Incidental Mutation 'B6584:Acadl'
ID634
Institutional Source Beutler Lab
Gene Symbol Acadl
Ensembl Gene ENSMUSG00000026003
Gene Nameacyl-Coenzyme A dehydrogenase, long-chain
SynonymsLCAD, C79855
Accession Numbers

Genbank: NM_007381.3; Ensembl: ENSMUST00000027153, ENSMUST00000139208

Is this an essential gene? Possibly essential (E-score: 0.643) question?
Stock #B6584 (G3) of strain supermodel
Quality Score
Status Validated
Chromosome1
Chromosomal Location66830839-66863277 bp(-) (GRCm38)
Type of Mutationsplice site
DNA Base Change (assembly) T to A at 66848473 bp
ZygosityHeterozygous
Amino Acid Change
Ref Sequence ENSEMBL: ENSMUSP00000027153 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000027153]
Predicted Effect probably benign
Transcript: ENSMUST00000027153
SMART Domains Protein: ENSMUSP00000027153
Gene: ENSMUSG00000026003

DomainStartEndE-ValueType
low complexity region 2 18 N/A INTRINSIC
Pfam:Acyl-CoA_dh_N 54 165 1.3e-33 PFAM
Pfam:Acyl-CoA_dh_M 169 266 9.2e-29 PFAM
Pfam:Acyl-CoA_dh_1 278 427 5.1e-44 PFAM
Pfam:Acyl-CoA_dh_2 293 416 3.4e-11 PFAM
Predicted Effect noncoding transcript
Transcript: ENSMUST00000121857
Predicted Effect noncoding transcript
Transcript: ENSMUST00000139208
Coding Region Coverage
  • 1x: 85.5%
  • 3x: 70.0%
Het Detection Efficiency43.9%
Validation Efficiency 89% (133/150)
MGI Phenotype FUNCTION: This gene encodes a homotetrameric mitochondrial flavoprotein and is a member of the acyl-CoA dehydrogenase family. Members of this family catalyze the first step of fatty acid beta-oxidation, forming a C2-C3 trans-double bond in a FAD-dependent reaction. As beta-oxidation cycles through its four steps, each member of the acyl-CoA dehydrogenase family works at an optimum fatty acid chain-length. This enzyme has its optimum length between C12- and C16-acylCoA. In mice, deficiency of this gene can cause sudden death, cardiomyopathy as well as fasting and cold intolerance. [provided by RefSeq, Nov 2012]
PHENOTYPE: Homozygous mutation of this gene results in reduced litter size, sudden death between 2-14 weeks of age, reduced serum glucose levels, lipid accumulation in the liver and heart, and cardiomyopathy. Heterozygous mutant animals exhibit reduced litter size. [provided by MGI curators]
Allele List at MGI

All alleles(1) : Targeted, knock-out(1)

Other mutations in this stock
Total: 12 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
1700102H20Rik C T 17: 3,559,578 probably benign Homo
2810474O19Rik C T 6: 149,329,346 H1297Y probably damaging Het
Astn2 C T 4: 65,992,387 V403M probably damaging Het
Clcc1 C T 3: 108,672,913 T302I probably damaging Homo
Hormad1 T A 3: 95,570,696 probably benign Homo
Rnf213 C T 11: 119,426,069 T1007I probably damaging Het
Rrh T C 3: 129,811,742 N239D probably damaging Homo
Samd4 A C 14: 47,016,337 H86P probably damaging Homo
Slc27a2 T C 2: 126,561,642 L195P possibly damaging Het
Srek1ip1 T C 13: 104,817,374 probably benign Het
Tars2 T C 3: 95,742,150 probably null Homo
Zfp37 A T 4: 62,191,378 V521E probably damaging Het
Other mutations in Acadl
AlleleSourceChrCoordTypePredicted EffectPPH Score
IGL01296:Acadl APN 1 66841705 missense probably damaging 0.97
IGL01983:Acadl APN 1 66841624 nonsense probably null
IGL02550:Acadl APN 1 66845166 critical splice donor site probably null
IGL02934:Acadl APN 1 66836975 missense probably benign 0.33
IGL03002:Acadl APN 1 66836969 missense probably benign 0.01
PIT4377001:Acadl UTSW 1 66838405 missense probably damaging 1.00
R0426:Acadl UTSW 1 66841646 missense probably damaging 0.99
R0639:Acadl UTSW 1 66857408 missense probably benign
R1264:Acadl UTSW 1 66857553 missense probably benign 0.00
R1589:Acadl UTSW 1 66853223 missense probably benign 0.04
R2066:Acadl UTSW 1 66841746 splice site probably null
R3735:Acadl UTSW 1 66853289 missense probably benign 0.41
R4646:Acadl UTSW 1 66831443 missense probably benign 0.00
R5690:Acadl UTSW 1 66853286 missense probably damaging 1.00
R6185:Acadl UTSW 1 66838363 missense possibly damaging 0.72
R7686:Acadl UTSW 1 66848398 critical splice donor site probably null
R7699:Acadl UTSW 1 66838363 missense possibly damaging 0.72
R7700:Acadl UTSW 1 66838363 missense possibly damaging 0.72
R7858:Acadl UTSW 1 66838324 missense probably benign 0.11
R7941:Acadl UTSW 1 66838324 missense probably benign 0.11
R8052:Acadl UTSW 1 66853178 missense probably benign 0.35
Nature of Mutation

DNA sequencing using the SOLiD technique identified an A to T transversion at base pair 66895047 NC_000067 for the Acadl gene on chromosome 1 (CCCACTATAG ->CCCTCTATAG). Two  transcripts of the Acadl gene are displayed on Ensembl and Vega. The mutation is located within intron 4 from the ATG exon, seven nucleotides to the next exon. The Acadl gene contains 11 total exons using Genbank record NM_007381.3. The mutation has been confirmed by DNA sequencing using the Sanger method (Figure 1).

Protein Function and Prediction

The Acadl gene encodes the 430 amino acid long-chain acyl-CoA dehydrogenase (LCAD), an enzyme involved in fatty acid beta-oxidation. (Uniprot P51174).  Homozygous mutation of this gene in mice results in reduced litter size, sudden death between 2-14 weeks of age, reduced serum glucose levels, lipid accumulation in the liver and heart, and cardiomyopathy. Heterozygous mutant animals exhibit reduced litter size. LCAD deficiency (OMIM 201460) in humans causes a defect in mitochondrial fatty acid oxidation with nonketotic hypoglycemia and episodes of cardiorespiratory arrest associated with fasting. Other features included hepatomegaly, cardiomegaly, and hypotonia.

Posted On2011-04-12