Incidental Mutation 'R7997:Hmgcl'
ID 616125
Institutional Source Beutler Lab
Gene Symbol Hmgcl
Ensembl Gene ENSMUSG00000028672
Gene Name 3-hydroxy-3-methylglutaryl-Coenzyme A lyase
Synonyms
MMRRC Submission 046037-MU
Accession Numbers
Essential gene? Essential (E-score: 1.000) question?
Stock # R7997 (G1)
Quality Score 225.009
Status Not validated
Chromosome 4
Chromosomal Location 135673759-135689928 bp(+) (GRCm39)
Type of Mutation nonsense
DNA Base Change (assembly) T to A at 135687320 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Tyrosine to Stop codon at position 198 (Y198*)
Ref Sequence ENSEMBL: ENSMUSP00000030432 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000030432] [ENSMUST00000102541] [ENSMUST00000143304] [ENSMUST00000149636]
AlphaFold P38060
Predicted Effect probably null
Transcript: ENSMUST00000030432
AA Change: Y198*
SMART Domains Protein: ENSMUSP00000030432
Gene: ENSMUSG00000028672
AA Change: Y198*

DomainStartEndE-ValueType
Pfam:HMGL-like 32 306 2.4e-73 PFAM
Predicted Effect probably benign
Transcript: ENSMUST00000102541
SMART Domains Protein: ENSMUSP00000099600
Gene: ENSMUSG00000028671

DomainStartEndE-ValueType
Pfam:RmlD_sub_bind 1 184 3.5e-14 PFAM
Pfam:KR 3 144 9.5e-10 PFAM
Pfam:Polysacc_synt_2 4 193 7.6e-14 PFAM
Pfam:Epimerase 4 269 3.5e-54 PFAM
Pfam:3Beta_HSD 5 172 2e-18 PFAM
Pfam:GDP_Man_Dehyd 5 332 2.5e-60 PFAM
Pfam:NAD_binding_4 62 233 2.5e-7 PFAM
Predicted Effect probably benign
Transcript: ENSMUST00000143304
SMART Domains Protein: ENSMUSP00000119514
Gene: ENSMUSG00000028671

DomainStartEndE-ValueType
Pfam:Epimerase 4 55 1.2e-8 PFAM
Predicted Effect probably benign
Transcript: ENSMUST00000149636
SMART Domains Protein: ENSMUSP00000117923
Gene: ENSMUSG00000028671

