Mutagenetix > Incidental Mutations

Incidental Mutation 'R5137:Large1'

396212

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

042723-MU

Accession Numbers

Is this an essential gene?

Possibly essential (E-score: 0.588) question?

Stock #

R5137 (G1)

Quality Score

225

Status

Not validated

Chromosome

Chromosomal Location

72814599-73353540 bp(-) (GRCm38)

Type of Mutation

missense

DNA Base Change (assembly)

A to G at 73048309 bp (GRCm38)

Zygosity

Heterozygous

Amino Acid Change

Phenylalanine to Leucine at position 258 (F258L)

Ref Sequence

ENSEMBL: ENSMUSP00000148336 (fasta)

Gene Model

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

AlphaFold

Q9Z1M7

Predicted Effect

possibly damaging
Transcript: ENSMUST00000004497
AA Change: F258L

PolyPhen 2 Score 0.583 (Sensitivity: 0.88; Specificity: 0.91)

SMART Domains

Protein: ENSMUSP00000004497
Gene: ENSMUSG00000004383
AA Change: F258L

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

possibly damaging
Transcript: ENSMUST00000119826
AA Change: F258L

PolyPhen 2 Score 0.583 (Sensitivity: 0.88; Specificity: 0.91)

SMART Domains

Protein: ENSMUSP00000112617
Gene: ENSMUSG00000004383
AA Change: F258L

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

noncoding transcript
Transcript: ENSMUST00000146249

Predicted Effect

possibly damaging
Transcript: ENSMUST00000212459
AA Change: F258L

PolyPhen 2 Score 0.583 (Sensitivity: 0.88; Specificity: 0.91)

