Incidental Mutation '0152:Adck1'
ID |
11 |
Institutional Source |
Beutler Lab
|
Gene Symbol |
Adck1
|
Ensembl Gene |
ENSMUSG00000021044 |
Gene Name |
aarF domain containing kinase 1 |
Synonyms |
2610005A10Rik |
Accession Numbers |
|
Essential gene? |
Non essential
(E-score: 0.000)
|
Stock # |
0152
of strain
feeble
|
Quality Score |
|
Status
|
Validated
|
Chromosome |
12 |
Chromosomal Location |
88327324-88428494 bp(+) (GRCm39) |
Type of Mutation |
missense |
DNA Base Change (assembly) |
A to T
at 88397921 bp (GRCm39)
|
Zygosity |
Heterozygous |
Amino Acid Change |
Glutamine to Leucine
at position 185
(Q185L)
|
Ref Sequence |
ENSEMBL: ENSMUSP00000152821
(fasta)
|
Gene Model |
predicted gene model for transcript(s):
[ENSMUST00000101165]
[ENSMUST00000166940]
[ENSMUST00000222695]
|
AlphaFold |
Q9D0L4 |
Predicted Effect |
probably benign
Transcript: ENSMUST00000101165
AA Change: Q185L
PolyPhen 2
Score 0.034 (Sensitivity: 0.95; Specificity: 0.82)
|
SMART Domains |
Protein: ENSMUSP00000098724 Gene: ENSMUSG00000021044 AA Change: Q185L
Domain | Start | End | E-Value | Type |
signal peptide
|
1 |
17 |
N/A |
INTRINSIC |
low complexity region
|
35 |
48 |
N/A |
INTRINSIC |
Pfam:ABC1
|
136 |
252 |
1.7e-42 |
PFAM |
Pfam:Pkinase
|
150 |
348 |
1.3e-5 |
PFAM |
low complexity region
|
498 |
508 |
N/A |
INTRINSIC |
|
Predicted Effect |
probably benign
Transcript: ENSMUST00000166940
AA Change: Q185L
PolyPhen 2
Score 0.034 (Sensitivity: 0.95; Specificity: 0.82)
|
SMART Domains |
Protein: ENSMUSP00000127254 Gene: ENSMUSG00000021044 AA Change: Q185L
Domain | Start | End | E-Value | Type |
signal peptide
|
1 |
17 |
N/A |
INTRINSIC |
low complexity region
|
35 |
48 |
N/A |
INTRINSIC |
Pfam:ABC1
|
136 |
252 |
2.2e-42 |
PFAM |
Pfam:Pkinase
|
150 |
357 |
6.2e-6 |
PFAM |
low complexity region
|
498 |
508 |
N/A |
INTRINSIC |
|
Predicted Effect |
noncoding transcript
Transcript: ENSMUST00000222124
|
Predicted Effect |
probably benign
Transcript: ENSMUST00000222695
AA Change: Q185L
PolyPhen 2
Score 0.034 (Sensitivity: 0.95; Specificity: 0.82)
|
Predicted Effect |
noncoding transcript
Transcript: ENSMUST00000223538
|
Meta Mutation Damage Score |
0.2550 |
Coding Region Coverage |
|
Validation Efficiency |
83% (65/78) |
Allele List at MGI |
All alleles(1) : Gene trapped(1) |
Other mutations in this stock |
Total: 6 list
Gene | Ref | Var | Chr/Loc | Mutation | Predicted Effect | Zygosity |
Fscn3 |
A |
G |
6: 28,429,966 (GRCm39) |
|
probably benign |
Homo |
Per1 |
T |
G |
11: 68,994,848 (GRCm39) |
|
probably benign |
Het |
Pkhd1 |
A |
C |
1: 20,593,118 (GRCm39) |
I1665S |
possibly damaging |
Het |
Tnrc6a |
C |
A |
7: 122,779,877 (GRCm39) |
P1303T |
probably damaging |
Het |
Usp47 |
T |
C |
7: 111,655,784 (GRCm39) |
Y154H |
probably damaging |
Het |
Zfp952 |
T |
A |
17: 33,222,195 (GRCm39) |
|
probably null |
Het |
|
Other mutations in Adck1 |
Allele | Source | Chr | Coord | Type | Predicted Effect | PPH Score |
IGL00501:Adck1
|
APN |
12 |
88,335,192 (GRCm39) |
missense |
probably benign |
0.00 |
IGL00822:Adck1
|
APN |
12 |
88,422,286 (GRCm39) |
missense |
