Mutagenetix > Incidental Mutation

Incidental Mutation 'R7452:Skp2'

577826

Institutional Source

Beutler Lab

Gene Symbol

Skp2

Ensembl Gene

ENSMUSG00000054115

Gene Name

S-phase kinase-associated protein 2

Synonyms

FBXL1

MMRRC Submission

045526-MU

Accession Numbers

Essential gene?

Non essential (E-score: 0.000) question?

Stock #

R7452 (G1)

Quality Score

225.009

Status

Validated

Chromosome

Chromosomal Location

9112073-9155512 bp(-) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

T to A at 9113920 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Glutamine to Leucine at position 366 (Q366L)

Ref Sequence

ENSEMBL: ENSMUSP00000094225 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000067760] [ENSMUST00000096482] [ENSMUST00000100789] [ENSMUST00000100790] [ENSMUST00000110585] [ENSMUST00000190131]

AlphaFold

Q9Z0Z3

Predicted Effect

probably benign
Transcript: ENSMUST00000067760

SMART Domains

Protein: ENSMUSP00000068318
Gene: ENSMUSG00000022253

Domain	Start	End	E-Value	Type
low complexity region	13	33	N/A	INTRINSIC
Pfam:NAD_kinase	58	334	4.7e-11	PFAM

Predicted Effect

probably damaging
Transcript: ENSMUST00000096482
AA Change: Q366L

PolyPhen 2 Score 0.999 (Sensitivity: 0.14; Specificity: 0.99)

SMART Domains

Protein: ENSMUSP00000094225
Gene: ENSMUSG00000054115
AA Change: Q366L

Domain	Start	End	E-Value	Type
FBOX	100	140	3.7e-8	SMART
LRR	205	229	1.27e2	SMART
LRR	230	254	1.28e1	SMART
LRR	255	280	2.91e1	SMART
LRR	334	359	2.83e1	SMART

Predicted Effect

probably benign
Transcript: ENSMUST00000100789

SMART Domains

Protein: ENSMUSP00000098353
Gene: ENSMUSG00000022253

Domain	Start	End	E-Value	Type
low complexity region	13	33	N/A	INTRINSIC
Pfam:NAD_kinase	58	171	8.2e-10	PFAM

Predicted Effect

probably benign
Transcript: ENSMUST00000100790

SMART Domains

Protein: ENSMUSP00000098354
Gene: ENSMUSG00000022253

Domain	Start	End	E-Value	Type
low complexity region	13	33	N/A	INTRINSIC
Pfam:NAD_kinase	58	312	3.9e-12	PFAM

Predicted Effect

probably benign
Transcript: ENSMUST00000110585

SMART Domains

Protein: ENSMUSP00000106215
Gene: ENSMUSG00000054115

Domain	Start	End	E-Value	Type
FBOX	100	140	3.7e-8	SMART
Blast:LRR	205	229	5e-7	BLAST
Blast:LRR	229	253	3e-7	BLAST
Blast:LRR	255	284	3e-10	BLAST
Blast:LRR	309	334	3e-8	BLAST

Predicted Effect

probably damaging
Transcript: ENSMUST00000190131
AA Change: Q331L

PolyPhen 2 Score 0.999 (Sensitivity: 0.14; Specificity: 0.99)

SMART Domains

Protein: ENSMUSP00000139997
Gene: ENSMUSG00000054115
AA Change: Q331L

Domain	Start	End	E-Value	Type
FBOX	65	105	2.3e-10	SMART
LRR	170	194	5.3e-1	SMART
LRR	195	219	5.3e-2	SMART
LRR	220	245	1.2e-1	SMART
LRR	299	324	1.2e-1	SMART

Meta Mutation Damage Score

0.4474

Coding Region Coverage

1x: 100.0%
3x: 100.0%
10x: 99.7%
20x: 98.8%

Validation Efficiency

100% (75/75)

