Mutagenetix > Incidental Mutations

Incidental Mutation 'R2017:Large1'

223211

Institutional Source

Beutler Lab

Gene Symbol

Large1

Ensembl Gene

ENSMUSG00000004383

Gene Name

LARGE xylosyl- and glucuronyltransferase 1

Synonyms

froggy, BPFD#36, fg, enr

MMRRC Submission

040026-MU

Accession Numbers

Is this an essential gene?

Possibly essential (E-score: 0.588) question?

Stock #

R2017 (G1)

Quality Score

186

Status

Not validated

Chromosome

Chromosomal Location

72814599-73353540 bp(-) (GRCm38)

Type of Mutation

missense

DNA Base Change (assembly)

A to G at 72852197 bp (GRCm38)

Zygosity

Heterozygous

Amino Acid Change

Phenylalanine to Serine at position 460 (F460S)

Ref Sequence

ENSEMBL: ENSMUSP00000148336 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000004497] [ENSMUST00000119826] [ENSMUST00000212459]

AlphaFold

Q9Z1M7

Predicted Effect

probably damaging
Transcript: ENSMUST00000004497
AA Change: F460S

PolyPhen 2 Score 0.997 (Sensitivity: 0.41; Specificity: 0.98)

SMART Domains

Protein: ENSMUSP00000004497
Gene: ENSMUSG00000004383
AA Change: F460S

Domain	Start	End	E-Value	Type
transmembrane domain	12	34	N/A	INTRINSIC
coiled coil region	55	90	N/A	INTRINSIC
Pfam:Glyco_transf_8	141	387	6.2e-22	PFAM
Pfam:Glyco_transf_49	473	540	5.2e-15	PFAM
Pfam:Glyco_transf_49	535	743	1.1e-47	PFAM

Predicted Effect

probably damaging
Transcript: ENSMUST00000119826
AA Change: F460S

PolyPhen 2 Score 0.997 (Sensitivity: 0.41; Specificity: 0.98)

SMART Domains

Protein: ENSMUSP00000112617
Gene: ENSMUSG00000004383
AA Change: F460S

Domain	Start	End	E-Value	Type
transmembrane domain	12	34	N/A	INTRINSIC
coiled coil region	55	90	N/A	INTRINSIC
Pfam:Glyco_transf_8	142	386	3e-23	PFAM
Pfam:Glyco_transf_49	473	540	2.3e-11	PFAM
Pfam:Glyco_transf_49	520	743	2.7e-44	PFAM

Predicted Effect

probably damaging
Transcript: ENSMUST00000212459
AA Change: F460S

PolyPhen 2 Score 0.997 (Sensitivity: 0.41; Specificity: 0.98)

Coding Region Coverage

1x: 99.1%
3x: 98.4%
10x: 96.7%
20x: 93.7%

Validation Efficiency

MGI Phenotype

FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene, which is one of the largest in the human genome, encodes a member of the N-acetylglucosaminyltransferase gene family. It encodes a glycosyltransferase which participates in glycosylation of alpha-dystroglycan, and may carry out the synthesis of glycoprotein and glycosphingolipid sugar chains. It may also be involved in the addition of a repeated disaccharide unit. Mutations in this gene cause MDC1D, a novel form of congenital muscular dystrophy with severe mental retardation and abnormal glycosylation of alpha-dystroglycan. Alternative splicing of this gene results in two transcript variants that encode the same protein. [provided by RefSeq, Jul 2008]
PHENOTYPE: Homozygotes exhibit a progressive myopathy, abnormal posture, thoracic kyphosis, calcium deposits in muscle, loss of Schwann cells and myelin, eye and CNS defects, deafness, reduced growth, and death around 4 months. [provided by MGI curators]

