Incidental Mutation 'P0014:Nek1'
ID |
7607 |
Institutional Source |
Beutler Lab
|
Gene Symbol |
Nek1
|
Ensembl Gene |
ENSMUSG00000031644 |
Gene Name |
NIMA (never in mitosis gene a)-related expressed kinase 1 |
Synonyms |
kat, D8Ertd790e, kidney, anemia and testis |
MMRRC Submission |
038267-MU
|
Accession Numbers |
|
Essential gene? |
Non essential
(E-score: 0.000)
|
Stock # |
P0014 (G1)
|
Quality Score |
|
Status
|
Validated
|
Chromosome |
8 |
Chromosomal Location |
61446229-61584380 bp(+) (GRCm39) |
Type of Mutation |
splice site |
DNA Base Change (assembly) |
A to T
at 61524781 bp (GRCm39)
|
Zygosity |
Heterozygous |
Amino Acid Change |
|
Ref Sequence |
ENSEMBL: ENSMUSP00000147809
(fasta)
|
Gene Model |
predicted gene model for transcript(s):
[ENSMUST00000034065]
[ENSMUST00000120689]
[ENSMUST00000211256]
[ENSMUST00000211672]
|
AlphaFold |
P51954 |
Predicted Effect |
probably benign
Transcript: ENSMUST00000034065
|
SMART Domains |
Protein: ENSMUSP00000034065 Gene: ENSMUSG00000031644
Domain | Start | End | E-Value | Type |
S_TKc
|
4 |
258 |
4.23e-95 |
SMART |
Blast:S_TKc
|
266 |
303 |
3e-7 |
BLAST |
low complexity region
|
321 |
337 |
N/A |
INTRINSIC |
coiled coil region
|
372 |
402 |
N/A |
INTRINSIC |
coiled coil region
|
556 |
592 |
N/A |
INTRINSIC |
coiled coil region
|
647 |
685 |
N/A |
INTRINSIC |
low complexity region
|
767 |
780 |
N/A |
INTRINSIC |
low complexity region
|
1130 |
1141 |
N/A |
INTRINSIC |
|
Predicted Effect |
probably benign
Transcript: ENSMUST00000120689
|
SMART Domains |
Protein: ENSMUSP00000113932 Gene: ENSMUSG00000031644
Domain | Start | End | E-Value | Type |
S_TKc
|
4 |
258 |
4.23e-95 |
SMART |
Blast:S_TKc
|
266 |
303 |
3e-7 |
BLAST |
low complexity region
|
321 |
337 |
N/A |
INTRINSIC |
coiled coil region
|
372 |
402 |
N/A |
INTRINSIC |
coiled coil region
|
487 |
510 |
N/A |
INTRINSIC |
low complexity region
|
521 |
533 |
N/A |
INTRINSIC |
coiled coil region
|
584 |
620 |
N/A |
INTRINSIC |
coiled coil region
|
675 |
713 |
N/A |
INTRINSIC |
low complexity region
|
795 |
808 |
N/A |
INTRINSIC |
low complexity region
|
1158 |
1169 |
N/A |
INTRINSIC |
|
Predicted Effect |
noncoding transcript
Transcript: ENSMUST00000142601
|
SMART Domains |
Protein: ENSMUSP00000121479 Gene: ENSMUSG00000031644
Domain | Start | End | E-Value | Type |
low complexity region
|
38 |
47 |
N/A |
INTRINSIC |
coiled coil region
|
162 |
198 |
N/A |
INTRINSIC |
|
Predicted Effect |
noncoding transcript
Transcript: ENSMUST00000155664
|
Predicted Effect |
noncoding transcript
Transcript: ENSMUST00000209845
|
Predicted Effect |
probably benign
Transcript: ENSMUST00000211256
|
Predicted Effect |
probably benign
Transcript: ENSMUST00000211672
|
Coding Region Coverage |
- 1x: 85.4%
- 3x: 80.7%
- 10x: 66.7%
- 20x: 50.4%
|
Validation Efficiency |
95% (100/105) |
MGI Phenotype |
FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] The protein encoded by this gene is a serine/threonine kinase involved in cell cycle regulation. The encoded protein is found in a centrosomal complex with FEZ1, a neuronal protein that plays a role in axonal development. Defects in this gene are a cause of polycystic kidney disease (PKD). Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2010] PHENOTYPE: Spontaneous mutations of this gene result in pleiotropic effects that include facial dysmorphism, dwarfism, male sterility, anemia, cystic choroid plexus, a late-onset slowly progressive polycystic kidney disease, and premature death. Postnatal survival is sensitive to genetic background. [provided by MGI curators]
|
Allele List at MGI |
All alleles(4) : Targeted(1) Gene trapped(1) Spontaneous(2)
|
Other mutations in this stock |
Total: 19 list
Gene | Ref | Var | Chr/Loc | Mutation | Predicted Effect | Zygosity |
Abcb4 |
A |
G |
5: 9,000,083 (GRCm39) |
Y1017C |
probably benign |
Het |
Acly |
T |
C |
11: 100,375,430 (GRCm39) |
I787V |
probably benign |
Het |
Aldob |
T |
C |
4: 49,538,153 (GRCm39) |
Q325R |
probably benign |
Het |
Armh4 |
C |
T |
14: 49,989,116 (GRCm39) |
E618K |
probably damaging |
Het |
Capns2 |
A |
G |
8: 93,628,842 (GRCm39) |
T244A |
probably damaging |
Het |
Clec16a |
C |
T |
16: 10,378,020 (GRCm39) |
|
probably benign |
Het |
Creb3 |
A |
G |
4: 43,563,265 (GRCm39) |
T121A |
possibly damaging |
Het |
Ddah1 |
A |
G |
3: 145,558,913 (GRCm39) |
D160G |
probably benign |
Het |
Dhx57 |
A |
T |
17: 80,582,620 (GRCm39) |
H328Q |
probably benign |
Het |
Dmxl2 |
A |
C |
9: 54,309,048 (GRCm39) |
L1901R |
probably damaging |
Het |
Dnah5 |
T |
A |
15: 28,403,619 (GRCm39) |
L3448Q |
probably damaging |
Het |
Gcdh |
A |
G |
8: 85,615,154 (GRCm39) |
|
probably null |
Het |
Lrrc8c |
T |
C |
5: 105,755,110 (GRCm39) |
V295A |
probably benign |
Het |
Pkp2 |
C |
T |
16: 16,058,386 (GRCm39) |
P356L |
probably benign |
Het |
Sipa1l3 |
T |
C |
7: 29,082,640 (GRCm39) |
T752A |
probably damaging |
Het |
Slc38a2 |
C |
A |
15: 96,588,042 (GRCm39) |
W494L |
probably damaging |
Het |
Ttn |
T |
C |
2: 76,628,814 (GRCm39) |
D12734G |
probably damaging |
Het |
Uggt2 |
A |
G |
14: 119,281,950 (GRCm39) |
S742P |
probably damaging |
Het |
Vwa3b |
C |
T |
1: 37,212,995 (GRCm39) |
|
probably benign |
Het |
|
Other mutations in Nek1 |
Allele | Source | Chr | Coord | Type | Predicted Effect | PPH Score |
IGL00471:Nek1
|
APN |
8 |
61,496,318 (GRCm39) |
missense |
probably benign |
0.00 |
IGL01075:Nek1
|
APN |
8 |
61,577,166 (GRCm39) |
missense |
possibly damaging |
0.64 |
IGL01122:Nek1
|
APN |
8 |
61,574,000 (GRCm39) |
missense |
possibly damaging |
0.80 |
IGL01151:Nek1
|
APN |
8 |
61,473,111 (GRCm39) |
missense |
probably damaging |
1.00 |
IGL01286:Nek1
|
APN |
8 |
61,577,250 (GRCm39) |
missense |
possibly damaging |
0.64 |
IGL01377:Nek1
|
APN |
8 |
61,542,490 (GRCm39) |
missense |
probably benign |
|
IGL01485:Nek1
|
APN |
8 |
61,502,860 (GRCm39) |
missense |
probably benign |
0.02 |
IGL01688:Nek1
|
APN |
8 |
61,558,631 (GRCm39) |
nonsense |
probably null |
|
IGL01806:Nek1
|
APN |
8 |
61,577,246 (GRCm39) |
missense |
possibly damaging |
0.82 |
IGL02006:Nek1
|
APN |
8 |
61,557,226 (GRCm39) |
missense |
probably benign |
0.20 |
IGL02304:Nek1
|
APN |
8 |
61,465,201 (GRCm39) |
missense |
probably damaging |
1.00 |
IGL02659:Nek1
|
APN |
8 |
61,542,514 (GRCm39) |
missense |
