Mutagenetix > Incidental Mutation

Incidental Mutation 'P0007:Magi1'

7614

Institutional Source

Beutler Lab

Gene Symbol

Magi1

Ensembl Gene

ENSMUSG00000045095

Gene Name

membrane associated guanylate kinase, WW and PDZ domain containing 1

Synonyms

Baiap1, Gukmi1, AIP3, BAP1, WWP3

MMRRC Submission

038263-MU

Accession Numbers

Essential gene?

Possibly essential (E-score: 0.561) question?

Stock #

P0007 (G1)

Quality Score

Status

Validated

Chromosome

Chromosomal Location

93652436-94260898 bp(-) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

A to G at 93722969 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Isoleucine to Threonine at position 530 (I530T)

Ref Sequence

ENSEMBL: ENSMUSP00000086730 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000055224] [ENSMUST00000089317] [ENSMUST00000093769] [ENSMUST00000203519] [ENSMUST00000203688] [ENSMUST00000204347] [ENSMUST00000204532]

AlphaFold

Q6RHR9

PDB Structure

X-ray crystal structure of MAGI-1 PDZ1 bound to the C-terminal peptide of HPV18 E6 [X-RAY DIFFRACTION]

Predicted Effect

probably damaging
Transcript: ENSMUST00000055224
AA Change: I518T

PolyPhen 2 Score 0.991 (Sensitivity: 0.71; Specificity: 0.97)

SMART Domains

Protein: ENSMUSP00000062085
Gene: ENSMUSG00000045095
AA Change: I518T

Domain	Start	End	E-Value	Type
PDZ	26	105	8.04e-5	SMART
GuKc	111	295	2.55e-49	SMART
WW	301	333	9.65e-11	SMART
WW	348	380	2.88e-9	SMART
low complexity region	390	402	N/A	INTRINSIC
low complexity region	410	428	N/A	INTRINSIC
PDZ	460	536	3.71e-18	SMART
PDZ	631	703	4.68e-15	SMART
low complexity region	707	714	N/A	INTRINSIC
low complexity region	720	733	N/A	INTRINSIC
PDZ	800	876	4.64e-19	SMART
low complexity region	920	942	N/A	INTRINSIC
PDB:1UEW\|A	945	977	2e-6	PDB
PDZ	1043	1117	1.26e-20	SMART
low complexity region	1152	1164	N/A	INTRINSIC

Predicted Effect

probably damaging
Transcript: ENSMUST00000089317
AA Change: I530T

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)

SMART Domains

Protein: ENSMUSP00000086730
Gene: ENSMUSG00000045095
AA Change: I530T

Domain	Start	End	E-Value	Type
PDZ	26	105	4e-7	SMART
GuKc	111	295	1.3e-51	SMART
WW	301	333	5.8e-13	SMART
WW	360	392	1.7e-11	SMART
low complexity region	402	414	N/A	INTRINSIC
low complexity region	422	440	N/A	INTRINSIC
PDZ	472	548	1.9e-20	SMART
PDZ	643	715	2.3e-17	SMART
low complexity region	733	746	N/A	INTRINSIC
PDZ	841	917	2.4e-21	SMART
low complexity region	961	983	N/A	INTRINSIC
PDZ	999	1074	6.1e-25	SMART
PDZ	1140	1214	6.1e-23	SMART
low complexity region	1347	1357	N/A	INTRINSIC
low complexity region	1366	1423	N/A	INTRINSIC

Predicted Effect

probably damaging
Transcript: ENSMUST00000093769
AA Change: I303T

PolyPhen 2 Score 0.992 (Sensitivity: 0.70; Specificity: 0.97)

