Mutagenetix > Incidental Mutation

Incidental Mutation 'R9622:Metap2'

724886

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

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R9622 (G1)

Quality Score

225.009

Status

Not validated

Chromosome

Chromosomal Location

93694351-93732952 bp(-) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

T to C at 93707366 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Threonine to Alanine at position 202 (T202A)

Ref Sequence

ENSEMBL: ENSMUSP00000138083 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000047910] [ENSMUST00000180688] [ENSMUST00000180840] [ENSMUST00000181091] [ENSMUST00000181217]

AlphaFold

O08663

Predicted Effect

probably benign
Transcript: ENSMUST00000047910
AA Change: T192A

PolyPhen 2 Score 0.021 (Sensitivity: 0.95; Specificity: 0.80)

SMART Domains

Protein: ENSMUSP00000048285
Gene: ENSMUSG00000036112
AA Change: T192A

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: ENSMUST00000180688
AA Change: T191A

PolyPhen 2 Score 0.207 (Sensitivity: 0.92; Specificity: 0.88)

SMART Domains

Protein: ENSMUSP00000137652
Gene: ENSMUSG00000036112
AA Change: T191A

Domain	Start	End	E-Value	Type
low complexity region	24	48	N/A	INTRINSIC
low complexity region	76	107	N/A	INTRINSIC
Pfam:Peptidase_M24	166	233	2e-14	PFAM

Predicted Effect

probably benign
Transcript: ENSMUST00000180840
AA Change: T192A

PolyPhen 2 Score 0.021 (Sensitivity: 0.95; Specificity: 0.80)

SMART Domains

Protein: ENSMUSP00000138006
Gene: ENSMUSG00000036112
AA Change: T192A

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

probably benign
Transcript: ENSMUST00000181091
AA Change: T169A

PolyPhen 2 Score 0.021 (Sensitivity: 0.95; Specificity: 0.80)

SMART Domains

Protein: ENSMUSP00000137904
Gene: ENSMUSG00000036112
AA Change: T169A

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

probably benign
Transcript: ENSMUST00000181217
AA Change: T202A

PolyPhen 2 Score 0.021 (Sensitivity: 0.95; Specificity: 0.80)