probably damaging |
0.99 |
IGL01370:Adck1
|
APN |
12 |
88,423,503 (GRCm39) |
splice site |
probably benign |
|
IGL01480:Adck1
|
APN |
12 |
88,423,635 (GRCm39) |
nonsense |
probably null |
|
IGL01994:Adck1
|
APN |
12 |
88,397,926 (GRCm39) |
missense |
possibly damaging |
0.50 |
IGL02089:Adck1
|
APN |
12 |
88,413,480 (GRCm39) |
missense |
probably damaging |
0.96 |
IGL03058:Adck1
|
APN |
12 |
88,425,900 (GRCm39) |
missense |
probably benign |
|
IGL03196:Adck1
|
APN |
12 |
88,397,885 (GRCm39) |
missense |
probably damaging |
1.00 |
IGL03307:Adck1
|
APN |
12 |
88,425,823 (GRCm39) |
missense |
possibly damaging |
0.94 |
full-figured
|
UTSW |
12 |
88,407,887 (GRCm39) |
missense |
possibly damaging |
0.63 |
R0107:Adck1
|
UTSW |
12 |
88,413,426 (GRCm39) |
missense |
possibly damaging |
0.62 |
R0164:Adck1
|
UTSW |
12 |
88,422,280 (GRCm39) |
missense |
probably damaging |
0.99 |
R0164:Adck1
|
UTSW |
12 |
88,422,280 (GRCm39) |
missense |
probably damaging |
0.99 |
R0179:Adck1
|
UTSW |
12 |
88,425,942 (GRCm39) |
missense |
possibly damaging |
0.91 |
R0505:Adck1
|
UTSW |
12 |
88,338,461 (GRCm39) |
splice site |
probably benign |
|
R0561:Adck1
|
UTSW |
12 |
88,335,204 (GRCm39) |
missense |
possibly damaging |
0.49 |
R0831:Adck1
|
UTSW |
12 |
88,335,118 (GRCm39) |
start codon destroyed |
probably null |
1.00 |
R1005:Adck1
|
UTSW |
12 |
88,368,872 (GRCm39) |
missense |
probably damaging |
0.98 |
R1524:Adck1
|
UTSW |
12 |
88,368,854 (GRCm39) |
missense |
probably damaging |
1.00 |
R2016:Adck1
|
UTSW |
12 |
88,427,862 (GRCm39) |
missense |
probably damaging |
1.00 |
R4438:Adck1
|
UTSW |
12 |
88,397,920 (GRCm39) |
nonsense |
probably null |
|
R4745:Adck1
|
UTSW |
12 |
88,368,949 (GRCm39) |
splice site |
probably null |
|
R4827:Adck1
|
UTSW |
12 |
88,413,489 (GRCm39) |
missense |
probably benign |
0.06 |
R4859:Adck1
|
UTSW |
12 |
88,407,865 (GRCm39) |
missense |
probably benign |
0.02 |
R4885:Adck1
|
UTSW |
12 |
88,407,865 (GRCm39) |
missense |
probably benign |
0.02 |
R4921:Adck1
|
UTSW |
12 |
88,407,908 (GRCm39) |
missense |
probably benign |
0.10 |
R5383:Adck1
|
UTSW |
12 |
88,422,373 (GRCm39) |
missense |
probably benign |
0.04 |
R5958:Adck1
|
UTSW |
12 |
88,425,822 (GRCm39) |
missense |
probably benign |
0.33 |
R6028:Adck1
|
UTSW |
12 |
88,368,902 (GRCm39) |
missense |
probably benign |
|
R6199:Adck1
|
UTSW |
12 |
88,407,887 (GRCm39) |
missense |
possibly damaging |
0.63 |
R6317:Adck1
|
UTSW |
12 |
88,368,921 (GRCm39) |
missense |
probably damaging |
1.00 |
R6616:Adck1
|
UTSW |
12 |
88,427,958 (GRCm39) |
missense |
unknown |
|
R6715:Adck1
|
UTSW |
12 |
88,425,850 (GRCm39) |
missense |
probably damaging |
1.00 |
R6915:Adck1
|
UTSW |
12 |
88,422,390 (GRCm39) |
missense |
probably damaging |
1.00 |
R7295:Adck1
|
UTSW |
12 |
88,397,815 (GRCm39) |
missense |
probably damaging |
1.00 |
R7387:Adck1
|
UTSW |
12 |
88,427,822 (GRCm39) |
missense |
probably benign |
|
R7520:Adck1
|
UTSW |
12 |
88,425,975 (GRCm39) |
critical splice donor site |
probably null |
|
R7562:Adck1
|
UTSW |
12 |
88,335,203 (GRCm39) |
missense |
possibly damaging |
