Mutagenetix > Incidental Mutation

Incidental Mutation 'R7469:Numb'

579052

Institutional Source

Beutler Lab

Gene Symbol

Numb

Ensembl Gene

ENSMUSG00000021224

Gene Name

NUMB endocytic adaptor protein

Synonyms

m-numb

MMRRC Submission

045543-MU

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R7469 (G1)

Quality Score

225.009

Status

Validated

Chromosome

Chromosomal Location

83840808-83968708 bp(-) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

T to C at 83850578 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Lysine to Glutamic Acid at position 211 (K211E)

Ref Sequence

ENSEMBL: ENSMUSP00000119303 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000021647] [ENSMUST00000085215] [ENSMUST00000110298] [ENSMUST00000117217] [ENSMUST00000129335] [ENSMUST00000135962] [ENSMUST00000136848] [ENSMUST00000154043] [ENSMUST00000155112]

AlphaFold

Q9QZS3

Predicted Effect

probably benign
Transcript: ENSMUST00000021647
AA Change: K211E

PolyPhen 2 Score 0.316 (Sensitivity: 0.90; Specificity: 0.89)

SMART Domains

Protein: ENSMUSP00000021647
Gene: ENSMUSG00000021224
AA Change: K211E

Domain	Start	End	E-Value	Type
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
AA Change: K211E

PolyPhen 2 Score 0.072 (Sensitivity: 0.94; Specificity: 0.84)

SMART Domains

Protein: ENSMUSP00000082311
Gene: ENSMUSG00000021224
AA Change: K211E

Domain	Start	End	E-Value	Type
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

Domain	Start	End	E-Value	Type
Pfam:PID	39	76	2.3e-7	PFAM

Predicted Effect

possibly damaging
Transcript: ENSMUST00000117217
AA Change: K200E

PolyPhen 2 Score 0.459 (Sensitivity: 0.89; Specificity: 0.90)

SMART Domains

Protein: ENSMUSP00000113591
Gene: ENSMUSG00000021224
AA Change: K200E

Domain	Start	End	E-Value	Type
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 benign
Transcript: ENSMUST00000129335
AA Change: K211E

PolyPhen 2 Score 0.374 (Sensitivity: 0.90; Specificity: 0.89)

SMART Domains

Protein: ENSMUSP00000119303
Gene: ENSMUSG00000021224
AA Change: K211E

Domain	Start	End	E-Value	Type
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

probably benign
Transcript: ENSMUST00000135962

SMART Domains

Protein: ENSMUSP00000122977
Gene: ENSMUSG00000021224

Domain	Start	End	E-Value	Type
Pfam:PTB	38	147	9.3e-8	PFAM
Pfam:PID	39	148	4.7e-32	PFAM

Predicted Effect

probably benign
Transcript: ENSMUST00000136848

SMART Domains

Protein: ENSMUSP00000122597
Gene: ENSMUSG00000021224

Domain	Start	End	E-Value	Type
Pfam:PTB	38	112	2.4e-8	PFAM
Pfam:PID	39	113	2.5e-18	PFAM

Predicted Effect

probably benign
Transcript: ENSMUST00000154043
AA Change: K200E

PolyPhen 2 Score 0.299 (Sensitivity: 0.91; Specificity: 0.89)

SMART Domains

Protein: ENSMUSP00000117899
Gene: ENSMUSG00000021224
AA Change: K200E

Domain	Start	End	E-Value	Type
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

Domain	Start	End	E-Value	Type
PTB	34	163	5.63e-26	SMART

Meta Mutation Damage Score

0.0883

Coding Region Coverage

1x: 100.0%
3x: 100.0%
10x: 99.7%
20x: 99.1%

Validation Efficiency

97% (77/79)

