Mutagenetix > Incidental Mutation

Incidental Mutation 'R5849:Tnfsf12'

453789

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

044066-MU

Accession Numbers

Essential gene?

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

Stock #

R5849 (G1)

Quality Score

186

Status

Validated

Chromosome

Chromosomal Location

69577076-69586675 bp(-) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

C to A at 69577793 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Arginine to Leucine at position 208 (R208L)

Ref Sequence

ENSEMBL: ENSMUSP00000137972 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000018896] [ENSMUST00000066760] [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: 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

noncoding transcript
Transcript: ENSMUST00000140371

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000144033

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000145435

Predicted Effect

probably benign
Transcript: ENSMUST00000174159
AA Change: R208L

PolyPhen 2 Score 0.002 (Sensitivity: 0.99; Specificity: 0.30)

SMART Domains

Protein: ENSMUSP00000133951
Gene: ENSMUSG00000018752
AA Change: R208L

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
AA Change: R209L

PolyPhen 2 Score 0.000 (Sensitivity: 1.00; Specificity: 0.00)

SMART Domains

Protein: ENSMUSP00000137973
Gene: ENSMUSG00000018752
AA Change: R209L

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: R208L

PolyPhen 2 Score 0.969 (Sensitivity: 0.77; Specificity: 0.95)

SMART Domains

Protein: ENSMUSP00000137972
Gene: ENSMUSG00000097328
AA Change: R208L

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

0.3240

Coding Region Coverage

1x: 99.9%
3x: 99.6%
10x: 98.1%
20x: 94.3%

Validation Efficiency

96% (72/75)

