Mutagenetix > Incidental Mutation

Incidental Mutation 'R5156:Tnfsf12'

396742

Institutional Source

Beutler Lab

Gene Symbol

Tnfsf12

Ensembl Gene

ENSMUSG00000097328

Gene Name

tumor necrosis factor (ligand) superfamily, member 12

Synonyms

DR3L, Tweak, APO3L

MMRRC Submission

042738-MU

Accession Numbers

Essential gene?

Probably non essential (E-score: 0.174) question?

Stock #

R5156 (G1)

Quality Score

225

Status

Validated

Chromosome

Chromosomal Location

69577076-69586675 bp(-) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

A to G at 69578155 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Serine to Proline at position 141 (S141P)

Ref Sequence

ENSEMBL: ENSMUSP00000137972 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000018896] [ENSMUST00000108648] [ENSMUST00000108649] [ENSMUST00000174159] [ENSMUST00000180587] [ENSMUST00000181810] [ENSMUST00000181261]

AlphaFold

O54907

Predicted Effect

probably benign
Transcript: ENSMUST00000018896

SMART Domains

Protein: ENSMUSP00000018896
Gene: ENSMUSG00000089669

Domain	Start	End	E-Value	Type
Blast:TNF	39	87	1e-22	BLAST
low complexity region	101	106	N/A	INTRINSIC
TNF	107	240	7.41e-3	SMART

Predicted Effect

probably benign
Transcript: ENSMUST00000108648

SMART Domains

Protein: ENSMUSP00000104288
Gene: ENSMUSG00000089669

Domain	Start	End	E-Value	Type
Blast:TNF	39	87	1e-22	BLAST
TNF	97	224	6.21e-2	SMART

Predicted Effect

probably damaging
Transcript: ENSMUST00000108649
AA Change: S141P

PolyPhen 2 Score 0.988 (Sensitivity: 0.73; Specificity: 0.96)

SMART Domains

Protein: ENSMUSP00000104289
Gene: ENSMUSG00000018752
AA Change: S141P

Domain	Start	End	E-Value	Type
low complexity region	4	14	N/A	INTRINSIC
transmembrane domain	20	42	N/A	INTRINSIC
low complexity region	90	109	N/A	INTRINSIC
PDB:4HT1\|T	110	166	1e-31	PDB
Blast:TNF	117	166	4e-27	BLAST
low complexity region	190	195	N/A	INTRINSIC
TNF	196	329	7.41e-3	SMART

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000140371

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000144033

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000145435

Predicted Effect

probably damaging
Transcript: ENSMUST00000174159
AA Change: S141P

PolyPhen 2 Score 0.989 (Sensitivity: 0.72; Specificity: 0.97)

SMART Domains

Protein: ENSMUSP00000133951
Gene: ENSMUSG00000018752
AA Change: S141P

Domain	Start	End	E-Value	Type
low complexity region	4	14	N/A	INTRINSIC
transmembrane domain	20	42	N/A	INTRINSIC
low complexity region	90	109	N/A	INTRINSIC
TNF	117	255	6.18e-10	SMART
low complexity region	269	274	N/A	INTRINSIC
TNF	275	408	7.41e-3	SMART

Predicted Effect

probably damaging
Transcript: ENSMUST00000180587
AA Change: S142P

PolyPhen 2 Score 0.994 (Sensitivity: 0.69; Specificity: 0.97)

SMART Domains

Protein: ENSMUSP00000137973
Gene: ENSMUSG00000018752
AA Change: S142P

Domain	Start	End	E-Value	Type
low complexity region	4	14	N/A	INTRINSIC
transmembrane domain	20	42	N/A	INTRINSIC
low complexity region	91	110	N/A	INTRINSIC
TNF	118	256	6.18e-10	SMART
low complexity region	270	275	N/A	INTRINSIC
TNF	276	410	1.91e-2	SMART

Predicted Effect

probably damaging
Transcript: ENSMUST00000181810
AA Change: S141P

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)

