Mutagenetix > Incidental Mutation

Incidental Mutation 'R2239:Tnfsf11'

240570

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

040239-MU

Accession Numbers

Essential gene?

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

Stock #

R2239 (G1)

Quality Score

225

Status

Validated

Chromosome

Chromosomal Location

78514886-78545483 bp(-) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

A to T at 78537421 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Serine to Threonine at position 81 (S81T)

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

possibly damaging
Transcript: ENSMUST00000022592
AA Change: S81T

PolyPhen 2 Score 0.768 (Sensitivity: 0.85; Specificity: 0.92)

SMART Domains

Protein: ENSMUSP00000022592
Gene: ENSMUSG00000022015
AA Change: S81T

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

0.4005

Coding Region Coverage

1x: 99.2%
3x: 98.6%
10x: 97.2%
20x: 94.9%

Validation Efficiency

94% (68/72)

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: 67 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Adam18	T	C	8: 25,136,303 (GRCm39)	E406G	probably benign	Het
Ago3	G	A	4: 126,262,315 (GRCm39)	R412C	probably damaging	Het
Arhgap36	G	T	X: 48,582,282 (GRCm39)	V60L	possibly damaging	Het
Arl10	G	T	13: 54,722,962 (GRCm39)	V19L	probably benign	Het
Aspm	T	A	1: 139,384,584 (GRCm39)	I127K	possibly damaging	Het
Atp8b3	A	G	10: 80,366,822 (GRCm39)	C259R	probably damaging	Het
Camk2g	A	G	14: 20,789,455 (GRCm39)	I205T	probably damaging	Het
Ccdc47	G	T	11: 106,092,960 (GRCm39)	N100K	possibly damaging	Het
Cd200r4	T	A	16: 44,641,260 (GRCm39)	M1K	probably null	Het
Cdc37	G	A	9: 21,053,829 (GRCm39)	Q176*	probably null	Het
Cdh5	C	A	8: 104,852,304 (GRCm39)	H140N	possibly damaging	Het
Cep128	T	C	12: 91,314,341 (GRCm39)	T146A	probably benign	Het
Cnnm4	T	A	1: 36,544,759 (GRCm39)	S673T	probably benign	Het
Cnot1	T	C	8: 96,496,149 (GRCm39)	I342V	probably benign	Het
Cog8	C	A	8: 107,782,993 (GRCm39)	G99W	probably damaging	Het
Dars2	T	C	1: 160,890,852 (GRCm39)	T120A	possibly damaging	Het
Dnah7b	C	A	1: 46,240,344 (GRCm39)		probably benign	Het
Emilin2	T	A	17: 71,617,219 (GRCm39)	Q64L	probably benign	Het
Eomes	A	G	9: 118,311,359 (GRCm39)	D394G	probably damaging	Het
Epn1	A	G	7: 5,100,601 (GRCm39)	N518S	probably damaging	Het
Exoc1	T	C	5: 76,707,557 (GRCm39)		probably benign	Het
Fam186a	C	T	15: 99,852,745 (GRCm39)	V158M	unknown	Het
Fryl	A	G	5: 73,265,890 (GRCm39)	L477P	probably damaging	Het
Gbf1	T	C	19: 46,152,057 (GRCm39)	I30T	probably benign	Het
Hsd17b1	A	T	11: 100,969,289 (GRCm39)	I8F	probably damaging	Het
Htatsf1	G	T	X: 56,111,864 (GRCm39)	D642Y	unknown	Het
Ift88	A	G	14: 57,692,961 (GRCm39)	I387V	probably damaging	Het
Kcnh5	T	A	12: 75,054,493 (GRCm39)	M484L	probably benign	Het