DomainStartEndE-ValueType
Pfam:Epimerase 4 58 1.3e-8 PFAM
Coding Region Coverage
  • 1x: 100.0%
  • 3x: 99.9%
  • 10x: 99.7%
  • 20x: 99.1%
Validation Efficiency
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: 51 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
1700024B05Rik G A 14: 41,766,209 (GRCm39) probably benign Het
Abra A C 15: 41,729,593 (GRCm39) M269R probably damaging Het
Atp6v0e2 A G 6: 48,514,718 (GRCm39) I12V probably benign Het
Bicral T A 17: 47,112,534 (GRCm39) I889F probably benign Het
Cabin1 A G 10: 75,569,609 (GRCm39) V826A probably benign Het
Casq2 A T 3: 101,994,158 (GRCm39) K68N probably damaging Het
Cdh23 C A 10: 60,432,518 (GRCm39) Q135H possibly damaging Het
Chn2 A T 6: 54,267,270 (GRCm39) H253L probably damaging Het
Dnajc22 A G 15: 98,999,514 (GRCm39) E233G probably damaging Het
Fbxo6 A G 4: 148,231,852 (GRCm39) S96P possibly damaging Het
Gimap6 G T 6: 48,679,249 (GRCm39) N262K probably damaging Het
Gpr137b T C 13: 13,533,991 (GRCm39) Y355C Het
Grid2 C A 6: 64,297,120 (GRCm39) H494Q possibly damaging Het
Hmgxb4 A T 8: 75,727,956 (GRCm39) Y313F probably damaging Het
Hr G A 14: 70,801,043 (GRCm39) W676* probably null Het
Insc A G 7: 114,444,372 (GRCm39) D453G probably damaging Het
Iqub T C 6: 24,501,413 (GRCm39) N179S possibly damaging Het
Kdm3b T A 18: 34,941,336 (GRCm39) S276T probably benign Het
Kmt2a C A 9: 44,745,220 (GRCm39) K1597N unknown Het
Kntc1 T C 5: 123,916,117 (GRCm39) V682A probably damaging Het
Mcm9 T A 10: 53,473,502 (GRCm39) probably benign Het
Med30 T C 15: 52,593,467 (GRCm39) L149P probably damaging Het
Mmd2 T A 5: 142,560,615 (GRCm39) H102L possibly damaging Het
Mtres1 T C 10: 43,401,356 (GRCm39) T198A probably benign Het
Mybph G A 1: 134,122,405 (GRCm39) R150H probably damaging Het
Ndufaf4 A G 4: 24,901,919 (GRCm39) T156A probably benign Het
Or2g1 T A 17: 38,107,053 (GRCm39) C239* probably null Het
Pecr T A 1: 72,315,475 (GRCm39) K92* probably null Het
Pithd1 T C 4: 135,703,723 (GRCm39) T207A probably benign Het
Prdm10 T A 9: 31,264,721 (GRCm39) C719S probably damaging Het
Rasef C A 4: 73,658,799 (GRCm39) W316L possibly damaging Het
Robo1 T C 16: 72,701,581 (GRCm39) V149A probably damaging Het
Ryr1 A T 7: 28,702,968 (GRCm39) V5034D unknown Het
Slc26a10 A G 10: 127,009,178 (GRCm39) V661A possibly damaging Het
Slc30a8 T G 15: 52,189,081 (GRCm39) I232S possibly damaging Het
Smg1 A G 7: 117,772,364 (GRCm39) F1464L unknown Het
Smg1 A C 7: 117,772,365 (GRCm39) H1463Q unknown Het
Spata1 G A 3: 146,182,035 (GRCm39) A245V probably benign Het
St8sia1 C T 6: 142,909,376 (GRCm39) C40Y probably damaging Het
Strn T C 17: 78,991,672 (GRCm39) T216A probably benign Het
Tecpr2 G A 12: 110,900,037 (GRCm39) E802K probably benign Het
Tenm4 A G 7: 96,523,512 (GRCm39) I1685V probably benign Het
Tyw5 T C 1: 57,427,683 (GRCm39) D307G probably benign Het
Usp17le A T 7: 104,418,046 (GRCm39) D365E possibly damaging Het
Vmn1r13 T G 6: 57,187,329 (GRCm39) S163A possibly damaging Het
Vmn1r75 A T 7: 11,614,600 (GRCm39) T111S probably damaging Het
Wdr95 G T 5: 149,502,622 (GRCm39) probably null Het
Zfp292 G A 4: 34,808,688 (GRCm39) P1457L probably damaging Het
Zfp606 T A 7: 12,223,519 (GRCm39) V10E probably damaging Het
Zfp606 T C 7: 12,228,134 (GRCm39) S752P possibly damaging Het
Zscan29 T G 2: 120,991,221 (GRCm39) S856R probably benign Het
Other mutations in Hmgcl
AlleleSourceChrCoordTypePredicted EffectPPH 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
R4063:Hmgcl UTSW 4 135,686,035 (GRCm39) missense probably damaging 1.00
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
R8941:Hmgcl UTSW 4 135,683,015 (GRCm39) missense probably damaging 0.96
Predicted Primers PCR Primer
(F):5'- TTGCAGCCACTGGGTAATG -3'
(R):5'- TGAAATGGTACTTCCCTGCCC -3'

Sequencing Primer
(F):5'- AGCCACTGGGTAATGCTGGTC -3'
(R):5'- AATATGGGCGCACGGCTTTC -3'
Posted On 2020-01-23