Mutagenetix > Incidental Mutation

Incidental Mutation 'R4546:Mfn2'

333761

Institutional Source

Beutler Lab

Gene Symbol

Mfn2

Ensembl Gene

ENSMUSG00000029020

Gene Name

mitofusin 2

Synonyms

hypertension related protein 1, Fzo, D630023P19Rik

MMRRC Submission

041780-MU

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R4546 (G1)

Quality Score

225

Status

Validated

Chromosome

Chromosomal Location

147958056-147989161 bp(-) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

A to G at 147971909 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Valine to Alanine at position 224 (V224A)

Ref Sequence

ENSEMBL: ENSMUSP00000101341 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000030884] [ENSMUST00000105714] [ENSMUST00000105715] [ENSMUST00000105716] [ENSMUST00000134172]

AlphaFold

Q80U63

Predicted Effect

probably benign
Transcript: ENSMUST00000030884
AA Change: V224A

PolyPhen 2 Score 0.116 (Sensitivity: 0.93; Specificity: 0.86)

SMART Domains

Protein: ENSMUSP00000030884
Gene: ENSMUSG00000029020
AA Change: V224A

Domain	Start	End	E-Value	Type
Pfam:MMR_HSR1	98	258	3.8e-6	PFAM
Pfam:Dynamin_N	99	259	2e-24	PFAM
low complexity region	336	347	N/A	INTRINSIC
coiled coil region	406	433	N/A	INTRINSIC
Pfam:Fzo_mitofusin	594	754	1.6e-77	PFAM

Predicted Effect

probably benign
Transcript: ENSMUST00000105714
AA Change: V224A

PolyPhen 2 Score 0.116 (Sensitivity: 0.93; Specificity: 0.86)

SMART Domains

Protein: ENSMUSP00000101339
Gene: ENSMUSG00000029020
AA Change: V224A

Domain	Start	End	E-Value	Type
Pfam:MMR_HSR1	98	258	6.1e-7	PFAM
Pfam:Dynamin_N	99	259	3.6e-25	PFAM
low complexity region	336	347	N/A	INTRINSIC
coiled coil region	406	433	N/A	INTRINSIC

Predicted Effect

probably benign
Transcript: ENSMUST00000105715
AA Change: V224A

PolyPhen 2 Score 0.116 (Sensitivity: 0.93; Specificity: 0.86)

SMART Domains

Protein: ENSMUSP00000101340
Gene: ENSMUSG00000029020
AA Change: V224A

Domain	Start	End	E-Value	Type
Pfam:MMR_HSR1	98	258	9e-7	PFAM
Pfam:Dynamin_N	99	259	5.4e-25	PFAM
low complexity region	336	347	N/A	INTRINSIC
coiled coil region	406	433	N/A	INTRINSIC
Pfam:Fzo_mitofusin	586	756	3.9e-86	PFAM

Predicted Effect

probably benign
Transcript: ENSMUST00000105716
AA Change: V224A

PolyPhen 2 Score 0.116 (Sensitivity: 0.93; Specificity: 0.86)

SMART Domains

Protein: ENSMUSP00000101341
Gene: ENSMUSG00000029020
AA Change: V224A

Domain	Start	End	E-Value	Type
Pfam:MMR_HSR1	98	258	9e-7	PFAM
Pfam:Dynamin_N	99	259	5.4e-25	PFAM
low complexity region	336	347	N/A	INTRINSIC
coiled coil region	406	433	N/A	INTRINSIC
Pfam:Fzo_mitofusin	586	756	3.9e-86	PFAM

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000124646

Predicted Effect

probably benign
Transcript: ENSMUST00000134172

SMART Domains

Protein: ENSMUSP00000123021
Gene: ENSMUSG00000029020

Domain	Start	End	E-Value	Type
Pfam:Dynamin_N	99	208	5.1e-16	PFAM

Meta Mutation Damage Score

0.2187

Coding Region Coverage

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

Validation Efficiency

97% (65/67)