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: 62 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
4930553M12Rik	T	C	4: 88,786,596 (GRCm39)	I7M	unknown	Het
Abca8b	C	A	11: 109,868,639 (GRCm39)	G175V	probably damaging	Het
Agbl1	T	C	7: 75,974,846 (GRCm39)	S113P	probably benign	Het
Ak9	A	G	10: 41,224,045 (GRCm39)	D486G	probably benign	Het
Aopep	A	G	13: 63,163,312 (GRCm39)	D111G	probably benign	Het
Arhgap11a	T	C	2: 113,665,192 (GRCm39)	S469G	probably null	Het
Comtd1	C	T	14: 21,898,188 (GRCm39)	G48D	probably damaging	Het
Cyp27a1	T	C	1: 74,775,843 (GRCm39)	S343P	probably damaging	Het
Dcun1d1	T	A	3: 35,970,333 (GRCm39)		probably benign	Het
Dennd4c	T	C	4: 86,744,223 (GRCm39)	I1404T	possibly damaging	Het
Dlgap5	A	G	14: 47,626,892 (GRCm39)	S766P	possibly damaging	Het
Ebf1	T	A	11: 44,881,331 (GRCm39)		probably null	Het
Flcn	T	A	11: 59,695,586 (GRCm39)	I4L	probably damaging	Het
Gm57858	A	T	3: 36,087,026 (GRCm39)	D189E	possibly damaging	Het
Grin2c	T	C	11: 115,151,817 (GRCm39)	T48A	probably benign	Het
Hyal5	T	A	6: 24,891,555 (GRCm39)	S456R	probably benign	Het
Igf1r	A	G	7: 67,839,781 (GRCm39)	D696G	probably benign	Het
Iqgap1	A	T	7: 80,452,906 (GRCm39)	V13D	probably benign	Het
Itgal	A	G	7: 126,916,492 (GRCm39)	N728S	probably benign	Het
Kcnb1	T	A	2: 166,947,946 (GRCm39)	I301F	probably damaging	Het
Kcnd3	A	G	3: 105,366,111 (GRCm39)		probably benign	Het
Kdm4a	C	T	4: 118,019,037 (GRCm39)	R393Q	probably benign	Het
Lcn9	G	A	2: 25,713,268 (GRCm39)		probably null	Het
Madcam1	T	A	10: 79,500,824 (GRCm39)	M47K	probably benign	Het
Matn3	A	G	12: 9,008,829 (GRCm39)	Q314R	probably benign	Het
Msh3	A	T	13: 92,386,386 (GRCm39)	D826E	possibly damaging	Het
Muc4	A	T	16: 32,595,213 (GRCm39)	T3088S	possibly damaging	Het
Mup3	T	G	4: 62,005,172 (GRCm39)		probably null	Het
Myo15b	A	G	11: 115,772,759 (GRCm39)	K1807E	probably damaging	Het
Myrip	A	G	9: 120,282,759 (GRCm39)	D688G	probably damaging	Het
Nup153	A	G	13: 46,840,452 (GRCm39)	F1052S	probably damaging	Het
Oplah	T	A	15: 76,181,547 (GRCm39)		probably benign	Het
Or4f14d	A	T	2: 111,960,223 (GRCm39)	I311K	probably benign	Het
Or52r1c	T	A	7: 102,734,728 (GRCm39)	M1K	probably null	Het
Or6z3	A	T	7: 6,463,993 (GRCm39)	I162F	possibly damaging	Het
Or9g19	A	T	2: 85,600,768 (GRCm39)	I208F	probably benign	Het
Pacsin2	A	G	15: 83,274,719 (GRCm39)	F120L	possibly damaging	Het
Ppp1r36	C	A	12: 76,485,931 (GRCm39)	P363Q	probably damaging	Het
Rai1	C	A	11: 60,081,347 (GRCm39)	H1804N	possibly damaging	Het
Rictor	G	A	15: 6,823,487 (GRCm39)	E1555K	probably benign	Het
Rnf214	G	A	9: 45,779,386 (GRCm39)	P455S	probably damaging	Het
Rnf220	T	C	4: 117,134,809 (GRCm39)	T188A	possibly damaging	Het
S1pr4	C	T	10: 81,335,157 (GRCm39)	V106M	possibly damaging	Het
Sall2	C	A	14: 52,551,704 (GRCm39)	S495I	probably benign	Het
Sars2	A	G	7: 28,443,683 (GRCm39)	E95G	possibly damaging	Het
Sema3f	G	A	9: 107,559,815 (GRCm39)	T693M	probably damaging	Het
Slfn2	C	A	11: 82,960,402 (GRCm39)	T127K	probably benign	Het
Snrpe	T	A	1: 133,536,652 (GRCm39)	I43L	probably benign	Het
Srsf1	T	C	11: 87,938,684 (GRCm39)	I7T	possibly damaging	Het
Ssbp1	T	A	6: 40,453,837 (GRCm39)		probably benign	Het
Stbd1	T	G	5: 92,752,854 (GRCm39)	F115V	probably benign	Het
Stk11ip	T	A	1: 75,503,999 (GRCm39)		probably null	Het
Taf1b	T	A	12: 24,550,524 (GRCm39)	N36K	probably damaging	Het
Tanc1	A	T	2: 59,630,248 (GRCm39)	M743L	probably benign	Het
Trafd1	T	C	5: 121,511,534 (GRCm39)	D428G	probably damaging	Het
Trim24	A	G	6: 37,934,664 (GRCm39)	E793G	probably damaging	Het
Tspan32	T	C	7: 142,569,324 (GRCm39)	C100R	probably damaging	Het
Ttn	T	C	2: 76,576,586 (GRCm39)	D16442G	probably damaging	Het
Ube3c	T	A	5: 29,863,407 (GRCm39)	L894Q	probably damaging	Het
Wfs1	C	G	5: 37,130,608 (GRCm39)	G213R	probably damaging	Het
Zfp384	G	A	6: 125,001,062 (GRCm39)	A45T	possibly damaging	Het
Zfp865	G	T	7: 5,034,086 (GRCm39)	K690N	probably damaging	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
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'- TGCCTTTGAGGAGAGGACAG -3'
(R):5'- AGATGCCTGGCTTTCGATGAG -3'

Sequencing Primer
(F):5'- CTGGACCAAGGAGCAGC -3'
(R):5'- CTTTCGATGAGGGAGGCAG -3'

Posted On

2017-02-10