Allele List at MGI

Other mutations in this stock

Total: 85 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
1700025C18Rik	T	C	2: 165,079,026	D29G	unknown	Het
Abca13	A	T	11: 9,290,619	L827F	probably damaging	Het
Abcc1	T	A	16: 14,461,204	V1126E	probably damaging	Het
Abcc12	A	G	8: 86,563,988	L41S	probably damaging	Het
Adgrg7	T	C	16: 56,732,806	T643A	probably benign	Het
Angpt2	T	C	8: 18,705,731	N240S	probably damaging	Het
Apc	A	G	18: 34,313,602	T1150A	probably benign	Het
Apob	G	A	12: 8,007,751	D2078N	possibly damaging	Het
Apool	T	A	X: 112,364,561	S234T	probably benign	Het
Ascc3	C	T	10: 50,690,211	P751S	probably benign	Het
Astn2	G	A	4: 65,540,941	T1079I	probably damaging	Het
Atp8b1	T	C	18: 64,540,334	N989S	probably damaging	Het
B3gnt2	T	C	11: 22,836,621	D189G	probably damaging	Het
Bcas1	A	C	2: 170,348,161		probably null	Het
Btk	T	C	X: 134,547,601	D355G	probably benign	Het
C2cd4c	A	G	10: 79,612,989	V108A	possibly damaging	Het
Cbfa2t2	T	C	2: 154,517,807	L264P	probably damaging	Het
Cd22	A	T	7: 30,872,780	L423Q	probably damaging	Het
Cep128	T	C	12: 91,366,464	D9G	probably damaging	Het
Cer1	A	T	4: 82,882,883	V181D	probably damaging	Het
Ciita	T	C	16: 10,511,676	L584P	probably damaging	Het
Cmss1	T	C	16: 57,316,278	D77G	probably damaging	Het
Col4a2	T	C	8: 11,445,086	F1515L	probably benign	Het
Dcaf1	T	A	9: 106,839,088	D360E	probably benign	Het
Dcaf1	A	G	9: 106,847,923	E536G	probably damaging	Het
Dnah2	T	A	11: 69,437,070	I3370F	probably damaging	Het
Dsg1c	T	C	18: 20,266,196	V119A	possibly damaging	Het
Edn3	A	G	2: 174,778,662	E103G	probably benign	Het
Efemp1	G	T	11: 28,921,613	R376L	probably damaging	Het
Eid1	A	G	2: 125,673,201	M4V	probably benign	Het
Emilin3	G	A	2: 160,909,610	R170C	possibly damaging	Het
Epx	T	C	11: 87,874,337	D178G	probably damaging	Het
Fam208b	A	T	13: 3,576,770	I1060K	probably benign	Het
Fam49a	T	A	12: 12,362,361	V208D	probably damaging	Het
Fkbp10	G	A	11: 100,421,673	V252I	possibly damaging	Het
Flnc	G	A	6: 29,443,797		probably null	Het
Fsip2	A	G	2: 82,982,732	K3132E	possibly damaging	Het
Gla	C	T	X: 134,596,322	A39T	probably damaging	Het
H2-Ke6	A	T	17: 34,026,213	M259K	probably damaging	Het
Hivep2	C	T	10: 14,130,757	T1033M	probably damaging	Het
Ikzf4	C	T	10: 128,634,157	G498D	probably damaging	Het
Impg1	T	C	9: 80,440,667	Y95C	probably damaging	Het
Ino80c	T	A	18: 24,111,753	K136*	probably null	Het
Iqsec1	A	C	6: 90,689,930	H508Q	probably benign	Het
Itgb3	A	G	11: 104,637,962	H305R	possibly damaging	Het
Jup	T	A	11: 100,386,341	T14S	probably benign	Het
Kcnh8	GAGACCAACGAGCAGCTGATGCTTCAGA	GAGA	17: 52,725,906	74	probably benign	Het
Klf12	T	C	14: 100,022,637	R219G	possibly damaging	Het
Klhl42	G	T	6: 147,107,793	V377L	probably benign	Het
Loxl3	A	T	6: 83,048,977	D402V	probably damaging	Het
Lrrc37a	T	A	11: 103,501,125	Y1158F	probably benign	Het
Map2	T	A	1: 66,412,799	S365T	probably damaging	Het
Mapk8ip1	A	G	2: 92,391,034		probably null	Het
Med26	A	G	8: 72,496,947	S103P	probably damaging	Het
Muc4	T	C	16: 32,751,303	S394P	possibly damaging	Het
Nle1	G	T	11: 82,905,547	P166Q	probably damaging	Het
Obox5	T	C	7: 15,758,882	I254T	probably benign	Het
Olfr1288	G	T	2: 111,479,187	M134I	probably benign	Het
Olfr371	T	C	8: 85,230,744	L83P	possibly damaging	Het
Olfr406	T	A	11: 74,270,333	W315R	probably benign	Het
Olfr592	T	C	7: 103,186,930	F110L	probably benign	Het
Pacs2	A	T	12: 113,062,457	N545Y	probably damaging	Het
Palld	T	C	8: 61,684,765	E652G	probably damaging	Het
Pgm5	T	C	19: 24,824,312	N184S	probably benign	Het
Pitpnm1	T	C	19: 4,111,873	V955A	probably benign	Het
Plcb1	T	A	2: 135,362,420	I898N	possibly damaging	Het
Pramef12	A	G	4: 144,394,674	V260A	possibly damaging	Het
Prr36	T	A	8: 4,215,205	T182S	probably benign	Het
Prss35	A	G	9: 86,755,512	S112G	probably benign	Het
Ptprj	C	T	2: 90,464,614	V417M	probably damaging	Het
Ptprm	G	T	17: 66,957,153		probably null	Het
Rasgrp2	T	C	19: 6,413,165	V498A	probably benign	Het
Rfx6	A	G	10: 51,721,604	N513S	possibly damaging	Het
Rhbdf1	A	G	11: 32,210,471	I693T	probably damaging	Het
Scn9a	T	C	2: 66,515,321	T1143A	probably damaging	Het
Spata17	A	G	1: 187,048,453	S366P	possibly damaging	Het
Svep1	A	G	4: 58,070,568	L2406P	probably benign	Het
Tgfb2	A	T	1: 186,630,765	Y287*	probably null	Het
Trip11	A	T	12: 101,885,360	V815E	probably benign	Het
Trp53bp2	G	T	1: 182,449,015	V854L	probably benign	Het
Ttc30a1	A	G	2: 75,981,457	L94P	probably benign	Het
Vmn1r78	T	C	7: 12,153,343	S294P	possibly damaging	Het
Vmn2r86	T	C	10: 130,446,713	K678R	probably benign	Het
Yeats2	T	A	16: 20,159,181	N138K	probably benign	Het
Zufsp	A	T	10: 33,927,464	N541K	possibly damaging	Het

