Mutagenetix > Incidental Mutation

Incidental Mutation 'R2062:Tnfsf11'

228796

Institutional Source

Beutler Lab

Gene Symbol

Tnfsf11

Ensembl Gene

ENSMUSG00000022015

Gene Name

tumor necrosis factor (ligand) superfamily, member 11

Synonyms

Ly109l, Trance, osteoclast differentiation factor, RANKL, OPGL, OPGL, ODF

MMRRC Submission

040067-MU

Accession Numbers

Essential gene?

Possibly non essential (E-score: 0.435) question?

Stock #

R2062 (G1)

Quality Score

225

Status

Validated

Chromosome

Chromosomal Location

78514886-78545483 bp(-) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

T to A at 78516362 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Asparagine to Isoleucine at position 202 (N202I)

Ref Sequence

ENSEMBL: ENSMUSP00000022592 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000022592]

AlphaFold

O35235

PDB Structure

CRYSTAL STRUCTURE OF THE EXTRACELLULAR DOMAIN OF MOUSE RANK LIGAND [X-RAY DIFFRACTION]
CRYSTAL STRUCTURE OF TRANCE/RANKL CYTOKINE. [X-RAY DIFFRACTION]
Mouse RANKL Structure at 1.9A Resolution [X-RAY DIFFRACTION]
Crystal structure of mouse RANKL-RANK complex [X-RAY DIFFRACTION]
Crystal structure of extracellular domains of mouse RANK-RANKL complex [X-RAY DIFFRACTION]
Crystal structure of mouse RANKL-OPG complex [X-RAY DIFFRACTION]
Crystal Structure of mouse RANK bound to RANKL [X-RAY DIFFRACTION]

Predicted Effect

probably damaging
Transcript: ENSMUST00000022592
AA Change: N202I

PolyPhen 2 Score 0.997 (Sensitivity: 0.41; Specificity: 0.98)

SMART Domains

Protein: ENSMUSP00000022592
Gene: ENSMUSG00000022015
AA Change: N202I

Domain	Start	End	E-Value	Type
low complexity region	32	46	N/A	INTRINSIC
transmembrane domain	49	71	N/A	INTRINSIC
TNF	163	312	7.37e-58	SMART

Meta Mutation Damage Score

0.8331

Coding Region Coverage

1x: 99.2%
3x: 98.5%
10x: 96.8%
20x: 94.0%

Validation Efficiency

99% (84/85)

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 tumor necrosis factor (TNF) cytokine family which is a ligand for osteoprotegerin and functions as a key factor for osteoclast differentiation and activation. This protein was shown to be a dentritic cell survival factor and is involved in the regulation of T cell-dependent immune response. T cell activation was reported to induce expression of this gene and lead to an increase of osteoclastogenesis and bone loss. This protein was shown to activate antiapoptotic kinase AKT/PKB through a signaling complex involving SRC kinase and tumor necrosis factor receptor-associated factor (TRAF) 6, which indicated this protein may have a role in the regulation of cell apoptosis. Targeted disruption of the related gene in mice led to severe osteopetrosis and a lack of osteoclasts. The deficient mice exhibited defects in early differentiation of T and B lymphocytes, and failed to form lobulo-alveolar mammary structures during pregnancy. Two alternatively spliced transcript variants have been found. [provided by RefSeq, Jul 2008]
PHENOTYPE: Mice homozygous for a null allele exhibit a failure of tooth eruption, osteopetrosis, failure to lactate and arrested alveolar bud differentiation during pregnancy. [provided by MGI curators]