MGI Phenotype

FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene encodes a member of the F-box protein family which is characterized by an approximately 40 amino acid motif, the F-box. The F-box proteins constitute one of the four subunits of ubiquitin protein ligase complex called SCFs (SKP1-cullin-F-box), which function in phosphorylation-dependent ubiquitination. The F-box proteins are divided into 3 classes: Fbws containing WD-40 domains, Fbls containing leucine-rich repeats, and Fbxs containing either different protein-protein interaction modules or no recognizable motifs. The protein encoded by this gene belongs to the Fbls class; in addition to an F-box, this protein contains 10 tandem leucine-rich repeats. This protein is an essential element of the cyclin A-CDK2 S-phase kinase. It specifically recognizes phosphorylated cyclin-dependent kinase inhibitor 1B (CDKN1B, also referred to as p27 or KIP1) predominantly in S phase and interacts with S-phase kinase-associated protein 1 (SKP1 or p19). In addition, this gene is established as a protooncogene causally involved in the pathogenesis of lymphomas. Alternative splicing of this gene generates three transcript variants encoding different isoforms. [provided by RefSeq, Jul 2011]
PHENOTYPE: Mice homozygous for a knock-out allele exhibit reduced body weight, enlarged cell and nuclear sizes, polyploidy, reduced cell growth rate, overduplication of centrosomes, increased apoptosis rate, delayed wound healing, and aberrant immunoglobulin V(D)J recombination. [provided by MGI curators]