0.77 |
R7745:Adck1
|
UTSW |
12 |
88,423,570 (GRCm39) |
missense |
probably benign |
|
R7759:Adck1
|
UTSW |
12 |
88,368,887 (GRCm39) |
missense |
possibly damaging |
0.65 |
R8092:Adck1
|
UTSW |
12 |
88,427,831 (GRCm39) |
missense |
possibly damaging |
0.68 |
R8336:Adck1
|
UTSW |
12 |
88,335,249 (GRCm39) |
missense |
probably damaging |
1.00 |
R9145:Adck1
|
UTSW |
12 |
88,335,193 (GRCm39) |
missense |
probably benign |
0.00 |
R9443:Adck1
|
UTSW |
12 |
88,338,550 (GRCm39) |
critical splice donor site |
probably null |
|
|
Nature of Mutation |
DNA sequencing using the SOLiD technique identified an A to T transversion at position 737 of the Adck1 transcript, in exon 5 of 11 total exons (Figure 1).
721 CCGAAGGTTCAGGCTCAAAGCTCTAAGGACATT
180 -P--K--V--Q--A--Q--S--S--K--D--I-
The mutated nucleotide is indicated in red lettering, and causes a glutamine to leucine substitution at amino acid 185 of the encoded protein. The mutation has been confirmed by DNA sequencing using the Sanger method (Figure 2).
|
Protein Function and Prediction |
Adck1 is an uncharacterized gene with evidence at the transcript level for the existence of the encoded protein (Uniprot Q9D0L4). The predicted 525 amino acid protein contains a protein kinase domain, but it is not known if the protein has protein kinase activity or what type of substrate it would phosphorylate. Mammals contain five ADCK proteins that are proposed to belong to the “atypical kinases” of the protein-kinase-like superfamily (1). The protein kinase domain of ADCK1 occurs at amino acids 148-477, with the active loop involved in nucleotide binding and phosphoryl transfer occurring at residues 154-162. The ATP-binding lysine and canonical proton-accepting aspartic acid are found at amino acids 176 and 308, respectively (2). 3D structure of a protein kinase domain is depicted in Figure 3 ( NCBI cl09925).
The predicted kinase also shows similarity to the ABC1 protein found in yeast and the AarF and UbiB proteins from bacteria (1;3;4). The region of homology overlaps with the protein kinase domain and occurs at amino acids 136-252. These proteins are suggested to have chaperonin activity.
By sequence homology, the first 17 amino acids are a signal peptide suggesting that the ADCK1 protein is processed to a mature form. ADCK1 is predicted to have another isoform produced by alternative splicing. This isoform would be missing amino acids 1-192 (Uniprot Q9D0L4).
The Q185L alteration in ADCK1 occurs in the kinase domain (Figure 3), and is predicted to be possibly damaging by the PolyPhen program.
|
References |
1. Lagier-Tourenne, C., Tazir, M., Lopez, L. C., Quinzii, C. M., Assoum, M., Drouot, N., Busso, C., Makri, S., Ali-Pacha, L., Benhassine, T., Anheim, M., Lynch, D. R., Thibault, C., Plewniak, F., Bianchetti, L., Tranchant, C., Poch, O., DiMauro, S., Mandel, J. L., Barros, M. H., Hirano, M., and Koenig, M. (2008) ADCK3, an Ancestral Kinase, is Mutated in a Form of Recessive Ataxia Associated with Coenzyme Q10 Deficiency. Am. J. Hum. Genet. 82, 661-672.
|
Posted On |
2009-11-03 |