probably benign |
0.16 |
IGL02662:Nek1
|
APN |
8 |
61,557,218 (GRCm39) |
missense |
probably benign |
0.00 |
IGL02801:Nek1
|
APN |
8 |
61,574,095 (GRCm39) |
critical splice donor site |
probably null |
|
IGL02806:Nek1
|
APN |
8 |
61,497,120 (GRCm39) |
missense |
probably benign |
0.15 |
IGL03037:Nek1
|
APN |
8 |
61,487,086 (GRCm39) |
missense |
probably benign |
0.16 |
IGL03252:Nek1
|
APN |
8 |
61,525,364 (GRCm39) |
nonsense |
probably null |
|
R0019:Nek1
|
UTSW |
8 |
61,542,768 (GRCm39) |
missense |
probably benign |
0.01 |
R0403:Nek1
|
UTSW |
8 |
61,559,889 (GRCm39) |
missense |
probably damaging |
0.99 |
R0464:Nek1
|
UTSW |
8 |
61,525,307 (GRCm39) |
splice site |
probably benign |
|
R0726:Nek1
|
UTSW |
8 |
61,542,626 (GRCm39) |
missense |
probably damaging |
1.00 |
R0761:Nek1
|
UTSW |
8 |
61,542,489 (GRCm39) |
missense |
probably benign |
|
R0827:Nek1
|
UTSW |
8 |
61,558,682 (GRCm39) |
splice site |
probably benign |
|
R0972:Nek1
|
UTSW |
8 |
61,542,465 (GRCm39) |
splice site |
probably null |
|
R1268:Nek1
|
UTSW |
8 |
61,475,298 (GRCm39) |
missense |
probably damaging |
1.00 |
R1343:Nek1
|
UTSW |
8 |
61,481,709 (GRCm39) |
missense |
probably damaging |
1.00 |
R1415:Nek1
|
UTSW |
8 |
61,542,720 (GRCm39) |
missense |
probably benign |
0.00 |
R1466:Nek1
|
UTSW |
8 |
61,578,170 (GRCm39) |
splice site |
probably benign |
|
R1480:Nek1
|
UTSW |
8 |
61,577,360 (GRCm39) |
splice site |
probably null |
|
R1526:Nek1
|
UTSW |
8 |
61,502,975 (GRCm39) |
missense |
probably benign |
0.26 |
R1552:Nek1
|
UTSW |
8 |
61,459,771 (GRCm39) |
missense |
probably damaging |
0.99 |
R1606:Nek1
|
UTSW |
8 |
61,577,310 (GRCm39) |
missense |
possibly damaging |
0.82 |
R1650:Nek1
|
UTSW |
8 |
61,489,110 (GRCm39) |
missense |
probably benign |
0.00 |
R1757:Nek1
|
UTSW |
8 |
61,542,847 (GRCm39) |
splice site |
probably null |
|
R1808:Nek1
|
UTSW |
8 |
61,469,264 (GRCm39) |
missense |
probably damaging |
1.00 |
R1966:Nek1
|
UTSW |
8 |
61,469,330 (GRCm39) |
missense |
probably damaging |
1.00 |
R2067:Nek1
|
UTSW |
8 |
61,460,196 (GRCm39) |
missense |
probably damaging |
1.00 |
R2111:Nek1
|
UTSW |
8 |
61,577,360 (GRCm39) |
splice site |
probably null |
|
R2113:Nek1
|
UTSW |
8 |
61,469,327 (GRCm39) |
missense |
probably damaging |
1.00 |
R2143:Nek1
|
UTSW |
8 |
61,481,730 (GRCm39) |
missense |
probably damaging |
1.00 |
R2255:Nek1
|
UTSW |
8 |
61,542,807 (GRCm39) |
missense |
probably damaging |
1.00 |
R2422:Nek1
|
UTSW |
8 |
61,472,935 (GRCm39) |
missense |
probably damaging |
1.00 |
R3848:Nek1
|
UTSW |
8 |
61,525,349 (GRCm39) |
missense |
probably damaging |
0.99 |
R3849:Nek1
|
UTSW |
8 |
61,525,349 (GRCm39) |
missense |
probably damaging |
0.99 |
R3850:Nek1
|
UTSW |
8 |
61,525,349 (GRCm39) |
missense |
probably damaging |
0.99 |
R4418:Nek1
|
UTSW |
8 |
61,559,898 (GRCm39) |
missense |
probably damaging |
1.00 |
R4526:Nek1
|
UTSW |
8 |
61,559,978 (GRCm39) |
missense |
probably damaging |
0.99 |
R4533:Nek1
|
UTSW |
8 |
61,460,247 (GRCm39) |
missense |
possibly damaging |
0.95 |
R4544:Nek1
|
UTSW |
8 |
61,469,338 (GRCm39) |
nonsense |
probably null |
|
R4677:Nek1
|
UTSW |
8 |
61,481,840 (GRCm39) |
