Mutagenetix > Incidental Mutation

Incidental Mutation 'F6893:Mpi'

194

Institutional Source

Beutler Lab

Gene Symbol

Mpi

Ensembl Gene

ENSMUSG00000032306

Gene Name

mannose phosphate isomerase

Synonyms

Mpi-1, 1110002E17Rik, Mpi1

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

F6893 (G3) of strain busy

Quality Score

Status

Validated

Chromosome

Chromosomal Location

57451539-57460046 bp(-) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

A to T at 57453832 bp (GRCm39)

Zygosity

Homozygous

Amino Acid Change

Methionine to Lysine at position 230 (M230K)

Ref Sequence

ENSEMBL: ENSMUSP00000034856 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000034856] [ENSMUST00000093833] [ENSMUST00000114200]

AlphaFold

Q924M7

Predicted Effect

probably benign
Transcript: ENSMUST00000034856
AA Change: M230K

PolyPhen 2 Score 0.115 (Sensitivity: 0.93; Specificity: 0.86)

SMART Domains

Protein: ENSMUSP00000034856
Gene: ENSMUSG00000032306
AA Change: M230K

Domain	Start	End	E-Value	Type
Pfam:PMI_typeI	6	384	4.3e-145	PFAM

Predicted Effect

probably benign
Transcript: ENSMUST00000093833

SMART Domains

Protein: ENSMUSP00000091353
Gene: ENSMUSG00000032305

Domain	Start	End	E-Value	Type
Pfam:FAM219A	72	128	4.2e-18	PFAM

Predicted Effect

probably benign
Transcript: ENSMUST00000114200

SMART Domains

Protein: ENSMUSP00000109838
Gene: ENSMUSG00000032305

Domain	Start	End	E-Value	Type
Pfam:FAM219A	72	197	1.6e-62	PFAM

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000124593

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000140671

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000145543

Predicted Effect

probably benign
Transcript: ENSMUST00000156428

SMART Domains

Protein: ENSMUSP00000119342
Gene: ENSMUSG00000032306

Domain	Start	End	E-Value	Type
Pfam:PMI_typeI	3	119	3.1e-45	PFAM

Meta Mutation Damage Score

0.0643

Coding Region Coverage

1x: 88.7%
3x: 74.0%

Validation Efficiency

88% (165/188)

MGI Phenotype

FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] Phosphomannose isomerase catalyzes the interconversion of fructose-6-phosphate and mannose-6-phosphate and plays a critical role in maintaining the supply of D-mannose derivatives, which are required for most glycosylation reactions. Mutations in the MPI gene were found in patients with carbohydrate-deficient glycoprotein syndrome, type Ib. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2014]
PHENOTYPE: Homozygous null mice display embryonic lethality during organogenesis, variable abnormalities of the yolk sac and embryonic vasculature, and partial penetrance of abnormal chorioallantoic fusion, placental defects, impaired emrbyo turning, increased apoptosis, and posterior axial truncations. [provided by MGI curators]

Allele List at MGI

All alleles(6) : Targeted, other(2) Gene trapped(4)

Other mutations in this stock

Total: 35 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Abca14	G	A	7: 119,924,261 (GRCm39)	V1638M	probably damaging	Het
Agrn	C	T	4: 156,258,636 (GRCm39)	R972Q	probably benign	Het
Anxa3	T	C	5: 96,972,853 (GRCm39)		probably benign	Het
Bpifa6	G	T	2: 153,829,078 (GRCm39)	D202Y	probably damaging	Het
Ccdc15	G	A	9: 37,226,936 (GRCm39)	T346I	probably damaging	Homo
Celsr3	G	A	9: 108,712,266 (GRCm39)	R1731H	probably benign	Het
Ces4a	A	G	8: 105,873,859 (GRCm39)	R443G	possibly damaging	Het
Chd2	T	C	7: 73,157,620 (GRCm39)	Q175R	possibly damaging	Het
Dpyd	T	A	3: 118,597,783 (GRCm39)		probably null	Het
Dscam	G	T	16: 96,857,660 (GRCm39)	H117N	possibly damaging	Het
F13a1	A	G	13: 37,155,999 (GRCm39)	Y205H	probably damaging	Het
Fat3	A	C	9: 15,918,085 (GRCm39)	L1446R	probably damaging	Homo
Golga4	T	C	9: 118,382,525 (GRCm39)	L515S	probably damaging	Het
Hoxb1	A	T	11: 96,256,728 (GRCm39)	T26S	probably benign	Het
Igsf10	T	G	3: 59,238,481 (GRCm39)	T567P	probably damaging	Het
Lamb2	T	C	9: 108,359,755 (GRCm39)	V365A	probably benign	Het
Mepe	A	G	5: 104,485,242 (GRCm39)	I127M	possibly damaging	Het
Myh4	A	G	11: 67,146,283 (GRCm39)	D1447G	probably null	Homo
Or1f19	A	G	16: 3,411,027 (GRCm39)	I256V	possibly damaging	Het
Or1j4	A	G	2: 36,740,819 (GRCm39)	T254A	probably benign	Het
Panx2	T	C	15: 88,952,213 (GRCm39)	Y227H	probably damaging	Homo
Pdzd7	A	G	19: 45,025,173 (GRCm39)	W441R	probably damaging	Het
Poldip2	A	G	11: 78,410,020 (GRCm39)	I267M	probably damaging	Homo
Pros1	T	A	16: 62,745,002 (GRCm39)	V539E	probably damaging	Het
Sacs	T	C	14: 61,450,425 (GRCm39)	M4157T	probably benign	Het
Slc45a3	A	G	1: 131,909,075 (GRCm39)	E424G	probably benign	Homo
Slc9a1	A	G	4: 133,149,457 (GRCm39)	E761G	probably benign	Homo
Stab2	G	A	10: 86,691,035 (GRCm39)	P2178L	probably damaging	Het
Syt4	C	T	18: 31,577,274 (GRCm39)	V27I	possibly damaging	Homo
Thumpd1	T	A	7: 119,319,799 (GRCm39)	K56*	probably null	Het
Tpr	A	G	1: 150,269,313 (GRCm39)	K19E	possibly damaging	Homo
Ttll10	A	G	4: 156,132,775 (GRCm39)	I74T	probably benign	Het
Txnrd1	C	T	10: 82,702,823 (GRCm39)	Q95*	probably null	Homo
Zc3h7b	A	G	15: 81,662,872 (GRCm39)	E421G	possibly damaging	Homo
Zc3hc1	G	T	6: 30,387,525 (GRCm39)	D51E	probably benign	Homo

