Incidental Mutation 'R0799:Cdk4'
| ID |
76539 |
| Institutional Source |
Beutler Lab
|
| Gene Symbol |
Cdk4
|
| Ensembl Gene |
ENSMUSG00000006728 |
| Gene Name |
cyclin dependent kinase 4 |
| Synonyms |
Crk3, p34/cdk4 |
| MMRRC Submission |
038979-MU
|
| Accession Numbers |
|
| Essential gene? |
Probably essential
(E-score: 0.914)
|
| Stock # |
R0799 (G1)
|
| Quality Score |
225 |
|
Status
|
Validated
|
| Chromosome |
10 |
| Chromosomal Location |
126899404-126903157 bp(+) (GRCm39) |
| Type of Mutation |
missense |
| DNA Base Change (assembly) |
A to G
at 126900863 bp (GRCm39)
|
| Zygosity |
Heterozygous |
| Amino Acid Change |
Threonine to Alanine
at position 172
(T172A)
|
| Ref Sequence |
ENSEMBL: ENSMUSP00000117234
(fasta)
|
| Gene Model |
predicted gene model for transcript(s):
[ENSMUST00000006911]
[ENSMUST00000040307]
[ENSMUST00000060991]
[ENSMUST00000120226]
[ENSMUST00000125682]
[ENSMUST00000133115]
[ENSMUST00000142558]
|
| AlphaFold |
P30285 |
| Predicted Effect |
probably damaging
Transcript: ENSMUST00000006911
AA Change: T172A
PolyPhen 2
Score 0.982 (Sensitivity: 0.75; Specificity: 0.96)
|
| SMART Domains |
Protein: ENSMUSP00000006911
Gene: ENSMUSG00000006728
AA Change: T172A
| Domain | Start | End | E-Value | Type |
|---|
|
S_TKc
|
6 |
295 |
9.2e-96 |
SMART |
|
| Predicted Effect |
probably benign
Transcript: ENSMUST00000040307
|
| SMART Domains |
Protein: ENSMUSP00000041581
Gene: ENSMUSG00000040502
| Domain | Start | End | E-Value | Type |
|---|
|
low complexity region
|
20 |
45 |
N/A |
INTRINSIC |
|
low complexity region
|
50 |
60 |
N/A |
INTRINSIC |
|
low complexity region
|
76 |
105 |
N/A |
INTRINSIC |
|
RINGv
|
109 |
156 |
7.51e-18 |
SMART |
|
transmembrane domain
|
183 |
205 |
N/A |
INTRINSIC |
|
Blast:AAA
|
211 |
238 |
2e-9 |
BLAST |
|
low complexity region
|
267 |
284 |
N/A |
INTRINSIC |
|
low complexity region
|
291 |
302 |
N/A |
INTRINSIC |
|
| Predicted Effect |
probably benign
Transcript: ENSMUST00000060991
|
| SMART Domains |
Protein: ENSMUSP00000057751
Gene: ENSMUSG00000006736
| Domain | Start | End | E-Value | Type |
|---|
|
Pfam:Tetraspannin
|
8 |
200 |
1.2e-19 |
PFAM |
|
| Predicted Effect |
probably benign
Transcript: ENSMUST00000120226
|
| SMART Domains |
Protein: ENSMUSP00000112549
Gene: ENSMUSG00000006728
| Domain | Start | End | E-Value | Type |
|---|
|
Pfam:Pkinase
|
6 |
103 |
6e-10 |
PFAM |
|
low complexity region
|
121 |
138 |
N/A |
INTRINSIC |
|
| Predicted Effect |
noncoding transcript
Transcript: ENSMUST00000123456
|
| Predicted Effect |
probably damaging
Transcript: ENSMUST00000125682
AA Change: T172A
PolyPhen 2
Score 0.982 (Sensitivity: 0.75; Specificity: 0.96)
|
| SMART Domains |
Protein: ENSMUSP00000117234
Gene: ENSMUSG00000006728
AA Change: T172A
| Domain | Start | End | E-Value | Type |
|---|
|
S_TKc
|
6 |
261 |
5.19e-72 |
SMART |
|
| Predicted Effect |
possibly damaging
Transcript: ENSMUST00000133115
AA Change: T172A
PolyPhen 2
Score 0.928 (Sensitivity: 0.81; Specificity: 0.94)