SMART Domains

Protein: ENSMUSP00000091283
Gene: ENSMUSG00000045095
AA Change: I303T

Domain	Start	End	E-Value	Type
low complexity region	10	15	N/A	INTRINSIC
WW	74	106	9.65e-11	SMART
WW	133	165	2.88e-9	SMART
low complexity region	175	187	N/A	INTRINSIC
low complexity region	195	213	N/A	INTRINSIC
PDZ	245	321	3.71e-18	SMART
PDZ	416	488	4.68e-15	SMART
low complexity region	492	499	N/A	INTRINSIC
low complexity region	505	518	N/A	INTRINSIC
PDZ	613	689	4.64e-19	SMART
low complexity region	733	755	N/A	INTRINSIC
PDZ	771	858	2.3e-23	SMART
PDZ	924	998	1.26e-20	SMART
low complexity region	1131	1141	N/A	INTRINSIC
low complexity region	1150	1207	N/A	INTRINSIC

Predicted Effect

probably damaging
Transcript: ENSMUST00000203519
AA Change: I530T

PolyPhen 2 Score 0.991 (Sensitivity: 0.71; Specificity: 0.97)

SMART Domains

Protein: ENSMUSP00000145244
Gene: ENSMUSG00000045095
AA Change: I530T

Domain	Start	End	E-Value	Type
PDZ	26	105	8.04e-5	SMART
GuKc	111	295	2.55e-49	SMART
WW	301	333	9.65e-11	SMART
WW	360	392	2.88e-9	SMART
low complexity region	402	414	N/A	INTRINSIC
low complexity region	422	440	N/A	INTRINSIC
PDZ	472	548	3.71e-18	SMART
PDZ	643	715	4.68e-15	SMART
low complexity region	719	726	N/A	INTRINSIC
low complexity region	732	745	N/A	INTRINSIC
PDZ	812	888	4.64e-19	SMART
low complexity region	932	954	N/A	INTRINSIC
PDB:1UEW\|A	957	989	2e-6	PDB
PDZ	1055	1115	1.13e-8	SMART

Predicted Effect

possibly damaging
Transcript: ENSMUST00000203688
AA Change: I303T

PolyPhen 2 Score 0.613 (Sensitivity: 0.87; Specificity: 0.91)

SMART Domains

Protein: ENSMUSP00000145515
Gene: ENSMUSG00000045095
AA Change: I303T

Domain	Start	End	E-Value	Type
Pfam:MAGI_u1	1	34	2.9e-17	PFAM
WW	74	106	9.65e-11	SMART
WW	133	165	2.88e-9	SMART
low complexity region	175	187	N/A	INTRINSIC
low complexity region	195	213	N/A	INTRINSIC
PDZ	245	321	3.71e-18	SMART
PDZ	416	488	4.68e-15	SMART
low complexity region	506	519	N/A	INTRINSIC
PDZ	614	690	4.64e-19	SMART
low complexity region	734	756	N/A	INTRINSIC
PDZ	772	858	1.74e-23	SMART
PDZ	924	998	1.26e-20	SMART

Predicted Effect

probably benign
Transcript: ENSMUST00000204347
AA Change: I530T

PolyPhen 2 Score 0.436 (Sensitivity: 0.89; Specificity: 0.90)

SMART Domains

Protein: ENSMUSP00000144881
Gene: ENSMUSG00000045095
AA Change: I530T

Domain	Start	End	E-Value	Type
PDZ	26	105	4e-7	SMART
GuKc	111	295	1.3e-51	SMART
WW	301	333	5.8e-13	SMART
WW	360	392	1.7e-11	SMART
low complexity region	402	414	N/A	INTRINSIC
low complexity region	422	440	N/A	INTRINSIC
PDZ	472	548	1.9e-20	SMART
PDZ	643	715	2.3e-17	SMART
low complexity region	733	746	N/A	INTRINSIC
PDZ	841	917	2.4e-21	SMART
low complexity region	961	983	N/A	INTRINSIC
PDZ	999	1086	1.1e-25	SMART
PDZ	1152	1226	6.1e-23	SMART
low complexity region	1261	1273	N/A	INTRINSIC

Predicted Effect

probably damaging
Transcript: ENSMUST00000204532
AA Change: I303T

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

SMART Domains

Protein: ENSMUSP00000144769
Gene: ENSMUSG00000045095
AA Change: I303T

Domain	Start	End	E-Value	Type
Pfam:MAGI_u1	1	34	1.8e-14	PFAM
WW	74	106	5.8e-13	SMART
WW	133	165	1.7e-11	SMART
low complexity region	175	187	N/A	INTRINSIC
low complexity region	195	213	N/A	INTRINSIC
PDZ	245	321	1.9e-20	SMART
PDZ	416	488	7.3e-17	SMART

