Mutagenetix > Incidental Mutation

Incidental Mutation 'R0037:Mast3'

15593

Institutional Source

Beutler Lab

Gene Symbol

Mast3

Ensembl Gene

ENSMUSG00000031833

Gene Name

microtubule associated serine/threonine kinase 3

Synonyms

MMRRC Submission

038331-MU

Accession Numbers

Ncbi RefSeq: NM_199308.2. MGI:2683541

Essential gene?

Non essential (E-score: 0.000) question?

Stock #

R0037 (G1)

Quality Score

Status

Validated

Chromosome

Chromosomal Location

70778117-70805054 bp(-) (GRCm38)

Type of Mutation

critical splice donor site (1 bp from exon)

DNA Base Change (assembly)

C to T at 70783699 bp (GRCm38)

Zygosity

Heterozygous

Amino Acid Change

Ref Sequence

ENSEMBL: ENSMUSP00000148686 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000166004] [ENSMUST00000166004] [ENSMUST00000211948]

AlphaFold

Q3U214

Predicted Effect

probably null
Transcript: ENSMUST00000166004

SMART Domains

Protein: ENSMUSP00000128703
Gene: ENSMUSG00000031833

Domain	Start	End	E-Value	Type
low complexity region	43	59	N/A	INTRINSIC
Pfam:DUF1908	64	337	4.4e-128	PFAM
S_TKc	373	646	2.77e-99	SMART
S_TK_X	647	710	2.39e-1	SMART
low complexity region	820	833	N/A	INTRINSIC
low complexity region	910	942	N/A	INTRINSIC
PDZ	958	1038	3.8e-15	SMART
low complexity region	1053	1074	N/A	INTRINSIC
low complexity region	1089	1121	N/A	INTRINSIC
low complexity region	1124	1150	N/A	INTRINSIC
low complexity region	1180	1204	N/A	INTRINSIC
low complexity region	1231	1248	N/A	INTRINSIC

Predicted Effect

probably null
Transcript: ENSMUST00000166004

SMART Domains

Protein: ENSMUSP00000128703
Gene: ENSMUSG00000031833

Domain	Start	End	E-Value	Type
low complexity region	43	59	N/A	INTRINSIC
Pfam:DUF1908	64	337	4.4e-128	PFAM
S_TKc	373	646	2.77e-99	SMART
S_TK_X	647	710	2.39e-1	SMART
low complexity region	820	833	N/A	INTRINSIC
low complexity region	910	942	N/A	INTRINSIC
PDZ	958	1038	3.8e-15	SMART
low complexity region	1053	1074	N/A	INTRINSIC
low complexity region	1089	1121	N/A	INTRINSIC
low complexity region	1124	1150	N/A	INTRINSIC
low complexity region	1180	1204	N/A	INTRINSIC
low complexity region	1231	1248	N/A	INTRINSIC

Predicted Effect

probably null
Transcript: ENSMUST00000211948

Predicted Effect

probably benign
Transcript: ENSMUST00000212140

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000212172

Meta Mutation Damage Score

0.9593

Coding Region Coverage

1x: 81.5%
3x: 73.9%
10x: 52.8%
20x: 32.9%

Validation Efficiency

94% (83/88)

Allele List at MGI

All alleles(2) : Targeted(1) Gene trapped(1)

