Mutagenetix > Incidental Mutation

Incidental Mutation 'R5864:Mettl8'

454041

Institutional Source

Beutler Lab

Gene Symbol

Mettl8

Ensembl Gene

ENSMUSG00000041975

Gene Name

methyltransferase 8, methylcytidine

Synonyms

TIP

Accession Numbers

Essential gene?

Probably essential (E-score: 0.880) question?

Stock #

R5864 (G1)

Quality Score

225

Status

Not validated

Chromosome

Chromosomal Location

70794905-70885927 bp(-) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

T to C at 70812357 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Threonine to Alanine at position 58 (T58A)

Ref Sequence

ENSEMBL: ENSMUSP00000119863 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000090849] [ENSMUST00000100037] [ENSMUST00000112179] [ENSMUST00000112186] [ENSMUST00000121586] [ENSMUST00000148876] [ENSMUST00000149181]

AlphaFold

A2AUU0

Predicted Effect

probably benign
Transcript: ENSMUST00000090849

Predicted Effect

probably benign
Transcript: ENSMUST00000100037
AA Change: T93A

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

SMART Domains

Protein: ENSMUSP00000097615
Gene: ENSMUSG00000041975
AA Change: T93A

Domain	Start	End	E-Value	Type
Pfam:Methyltransf_23	115	304	1.4e-14	PFAM
Pfam:Ubie_methyltran	126	265	1.4e-7	PFAM
Pfam:Methyltransf_31	137	304	5.6e-10	PFAM
Pfam:Methyltransf_26	140	251	4.2e-8	PFAM
Pfam:Methyltransf_25	143	246	5.3e-13	PFAM
Pfam:Methyltransf_12	144	248	1e-12	PFAM
Pfam:Methyltransf_11	144	250	7.4e-14	PFAM

Predicted Effect

probably benign
Transcript: ENSMUST00000112179
AA Change: T140A

PolyPhen 2 Score 0.010 (Sensitivity: 0.96; Specificity: 0.77)

SMART Domains

Protein: ENSMUSP00000107800
Gene: ENSMUSG00000041975
AA Change: T140A

Domain	Start	End	E-Value	Type
low complexity region	190	206	N/A	INTRINSIC

Predicted Effect

probably benign
Transcript: ENSMUST00000112186
AA Change: T140A

PolyPhen 2 Score 0.010 (Sensitivity: 0.96; Specificity: 0.77)

SMART Domains

Protein: ENSMUSP00000107804
Gene: ENSMUSG00000041975
AA Change: T140A

Domain	Start	End	E-Value	Type
Pfam:Methyltransf_23	158	349	5.1e-15	PFAM
Pfam:Ubie_methyltran	173	312	8.7e-8	PFAM
Pfam:Methyltransf_31	184	348	3.7e-9	PFAM
Pfam:Methyltransf_25	190	293	3.9e-13	PFAM
Pfam:Methyltransf_12	191	295	7e-13	PFAM
Pfam:Methyltransf_11	191	297	6.2e-13	PFAM

Predicted Effect

probably benign
Transcript: ENSMUST00000121586
AA Change: T140A

PolyPhen 2 Score 0.010 (Sensitivity: 0.96; Specificity: 0.77)

SMART Domains

Protein: ENSMUSP00000113642
Gene: ENSMUSG00000041975
AA Change: T140A

Domain	Start	End	E-Value	Type
Pfam:Methyltransf_25	190	279	1.4e-6	PFAM
Pfam:Methyltransf_11	191	280	5.6e-7	PFAM

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000124208

Predicted Effect

probably benign
Transcript: ENSMUST00000148876
AA Change: T140A

PolyPhen 2 Score 0.010 (Sensitivity: 0.96; Specificity: 0.77)

SMART Domains

Protein: ENSMUSP00000115855
Gene: ENSMUSG00000041975
AA Change: T140A

Domain	Start	End	E-Value	Type
Pfam:Methyltransf_25	190	281	1.9e-8	PFAM
Pfam:Methyltransf_11	191	280	2.8e-8	PFAM

Predicted Effect

probably benign
Transcript: ENSMUST00000149181
AA Change: T58A

PolyPhen 2 Score 0.101 (Sensitivity: 0.93; Specificity: 0.86)

