Mutagenetix > Incidental Mutation

Incidental Mutation 'D6062:Nell1'

241

Institutional Source

Beutler Lab

Gene Symbol

Nell1

Ensembl Gene

ENSMUSG00000055409

Gene Name

NEL-like 1

Synonyms

l7R6, B230343H07Rik

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

D6062 of strain 376

Quality Score

Status

Validated

Chromosome

Chromosomal Location

49625098-50513037 bp(+) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

A to G at 49907939 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Glutamic Acid to Glycine at position 366 (E366G)

Ref Sequence

ENSEMBL: ENSMUSP00000103229 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000081872] [ENSMUST00000107603] [ENSMUST00000151721]

AlphaFold

Q2VWQ2

Predicted Effect

probably benign
Transcript: ENSMUST00000081872
AA Change: E366G

PolyPhen 2 Score 0.027 (Sensitivity: 0.95; Specificity: 0.81)

SMART Domains

Protein: ENSMUSP00000080550
Gene: ENSMUSG00000055409
AA Change: E366G

Domain	Start	End	E-Value	Type
signal peptide	1	21	N/A	INTRINSIC
TSPN	29	213	8.5e-72	SMART
LamG	81	208	1.77e-14	SMART
coiled coil region	240	266	N/A	INTRINSIC
VWC	273	331	1.45e-6	SMART
VWC	335	389	1.34e0	SMART
EGF	394	433	1.06e0	SMART
EGF_CA	434	475	7.93e-9	SMART
EGF	479	516	1.1e-2	SMART
EGF	518	547	8.32e-3	SMART
EGF_CA	549	595	1.08e-10	SMART
EGF_like	596	635	1.84e-4	SMART
VWC	634	686	1.42e0	SMART
VWC	694	749	1.83e-12	SMART

Predicted Effect

probably benign
Transcript: ENSMUST00000107603
AA Change: E366G

PolyPhen 2 Score 0.209 (Sensitivity: 0.92; Specificity: 0.88)

SMART Domains

Protein: ENSMUSP00000103229
Gene: ENSMUSG00000055409
AA Change: E366G

Domain	Start	End	E-Value	Type
signal peptide	1	21	N/A	INTRINSIC
TSPN	29	213	8.5e-72	SMART
LamG	81	208	1.77e-14	SMART
coiled coil region	240	266	N/A	INTRINSIC
VWC	273	331	1.45e-6	SMART
VWC	335	389	1.34e0	SMART
EGF	394	433	1.06e0	SMART
EGF_CA	434	475	7.93e-9	SMART
EGF	479	516	1.1e-2	SMART
EGF	518	547	8.32e-3	SMART
EGF_like	549	588	1.84e-4	SMART
VWC	587	639	1.42e0	SMART
VWC	647	702	1.83e-12	SMART

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000145096

Predicted Effect

probably benign
Transcript: ENSMUST00000151721

SMART Domains

Protein: ENSMUSP00000114706
Gene: ENSMUSG00000055409

Domain	Start	End	E-Value	Type
signal peptide	1	21	N/A	INTRINSIC
TSPN	29	213	8.5e-72	SMART
LamG	81	208	1.77e-14	SMART

Meta Mutation Damage Score

0.1253

Coding Region Coverage

1x: 71.6%
3x: 37.9%

Validation Efficiency

85% (121/143)

MGI Phenotype

FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene encodes a cytoplasmic protein that contains epidermal growth factor (EGF)-like repeats. The encoded heterotrimeric protein may be involved in cell growth regulation and differentiation. A similar protein in rodents is involved in craniosynostosis. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2013]
PHENOTYPE: Homozygous mice display perinatal lethality, respiratory failure, impaired development of the intervertebral disks, vertebrae and calvarial bones, increased skull length, and abnormal curvature of the spine. [provided by MGI curators]

Allele List at MGI

All alleles(11) : Gene trapped(2) Chemically induced(9)

Other mutations in this stock

Total: 4 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Ccdc117	T	A	11: 5,475,039 (GRCm39)		probably benign	Homo
Ncoa7	A	G	10: 30,598,651 (GRCm39)	Y91H	probably damaging	Homo
Rpl29	T	C	9: 106,307,186 (GRCm39)	S4P	probably damaging	Het
Zbtb7a	C	T	10: 80,980,192 (GRCm39)	R129C	probably damaging	Het