SMART Domains

Protein: ENSMUSP00000138083
Gene: ENSMUSG00000036112
AA Change: T202A

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

Coding Region Coverage

1x: 100.0%
3x: 99.9%
10x: 99.7%
20x: 99.2%

Validation Efficiency

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: 80 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Ablim2	A	G	5: 36,006,889 (GRCm39)	K435E	probably damaging	Het
Acly	T	C	11: 100,395,785 (GRCm39)	T412A	probably damaging	Het
Aldh3b2	T	A	19: 4,029,489 (GRCm39)	D287E	probably benign	Het
Asphd1	G	A	7: 126,547,974 (GRCm39)	P110S		Het
Atg7	T	C	6: 114,654,993 (GRCm39)	L142P	probably benign	Het
Atp13a4	T	C	16: 29,239,277 (GRCm39)	I796V		Het
Bbx	A	G	16: 50,095,022 (GRCm39)	V98A	probably damaging	Het
Brca2	T	C	5: 150,480,410 (GRCm39)	S2727P	probably damaging	Het
Camk1	T	A	6: 113,318,850 (GRCm39)	D21V	possibly damaging	Het
Cdc5l	A	T	17: 45,715,709 (GRCm39)	D634E	probably benign	Het
Cfap418	T	C	4: 10,893,304 (GRCm39)	I141T	possibly damaging	Het
Cyfip1	A	T	7: 55,528,853 (GRCm39)	D275V	possibly damaging	Het
Cyp4a30b	A	G	4: 115,328,162 (GRCm39)	E477G	probably damaging	Het
Cyp4f16	C	T	17: 32,769,246 (GRCm39)	P379S	probably damaging	Het
Dchs2	C	T	3: 83,263,766 (GRCm39)	Q3345*	probably null	Het
Dnaaf1	A	G	8: 120,315,001 (GRCm39)	T270A	possibly damaging	Het
Dnah3	A	G	7: 119,561,356 (GRCm39)	V334A		Het
Dnhd1	T	C	7: 105,353,342 (GRCm39)	F2832L	probably benign	Het
Dock8	A	G	19: 25,098,545 (GRCm39)	N623S	probably null	Het
Eif4enif1	T	C	11: 3,165,714 (GRCm39)	I97T	probably benign	Het
Elmo1	C	G	13: 20,392,310 (GRCm39)	P29A	probably benign	Het
Erich6	G	C	3: 58,544,162 (GRCm39)	P142A	possibly damaging	Het
Fam135b	T	C	15: 71,397,686 (GRCm39)	R125G	probably damaging	Het
Fcrla	T	A	1: 170,749,808 (GRCm39)	H83L	probably damaging	Het
Flt3	C	T	5: 147,303,841 (GRCm39)	E366K	possibly damaging	Het
Gabbr2	C	T	4: 46,724,283 (GRCm39)		probably null	Het
Gigyf1	T	A	5: 137,522,926 (GRCm39)	L809*	probably null	Het
Glg1	C	T	8: 111,899,133 (GRCm39)	G711R	probably damaging	Het
Gp1bb	T	C	16: 18,439,527 (GRCm39)	E189G	probably benign	Het
H2-Q1	A	T	17: 35,542,532 (GRCm39)	I326F	probably benign	Het
Hoxb3	A	T	11: 96,235,420 (GRCm39)	K116*	probably null	Het
Kcnb1	T	C	2: 167,030,161 (GRCm39)	Y128C	probably damaging	Het
Kif5b	G	A	18: 6,225,672 (GRCm39)	R171C	probably damaging	Het
Lcn4	G	A	2: 26,561,228 (GRCm39)	Q18*	probably null	Het
Lrp1b	G	A	2: 40,779,354 (GRCm39)	Q2677*	probably null	Het
Map4k3	T	A	17: 80,958,538 (GRCm39)	T145S	probably damaging	Het
Mas1	T	C	17: 13,060,898 (GRCm39)	E175G	probably benign	Het
Mras	A	T	9: 99,275,054 (GRCm39)	M131K	probably benign	Het
Mtor	T	C	4: 148,568,169 (GRCm39)	V1092A	probably damaging	Het
Mug2	T	C	6: 122,028,751 (GRCm39)	S582P	probably benign	Het
Myo5b	A	G	18: 74,848,017 (GRCm39)	N1085S	probably damaging	Het
Nav3	T	C	10: 109,603,103 (GRCm39)	T1149A	probably benign	Het
Nipbl	A	T	15: 8,366,373 (GRCm39)	S1239T	probably benign	Het
Nkpd1	C	A	7: 19,257,867 (GRCm39)	R549S	probably benign	Het
Or10a3m	T	A	7: 108,312,677 (GRCm39)	M39K	probably benign	Het
Or10p1	G	A	10: 129,444,084 (GRCm39)	H89Y	probably benign	Het
Or1j1	A	G	2: 36,702,621 (GRCm39)	L161P	probably damaging	Het
Or51i2	T	A	7: 103,689,522 (GRCm39)	V173D	probably damaging	Het
Pcdh18	T	C	3: 49,711,229 (GRCm39)	N29D	probably benign	Het
Pdzrn4	T	C	15: 92,294,949 (GRCm39)	W52R	probably benign	Het
Plekhb1	T	C	7: 100,304,588 (GRCm39)	K39E	probably damaging	Het
Pramel28	A	G	4: 143,692,348 (GRCm39)	S218P	probably benign	Het
Psmb4	C	A	3: 94,792,285 (GRCm39)	E212D	probably benign	Het
Rcc1l	A	G	5: 134,205,348 (GRCm39)	L69P	probably damaging	Het
Robo2	T	C	16: 73,729,952 (GRCm39)	R1082G	probably benign	Het
Rorb	T	C	19: 18,955,115 (GRCm39)	Y167C	probably damaging	Het
Sanbr	T	A	11: 23,534,590 (GRCm39)	K589I	probably damaging	Het
Sbsn	GGAAATATGGCAGACAAGTTTGGTCAGGGGGCCCACCATGCTTTTGGTCAGGGCAG	GG	7: 30,452,067 (GRCm39)		probably benign	Het
Scaf8	T	A	17: 3,248,170 (GRCm39)	F1164L	probably benign	Het
Scn10a	A	T	9: 119,438,046 (GRCm39)	M1940K	probably benign	Het
Serpinb2	A	G	1: 107,452,298 (GRCm39)	N292S	probably benign	Het
Sparcl1	C	A	5: 104,234,998 (GRCm39)	V506L	possibly damaging	Het
Stt3a	A	G	9: 36,661,025 (GRCm39)	V262A	possibly damaging	Het
Syt17	C	A	7: 118,036,191 (GRCm39)	M58I	probably benign	Het
Tas2r134	A	C	2: 51,518,358 (GRCm39)	N279T	possibly damaging	Het
Tbc1d2	T	C	4: 46,609,065 (GRCm39)	E724G	probably damaging	Het
Teddm1b	T	A	1: 153,750,620 (GRCm39)	L143Q		Het
Tlk1	T	A	2: 70,617,281 (GRCm39)	R66S	probably damaging	Het
Tmem139	A	T	6: 42,240,176 (GRCm39)		probably null	Het
Tom1l2	T	C	11: 60,151,942 (GRCm39)	Y155C	possibly damaging	Het
Trmt1l	C	A	1: 151,304,710 (GRCm39)	S28*	probably null	Het
Ttf2	T	C	3: 100,859,918 (GRCm39)	I679V	probably benign	Het
Unc13b	T	G	4: 43,172,513 (GRCm39)	F1114V		Het
Vmn2r25	T	A	6: 123,816,579 (GRCm39)	D334V	probably damaging	Het
Vps13c	T	G	9: 67,856,715 (GRCm39)	Y2581D	probably damaging	Het
Xkr5	A	G	8: 18,984,247 (GRCm39)	S432P	probably benign	Het
Zc2hc1b	G	A	10: 13,043,677 (GRCm39)	P73S	possibly damaging	Het
Zfhx2	A	C	14: 55,303,483 (GRCm39)	F1500L	probably benign	Het
Zfp3	T	G	11: 70,662,739 (GRCm39)	S233A	possibly damaging	Het
Zmat5	T	C	11: 4,687,453 (GRCm39)	W169R	probably 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
R8311:Metap2	UTSW	10	93,697,384 (GRCm39)	missense	possibly damaging	0.71

Predicted Primers

PCR Primer
(F):5'- GGAGACACAGAATCTCTACCTAAG -3'
(R):5'- ATGACTCATACTATGCTGTGCC -3'

Sequencing Primer
(F):5'- AGCTAGTCAGGACTAAAATGACC -3'
(R):5'- ATGCTGTGCCTATTCCAAAGG -3'

Posted On

2022-09-12