Mutagenetix > Incidental Mutation

Incidental Mutation 'R8436:Tnfsf12'

654008

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

067777-MU

Accession Numbers

Essential gene?

Probably non essential (E-score: 0.147) question?

Stock #

R8436 (G1)

Quality Score

225.009

Status

Not validated

Chromosome

Chromosomal Location

69577076-69586675 bp(-) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

T to C at 69577713 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Lysine to Glutamic Acid at position 235 (K235E)

Ref Sequence

ENSEMBL: ENSMUSP00000137972 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000018896] [ENSMUST00000066760] [ENSMUST00000108648] [ENSMUST00000108649] [ENSMUST00000174159] [ENSMUST00000180587] [ENSMUST00000181261] [ENSMUST00000181810]

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: ENSMUST00000066760

SMART Domains

Protein: ENSMUSP00000066581
Gene: ENSMUSG00000005204

Domain	Start	End	E-Value	Type
low complexity region	25	40	N/A	INTRINSIC
low complexity region	42	53	N/A	INTRINSIC
low complexity region	74	86	N/A	INTRINSIC
low complexity region	118	131	N/A	INTRINSIC
low complexity region	183	195	N/A	INTRINSIC
Pfam:Peptidase_C48	394	566	4.9e-49	PFAM

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 benign
Transcript: ENSMUST00000108649

SMART Domains

Protein: ENSMUSP00000104289
Gene: ENSMUSG00000018752

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

probably benign
Transcript: ENSMUST00000174159

SMART Domains

Protein: ENSMUSP00000133951
Gene: ENSMUSG00000018752

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 benign
Transcript: ENSMUST00000180587

SMART Domains

Protein: ENSMUSP00000137973
Gene: ENSMUSG00000018752

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 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

Predicted Effect

probably damaging
Transcript: ENSMUST00000181810
AA Change: K235E

PolyPhen 2 Score 0.998 (Sensitivity: 0.27; Specificity: 0.99)

SMART Domains

Protein: ENSMUSP00000137972
Gene: ENSMUSG00000097328
AA Change: K235E

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

Coding Region Coverage

1x: 100.0%
3x: 100.0%
10x: 99.7%
20x: 99.2%

Validation Efficiency

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: 46 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
4930407I10Rik	A	G	15: 81,949,936 (GRCm39)	I1278V	possibly damaging	Het
Baz1b	A	G	5: 135,266,821 (GRCm39)	H1210R	probably damaging	Het
Cdt1	C	T	8: 123,296,070 (GRCm39)	S128L	probably benign	Het
Cfap54	A	T	10: 92,800,398 (GRCm39)	N1603K	unknown	Het
Cfap99	A	G	5: 34,469,026 (GRCm39)	N300S	possibly damaging	Het
Chrdl2	G	A	7: 99,676,940 (GRCm39)		probably null	Het
Cpb2	C	A	14: 75,510,015 (GRCm39)	F258L	probably damaging	Het
Csmd3	A	T	15: 47,868,218 (GRCm39)	D767E	probably damaging	Het
Dennd3	C	T	15: 73,434,198 (GRCm39)	T956I	probably damaging	Het
Emcn	A	G	3: 137,129,228 (GRCm39)	T245A	possibly damaging	Het
Gm4353	A	G	7: 115,682,864 (GRCm39)	V239A	probably damaging	Het
Gm4884	G	A	7: 40,692,810 (GRCm39)	A260T	probably damaging	Het
Hectd4	A	G	5: 121,446,421 (GRCm39)	D205G	possibly damaging	Het
Hectd4	A	G	5: 121,481,210 (GRCm39)	S3005G	probably benign	Het
Ifngr1	T	C	10: 19,479,553 (GRCm39)	L148P	probably damaging	Het
Irf2	C	T	8: 47,271,929 (GRCm39)	T172M	probably damaging	Het
Irs1	T	C	1: 82,267,970 (GRCm39)	H82R	possibly damaging	Het
Kcnc4	G	T	3: 107,366,084 (GRCm39)	N41K	probably damaging	Het
Lig3	C	T	11: 82,682,870 (GRCm39)	A490V	possibly damaging	Het
Megf6	G	A	4: 154,349,649 (GRCm39)	E946K	probably damaging	Het
Mpi	A	T	9: 57,452,200 (GRCm39)	Y359N	probably damaging	Het
Nf1	A	G	11: 79,349,709 (GRCm39)	S1365G	probably damaging	Het
P3h3	C	A	6: 124,828,041 (GRCm39)		probably null	Het
Pdk2	A	T	11: 94,930,259 (GRCm39)	V59D	probably damaging	Het
Ppip5k2	T	C	1: 97,683,613 (GRCm39)	K168R	probably benign	Het
Prg4	G	T	1: 150,331,318 (GRCm39)	P452T	unknown	Het
Prl2b1	T	C	13: 27,567,442 (GRCm39)	N234S	possibly damaging	Het
Rnd1	T	A	15: 98,574,455 (GRCm39)	T41S	possibly damaging	Het
Sall4	G	A	2: 168,597,830 (GRCm39)	P337S	probably damaging	Het
Slc1a2	G	A	2: 102,586,298 (GRCm39)	A301T	possibly damaging	Het
Sorcs3	C	T	19: 48,194,913 (GRCm39)	R99W	possibly damaging	Het
Svep1	G	A	4: 58,044,053 (GRCm39)	T3531I	possibly damaging	Het
Sycp2	T	C	2: 178,004,761 (GRCm39)	D894G	probably benign	Het
Syne1	T	C	10: 5,178,659 (GRCm39)	N4605S	probably benign	Het
Syt4	A	C	18: 31,573,472 (GRCm39)	C348G	possibly damaging	Het
Tceanc2	G	A	4: 107,034,778 (GRCm39)	T28M	probably damaging	Het
Tmco1	A	G	1: 167,136,254 (GRCm39)	D5G		Het
Trank1	T	C	9: 111,220,450 (GRCm39)	S2396P	possibly damaging	Het
Vipas39	T	A	12: 87,304,191 (GRCm39)	D125V	probably damaging	Het
Vmn1r86	A	G	7: 12,836,771 (GRCm39)	F35S	probably benign	Het
Vmn2r16	A	G	5: 109,511,649 (GRCm39)	N619D	probably damaging	Het
Vps13a	A	G	19: 16,718,157 (GRCm39)	V521A	probably benign	Het
Wdr20rt	T	A	12: 65,273,035 (GRCm39)	L166Q	probably damaging	Het
Zbtb11	T	A	16: 55,821,022 (GRCm39)	C706*	probably null	Het
Zfp764l1	C	T	7: 126,992,496 (GRCm39)	C38Y	probably null	Het
Zscan21	A	T	5: 138,116,178 (GRCm39)	Y30F	unknown	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
R5156:Tnfsf12	UTSW	11	69,578,155 (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
Z1176:Tnfsf12	UTSW	11	69,586,529 (GRCm39)	missense	unknown

Predicted Primers

PCR Primer
(F):5'- CGTCTGTGGAATGGAAAACATG -3'
(R):5'- AGGCTGTCTACCTGAAGCTG -3'

Sequencing Primer
(F):5'- ACATGTGAACAAGCTCTGGC -3'
(R):5'- TACCTGAAGCTGGACTTGC -3'

Posted On

2020-10-20