Other mutations in this stock

Total: 38 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Aars	G	A	8: 111,043,259	R330Q	possibly damaging	Het
Amph	A	T	13: 19,100,653	S250C	possibly damaging	Het
Ankrd61	T	C	5: 143,894,977	N3S	probably damaging	Het
Camsap2	C	T	1: 136,281,892	E621K	probably damaging	Het
Cpt2	A	G	4: 107,907,974	S152P	probably damaging	Het
Csmd1	T	A	8: 15,917,248	Q3205L	probably damaging	Het
Dag1	G	T	9: 108,207,353	P863Q	probably damaging	Het
Dclk1	A	G	3: 55,256,059	I191V	probably benign	Het
Ddhd1	A	G	14: 45,610,510	L567P	probably damaging	Het
Enox1	T	C	14: 77,699,310		probably benign	Het
Exoc3	T	C	13: 74,199,539	E104G	probably damaging	Het
Foxp1	T	A	6: 99,162,969	Q17L	probably damaging	Het
Fscn1	A	G	5: 142,970,694		probably benign	Het
Fut8	T	C	12: 77,365,037	V91A	probably benign	Het
Gm5475	T	A	15: 100,424,202	Y77*	probably null	Het
Gm5800	T	C	14: 51,716,148		probably benign	Het
Hs2st1	T	A	3: 144,437,644	K213*	probably null	Het
Il5ra	T	A	6: 106,742,686	Y62F	probably damaging	Het
Inpp5d	A	G	1: 87,708,129	E734G	probably damaging	Het
Insig2	A	T	1: 121,306,920	C194S	probably damaging	Het
Lemd3	A	C	10: 120,925,456	H898Q	possibly damaging	Het
Lrp4	A	G	2: 91,471,203	T43A	probably benign	Het
Melk	T	C	4: 44,360,864		probably benign	Het
Myo10	C	T	15: 25,666,532		probably benign	Het
Nlrc5	G	A	8: 94,489,535	V967M	probably benign	Het
Nlrp9b	T	A	7: 20,023,722	F295I	probably damaging	Het
Phf3	A	T	1: 30,804,918	D1653E	probably benign	Het
Ppfia4	A	T	1: 134,324,089	L449Q	probably damaging	Het
Ppp1r16b	T	A	2: 158,757,209	I367N	probably damaging	Het
Ralgapb	T	C	2: 158,437,411	L139S	probably damaging	Het
Slc20a1	T	C	2: 129,210,772	V658A	probably damaging	Het
Son	C	A	16: 91,664,728	A347E	probably damaging	Het
Tprgl	C	A	4: 154,160,137	V134L	possibly damaging	Het
Trim24	A	T	6: 37,957,549	N733I	probably damaging	Het
Uggt1	A	T	1: 36,185,932	D540E	probably benign	Het
Urb2	T	A	8: 124,047,195	F1488L	probably damaging	Het
Utp20	T	C	10: 88,798,404	D810G	probably benign	Het
Zfp473	T	A	7: 44,733,900	K335N	probably damaging	Het

