
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: 40 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
Aste1 T A 9: 105,273,823 (GRCm39) L21* probably null Het
Btbd10 G A 7: 112,924,988 (GRCm39) Q287* probably null Het
Cd244a A G 1: 171,401,330 (GRCm39) D48G probably benign Het
Cdc20 T A 4: 118,292,686 (GRCm39) H354L probably damaging Het
Cdhr3 G A 12: 33,132,263 (GRCm39) T120I probably damaging Het
Chd8 A T 14: 52,470,312 (GRCm39) S433T probably benign Het
Col1a2 G A 6: 4,518,822 (GRCm39) probably benign Het
Col9a3 A G 2: 180,261,549 (GRCm39) D613G probably damaging Het
Coro7 C T 16: 4,451,168 (GRCm39) R507H probably benign Het
Cracdl C T 1: 37,667,326 (GRCm39) R240Q probably damaging Het
Csf1 A T 3: 107,661,178 (GRCm39) V113E probably damaging Het
Dclre1b G T 3: 103,710,464 (GRCm39) H482Q probably benign Het
Ephb6 T C 6: 41,591,503 (GRCm39) V220A probably damaging Het
Ggct C A 6: 54,962,887 (GRCm39) E175* probably null Het
Gm5316 T C 6: 122,877,354 (GRCm39) noncoding transcript Het
Gzmn A G 14: 56,404,382 (GRCm39) S152P probably damaging Het
Hoxa7 T C 6: 52,194,363 (GRCm39) N8S probably damaging Het
Il12rb2 A G 6: 67,275,903 (GRCm39) F630S probably damaging Het
Kit A G 5: 75,783,657 (GRCm39) N378S probably benign Het
Lrp1b A T 2: 40,888,050 (GRCm39) probably benign Het
Ltbp1 T A 17: 75,671,355 (GRCm39) V1194D probably damaging Het
Mc5r T G 18: 68,471,853 (GRCm39) S71A probably benign Het
Naa25 C A 5: 121,556,039 (GRCm39) L276M probably damaging Het
Nlrp1b T G 11: 71,052,755 (GRCm39) K888T possibly damaging Het
Pabpc6 A T 17: 9,888,145 (GRCm39) N135K probably benign Het
Pik3r2 A G 8: 71,223,545 (GRCm39) F346S probably damaging Het
Pkd1 T C 17: 24,813,793 (GRCm39) W4086R probably damaging Het
Pmfbp1 C T 8: 110,252,039 (GRCm39) R395W probably damaging Het
Ppp1ca T G 19: 4,244,580 (GRCm39) V213G possibly damaging Het
Ptpro T A 6: 137,420,592 (GRCm39) V1007D probably damaging Het
Rapgef2 G A 3: 78,995,207 (GRCm39) R814C probably damaging Het
Rnasel A T 1: 153,636,521 (GRCm39) I634F probably damaging Het
Rnf157 A T 11: 116,240,276 (GRCm39) probably benign Het
Ryr3 A G 2: 112,471,011 (GRCm39) S4567P probably damaging Het
Sephs1 A G 2: 4,904,371 (GRCm39) T250A probably benign Het
Smcr8 T A 11: 60,671,185 (GRCm39) W778R probably damaging Het
Stat1 T A 1: 52,179,789 (GRCm39) L333Q probably damaging Het
Taar1 G T 10: 23,796,625 (GRCm39) A108S probably benign Het
Tro C G X: 149,430,508 (GRCm39) probably benign Het
Ubr1 A T 2: 120,791,654 (GRCm39) probably benign Het
Other mutations in Mcc
AlleleSourceChrCoordTypePredicted EffectPPH Score
IGL00489:Mcc APN 18 44,582,283 (GRCm39) missense possibly damaging 0.93
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
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
Posted On 2012-12-12
Science Writer Anne Murray