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) question?
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

DomainStartEndE-ValueType
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

DomainStartEndE-ValueType
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 question?
Coding Region Coverage
  • 1x: 77.9%
  • 3x: 41.0%
Validation Efficiency 83% (65/78)
Allele List at MGI

All alleles(1) : Gene trapped(1)

Other mutations in this stock
Total: 6 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
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
AlleleSourceChrCoordTypePredicted EffectPPH 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
Posted On 2009-11-03