Mutagenetix > Incidental Mutation

Incidental Mutation 'R4063:Hmgcl'

368212

Institutional Source

Beutler Lab

Gene Symbol

Hmgcl

Ensembl Gene

ENSMUSG00000028672

Gene Name

3-hydroxy-3-methylglutaryl-Coenzyme A lyase

Synonyms

MMRRC Submission

041619-MU

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R4063 (G1)

Quality Score

225

Status

Validated

Chromosome

Chromosomal Location

135673759-135689928 bp(+) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

T to C at 135686035 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Tyrosine to Histidine at position 167 (Y167H)

Ref Sequence

ENSEMBL: ENSMUSP00000030432 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000030432]

AlphaFold

P38060

Predicted Effect

probably damaging
Transcript: ENSMUST00000030432
AA Change: Y167H

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)

SMART Domains

Protein: ENSMUSP00000030432
Gene: ENSMUSG00000028672
AA Change: Y167H

Domain	Start	End	E-Value	Type
Pfam:HMGL-like	32	306	2.4e-73	PFAM

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000134135

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000135644

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000148613

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000151879

Meta Mutation Damage Score

0.9681

Coding Region Coverage

1x: 99.3%
3x: 98.7%
10x: 97.5%
20x: 95.9%

Validation Efficiency

97% (59/61)

MGI Phenotype

FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] The protein encoded by this gene belongs to the HMG-CoA lyase family. It is a mitochondrial enzyme that catalyzes the final step of leucine degradation and plays a key role in ketone body formation. Mutations in this gene are associated with HMG-CoA lyase deficiency. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2009]
PHENOTYPE: Mice homozygous for a knock-out allele die at midgestation exhibiting reduced embryo size, frequent cytoplasmic vacuolization in liver, heart and placenta, and marked focal hydropic swelling of mitochondria in hepatocytes. [provided by MGI curators]

Allele List at MGI

Other mutations in this stock

Total: 54 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
1700034J05Rik	A	T	6: 146,854,606 (GRCm39)	F145L	probably benign	Het
Abcc9	T	C	6: 142,551,645 (GRCm39)	D1221G	possibly damaging	Het
Adamtsl4	T	C	3: 95,584,864 (GRCm39)	K935E	probably benign	Het
Ago4	A	T	4: 126,409,655 (GRCm39)		probably benign	Het
Arhgef28	T	C	13: 98,130,575 (GRCm39)	D421G	probably benign	Het
Armh4	T	A	14: 50,011,444 (GRCm39)	M88L	probably benign	Het
Atl2	T	C	17: 80,157,588 (GRCm39)	*413W	probably null	Het
B4galt7	C	A	13: 55,756,152 (GRCm39)		probably null	Het
Bltp3b	A	G	10: 89,651,917 (GRCm39)	N247S	probably benign	Het
C8g	A	T	2: 25,389,425 (GRCm39)	S147T	probably damaging	Het
Clstn3	A	T	6: 124,426,792 (GRCm39)	Y510N	possibly damaging	Het
Cnot2	A	G	10: 116,373,301 (GRCm39)	V34A	possibly damaging	Het
Cyb5d2	A	T	11: 72,686,606 (GRCm39)		probably benign	Het
Dnah5	T	C	15: 28,421,144 (GRCm39)	I3827T	probably damaging	Het
Dnah7a	G	T	1: 53,464,376 (GRCm39)	Q3672K	probably benign	Het
Dock1	A	T	7: 134,717,021 (GRCm39)	Y1219F	possibly damaging	Het
Espl1	A	G	15: 102,221,424 (GRCm39)	I944V	probably damaging	Het
Fat1	A	T	8: 45,478,518 (GRCm39)	E2521D	probably benign	Het
Gm10719	G	T	9: 3,019,043 (GRCm39)	W96L	probably damaging	Het
H2-M2	G	A	17: 37,792,399 (GRCm39)	H291Y	probably damaging	Het
Il22ra2	A	T	10: 19,502,400 (GRCm39)	D73V	possibly damaging	Het
Incenp	A	T	19: 9,861,142 (GRCm39)	M480K	unknown	Het
Irag1	G	T	7: 110,522,984 (GRCm39)	A359D	probably benign	Het
Kdm6a	A	G	X: 18,117,114 (GRCm39)	T266A	probably benign	Het
Lipf	A	G	19: 33,942,965 (GRCm39)	N91S	probably benign	Het
M1ap	A	T	6: 82,980,756 (GRCm39)	N214I	probably damaging	Het
Mast3	A	G	8: 71,233,838 (GRCm39)	V969A	probably damaging	Het
Mdga1	A	G	17: 30,057,005 (GRCm39)	C826R	probably damaging	Het
Msx1	C	A	5: 37,981,365 (GRCm39)	A105S	probably benign	Het
Or5ac23	A	C	16: 59,149,243 (GRCm39)	S210A	probably benign	Het
Otogl	A	T	10: 107,626,510 (GRCm39)	D1451E	probably benign	Het
Otop2	G	A	11: 115,220,201 (GRCm39)	G347D	probably damaging	Het
Ppp1r13l	A	T	7: 19,103,978 (GRCm39)	H153L	probably benign	Het
Pramel21	A	G	4: 143,342,559 (GRCm39)	D222G	possibly damaging	Het
Pramel29	T	C	4: 143,935,265 (GRCm39)	K161E	possibly damaging	Het
Proz	A	G	8: 13,114,621 (GRCm39)	Y85C	probably damaging	Het
Prss50	A	G	9: 110,687,480 (GRCm39)	D141G	probably benign	Het
Rad54l2	T	A	9: 106,597,613 (GRCm39)	Q131L	probably benign	Het
Sdha	A	G	13: 74,472,077 (GRCm39)		probably benign	Het
Sema3d	T	A	5: 12,635,091 (GRCm39)	I719N	probably benign	Het
Slc18b1	A	T	10: 23,681,879 (GRCm39)	I148L	probably benign	Het
Tacc2	G	T	7: 130,330,852 (GRCm39)	D2086Y	probably damaging	Het
Tchh	T	C	3: 93,354,298 (GRCm39)	L1246P	unknown	Het
Tmprss11d	T	C	5: 86,457,177 (GRCm39)	I161V	probably benign	Het
Trpc3	T	C	3: 36,725,172 (GRCm39)	D268G	probably damaging	Het
Trpm8	G	A	1: 88,289,727 (GRCm39)	R895H	probably damaging	Het
Txndc2	A	G	17: 65,945,079 (GRCm39)	I366T	possibly damaging	Het
Ugt2a3	T	C	5: 87,484,725 (GRCm39)	I100V	probably benign	Het
Upp1	C	A	11: 9,081,709 (GRCm39)	P82Q	probably damaging	Het
Vim	A	G	2: 13,584,827 (GRCm39)		probably null	Het
Vmn2r12	A	T	5: 109,240,058 (GRCm39)	N168K	possibly damaging	Het
Zdhhc14	G	T	17: 5,802,983 (GRCm39)	C362F	probably damaging	Het
Zfp292	A	G	4: 34,810,863 (GRCm39)	V727A	probably damaging	Het
Zswim5	G	A	4: 116,735,177 (GRCm39)	G174D	unknown	Het