Other mutations in Mpi

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL00921:Mpi	APN	9	57,459,549 (GRCm39)	missense	probably damaging	1.00
IGL01071:Mpi	APN	9	57,457,875 (GRCm39)	missense	probably damaging	1.00
IGL01604:Mpi	APN	9	57,458,025 (GRCm39)	missense	possibly damaging	0.85
IGL02090:Mpi	APN	9	57,457,936 (GRCm39)	missense	probably benign	0.00
benadryl	UTSW	9	57,458,040 (GRCm39)	missense	probably damaging	1.00
sleepies	UTSW	9	57,452,472 (GRCm39)	unclassified	probably benign
Zyrtec	UTSW	9	57,452,500 (GRCm39)	missense	probably damaging	1.00
R0751:Mpi	UTSW	9	57,457,897 (GRCm39)	missense	probably damaging	1.00
R1146:Mpi	UTSW	9	57,452,472 (GRCm39)	unclassified	probably benign
R3727:Mpi	UTSW	9	57,452,132 (GRCm39)	missense	possibly damaging	0.69
R3944:Mpi	UTSW	9	57,452,536 (GRCm39)	missense	probably damaging	1.00
R4645:Mpi	UTSW	9	57,458,040 (GRCm39)	missense	probably damaging	1.00
R4772:Mpi	UTSW	9	57,452,181 (GRCm39)	missense	probably damaging	1.00
R4856:Mpi	UTSW	9	57,452,590 (GRCm39)	missense	probably damaging	1.00
R5088:Mpi	UTSW	9	57,457,887 (GRCm39)	missense	probably damaging	0.97
R5504:Mpi	UTSW	9	57,452,500 (GRCm39)	missense	probably damaging	1.00
R5886:Mpi	UTSW	9	57,455,745 (GRCm39)	unclassified	probably benign
R7038:Mpi	UTSW	9	57,452,500 (GRCm39)	missense	probably damaging	1.00
R7953:Mpi	UTSW	9	57,457,881 (GRCm39)	missense	probably damaging	1.00
R8043:Mpi	UTSW	9	57,457,881 (GRCm39)	missense	probably damaging	1.00
R8296:Mpi	UTSW	9	57,455,954 (GRCm39)	missense	probably benign	0.00
R8436:Mpi	UTSW	9	57,452,200 (GRCm39)	missense	probably damaging	1.00
R9696:Mpi	UTSW	9	57,452,539 (GRCm39)	missense	probably benign	0.01
R9742:Mpi	UTSW	9	57,452,606 (GRCm39)	missense	probably damaging	1.00
RF013:Mpi	UTSW	9	57,455,924 (GRCm39)	missense	probably benign	0.31

Nature of Mutation

DNA sequencing using the SOLiD technique identified a T to A transversion at position 722 of the Mpi transcript in exon 6 of 8 total exons. Multiple transcripts of the Mpi gene are displayed on Ensembl. The mutated nucleotide causes a methione to lysine substitution at amino acid 230 of the encoded protein. The mutation has been confirmed by DNA sequencing using the Sanger method (Figure 1).

Protein Function and Prediction

The Mpi gene encodes a 423 amino acid zinc-binding protein that is involved in the synthesis of the GDP-mannose and dolichol-phosphate-mannose required for a number of critical mannosyl transfer reactions (Uniprot Q924M7). Homozygous null mice display embryonic lethality during organogenesis, variable abnormalities of the yolk sac and embryonic vasculature, and partial penetrance of abnormal chorioallantoic fusion, placental defects, impaired emrbyo turning, increased apoptosis, and posterior axial truncations.

The M230K change is predicted to be benign by the PolyPhen program.

Posted On

2010-05-03