Other mutations in Large1

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL00095:Large1	APN	8	72837497	missense	probably damaging	1.00
IGL00326:Large1	APN	8	73131983	missense	probably benign
IGL00418:Large1	APN	8	72823841	critical splice acceptor site	probably null
IGL01155:Large1	APN	8	73131989	missense	probably benign	0.01
IGL01793:Large1	APN	8	72859181	splice site	probably benign
IGL01929:Large1	APN	8	72859275	missense	probably damaging	1.00
IGL02218:Large1	APN	8	72912122	missense	probably damaging	1.00
IGL02276:Large1	APN	8	72818093	missense	probably benign	0.00
IGL02329:Large1	APN	8	73048317	missense	possibly damaging	0.80
IGL02543:Large1	APN	8	73048414	missense	probably benign	0.00
IGL02887:Large1	APN	8	73132039	missense	probably benign	0.07
biggs	UTSW	8	73116419	missense	probably damaging	1.00
umber	UTSW	8	72883264	nonsense	probably null
R0179:Large1	UTSW	8	73098846	missense	probably benign	0.09
R0477:Large1	UTSW	8	72818082	missense	probably damaging	1.00
R0587:Large1	UTSW	8	72859333	missense	probably damaging	1.00
R0791:Large1	UTSW	8	73048479	splice site	probably benign
R1253:Large1	UTSW	8	73048422	missense	probably damaging	0.98
R1695:Large1	UTSW	8	72818082	missense	probably damaging	1.00
R4835:Large1	UTSW	8	73048347	missense	probably damaging	1.00
R5105:Large1	UTSW	8	72852244	nonsense	probably null
R5120:Large1	UTSW	8	72859341	missense	probably damaging	1.00
R5135:Large1	UTSW	8	72818096	missense	probably benign	0.38
R5137:Large1	UTSW	8	73048309	missense	possibly damaging	0.58
R5567:Large1	UTSW	8	72837453	missense	possibly damaging	0.93
R5945:Large1	UTSW	8	72852200	missense	probably damaging	0.99
R6619:Large1	UTSW	8	72883264	nonsense	probably null
R6951:Large1	UTSW	8	73116419	missense	probably damaging	1.00
R7041:Large1	UTSW	8	73116464	missense	probably damaging	0.98
R7300:Large1	UTSW	8	72837596	missense	probably damaging	1.00
R7493:Large1	UTSW	8	72823715	missense	probably benign	0.23
R7877:Large1	UTSW	8	73116443	missense	probably damaging	1.00
R8118:Large1	UTSW	8	73131944	missense	probably benign	0.40
R8129:Large1	UTSW	8	72815957	missense	probably damaging	1.00
R8525:Large1	UTSW	8	72837492	missense	probably damaging	1.00
R8963:Large1	UTSW	8	72815984	missense	probably damaging	1.00
R9170:Large1	UTSW	8	72816017	missense	probably benign	0.00
Z1088:Large1	UTSW	8	72912103	nonsense	probably null

Predicted Primers

PCR Primer
(F):5'- TGTGCAGCACTGGAGATGAG -3'
(R):5'- AGTCCTTTCTGTTGAACCACCAG -3'

Sequencing Primer
(F):5'- CTGAGATCAACCTCAAGTGTACTAG -3'
(R):5'- TTTCTGTTGAACCACCAGCAAGG -3'

Posted On

2014-08-25