|
| SMART Domains |
Protein: ENSMUSP00000122973
Gene: ENSMUSG00000006728
AA Change: T172A
| Domain | Start | End | E-Value | Type |
|---|
|
S_TKc
|
6 |
250 |
1.55e-70 |
SMART |
|
| Predicted Effect |
noncoding transcript
Transcript: ENSMUST00000145670
|
| Predicted Effect |
noncoding transcript
Transcript: ENSMUST00000140254
|
| Predicted Effect |
noncoding transcript
Transcript: ENSMUST00000135179
|
| Predicted Effect |
probably benign
Transcript: ENSMUST00000142558
|
| SMART Domains |
Protein: ENSMUSP00000116190
Gene: ENSMUSG00000006728
| Domain | Start | End | E-Value | Type |
|---|
|
Pfam:Pkinase
|
6 |
74 |
1.6e-8 |
PFAM |
|
| Predicted Effect |
noncoding transcript
Transcript: ENSMUST00000218603
|
| Predicted Effect |
noncoding transcript
Transcript: ENSMUST00000218488
|
| Predicted Effect |
noncoding transcript
Transcript: ENSMUST00000220344
|
| Predicted Effect |
noncoding transcript
Transcript: ENSMUST00000217875
|
| Meta Mutation Damage Score |
0.8360 |
| Coding Region Coverage |
- 1x: 99.4%
- 3x: 98.8%
- 10x: 97.4%
- 20x: 94.9%
|
| Validation Efficiency |
100% (60/60) |
| 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 member of the Ser/Thr protein kinase family. This protein is highly similar to the gene products of S. cerevisiae cdc28 and S. pombe cdc2. It is a catalytic subunit of the protein kinase complex that is important for cell cycle G1 phase progression. The activity of this kinase is restricted to the G1-S phase, which is controlled by the regulatory subunits D-type cyclins and CDK inhibitor p16(INK4a). This kinase was shown to be responsible for the phosphorylation of retinoblastoma gene product (Rb). Mutations in this gene as well as in its related proteins including D-type cyclins, p16(INK4a) and Rb were all found to be associated with tumorigenesis of a variety of cancers. Multiple polyadenylation sites of this gene have been reported. [provided by RefSeq, Jul 2008]
PHENOTYPE: Homozygous null mutants have small size, insulin-deficient diabetes, sterility in females; near-sterility in males and impaired prolactin secretion due to hypoplastic pituitary development. Locomotor and endocrine gland defects are seen with some alleles. [provided by MGI curators]
|
| Allele List at MGI |
|
| Other mutations in this stock |
Total: 59 list
| Gene | Ref | Var | Chr/Loc | Mutation | Predicted Effect | Zygosity |
|---|
| 4921539E11Rik |
G |
A |
4: 103,100,101 (GRCm39) |
T33I |
possibly damaging |
Het |
| 4930555F03Rik |
A |
G |
8: 49,948,474 (GRCm39) |
|
noncoding transcript |
Het |
| Abcf3 |
T |
C |
16: 20,378,084 (GRCm39) |
L538P |
probably damaging |
Het |
| Adamts6 |
T |
C |
13: 104,450,779 (GRCm39) |
S321P |
probably damaging |
Het |
| Adgra2 |
G |
A |
8: 27,602,523 (GRCm39) |
R362H |
probably damaging |
Het |
| AI597479 |
T |
G |
1: 43,150,330 (GRCm39) |
S147A |
probably benign |
Het |
| Ajm1 |
A |
G |
2: 25,468,574 (GRCm39) |
S446P |
possibly damaging |
Het |
| Ampd3 |
T |
C |