SMART Domains

Protein: ENSMUSP00000119863
Gene: ENSMUSG00000041975
AA Change: T58A

Domain	Start	End	E-Value	Type
SCOP:d1af7_2	107	137	7e-3	SMART

Coding Region Coverage

1x: 99.9%
3x: 99.5%
10x: 97.7%
20x: 93.0%

Validation Efficiency

MGI Phenotype

FUNCTION: This locus encodes a member of the methyltransferase family, and is involved in chromatin remodeling. Transcripts from this locus can be induced or inhibited by cell stretch and affect cell differentiation in the myogenic or adipogenic pathways. Multiple transcript variants encoding different isoforms have been found for this gene. Additional splice variants have been described in the literature but they meet nonsense-mediated decay (NMD) criteria and are likely to be degraded as soon as they are transcribed. [provided by RefSeq, Jul 2008]
PHENOTYPE: Mice homozygous for a knock-out allele exhibit reduced 3-methylcytidine (m3C) methyltransferases modification of mRNA. [provided by MGI curators]

Allele List at MGI

Other mutations in this stock

Total: 56 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Acot4	A	T	12: 84,090,178 (GRCm39)	I292F	probably benign	Het
Adamdec1	A	G	14: 68,807,551 (GRCm39)	S370P	probably damaging	Het
Ankar	T	C	1: 72,698,324 (GRCm39)	K692R	probably benign	Het
Ano6	T	C	15: 95,818,261 (GRCm39)		probably null	Het
Asns	G	A	6: 7,675,443 (GRCm39)	Q520*	probably null	Het
Bbs12	C	T	3: 37,373,639 (GRCm39)	T144I	probably damaging	Het
C8g	C	T	2: 25,388,955 (GRCm39)	G186D	probably damaging	Het
Clptm1l	T	C	13: 73,754,403 (GRCm39)	F109S	probably damaging	Het
Coa8	G	A	12: 111,717,652 (GRCm39)	V171I	probably benign	Het
Col4a1	G	A	8: 11,252,973 (GRCm39)		probably benign	Het
Cpn2	T	C	16: 30,078,501 (GRCm39)	D400G	probably damaging	Het
Dgke	G	C	11: 88,941,288 (GRCm39)	Y298*	probably null	Het
Dnah5	G	A	15: 28,297,159 (GRCm39)	R1451Q	possibly damaging	Het
Dock8	A	G	19: 25,038,584 (GRCm39)	D90G	probably damaging	Het
Dok7	A	C	5: 35,223,890 (GRCm39)	D143A	probably damaging	Het
Elk3	G	A	10: 93,120,653 (GRCm39)	A62V	probably damaging	Het
Epha2	T	A	4: 141,035,738 (GRCm39)	M58K	probably damaging	Het
Erp27	G	T	6: 136,885,098 (GRCm39)	D233E	probably benign	Het
Gm5174	T	A	10: 86,493,045 (GRCm39)		noncoding transcript	Het
Gxylt2	A	G	6: 100,760,107 (GRCm39)	D214G	probably damaging	Het
Hrob	G	A	11: 102,145,972 (GRCm39)	E83K	probably benign	Het
Ifi35	A	T	11: 101,349,069 (GRCm39)	I238F	probably damaging	Het
Ighmbp2	T	C	19: 3,311,467 (GRCm39)	T983A	probably benign	Het
Itgb4	C	T	11: 115,881,748 (GRCm39)	R766W	probably damaging	Het
Lrp1	C	A	10: 127,403,374 (GRCm39)	K2066N	possibly damaging	Het
Mansc1	T	G	6: 134,587,816 (GRCm39)		probably null	Het
Mapre3	T	C	5: 31,020,582 (GRCm39)	F101S	probably damaging	Het
Mical1	G	T	10: 41,362,064 (GRCm39)	R857L	possibly damaging	Het
Nacad	T	C	11: 6,550,581 (GRCm39)	D870G	probably benign	Het
Nectin1	A	G	9: 43,702,607 (GRCm39)	D118G	probably damaging	Het
Nlrp2	A	T	7: 5,325,380 (GRCm39)	L26Q	probably damaging	Het
Or10a3m	A	G	7: 108,312,671 (GRCm39)	D25G	probably benign	Het
Pamr1	T	C	2: 102,464,693 (GRCm39)	S281P	possibly damaging	Het
Pcdhgc5	T	A	18: 37,954,814 (GRCm39)	V696E	probably damaging	Het
Pde4d	G	T	13: 110,074,582 (GRCm39)	A396S	probably benign	Het
Pecam1	G	T	11: 106,575,076 (GRCm39)	C510*	probably null	Het
Pga5	C	T	19: 10,652,513 (GRCm39)	G76S	probably damaging	Het
Phldb3	A	T	7: 24,323,571 (GRCm39)	H435L	possibly damaging	Het
Piezo1	T	C	8: 123,213,112 (GRCm39)	R1884G	possibly damaging	Het
Ripk4	T	C	16: 97,564,782 (GRCm39)	H43R	probably damaging	Het
Rtn3	A	G	19: 7,412,476 (GRCm39)	V785A	probably damaging	Het
Safb2	A	G	17: 56,873,491 (GRCm39)		probably benign	Het
Sephs1	T	C	2: 4,910,393 (GRCm39)	F288L	probably damaging	Het
Sez6l	A	G	5: 112,586,266 (GRCm39)		probably null	Het
Siglece	A	G	7: 43,308,741 (GRCm39)	L204P	probably damaging	Het
Sis	T	C	3: 72,857,151 (GRCm39)	D380G	probably damaging	Het
Slamf9	G	T	1: 172,304,033 (GRCm39)	R126L	probably benign	Het
Sorl1	A	G	9: 42,003,669 (GRCm39)	L209P	probably damaging	Het
Sptbn1	A	C	11: 30,095,925 (GRCm39)	I310S	probably damaging	Het
Tex52	A	G	6: 128,356,645 (GRCm39)	T113A	probably benign	Het
Trav6-3	T	A	14: 53,667,628 (GRCm39)	Y33*	probably null	Het
Vmn2r102	A	G	17: 19,914,943 (GRCm39)	E836G	possibly damaging	Het
Wdsub1	C	T	2: 59,708,819 (GRCm39)	C18Y	probably damaging	Het
Zfp341	C	A	2: 154,485,474 (GRCm39)	H637N	possibly damaging	Het
Zfp445	C	T	9: 122,682,552 (GRCm39)	S463N	probably benign	Het
Zfp612	G	A	8: 110,816,358 (GRCm39)	D522N	probably damaging	Het

