Mutagenetix > Incidental Mutation

Incidental Mutation 'R0066:Wdr18'

16861

Institutional Source

Beutler Lab

Gene Symbol

Wdr18

Ensembl Gene

ENSMUSG00000035754

Gene Name

WD repeat domain 18

Synonyms

2310012I10Rik

MMRRC Submission

038357-MU

Accession Numbers

Essential gene?

Probably essential (E-score: 0.964) question?

Stock #

R0066 (G1)

Quality Score

Status

Validated

Chromosome

Chromosomal Location

79795989-79805081 bp(+) (GRCm39)

Type of Mutation

nonsense

DNA Base Change (assembly)

C to A at 79796937 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Tyrosine to Stop codon at position 104 (Y104*)

Ref Sequence

ENSEMBL: ENSMUSP00000041049 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000045247]

AlphaFold

Q4VBE8

Predicted Effect

probably null
Transcript: ENSMUST00000045247
AA Change: Y104*

SMART Domains

Protein: ENSMUSP00000041049
Gene: ENSMUSG00000035754
AA Change: Y104*

Domain	Start	End	E-Value	Type
Blast:WD40	27	66	3e-17	BLAST
WD40	70	107	1.48e1	SMART
WD40	110	149	1.24e-4	SMART
WD40	161	202	2.49e-1	SMART
WD40	205	243	2.05e1	SMART
WD40	258	297	2.32e-9	SMART
low complexity region	353	367	N/A	INTRINSIC
Pfam:WD40_alt	383	429	4.3e-26	PFAM

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000218449

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000220272

Meta Mutation Damage Score

0.9755

Coding Region Coverage

1x: 89.0%
3x: 85.6%
10x: 75.4%
20x: 57.8%

Validation Efficiency

94% (112/119)

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 WD repeat protein family. WD repeats are minimally conserved regions of approximately 40 amino acids typically bracketed by gly-his and trp-asp (GH-WD), which may facilitate formation of heterotrimeric or multiprotein complexes. Members of this family are involved in a variety of cellular processes, including cell cycle progression, signal transduction, apoptosis, and gene regulation. [provided by RefSeq, Jul 2008]

Allele List at MGI

All alleles(8) : Targeted(1) Gene trapped(7)