7: 110,399,904 (GRCm39) |
F340L |
probably damaging |
Het |
| Atad3a |
A |
G |
4: 155,831,927 (GRCm39) |
V449A |
probably damaging |
Het |
| Bmal2 |
T |
C |
6: 146,724,751 (GRCm39) |
|
probably benign |
Het |
| Bpifa6 |
A |
T |
2: 153,834,192 (GRCm39) |
D328V |
probably benign |
Het |
| Brca2 |
T |
C |
5: 150,483,658 (GRCm39) |
S2903P |
probably damaging |
Het |
| Cct3 |
A |
T |
3: 88,206,652 (GRCm39) |
|
probably null |
Het |
| Chd5 |
A |
G |
4: 152,468,616 (GRCm39) |
D1760G |
probably damaging |
Het |
| Chd7 |
A |
G |
4: 8,801,310 (GRCm39) |
|
probably benign |
Het |
| Crybb2 |
T |
C |
5: 113,210,037 (GRCm39) |
I109V |
probably benign |
Het |
| Csmd3 |
A |
G |
15: 48,048,780 (GRCm39) |
|
probably benign |
Het |
| Dach1 |
G |
T |
14: 98,406,051 (GRCm39) |
T232K |
possibly damaging |
Het |
| Dnlz |
A |
G |
2: 26,241,485 (GRCm39) |
V81A |
possibly damaging |
Het |
| Epb41l4b |
A |
G |
4: 57,086,003 (GRCm39) |
S191P |
probably damaging |
Het |
| Eps15l1 |
C |
T |
8: 73,099,929 (GRCm39) |
D821N |
probably damaging |
Het |
| Fam186a |
G |
A |
15: 99,839,893 (GRCm39) |
P2117L |
probably damaging |
Het |
| Fam83d |
T |
A |
2: 158,621,808 (GRCm39) |
F173Y |
probably damaging |
Het |
| Gm9116 |
A |
T |
3: 93,817,772 (GRCm39) |
R214S |
probably benign |
Het |
| Gtpbp1 |
A |
G |
15: 79,600,401 (GRCm39) |
I445V |
probably damaging |
Het |
| H2-M2 |
G |
A |
17: 37,793,640 (GRCm39) |
T122I |
probably damaging |
Het |
| Hgd |
C |
T |
16: 37,448,971 (GRCm39) |
|
probably benign |
Het |
| Hip1r |
A |
G |
5: 124,135,004 (GRCm39) |
Y380C |
probably benign |
Het |
| Hspa8 |
G |
A |
9: 40,715,137 (GRCm39) |
G389R |
probably damaging |
Het |
| Htt |
C |
A |
5: 34,975,097 (GRCm39) |
D622E |
probably benign |
Het |
| Iqca1 |
C |
A |
1: 90,070,453 (GRCm39) |
G133V |
probably null |
Het |
| Kdm4a |
A |
G |
4: 118,004,189 (GRCm39) |
|
probably null |
Het |
| Map3k9 |
G |
A |
12: 81,769,043 (GRCm39) |
P1025S |
probably benign |
Het |
| Or8b47 |
G |
A |
9: 38,435,437 (GRCm39) |
M136I |
probably benign |
Het |
| Pabpc1l |
C |
A |
2: 163,873,134 (GRCm39) |
H135N |
probably benign |
Het |
| Pacsin2 |
A |
T |
15: 83,263,998 (GRCm39) |
S346R |
probably benign |
Het |
| Pcdhb20 |
A |
G |
18: 37,638,938 (GRCm39) |
Y488C |
probably damaging |
Het |
| Pkdcc |
G |
A |
17: 83,531,347 (GRCm39) |
C452Y |
probably damaging |
Het |
| Poglut1 |
T |
C |
16: 38,355,083 (GRCm39) |
|
probably null |
Het |
| Prss59 |
A |
G |
6: 40,905,533 (GRCm39) |
M41T |
probably damaging |
Het |
| Pxk |
T |
C |
14: 8,148,123 (GRCm38) |
F409L |
probably benign |
Het |
| Pygm |
G |
A |
19: 6,436,048 (GRCm39) |
|
probably benign |
Het |
| Rabep2 |
T |
C |
7: 126,037,896 (GRCm39) |
S223P |
probably damaging |
Het |
| Rpp40 |
C |
T |
13: 36,086,034 (GRCm39) |
R109H |
probably benign |
Het |
| Sbf2 |
T |
C |
7: 109,940,562 (GRCm39) |
Y1266C |
possibly damaging |
Het |
| Slc5a4a |
T |
C |
10: 76,012,368 (GRCm39) |
V346A |
probably benign |
Het |
| Smpd3 |
G |
T |
8: 106,991,421 (GRCm39) |
H377Q |
