Mutagenetix > Incidental Mutation

Incidental Mutation 'R5355:Mfn2'

424030

Institutional Source

Beutler Lab

Gene Symbol

Mfn2

Ensembl Gene

ENSMUSG00000029020

Gene Name

mitofusin 2

Synonyms

hypertension related protein 1, Fzo, D630023P19Rik

MMRRC Submission

042934-MU

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R5355 (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 147979035 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Valine to Alanine at position 99 (V99A)

Ref Sequence

ENSEMBL: ENSMUSP00000123021 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000030884] [ENSMUST00000105714] [ENSMUST00000105715] [ENSMUST00000105716] [ENSMUST00000134172] [ENSMUST00000150881]

AlphaFold

Q80U63

Predicted Effect

probably damaging
Transcript: ENSMUST00000030884
AA Change: V99A

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

SMART Domains

Protein: ENSMUSP00000030884
Gene: ENSMUSG00000029020
AA Change: V99A

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 damaging
Transcript: ENSMUST00000105714
AA Change: V99A

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

SMART Domains

Protein: ENSMUSP00000101339
Gene: ENSMUSG00000029020
AA Change: V99A

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 damaging
Transcript: ENSMUST00000105715
AA Change: V99A

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

SMART Domains

Protein: ENSMUSP00000101340
Gene: ENSMUSG00000029020
AA Change: V99A

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 damaging
Transcript: ENSMUST00000105716
AA Change: V99A

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

SMART Domains

Protein: ENSMUSP00000101341
Gene: ENSMUSG00000029020
AA Change: V99A

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: ENSMUST00000118348

Predicted Effect

probably damaging
Transcript: ENSMUST00000134172
AA Change: V99A

PolyPhen 2 Score 0.999 (Sensitivity: 0.14; Specificity: 0.99)

SMART Domains

Protein: ENSMUSP00000123021
Gene: ENSMUSG00000029020
AA Change: V99A

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

Predicted Effect

probably benign
Transcript: ENSMUST00000150881

Meta Mutation Damage Score

0.4077

Coding Region Coverage

1x: 99.4%
3x: 98.8%
10x: 97.6%
20x: 96.2%

Validation Efficiency

94% (50/53)

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: 51 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Abcb1a	T	C	5: 8,776,873 (GRCm39)	L857P	probably damaging	Het
Adam12	T	C	7: 133,489,671 (GRCm39)	*582W	probably null	Het
Adra1d	A	G	2: 131,403,007 (GRCm39)	V361A	probably damaging	Het
Ank2	A	G	3: 126,737,698 (GRCm39)		probably benign	Het
Atxn10	T	A	15: 85,346,515 (GRCm39)	N424K	probably damaging	Het
C8b	A	G	4: 104,637,860 (GRCm39)	T111A	probably benign	Het
Ccdc168	A	C	1: 44,097,139 (GRCm39)	C1320G	possibly damaging	Het
Cdc45	C	T	16: 18,614,647 (GRCm39)	R205H	probably damaging	Het
Cdr2l	T	C	11: 115,284,396 (GRCm39)	V244A	possibly damaging	Het
Col11a2	A	G	17: 34,270,775 (GRCm39)	M468V	probably benign	Het
Col4a2	G	A	8: 11,495,984 (GRCm39)	R1535H	probably damaging	Het
Cryab	A	T	9: 50,664,751 (GRCm39)	S59C	probably damaging	Het
Cuzd1	G	A	7: 130,917,853 (GRCm39)	T249I	probably damaging	Het
Disp2	G	A	2: 118,617,392 (GRCm39)	V129M	probably benign	Het
Dlg2	G	T	7: 91,099,011 (GRCm39)	R31L	probably benign	Het
Dthd1	A	C	5: 62,996,730 (GRCm39)	L488F	probably damaging	Het
Dusp29	G	A	14: 21,727,091 (GRCm39)	R186W	probably benign	Het
Fat2	T	G	11: 55,172,992 (GRCm39)	I2574L	probably damaging	Het
Fchsd1	C	T	18: 38,092,926 (GRCm39)		probably benign	Het
Fryl	T	C	5: 73,231,247 (GRCm39)	D1610G	probably damaging	Het
Gm10330	T	A	12: 23,830,131 (GRCm39)	N17Y	probably damaging	Het
Gm4787	T	A	12: 81,424,239 (GRCm39)	R640*	probably null	Het
H2bc13	A	T	13: 21,900,030 (GRCm39)	I95N	probably damaging	Het
Ift88	T	A	14: 57,675,699 (GRCm39)	S71T	probably benign	Het
Isoc2b	A	G	7: 4,852,357 (GRCm39)		probably benign	Het
Itgb2	G	T	10: 77,393,886 (GRCm39)	R442L	probably benign	Het
Lama5	A	T	2: 179,823,444 (GRCm39)	N2658K	possibly damaging	Het
Lemd3	A	T	10: 120,769,538 (GRCm39)	I598K	probably damaging	Het
Lrp2	A	T	2: 69,285,182 (GRCm39)	C3825*	probably null	Het
Mep1a	T	C	17: 43,788,037 (GRCm39)	D673G	probably damaging	Het
Met	A	G	6: 17,491,361 (GRCm39)	Y41C	probably damaging	Het
Mmadhc	A	G	2: 50,181,436 (GRCm39)	I78T	probably benign	Het
Mmp9	C	A	2: 164,792,912 (GRCm39)	P389T	possibly damaging	Het
Mvk	T	G	5: 114,590,499 (GRCm39)	S7A	probably damaging	Het
Nlrp1a	T	A	11: 71,015,077 (GRCm39)	T58S	probably benign	Het
Nlrp1c-ps	C	A	11: 71,148,839 (GRCm39)		noncoding transcript	Het
Nr1h3	A	G	2: 91,022,253 (GRCm39)	I125T	possibly damaging	Het
Or2a55-ps1	C	T	6: 43,071,598 (GRCm39)		noncoding transcript	Het
Or8k39	A	T	2: 86,563,680 (GRCm39)	I92K	probably damaging	Het
Parn	A	G	16: 13,485,886 (GRCm39)	I3T	possibly damaging	Het
Parp8	A	G	13: 116,998,740 (GRCm39)		probably null	Het
Parva	T	C	7: 112,143,475 (GRCm39)		probably null	Het
Pwp2	A	C	10: 78,011,378 (GRCm39)	I672M	possibly damaging	Het
Sfswap	C	T	5: 129,616,810 (GRCm39)	T418I	probably benign	Het
Slc6a3	A	G	13: 73,709,078 (GRCm39)	Y334C	probably damaging	Het
Slc7a13	C	A	4: 19,839,267 (GRCm39)	T290K	probably benign	Het
Spry2	A	G	14: 106,130,712 (GRCm39)	L158P	probably damaging	Het
Usp25	A	G	16: 76,847,342 (GRCm39)	E150G	probably damaging	Het
Zfp747	A	G	7: 126,973,769 (GRCm39)	F134L	possibly damaging	Het
Zp3r	A	G	1: 130,524,518 (GRCm39)	F175S	probably benign	Het
Zscan22	C	A	7: 12,640,435 (GRCm39)	N67K	probably benign	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
R4546: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
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'- AAGTGAAAGTAGATGTGTGCTCC -3'
(R):5'- AGTCAACAGAGGTGGTCTTGTG -3'

Sequencing Primer
(F):5'- CCTGGTCTACAAAGTGAGTTCCAG -3'
(R):5'- TGTGGGAGATGGAGACTGTCAG -3'

Posted On

2016-08-04