Mutagenetix > Incidental Mutation

Incidental Mutation 'R8118:Large1'

631343

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

067547-MU

Accession Numbers

Essential gene?

Possibly essential (E-score: 0.647) question?

Stock #

R8118 (G1)

Quality Score

225.009

Status

Validated

Chromosome

Chromosomal Location

72814599-73353540 bp(-) (GRCm38)

Type of Mutation

missense

DNA Base Change (assembly)

A to G at 73131944 bp (GRCm38)

Zygosity

Heterozygous

Amino Acid Change

Serine to Proline at position 99 (S99P)

Ref Sequence

ENSEMBL: ENSMUSP00000004497 (fasta)

Gene Model

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

AlphaFold

Q9Z1M7

Predicted Effect

probably benign
Transcript: ENSMUST00000004497
AA Change: S99P

PolyPhen 2 Score 0.403 (Sensitivity: 0.89; Specificity: 0.89)

SMART Domains

Protein: ENSMUSP00000004497
Gene: ENSMUSG00000004383
AA Change: S99P

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 benign
Transcript: ENSMUST00000119826
AA Change: S99P

PolyPhen 2 Score 0.403 (Sensitivity: 0.89; Specificity: 0.89)

SMART Domains

Protein: ENSMUSP00000112617
Gene: ENSMUSG00000004383
AA Change: S99P

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 benign
Transcript: ENSMUST00000212459
AA Change: S99P

PolyPhen 2 Score 0.403 (Sensitivity: 0.89; Specificity: 0.89)

Coding Region Coverage

1x: 99.8%
3x: 99.5%
10x: 98.2%
20x: 91.1%

Validation Efficiency

97% (68/70)