Other mutations in Hmgcl

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
R0226:Hmgcl	UTSW	4	135,686,039 (GRCm39)	missense	probably damaging	1.00
R0825:Hmgcl	UTSW	4	135,687,381 (GRCm39)	missense	probably benign
R2400:Hmgcl	UTSW	4	135,679,679 (GRCm39)	splice site	probably null
R3791:Hmgcl	UTSW	4	135,687,298 (GRCm39)	missense	probably benign	0.00
R5000:Hmgcl	UTSW	4	135,689,511 (GRCm39)	missense	probably benign	0.01
R5754:Hmgcl	UTSW	4	135,677,898 (GRCm39)	missense	probably damaging	0.98
R6024:Hmgcl	UTSW	4	135,682,926 (GRCm39)	missense	probably benign	0.09
R6658:Hmgcl	UTSW	4	135,682,962 (GRCm39)	missense	probably damaging	0.96
R6889:Hmgcl	UTSW	4	135,682,953 (GRCm39)	missense	probably benign	0.33
R7074:Hmgcl	UTSW	4	135,681,178 (GRCm39)	missense	probably benign	0.00
R7238:Hmgcl	UTSW	4	135,689,424 (GRCm39)	missense	possibly damaging	0.92
R7733:Hmgcl	UTSW	4	135,687,394 (GRCm39)	missense	probably benign	0.01
R7997:Hmgcl	UTSW	4	135,687,320 (GRCm39)	nonsense	probably null
R8941:Hmgcl	UTSW	4	135,683,015 (GRCm39)	missense	probably damaging	0.96

Predicted Primers

PCR Primer
(F):5'- AATTCTCAGCCACCTGCAG -3'
(R):5'- GGGCTCGCAGTATATGAGTGAG -3'

Sequencing Primer
(F):5'- GTCCAGTGGCCTCTAAGC -3'
(R):5'- CTCGCAGTATATGAGTGAGTGTGTG -3'

Posted On

2016-01-06