Allele List at MGI

Other mutations in this stock

Total: 82 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
4933436I01Rik	T	A	X: 66,964,308 (GRCm39)	I184L	probably benign	Het
A2ml1	A	T	6: 128,529,271 (GRCm39)	M957K	probably benign	Het
Adam7	C	A	14: 68,742,610 (GRCm39)	V668F	probably benign	Het
Adcy7	T	G	8: 89,038,902 (GRCm39)	L306R	probably damaging	Het
Akt3	A	G	1: 176,930,551 (GRCm39)	S136P	possibly damaging	Het
Alox12e	G	A	11: 70,206,828 (GRCm39)	R620W	probably damaging	Het
Amy2a1	T	C	3: 113,324,217 (GRCm39)	I108V	probably benign	Het
Ano7	T	C	1: 93,318,035 (GRCm39)	V249A	probably benign	Het
Aox1	T	C	1: 58,098,351 (GRCm39)		probably null	Het
Asah2	A	T	19: 32,002,274 (GRCm39)	V290E	probably damaging	Het
Ascc2	A	T	11: 4,631,496 (GRCm39)	M646L	probably benign	Het
Atxn2l	T	A	7: 126,095,038 (GRCm39)	K421N	probably damaging	Het
Cars2	T	C	8: 11,597,747 (GRCm39)	I110V	probably damaging	Het
Ccdc74a	A	G	16: 17,467,890 (GRCm39)	N249S	probably benign	Het
Cenpe	T	C	3: 134,928,082 (GRCm39)		probably benign	Het
Clptm1l	C	T	13: 73,755,842 (GRCm39)	Q153*	probably null	Het
Cnep1r1	G	T	8: 88,845,445 (GRCm39)		probably benign	Het
Cyp2d37-ps	C	T	15: 82,574,289 (GRCm39)		noncoding transcript	Het
Cyp3a25	A	G	5: 145,923,779 (GRCm39)		probably benign	Het
Dis3l	G	T	9: 64,246,855 (GRCm39)	Q67K	probably benign	Het
Dnah1	A	G	14: 30,993,086 (GRCm39)	V2936A	probably damaging	Het
Dnah5	C	T	15: 28,366,416 (GRCm39)	R2710C	probably damaging	Het
Dtx2	C	T	5: 136,059,431 (GRCm39)	S493F	probably damaging	Het
Dvl3	G	A	16: 20,345,101 (GRCm39)	S361N	probably benign	Het
Ehd1	T	C	19: 6,348,108 (GRCm39)	L362P	probably benign	Het
Eif2ak3	T	C	6: 70,881,181 (GRCm39)	V1085A	probably benign	Het
Eif3b	T	C	5: 140,412,208 (GRCm39)	Y226H	probably damaging	Het
Endov	T	C	11: 119,390,408 (GRCm39)	F12S	probably damaging	Het
Ercc1	A	G	7: 19,088,295 (GRCm39)	*37W	probably null	Het
Evi2a	G	A	11: 79,418,593 (GRCm39)	Q6*	probably null	Het
Faah	C	T	4: 115,855,770 (GRCm39)	V552M	probably damaging	Het
Fat1	T	A	8: 45,477,369 (GRCm39)	N2138K	probably damaging	Het
Fat1	T	A	8: 45,479,741 (GRCm39)	V2929E	probably damaging	Het
Gm2959	A	G	14: 42,235,658 (GRCm39)		noncoding transcript	Het
Gm6327	A	T	16: 12,578,979 (GRCm39)		noncoding transcript	Het
Gm9912	T	C	3: 148,890,795 (GRCm39)	T113A	unknown	Het
Gtf2f2	A	G	14: 76,155,136 (GRCm39)	S142P	possibly damaging	Het
Hspg2	A	T	4: 137,286,678 (GRCm39)	T3666S	possibly damaging	Het
Htt	C	T	5: 34,983,326 (GRCm39)	T975I	probably benign	Het
Il2rg	A	G	X: 100,311,416 (GRCm39)	L57P	possibly damaging	Het
Iqgap1	G	A	7: 80,373,727 (GRCm39)	Q1421*	probably null	Het
Itga3	T	A	11: 94,944,902 (GRCm39)	Q802L	possibly damaging	Het
Lonp2	A	G	8: 87,392,403 (GRCm39)	T490A	probably damaging	Het
Lztr1	T	C	16: 17,327,534 (GRCm39)	V79A	probably damaging	Het
Mast4	C	T	13: 102,895,601 (GRCm39)	E736K	probably benign	Het
Mpp4	G	A	1: 59,182,941 (GRCm39)	P322L	possibly damaging	Het
Mrto4	T	C	4: 139,076,334 (GRCm39)	K86E	probably benign	Het
Myof	A	G	19: 37,904,194 (GRCm39)	V2A	possibly damaging	Het
Naf1	A	G	8: 67,340,432 (GRCm39)	D414G	probably damaging	Het
Nav3	G	A	10: 109,555,882 (GRCm39)	T1683M	probably damaging	Het
Nbea	A	G	3: 55,993,578 (GRCm39)		probably benign	Het
Nebl	A	T	2: 17,401,932 (GRCm39)	M427K	probably benign	Het
Ngdn	T	C	14: 55,259,564 (GRCm39)	V205A	possibly damaging	Het
Nup133	C	A	8: 124,641,314 (GRCm39)	D869Y	probably damaging	Het
Oas1g	T	C	5: 121,023,946 (GRCm39)	E121G	probably damaging	Het
Or10j3b	T	C	1: 173,043,277 (GRCm39)	F20L	probably benign	Het
Or2ab1	A	G	11: 58,488,396 (GRCm39)	N58S	probably damaging	Het
Or2w3	G	T	11: 58,556,808 (GRCm39)	C141F	probably damaging	Het
Or5m9	A	G	2: 85,877,299 (GRCm39)	T158A	probably damaging	Het
Or6c205	T	A	10: 129,087,001 (GRCm39)	Y199*	probably null	Het
Park7	T	C	4: 150,989,732 (GRCm39)	N76S	probably benign	Het
Pcdh8	A	T	14: 80,005,651 (GRCm39)	S912R	probably damaging	Het
Pkhd1	A	G	1: 20,271,559 (GRCm39)	I2998T	probably damaging	Het
Plxnb3	T	A	X: 72,815,357 (GRCm39)	Y1845*	probably null	Het
Ppard	A	G	17: 28,518,663 (GRCm39)	H388R	probably damaging	Het
Psma1	A	G	7: 113,869,001 (GRCm39)	S142P	possibly damaging	Het
Pth2r	T	C	1: 65,382,721 (GRCm39)	I158T	probably damaging	Het
Rbl2	C	A	8: 91,833,367 (GRCm39)	P714Q	probably damaging	Het
Rexo2	A	T	9: 48,385,813 (GRCm39)	S104T	possibly damaging	Het
Sema5a	T	C	15: 32,609,363 (GRCm39)		probably benign	Het
Spmip10	C	T	18: 56,721,535 (GRCm39)	Q25*	probably null	Het
Sun2	A	G	15: 79,622,852 (GRCm39)	L109P	probably damaging	Het
Tdg	A	G	10: 82,477,368 (GRCm39)	T116A	probably benign	Het
Terb1	A	T	8: 105,195,380 (GRCm39)	M587K	possibly damaging	Het
Tmcc1	C	T	6: 116,020,019 (GRCm39)	V118M	probably benign	Het
Togaram2	T	C	17: 72,023,360 (GRCm39)	S759P	probably benign	Het
Ttc7b	G	A	12: 100,291,948 (GRCm39)	A208V	probably damaging	Het
Tti2	T	C	8: 31,644,338 (GRCm39)		probably benign	Het
Wnk1	T	C	6: 119,905,118 (GRCm39)		probably null	Het
Zfyve26	T	C	12: 79,330,806 (GRCm39)		probably null	Het
Zfyve28	T	C	5: 34,391,681 (GRCm39)	M157V	probably null	Het
Zgrf1	T	C	3: 127,406,999 (GRCm39)	C1589R	probably damaging	Het