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: 67 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Adamts1	T	C	16: 85,795,933 (GRCm38)	D792G	probably damaging	Het
Adcy7	A	G	8: 88,315,756 (GRCm38)	H417R	probably damaging	Het
Agr2	A	G	12: 35,996,107 (GRCm38)	D79G	probably benign	Het
Ankle1	T	C	8: 71,407,635 (GRCm38)	S286P	probably benign	Het
Arhgef11	T	C	3: 87,735,857 (GRCm38)	S1488P	probably damaging	Het
Atp6v0a2	T	C	5: 124,712,773 (GRCm38)	M421T	probably damaging	Het
Cdk17	C	A	10: 93,216,390 (GRCm38)	Q111K	possibly damaging	Het
Cobl	A	G	11: 12,254,834 (GRCm38)	S623P	probably benign	Het
Dgka	C	T	10: 128,722,449 (GRCm38)		probably null	Het
Dsc2	C	T	18: 20,032,274 (GRCm38)	G881R	possibly damaging	Het
Dsg2	A	G	18: 20,582,801 (GRCm38)	I267V	probably benign	Het
Exoc4	T	C	6: 33,971,918 (GRCm38)	Y899H	probably damaging	Het
Fat3	A	G	9: 15,960,104 (GRCm38)	F3664L	probably benign	Het
Fbxo47	C	T	11: 97,879,515 (GRCm38)	C17Y	probably benign	Het
Gm2888	G	T	14: 3,037,628 (GRCm38)	V207F	probably benign	Het
Gm7030	C	T	17: 36,127,690 (GRCm38)	V270M	probably damaging	Het
Gpr61	A	G	3: 108,150,572 (GRCm38)	S258P	probably damaging	Het
Hectd4	C	T	5: 121,286,376 (GRCm38)	H700Y	probably benign	Het
Hs3st2	C	T	7: 121,397,428 (GRCm38)	T154I	probably benign	Het
Inf2	A	T	12: 112,601,437 (GRCm38)	H167L	probably damaging	Het
Ints3	C	T	3: 90,400,299 (GRCm38)		probably null	Het
Ippk	C	T	13: 49,446,342 (GRCm38)	P226S		Het
Itgal	C	A	7: 127,311,245 (GRCm38)	Q509K	probably benign	Het
Klhl20	A	T	1: 161,098,401 (GRCm38)		probably null	Het
Krtap4-13	C	T	11: 99,809,398 (GRCm38)	C145Y	unknown	Het
Lexm	T	A	4: 106,613,398 (GRCm38)	R192S	possibly damaging	Het
Lrba	A	T	3: 86,354,226 (GRCm38)	I1496L	probably benign	Het
Map2	A	T	1: 66,425,391 (GRCm38)	I1647F	probably damaging	Het
Map3k10	A	G	7: 27,673,417 (GRCm38)	V203A	possibly damaging	Het
Mcmdc2	T	A	1: 9,916,374 (GRCm38)	N166K	possibly damaging	Het
Mlxipl	T	G	5: 135,137,248 (GRCm38)	L828R	possibly damaging	Het
Mnat1	A	G	12: 73,219,090 (GRCm38)	I253V	probably benign	Het
Mtfp1	A	G	11: 4,093,910 (GRCm38)	S107P	probably damaging	Het
Nebl	T	A	2: 17,379,820 (GRCm38)	Y65F	possibly damaging	Het
Nelfb	A	T	2: 25,205,159 (GRCm38)	D339E	possibly damaging	Het
Nlrc3	T	A	16: 3,965,631 (GRCm38)	I20L	probably benign	Het
Nup205	T	A	6: 35,230,516 (GRCm38)	M1501K	probably benign	Het
Olfr1487	T	A	19: 13,619,745 (GRCm38)	N151K	probably damaging	Het
Olfr304	A	T	7: 86,385,768 (GRCm38)	C297*	probably null	Het
Olfr51	A	G	11: 51,007,500 (GRCm38)	H176R	probably damaging	Het
Olfr720	A	G	14: 14,175,863 (GRCm38)	I73T	probably damaging	Het
Olfr725	T	C	14: 50,035,151 (GRCm38)	D84G	probably benign	Het
Olfr998	T	A	2: 85,590,988 (GRCm38)	Y149*	probably null	Het
Palm3	A	G	8: 84,029,809 (GRCm38)	E650G	probably damaging	Het
Prps1l1	C	A	12: 34,985,341 (GRCm38)	L152M	probably damaging	Het
Rgs7bp	C	A	13: 105,053,121 (GRCm38)	V57F	probably damaging	Het
Scaf8	T	A	17: 3,164,183 (GRCm38)	V171D	unknown	Het
Sf3a2	T	C	10: 80,803,640 (GRCm38)	Y155H	probably damaging	Het
Sfrp1	T	G	8: 23,411,984 (GRCm38)	L67R	probably damaging	Het
Shank2	A	T	7: 144,409,875 (GRCm38)	I407L	probably benign	Het
Skint6	A	C	4: 113,156,494 (GRCm38)	S353R	possibly damaging	Het
Skint6	T	C	4: 112,865,675 (GRCm38)	T902A	possibly damaging	Het
Srrm2	T	A	17: 23,808,083 (GRCm38)	I87N	unknown	Het
Stard9	G	A	2: 120,704,430 (GRCm38)	G3723S	probably benign	Het
Svs3b	A	G	2: 164,256,006 (GRCm38)	S132P	probably damaging	Het
Tbc1d17	G	T	7: 44,843,002 (GRCm38)	F412L	probably benign	Het
Tex29	A	T	8: 11,854,263 (GRCm38)	E116D	unknown	Het
Tmem204	T	C	17: 25,080,338 (GRCm38)	D69G	possibly damaging	Het
Ttll10	G	A	4: 156,044,762 (GRCm38)	R308C	probably benign	Het
Ttn	T	A	2: 76,747,164 (GRCm38)	I24462F	probably damaging	Het
Tubg2	A	G	11: 101,161,478 (GRCm38)	E411G	probably damaging	Het
Ugt2b38	T	C	5: 87,423,771 (GRCm38)	N134S	probably damaging	Het
Usp31	T	C	7: 121,677,262 (GRCm38)	T351A	probably damaging	Het
Usp33	T	C	3: 152,360,359 (GRCm38)	L92S	probably damaging	Het
Vmn2r20	A	T	6: 123,396,470 (GRCm38)	I471N	probably damaging	Het
Wdfy4	G	A	14: 33,104,115 (GRCm38)	P1193L		Het
Wnk2	A	G	13: 49,090,983 (GRCm38)	V459A	probably damaging	Het