missense |
probably damaging |
0.99 |
R4739:Nek1
|
UTSW |
8 |
61,551,545 (GRCm39) |
missense |
probably benign |
0.32 |
R5068:Nek1
|
UTSW |
8 |
61,469,330 (GRCm39) |
missense |
probably damaging |
1.00 |
R5421:Nek1
|
UTSW |
8 |
61,459,711 (GRCm39) |
missense |
possibly damaging |
0.81 |
R5516:Nek1
|
UTSW |
8 |
61,542,523 (GRCm39) |
missense |
probably benign |
0.03 |
R5855:Nek1
|
UTSW |
8 |
61,469,306 (GRCm39) |
missense |
probably damaging |
1.00 |
R6125:Nek1
|
UTSW |
8 |
61,481,735 (GRCm39) |
missense |
probably damaging |
1.00 |
R6267:Nek1
|
UTSW |
8 |
61,525,343 (GRCm39) |
nonsense |
probably null |
|
R6292:Nek1
|
UTSW |
8 |
61,507,770 (GRCm39) |
splice site |
probably null |
|
R6296:Nek1
|
UTSW |
8 |
61,525,343 (GRCm39) |
nonsense |
probably null |
|
R6458:Nek1
|
UTSW |
8 |
61,553,046 (GRCm39) |
missense |
probably benign |
0.00 |
R6568:Nek1
|
UTSW |
8 |
61,559,855 (GRCm39) |
missense |
probably benign |
0.00 |
R6629:Nek1
|
UTSW |
8 |
61,507,367 (GRCm39) |
splice site |
probably null |
|
R6867:Nek1
|
UTSW |
8 |
61,525,364 (GRCm39) |
missense |
possibly damaging |
0.81 |
R7122:Nek1
|
UTSW |
8 |
61,559,829 (GRCm39) |
missense |
probably benign |
0.00 |
R7193:Nek1
|
UTSW |
8 |
61,526,612 (GRCm39) |
missense |
probably damaging |
0.99 |
R7272:Nek1
|
UTSW |
8 |
61,578,120 (GRCm39) |
missense |
probably benign |
0.34 |
R7356:Nek1
|
UTSW |
8 |
61,573,994 (GRCm39) |
missense |
probably benign |
0.02 |
R7368:Nek1
|
UTSW |
8 |
61,542,741 (GRCm39) |
missense |
probably benign |
0.24 |
R7478:Nek1
|
UTSW |
8 |
61,583,179 (GRCm39) |
missense |
probably benign |
0.03 |
R7479:Nek1
|
UTSW |
8 |
61,583,179 (GRCm39) |
missense |
probably benign |
0.03 |
R7512:Nek1
|
UTSW |
8 |
61,583,179 (GRCm39) |
missense |
probably benign |
0.03 |
R7715:Nek1
|
UTSW |
8 |
61,459,794 (GRCm39) |
missense |
probably damaging |
0.98 |
R7984:Nek1
|
UTSW |
8 |
61,574,087 (GRCm39) |
nonsense |
probably null |
|
R8271:Nek1
|
UTSW |
8 |
61,558,646 (GRCm39) |
missense |
probably benign |
0.04 |
R8431:Nek1
|
UTSW |
8 |
61,487,066 (GRCm39) |
missense |
possibly damaging |
0.95 |
R9076:Nek1
|
UTSW |
8 |
61,481,768 (GRCm39) |
missense |
probably damaging |
0.96 |
R9149:Nek1
|
UTSW |
8 |
61,574,055 (GRCm39) |
missense |
probably damaging |
1.00 |
R9250:Nek1
|
UTSW |
8 |
61,465,151 (GRCm39) |
missense |
probably damaging |
0.99 |
R9429:Nek1
|
UTSW |
8 |
61,559,892 (GRCm39) |
missense |
probably benign |
|
R9563:Nek1
|
UTSW |
8 |
61,577,157 (GRCm39) |
missense |
probably benign |
0.36 |
R9616:Nek1
|
UTSW |
8 |
61,473,107 (GRCm39) |
missense |
probably damaging |
0.99 |
RF023:Nek1
|
UTSW |
8 |
61,525,779 (GRCm39) |
splice site |
probably null |
|
X0028:Nek1
|
UTSW |
8 |
61,496,292 (GRCm39) |
missense |
probably benign |
0.19 |
X0066:Nek1
|
UTSW |
8 |
61,578,162 (GRCm39) |
critical splice donor site |
probably null |
|
|
Protein Function and Prediction |
NEK1 is a serine/threonine kinase that functions in cell cycle control and cilia regulation [(1); OMIM *604588]. NEK1 is proposed to function in DNA double-strand repair (2), neuronal development (3), and coordination of cell cycle-associated ciliogenesis (1).
