Incidental Mutation 'R3771:Numb'
ID 273300
Institutional Source Beutler Lab
Gene Symbol Numb
Ensembl Gene ENSMUSG00000021224
Gene Name NUMB endocytic adaptor protein
Synonyms m-numb
MMRRC Submission 040747-MU
Accession Numbers
Essential gene? Essential (E-score: 1.000) question?
Stock # R3771 (G1)
Quality Score 225
Status Validated
Chromosome 12
Chromosomal Location 83840808-83968708 bp(-) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) T to C at 83846350 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Aspartic acid to Glycine at position 344 (D344G)
Ref Sequence ENSEMBL: ENSMUSP00000119303 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000021647] [ENSMUST00000085215] [ENSMUST00000110298] [ENSMUST00000117217] [ENSMUST00000129335] [ENSMUST00000154043] [ENSMUST00000155112]
AlphaFold Q9QZS3
Predicted Effect probably benign
Transcript: ENSMUST00000021647
AA Change: D344G

PolyPhen 2 Score 0.320 (Sensitivity: 0.90; Specificity: 0.89)
SMART Domains Protein: ENSMUSP00000021647
Gene: ENSMUSG00000021224
AA Change: D344G

DomainStartEndE-ValueType
PTB 34 175 2.19e-37 SMART
low complexity region 231 253 N/A INTRINSIC
Pfam:NumbF 257 339 4.7e-42 PFAM
low complexity region 413 434 N/A INTRINSIC
low complexity region 445 453 N/A INTRINSIC
Predicted Effect probably benign
Transcript: ENSMUST00000085215
SMART Domains Protein: ENSMUSP00000082311
Gene: ENSMUSG00000021224

DomainStartEndE-ValueType
PTB 34 175 2.19e-37 SMART
low complexity region 231 253 N/A INTRINSIC
Pfam:NumbF 257 322 5.6e-34 PFAM
Predicted Effect probably benign
Transcript: ENSMUST00000110298
SMART Domains Protein: ENSMUSP00000105927
Gene: ENSMUSG00000021224

DomainStartEndE-ValueType
Pfam:PID 39 76 2.3e-7 PFAM
Predicted Effect possibly damaging
Transcript: ENSMUST00000117217
AA Change: D333G

PolyPhen 2 Score 0.628 (Sensitivity: 0.87; Specificity: 0.91)
SMART Domains Protein: ENSMUSP00000113591
Gene: ENSMUSG00000021224
AA Change: D333G

DomainStartEndE-ValueType
PTB 34 164 3.62e-38 SMART
low complexity region 220 242 N/A INTRINSIC
Pfam:NumbF 246 328 4.5e-42 PFAM
low complexity region 402 423 N/A INTRINSIC
low complexity region 434 442 N/A INTRINSIC
Predicted Effect probably damaging
Transcript: ENSMUST00000129335
AA Change: D344G

PolyPhen 2 Score 0.994 (Sensitivity: 0.69; Specificity: 0.97)
SMART Domains Protein: ENSMUSP00000119303
Gene: ENSMUSG00000021224
AA Change: D344G

DomainStartEndE-ValueType
PTB 34 175 2.19e-37 SMART
low complexity region 231 253 N/A INTRINSIC
Pfam:NumbF 258 338 9.9e-32 PFAM
low complexity region 462 483 N/A INTRINSIC
low complexity region 494 502 N/A INTRINSIC
Predicted Effect possibly damaging
Transcript: ENSMUST00000154043
AA Change: D333G

PolyPhen 2 Score 0.634 (Sensitivity: 0.87; Specificity: 0.91)
SMART Domains Protein: ENSMUSP00000117899
Gene: ENSMUSG00000021224
AA Change: D333G

DomainStartEndE-ValueType
PTB 34 164 3.62e-38 SMART
low complexity region 220 242 N/A INTRINSIC
Pfam:NumbF 246 328 5.1e-42 PFAM
low complexity region 451 472 N/A INTRINSIC
low complexity region 483 491 N/A INTRINSIC
Predicted Effect probably benign
Transcript: ENSMUST00000155112
SMART Domains Protein: ENSMUSP00000116863
Gene: ENSMUSG00000021224