Other mutations in Mast3

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL00952:Mast3	APN	8	70780683	splice site	probably benign
IGL01411:Mast3	APN	8	70779583	missense	possibly damaging	0.50
IGL01475:Mast3	APN	8	70779530	missense	probably damaging	1.00
IGL01886:Mast3	APN	8	70782139	missense	possibly damaging	0.94
IGL02104:Mast3	APN	8	70787906	missense	possibly damaging	0.78
IGL02236:Mast3	APN	8	70789244	missense	probably benign	0.36
IGL02437:Mast3	APN	8	70780558	missense	possibly damaging	0.79
IGL02704:Mast3	APN	8	70786875	missense	probably damaging	1.00
IGL03155:Mast3	APN	8	70789217	missense	probably damaging	1.00
IGL03366:Mast3	APN	8	70781563	nonsense	probably null
gravy	UTSW	8	70786635	missense	probably damaging	1.00
stuffing	UTSW	8	70784797	frame shift	probably null
turkey	UTSW	8	70785482	missense	probably damaging	1.00
BB010:Mast3	UTSW	8	70786635	missense	probably damaging	1.00
BB020:Mast3	UTSW	8	70786635	missense	probably damaging	1.00
R0280:Mast3	UTSW	8	70783795	missense	probably damaging	1.00
R0280:Mast3	UTSW	8	70787920	missense	possibly damaging	0.65
R0731:Mast3	UTSW	8	70781321	missense	probably damaging	1.00
R1101:Mast3	UTSW	8	70786663	missense	probably damaging	1.00
R1177:Mast3	UTSW	8	70780324	missense	probably damaging	1.00
R1208:Mast3	UTSW	8	70788272	splice site	probably null
R1208:Mast3	UTSW	8	70788272	splice site	probably null
R1333:Mast3	UTSW	8	70781294	missense	probably damaging	1.00
R1543:Mast3	UTSW	8	70792311	missense	possibly damaging	0.93
R1544:Mast3	UTSW	8	70786172	missense	probably damaging	1.00
R1738:Mast3	UTSW	8	70784556	missense	probably benign	0.38
R1842:Mast3	UTSW	8	70780393	missense	possibly damaging	0.91
R1936:Mast3	UTSW	8	70784800	missense	probably damaging	1.00
R2015:Mast3	UTSW	8	70787363	missense	probably benign	0.00
R2219:Mast3	UTSW	8	70780963	missense	probably damaging	0.99
R2220:Mast3	UTSW	8	70780963	missense	probably damaging	0.99
R3711:Mast3	UTSW	8	70779607	missense	probably benign	0.13
R3919:Mast3	UTSW	8	70779422	missense	probably benign	0.02
R4027:Mast3	UTSW	8	70787908	missense	probably damaging	1.00
R4060:Mast3	UTSW	8	70781194	missense	probably damaging	1.00
R4061:Mast3	UTSW	8	70781194	missense	probably damaging	1.00
R4062:Mast3	UTSW	8	70781194	missense	probably damaging	1.00
R4063:Mast3	UTSW	8	70781194	missense	probably damaging	1.00
R4588:Mast3	UTSW	8	70780607	nonsense	probably null
R4672:Mast3	UTSW	8	70784797	frame shift	probably null
R4770:Mast3	UTSW	8	70786220	missense	probably damaging	1.00
R4822:Mast3	UTSW	8	70780366	missense	probably damaging	1.00
R4830:Mast3	UTSW	8	70788915	missense	possibly damaging	0.87
R5196:Mast3	UTSW	8	70788245	missense	probably damaging	1.00
R5333:Mast3	UTSW	8	70783501	missense	probably benign	0.03
R5428:Mast3	UTSW	8	70784733	missense	possibly damaging	0.95
R5656:Mast3	UTSW	8	70786221	missense	probably damaging	1.00
R5920:Mast3	UTSW	8	70787933	missense	probably benign	0.00
R6177:Mast3	UTSW	8	70790018	missense	probably damaging	1.00
R6186:Mast3	UTSW	8	70785483	missense	probably damaging	1.00
R6407:Mast3	UTSW	8	70782128	missense	probably benign	0.02
R6614:Mast3	UTSW	8	70781966	missense	possibly damaging	0.95
R6804:Mast3	UTSW	8	70786732	missense	probably benign	0.29
R6873:Mast3	UTSW	8	70786592	nonsense	probably null
R6930:Mast3	UTSW	8	70799471	nonsense	probably null
R6948:Mast3	UTSW	8	70785482	missense	probably damaging	1.00
R7084:Mast3	UTSW	8	70779473	missense	probably benign	0.14
R7253:Mast3	UTSW	8	70789682	critical splice donor site	probably null
R7316:Mast3	UTSW	8	70779788	missense	probably damaging	1.00
R7357:Mast3	UTSW	8	70784859	missense	probably damaging	1.00
R7405:Mast3	UTSW	8	70786171	missense	probably damaging	1.00
R7429:Mast3	UTSW	8	70780303	missense	probably damaging	1.00
R7430:Mast3	UTSW	8	70780303	missense	probably damaging	1.00
R7521:Mast3	UTSW	8	70788768	missense	probably benign	0.16
R7576:Mast3	UTSW	8	70781194	missense	probably damaging	1.00
R7933:Mast3	UTSW	8	70786635	missense	probably damaging	1.00
R7998:Mast3	UTSW	8	70783570	missense	probably benign
R8021:Mast3	UTSW	8	70788252	missense	probably benign	0.02
R8204:Mast3	UTSW	8	70788281	missense	probably benign	0.00
R8327:Mast3	UTSW	8	70779418	missense	probably damaging	1.00
R8357:Mast3	UTSW	8	70780441	missense	probably benign	0.39
R8415:Mast3	UTSW	8	70781222	missense	probably damaging	1.00
R8457:Mast3	UTSW	8	70780441	missense	probably benign	0.39
R8530:Mast3	UTSW	8	70788233	missense	possibly damaging	0.92
R8891:Mast3	UTSW	8	70781157	missense	probably damaging	1.00
R8930:Mast3	UTSW	8	70781733	splice site	probably benign
R9002:Mast3	UTSW	8	70781260	missense	probably damaging	1.00
R9085:Mast3	UTSW	8	70796717	missense	unknown
R9087:Mast3	UTSW	8	70789686	missense	possibly damaging	0.93
R9148:Mast3	UTSW	8	70780447	missense	probably damaging	0.98
R9364:Mast3	UTSW	8	70786182	missense	probably damaging	1.00
R9779:Mast3	UTSW	8	70785483	missense	probably damaging	1.00
Z1177:Mast3	UTSW	8	70789038	critical splice acceptor site	probably null

