Mutagenetix > Incidental Mutation

Incidental Mutation 'R2238:Tnfsf11'

240263

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

040238-MU

Accession Numbers

Essential gene?

Possibly non essential (E-score: 0.478) question?

Stock #

R2238 (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: 99.1%
3x: 98.6%
10x: 97.3%
20x: 95.0%

Validation Efficiency

98% (59/60)

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: 58 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Aadacl4fm1	T	A	4: 144,246,469 (GRCm39)	V5E	possibly damaging	Het
Acaca	T	C	11: 84,282,331 (GRCm39)		probably benign	Het
Adam18	T	C	8: 25,136,303 (GRCm39)	E406G	probably benign	Het
Adgrl4	A	T	3: 151,205,779 (GRCm39)	I164F	probably damaging	Het
Arhgap36	G	T	X: 48,582,282 (GRCm39)	V60L	possibly damaging	Het
Bmi1	T	C	2: 18,688,225 (GRCm39)		probably benign	Het
Carf	T	C	1: 60,187,193 (GRCm39)	S599P	probably benign	Het
Cdc37	G	A	9: 21,053,829 (GRCm39)	Q176*	probably null	Het
Clca3a1	T	A	3: 144,457,766 (GRCm39)	I373F	possibly damaging	Het
Clnk	A	G	5: 38,921,694 (GRCm39)		probably benign	Het
Cnot1	T	C	8: 96,496,149 (GRCm39)	I342V	probably benign	Het
Dact2	A	T	17: 14,417,312 (GRCm39)	L296Q	probably damaging	Het
Dctn2	C	T	10: 127,112,257 (GRCm39)	T123I	probably damaging	Het
Deup1	A	C	9: 15,486,597 (GRCm39)	I455S	probably damaging	Het
Dnmbp	A	G	19: 43,857,303 (GRCm39)	V957A	possibly damaging	Het
Emilin2	T	C	17: 71,581,734 (GRCm39)	R331G	possibly damaging	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
Gbf1	T	C	19: 46,152,057 (GRCm39)	I30T	probably benign	Het
Gcc1	A	G	6: 28,420,462 (GRCm39)	V285A	probably benign	Het
Gopc	T	C	10: 52,229,499 (GRCm39)	H188R	probably damaging	Het
Herc6	A	G	6: 57,631,386 (GRCm39)	N693D	probably benign	Het
Hipk2	A	G	6: 38,706,850 (GRCm39)		probably benign	Het
Htatsf1	G	T	X: 56,111,864 (GRCm39)	D642Y	unknown	Het
Ints1	G	A	5: 139,750,955 (GRCm39)	T814M	possibly damaging	Het
Kdm6a	T	C	X: 18,065,476 (GRCm39)	F104S	probably damaging	Het
Kdr	T	A	5: 76,110,179 (GRCm39)	Y936F	possibly damaging	Het
Ly6k	T	C	15: 74,669,018 (GRCm39)	E87G	probably benign	Het
Lyst	A	G	13: 13,917,848 (GRCm39)	N3303D	probably benign	Het
Mindy4	T	C	6: 55,278,055 (GRCm39)	F633S	probably damaging	Het
Msl2	T	A	9: 100,978,569 (GRCm39)	N314K	probably benign	Het
Ncapd3	A	G	9: 26,978,320 (GRCm39)	T840A	probably benign	Het
Neil3	T	C	8: 54,052,311 (GRCm39)	D429G	possibly damaging	Het
Nt5c1b	C	A	12: 10,425,558 (GRCm39)	T309K	probably damaging	Het
Nt5c1b	A	G	12: 10,440,108 (GRCm39)	Y550C	probably damaging	Het
Or10v5	T	C	19: 11,805,814 (GRCm39)	D192G	probably damaging	Het
Pabpc4l	A	C	3: 46,401,137 (GRCm39)	V169G	probably damaging	Het
Pcgf5	A	T	19: 36,414,754 (GRCm39)	N105I	probably damaging	Het
Phka2	A	G	X: 159,324,408 (GRCm39)	E254G	probably damaging	Het
Pik3cb	A	G	9: 98,923,081 (GRCm39)	Y984H	probably damaging	Het
Ptprz1	A	T	6: 22,987,376 (GRCm39)	Q387L	probably damaging	Het
Rassf8	T	C	6: 145,762,910 (GRCm39)	V419A	probably damaging	Het
Rnf148	T	C	6: 23,654,345 (GRCm39)	Y217C	probably benign	Het
Sec24d	T	A	3: 123,143,543 (GRCm39)		probably null	Het
Sesn3	T	C	9: 14,219,761 (GRCm39)	V50A	probably benign	Het
Sgcd	T	C	11: 47,023,509 (GRCm39)	N99D	possibly damaging	Het
Sncaip	T	C	18: 53,001,619 (GRCm39)	S47P	probably damaging	Het
Sp2	C	T	11: 96,846,762 (GRCm39)	C527Y	probably damaging	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
Srcin1	T	C	11: 97,425,645 (GRCm39)	T471A	probably benign	Het
Stac	G	A	9: 111,519,190 (GRCm39)		probably benign	Het
Tcaf3	A	G	6: 42,570,262 (GRCm39)	Y497H	probably benign	Het
Tmem40	C	T	6: 115,708,038 (GRCm39)	W150*	probably null	Het
Tmem59l	T	C	8: 70,937,772 (GRCm39)	T203A	probably damaging	Het
Topaz1	C	T	9: 122,600,212 (GRCm39)	T984I	probably benign	Het
Vmn1r204	A	G	13: 22,740,993 (GRCm39)	H208R	probably benign	Het
Vmn2r98	T	A	17: 19,286,213 (GRCm39)	M237K	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
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
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'- TTTACGACGTCAGGGAGGAC -3'
(R):5'- GTGTGCATACATACTTACACACTC -3'

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

Posted On

2014-10-15