Other mutations in this stock

Total: 75 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
1810064F22Rik	A	G	9: 22,119,177 (GRCm39)		noncoding transcript	Het
Aco2	T	C	15: 81,787,666 (GRCm39)		probably benign	Het
Arsa	T	A	15: 89,358,539 (GRCm39)	M288L	possibly damaging	Het
Atg2b	A	T	12: 105,614,708 (GRCm39)	D1074E	probably benign	Het
Baiap2l1	A	T	5: 144,221,372 (GRCm39)	I174N	probably damaging	Het
Bptf	A	G	11: 106,952,962 (GRCm39)	V199A	possibly damaging	Het
Btn2a2	T	A	13: 23,662,655 (GRCm39)	I432L	probably benign	Het
Ccdc150	A	G	1: 54,395,850 (GRCm39)	I778V	probably benign	Het
Cd200r2	G	A	16: 44,730,037 (GRCm39)	V194I	possibly damaging	Het
Cep350	A	C	1: 155,786,964 (GRCm39)	L1421R	probably damaging	Het
Col6a6	A	T	9: 105,579,412 (GRCm39)	C1938S	probably damaging	Het
Cspg4	A	T	9: 56,795,418 (GRCm39)	D1051V	probably damaging	Het
Cstf1	T	A	2: 172,214,976 (GRCm39)	N32K	probably benign	Het
Ctrb1	G	A	8: 112,413,269 (GRCm39)	R248*	probably null	Het
Cyp2d11	T	A	15: 82,275,958 (GRCm39)	M208L	probably benign	Het
Dbt	A	G	3: 116,337,478 (GRCm39)	Q334R	probably benign	Het
Dcaf12	A	G	4: 41,298,338 (GRCm39)	V270A	probably damaging	Het
Dis3l	T	A	9: 64,226,447 (GRCm39)	N361I	probably benign	Het
Dnm3	A	G	1: 162,234,930 (GRCm39)	V70A	probably damaging	Het
Dpy19l2	G	A	9: 24,557,679 (GRCm39)		probably benign	Het
Dst	C	A	1: 34,228,634 (GRCm39)	H2254N	possibly damaging	Het
Eif2b1	T	G	5: 124,711,858 (GRCm39)		probably null	Het
Epm2aip1	A	G	9: 111,101,531 (GRCm39)	N168S	probably benign	Het
Fchsd2	A	G	7: 100,927,631 (GRCm39)	Y691C	possibly damaging	Het
Fndc8	A	T	11: 82,788,398 (GRCm39)	D76V	probably benign	Het
Frmd4a	T	C	2: 4,477,963 (GRCm39)	L48P	probably damaging	Het
Gimap6	T	A	6: 48,679,404 (GRCm39)	I211F	probably damaging	Het
Gm15130	A	G	2: 110,969,284 (GRCm39)		probably benign	Het
Gm19618	A	T	6: 87,691,227 (GRCm39)			Het
Gpatch1	G	A	7: 34,986,652 (GRCm39)	S768L	probably damaging	Het
Grb14	T	G	2: 64,768,836 (GRCm39)		probably null	Het
Hnrnpd	T	C	5: 100,112,560 (GRCm39)	E222G	probably damaging	Het
Ighv1-4	A	G	12: 114,450,989 (GRCm39)	S40P	possibly damaging	Het
Kcnh4	T	C	11: 100,648,626 (GRCm39)	H26R	probably benign	Het
Kctd2	T	G	11: 115,320,343 (GRCm39)		probably benign	Het
Macf1	G	A	4: 123,325,943 (GRCm39)	Q3066*	probably null	Het
Mfn2	G	A	4: 147,969,902 (GRCm39)		probably benign	Het
Mmab	T	C	5: 114,574,526 (GRCm39)		probably benign	Het
Mrc1	T	C	2: 14,266,011 (GRCm39)	S310P	probably benign	Het
Mrps21	T	C	3: 95,770,197 (GRCm39)	Y44C	probably null	Het
Myh10	T	A	11: 68,590,317 (GRCm39)	F121Y	probably damaging	Het
Myo1f	A	G	17: 33,820,677 (GRCm39)	D840G	probably damaging	Het
Nol6	G	T	4: 41,119,572 (GRCm39)		probably benign	Het
Ntsr2	T	C	12: 16,704,120 (GRCm39)	I207T	probably benign	Het
Nwd1	T	A	8: 73,438,484 (GRCm39)	S1552T	probably benign	Het
Or11j4	T	A	14: 50,630,659 (GRCm39)	F149I	probably benign	Het
Pkd1l3	G	T	8: 110,347,103 (GRCm39)	G159C	unknown	Het
Plcb4	T	C	2: 135,803,689 (GRCm39)	S521P	probably benign	Het
Plcl1	A	T	1: 55,752,634 (GRCm39)	I993F	probably damaging	Het
Plekha7	T	C	7: 115,756,743 (GRCm39)	S640G	probably damaging	Het
Ptprn2	A	C	12: 117,240,222 (GRCm39)	N993T	probably benign	Het
Reck	A	G	4: 43,930,936 (GRCm39)	N646D	probably damaging	Het
Rfx2	A	T	17: 57,093,736 (GRCm39)		probably benign	Het
Ripk2	G	A	4: 16,123,868 (GRCm39)	Q436*	probably null	Het
Ryr1	C	T	7: 28,704,992 (GRCm39)		probably benign	Het
Sema6b	A	G	17: 56,435,271 (GRCm39)	V324A	possibly damaging	Het
Sik2	C	A	9: 50,909,833 (GRCm39)	M73I	probably benign	Het
Slc39a6	T	C	18: 24,732,326 (GRCm39)	K321E	probably damaging	Het
Slc7a4	C	A	16: 17,391,875 (GRCm39)	V520F	probably benign	Het
Sptan1	C	A	2: 29,893,679 (GRCm39)		probably benign	Het
Stab1	C	T	14: 30,879,027 (GRCm39)		probably benign	Het
Tbc1d17	C	T	7: 44,493,495 (GRCm39)		probably benign	Het
Tbcd	T	A	11: 121,394,590 (GRCm39)	L49*	probably null	Het
Tulp4	A	T	17: 6,252,008 (GRCm39)	N60I	probably damaging	Het
Ubqlnl	A	T	7: 103,798,145 (GRCm39)	W451R	probably damaging	Het
Usp53	G	T	3: 122,746,956 (GRCm39)	C363*	probably null	Het
Utp4	A	G	8: 107,649,530 (GRCm39)	T660A	possibly damaging	Het
Vmn1r194	A	T	13: 22,428,641 (GRCm39)	Y86F	probably benign	Het
Vmn1r195	A	T	13: 22,463,409 (GRCm39)	H293L	possibly damaging	Het
Vmn1r231	T	C	17: 21,109,998 (GRCm39)	R306G	probably benign	Het
Vmn2r77	T	C	7: 86,449,964 (GRCm39)	V70A	probably benign	Het
Vps8	A	G	16: 21,296,273 (GRCm39)	E515G	possibly damaging	Het
Xab2	A	T	8: 3,663,880 (GRCm39)	N346K	probably damaging	Het
Zdhhc12	C	T	2: 29,982,547 (GRCm39)	R50H	probably damaging	Het
Zdhhc8	A	G	16: 18,043,064 (GRCm39)	S379P	probably benign	Het