MGI Phenotype

FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene encodes a mitochondrial membrane protein that participates in mitochondrial fusion and contributes to the maintenance and operation of the mitochondrial network. This protein is involved in the regulation of vascular smooth muscle cell proliferation, and it may play a role in the pathophysiology of obesity. Mutations in this gene cause Charcot-Marie-Tooth disease type 2A2, and hereditary motor and sensory neuropathy VI, which are both disorders of the peripheral nervous system. Defects in this gene have also been associated with early-onset stroke. Two transcript variants encoding the same protein have been identified. [provided by RefSeq, Jul 2008]
PHENOTYPE: Mice homozygous for disruptions in this gene die in mid-gestation. Structural and functional abnormalities of mitochondria are reported. [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
9930012K11Rik	G	A	14: 70,393,927 (GRCm39)	S236L	probably benign	Het
Ahcyl	C	T	16: 45,974,330 (GRCm39)	C349Y	possibly damaging	Het
Alg9	C	T	9: 50,716,654 (GRCm39)	T409M	possibly damaging	Het
Alpi	T	A	1: 87,026,839 (GRCm39)	Y413F	probably damaging	Het
Asmt	T	C	X: 169,110,230 (GRCm39)		probably null	Het
Atf7	A	G	15: 102,442,762 (GRCm39)	V449A	probably benign	Het
Bnc2	A	G	4: 84,210,213 (GRCm39)	F744L	probably benign	Het
Ccnyl1	G	T	1: 64,762,735 (GRCm39)	M347I	probably benign	Het
Cdk13	T	C	13: 17,941,159 (GRCm39)	K21R	probably damaging	Het
Cenpf	A	C	1: 189,386,847 (GRCm39)	L1811R	probably damaging	Het
Cfap91	C	T	16: 38,155,885 (GRCm39)	V113I	probably benign	Het
Cr2	A	G	1: 194,853,349 (GRCm39)	I43T	possibly damaging	Het
Cspg4	T	A	9: 56,795,913 (GRCm39)	L1216Q	possibly damaging	Het
Cylc2	A	T	4: 51,229,840 (GRCm39)	D394V	unknown	Het
Cylc2	C	G	4: 51,229,651 (GRCm39)	T331R	unknown	Het
Dcaf8	T	C	1: 172,007,460 (GRCm39)		probably benign	Het
Dlec1	A	T	9: 118,957,146 (GRCm39)	I796F	probably damaging	Het
Dnah12	A	T	14: 26,494,971 (GRCm39)	Q1343L	probably damaging	Het
Dnajc21	T	C	15: 10,447,183 (GRCm39)	R522G	probably benign	Het
F2rl3	C	T	8: 73,489,211 (GRCm39)	A146V	probably benign	Het
Fastkd1	C	T	2: 69,542,655 (GRCm39)	E51K	probably damaging	Het
Glrb	T	C	3: 80,786,993 (GRCm39)	S57G	probably damaging	Het
Gm5507	T	A	18: 54,117,409 (GRCm39)		noncoding transcript	Het
Golga4	A	G	9: 118,385,913 (GRCm39)	K22E	probably damaging	Het
Hdac1-ps	A	T	17: 78,800,388 (GRCm39)	T460S	probably benign	Het
Ift122	T	A	6: 115,867,549 (GRCm39)	L433Q	probably damaging	Het
Il21r	A	G	7: 125,228,071 (GRCm39)	R181G	probably damaging	Het
Il5ra	G	T	6: 106,715,459 (GRCm39)	S125*	probably null	Het
Kdm7a	T	C	6: 39,152,406 (GRCm39)	R97G	probably benign	Het
Lepr	T	A	4: 101,671,838 (GRCm39)	I954N	probably benign	Het
Lims1	T	C	10: 58,254,612 (GRCm39)		probably benign	Het
Mest	T	C	6: 30,740,679 (GRCm39)	W13R	probably damaging	Het
Muc15	T	C	2: 110,567,844 (GRCm39)	S330P	probably damaging	Het
Ncapg	T	C	5: 45,828,554 (GRCm39)	F102L	probably damaging	Het
Nkd2	T	C	13: 73,971,475 (GRCm39)	D187G	probably benign	Het
Nphp1	C	T	2: 127,607,939 (GRCm39)		probably null	Het
Or10ag59	T	C	2: 87,405,530 (GRCm39)	F34S	probably benign	Het
Or1e19	T	C	11: 73,316,012 (GRCm39)	N266D	probably benign	Het
Or2a12	C	T	6: 42,904,348 (GRCm39)	S61L	probably damaging	Het
Osbpl6	T	C	2: 76,414,836 (GRCm39)	V409A	possibly damaging	Het
Pdhx	A	T	2: 102,903,742 (GRCm39)	L18Q	probably null	Het
Pear1	C	T	3: 87,661,968 (GRCm39)	G469D	probably damaging	Het
Plec	T	C	15: 76,065,757 (GRCm39)	T1506A	probably benign	Het
Plod3	T	A	5: 137,017,801 (GRCm39)	D192E	possibly damaging	Het
Rbks	T	C	5: 31,781,912 (GRCm39)	N296S	probably benign	Het
Sema3c	G	A	5: 17,899,770 (GRCm39)	V421I	probably benign	Het
Slc15a4	A	G	5: 127,681,600 (GRCm39)		probably null	Het
Slc7a8	C	G	14: 54,973,247 (GRCm39)	G240A	possibly damaging	Het
Tmem200c	A	G	17: 69,149,166 (GRCm39)	D583G	probably benign	Het
Trpm6	A	G	19: 18,809,841 (GRCm39)	Y1079C	probably damaging	Het
Ttn	T	C	2: 76,652,932 (GRCm39)		probably null	Het
Vcp	T	C	4: 42,988,813 (GRCm39)		probably benign	Het
Vmn2r78	T	C	7: 86,603,811 (GRCm39)	V663A	probably damaging	Het
Vmn2r9	T	G	5: 108,995,551 (GRCm39)	M366L	probably benign	Het
Wdr11	A	G	7: 129,230,729 (GRCm39)	E878G	probably damaging	Het
Zan	C	G	5: 137,382,096 (GRCm39)	M5150I	unknown	Het