DomainStartEndE-ValueType
PTB 34 163 5.63e-26 SMART
Meta Mutation Damage Score 0.2396 question?
Coding Region Coverage
  • 1x: 99.2%
  • 3x: 98.6%
  • 10x: 97.3%
  • 20x: 95.3%
Validation Efficiency 99% (69/70)
MGI Phenotype FUNCTION: This gene encodes a conserved protein that is distributed asymmetrically during cell division in the developing embryo. The encoded protein participates in cell fate decisions by interacting with the Notch receptor. Loss of function of this gene results in severe defects in neural development and loss of viability. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2013]
PHENOTYPE: Mice homozygous for a null allele die at ~E11.5 with neural tube closure defects and precocious cortical neurogenesis. Mice homozygous for another null allele show impaired axial rotation, neural tube closure, angiogenic remodeling, placenta formation, and motor and sensory neuron differentiation. [provided by MGI curators]
Allele List at MGI
Other mutations in this stock
Total: 65 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
Aanat G T 11: 116,487,697 (GRCm39) G132V probably damaging Het
Abcb11 T A 2: 69,159,720 (GRCm39) probably benign Het
Adam26b T A 8: 43,973,751 (GRCm39) D417V probably damaging Het
Ank1 T C 8: 23,613,913 (GRCm39) S1482P probably benign Het
Aoc1l2 T C 6: 48,908,130 (GRCm39) Y377H probably damaging Het
Armc2 C T 10: 41,798,223 (GRCm39) V768M probably damaging Het
Ascc3 C T 10: 50,596,814 (GRCm39) probably benign Het
Birc6 T A 17: 74,925,424 (GRCm39) probably benign Het
Cd109 CATTTATTTATTTATTTATTTATTTATTTATTTAT CATTTATTTATTTATTTATTTATTTATTTATTTATTTAT 9: 78,619,782 (GRCm39) probably benign Het
Cdh12 A T 15: 21,578,640 (GRCm39) probably benign Het
Chd1 A G 17: 17,594,913 (GRCm39) D16G probably damaging Het
Clstn2 A G 9: 97,464,615 (GRCm39) I180T probably damaging Het
Cxcr6 A G 9: 123,639,550 (GRCm39) I184V probably benign Het
Dagla G A 19: 10,225,831 (GRCm39) P778S possibly damaging Het
Ddx19b T C 8: 111,747,613 (GRCm39) K107R probably benign Het
Dpyd G A 3: 119,205,927 (GRCm39) probably null Het
Elf1 T C 14: 79,804,650 (GRCm39) V105A possibly damaging Het
Fam13a T G 6: 58,964,171 (GRCm39) K87T probably benign Het
Fap C A 2: 62,363,354 (GRCm39) S359I probably damaging Het
Fbxo39 T C 11: 72,208,041 (GRCm39) I131T possibly damaging Het
Fmn1 T G 2: 113,412,463 (GRCm39) S996A probably damaging Het
Gm5866 T C 5: 52,740,088 (GRCm39) noncoding transcript Het
Hmcn2 C T 2: 31,250,908 (GRCm39) T790M probably damaging Het
Irf2bp2 T C 8: 127,318,550 (GRCm39) K339E probably damaging Het
Kat6b A G 14: 21,567,166 (GRCm39) D75G probably damaging Het
Kcnab3 A G 11: 69,219,389 (GRCm39) T127A probably damaging Het
Kdm5b G T 1: 134,541,083 (GRCm39) C725F probably damaging Het
Lrp5 G A 19: 3,662,330 (GRCm39) R173C probably damaging Het
Lrrn3 T A 12: 41,502,869 (GRCm39) I483L probably damaging Het
Man2c1 C A 9: 57,047,661 (GRCm39) probably benign Het
Med23 G T 10: 24,778,099 (GRCm39) G810C probably damaging Het
Nhlrc4 T A 17: 26,162,367 (GRCm39) K127* probably null Het
Nup210l T G 3: 90,027,201 (GRCm39) Y194* probably null Het
Ogg1 T C 6: 113,310,804 (GRCm39) V317A possibly damaging Het
Or1o2 T A 17: 37,542,356 (GRCm39) I302F possibly damaging Het
Or6c69c A G 10: 129,911,143 (GRCm39) Y288C probably damaging Het
Pclo A T 5: 14,589,422 (GRCm39) probably null Het
Pnpt1 T C 11: 29,088,174 (GRCm39) M195T probably benign Het
Polr3c T A 3: 96,633,170 (GRCm39) T43S probably damaging Het
Ptprs T C 17: 56,735,978 (GRCm39) T152A possibly damaging Het
Rasl10b A T 11: 83,309,349 (GRCm39) T134S probably benign Het
