Incidental Mutation 'R2178:Tnfsf11'
ID 237018
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 040180-MU
Accession Numbers
Essential gene? Possibly non essential (E-score: 0.435) question?
Stock # R2178 (G1)
Quality Score 225
Status Not validated
Chromosome 14
Chromosomal Location 78514886-78545483 bp(-) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) A to G at 78521682 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Serine to Proline at position 176 (S176P)
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 benign
Transcript: ENSMUST00000022592
AA Change: S176P

PolyPhen 2 Score 0.004 (Sensitivity: 0.98; Specificity: 0.59)
SMART Domains Protein: ENSMUSP00000022592
Gene: ENSMUSG00000022015
AA Change: S176P

DomainStartEndE-ValueType
low complexity region 32 46 N/A INTRINSIC
transmembrane domain 49 71 N/A INTRINSIC
TNF 163 312 7.37e-58 SMART
Coding Region Coverage
  • 1x: 99.2%
  • 3x: 98.7%
  • 10x: 97.6%
  • 20x: 95.9%
Validation Efficiency
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: 40 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
Adcy6 A T 15: 98,492,236 (GRCm39) N1007K probably damaging Het
Apon C A 10: 128,090,634 (GRCm39) A104E probably benign Het
Cdh15 T A 8: 123,591,715 (GRCm39) probably null Het
Cep135 T C 5: 76,779,297 (GRCm39) V769A probably benign Het
Cep152 A T 2: 125,421,954 (GRCm39) probably null Het
Clca3a1 T C 3: 144,711,863 (GRCm39) N711D probably damaging Het
Col1a2 T C 6: 4,531,143 (GRCm39) F731L unknown Het
Cpt1b T C 15: 89,303,246 (GRCm39) E603G probably damaging Het
Cspp1 T G 1: 10,174,471 (GRCm39) D641E possibly damaging Het
Ddr2 C T 1: 169,822,251 (GRCm39) R399Q probably benign Het
Dzip1 T C 14: 119,126,816 (GRCm39) probably null Het
Greb1 A G 12: 16,746,388 (GRCm39) V1294A probably damaging Het
Hmgb4 A G 4: 128,154,275 (GRCm39) S98P probably damaging Het
Kif12 G A 4: 63,085,196 (GRCm39) P515L probably benign Het
Kmt5b A C 19: 3,865,372 (GRCm39) E789A possibly damaging Het
Lama1 G T 17: 68,076,510 (GRCm39) V1095F probably benign Het
Leprot T C 4: 101,513,308 (GRCm39) V32A probably benign Het
Mcoln1 A G 8: 3,558,766 (GRCm39) T255A probably damaging Het
Mertk G A 2: 128,634,984 (GRCm39) E765K probably damaging Het
Muc5b A G 7: 141,417,853 (GRCm39) T3600A possibly damaging Het
Ncapd3 A T 9: 26,999,845 (GRCm39) E1395V probably benign Het
Ntrk2 T C 13: 58,956,616 (GRCm39) F25S probably benign Het
Or2a5 A G 6: 42,873,732 (GRCm39) M116V probably benign Het
Or6z1 G T 7: 6,504,487 (GRCm39) A246D probably damaging Het
Or7c70 T A 10: 78,683,612 (GRCm39) I46F probably damaging Het
Pappa C A 4: 65,269,924 (GRCm39) H1613N probably benign Het
Polq T C 16: 36,883,191 (GRCm39) V1785A probably damaging Het
Pramel23 A T 4: 143,424,612 (GRCm39) I277K possibly damaging Het
Prkar2a T C 9: 108,617,737 (GRCm39) probably null Het
Qrich2 T C 11: 116,334,603 (GRCm39) D2194G probably damaging Het
Rnf183 T C 4: 62,346,333 (GRCm39) N155S probably benign Het
S1pr5 T C 9: 21,155,760 (GRCm39) N222S probably benign Het
Scnn1a C T 6: 125,307,965 (GRCm39) R170C probably damaging Het
Slc25a2 T C 18: 37,771,311 (GRCm39) T73A probably benign Het
Tgfb1 A G 7: 25,404,234 (GRCm39) N347S probably damaging Het
Ticrr T C 7: 79,315,433 (GRCm39) V229A probably benign Het
Tjp3 T C 10: 81,115,941 (GRCm39) E313G probably benign Het
Vmn2r68 TCC TC 7: 84,870,758 (GRCm39) probably null Het
Vps39 C A 2: 120,154,160 (GRCm39) E612* probably null Het
Vwf T A 6: 125,619,095 (GRCm39) Y1258N possibly damaging Het
Other mutations in Tnfsf11
AlleleSourceChrCoordTypePredicted EffectPPH 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
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'- GGAACTGTGAGCAATTACACCC -3'
(R):5'- TCTCAGGAGCTCCAGGTAAC -3'

Sequencing Primer
(F):5'- CCGGCAGGAGCTCAAAC -3'
(R):5'- GATGGAAGGCTCATGGTT -3'
Posted On 2014-10-02