SMART Domains

Protein: ENSMUSP00000137972
Gene: ENSMUSG00000097328
AA Change: S141P

Domain	Start	End	E-Value	Type
low complexity region	4	14	N/A	INTRINSIC
transmembrane domain	20	42	N/A	INTRINSIC
low complexity region	90	109	N/A	INTRINSIC
TNF	117	248	3.67e-35	SMART

Predicted Effect

probably benign
Transcript: ENSMUST00000181261

SMART Domains

Protein: ENSMUSP00000137916
Gene: ENSMUSG00000097328

Domain	Start	End	E-Value	Type
low complexity region	52	71	N/A	INTRINSIC
Blast:TNF	72	98	8e-8	BLAST
PDB:4HT1\|T	72	98	1e-12	PDB

Meta Mutation Damage Score

0.6632

Coding Region Coverage

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

Validation Efficiency

100% (52/52)

MGI Phenotype

FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] The protein encoded by this gene is a cytokine that belongs to the tumor necrosis factor (TNF) ligand family. This protein is a ligand for the FN14/TWEAKR receptor. This cytokine has overlapping signaling functions with TNF, but displays a much wider tissue distribution. This cytokine, which exists in both membrane-bound and secreted forms, can induce apoptosis via multiple pathways of cell death in a cell type-specific manner. This cytokine is also found to promote proliferation and migration of endothelial cells, and thus acts as a regulator of angiogenesis. Alternative splicing results in multiple transcript variants. Some transcripts skip the last exon of this gene and continue into the second exon of the neighboring TNFSF13 gene; such read-through transcripts are contained in GeneID 407977, TNFSF12-TNFSF13. [provided by RefSeq, Oct 2010]
PHENOTYPE: Mice homozygous for disruptions in this gene have increased numbers of natural killer cells, particulalry in secondary lymph organs. They display an enhanced inflammatory response, increased susceptibility to lipopolysaccharide, and increased tumor resistance. [provided by MGI curators]

