Mutagenetix > Incidental Mutation

Incidental Mutation 'R1700:Gclc'

189666

Institutional Source

Beutler Lab

Gene Symbol

Gclc

Ensembl Gene

ENSMUSG00000032350

Gene Name

glutamate-cysteine ligase, catalytic subunit

Synonyms

D9Wsu168e, gamma GCS-HS, Glclc, GLCL-H

MMRRC Submission

039733-MU

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R1700 (G1)

Quality Score

225

Status

Not validated

Chromosome

Chromosomal Location

77661817-77701767 bp(+) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

A to G at 77683571 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Threonine to Alanine at position 143 (T143A)

Ref Sequence

ENSEMBL: ENSMUSP00000034905 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000034905]

AlphaFold

P97494

Predicted Effect

probably benign
Transcript: ENSMUST00000034905
AA Change: T143A

PolyPhen 2 Score 0.035 (Sensitivity: 0.94; Specificity: 0.82)

SMART Domains

Protein: ENSMUSP00000034905
Gene: ENSMUSG00000032350
AA Change: T143A

Domain	Start	End	E-Value	Type
Pfam:GCS	236	608	1.3e-185	PFAM

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000216315

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000216848

Coding Region Coverage

1x: 99.1%
3x: 98.4%
10x: 96.4%
20x: 92.8%

Validation Efficiency

MGI Phenotype

FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] Glutamate-cysteine ligase, also known as gamma-glutamylcysteine synthetase is the first rate-limiting enzyme of glutathione synthesis. The enzyme consists of two subunits, a heavy catalytic subunit and a light regulatory subunit. This locus encodes the catalytic subunit, while the regulatory subunit is derived from a different gene located on chromosome 1p22-p21. Mutations at this locus have been associated with hemolytic anemia due to deficiency of gamma-glutamylcysteine synthetase and susceptibility to myocardial infarction.[provided by RefSeq, Oct 2010]
PHENOTYPE: Homozygous mutant mice are embryonic lethal. One model shows lethality before E13 while another shows lethality between E7.5-E8.5. In this second model, embryos are arrested at the egg cylinder stage, fail to gastrulate, do not form mesoderm, and exhibitincreased apoptosis. [provided by MGI curators]