Rin2 C T 2: 145,702,366 (GRCm39) T354I probably benign Het
Rnf39 T C 17: 37,258,121 (GRCm39) W96R probably damaging Het
Ros1 G T 10: 52,005,087 (GRCm39) A949E probably damaging Het
Rwdd2a A C 9: 86,456,214 (GRCm39) N130T possibly damaging Het
Scn9a T C 2: 66,313,992 (GRCm39) N1909D probably benign Het
Shisal1 A T 15: 84,290,886 (GRCm39) Y120* probably null Het
Ska3 C T 14: 58,047,534 (GRCm39) V334I probably benign Het
Srebf2 A G 15: 82,066,309 (GRCm39) K579R probably benign Het
Sun1 A G 5: 139,224,575 (GRCm39) probably benign Het
Tc2n T A 12: 101,660,833 (GRCm39) Q133L possibly damaging Het
Tecta T C 9: 42,242,292 (GRCm39) T2094A probably damaging Het
Tex2 T C 11: 106,437,720 (GRCm39) D650G unknown Het
Trio A G 15: 27,748,177 (GRCm39) S2492P probably damaging Het
Ttn T C 2: 76,601,711 (GRCm39) T16872A probably benign Het
Ugcg T C 4: 59,189,690 (GRCm39) F16S probably benign Het
Usp16 T C 16: 87,255,571 (GRCm39) M1T probably null Het
Vmn1r60 C A 7: 5,547,710 (GRCm39) C130F possibly damaging Het
Vmn2r101 A G 17: 19,809,919 (GRCm39) D235G probably benign Het
Vpreb3 A T 10: 75,775,800 (GRCm39) V26E probably benign Het
Vps39 C T 2: 120,172,497 (GRCm39) V179I possibly damaging Het
Xrn2 T C 2: 146,903,207 (GRCm39) V765A probably benign Het
Zfp251 A G 15: 76,737,836 (GRCm39) I414T possibly damaging Het
Zfp426 A T 9: 20,384,413 (GRCm39) probably null Het
Zfp61 T C 7: 23,995,406 (GRCm39) M1V probably null Het
Other mutations in Numb
AlleleSourceChrCoordTypePredicted EffectPPH Score
IGL00335:Numb APN 12 83,854,906 (GRCm39) missense probably damaging 1.00
IGL01979:Numb APN 12 83,889,051 (GRCm39) missense probably damaging 1.00
IGL02318:Numb APN 12 83,878,692 (GRCm39) splice site probably null
IGL02716:Numb APN 12 83,847,982 (GRCm39) missense possibly damaging 0.79
IGL03206:Numb APN 12 83,872,070 (GRCm39) splice site probably benign
PIT4468001:Numb UTSW 12 83,854,921 (GRCm39) missense probably damaging 0.99
R0086:Numb UTSW 12 83,842,704 (GRCm39) missense probably damaging 1.00
R0626:Numb UTSW 12 83,842,614 (GRCm39) missense probably damaging 0.97
R0652:Numb UTSW 12 83,842,566 (GRCm39) missense probably damaging 1.00
R1201:Numb UTSW 12 83,848,059 (GRCm39) missense probably damaging 0.99
R1295:Numb UTSW 12 83,842,935 (GRCm39) splice site probably benign
R1433:Numb UTSW 12 83,844,033 (GRCm39) missense probably damaging 0.98
R1489:Numb UTSW 12 83,842,217 (GRCm39) missense probably damaging 1.00
R1606:Numb UTSW 12 83,847,784 (GRCm39) splice site probably null
R1980:Numb UTSW 12 83,844,118 (GRCm39) critical splice acceptor site probably null
R5382:Numb UTSW 12 83,854,979 (GRCm39) missense probably damaging 1.00
R5818:Numb UTSW 12 83,872,028 (GRCm39) splice site probably null
R5846:Numb UTSW 12 83,923,521 (GRCm39) utr 5 prime probably benign
R6360:Numb UTSW 12 83,844,036 (GRCm39) missense probably damaging 0.99
R6384:Numb UTSW 12 83,850,748 (GRCm39) missense probably damaging 1.00
R7186:Numb UTSW 12 83,842,920 (GRCm39) missense probably damaging 1.00
R7469:Numb UTSW 12 83,850,578 (GRCm39) missense probably benign 0.37
R7749:Numb UTSW 12 83,848,051 (GRCm39) missense not run
R8342:Numb UTSW 12 83,854,990 (GRCm39) missense probably benign 0.02
R8370:Numb UTSW 12 83,854,974 (GRCm39) nonsense probably null
R9448:Numb UTSW 12 83,888,990 (GRCm39) critical splice donor site probably null
Predicted Primers PCR Primer
(F):5'- AGCCCAAAGATGTGACTGACAG -3'
(R):5'- ACAGTTGAGACTTGTCCTTCG -3'

Sequencing Primer
(F):5'- CCAAAGATGTGACTGACAGGGAAAC -3'
(R):5'- AGACTTGTCCTTCGGCAAG -3'
Posted On 2015-03-25