Other mutations in Nell1

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL00327:Nell1	APN	7	49,770,421 (GRCm39)	missense	probably damaging	0.96
IGL01434:Nell1	APN	7	50,350,956 (GRCm39)	missense	probably benign	0.01
IGL01796:Nell1	APN	7	49,825,964 (GRCm39)	splice site	probably benign
IGL02048:Nell1	APN	7	49,869,355 (GRCm39)	missense	probably damaging	0.96
IGL02239:Nell1	APN	7	49,899,398 (GRCm39)	missense	probably benign	0.08
IGL02860:Nell1	APN	7	50,498,233 (GRCm39)	missense	probably damaging	0.99
IGL02958:Nell1	APN	7	49,870,085 (GRCm39)	critical splice donor site	probably null
IGL03143:Nell1	APN	7	49,929,281 (GRCm39)	nonsense	probably null
IGL03334:Nell1	APN	7	49,712,359 (GRCm39)	splice site	probably null
P0018:Nell1	UTSW	7	49,770,439 (GRCm39)	missense	probably damaging	1.00
R0004:Nell1	UTSW	7	50,210,507 (GRCm39)	splice site	probably benign
R0029:Nell1	UTSW	7	49,770,463 (GRCm39)	splice site	probably benign
R0029:Nell1	UTSW	7	49,770,463 (GRCm39)	splice site	probably benign
R0468:Nell1	UTSW	7	49,878,594 (GRCm39)	missense	probably damaging	0.97
R0483:Nell1	UTSW	7	49,879,928 (GRCm39)	missense	probably benign	0.07
R0732:Nell1	UTSW	7	50,506,135 (GRCm39)	missense	probably damaging	1.00
R0945:Nell1	UTSW	7	49,869,333 (GRCm39)	missense	probably benign	0.07
R1022:Nell1	UTSW	7	49,770,411 (GRCm39)	missense	probably damaging	1.00
R1024:Nell1	UTSW	7	49,770,411 (GRCm39)	missense	probably damaging	1.00
R1075:Nell1	UTSW	7	50,503,588 (GRCm39)	missense	probably damaging	0.98
R1291:Nell1	UTSW	7	49,879,998 (GRCm39)	missense	probably benign	0.00
R1404:Nell1	UTSW	7	50,503,621 (GRCm39)	missense	possibly damaging	0.91
R1404:Nell1	UTSW	7	50,503,621 (GRCm39)	missense	possibly damaging	0.91
R1634:Nell1	UTSW	7	50,498,306 (GRCm39)	missense	possibly damaging	0.82
R1928:Nell1	UTSW	7	50,350,943 (GRCm39)	missense	possibly damaging	0.51
R2060:Nell1	UTSW	7	50,210,578 (GRCm39)	missense	possibly damaging	0.58
R2261:Nell1	UTSW	7	50,210,569 (GRCm39)	missense	possibly damaging	0.95
R2262:Nell1	UTSW	7	50,210,569 (GRCm39)	missense	possibly damaging	0.95
R2263:Nell1	UTSW	7	50,210,569 (GRCm39)	missense	possibly damaging	0.95
R2448:Nell1	UTSW	7	50,506,135 (GRCm39)	missense	probably damaging	1.00
R2869:Nell1	UTSW	7	49,899,405 (GRCm39)	intron	probably benign
R2870:Nell1	UTSW	7	49,899,405 (GRCm39)	intron	probably benign
R2871:Nell1	UTSW	7	49,899,405 (GRCm39)	intron	probably benign
R3498:Nell1	UTSW	7	49,907,927 (GRCm39)	missense	possibly damaging	0.55
R4044:Nell1	UTSW	7	49,869,367 (GRCm39)	missense	probably damaging	1.00
R4623:Nell1	UTSW	7	49,770,310 (GRCm39)	missense	possibly damaging	0.84
R4732:Nell1	UTSW	7	50,505,965 (GRCm39)	missense	probably damaging	1.00
R4733:Nell1	UTSW	7	50,505,965 (GRCm39)	missense	probably damaging	1.00
R4941:Nell1	UTSW	7	49,712,386 (GRCm39)	missense	probably benign	0.10
R4942:Nell1	UTSW	7	49,770,397 (GRCm39)	missense	possibly damaging	0.84
R5233:Nell1	UTSW	7	49,826,062 (GRCm39)	missense	probably damaging	0.99