Allele List at MGI

Other mutations in this stock

Total: 74 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
A2m	C	A	6: 121,618,291 (GRCm39)	Q195K	probably damaging	Het
Abcg4	C	T	9: 44,190,897 (GRCm39)	G249R	probably damaging	Het
Actn1	T	C	12: 80,230,376 (GRCm39)	T293A	probably benign	Het
Adamts5	T	A	16: 85,674,869 (GRCm39)	T432S	probably benign	Het
Adh5	A	G	3: 138,160,506 (GRCm39)	T347A	probably benign	Het
Agbl5	A	G	5: 31,050,735 (GRCm39)	D432G	probably damaging	Het
Ank3	A	G	10: 69,734,881 (GRCm39)	T797A	possibly damaging	Het
Aoc1	T	G	6: 48,885,724 (GRCm39)	V743G	probably benign	Het
Arap2	A	T	5: 62,833,892 (GRCm39)	S858R	probably benign	Het
Arid1a	A	C	4: 133,480,438 (GRCm39)	V162G	possibly damaging	Het
Armc9	A	G	1: 86,140,814 (GRCm39)	D588G	possibly damaging	Het
Art3	A	G	5: 92,540,539 (GRCm39)	Y94C	probably damaging	Het
Btaf1	T	A	19: 36,946,527 (GRCm39)	D444E	probably damaging	Het
Cav2	A	G	6: 17,282,075 (GRCm39)	H111R	probably damaging	Het
Ccdc148	A	G	2: 58,717,596 (GRCm39)	L469P	probably damaging	Het
Celsr2	T	A	3: 108,320,406 (GRCm39)	E802V	possibly damaging	Het
Cfap57	T	C	4: 118,452,981 (GRCm39)	D574G	probably damaging	Het
Chd7	A	C	4: 8,854,731 (GRCm39)	D2024A	probably benign	Het
Corin	T	A	5: 72,592,590 (GRCm39)	D269V	possibly damaging	Het
Cyp4a12a	A	T	4: 115,184,795 (GRCm39)	I359F	probably damaging	Het
Defb6	T	C	8: 19,275,540 (GRCm39)	L7P	probably damaging	Het
Dnah7c	A	T	1: 46,686,196 (GRCm39)	M1817L	possibly damaging	Het
Dock3	A	G	9: 106,866,664 (GRCm39)	F682S	probably damaging	Het
Enpep	T	A	3: 129,065,052 (GRCm39)	Y879F	possibly damaging	Het
Enpp2	T	C	15: 54,730,132 (GRCm39)	N462S	probably damaging	Het
Ephb3	T	C	16: 21,036,107 (GRCm39)		probably null	Het
F7	C	T	8: 13,085,215 (GRCm39)	H414Y	probably benign	Het
Fbn1	T	C	2: 125,347,375 (GRCm39)	H50R	possibly damaging	Het
Fig4	T	C	10: 41,116,633 (GRCm39)	D586G	possibly damaging	Het
Fryl	A	G	5: 73,181,331 (GRCm39)	L2825P	probably damaging	Het
Gal3st2	T	A	1: 93,800,240 (GRCm39)	H30Q	possibly damaging	Het
Garre1	A	G	7: 33,945,096 (GRCm39)	S595P	probably benign	Het
Gm12886	G	A	4: 121,274,671 (GRCm39)	Q70*	probably null	Het
Gm8104	A	C	14: 42,967,501 (GRCm39)	T190P	probably benign	Het
Hps3	A	T	3: 20,065,592 (GRCm39)	N749K	probably damaging	Het
Hr	A	G	14: 70,808,926 (GRCm39)	T1101A	probably damaging	Het
Htatip2	T	A	7: 49,423,074 (GRCm39)	S210T	probably benign	Het
Ift80	T	C	3: 68,901,615 (GRCm39)		probably null	Het
Iqgap1	A	G	7: 80,410,577 (GRCm39)	V212A	possibly damaging	Het
Itih5	A	G	2: 10,243,607 (GRCm39)	E448G	probably damaging	Het
Kdm5b	T	C	1: 134,552,686 (GRCm39)	C1221R	probably damaging	Het
Lrrc72	T	C	12: 36,262,692 (GRCm39)	Y52C	probably benign	Het
Map1b	C	T	13: 99,644,648 (GRCm39)	R85Q	probably damaging	Het
Mdn1	T	C	4: 32,739,030 (GRCm39)	I3617T	possibly damaging	Het
Mtpap	T	A	18: 4,379,705 (GRCm39)	H98Q	possibly damaging	Het
Nemf	A	T	12: 69,384,733 (GRCm39)		probably null	Het
Neto1	A	T	18: 86,517,056 (GRCm39)	I458L	probably benign	Het
Nfam1	T	A	15: 82,899,163 (GRCm39)	M128L	probably benign	Het
Or2y13	C	A	11: 49,415,208 (GRCm39)	H219Q	probably benign	Het
Or4g16	A	G	2: 111,137,266 (GRCm39)	T239A	probably damaging	Het
Or5p75-ps1	C	T	7: 108,107,800 (GRCm39)	T179I	unknown	Het
Or8b50	A	T	9: 38,518,384 (GRCm39)	I208F	probably benign	Het
P2ry14	C	T	3: 59,023,466 (GRCm39)	G7D	probably benign	Het
Pde11a	A	G	2: 75,966,758 (GRCm39)	Y564H	probably damaging	Het
Pex5l	C	T	3: 33,058,467 (GRCm39)	V262I	probably benign	Het
Poli	A	G	18: 70,642,049 (GRCm39)	V717A	possibly damaging	Het
Prdm14	A	T	1: 13,195,783 (GRCm39)	W93R	probably damaging	Het
Rbm46	T	C	3: 82,771,428 (GRCm39)	M396V	probably benign	Het
Rcor2	T	C	19: 7,248,587 (GRCm39)	V212A	probably benign	Het
Rcor3	C	A	1: 191,822,173 (GRCm39)	G8V	probably damaging	Het
Rhox4d	G	A	X: 36,700,645 (GRCm39)	G191E	unknown	Het
Rictor	C	T	15: 6,801,635 (GRCm39)	S441L	probably benign	Het
Slc13a3	A	T	2: 165,269,034 (GRCm39)	S312T	probably benign	Het
Sstr1	T	C	12: 58,260,142 (GRCm39)	L255P	probably damaging	Het
Steap3	T	C	1: 120,155,585 (GRCm39)	E458G	possibly damaging	Het
Sv2b	T	A	7: 74,797,461 (GRCm39)	D311V	probably damaging	Het
Tmem132b	A	G	5: 125,715,332 (GRCm39)	D347G	probably benign	Het
Tmem161a	A	G	8: 70,630,138 (GRCm39)	D108G	probably damaging	Het
Traf5	T	A	1: 191,731,792 (GRCm39)	I47F		Het
Trp53bp2	C	T	1: 182,274,133 (GRCm39)	Q95*	probably null	Het
Ttn	G	T	2: 76,707,487 (GRCm39)		probably null	Het
Usf3	T	C	16: 44,040,397 (GRCm39)	S1626P	probably benign	Het
Usp3	T	C	9: 66,474,180 (GRCm39)	R33G	probably benign	Het
Zbtb20	G	T	16: 43,431,039 (GRCm39)	A517S	probably damaging	Het

