Mutagenetix > Incidental Mutation

Incidental Mutation 'R6360:Numb'

513082

Institutional Source

Beutler Lab

Gene Symbol

Numb

Ensembl Gene

ENSMUSG00000021224

Gene Name

NUMB endocytic adaptor protein

Synonyms

m-numb

MMRRC Submission

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R6360 (G1)

Quality Score

225.009

Status

Validated

Chromosome

Chromosomal Location

83794034-83921934 bp(-) (GRCm38)

Type of Mutation

missense

DNA Base Change (assembly)

C to A at 83797262 bp (GRCm38)

Zygosity

Heterozygous

Amino Acid Change

Arginine to Leucine at position 383 (R383L)

Ref Sequence

ENSEMBL: ENSMUSP00000117899 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000021646] [ENSMUST00000021647] [ENSMUST00000085215] [ENSMUST00000110298] [ENSMUST00000117217] [ENSMUST00000121733] [ENSMUST00000129335] [ENSMUST00000154043]

AlphaFold

Q9QZS3

Predicted Effect

probably benign
Transcript: ENSMUST00000021646

SMART Domains

Protein: ENSMUSP00000021646
Gene: ENSMUSG00000021223

Domain	Start	End	E-Value	Type
signal peptide	1	20	N/A	INTRINSIC
TSP1	30	81	3.36e-11	SMART
low complexity region	147	161	N/A	INTRINSIC
Pfam:ADAM_spacer1	184	299	3.3e-39	PFAM
TSP1	309	362	1.2e-7	SMART
TSP1	366	426	2.76e-7	SMART
TSP1	427	482	1.42e-9	SMART
TSP1	488	540	2.47e-9	SMART
low complexity region	604	621	N/A	INTRINSIC
KU	748	801	1.83e-22	SMART
low complexity region	822	831	N/A	INTRINSIC
IGc2	917	980	2.88e-4	SMART
IGc2	1056	1119	2.66e-17	SMART
IGc2	1145	1209	2.13e-7	SMART
Pfam:PLAC	1234	1268	2.3e-14	PFAM

Predicted Effect

probably benign
Transcript: ENSMUST00000021647

SMART Domains

Protein: ENSMUSP00000021647
Gene: ENSMUSG00000021224

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

SMART Domains

Protein: ENSMUSP00000082311
Gene: ENSMUSG00000021224

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

probably benign
Transcript: ENSMUST00000117217

SMART Domains

Protein: ENSMUSP00000113591
Gene: ENSMUSG00000021224

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: ENSMUST00000121733

SMART Domains

Protein: ENSMUSP00000113806
Gene: ENSMUSG00000021223

Domain	Start	End	E-Value	Type
low complexity region	3	16	N/A	INTRINSIC
TSP1	30	81	3.36e-11	SMART
low complexity region	147	161	N/A	INTRINSIC
Pfam:ADAM_spacer1	184	299	2.8e-38	PFAM
TSP1	309	362	1.2e-7	SMART
TSP1	388	448	1.82e-7	SMART
TSP1	449	504	1.42e-9	SMART
TSP1	510	562	2.47e-9	SMART
low complexity region	626	643	N/A	INTRINSIC
KU	770	823	1.83e-22	SMART
Pfam:Papilin_u7	831	922	1.9e-40	PFAM
IGc2	939	1002	2.88e-4	SMART
IGc2	1078	1141	2.66e-17	SMART
IGc2	1167	1231	2.13e-7	SMART
Pfam:PLAC	1257	1289	1.1e-13	PFAM

Predicted Effect

probably damaging
Transcript: ENSMUST00000129335
AA Change: R394L

PolyPhen 2 Score 0.976 (Sensitivity: 0.76; Specificity: 0.96)

SMART Domains

Protein: ENSMUSP00000119303
Gene: ENSMUSG00000021224
AA Change: R394L

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 damaging
Transcript: ENSMUST00000154043
AA Change: R383L

PolyPhen 2 Score 0.989 (Sensitivity: 0.72; Specificity: 0.97)

SMART Domains

Protein: ENSMUSP00000117899
Gene: ENSMUSG00000021224
AA Change: R383L

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

Coding Region Coverage

1x: 99.9%
3x: 99.6%
10x: 98.3%
20x: 95.2%

Validation Efficiency

98% (59/60)