Other mutations in Mfn2

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL02313:Mfn2	APN	4	147,969,947 (GRCm39)	missense	probably damaging	1.00
IGL03236:Mfn2	APN	4	147,966,562 (GRCm39)	missense	probably damaging	1.00
milkshake	UTSW	4	147,971,909 (GRCm39)	missense	probably benign	0.12
R0066:Mfn2	UTSW	4	147,969,902 (GRCm39)	unclassified	probably benign
R0066:Mfn2	UTSW	4	147,969,902 (GRCm39)	unclassified	probably benign
R0326:Mfn2	UTSW	4	147,967,745 (GRCm39)	missense	probably damaging	1.00
R0376:Mfn2	UTSW	4	147,969,983 (GRCm39)	missense	probably benign	0.24
R0564:Mfn2	UTSW	4	147,967,712 (GRCm39)	missense	probably damaging	1.00
R0962:Mfn2	UTSW	4	147,966,658 (GRCm39)	missense	probably benign
R1595:Mfn2	UTSW	4	147,979,153 (GRCm39)	missense	probably benign	0.08
R2105:Mfn2	UTSW	4	147,973,162 (GRCm39)	nonsense	probably null
R2260:Mfn2	UTSW	4	147,979,063 (GRCm39)	nonsense	probably null
R4544:Mfn2	UTSW	4	147,971,909 (GRCm39)	missense	probably benign	0.12
R4561:Mfn2	UTSW	4	147,961,492 (GRCm39)	missense	probably damaging	1.00
R5151:Mfn2	UTSW	4	147,970,785 (GRCm39)	missense	probably benign	0.10
R5355:Mfn2	UTSW	4	147,979,035 (GRCm39)	missense	probably damaging	1.00
R6645:Mfn2	UTSW	4	147,979,069 (GRCm39)	missense	probably damaging	1.00
R8309:Mfn2	UTSW	4	147,974,693 (GRCm39)	missense	probably benign	0.03
R9345:Mfn2	UTSW	4	147,966,649 (GRCm39)	missense	probably benign	0.38

Predicted Primers

PCR Primer
(F):5'- AGACGTTCACTCACTTTGTGG -3'
(R):5'- ACAAACTGGGCATCCCTCAG -3'

Sequencing Primer
(F):5'- CACTCACTTTGTGGAAGAACTGC -3'
(R):5'- ATCCCTCAGTGGTCTGGAAG -3'

Posted On

2015-08-18