Other mutations in Mettl8

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL00795:Mettl8	APN	2	70,812,434 (GRCm39)	missense	probably damaging	1.00
IGL01370:Mettl8	APN	2	70,812,383 (GRCm39)	missense	probably damaging	1.00
R1709:Mettl8	UTSW	2	70,812,495 (GRCm39)	missense	probably benign	0.02
R1944:Mettl8	UTSW	2	70,803,623 (GRCm39)	missense	probably damaging	1.00
R5107:Mettl8	UTSW	2	70,795,901 (GRCm39)	missense	probably damaging	1.00
R5278:Mettl8	UTSW	2	70,803,641 (GRCm39)	missense	probably damaging	1.00
R5629:Mettl8	UTSW	2	70,795,913 (GRCm39)	missense	probably benign
R6272:Mettl8	UTSW	2	70,806,419 (GRCm39)	splice site	probably null
R6402:Mettl8	UTSW	2	70,796,805 (GRCm39)	nonsense	probably null
R6535:Mettl8	UTSW	2	70,803,733 (GRCm39)	missense	possibly damaging	0.73
R7181:Mettl8	UTSW	2	70,803,706 (GRCm39)	missense	possibly damaging	0.79
R7288:Mettl8	UTSW	2	70,812,382 (GRCm39)	missense	probably benign	0.01
R7409:Mettl8	UTSW	2	70,803,687 (GRCm39)	missense	probably damaging	1.00
R7498:Mettl8	UTSW	2	70,795,969 (GRCm39)	missense	probably damaging	0.98
R7639:Mettl8	UTSW	2	70,812,526 (GRCm39)	missense	probably benign
R7789:Mettl8	UTSW	2	70,796,806 (GRCm39)	missense	probably damaging	1.00
R7795:Mettl8	UTSW	2	70,812,243 (GRCm39)	missense	probably benign
R8934:Mettl8	UTSW	2	70,882,062 (GRCm39)	unclassified	probably benign
R9600:Mettl8	UTSW	2	70,812,383 (GRCm39)	missense	possibly damaging	0.46
X0062:Mettl8	UTSW	2	70,812,318 (GRCm39)	missense	probably benign	0.33
Z1177:Mettl8	UTSW	2	70,803,682 (GRCm39)	missense	probably damaging	1.00

Predicted Primers

PCR Primer
(F):5'- GATCTTTCCACCTGGACAGTC -3'
(R):5'- TGAAAGTGACGCTAACAAATACTGG -3'

Sequencing Primer
(F):5'- GTCTGGACCACTCATAAAATAGCGTG -3'
(R):5'- ACTGGGATATATTTTACCAGACCC -3'

Posted On

2017-02-10