Other mutations in Skp2

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL00841:Skp2	APN	15	9,139,574 (GRCm39)	missense	probably benign	0.00
IGL02135:Skp2	APN	15	9,125,234 (GRCm39)	missense	probably benign
R0050:Skp2	UTSW	15	9,125,178 (GRCm39)	missense	probably benign	0.03
R0129:Skp2	UTSW	15	9,125,280 (GRCm39)	missense	probably damaging	1.00
R0238:Skp2	UTSW	15	9,127,971 (GRCm39)	critical splice donor site	probably null
R0238:Skp2	UTSW	15	9,127,971 (GRCm39)	critical splice donor site	probably null
R1404:Skp2	UTSW	15	9,117,012 (GRCm39)	nonsense	probably null
R1404:Skp2	UTSW	15	9,117,012 (GRCm39)	nonsense	probably null
R1503:Skp2	UTSW	15	9,127,998 (GRCm39)	missense	probably damaging	1.00
R1660:Skp2	UTSW	15	9,125,201 (GRCm39)	missense	probably benign	0.03
R1746:Skp2	UTSW	15	9,139,530 (GRCm39)	missense	possibly damaging	0.58
R2031:Skp2	UTSW	15	9,113,786 (GRCm39)	missense	probably damaging	1.00
R2034:Skp2	UTSW	15	9,113,786 (GRCm39)	missense	probably damaging	1.00
R2087:Skp2	UTSW	15	9,113,786 (GRCm39)	missense	probably damaging	1.00
R2088:Skp2	UTSW	15	9,113,786 (GRCm39)	missense	probably damaging	1.00
R2090:Skp2	UTSW	15	9,113,786 (GRCm39)	missense	probably damaging	1.00
R2091:Skp2	UTSW	15	9,113,786 (GRCm39)	missense	probably damaging	1.00
R4272:Skp2	UTSW	15	9,116,947 (GRCm39)	critical splice donor site	probably null
R4428:Skp2	UTSW	15	9,117,034 (GRCm39)	missense	probably benign	0.21
R4747:Skp2	UTSW	15	9,113,927 (GRCm39)	missense	possibly damaging	0.93
R5734:Skp2	UTSW	15	9,139,566 (GRCm39)	missense	possibly damaging	0.85
R6963:Skp2	UTSW	15	9,139,515 (GRCm39)	splice site	probably null
R7481:Skp2	UTSW	15	9,113,905 (GRCm39)	missense	probably damaging	0.97
R7855:Skp2	UTSW	15	9,122,328 (GRCm39)	missense	probably benign	0.00
R7989:Skp2	UTSW	15	9,127,979 (GRCm39)	missense	probably benign	0.00
R8046:Skp2	UTSW	15	9,139,687 (GRCm39)	missense	probably damaging	1.00
R8497:Skp2	UTSW	15	9,127,971 (GRCm39)	critical splice donor site	probably null
R9062:Skp2	UTSW	15	9,113,821 (GRCm39)	missense	probably damaging	1.00

Predicted Primers

PCR Primer
(F):5'- GTAAGCACTTCATAGACAACTGGG -3'
(R):5'- CGGGTCAGGCTGCTTTATATCC -3'

Sequencing Primer
(F):5'- CATAGACAACTGGGCTTTTGC -3'
(R):5'- ATGATGTCAGTAGGCTGC -3'

Posted On

2019-10-07