Mutagenetix > Incidental Mutation

Incidental Mutation 'R8311:Metap2'

641387

Institutional Source

Beutler Lab

Gene Symbol

Metap2

Ensembl Gene

ENSMUSG00000036112

Gene Name

methionine aminopeptidase 2

Synonyms

eIF-2-associated p67, 4930584B20Rik, A930035J23Rik, p67

MMRRC Submission

067796-MU

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R8311 (G1)

Quality Score

225.009

Status

Validated

Chromosome

Chromosomal Location

93694351-93732952 bp(-) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

C to T at 93697384 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Arginine to Histidine at position 432 (R432H)

Ref Sequence

ENSEMBL: ENSMUSP00000138083 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000047910] [ENSMUST00000180840] [ENSMUST00000181091] [ENSMUST00000181217] [ENSMUST00000181470]

AlphaFold

O08663

Predicted Effect

possibly damaging
Transcript: ENSMUST00000047910
AA Change: R422H

PolyPhen 2 Score 0.845 (Sensitivity: 0.83; Specificity: 0.93)

SMART Domains

Protein: ENSMUSP00000048285
Gene: ENSMUSG00000036112
AA Change: R422H

Domain	Start	End	E-Value	Type
low complexity region	24	48	N/A	INTRINSIC
low complexity region	77	108	N/A	INTRINSIC
Pfam:Peptidase_M24	167	466	1.2e-47	PFAM

Predicted Effect

probably benign
Transcript: ENSMUST00000180392

Predicted Effect

possibly damaging
Transcript: ENSMUST00000180840
AA Change: R422H

PolyPhen 2 Score 0.845 (Sensitivity: 0.83; Specificity: 0.93)

SMART Domains

Protein: ENSMUSP00000138006
Gene: ENSMUSG00000036112
AA Change: R422H

Domain	Start	End	E-Value	Type
low complexity region	24	48	N/A	INTRINSIC
low complexity region	77	108	N/A	INTRINSIC
Pfam:Peptidase_M24	167	466	2.8e-50	PFAM

Predicted Effect

possibly damaging
Transcript: ENSMUST00000181091
AA Change: R399H

PolyPhen 2 Score 0.653 (Sensitivity: 0.87; Specificity: 0.91)

SMART Domains

Protein: ENSMUSP00000137904
Gene: ENSMUSG00000036112
AA Change: R399H

Domain	Start	End	E-Value	Type
low complexity region	24	48	N/A	INTRINSIC
low complexity region	77	108	N/A	INTRINSIC
Pfam:Peptidase_M24	144	443	2.2e-50	PFAM

Predicted Effect

possibly damaging
Transcript: ENSMUST00000181217
AA Change: R432H

PolyPhen 2 Score 0.708 (Sensitivity: 0.86; Specificity: 0.92)

SMART Domains

Protein: ENSMUSP00000138083
Gene: ENSMUSG00000036112
AA Change: R432H

Domain	Start	End	E-Value	Type
low complexity region	24	48	N/A	INTRINSIC
low complexity region	77	108	N/A	INTRINSIC
Pfam:Peptidase_M24	177	476	2.7e-50	PFAM

Predicted Effect

probably benign
Transcript: ENSMUST00000181470

SMART Domains

Protein: ENSMUSP00000138050
Gene: ENSMUSG00000036112

Domain	Start	End	E-Value	Type
Pfam:Peptidase_M24	1	97	6.6e-15	PFAM

Coding Region Coverage

1x: 100.0%
3x: 99.9%
10x: 99.6%
20x: 98.8%

Validation Efficiency

100% (53/53)

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 member of the methionyl aminopeptidase family. The encoded protein functions both by protecting the alpha subunit of eukaryotic initiation factor 2 from inhibitory phosphorylation and by removing the amino-terminal methionine residue from nascent proteins. Increased expression of this gene is associated with various forms of cancer, and the anti-cancer drugs fumagillin and ovalicin inhibit the protein by irreversibly binding to its active site. Inhibitors of this gene have also been shown to be effective for the treatment of obesity. A pseudogene of this gene is located on chromosome 2. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2015]
PHENOTYPE: Homozygous mutation of this gene results in embryonic lethality around E8.5, smaller size, failure to gastrulate, reduced cell proliferation and absence of a distinct mesoderm. [provided by MGI curators]