Allele List at MGI

Other mutations in this stock

Total: 72 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Abcb1b	T	C	5: 8,899,537 (GRCm39)	F936L	probably benign	Het
Adamts12	T	A	15: 11,152,143 (GRCm39)	I211N	probably benign	Het
Adamts16	G	A	13: 70,927,637 (GRCm39)		probably benign	Het
Alas1	C	T	9: 106,116,845 (GRCm39)	V293I	possibly damaging	Het
Ap1g1	T	C	8: 110,580,244 (GRCm39)	Y569H	probably damaging	Het
Apc2	A	G	10: 80,148,603 (GRCm39)	D1190G	probably damaging	Het
Astn2	G	A	4: 65,664,591 (GRCm39)	Q679*	probably null	Het
Atp2a1	T	A	7: 126,062,081 (GRCm39)	H5L	probably damaging	Het
Baiap3	T	C	17: 25,468,302 (GRCm39)	K279E	probably damaging	Het
C2cd2l	G	A	9: 44,227,909 (GRCm39)	P111S	probably benign	Het
C7	T	A	15: 5,032,274 (GRCm39)	K646*	probably null	Het
Ccp110	C	T	7: 118,334,536 (GRCm39)	T1003I	probably damaging	Het
Cdh22	T	C	2: 165,012,716 (GRCm39)	D123G	probably damaging	Het
Cep295	C	T	9: 15,252,179 (GRCm39)	E397K	probably damaging	Het
Clip1	A	G	5: 123,768,433 (GRCm39)	V722A	probably benign	Het
Cpsf4l	A	G	11: 113,592,901 (GRCm39)	F174S	probably benign	Het
Ctnna3	T	C	10: 63,688,551 (GRCm39)	C332R	probably damaging	Het
Cxcl10	A	T	5: 92,495,714 (GRCm39)	N76K	probably damaging	Het
Dnaaf9	G	A	2: 130,551,858 (GRCm39)	L1010F	probably damaging	Het
Dnaja3	G	A	16: 4,502,029 (GRCm39)	R11K	probably null	Het
Efcab10	A	G	12: 33,445,170 (GRCm39)	T28A	possibly damaging	Het
Esrrg	A	G	1: 187,775,850 (GRCm39)	R103G	probably damaging	Het
Exosc2	A	G	2: 31,560,818 (GRCm39)	K23E	probably benign	Het
Flot2	C	T	11: 77,940,373 (GRCm39)	S40L	possibly damaging	Het
Fsip2	T	C	2: 82,822,081 (GRCm39)	V5938A	probably benign	Het
Gpr37	A	G	6: 25,669,623 (GRCm39)	V407A	probably benign	Het
Gucy2e	A	T	11: 69,122,884 (GRCm39)	M497K	probably benign	Het
Herc1	T	A	9: 66,357,960 (GRCm39)		probably null	Het
Hnrnpll	A	C	17: 80,341,534 (GRCm39)	S502A	probably benign	Het
Ipo11	G	T	13: 106,932,170 (GRCm39)	T975N	probably benign	Het
Kif17	C	T	4: 137,990,009 (GRCm39)	Q66*	probably null	Het
Lrp10	T	C	14: 54,707,209 (GRCm39)	V682A	possibly damaging	Het
Lsmem1	A	T	12: 40,230,677 (GRCm39)	L75Q	probably damaging	Het
Med16	A	T	10: 79,735,169 (GRCm39)	Y430N	probably benign	Het
Med8	C	T	4: 118,269,931 (GRCm39)	S72L	possibly damaging	Het
Mex3a	A	G	3: 88,443,682 (GRCm39)	T253A	probably damaging	Het
Myf6	T	C	10: 107,329,220 (GRCm39)	K242E	probably damaging	Het
Ncald	T	A	15: 37,397,587 (GRCm39)	Y31F	probably benign	Het
Ndufa12	T	A	10: 94,035,855 (GRCm39)	Y48N	probably damaging	Het
Or12e10	T	C	2: 87,641,112 (GRCm39)	V316A	probably benign	Het
Or51q1c	T	A	7: 103,653,329 (GRCm39)	Y282*	probably null	Het
Or5as1	T	G	2: 86,980,123 (GRCm39)	N294T	probably damaging	Het
Pde4dip	T	C	3: 97,610,639 (GRCm39)	T1858A	probably benign	Het
Pgbd1	A	G	13: 21,618,651 (GRCm39)	L2P	probably damaging	Het
Piezo1	C	T	8: 123,214,241 (GRCm39)	R1642H	probably damaging	Het
Plxna1	A	T	6: 89,333,990 (GRCm39)	M213K	probably damaging	Het
Polr1b	A	G	2: 128,965,041 (GRCm39)	N709S	probably damaging	Het
Pramel1	T	A	4: 143,124,999 (GRCm39)	W308R	probably damaging	Het
Prkag2	A	T	5: 25,076,539 (GRCm39)	I208N	probably damaging	Het
Ptpro	T	A	6: 137,420,592 (GRCm39)	V1007D	probably damaging	Het
Rngtt	T	A	4: 33,330,864 (GRCm39)	F156I	probably damaging	Het
Rpusd3	A	G	6: 113,392,494 (GRCm39)	*345Q	probably null	Het
Rrp1b	A	G	17: 32,276,178 (GRCm39)	K575R	probably benign	Het
Shd	G	A	17: 56,281,307 (GRCm39)	V250I	probably damaging	Het
Slc12a5	C	A	2: 164,834,296 (GRCm39)	N749K	possibly damaging	Het
Sorbs2	T	A	8: 46,254,021 (GRCm39)	V488D	probably damaging	Het
Sphkap	G	A	1: 83,255,236 (GRCm39)	R838*	probably null	Het
Srsf4	C	A	4: 131,627,871 (GRCm39)		probably benign	Het
Strn	T	C	17: 78,999,831 (GRCm39)	Y135C	probably damaging	Het
Synm	T	C	7: 67,409,376 (GRCm39)	M1V	probably null	Het
Tas1r3	T	G	4: 155,946,027 (GRCm39)	Q489P	probably benign	Het
Tas2r103	A	T	6: 133,013,774 (GRCm39)	N97K	probably damaging	Het
Tas2r113	A	G	6: 132,870,755 (GRCm39)	Y261C	possibly damaging	Het
Tex21	T	C	12: 76,268,446 (GRCm39)	E112G	probably damaging	Het
Trappc8	T	C	18: 20,966,055 (GRCm39)	S1128G	probably damaging	Het
Ubap1l	A	G	9: 65,279,025 (GRCm39)		probably benign	Het
Ubash3a	A	G	17: 31,434,018 (GRCm39)	D121G	probably damaging	Het
Ubxn4	A	G	1: 128,180,023 (GRCm39)	I56V	possibly damaging	Het
Uri1	T	C	7: 37,662,949 (GRCm39)	I348M	probably damaging	Het
Usp21	C	A	1: 171,111,295 (GRCm39)	L379F	probably damaging	Het
Vmn1r159	T	A	7: 22,542,390 (GRCm39)	H214L	probably damaging	Het
Zdbf2	A	G	1: 63,341,900 (GRCm39)	E93G	unknown	Het

Other mutations in Gclc

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL02026:Gclc	APN	9	77,699,342 (GRCm39)	missense	probably benign
IGL02059:Gclc	APN	9	77,695,098 (GRCm39)	missense	probably damaging	1.00
R0671:Gclc	UTSW	9	77,694,080 (GRCm39)	missense	probably damaging	1.00
R1469:Gclc	UTSW	9	77,688,419 (GRCm39)	missense	probably benign	0.01
R1469:Gclc	UTSW	9	77,688,419 (GRCm39)	missense	probably benign	0.01
R3120:Gclc	UTSW	9	77,688,552 (GRCm39)	missense	possibly damaging	0.84
R3830:Gclc	UTSW	9	77,699,242 (GRCm39)	missense	probably benign	0.24
R6747:Gclc	UTSW	9	77,695,527 (GRCm39)	missense	probably damaging	0.96
R7028:Gclc	UTSW	9	77,695,498 (GRCm39)	missense	probably damaging	1.00
R7120:Gclc	UTSW	9	77,694,032 (GRCm39)	missense	probably damaging	1.00
R7242:Gclc	UTSW	9	77,692,653 (GRCm39)	missense	probably benign	0.00
R7329:Gclc	UTSW	9	77,683,473 (GRCm39)	missense	probably damaging	1.00
R7716:Gclc	UTSW	9	77,662,209 (GRCm39)	missense	probably damaging	1.00
X0021:Gclc	UTSW	9	77,695,491 (GRCm39)	missense	probably damaging	1.00
Z1088:Gclc	UTSW	9	77,688,649 (GRCm39)	splice site	probably null
Z1177:Gclc	UTSW	9	77,694,021 (GRCm39)	missense	probably benign	0.06

Predicted Primers

PCR Primer
(F):5'- CTTACAGCCTGTTAGGCTCAGTTCC -3'
(R):5'- GCAGCCCTACAGCAAGAGTGTATC -3'

Sequencing Primer
(F):5'- CACTTAGCAGTCCTAAGGAGTTG -3'
(R):5'- aggcaaatccaacccacag -3'

Posted On

2014-05-14