Allele List at MGI

Other mutations in this stock

Total: 52 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
4921513D11Rik	G	T	17: 79,935,638 (GRCm39)		probably benign	Het
Apeh	C	T	9: 107,971,486 (GRCm39)	A29T	probably damaging	Het
Arap2	A	T	5: 62,826,524 (GRCm39)	Y1013*	probably null	Het
Arhgef4	A	G	1: 34,762,355 (GRCm39)	E537G	unknown	Het
Asf1b	T	C	8: 84,682,540 (GRCm39)	F28S	probably damaging	Het
Cd46	T	A	1: 194,767,693 (GRCm39)	I123L	possibly damaging	Het
Cdca7	A	T	2: 72,309,370 (GRCm39)	T48S	probably damaging	Het
Cfap53	T	A	18: 74,492,838 (GRCm39)		probably benign	Het
Clca3a2	T	A	3: 144,511,599 (GRCm39)	T599S	probably benign	Het
Csf1	T	A	3: 107,656,252 (GRCm39)	T148S	probably benign	Het
Dmbt1	T	C	7: 130,699,400 (GRCm39)		probably null	Het
Dmpk	A	G	7: 18,818,050 (GRCm39)	D44G	probably damaging	Het
Dnajb12	T	A	10: 59,728,782 (GRCm39)	N223K	probably damaging	Het
Dync1h1	T	A	12: 110,595,264 (GRCm39)	M1392K	probably benign	Het
Edrf1	C	T	7: 133,261,908 (GRCm39)	A867V	probably damaging	Het
Efemp2	T	A	19: 5,527,706 (GRCm39)	C94S	possibly damaging	Het
Epha8	C	T	4: 136,666,037 (GRCm39)	S373N	probably benign	Het
Foxk1	A	G	5: 142,434,588 (GRCm39)	D284G	possibly damaging	Het
Fzd10	C	A	5: 128,678,366 (GRCm39)	R29S	possibly damaging	Het
Gm13991	T	C	2: 116,358,665 (GRCm39)		noncoding transcript	Het
Gm6818	A	T	7: 38,101,471 (GRCm39)		noncoding transcript	Het
Hydin	T	A	8: 111,336,333 (GRCm39)	C5037S	probably benign	Het
Ikzf1	T	A	11: 11,719,448 (GRCm39)	M492K	probably damaging	Het
Krt20	G	T	11: 99,320,879 (GRCm39)	S394R	possibly damaging	Het
Lrrc71	T	A	3: 87,653,094 (GRCm39)	R107S	probably benign	Het
Mia2	A	G	12: 59,219,323 (GRCm39)	T436A	possibly damaging	Het
Muc19	T	A	15: 91,784,614 (GRCm39)		noncoding transcript	Het
Neu4	T	C	1: 93,952,177 (GRCm39)	V182A	probably damaging	Het
Notch2	T	G	3: 98,031,626 (GRCm39)	F1167V	possibly damaging	Het
Nrap	A	G	19: 56,360,277 (GRCm39)	M189T	possibly damaging	Het
Nt5m	A	T	11: 59,765,487 (GRCm39)	I172F	probably damaging	Het
Or5b118	G	T	19: 13,449,037 (GRCm39)	K234N	probably damaging	Het
Or5w15	G	A	2: 87,568,119 (GRCm39)	P183L	possibly damaging	Het
Or8k41	A	T	2: 86,313,362 (GRCm39)	C241*	probably null	Het
Plekha5	C	T	6: 140,372,254 (GRCm39)	T68M	probably damaging	Het
Ppef2	A	G	5: 92,392,461 (GRCm39)		probably null	Het
Ppp1r37	T	C	7: 19,295,900 (GRCm39)		probably benign	Het
Rfx4	T	C	10: 84,704,218 (GRCm39)	Y238H	probably damaging	Het
Sanbr	A	G	11: 23,543,424 (GRCm39)		probably null	Het
Sec13	G	A	6: 113,707,837 (GRCm39)	A161V	probably benign	Het
Serhl	G	A	15: 82,986,895 (GRCm39)		probably benign	Het
Slco4a1	T	C	2: 180,114,572 (GRCm39)	V588A	probably benign	Het
Slitrk3	T	C	3: 72,956,592 (GRCm39)	T727A	probably benign	Het
Sp100	T	A	1: 85,601,404 (GRCm39)	D241E	probably damaging	Het
Spata2	G	T	2: 167,325,494 (GRCm39)	H442N	probably damaging	Het
Speg	T	C	1: 75,404,731 (GRCm39)	V2588A	probably damaging	Het
Trank1	A	G	9: 111,219,762 (GRCm39)	I2166M	probably damaging	Het
Trim10	T	A	17: 37,187,948 (GRCm39)	V388E	probably damaging	Het
Ttc23l	G	T	15: 10,551,636 (GRCm39)	T30K	possibly damaging	Het
Vmn2r10	A	G	5: 109,143,466 (GRCm39)	V828A	probably benign	Het
Vmn2r75	T	A	7: 85,813,436 (GRCm39)	L455F	possibly damaging	Het
Vwa8	T	A	14: 79,221,666 (GRCm39)	S541T	probably benign	Het

Other mutations in Tnfsf12

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
PIT4519001:Tnfsf12	UTSW	11	69,586,230 (GRCm39)	missense	probably benign	0.00
R2100:Tnfsf12	UTSW	11	69,578,175 (GRCm39)	missense	probably damaging	1.00
R5849:Tnfsf12	UTSW	11	69,577,793 (GRCm39)	missense	probably damaging	0.97
R7383:Tnfsf12	UTSW	11	69,577,892 (GRCm39)	missense	probably damaging	1.00
R8436:Tnfsf12	UTSW	11	69,577,713 (GRCm39)	missense	probably damaging	1.00
Z1176:Tnfsf12	UTSW	11	69,586,529 (GRCm39)	missense	unknown

Predicted Primers

PCR Primer
(F):5'- GCCAGGCATCTTCCTTCATG -3'
(R):5'- CCACCTATACTCTGGGCAAG -3'

Sequencing Primer
(F):5'- TTCCTTCATGAGTCGCAGAG -3'
(R):5'- ATACTCTGGGCAAGCTGTAC -3'

Posted On

2016-06-21