Incidental Mutation 'P0018:Nell1'
ID |
7742 |
Institutional Source |
Beutler Lab
|
Gene Symbol |
Nell1
|
Ensembl Gene |
ENSMUSG00000055409 |
Gene Name |
NEL-like 1 |
Synonyms |
l7R6, B230343H07Rik |
MMRRC Submission |
038271-MU
|
Accession Numbers |
|
Essential gene? |
Essential
(E-score: 1.000)
|
Stock # |
P0018 (G1)
|
Quality Score |
|
Status
|
Validated
|
Chromosome |
7 |
Chromosomal Location |
49625098-50513037 bp(+) (GRCm39) |
Type of Mutation |
missense |
DNA Base Change (assembly) |
A to G
at 49770439 bp (GRCm39)
|
Zygosity |
Heterozygous |
Amino Acid Change |
Aspartic acid to Glycine
at position 166
(D166G)
|
Ref Sequence |
ENSEMBL: ENSMUSP00000103229
(fasta)
|
Gene Model |
predicted gene model for transcript(s):
[ENSMUST00000081872]
[ENSMUST00000107603]
[ENSMUST00000151721]
|
AlphaFold |
Q2VWQ2 |
Predicted Effect |
probably damaging
Transcript: ENSMUST00000081872
AA Change: D166G
PolyPhen 2
Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)
|
SMART Domains |
Protein: ENSMUSP00000080550 Gene: ENSMUSG00000055409 AA Change: D166G
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 damaging
Transcript: ENSMUST00000107603
AA Change: D166G
PolyPhen 2
Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)
|
SMART Domains |
Protein: ENSMUSP00000103229 Gene: ENSMUSG00000055409 AA Change: D166G
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 damaging
Transcript: ENSMUST00000151721
AA Change: D166G
PolyPhen 2
Score 0.999 (Sensitivity: 0.14; Specificity: 0.99)
|
SMART Domains |
Protein: ENSMUSP00000114706 Gene: ENSMUSG00000055409 AA Change: D166G
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 |
|
Predicted Effect |
noncoding transcript
Transcript: ENSMUST00000154410
|
Meta Mutation Damage Score |
0.8339 |
Coding Region Coverage |
- 1x: 83.8%
- 3x: 77.4%
- 10x: 57.9%
- 20x: 38.3%
|
Validation Efficiency |
72% (76/106) |
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: 14 list
Gene | Ref | Var | Chr/Loc | Mutation | Predicted Effect | Zygosity |
AAdacl4fm3 |
A |
T |
4: 144,429,767 (GRCm39) |
D407E |
probably benign |
Het |
Brip1 |
C |
T |
11: 85,999,694 (GRCm39) |
V763I |
possibly damaging |
Het |
Cspg4b |
A |
G |
13: 113,504,040 (GRCm39) |
D1723G |
possibly damaging |
Het |
Cxxc1 |
C |
T |
18: 74,353,992 (GRCm39) |
R593C |
probably damaging |
Het |
Erbb4 |
T |
A |
1: 68,110,835 (GRCm39) |
M993L |
probably benign |
Het |
Ftsj3 |
C |
A |
11: 106,145,634 (GRCm39) |
M66I |
possibly damaging |
Het |
Galnt2 |
T |
A |
8: 125,063,350 (GRCm39) |
Y357N |
probably damaging |
Het |
Hgsnat |
C |
T |
8: 26,458,382 (GRCm39) |
|
probably benign |
Het |
Katna1 |
A |
T |
10: 7,617,223 (GRCm39) |
T72S |
probably damaging |
Het |
Nlgn1 |
G |
T |
3: 25,490,741 (GRCm39) |
P329T |
probably damaging |
Het |
Pclo |
A |
T |
5: 14,727,735 (GRCm39) |
|
probably benign |
Het |
Robo2 |
T |
C |
16: 73,843,694 (GRCm39) |
I174V |
possibly damaging |
Het |
Sufu |
A |
G |
19: 46,463,933 (GRCm39) |
|
probably benign |
Het |
Tmub1 |
C |
A |
5: 24,651,755 (GRCm39) |
A55S |
possibly 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 |
|
D6062:Nell1
|
UTSW |
7 |
49,907,939 (GRCm39) |
missense |
probably benign |
0.21 |
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 |
Multiple transcripts of the Nell1 gene are displayed on Ensembl and Vega.
|
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). Loss of Nell1 expression results in the downregulation of several genes that encode extracellular matrix proteins such as collagens, thrombospondins, tenascins and matrilins; these proteins are essential for cell adhesion and communication as well as tissue strength and flexibility (2). Characterization of a mouse model with reduction in Nell1 expression indicates that Nell1 is involved in intramembranous and endochondral ossification during early mammalian development (2).
|
Expression/Localization |
NELL1 is expressed primarily in human adult and fetal brain and kidney tissues (3). In the adult mouse, Nell1 is expressed primarily in the brain (2). At sites of premature suture fusion in craniosynostosis, a congenital craniofacial deformity, NELL1 is localized primarily to the mesenchymal cells and osteoblastic cells at the osteogenic front, along the parasutural bone margins, and within the condensing mesenchymal cells of newly formed bone in sutural sites (4). NELL1 is preferentially expressed in cranial intramembranous bone and neural tissue, which are both of neural crest cell origin.
|
Background |
Nell1l7R6-6R/l7R6-6R; MGI:3626314
Not Specified
This is an ENU-induced point mutation that converts a cysteine to a premature stop codon; the Nell1 transcripts are reduced (2). 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 (2). These mice display considerable reduction in the amount of extracellular material surrounding cells in the developing vertebral bone and intervertebral discs, compared with the wild-type controls (2). In addition, histology data suggested lesser degree of bone and cartilage development in mutant animals (2).
|
References |
1. Zhang, X., Carpenter, D., Bokui, N., Soo, C., Miao, S., Truong, T., Wu, B., Chen, I., Vastardis, H., Tanizawa, K., Kuroda, S., and Ting, K. (2003) Overexpression of Nell-1, a Craniosynostosis-Associated Gene, Induces Apoptosis in Osteoblasts during Craniofacial Development. J Bone Miner Res. 18, 2126-2134.
2. Desai, J., Shannon, M. E., Johnson, M. D., Ruff, D. W., Hughes, L. A., Kerley, M. K., Carpenter, D. A., Johnson, D. K., Rinchik, E. M., and Culiat, C. T. (2006) Nell1-Deficient Mice have Reduced Expression of Extracellular Matrix Proteins Causing Cranial and Vertebral Defects. Hum Mol Genet. 15, 1329-1341.
3. Watanabe, T. K., Katagiri, T., Suzuki, M., Shimizu, F., Fujiwara, T., Kanemoto, N., Nakamura, Y., Hirai, Y., Maekawa, H., and Takahashi, E. (1996) Cloning and Characterization of Two Novel Human cDNAs (NELL1 and NELL2) Encoding Proteins with Six EGF-Like Repeats. Genomics. 38, 273-276.
4. Ting, K., Vastardis, H., Mulliken, J. B., Soo, C., Tieu, A., Do, H., Kwong, E., Bertolami, C. N., Kawamoto, H., Kuroda, S., and Longaker, M. T. (1999) Human NELL-1 Expressed in Unilateral Coronal Synostosis. J Bone Miner Res. 14, 80-89.
|
Posted On |
2012-10-29 |
Science Writer |
Anne Murray |