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: 79 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Abcc3	A	G	11: 94,259,014 (GRCm39)	L443P	probably damaging	Het
Abtb2	T	C	2: 103,397,292 (GRCm39)	V74A	probably benign	Het
Adam5	A	T	8: 25,305,541 (GRCm39)	F66I	probably benign	Het
Aff1	T	A	5: 103,981,413 (GRCm39)	D517E	probably benign	Het
Agbl3	A	G	6: 34,791,349 (GRCm39)	K559R	probably damaging	Het
Aldh1l2	A	C	10: 83,343,969 (GRCm39)	V482G	probably damaging	Het
Ankra2	C	T	13: 98,402,882 (GRCm39)	A43V	probably benign	Het
Ankrd50	C	A	3: 38,508,342 (GRCm39)	V419F	probably damaging	Het
Arhgef16	G	A	4: 154,375,763 (GRCm39)	T77M	probably damaging	Het
Best3	T	C	10: 116,840,290 (GRCm39)	V240A	probably damaging	Het
Btbd7	T	C	12: 102,779,027 (GRCm39)	Y413C	probably damaging	Het
Bzw2	A	T	12: 36,157,550 (GRCm39)	V305E	probably damaging	Het
Cacng8	G	A	7: 3,463,621 (GRCm39)	A258T	possibly damaging	Het
Cfap157	T	C	2: 32,670,696 (GRCm39)	Y184C	probably damaging	Het
Chmp3	T	A	6: 71,556,652 (GRCm39)	V184E	possibly damaging	Het
Cst5	C	T	2: 149,247,496 (GRCm39)	L71F	probably benign	Het
Ctdspl2	A	T	2: 121,837,362 (GRCm39)	E376D	possibly damaging	Het
Cyfip1	A	G	7: 55,527,468 (GRCm39)	D200G	possibly damaging	Het
Cylc2	T	A	4: 51,227,970 (GRCm39)		probably null	Het
Cyp2c66	T	A	19: 39,172,307 (GRCm39)	F407L	probably damaging	Het
Dcp2	T	C	18: 44,529,019 (GRCm39)	F45L	probably damaging	Het
Dhx34	C	T	7: 15,950,364 (GRCm39)	R268H	probably benign	Het
Dnajc7	A	T	11: 100,482,377 (GRCm39)	M205K	probably benign	Het
Dzip3	C	T	16: 48,765,242 (GRCm39)	V491M	probably benign	Het
Farp1	T	C	14: 121,512,833 (GRCm39)	L777P	probably damaging	Het
Fchsd2	T	G	7: 100,927,863 (GRCm39)		probably null	Het
Fer1l6	A	T	15: 58,462,419 (GRCm39)		probably null	Het
Fhip1a	T	C	3: 85,580,069 (GRCm39)	D712G	probably benign	Het
Fitm2	A	G	2: 163,311,742 (GRCm39)	F157S	probably damaging	Het
Flt1	G	T	5: 147,540,379 (GRCm39)	A770E	probably damaging	Het
Flt3	T	A	5: 147,268,084 (GRCm39)	E967V	probably benign	Het
Foxc1	G	C	13: 31,992,361 (GRCm39)	A391P	unknown	Het
Foxc1	C	T	13: 31,992,362 (GRCm39)	A391V	unknown	Het
Gimap6	T	A	6: 48,679,392 (GRCm39)	T215S	probably benign	Het
Gm2431	A	T	7: 141,811,518 (GRCm39)	C129S	unknown	Het
Itpr3	T	C	17: 27,340,028 (GRCm39)	S2636P	possibly damaging	Het
Lsg1	A	G	16: 30,380,635 (GRCm39)	Y601H	probably benign	Het
Map4	G	T	9: 109,856,865 (GRCm39)		probably null	Het
Mga	T	C	2: 119,733,527 (GRCm39)	M125T	probably damaging	Het
Mxi1	A	G	19: 53,360,091 (GRCm39)	D271G	probably damaging	Het
Ndst3	T	A	3: 123,465,310 (GRCm39)	T221S	possibly damaging	Het
Neto1	T	A	18: 86,516,813 (GRCm39)	S377T	probably benign	Het
Nkx6-2	T	C	7: 139,161,555 (GRCm39)	E210G	probably damaging	Het