Coding Region Coverage

1x: 99.3%
3x: 98.6%
10x: 97.2%
20x: 94.8%

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: 79 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Acad9	T	C	3: 36,069,771	V75A	probably benign	Het
Ace	G	C	11: 105,974,826	W628C	probably damaging	Het
Adh4	T	C	3: 138,422,235	S141P	probably benign	Het
Apob	T	C	12: 8,011,384	Y3256H	possibly damaging	Het
B3galnt1	G	T	3: 69,574,949	N326K	probably benign	Het
Catsperb	T	C	12: 101,549,811	F569L	probably damaging	Het
Cecr2	A	G	6: 120,755,517	I225V	probably benign	Het
Cox5b	A	G	1: 36,692,429		probably null	Het
Crybg1	T	C	10: 43,958,336	D1953G	probably damaging	Het
Dnaaf5	C	T	5: 139,181,460	T707M	probably damaging	Het
Dnase1l1	C	T	X: 74,277,038		probably null	Het
Ebf1	G	A	11: 44,991,468	R409Q	probably damaging	Het
Eef2k	G	A	7: 120,885,422	A256T	probably damaging	Het
Eef2k	C	A	7: 120,885,423	A256D	probably damaging	Het
Evl	C	G	12: 108,681,522	T294S	probably benign	Het
Eya2	T	C	2: 165,731,628	Y288H	probably damaging	Het
Ezh2	A	T	6: 47,532,080		probably null	Het
Fam171a1	T	C	2: 3,225,389	Y395H	probably benign	Het
Gas2l3	C	A	10: 89,413,975	R427L	probably damaging	Het
Gli2	T	A	1: 118,855,503	I91F	probably damaging	Het
Gm4884	T	C	7: 41,042,894	S96P	probably damaging	Het
Gprc5d	T	A	6: 135,116,033	D292V	probably benign	Het
Herc1	A	G	9: 66,448,223	K2252R	probably benign	Het
Il1rl1	A	T	1: 40,450,125	M346L	probably benign	Het
Kcna5	A	T	6: 126,533,983	V394D	probably damaging	Het
Kcng4	A	T	8: 119,625,878	M431K	possibly damaging	Het
Kif1bp	A	T	10: 62,578,241	V46E	probably damaging	Het
Mapkbp1	T	A	2: 120,022,181	C1001S	probably damaging	Het
Micu1	A	G	10: 59,827,232	Q328R	probably benign	Het
Mmp11	G	A	10: 75,925,456	P437S	probably damaging	Het
Msh6	T	A	17: 87,980,288	F119I	possibly damaging	Het
Myo6	A	G	9: 80,242,249	E159G	probably damaging	Het
Negr1	T	A	3: 157,016,196	Y136N	probably damaging	Het
Nol9	T	A	4: 152,045,971	C321S	probably damaging	Het
Nos1	T	C	5: 117,905,313	F551S	probably benign	Het
Nup153	C	A	13: 46,684,153	G1198C	probably damaging	Het
Olfr1	AGCGGTCGTAGGC	AGC	11: 73,395,654		probably null	Het
Olfr1225	C	A	2: 89,170,400	V271F	probably benign	Het
Olfr395	T	C	11: 73,906,626	I289V	probably damaging	Het
Olfr606	A	G	7: 103,451,712	Y125C	probably damaging	Het
Olfr606	C	A	7: 103,451,713	Y125*	probably null	Het
Omd	T	C	13: 49,590,076	S201P	probably benign	Het
Oxct1	G	T	15: 4,035,350	A57S	probably benign	Het
Pcdhga7	T	G	18: 37,717,380	S813R	probably damaging	Het
Pcmtd2	A	T	2: 181,854,994	I255F	possibly damaging	Het
Pdk1	T	G	2: 71,883,569	M186R	possibly damaging	Het
Pelp1	T	C	11: 70,395,099	T648A	probably damaging	Het
Phldb2	A	T	16: 45,808,258	S570R	possibly damaging	Het
Pramef25	T	A	4: 143,949,120	T379S	probably benign	Het
Ptprj	T	C	2: 90,469,648	T270A	possibly damaging	Het
Reln	C	T	5: 21,955,181	G2130D	probably damaging	Het
Rims1	A	T	1: 22,288,620	Y663*	probably null	Het
Rit2	T	C	18: 31,153,764	T123A	probably benign	Het
Rmdn2	A	T	17: 79,667,989	E302D	probably benign	Het
Ryr1	T	C	7: 29,101,858	E827G	possibly damaging	Het
Siglec1	C	T	2: 131,081,344	G494R	probably damaging	Het
Slc16a14	T	A	1: 84,912,597	Y329F	probably damaging	Het
Slc35d1	A	T	4: 103,214,781	L8Q	possibly damaging	Het
Smpdl3a	C	T	10: 57,801,067	S57L	possibly damaging	Het
Snx9	T	C	17: 5,928,253	V566A	probably damaging	Het
Spaca1	A	T	4: 34,029,095	I126N	probably damaging	Het
Spred1	T	G	2: 117,163,571	I94S	probably damaging	Het
Tardbp	T	C	4: 148,622,037	D105G	possibly damaging	Het
Tet2	T	C	3: 133,476,565	S1213G	probably benign	Het
Trak1	A	T	9: 121,367,055		probably benign	Het
Trem3	G	A	17: 48,249,728	V76M	possibly damaging	Het
Ttc13	G	T	8: 124,694,935	Y250*	probably null	Het
Ttll5	T	G	12: 85,923,045	S714R	possibly damaging	Het
Ube2l6	T	G	2: 84,802,876		probably null	Het
Ubr3	T	C	2: 69,973,335	S1090P	probably damaging	Het
Uhrf1bp1	T	G	17: 27,876,990		probably null	Het
Vezt	T	C	10: 93,970,510	T680A	probably benign	Het
Virma	A	G	4: 11,546,297	K1762E	probably damaging	Het
Vps53	A	G	11: 76,166,248	S57P	probably damaging	Het
Vwa7	G	T	17: 35,017,846	D130Y	probably damaging	Het
Vwa8	T	G	14: 79,064,902	F1004V	probably damaging	Het
Zfp35	A	T	18: 24,004,137	K513*	probably null	Het
Zfp384	ACAGCAGCAGCAGCAGCAGCAGC	ACAGCAGCAGCAGCAGCAGC	6: 125,036,509		probably benign	Het
Zfp521	C	A	18: 13,845,448	C636F	probably 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
R2017:Large1	UTSW	8	72852197	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
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'- ATGTCCTTTCTCAGATGTAACGC -3'
(R):5'- AGCAATGAATCCATGTGGTAAC -3'

Sequencing Primer
(F):5'- TTGCCTGGCACATATAAGGC -3'
(R):5'- CCTTTTCTGATTGTAACAGCTCAC -3'

Posted On

2016-06-21