R5590:Nell1	UTSW	7	49,929,359 (GRCm39)	missense	probably damaging	1.00
R5673:Nell1	UTSW	7	49,878,594 (GRCm39)	missense	probably damaging	0.99
R5741:Nell1	UTSW	7	50,210,638 (GRCm39)	splice site	probably null
R6345:Nell1	UTSW	7	49,625,171 (GRCm39)	missense	possibly damaging	0.91
R6916:Nell1	UTSW	7	50,350,927 (GRCm39)	missense	probably benign	0.00
R7051:Nell1	UTSW	7	50,098,592 (GRCm39)	missense	unknown
R7302:Nell1	UTSW	7	50,506,017 (GRCm39)	missense	probably benign
R7339:Nell1	UTSW	7	49,929,297 (GRCm39)	missense	probably benign	0.01
R7831:Nell1	UTSW	7	49,632,548 (GRCm39)	missense	possibly damaging	0.85
R7913:Nell1	UTSW	7	49,929,270 (GRCm39)	missense	possibly damaging	0.93
R8094:Nell1	UTSW	7	49,770,335 (GRCm39)	missense	probably benign	0.02
R8191:Nell1	UTSW	7	50,098,622 (GRCm39)	missense	unknown
R8207:Nell1	UTSW	7	49,869,760 (GRCm39)	splice site	probably null
R8292:Nell1	UTSW	7	49,907,995 (GRCm39)	missense	probably damaging	1.00
R8340:Nell1	UTSW	7	49,870,021 (GRCm39)	missense	probably damaging	0.98
R8673:Nell1	UTSW	7	49,869,343 (GRCm39)	missense	probably damaging	1.00
R8821:Nell1	UTSW	7	50,476,097 (GRCm39)	missense	probably damaging	0.98
R8987:Nell1	UTSW	7	50,498,399 (GRCm39)	missense	probably damaging	1.00
R8988:Nell1	UTSW	7	50,210,543 (GRCm39)	missense	unknown
R9095:Nell1	UTSW	7	50,506,150 (GRCm39)	missense	possibly damaging	0.92
R9300:Nell1	UTSW	7	49,712,368 (GRCm39)	missense	probably benign
R9370:Nell1	UTSW	7	49,770,292 (GRCm39)	missense	probably damaging	1.00
R9422:Nell1	UTSW	7	49,712,387 (GRCm39)	nonsense	probably null
R9428:Nell1	UTSW	7	50,503,683 (GRCm39)	missense	probably damaging	1.00
R9445:Nell1	UTSW	7	49,632,474 (GRCm39)	missense	possibly damaging	0.78
Z1176:Nell1	UTSW	7	50,210,630 (GRCm39)	missense	unknown

Nature of Mutation

DNA sequencing using the SOLiD technique identified an A to G transition at position 1136 of the Nell1 transcript in exon 11 of 20 total exons. Multiple transcripts of the Nell1 gene are displayed on Ensembl and Vega. The mutated nucleotide causes a glutamic acid to glycine substitution at amino acid 366 of the encoded protein. The mutation has been confirmed by DNA sequencing using the Sanger method (Figure 1).

Protein Function and Prediction

The Nell1 gene encodes an 810 amino acid secreted protein involved in the control of cell growth and differentiation. NELL1 may form a homotrimer and bind to protein kinase C beta (PKCbeta; see the record for Untied). The protein contains six epidermal growth factor (EGF)-like repeats, one TSP N-terminal domain at residues 81-230 and five VWFC (von Willebrand factor type C) domains (Uniprot Q2VWQ2). Homozygous mice display perinatal lethality, respiratory failure, impaired development of the intervertebral disks, vertebrae and calvarial bones, increased skull length, and abnormal curvature of the spine.

The E366G change occurs in the second VWFC domain, and is predicted to be possibly damaging by the PolyPhen program.

Posted On

2010-06-24