Incidental Mutation 'R6024:Hmgcl'
ID 479078
Institutional Source Beutler Lab
Gene Symbol Hmgcl
Ensembl Gene ENSMUSG00000028672
Gene Name 3-hydroxy-3-methylglutaryl-Coenzyme A lyase
Synonyms
MMRRC Submission 044196-MU
Accession Numbers
Essential gene? Essential (E-score: 1.000) question?
Stock # R6024 (G1)
Quality Score 176.009
Status Validated
Chromosome 4
Chromosomal Location 135673759-135689928 bp(+) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) T to C at 135682926 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Valine to Alanine at position 126 (V126A)
Ref Sequence ENSEMBL: ENSMUSP00000030432 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000030432]
AlphaFold P38060
Predicted Effect probably benign
Transcript: ENSMUST00000030432
AA Change: V126A

PolyPhen 2 Score 0.090 (Sensitivity: 0.93; Specificity: 0.85)
SMART Domains Protein: ENSMUSP00000030432
Gene: ENSMUSG00000028672
AA Change: V126A

DomainStartEndE-ValueType
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 0.0898 question?
Coding Region Coverage
  • 1x: 99.9%
  • 3x: 99.5%
  • 10x: 97.7%
  • 20x: 93.0%
Validation Efficiency 100% (56/56)
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: 55 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
Adgrv1 A G 13: 81,624,624 (GRCm39) F3782L probably benign Het
Akr1d1 T C 6: 37,535,417 (GRCm39) I267T probably benign Het
Aoc1l1 A T 6: 48,953,030 (GRCm39) K318N possibly damaging Het
Arhgef5 T C 6: 43,252,068 (GRCm39) S940P probably benign Het
Art2b A G 7: 101,229,587 (GRCm39) I104T probably benign Het
Avpr1a A G 10: 122,285,053 (GRCm39) Y115C probably damaging Het
Cdc42bpg T A 19: 6,367,526 (GRCm39) L995Q probably damaging Het
Cenatac T C 9: 44,329,249 (GRCm39) T13A possibly damaging Het
Clip1 T C 5: 123,753,152 (GRCm39) K210E possibly damaging Het
Cog4 C T 8: 111,608,112 (GRCm39) T735I probably damaging Het
Creb3l4 G A 3: 90,146,006 (GRCm39) S206L probably damaging Het
Csf3r C A 4: 125,931,310 (GRCm39) probably null Het
Dnah11 G T 12: 117,994,007 (GRCm39) S2346R probably benign Het
Dnai2 A T 11: 114,643,734 (GRCm39) I467F possibly damaging Het
Dpy19l4 A T 4: 11,276,876 (GRCm39) M523K probably damaging Het
Ebf3 T C 7: 136,802,264 (GRCm39) D407G probably damaging Het
Fbn2 A G 18: 58,209,908 (GRCm39) I991T probably benign Het
Gcc1 T C 6: 28,419,299 (GRCm39) T345A probably benign Het
Gm1527 C T 3: 28,974,752 (GRCm39) H522Y probably benign Het
Gm4846 T A 1: 166,317,696 (GRCm39) Y240F probably benign Het
Ifit1bl2 G T 19: 34,597,438 (GRCm39) S59R probably benign Het
Itga6 A G 2: 71,617,577 (GRCm39) N32S probably benign Het
Lcor C A 19: 41,572,396 (GRCm39) P384T possibly damaging Het
Macc1 T C 12: 119,414,160 (GRCm39) S779P probably benign Het
Mctp1 G T 13: 76,533,280 (GRCm39) L209F probably damaging Het
Mink1 A G 11: 70,489,915 (GRCm39) N97S possibly damaging Het
Mst1r T A 9: 107,785,350 (GRCm39) V336E probably benign Het
Muc16 A T 9: 18,557,967 (GRCm39) S2775R unknown Het
Muc6 T A 7: 141,227,841 (GRCm39) T1316S possibly damaging Het
Myh11 T A 16: 14,095,567 (GRCm39) N65I probably damaging Het
Myo9a A G 9: 59,762,671 (GRCm39) N801D possibly damaging Het
Nkain2 A T 10: 31,827,281 (GRCm39) M103K probably damaging Het
Nkx2-2 T A 2: 147,025,961 (GRCm39) Y259F probably benign Het
Nrxn1 T C 17: 90,897,526 (GRCm39) M877V possibly damaging Het
Nxf1 C T 19: 8,745,108 (GRCm39) L453F probably damaging Het
Pcnt T C 10: 76,255,871 (GRCm39) S790G possibly damaging Het
Phf3 T C 1: 30,902,307 (GRCm39) D2G probably damaging Het
Phrf1 T C 7: 140,838,898 (GRCm39) probably benign Het
Ptpn3 C A 4: 57,248,653 (GRCm39) probably null Het
Pygl T C 12: 70,243,841 (GRCm39) T625A probably benign Het
R3hdm2 T A 10: 127,295,349 (GRCm39) F239I probably damaging Het
Sesn1 A T 10: 41,772,196 (GRCm39) I242F probably damaging Het
Shank2 C T 7: 143,733,768 (GRCm39) T105I probably benign Het
Skint3 T C 4: 112,147,543 (GRCm39) F350S possibly damaging Het
Slco5a1 T C 1: 13,014,294 (GRCm39) Y320C probably damaging Het
Syt11 A G 3: 88,669,416 (GRCm39) S159P probably benign Het
Tanc2 G A 11: 105,758,543 (GRCm39) R768Q probably damaging Het
Tanc2 T C 11: 105,814,498 (GRCm39) S1981P probably damaging Het
Tmem200c A C 17: 69,148,722 (GRCm39) D435A possibly damaging Het
Trappc8 A G 18: 20,966,066 (GRCm39) V1125A probably damaging Het
Ttn A G 2: 76,644,487 (GRCm39) V4762A possibly damaging Het
Unc5d A G 8: 29,365,539 (GRCm39) S149P possibly damaging Het
Usf3 A T 16: 44,040,203 (GRCm39) N1561I probably damaging Het
Wdr4 A T 17: 31,720,272 (GRCm39) probably benign Het
Wdr49 T G 3: 75,209,133 (GRCm39) E612D 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
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'- GCAAGCCATCACAGAATTGCT -3'
(R):5'- GGGGAATCCACCTACACTCT -3'

Sequencing Primer
(F):5'- CCTGTTCCCAAGTAGGTAACATGG -3'
(R):5'- ACTCTACAAGGGTCCCGAG -3'
Posted On 2017-06-26