Meta Mutation Damage Score

0.2464

Coding Region Coverage

1x: 85.2%
3x: 80.2%
10x: 65.3%
20x: 42.8%

Validation Efficiency

94% (102/109)

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 membrane-associated guanylate kinase homologue (MAGUK) family. MAGUK proteins participate in the assembly of multiprotein complexes on the inner surface of the plasma membrane at regions of cell-cell contact. The product of this gene may play a role as scaffolding protein at cell-cell junctions. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]

Allele List at MGI

All alleles(165) : Targeted(2) Gene trapped(163)

Other mutations in this stock

Total: 8 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Adamts6	A	G	13: 104,433,999 (GRCm39)	T143A	possibly damaging	Het
Cfap74	T	A	4: 155,506,685 (GRCm39)	S139T	possibly damaging	Het
Fbxo7	T	C	10: 85,869,157 (GRCm39)	S204P	possibly damaging	Het
Itga2	A	T	13: 115,002,735 (GRCm39)	I585N	probably damaging	Het
Lgi3	A	G	14: 70,774,152 (GRCm39)	Y442C	probably damaging	Het
Med12l	T	C	3: 58,998,816 (GRCm39)		probably benign	Het
Nbeal1	A	G	1: 60,358,847 (GRCm39)	I1176M	probably damaging	Het
Ostn	G	T	16: 27,143,279 (GRCm39)	G36*	probably null	Het

