Mutagenetix > Incidental Mutation

Incidental Mutation 'R7065:Gclm'

548504

Institutional Source

Beutler Lab

Gene Symbol

Gclm

Ensembl Gene

ENSMUSG00000028124

Gene Name

glutamate-cysteine ligase, modifier subunit

Synonyms

Gcmc, Glclr

MMRRC Submission

045161-MU

Accession Numbers

Essential gene?

Possibly non essential (E-score: 0.326) question?

Stock #

R7065 (G1)

Quality Score

225.009

Status

Validated

Chromosome

Chromosomal Location

122039206-122060864 bp(+) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

A to G at 122056320 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Asparagine to Aspartic acid at position 137 (N137D)

Ref Sequence

ENSEMBL: ENSMUSP00000136987 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000029769] [ENSMUST00000149983] [ENSMUST00000178826]

AlphaFold

O09172

Predicted Effect

probably benign
Transcript: ENSMUST00000029769
AA Change: N137D

PolyPhen 2 Score 0.021 (Sensitivity: 0.95; Specificity: 0.80)

SMART Domains

Protein: ENSMUSP00000029769
Gene: ENSMUSG00000028124
AA Change: N137D

Domain	Start	End	E-Value	Type
low complexity region	5	16	N/A	INTRINSIC
Pfam:Aldo_ket_red	70	237	2.6e-8	PFAM

Predicted Effect

probably benign
Transcript: ENSMUST00000149983
AA Change: N81D

PolyPhen 2 Score 0.010 (Sensitivity: 0.96; Specificity: 0.77)

SMART Domains

Protein: ENSMUSP00000123683
Gene: ENSMUSG00000028124
AA Change: N81D

Domain	Start	End	E-Value	Type
Pfam:Aldo_ket_red	15	143	1.4e-7	PFAM

Predicted Effect

SMART Domains

Protein: ENSMUSP00000134906
Gene: ENSMUSG00000028124
AA Change: N105D

Domain	Start	End	E-Value	Type
Pfam:Aldo_ket_red	39	184	3.3e-8	PFAM

Predicted Effect

probably benign
Transcript: ENSMUST00000178826
AA Change: N137D

PolyPhen 2 Score 0.021 (Sensitivity: 0.95; Specificity: 0.80)

SMART Domains

Protein: ENSMUSP00000136987
Gene: ENSMUSG00000028124
AA Change: N137D

Domain	Start	End	E-Value	Type
low complexity region	5	16	N/A	INTRINSIC
Pfam:Aldo_ket_red	71	240	9.3e-10	PFAM

Predicted Effect

probably benign
Transcript: ENSMUST00000199699

Coding Region Coverage

1x: 100.0%
3x: 99.9%
10x: 99.7%
20x: 99.0%

Validation Efficiency

100% (62/62)

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. Gamma glutamylcysteine synthetase deficiency has been implicated in some forms of hemolytic anemia. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Apr 2015]
PHENOTYPE: Mice homozygous for one null allele demonstrate increased sensitivity to acetaminophen-induced hepatotoxicity and mice homozygous for another null allele exhibit increased cellular sensitivity to hydrogen peroxide. [provided by MGI curators]