|
Expression/Localization |
RT-PCR ELISA detected highest expression of NEK1 in the adult spinal cord, ovary, and kidney; moderate expression was observed in the other tissues (both adult and fetal) (4).
|
Background |
Mutations in NEK1 can cause short rib-polydactyly syndrome, type II (OMIM #263520), an autosomal recessive lethal condition characterized by short ribs, short limbs, polydactyly, and multiple anomalies of major organs, including heart, intestines, genitalia, kidney, liver, and pancreas (5).
Nek1kat/kat; MGI:1858030
B6.RBF(C3Fe)-Nek1kat/J
By generation N5 on the C57BL/6J background half of the homozygotes die before weaning (6). These mice also have decreased body size (dwarfing) and a domed cranium (6).
Nek1kat/kat; MGI:1858030
C3HeB/FeJLe * C57BL/6J * RBF/Dn
Only 22% of the homozygotes survive beyond 1 year (7). These mice also have abnormal renal tubule morphology, kidney cysts, polycystic kidney, hydrocephaly, craniofacial abnormalities, anemia, decreased body size, and abnormal olfactory bulb morphology (6;7).
Nek1kat/kat; MGI:1858030
involves: C3HeB/FeJLe * RBF/Dn
Homozygotes on this genetic background survive to adulthood, but still have a shortened lifespan (6). These mice also have reduced female fertility and male infertility (6). These mice also have decreased body size and length (6).
Nek1kat-2J/ kat-2J; MGI:1858122
C57BL/6J-Nek1kat-2J/J
Homozygotes exhibit premature death by 1 year (7). These mice also have abnormal renal tubule morphology (1), kidney cysts (6), polycystic kidney (6;7), hydrocephaly (6), craniofacial abnormalities (6), anemia (6;7), and decreased body size (7).
|
References |
2. Polci, R., Peng, A., Chen, P. L., Riley, D. J., and Chen, Y. (2004) NIMA-Related Protein Kinase 1 is Involved Early in the Ionizing Radiation-Induced DNA Damage Response. Cancer Res. 64, 8800-8803.
5. Thiel, C., Kessler, K., Giessl, A., Dimmler, A., Shalev, S. A., von der Haar, S., Zenker, M., Zahnleiter, D., Stoss, H., Beinder, E., Abou Jamra, R., Ekici, A. B., Schroder-Kress, N., Aigner, T., Kirchner, T., Reis, A., Brandstatter, J. H., and Rauch, A. (2011) NEK1 Mutations Cause Short-Rib Polydactyly Syndrome Type Majewski. Am J Hum Genet. 88, 106-114.
6. Janaswami, P. M., Birkenmeier, E. H., Cook, S. A., Rowe, L. B., Bronson, R. T., and Davisson, M. T. (1997) Identification and Genetic Mapping of a New Polycystic Kidney Disease on Mouse Chromosome 8. Genomics. 40, 101-107.
7. Vogler, C., Homan, S., Pung, A., Thorpe, C., Barker, J., Birkenmeier, E. H., and Upadhya, P. (1999) Clinical and Pathologic Findings in Two New Allelic Murine Models of Polycystic Kidney Disease. J Am Soc Nephrol. 10, 2534-2539.
|
Posted On |
2012-10-05 |
Science Writer |
Anne Murray |