Other mutations in Magi1

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL01376:Magi1	APN	6	94,260,074 (GRCm39)	missense	possibly damaging	0.86
IGL01457:Magi1	APN	6	93,724,205 (GRCm39)	missense	probably damaging	0.99
IGL01642:Magi1	APN	6	93,663,605 (GRCm39)	missense	possibly damaging	0.69
IGL01724:Magi1	APN	6	93,769,381 (GRCm39)	splice site	probably null
IGL01967:Magi1	APN	6	93,685,115 (GRCm39)	missense	probably damaging	1.00
IGL01984:Magi1	APN	6	93,685,155 (GRCm39)	missense	probably damaging	1.00
IGL02074:Magi1	APN	6	93,722,579 (GRCm39)	missense	probably damaging	1.00
IGL02098:Magi1	APN	6	93,655,768 (GRCm39)	missense	probably damaging	1.00
IGL02225:Magi1	APN	6	93,671,007 (GRCm39)	missense	probably damaging	1.00
IGL02522:Magi1	APN	6	93,655,617 (GRCm39)	missense	possibly damaging	0.89
IGL02659:Magi1	APN	6	93,762,591 (GRCm39)	missense	possibly damaging	0.68
IGL02900:Magi1	APN	6	93,663,854 (GRCm39)	missense	probably damaging	1.00
R0149:Magi1	UTSW	6	93,724,226 (GRCm39)	missense	probably damaging	1.00
R0512:Magi1	UTSW	6	93,671,045 (GRCm39)	missense	probably damaging	1.00
R1487:Magi1	UTSW	6	93,685,060 (GRCm39)	missense	probably benign	0.00
R1497:Magi1	UTSW	6	93,724,310 (GRCm39)	missense	probably damaging	1.00
R1502:Magi1	UTSW	6	93,671,151 (GRCm39)	missense	probably damaging	1.00
R1824:Magi1	UTSW	6	93,676,620 (GRCm39)	missense	possibly damaging	0.94
R2042:Magi1	UTSW	6	93,732,026 (GRCm39)	missense	probably benign
R2132:Magi1	UTSW	6	93,674,255 (GRCm39)	missense	probably damaging	0.99
R2331:Magi1	UTSW	6	93,662,543 (GRCm39)	missense	probably damaging	1.00
R2418:Magi1	UTSW	6	93,722,891 (GRCm39)	missense	probably damaging	1.00
R3076:Magi1	UTSW	6	93,734,668 (GRCm39)	missense	possibly damaging	0.63
R3551:Magi1	UTSW	6	93,676,610 (GRCm39)	missense	probably damaging	0.98
R4005:Magi1	UTSW	6	93,678,299 (GRCm39)	missense	probably damaging	1.00
R4455:Magi1	UTSW	6	93,762,438 (GRCm39)	missense	probably damaging	1.00
R4670:Magi1	UTSW	6	93,663,624 (GRCm39)	splice site	probably null
R4671:Magi1	UTSW	6	93,657,768 (GRCm39)	critical splice donor site	probably null
R4839:Magi1	UTSW	6	93,671,177 (GRCm39)	missense	probably damaging	1.00
R5132:Magi1	UTSW	6	93,660,072 (GRCm39)	critical splice acceptor site	probably null
R5147:Magi1	UTSW	6	93,724,248 (GRCm39)	missense	probably damaging	1.00
R5525:Magi1	UTSW	6	93,769,354 (GRCm39)	missense	possibly damaging	0.95
R5724:Magi1	UTSW	6	93,722,682 (GRCm39)	missense	probably damaging	1.00
R5724:Magi1	UTSW	6	93,657,852 (GRCm39)	missense	probably benign	0.03
R5846:Magi1	UTSW	6	93,662,584 (GRCm39)	missense	probably damaging	1.00
R5896:Magi1	UTSW	6	93,685,180 (GRCm39)	missense	probably damaging	1.00
R5912:Magi1	UTSW	6	93,685,126 (GRCm39)	missense	possibly damaging	0.95
R6112:Magi1	UTSW	6	93,722,571 (GRCm39)	missense	probably damaging	1.00
R6115:Magi1	UTSW	6	93,685,051 (GRCm39)	missense	possibly damaging	0.64
R6351:Magi1	UTSW	6	93,920,210 (GRCm39)	missense	possibly damaging	0.82
R6355:Magi1	UTSW	6	94,260,177 (GRCm39)	missense	probably benign	0.06
R6457:Magi1	UTSW	6	93,676,620 (GRCm39)	missense	probably damaging	1.00
R6464:Magi1	UTSW	6	93,676,770 (GRCm39)	missense	probably damaging	1.00
R6613:Magi1	UTSW	6	93,722,654 (GRCm39)	missense	probably damaging	1.00
R6661:Magi1	UTSW	6	93,920,289 (GRCm39)	missense	probably benign	0.08
R6755:Magi1	UTSW	6	93,685,158 (GRCm39)	missense	probably damaging	1.00
R6909:Magi1	UTSW	6	93,674,301 (GRCm39)	missense	probably damaging	1.00
R7180:Magi1	UTSW	6	93,792,731 (GRCm39)	missense	probably benign	0.10
R7224:Magi1	UTSW	6	93,660,070 (GRCm39)	missense	probably benign	0.34
R7447:Magi1	UTSW	6	93,722,562 (GRCm39)	missense	possibly damaging	0.63
R7517:Magi1	UTSW	6	93,685,189 (GRCm39)	missense	probably damaging	0.99
R7537:Magi1	UTSW	6	93,685,091 (GRCm39)	nonsense	probably null
R7549:Magi1	UTSW	6	93,685,095 (GRCm39)	missense	probably benign	0.19
R7566:Magi1	UTSW	6	93,655,308 (GRCm39)	missense	probably benign	0.03
R7805:Magi1	UTSW	6	93,659,927 (GRCm39)	missense	probably benign
R8022:Magi1	UTSW	6	93,674,346 (GRCm39)	missense	probably damaging	1.00
R8290:Magi1	UTSW	6	94,260,066 (GRCm39)	missense	probably damaging	1.00
R8519:Magi1	UTSW	6	93,681,330 (GRCm39)	missense	possibly damaging	0.83
R8762:Magi1	UTSW	6	93,792,789 (GRCm39)	nonsense	probably null
R8894:Magi1	UTSW	6	93,663,586 (GRCm39)	missense	probably benign	0.12
R8974:Magi1	UTSW	6	93,674,223 (GRCm39)	missense	probably damaging	1.00
R9225:Magi1	UTSW	6	93,762,511 (GRCm39)	missense	possibly damaging	0.64
R9277:Magi1	UTSW	6	93,920,234 (GRCm39)	missense	possibly damaging	0.48
R9300:Magi1	UTSW	6	93,724,209 (GRCm39)	missense	probably damaging	1.00
R9393:Magi1	UTSW	6	93,659,890 (GRCm39)	missense	probably benign	0.27
R9402:Magi1	UTSW	6	94,260,278 (GRCm39)	missense	probably benign	0.00
R9432:Magi1	UTSW	6	93,660,058 (GRCm39)	missense	probably damaging	1.00
R9567:Magi1	UTSW	6	93,659,931 (GRCm39)	critical splice donor site	probably null
R9567:Magi1	UTSW	6	93,655,431 (GRCm39)	missense	probably damaging	1.00