Allele List at MGI

Other mutations in this stock

Total: 63 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Abca1	G	T	4: 53,074,233 (GRCm39)	S1150Y	probably damaging	Het
Abca13	T	A	11: 9,242,595 (GRCm39)	V1486E	probably benign	Het
Abca17	T	A	17: 24,546,725 (GRCm39)	Y292F	probably damaging	Het
Adam3	A	G	8: 25,201,691 (GRCm39)		probably null	Het
Ankmy2	G	A	12: 36,237,707 (GRCm39)	E269K	probably damaging	Het
Cdan1	A	G	2: 120,549,402 (GRCm39)	S1201P	probably benign	Het
Cep57	T	C	9: 13,729,677 (GRCm39)	Y122C	probably damaging	Het
Cfh	T	A	1: 140,014,140 (GRCm39)	Y1210F	probably damaging	Het
Cflar	T	G	1: 58,770,368 (GRCm39)	L154V	probably damaging	Het
Chmp4b	A	G	2: 154,533,162 (GRCm39)	D134G	probably damaging	Het
Clec14a	A	G	12: 58,315,580 (GRCm39)	F14S	possibly damaging	Het
Ctnna1	A	T	18: 35,285,669 (GRCm39)	H5L	probably benign	Het
Cyp2e1	T	A	7: 140,343,906 (GRCm39)	L48Q	probably damaging	Het
Dnah6	T	G	6: 73,064,545 (GRCm39)	Q2627P	possibly damaging	Het
Ehmt1	T	C	2: 24,730,709 (GRCm39)	D569G	probably damaging	Het
Frmd4a	G	A	2: 4,570,923 (GRCm39)			Het
Fryl	T	C	5: 73,248,099 (GRCm39)	D1006G	probably damaging	Het
Gk5	A	G	9: 96,061,109 (GRCm39)	Y531C	probably damaging	Het
Gpm6a	C	A	8: 55,490,493 (GRCm39)	N56K	probably benign	Het
Grik4	A	C	9: 42,455,127 (GRCm39)	V656G	probably damaging	Het
Grip2	C	A	6: 91,760,550 (GRCm39)		probably null	Het
Gucy2c	T	C	6: 136,697,764 (GRCm39)	K636E	probably damaging	Het
Ifi44l	A	G	3: 151,465,429 (GRCm39)	I107T		Het
Kif1b	T	C	4: 149,286,982 (GRCm39)	T1237A	possibly damaging	Het
Klk1b11	A	G	7: 43,648,386 (GRCm39)	D131G	probably benign	Het
Lipe	A	G	7: 25,084,603 (GRCm39)		probably null	Het
Lrp4	A	G	2: 91,341,925 (GRCm39)	D1846G	probably damaging	Het
Madd	A	T	2: 90,985,402 (GRCm39)	M1273K	probably benign	Het
Matn3	T	A	12: 9,002,472 (GRCm39)	M228K	probably damaging	Het
Mterf4	T	A	1: 93,232,617 (GRCm39)	H78L	probably benign	Het
Ncoa4	T	A	14: 31,894,857 (GRCm39)	L128*	probably null	Het
Nedd4l	A	G	18: 65,329,040 (GRCm39)	N627S	probably benign	Het
Niban1	A	G	1: 151,575,858 (GRCm39)		probably null	Het
Nphp3	A	G	9: 103,919,189 (GRCm39)	Y1279C	probably damaging	Het
Nrp1	C	A	8: 129,187,193 (GRCm39)	T413N	probably benign	Het
Opn4	C	A	14: 34,317,834 (GRCm39)	A267S	probably benign	Het
Or4c11c	A	T	2: 88,661,730 (GRCm39)	I90F	probably damaging	Het
Or5ak24	A	G	2: 85,260,523 (GRCm39)	Y217H	probably damaging	Het
Or5al6	A	C	2: 85,976,345 (GRCm39)	H244Q	probably damaging	Het
Or5p78	G	A	7: 108,212,266 (GRCm39)	V251I	probably damaging	Het
Pax3	T	C	1: 78,170,648 (GRCm39)		probably null	Het
Pcdha12	A	G	18: 37,154,679 (GRCm39)	E466G	probably damaging	Het
Pdzk1	A	G	3: 96,775,748 (GRCm39)	E372G	probably benign	Het
Pigs	T	A	11: 78,227,565 (GRCm39)	V243D	possibly damaging	Het
Pla2g5	C	A	4: 138,527,915 (GRCm39)	C117F	probably damaging	Het
Ppt2	A	G	17: 34,841,829 (GRCm39)	S236P	probably damaging	Het
Raver1	T	C	9: 21,001,590 (GRCm39)	D81G	probably benign	Het
Rpgrip1	T	C	14: 52,378,650 (GRCm39)	L525P	possibly damaging	Het
Ryr1	T	C	7: 28,803,068 (GRCm39)	E662G	probably damaging	Het
Scaf8	G	A	17: 3,209,486 (GRCm39)	V66M	probably damaging	Het
Scn3a	A	C	2: 65,295,199 (GRCm39)	L1508R	probably benign	Het
Semp2l2b	T	C	10: 21,943,197 (GRCm39)	D261G	probably benign	Het
Slfn8	T	C	11: 82,907,794 (GRCm39)	R250G	probably benign	Het
Speer4d	A	C	5: 15,825,421 (GRCm39)	T49P	probably damaging	Het
Spice1	T	A	16: 44,175,898 (GRCm39)	D32E	probably damaging	Het
Stt3b	A	G	9: 115,095,224 (GRCm39)	L269P	probably damaging	Het
Ttn	A	G	2: 76,628,456 (GRCm39)	I14568T	possibly damaging	Het
U2surp	T	C	9: 95,367,712 (GRCm39)	T413A	probably benign	Het
Ubr3	A	G	2: 69,784,049 (GRCm39)	E755G	probably damaging	Het
Unc5a	A	T	13: 55,138,896 (GRCm39)	S92C	probably damaging	Het
Zfat	T	C	15: 68,052,969 (GRCm39)	Y275C	probably damaging	Het
Zfp874a	A	T	13: 67,590,401 (GRCm39)	S428T	probably damaging	Het
Zfy1	A	G	Y: 725,428 (GRCm39)	V779A	probably benign	Het

Other mutations in Gclm

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
R0359:Gclm	UTSW	3	122,049,269 (GRCm39)	splice site	probably benign
R1168:Gclm	UTSW	3	122,056,337 (GRCm39)	missense	possibly damaging	0.95
R5093:Gclm	UTSW	3	122,049,261 (GRCm39)	critical splice donor site	probably null
R5427:Gclm	UTSW	3	122,059,976 (GRCm39)	missense	probably damaging	0.98
R5696:Gclm	UTSW	3	122,059,936 (GRCm39)	missense	probably benign	0.11
R6607:Gclm	UTSW	3	122,049,264 (GRCm39)	splice site	probably null
R7430:Gclm	UTSW	3	122,039,729 (GRCm39)	missense	probably benign	0.43
R7690:Gclm	UTSW	3	122,039,705 (GRCm39)	missense	probably damaging	1.00
R8699:Gclm	UTSW	3	122,059,972 (GRCm39)	missense	possibly damaging	0.87

Predicted Primers

PCR Primer
(F):5'- ATTGTCAGGAGTGGCTGGTAAC -3'
(R):5'- TGCCTTCGATAAAGCCTGC -3'

Sequencing Primer
(F):5'- CAGACATTTCAGTGGGCCATG -3'
(R):5'- CACAGTGAACATGCACTAGATG -3'

Posted On

2019-05-13