Other mutations in Large1

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL00095:Large1	APN	8	72,837,497 (GRCm38)	missense	probably damaging	1.00
IGL00326:Large1	APN	8	73,131,983 (GRCm38)	missense	probably benign
IGL00418:Large1	APN	8	72,823,841 (GRCm38)	critical splice acceptor site	probably null
IGL01155:Large1	APN	8	73,131,989 (GRCm38)	missense	probably benign	0.01
IGL01793:Large1	APN	8	72,859,181 (GRCm38)	splice site	probably benign
IGL01929:Large1	APN	8	72,859,275 (GRCm38)	missense	probably damaging	1.00
IGL02218:Large1	APN	8	72,912,122 (GRCm38)	missense	probably damaging	1.00
IGL02276:Large1	APN	8	72,818,093 (GRCm38)	missense	probably benign	0.00
IGL02329:Large1	APN	8	73,048,317 (GRCm38)	missense	possibly damaging	0.80
IGL02543:Large1	APN	8	73,048,414 (GRCm38)	missense	probably benign	0.00
IGL02887:Large1	APN	8	73,132,039 (GRCm38)	missense	probably benign	0.07
biggs	UTSW	8	73,116,419 (GRCm38)	missense	probably damaging	1.00
umber	UTSW	8	72,883,264 (GRCm38)	nonsense	probably null
R0179:Large1	UTSW	8	73,098,846 (GRCm38)	missense	probably benign	0.09
R0477:Large1	UTSW	8	72,818,082 (GRCm38)	missense	probably damaging	1.00
R0587:Large1	UTSW	8	72,859,333 (GRCm38)	missense	probably damaging	1.00
R0791:Large1	UTSW	8	73,048,479 (GRCm38)	splice site	probably benign
R1253:Large1	UTSW	8	73,048,422 (GRCm38)	missense	probably damaging	0.98
R1695:Large1	UTSW	8	72,818,082 (GRCm38)	missense	probably damaging	1.00
R2017:Large1	UTSW	8	72,852,197 (GRCm38)	missense	probably damaging	1.00
R4835:Large1	UTSW	8	73,048,347 (GRCm38)	missense	probably damaging	1.00
R5105:Large1	UTSW	8	72,852,244 (GRCm38)	nonsense	probably null
R5120:Large1	UTSW	8	72,859,341 (GRCm38)	missense	probably damaging	1.00
R5135:Large1	UTSW	8	72,818,096 (GRCm38)	missense	probably benign	0.38
R5137:Large1	UTSW	8	73,048,309 (GRCm38)	missense	possibly damaging	0.58
R5567:Large1	UTSW	8	72,837,453 (GRCm38)	missense	possibly damaging	0.93
R5945:Large1	UTSW	8	72,852,200 (GRCm38)	missense	probably damaging	0.99
R6619:Large1	UTSW	8	72,883,264 (GRCm38)	nonsense	probably null
R6951:Large1	UTSW	8	73,116,419 (GRCm38)	missense	probably damaging	1.00
R7041:Large1	UTSW	8	73,116,464 (GRCm38)	missense	probably damaging	0.98
R7300:Large1	UTSW	8	72,837,596 (GRCm38)	missense	probably damaging	1.00
R7493:Large1	UTSW	8	72,823,715 (GRCm38)	missense	probably benign	0.23
R7877:Large1	UTSW	8	73,116,443 (GRCm38)	missense	probably damaging	1.00
R8129:Large1	UTSW	8	72,815,957 (GRCm38)	missense	probably damaging	1.00
R8525:Large1	UTSW	8	72,837,492 (GRCm38)	missense	probably damaging	1.00
R8963:Large1	UTSW	8	72,815,984 (GRCm38)	missense	probably damaging	1.00
R9170:Large1	UTSW	8	72,816,017 (GRCm38)	missense	probably benign	0.00
R9653:Large1	UTSW	8	72,837,478 (GRCm38)	missense	probably benign
Z1088:Large1	UTSW	8	72,912,103 (GRCm38)	nonsense	probably null

Predicted Primers

PCR Primer
(F):5'- CTGGGAAGTAGGATATCATTTGAGATG -3'
(R):5'- TCTCCTCCTCTAGATGGGAAAC -3'

Sequencing Primer
(F):5'- ACCTCACACTTTTCCACAG -3'
(R):5'- GGAAACCTGTGTCTCTGTCTC -3'

Posted On

2020-06-30