Protein Function and Prediction

Membrane-associated guanylate kinase (MAGI)-1/BAI-associated protein (BAP) 1 is a member of the membrane-associated guanylate kinase homologue (MAGUK) family (1). These proteins are structural and signaling scaffold proteins that assemble in complexes at subcellular sites of polarized epithelial cells and neurons (2). MAGI1/BAP1 has been identified as a tumor-suppressor protein (3) that can inhibit cancer cell migration and invasion via the regulation of PTEN (4;5). Studies have proposed a role for MAGI1 in bipolar affective disorder and schizophrenia, although more needs to be studied (6).

Expression/Localization

Northern blot analysis determined that BAP1 is expressed ubiquitously (1). BAP1 associates with BAI1 at cytoplasmic membrane in COS-7 cells (1). Immunofluourescense determined that the protein is localized at the apical portions of cell-cell junctions (7). In intestinal epithelial cells, BAP1 localized at tight junctions (7).

References

1. Shiratsuchi, T., Futamura, M., Oda, K., Nishimori, H., Nakamura, Y., and Tokino, T. (1998) Cloning and Characterization of BAI-Associated Protein 1: A PDZ Domain-Containing Protein that Interacts with BAI1. Biochem Biophys Res Commun. 247, 597-604.

2. Laura, R. P., Ross, S., Koeppen, H., and Lasky, L. A. (2002) MAGI-1: A Widely Expressed, Alternatively Spliced Tight Junction Protein. Exp Cell Res. 275, 155-170.

3. Zaric, J., Joseph, J. M., Tercier, S., Sengstag, T., Ponsonnet, L., Delorenzi, M., and Ruegg, C. (2012) Identification of MAGI1 as a Tumor-Suppressor Protein Induced by Cyclooxygenase-2 Inhibitors in Colorectal Cancer Cells. Oncogene. 31, 48-59.

4. Zhang, G., and Wang, Z. (2011) MAGI1 Inhibits Cancer Cell Migration and Invasion of Hepatocellular Carcinoma Via Regulating PTEN. Zhong Nan Da Xue Xue Bao Yi Xue Ban. 36, 381-385.

5. Zhang, G., Liu, T., and Wang, Z. (2012) Downregulation of MAGI1 Associates with Poor Prognosis of Hepatocellular Carcinoma. J Invest Surg. 25, 93-99.

6. Karlsson, R., Graae, L., Lekman, M., Wang, D., Favis, R., Axelsson, T., Galter, D., Belin, A. C., and Paddock, S. (2012) MAGI1 Copy Number Variation in Bipolar Affective Disorder and Schizophrenia. Biol Psychiatry. 71, 922-930.

7. Ide, N., Hata, Y., Nishioka, H., Hirao, K., Yao, I., Deguchi, M., Mizoguchi, A., Nishimori, H., Tokino, T., Nakamura, Y., and Takai, Y. (1999) Localization of Membrane-Associated Guanylate Kinase (MAGI)-1/BAI-Associated Protein (BAP) 1 at Tight Junctions of Epithelial Cells. Oncogene. 18, 7810-7815.

Posted On

2012-10-05

Science Writer

Anne Murray