Other mutations in Tnfsf11

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL02601:Tnfsf11	APN	14	78,537,385 (GRCm39)	nonsense	probably null
R0352:Tnfsf11	UTSW	14	78,516,408 (GRCm39)	missense	probably benign	0.17
R0377:Tnfsf11	UTSW	14	78,537,352 (GRCm39)	missense	probably benign	0.00
R2121:Tnfsf11	UTSW	14	78,537,333 (GRCm39)	missense	probably benign	0.32
R2178:Tnfsf11	UTSW	14	78,521,682 (GRCm39)	missense	probably benign	0.00
R2237:Tnfsf11	UTSW	14	78,537,421 (GRCm39)	missense	possibly damaging	0.77
R2238:Tnfsf11	UTSW	14	78,537,421 (GRCm39)	missense	possibly damaging	0.77
R2239:Tnfsf11	UTSW	14	78,537,421 (GRCm39)	missense	possibly damaging	0.77
R2430:Tnfsf11	UTSW	14	78,521,752 (GRCm39)	missense	probably benign	0.00
R4155:Tnfsf11	UTSW	14	78,537,309 (GRCm39)	missense	probably benign	0.28
R4197:Tnfsf11	UTSW	14	78,521,752 (GRCm39)	missense	probably benign	0.00
R4562:Tnfsf11	UTSW	14	78,516,020 (GRCm39)	missense	probably damaging	1.00
R6141:Tnfsf11	UTSW	14	78,545,299 (GRCm39)	missense	probably damaging	0.99
R8063:Tnfsf11	UTSW	14	78,516,098 (GRCm39)	missense	probably damaging	1.00
R8904:Tnfsf11	UTSW	14	78,516,119 (GRCm39)	missense	possibly damaging	0.88
X0020:Tnfsf11	UTSW	14	78,516,317 (GRCm39)	missense	probably damaging	1.00

Predicted Primers

PCR Primer
(F):5'- ATTTCTTCACCAGCTCGGAG -3'
(R):5'- TGTATGATGCTACCCCACCAG -3'

Sequencing Primer
(F):5'- GTGGAATTCAGAATTGCCCGACC -3'
(R):5'- TACCCCACCAGCCTGTG -3'

Posted On

2014-09-17