Nos2	G	T	11: 78,843,797 (GRCm39)	V915F	possibly damaging	Het
Nrros	G	A	16: 31,963,030 (GRCm39)	A329V	probably benign	Het
Nup210	T	A	6: 90,995,874 (GRCm39)	I1671F	probably benign	Het
Or12j3	G	A	7: 139,953,050 (GRCm39)	L158F	possibly damaging	Het
Or4c106	T	A	2: 88,682,847 (GRCm39)	D184E	probably benign	Het
Or4c31	T	A	2: 88,291,691 (GRCm39)	H2Q	probably benign	Het
Pcdh15	A	T	10: 74,481,812 (GRCm39)	M386L	probably benign	Het
Pcdhb3	C	A	18: 37,434,388 (GRCm39)	T118K	probably benign	Het
Pcdhb8	A	T	18: 37,489,011 (GRCm39)	I230F	probably damaging	Het
Peli2	G	A	14: 48,488,015 (GRCm39)	V120I	probably benign	Het
Pramel15	T	A	4: 144,099,673 (GRCm39)	Q364L	probably damaging	Het
Pramel7	T	A	2: 87,321,748 (GRCm39)	M96L	probably benign	Het
Prex2	T	A	1: 11,355,293 (GRCm39)	S1531R	probably damaging	Het
Prpf31	A	G	7: 3,636,392 (GRCm39)	T138A	possibly damaging	Het
Psme4	C	T	11: 30,752,837 (GRCm39)	T175I	probably benign	Het
Rasgrf2	A	G	13: 92,165,530 (GRCm39)		probably null	Het
Rps19	T	A	7: 24,589,190 (GRCm39)	*146K	probably null	Het
Rsu1	T	C	2: 13,082,371 (GRCm39)	N260S	probably benign	Het
Serpina3k	T	C	12: 104,311,594 (GRCm39)	C391R	not run	Het
Sipa1l1	T	G	12: 82,467,438 (GRCm39)		probably null	Het
Snd1	T	A	6: 28,626,126 (GRCm39)	Y394N	probably damaging	Het
Spaca4	A	T	7: 45,374,831 (GRCm39)	V57E	probably damaging	Het
Spata31d1b	A	G	13: 59,863,278 (GRCm39)	Y142C	probably benign	Het
Sptbn2	A	G	19: 4,795,146 (GRCm39)	K1535E	probably benign	Het
Srcin1	A	G	11: 97,425,435 (GRCm39)	S541P	probably damaging	Het
Tc2n	A	T	12: 101,631,934 (GRCm39)	F308I	probably damaging	Het
Tdrd5	T	C	1: 156,090,475 (GRCm39)	D857G	probably benign	Het
Timm22	A	G	11: 76,298,134 (GRCm39)	D35G	probably benign	Het
Tram1l1	C	A	3: 124,114,889 (GRCm39)	H16Q	probably benign	Het
Uggt1	T	C	1: 36,190,814 (GRCm39)	Y1382C	probably damaging	Het
Usp32	G	T	11: 84,879,379 (GRCm39)	D1443E	possibly damaging	Het
Uty	A	T	Y: 1,131,072 (GRCm39)	C1046S	possibly damaging	Het
Wdr31	T	A	4: 62,375,768 (GRCm39)	Q230L	probably damaging	Het
Wnt8b	C	A	19: 44,500,001 (GRCm39)	T196K	possibly damaging	Het
Xpo4	A	T	14: 57,835,436 (GRCm39)	H628Q	probably benign	Het
Zfp780b	C	T	7: 27,663,382 (GRCm39)	S391N	probably benign	Het

Other mutations in Numb

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH 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
R3771:Numb	UTSW	12	83,846,350 (GRCm39)	missense	probably damaging	0.99
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
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'- TGTGACTCAGGATTATTATACCAGTCC -3'
(R):5'- AAACCTGCTCTCTACAGGGG -3'

Sequencing Primer
(F):5'- ACAAGGGATGTTTCTCTGCAC -3'
(R):5'- CTGCTCTCTACAGGGGGAAAGAC -3'

Posted On

2019-10-07