Allele List at MGI

Other mutations in this stock

Total: 55 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
2700049A03Rik	A	G	12: 71,184,815 (GRCm39)		probably benign	Het
4930407I10Rik	T	C	15: 81,947,440 (GRCm39)	W446R	possibly damaging	Het
Aldh1l2	T	A	10: 83,326,479 (GRCm39)	E912D	probably damaging	Het
Apol9a	T	C	15: 77,289,220 (GRCm39)	D49G	possibly damaging	Het
Bnc2	A	T	4: 84,194,582 (GRCm39)	D847E	possibly damaging	Het
Ccdc91	A	G	6: 147,437,114 (GRCm39)	N100S	possibly damaging	Het
Copb2	G	T	9: 98,450,072 (GRCm39)	K10N	possibly damaging	Het
Cyp4a14	A	G	4: 115,348,275 (GRCm39)	S401P	probably damaging	Het
Cyp4f15	A	T	17: 32,916,914 (GRCm39)	Q277L	probably benign	Het
Dmxl2	A	T	9: 54,354,217 (GRCm39)	S410T	probably benign	Het
Dnah9	T	C	11: 65,880,644 (GRCm39)	N2651S	probably benign	Het
Efhb	A	G	17: 53,720,489 (GRCm39)		probably null	Het
Eif4ebp1	T	A	8: 27,765,124 (GRCm39)	F113L	probably damaging	Het
Emilin2	C	G	17: 71,562,141 (GRCm39)	D954H	probably damaging	Het
Eng	A	G	2: 32,569,005 (GRCm39)	T511A	probably benign	Het
Eps8l1	A	G	7: 4,474,817 (GRCm39)	D266G	probably damaging	Het
Fam120a	T	C	13: 49,087,433 (GRCm39)	H309R	possibly damaging	Het
Gga3	A	T	11: 115,477,834 (GRCm39)	S585T	probably benign	Het
Gm12117	T	C	11: 33,226,126 (GRCm39)	Q70R	probably damaging	Het
Gpr158	A	G	2: 21,373,701 (GRCm39)	H212R	probably benign	Het
Hmgb1	A	G	5: 148,987,427 (GRCm39)	F41L	possibly damaging	Het
Iqcm	T	A	8: 76,480,118 (GRCm39)		probably benign	Het
Itgav	T	A	2: 83,596,121 (GRCm39)	I214N	probably damaging	Het
Kcna1	T	A	6: 126,619,255 (GRCm39)	H355L	probably benign	Het
Lrrc37a	C	T	11: 103,394,247 (GRCm39)	V393I	probably benign	Het
Mak16	T	C	8: 31,658,697 (GRCm39)	D4G	probably damaging	Het
Nlrc4	G	A	17: 74,753,540 (GRCm39)	T281M	probably damaging	Het
Ntrk1	T	A	3: 87,688,870 (GRCm39)	Q561L	probably damaging	Het
Or10ak7	A	C	4: 118,791,347 (GRCm39)	S231A	probably damaging	Het
Or10w3	A	G	19: 13,704,035 (GRCm39)	T137A	possibly damaging	Het
Pira1	T	C	7: 3,739,482 (GRCm39)	D462G	probably benign	Het
Polr2a	T	C	11: 69,628,282 (GRCm39)	I1304V	probably null	Het
Ppp4r2	T	C	6: 100,843,343 (GRCm39)	S354P	probably benign	Het
Ptchd3	A	G	11: 121,727,299 (GRCm39)	H391R	possibly damaging	Het
Rchy1	T	C	5: 92,099,762 (GRCm39)	D192G	probably damaging	Het
Rmdn1	T	C	4: 19,575,329 (GRCm39)		probably null	Het
Rp1	T	A	1: 4,418,572 (GRCm39)	I847L	probably benign	Het
Rtn1	T	C	12: 72,350,838 (GRCm39)	E457G	probably damaging	Het
Serpind1	G	A	16: 17,160,730 (GRCm39)	S420N	possibly damaging	Het
Sirpa	T	C	2: 129,458,143 (GRCm39)	V253A	probably damaging	Het
Snapc4	A	T	2: 26,268,546 (GRCm39)	F38L	probably benign	Het
Spata31g1	T	C	4: 42,973,169 (GRCm39)	V834A	probably benign	Het
Srcap	T	C	7: 127,156,969 (GRCm39)	F2321S	probably damaging	Het
Stat4	A	T	1: 52,142,075 (GRCm39)	I641F	probably damaging	Het
Tmem216	A	T	19: 10,529,191 (GRCm39)	F65Y	probably benign	Het
Tmem37	C	T	1: 119,995,982 (GRCm39)	V32M	possibly damaging	Het
Tmprss11c	T	G	5: 86,383,412 (GRCm39)	Q338P	probably damaging	Het
Tonsl	C	T	15: 76,517,463 (GRCm39)	S752N	probably benign	Het
Vmn1r26	T	C	6: 57,985,518 (GRCm39)	K224E	probably benign	Het
Vps13b	T	A	15: 35,887,100 (GRCm39)	V3229D	probably benign	Het
Vwa5b2	C	T	16: 20,409,972 (GRCm39)	R21W	probably damaging	Het
Wdr37	T	C	13: 8,903,609 (GRCm39)	R165G	unknown	Het
Yars2	T	C	16: 16,125,147 (GRCm39)	F388L	probably benign	Het
Ykt6	T	A	11: 5,912,366 (GRCm39)	D106E	probably benign	Het
Zc3h12a	A	C	4: 125,020,788 (GRCm39)	S18R	possibly damaging	Het