possibly damaging |
Het |
| Sppl2a |
C |
A |
2: 126,762,227 (GRCm39) |
|
probably benign |
Het |
| Tas2r134 |
T |
C |
2: 51,518,385 (GRCm39) |
I288T |
probably benign |
Het |
| Trim35 |
T |
A |
14: 66,546,650 (GRCm39) |
H472Q |
probably damaging |
Het |
| Trpm5 |
C |
A |
7: 142,632,088 (GRCm39) |
R907L |
probably damaging |
Het |
| Ube2e2 |
G |
T |
14: 18,630,393 (GRCm38) |
S56* |
probably null |
Het |
| Vmn2r88 |
A |
C |
14: 51,651,959 (GRCm39) |
R432S |
possibly damaging |
Het |
| Wdr24 |
A |
G |
17: 26,045,102 (GRCm39) |
Y279C |
probably damaging |
Het |
| Wdr90 |
A |
G |
17: 26,079,104 (GRCm39) |
V246A |
probably benign |
Het |
| Xrn2 |
T |
A |
2: 146,871,818 (GRCm39) |
N385K |
probably benign |
Het |
| Zfp28 |
T |
A |
7: 6,387,182 (GRCm39) |
S73T |
possibly damaging |
Het |
| Zfp345 |
T |
C |
2: 150,314,271 (GRCm39) |
E422G |
probably benign |
Het |
| Zhx2 |
A |
G |
15: 57,684,709 (GRCm39) |
E26G |
probably benign |
Het |
|
| Other mutations in Cdk4 |
| Allele | Source | Chr | Coord | Type | Predicted Effect | PPH Score |
|---|
|
IGL00960:Cdk4
|
APN |
10 |
126,900,166 (GRCm39) |
missense |
probably damaging |
1.00 |
|
IGL01326:Cdk4
|
APN |
10 |
126,900,492 (GRCm39) |
missense |
possibly damaging |
0.95 |
|
R0140:Cdk4
|
UTSW |
10 |
126,900,214 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R1437:Cdk4
|
UTSW |
10 |
126,900,558 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R1575:Cdk4
|
UTSW |
10 |
126,900,520 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R1656:Cdk4
|
UTSW |
10 |
126,900,849 (GRCm39) |
missense |
probably benign |
0.00 |
|
R1761:Cdk4
|
UTSW |
10 |
126,900,546 (GRCm39) |
unclassified |
probably benign |
|
|
R2567:Cdk4
|
UTSW |
10 |
126,900,145 (GRCm39) |
missense |
probably benign |
0.01 |
|
R4679:Cdk4
|
UTSW |
10 |
126,900,780 (GRCm39) |
missense |
possibly damaging |
0.93 |
|
R4790:Cdk4
|
UTSW |
10 |
126,900,570 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R4897:Cdk4
|
UTSW |
10 |
126,900,444 (GRCm39) |
intron |
probably benign |
|
|
R4946:Cdk4
|
UTSW |
10 |
126,900,759 (GRCm39) |
splice site |
probably null |
|
|
R5755:Cdk4
|
UTSW |
10 |
126,900,591 (GRCm39) |
critical splice donor site |
probably null |
|
|
R6515:Cdk4
|
UTSW |
10 |
126,902,052 (GRCm39) |
missense |
probably null |
0.06 |
|
R6868:Cdk4
|
UTSW |
10 |
126,900,870 (GRCm39) |
missense |
probably benign |
0.43 |
|
R7488:Cdk4
|
UTSW |
10 |
126,900,106 (GRCm39) |
start codon destroyed |
probably null |
0.26 |
|
R7748:Cdk4
|
UTSW |
10 |
126,900,298 (GRCm39) |
missense |
possibly damaging |
0.78 |
|
R8956:Cdk4
|
UTSW |
10 |
126,900,546 (GRCm39) |
unclassified |
probably benign |
|
|
R9082:Cdk4
|
UTSW |
10 |
126,900,732 (GRCm39) |
missense |
probably damaging |
1.00 |
|
| Predicted Primers |
PCR Primer
(F):5'- CTGAGGACATACCTGGACAAAGCAC -3'
(R):5'- GTACCAGAGCGTAACCACCTGAAG -3'
Sequencing Primer
(F):5'- CTGCCGGTTGAGACCATTAAG -3'
(R):5'- CGTAACCACCTGAAGAGAATAGTAG -3'
|
| Posted On |
2013-10-16 |
Incidental Mutation