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: 59 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Arhgap10	G	A	8: 77,259,202	Q657*	probably null	Het
Car15	T	C	16: 17,838,066	T560A	probably benign	Het
Cass4	C	T	2: 172,432,611	H769Y	probably damaging	Het
Cdh6	A	G	15: 13,041,460	I506T	possibly damaging	Het
Clstn3	G	T	6: 124,438,429	R659S	possibly damaging	Het
Cntnap5b	C	T	1: 100,431,736	R695*	probably null	Het
Cpsf1	CCCCTGCATGAGGCAGGTCCC	CCCC	15: 76,597,455		probably null	Het
Dab2ip	A	G	2: 35,710,266	H355R	probably benign	Het
Dennd2a	C	T	6: 39,493,142	A539T	probably benign	Het
Dnajc18	T	C	18: 35,686,709	E173G	probably damaging	Het
Dock7	T	C	4: 98,969,662	I1472V	probably benign	Het
Esco1	A	T	18: 10,574,931	F714I	probably damaging	Het
Fam107a	T	G	14: 8,299,619	H73P	probably damaging	Het
Fam46b	T	C	4: 133,486,756	F313L	probably damaging	Het
Flg	A	G	3: 93,290,601		probably benign	Het
Fyn	C	A	10: 39,526,883	T217K	possibly damaging	Het
Gbp9	T	C	5: 105,083,730	D330G	probably benign	Het
Gin1	T	C	1: 97,792,539	S509P	possibly damaging	Het
Gm15922	A	T	7: 3,736,504	L455Q	probably damaging	Het
Gm17067	A	C	7: 42,708,482	S199A	probably benign	Het
Grk4	A	T	5: 34,674,537	K50M	probably damaging	Het
Inpp4b	A	G	8: 81,902,852	H272R	probably benign	Het
Ipo7	T	A	7: 110,027,129	L48Q	probably damaging	Het
Kbtbd2	A	G	6: 56,779,206	I515T	probably damaging	Het
Kcnu1	T	A	8: 25,861,180	S190R	possibly damaging	Het
Kpnb1	T	C	11: 97,173,270	N336S	probably benign	Het
Lbr	G	T	1: 181,832,155	D158E	probably benign	Het
Mphosph10	T	C	7: 64,389,955	Q89R	probably benign	Het
Nectin3	T	A	16: 46,411,109	T21S	probably benign	Het
Olfr1370	A	T	13: 21,072,583	N239K	probably damaging	Het
Olfr461	G	T	6: 40,544,713	Q89K	possibly damaging	Het
Park2	T	C	17: 12,004,052	F363S	probably damaging	Het
Pcdhb11	A	T	18: 37,422,159	I181F	probably benign	Het
Pcgf2	T	A	11: 97,692,409		probably null	Het
Pdzd8	T	C	19: 59,300,983	T662A	probably benign	Het
Pex13	A	C	11: 23,655,690	V180G	probably benign	Het
Pkp4	T	A	2: 59,214,747	V22D	probably benign	Het
Ppp1r32	T	C	19: 10,479,481	N167D	probably damaging	Het
Prpf4b	A	C	13: 34,901,433	D954A	probably damaging	Het
Rfx8	T	C	1: 39,680,965	I317V	probably benign	Het
Rnaseh2b	T	C	14: 62,361,419	S198P	probably damaging	Het
Rock1	A	T	18: 10,116,778	C453S	possibly damaging	Het
Scarf1	G	T	11: 75,515,669	G260W	probably damaging	Het
Scyl1	T	C	19: 5,760,571	E538G	probably damaging	Het
Sec14l5	A	T	16: 5,172,995	I267F	probably damaging	Het
Senp6	T	A	9: 80,113,806	V256D	probably benign	Het
Sf3b4	G	A	3: 96,176,728		probably benign	Het
Ssh1	T	C	5: 113,961,347		probably null	Het
Tas2r143	A	C	6: 42,400,835	M200L	probably benign	Het
Tbc1d22a	C	T	15: 86,214,629	P19S	probably damaging	Het
Tmc5	T	A	7: 118,633,966	M1K	probably null	Het
Tnc	T	C	4: 64,000,733	Y1151C	probably damaging	Het
Tshz3	A	G	7: 36,769,441	E285G	probably damaging	Het
Txndc11	C	T	16: 11,084,792	V664M	probably damaging	Het
Ube2g1	A	T	11: 72,663,082	N20Y	probably damaging	Het
Ufl1	T	A	4: 25,265,476	I369L	probably benign	Het
Vwf	A	T	6: 125,683,526	T2666S	probably benign	Het
Yif1a	A	G	19: 5,092,341	M259V	probably benign	Het
Zbtb46	T	C	2: 181,391,455	D471G	probably damaging	Het

Other mutations in Numb

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL00335:Numb	APN	12	83808132	missense	probably damaging	1.00
IGL01979:Numb	APN	12	83842277	missense	probably damaging	1.00
IGL02318:Numb	APN	12	83831918	splice site	probably null
IGL02716:Numb	APN	12	83801208	missense	possibly damaging	0.79
IGL03206:Numb	APN	12	83825296	splice site	probably benign
PIT4468001:Numb	UTSW	12	83808147	missense	probably damaging	0.99
R0086:Numb	UTSW	12	83795930	missense	probably damaging	1.00
R0626:Numb	UTSW	12	83795840	missense	probably damaging	0.97
R0652:Numb	UTSW	12	83795792	missense	probably damaging	1.00
R1201:Numb	UTSW	12	83801285	missense	probably damaging	0.99
R1295:Numb	UTSW	12	83796161	splice site	probably benign
R1433:Numb	UTSW	12	83797259	missense	probably damaging	0.98
R1489:Numb	UTSW	12	83795443	missense	probably damaging	1.00
R1606:Numb	UTSW	12	83801010	splice site	probably null
R1980:Numb	UTSW	12	83797344	critical splice acceptor site	probably null
R3771:Numb	UTSW	12	83799576	missense	probably damaging	0.99
R5382:Numb	UTSW	12	83808205	missense	probably damaging	1.00
R5818:Numb	UTSW	12	83825254	splice site	probably null
R5846:Numb	UTSW	12	83876747	utr 5 prime	probably benign
R6384:Numb	UTSW	12	83803974	missense	probably damaging	1.00
R7186:Numb	UTSW	12	83796146	missense	probably damaging	1.00
R7469:Numb	UTSW	12	83803804	missense	probably benign	0.37
R7749:Numb	UTSW	12	83801277	missense	not run
R8342:Numb	UTSW	12	83808216	missense	probably benign	0.02
R8370:Numb	UTSW	12	83808200	nonsense	probably null
R9448:Numb	UTSW	12	83842216	critical splice donor site	probably null

Predicted Primers

PCR Primer
(F):5'- CCACAGTCCTGAGAACAGTC -3'
(R):5'- ATTGTACGTTGGCCTGACTG -3'

Sequencing Primer
(F):5'- TCACAGCCACTTCTGTCTAGGAAAG -3'
(R):5'- GACTGACCCATCTCGTGTAG -3'

Posted On

2018-04-27