Kdm1b	T	A	13: 47,227,231 (GRCm39)	F574L	probably damaging	Het
Kdm6a	T	C	X: 18,065,476 (GRCm39)	F104S	probably damaging	Het
Kntc1	T	C	5: 123,941,733 (GRCm39)	V1809A	possibly damaging	Het
Lgr4	T	C	2: 109,842,738 (GRCm39)	Y908H	probably damaging	Het
Ltbp3	C	A	19: 5,801,551 (GRCm39)	C698*	probably null	Het
Map3k1	A	C	13: 111,885,478 (GRCm39)	S1480A	probably benign	Het
Map7	A	T	10: 20,154,028 (GRCm39)	N715Y	unknown	Het
Morn4	A	G	19: 42,066,471 (GRCm39)	Y39H	possibly damaging	Het
Myh14	A	T	7: 44,314,607 (GRCm39)	D105E	probably damaging	Het
Nfasc	T	C	1: 132,510,760 (GRCm39)		probably benign	Het
Nfe2l2	G	A	2: 75,506,898 (GRCm39)	P401S	probably benign	Het
Nt5c1b	C	A	12: 10,425,558 (GRCm39)	T309K	probably damaging	Het
Or10v5	T	C	19: 11,805,814 (GRCm39)	D192G	probably damaging	Het
Or2aa1	A	G	11: 59,480,097 (GRCm39)	S273P	possibly damaging	Het
Or5ac23	T	A	16: 59,149,738 (GRCm39)	I45F	probably damaging	Het
Or5b109	T	C	19: 13,212,085 (GRCm39)	V157A	probably benign	Het
Or5l13	T	C	2: 87,779,741 (GRCm39)	T279A	probably damaging	Het
P4hb	A	G	11: 120,454,108 (GRCm39)	Y329H	probably damaging	Het
Papolg	A	G	11: 23,826,378 (GRCm39)	Y259H	probably damaging	Het
Pcgf5	A	T	19: 36,414,754 (GRCm39)	N105I	probably damaging	Het
Pde4a	G	A	9: 21,122,564 (GRCm39)	C820Y	probably damaging	Het
Phka2	A	G	X: 159,324,408 (GRCm39)	E254G	probably damaging	Het
Phrf1	A	G	7: 140,817,605 (GRCm39)	E138G	probably damaging	Het
Rgs3	A	T	4: 62,544,124 (GRCm39)	T299S	probably benign	Het
Skint5	G	A	4: 113,403,733 (GRCm39)	T1163I	unknown	Het
Slc16a8	T	C	15: 79,137,147 (GRCm39)	M88V	probably damaging	Het
Slc35f4	A	G	14: 49,543,660 (GRCm39)		probably null	Het
Smr2l	T	G	5: 88,430,413 (GRCm39)	M103R	probably benign	Het
Spata4	A	C	8: 55,055,664 (GRCm39)	K185T	probably benign	Het
Spin2c	A	G	X: 152,616,672 (GRCm39)	I162V	probably damaging	Het
Stac	G	A	9: 111,519,190 (GRCm39)		probably benign	Het
Tet1	T	C	10: 62,715,513 (GRCm39)	D94G	probably benign	Het
Topaz1	C	T	9: 122,600,212 (GRCm39)	T984I	probably benign	Het
Trmt5	A	G	12: 73,331,888 (GRCm39)	I4T	probably benign	Het
Ttc7b	A	G	12: 100,321,260 (GRCm39)		probably null	Het
Ugcg	C	T	4: 59,207,798 (GRCm39)	P46S	probably benign	Het
Ush2a	C	A	1: 188,308,411 (GRCm39)	T2020K	probably benign	Het
Zan	G	A	5: 137,456,099 (GRCm39)	Q1354*	probably null	Het
Zpld2	A	C	4: 133,929,516 (GRCm39)	M263R	unknown	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
R2062:Tnfsf11	UTSW	14	78,516,362 (GRCm39)	missense	probably damaging	1.00
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
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'- TTGACTTTACGACGTCAGGG -3'
(R):5'- TGTGCATACATACTTACACACTCC -3'

Sequencing Primer
(F):5'- CTTTACGACGTCAGGGAGGACTTAC -3'
(R):5'- ACTCACTTTGTAGAGCAGGC -3'

Posted On

2014-10-15