Protein Function and Prediction

MAST3 is a MAST kinase and inflammatory bowel disease risk factor (1). MAST3 has a PDZ domain that mediates binding to PTEN (2) and two kinase domains. Knockdown of MAST3 results in a decrease in TLR4-dependent NF-κB activity after stimulation with lipopolysaccharide (LPS) (1). Labbe et al. propose that MAST3 stabilizes and/or phosphorylates a component of the TLR4 cascade downstream of the receptor and upstream of NF-κB activation to regulate NF-κB activity (1). Further studies determined that the MAST3-regulated genes (e.g., proinflammatory cytokines, regulators of NF-κB, interferon induced genes, and genes involved in adhesion and cell migration) are involved in immune responses to intestinal inflammation through changes in gene expression (3).

Expression/Localization

RT-PCR detected variable MAST3 expression in all tissues examined, with highest levels in kidney, brain, and small intestine (4). MAST3 is constitutively expressed in CD4+ and CD8+ T cells and CD19+ B cells (1).

References

1. Labbe, C., Goyette, P., Lefebvre, C., Stevens, C., Green, T., Tello-Ruiz, M. K., Cao, Z., Landry, A. L., Stempak, J., Annese, V., Latiano, A., Brant, S. R., Duerr, R. H., Taylor, K. D., Cho, J. H., Steinhart, A. H., Daly, M. J., Silverberg, M. S., Xavier, R. J., and Rioux, J. D. (2008) MAST3: A Novel IBD Risk Factor that Modulates TLR4 Signaling. Genes Immun. 9, 602-612.

2. Valiente, M., Andres-Pons, A., Gomar, B., Torres, J., Gil, A., Tapparel, C., Antonarakis, S. E., and Pulido, R. (2005) Binding of PTEN to Specific PDZ Domains Contributes to PTEN Protein Stability and Phosphorylation by Microtubule-Associated serine/threonine Kinases. J Biol Chem. 280, 28936-28943.

3. Labbe, C., Boucher, G., Foisy, S., Alikashani, A., Nkwimi, H., David, G., Beaudoin, M., Goyette, P., Charron, G., Xavier, R. J., and Rioux, J. D. (2012) Genome-Wide Expression Profiling Implicates a MAST3-Regulated Gene Set in Colonic Mucosal Inflammation of Ulcerative Colitis Patients. Inflamm Bowel Dis. 18, 1072-1080.

4. Nagase, T., Ishikawa, K., Suyama, M., Kikuno, R., Hirosawa, M., Miyajima, N., Tanaka, A., Kotani, H., Nomura, N., and Ohara, O. (1998) Prediction of the Coding Sequences of Unidentified Human Genes. XII. the Complete Sequences of 100 New cDNA Clones from Brain which Code for Large Proteins in Vitro. DNA Res. 5, 355-364.

Posted On

2012-12-21

Science Writer

Anne Murray