Other mutations in Metap2

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL01671:Metap2	APN	10	93,707,340 (GRCm39)	splice site	probably benign
IGL02553:Metap2	APN	10	93,701,311 (GRCm39)	missense	probably damaging	1.00
R0212:Metap2	UTSW	10	93,697,242 (GRCm39)	missense	probably damaging	1.00
R0749:Metap2	UTSW	10	93,715,429 (GRCm39)	missense	probably benign	0.43
R1183:Metap2	UTSW	10	93,706,046 (GRCm39)	missense	probably damaging	1.00
R1459:Metap2	UTSW	10	93,704,811 (GRCm39)	missense	probably damaging	1.00
R1468:Metap2	UTSW	10	93,707,345 (GRCm39)	splice site	probably null
R1468:Metap2	UTSW	10	93,707,345 (GRCm39)	splice site	probably null
R1646:Metap2	UTSW	10	93,706,059 (GRCm39)	missense	probably damaging	1.00
R3810:Metap2	UTSW	10	93,706,026 (GRCm39)	nonsense	probably null
R3811:Metap2	UTSW	10	93,706,026 (GRCm39)	nonsense	probably null
R3812:Metap2	UTSW	10	93,706,026 (GRCm39)	nonsense	probably null
R4174:Metap2	UTSW	10	93,715,427 (GRCm39)	missense	possibly damaging	0.68
R4801:Metap2	UTSW	10	93,704,757 (GRCm39)	missense	probably damaging	1.00
R4802:Metap2	UTSW	10	93,704,757 (GRCm39)	missense	probably damaging	1.00
R4983:Metap2	UTSW	10	93,725,462 (GRCm39)	missense	possibly damaging	0.86
R5030:Metap2	UTSW	10	93,715,539 (GRCm39)	splice site	probably null
R5276:Metap2	UTSW	10	93,704,794 (GRCm39)	missense	probably benign	0.02
R5276:Metap2	UTSW	10	93,704,784 (GRCm39)	missense	possibly damaging	0.93
R8191:Metap2	UTSW	10	93,701,267 (GRCm39)	critical splice donor site	probably null
R9622:Metap2	UTSW	10	93,707,366 (GRCm39)	missense	probably benign	0.02

Predicted Primers

PCR Primer
(F):5'- AATAGTCATCTCCTCTGCTGAC -3'
(R):5'- TGCAGACACAGCTTAGATTTGAC -3'

Sequencing Primer
(F):5'- GACAACTTCTTTACAGGTTGGACGC -3'
(R):5'- AGAAATCTGCCTGCCTCTGTCAAG -3'

Posted On

2020-07-28