Other mutations in Wdr18

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL01382:Wdr18	APN	10	79,801,106 (GRCm39)	missense	probably damaging	1.00
IGL02812:Wdr18	APN	10	79,796,898 (GRCm39)	missense	possibly damaging	0.68
IGL02949:Wdr18	APN	10	79,800,889 (GRCm39)	missense	probably benign	0.00
R0066:Wdr18	UTSW	10	79,796,937 (GRCm39)	nonsense	probably null
R0244:Wdr18	UTSW	10	79,802,242 (GRCm39)	missense	probably damaging	1.00
R0257:Wdr18	UTSW	10	79,796,953 (GRCm39)	splice site	probably benign
R0377:Wdr18	UTSW	10	79,803,336 (GRCm39)	missense	probably benign	0.40
R1844:Wdr18	UTSW	10	79,802,561 (GRCm39)	critical splice donor site	probably null
R4179:Wdr18	UTSW	10	79,800,875 (GRCm39)	missense	probably damaging	1.00
R4674:Wdr18	UTSW	10	79,801,069 (GRCm39)	missense	probably benign
R5573:Wdr18	UTSW	10	79,800,872 (GRCm39)	missense	probably benign
R6007:Wdr18	UTSW	10	79,801,177 (GRCm39)	missense	possibly damaging	0.94
R6455:Wdr18	UTSW	10	79,801,115 (GRCm39)	missense	probably damaging	1.00
R7042:Wdr18	UTSW	10	79,801,944 (GRCm39)	missense	probably benign	0.22
R7223:Wdr18	UTSW	10	79,796,202 (GRCm39)	missense	probably damaging	1.00
R7316:Wdr18	UTSW	10	79,801,059 (GRCm39)	missense	probably benign	0.00
R7777:Wdr18	UTSW	10	79,801,884 (GRCm39)	missense	probably benign	0.06
R9117:Wdr18	UTSW	10	79,801,154 (GRCm39)	missense	probably benign	0.01

Protein Function and Prediction

Wdr18 encodes the WD40-repeat protein 18 (WDR18) (1). WD40-repeat proteins have diverse functions including signal transduction, cell cycle control, cytoskeleton assembly, apoptosis, chromatin dynamics and transcriptional regulation by acting as scaffolds that interact with proteins, peptides, or nucleic acids (2;3). Human WDR18 is involved in ribosome biogenesis through the formation of a complex with Rix1, PELP, and TEX10 (4;5). WDR18 associates with TopBP1 in Xenopus egg extracts to facilitate AT70-induced Chk1 phosphorylation and also phosphorylates Chk1 itself through a direct interaction with Chk1 (1). The association of WDR18 with Chk1 indicates that WDR18 is a checkpoint protein that promotes DNA damage checkpoint signaling (1). In Zebrafish, wdr18 mRNA is detected in dorsal forerunner cells or the Kuppfer’s vesicle (KV) progenitor cells in early development; in early somitogenesis stages, wdr18 is expressed in the KV (6). Studies of a zebrafish model with morpholin-induced knockdown of wdr18 determined that wdr18 is involved in the laterality determination process. Furthermore, wdr18 in zebrafish regulates dorsal forerunner cell clustering and migration as well as Kuppfer’s vesicle formation (6).

References

1. Yan, S., and Willis, J. (2013) WD40-Repeat Protein WDR18 Collaborates with TopBP1 to Facilitate DNA Damage Checkpoint Signaling. Biochem Biophys Res Commun. 431, 466-471.

2. Stirnimann, C. U., Petsalaki, E., Russell, R. B., and Muller, C. W. (2010) WD40 Proteins Propel Cellular Networks. Trends Biochem Sci. 35, 565-574.

3. Xu, C., and Min, J. (2011) Structure and Function of WD40 Domain Proteins. Protein Cell. 2, 202-214.

4. Castle, C. D., Cassimere, E. K., and Denicourt, C. (2012) LAS1L Interacts with the Mammalian Rix1 Complex to Regulate Ribosome Biogenesis. Mol Biol Cell. 23, 716-728.

5. Finkbeiner, E., Haindl, M., and Muller, S. (2011) The SUMO System Controls Nucleolar Partitioning of a Novel Mammalian Ribosome Biogenesis Complex. EMBO J. 30, 1067-1078.

6. Gao, W., Xu, L., Guan, R., Liu, X., Han, Y., Wu, Q., Xiao, Y., Qi, F., Zhu, Z., Lin, S., and Zhang, B. (2011) Wdr18 is Required for Kupffer's Vesicle Formation and Regulation of Body Asymmetry in Zebrafish. PLoS One. 6, e23386.

Posted On

2013-01-20

Science Writer

Anne Murray